Pharmacokinetic interactions of curcuminoids with conventional drugs: A review

Publication date: 14 September 2017
Source:Journal of Ethnopharmacology, Volume 209
Author(s): Roodabeh Bahramsoltani, Roja Rahimi, Mohammad Hosein Farzaei
Ethnopharmacological relevanceHerb–drug interactions are of great concern in health practices. Curcumin is a natural polyphenol extracted from turmeric, a spice widely used all over the world. Curcumin is clinically used due to its acceptable safety profile and therapeutic efficacy.Aim of the studyCurrent paper aims to highlight the effect of curcumin on concomitantly used drugs.MethodsElectronic databases including PubMed, Scopus and Science Direct were searched with the keywords "curcumin" in the title/abstract and "drug interaction," "drug metabolism," "cytochrome," "P-glycoprotein" and "P450" in the whole text.ResultsCurcumin can induce pharmacokinetic alterations such as changes in Cmax and AUC when concomitantly used with pharmacological agents like cardiovascular drugs, antidepressants, anticoagulants, antibiotics, chemotherapeutic agents, and antihistamines. The underlying mechanisms of these interactions include inhibition of cytochrome (CYP) isoenzymes and P-glycoprotein. There is only one clinical trial which proved a significant alteration of conventional drugs in concomitant use with curcumin indicating the need for further human studies.ConclusionsAlthough in vitro and in vivo studies do not provide enough evidence to judge the clinical drug interactions of curcumin, physicians must remain cautious and avoid drug combinations which may lead to curcumin-drug interactions.

Graphical abstract

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Polysaccharides of Dendrobium officinale Kimura & Migo protect gastric mucosal cell against oxidative damage-induced apoptosis in vitro and in vivo

Publication date: 17 August 2017
Source:Journal of Ethnopharmacology, Volume 208
Author(s): Qiang Zeng, Chun-Hay Ko, Wing-Sum Siu, Long-Fei Li, Xiao-Qiang Han, Liu Yang, Clara Bik-San Lau, Jiang-Miao Hu, Ping-Chung Leung
Ethnopharmacological relevanceDendrobium officinale Kimura & Migo (DO) is a valuable Traditional Chinese Medicine to nourish stomach, in which polysaccharides are identified as active ingredients. However, limited scientific evidences have been reported on the gastroprotective efficacy of DO. The aim of the current study was to investigate the protective effects and underlying mechanism of polysaccharides from DO(DOP) on gastric mucosal injury.Material and methodsFor in vitro study, HFE145 cells were pretreated with DOP before induction of cell apoptosis by H2O2. Cell apoptosis and related proteins expression were detected. In the in vivo study, absolute ethanol was administered orally to induce gastric mucosal injury in rat. The gastric mucosal injury area and histological examination were used to evaluate the effects of DOP treatment on the recovery of the gastric mucosal injury.ResultsH2O2 treatment for 6h significantly induced cell apoptosis in HFE145 cells. However, the destructive effects of H2O2 on HFE 145 cells could be reversed by the pretreatment with DOP. The increased ROS level induced by H2O2 for 4h was reduced after DOP pretreatment. The number of apoptotic cells in both early and late apoptosis stages decreased significantly and the nuclei morphology changes were improved with DOP pretreatment. Furthermore, DOP inhibited caspase 3 activation and PARP cleavage, downregulated Bax expression and upregulated Bcl2 expression in cell model. Further study revealed that pretreatment of DOP inhibited p -NF-κBp65/NF-κBp65 level, indicating DOP inhibited H2O2-mediated apoptosis via suppression of NF-κB activation. In addition, DOP treatment could ameliorate gastric mucosal injury and inhibit mucin loss induced by ethanol in animal model. DOP treatment also interfered with ethanol-induced apoptosis process by downregulating Bax/Bcl2 ratio in gastric mucosa.ConclusionsThe present study was the first one to demonstrate the gastroprotective effect of DOP through inhibiting oxidative stress-induced apoptosis. This study provided a solid evidence for the potential use of DO as a therapy or health supplement for gastric mucosal diseases

Graphical abstract

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Comparative metabolic analysis in head and neck cancer and the normal gingiva

Abstract

Objectives

Chronic accumulation of lactate in malignant tumor tissue is associated with increased malignancy and radioresistance. For this study, biopsies of primary head and neck squamous cell carcinoma (HNSCC) and of the normal gingiva of the same patient were compared via metabolic profiling to the healthy gingiva from cancer-free patients.

Materials and methods

Cryobiopsies of 140 HNSCC patients were used to determine ATP, lactate, and glucose concentrations of the tumor and normal gingiva via induced metabolic bioluminescence imaging (imBI). Additionally, these metabolites were quantified in a collective of 79 healthy (non-tumor-bearing) patients. Furthermore, tumor samples were analyzed via immunofluorescence imaging and quantitative real-time PCR for the expression of lactate and glucose transporters.

Results

There were significant differences in ATP concentrations detectable between the tumor, normal gingiva of tumor patients, and gingiva from healthy patients. Lactate concentrations were significantly increased in tumor tissue compared to the normal gingiva of tumor patients as well as the gingiva from healthy patients. Concerning glucose, there was a significant decrease in glucose concentrations detectable in the tumor biopsies compared to the normal gingiva of tumor patients. On the other hand, tumor samples from patients revealed significantly elevated relative expression levels of monocarboxylate transporters (MCT-1 and MCT-4), as well as glucose transporters (GLUT-1 and GLUT-3) compared to the corresponding normal gingiva of each patient.

Conclusions

We could demonstrate that the lactate concentration in HNSCC correlates with primary tumor (T) stage.

Clinical relevance

The aim of this study was to identify metabolic parameters to improve early cancer diagnosis, allow predictions on the degree of malignancy, and contribute to a personalized tumor therapy.

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Approximal morphology as predictor of approximal caries in primary molar teeth

Abstract

Objective

To evaluate the predictive power of the morphology of the distal surface on 1st and mesial surface on 2nd primary molar teeth on caries development in young children.

Sample and methods

Out of 101 3-to 4-year-old children from an on-going study, 62 children, for whom parents' informed consent was given, participated. Upper and lower molar teeth of one randomly selected side received a 2-day temporarily separation. Bitewing radiographs and silicone impressions of interproximal area (IPA) were obtained. One-year procedures were repeated in 52 children (84%). The morphology of the distal surfaces of the first molar teeth and the mesial surfaces on the second molar teeth (n=208) was scored from the occlusal aspect on images from the baseline resin models resulting in four IPA variants: concave-concave; concave-convex; convex-concave, and convex-convex. Approximal caries on the surface in question was radiographically assessed as absent/present.

Results

Of the 52 children examined at follow-up, 31 children (60%) had 1–4 concave surfaces. In total 53 (25%) of the 208 surfaces were concave. A total of 22 children (43%) had 1–4 approximal lesions adding up to 59 lesions. Multiple logistic regression analyses disclosed that gender, surface morphology on one of the approximal surfaces (focus-surface), and adjacent-surface morphology were significantly related to caries development (p values ≤ 0.03). The odds ratio for developing caries in the focus-surface/adjacent-surface in the four IPA variants were convex-convex, 1.0; convex-concave, 5.5 (CI 2.0–14.7); concave-convex, 12.9 (CI 4.1–40.3); and concave-concave, 15.7 (CI 5.1–48.3).

Conclusion

Morphology of approximal surfaces in primary molar teeth, in particular both surfaces being concave, significantly influences the risk of developing caries.

Clinical relevance

The concave morphology of approximal surfaces can predict future caries lesions supporting specific home-care and in-office preventive strategies.

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Effect of processing conditions on degree of hydrolysis, ACE inhibition, and antioxidant activities of protein hydrolysate from Acetes indicus

Abstract

Protein hydrolysate was prepared from Acetes indicus which is a major bycatch among non-penaeid prawn landings of India. Hydrolysis conditions (enzyme to substrate ratio and time) for preparing protein hydrolysates using alcalase enzyme were optimized by response surface methodology using central composite design. The optimum conditions for enzyme-substrate ratio (mL/100 g) of 1.57, 1.69, 1.60, 1.56, and 1.50 and for hydrolysis time of 97.18, 96.5, 98.15 min, 102.48, and 88.44 min were established for attaining maximum yield, degree of hydrolysis, 2,2-diphenyl-1-picrylhydrazyl, angiotensin I-converting enzyme-inhibiting activity, and metal-chelating activity, respectively. ABTS radical scavenging activity and reducing power assay of optimized protein hydrolysate were found to be increased with the increase in concentration. The higher value of 7.04 (μM Trolox/g), 87.95, and 77.24%, respectively for DPPH, ACE, and metal-chelating activity indicated that the A. indicus protein hydrolysates have beneficial biological properties that could be well-utilized in the application of functional foods and nutraceuticals.

Graphical abstract

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Functional characterization of the Dsc E3 ligase complex in the citrus postharvest pathogen Penicillium digitatum

Publication date: Available online 21 July 2017
Source:Microbiological Research
Author(s): Ruoxin Ruan, Kuang-Ren Chung, Hongye Li
Sterol regulatory element binding proteins (SREBPs) are required for sterol homeostasis in eukaryotes. Activation of SREBPs is regulated by the Dsc E3 ligase complex in Schizosaccharomyces pombe and Aspergillus spp. Previous studies indicated that an SREBP-coding gene PdsreA is required for fungicide resistance and ergosterol biosynthesis in the citrus postharvest pathogen Penicillium digitatum. In this study, five genes, designated PddscA, PddscB, PddscC, PddscD, and PddscE encoding the Dsc E3 ligase complex were characterized to be required for fungicide resistance, ergosterol biosynthesis and CoCl2 tolerance in P. digitatum. Each of the dsc genes was inactivated by target gene disruption and the resulted phenotypes were analyzed and compared. Genetic analysis reveals that, of five Dsc complex components, PddscB is the core subunit gene in P. digitatum. Although the resultant dsc mutants were able to infect citrus fruit and induce maceration lesions as the wild-type, the mutants rarely produced aerial mycelia on affected citrus fruit peels. P. digitatum Dsc proteins regulated not only the expression of genes involved in ergosterol biosynthesis but also that of PdsreA. Yeast two-hybrid assays revealed a direct interaction between the PdSreA protein and the Dsc proteins. Ectopic expression of the PdSreA N-terminus restored fungicide resistance in the dsc mutants. Our results provide important evidence to understand the mechanisms underlying SREBP activation and regulation of ergosterol biosynthesis in plant pathogenic fungi.



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Human iPSC Glial Mouse Chimeras Reveal Glial Contributions to Schizophrenia

Publication date: Available online 20 July 2017
Source:Cell Stem Cell
Author(s): Martha S. Windrem, Mikhail Osipovitch, Zhengshan Liu, Janna Bates, Devin Chandler-Militello, Lisa Zou, Jared Munir, Steven Schanz, Katherine McCoy, Robert H. Miller, Su Wang, Maiken Nedergaard, Robert L. Findling, Paul J. Tesar, Steven A. Goldman
In this study, we investigated whether intrinsic glial dysfunction contributes to the pathogenesis of schizophrenia (SCZ). Our approach was to establish humanized glial chimeric mice using glial progenitor cells (GPCs) produced from induced pluripotent stem cells derived from patients with childhood-onset SCZ. After neonatal implantation into myelin-deficient shiverer mice, SCZ GPCs showed premature migration into the cortex, leading to reduced white matter expansion and hypomyelination relative to controls. The SCZ glial chimeras also showed delayed astrocytic differentiation and abnormal astrocytic morphologies. When established in myelin wild-type hosts, SCZ glial mice showed reduced prepulse inhibition and abnormal behavior, including excessive anxiety, antisocial traits, and disturbed sleep. RNA-seq of cultured SCZ human glial progenitor cells (hGPCs) revealed disrupted glial differentiation-associated and synaptic gene expression, indicating that glial pathology was cell autonomous. Our data therefore suggest a causal role for impaired glial maturation in the development of schizophrenia and provide a humanized model for its in vivo assessment.

Graphical abstract

Teaser

Goldman and colleagues use mice chimerized with human patient-derived glial progenitor cells to find out whether glia contribute to childhood-onset schizophrenia. The defects in cell differentiation, myelination, and behavior they see strongly suggest that glial cells do, in fact, have a previously unappreciated role in the pathogenesis of this disease.


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Pathogen-Induced TLR4-TRIF Innate Immune Signaling in Hematopoietic Stem Cells Promotes Proliferation but Reduces Competitive Fitness

Publication date: Available online 20 July 2017
Source:Cell Stem Cell
Author(s): Hitoshi Takizawa, Kristin Fritsch, Larisa V. Kovtonyuk, Yasuyuki Saito, Chakradhar Yakkala, Kurt Jacobs, Akshay K. Ahuja, Massimo Lopes, Annika Hausmann, Wolf-Dietrich Hardt, Álvaro Gomariz, César Nombela-Arrieta, Markus G. Manz
Bacterial infection leads to consumption of short-lived innate immune effector cells, which then need to be replenished from hematopoietic stem and progenitor cells (HSPCs). HSPCs express pattern recognition receptors, such as Toll-like receptors (TLRs), and ligation of these receptors induces HSPC mobilization, cytokine production, and myeloid differentiation. The underlying mechanisms involved in pathogen signal transduction in HSCs and the resulting biological consequences remain poorly defined. Here, we show that in vivo lipopolysaccharide (LPS) application induces proliferation of dormant HSCs directly via TLR4 and that sustained LPS exposure impairs HSC self-renewal and competitive repopulation activity. This process is mediated via TLR4-TRIF-ROS-p38, but not MyD88 signaling, and can be inhibited pharmacologically without preventing emergency granulopoiesis. Live Salmonella Typhimurium infection similarly induces proliferative stress in HSCs, in part via TLR4-TRIF signals. Thus, while direct TLR4 activation in HSCs might be beneficial for controlling systemic infection, prolonged TLR4 signaling has detrimental effects and may contribute to inflammation-associated HSPC dysfunction.

Graphical abstract

Teaser

Takizawa et al. show that self-renewing hematopoietic cells directly sense gram-negative bacterial infection through Toll-like receptor 4 (TLR4) activation, which leads to impaired function via proliferative stress. Genetic and pharmacological blockage of the TLR4-TRIF-ROS-p38 axis can maintain HSC function without disrupting emergency granulopoietic responses to infection.


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High-Content Screening in hPSC-Neural Progenitors Identifies Drug Candidates that Inhibit Zika Virus Infection in Fetal-like Organoids and Adult Brain

Publication date: Available online 20 July 2017
Source:Cell Stem Cell
Author(s): Ting Zhou, Lei Tan, Gustav Y. Cederquist, Yujie Fan, Brigham J. Hartley, Suranjit Mukherjee, Mark Tomishima, Kristen J. Brennand, Qisheng Zhang, Robert E. Schwartz, Todd Evans, Lorenz Studer, Shuibing Chen
Zika virus (ZIKV) infects fetal and adult human brain and is associated with serious neurological complications. To date, no therapeutic treatment is available to treat ZIKV-infected patients. We performed a high-content chemical screen using human pluripotent stem cell-derived cortical neural progenitor cells (hNPCs) and found that hippeastrine hydrobromide (HH) and amodiaquine dihydrochloride dihydrate (AQ) can inhibit ZIKV infection in hNPCs. Further validation showed that HH also rescues ZIKV-induced growth and differentiation defects in hNPCs and human fetal-like forebrain organoids. Finally, HH and AQ inhibit ZIKV infection in adult mouse brain in vivo. Strikingly, HH suppresses viral propagation when administered to adult mice with active ZIKV infection, highlighting its therapeutic potential. Our approach highlights the power of stem cell-based screens and validation in human forebrain organoids and mouse models in identifying drug candidates for treating ZIKV infection and related neurological complications in fetal and adult patients.

Graphical abstract

Teaser

Chen, Studer, and colleagues utilize human pluripotent stem cell-derived neural progenitors to perform a high-content screen for anti-ZIKV drug discovery. Hippeastrine hydrobromide was identified and shown to eliminate ZIKV in infected human neural progenitors, rescue a ZIKV-induced microcephaly phenotype in human forebrain organoids, and suppress virus propagation in adult mice with active ZIKV infection.


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The Feulgen reaction: A brief review and new perspectives

Publication date: Available online 21 July 2017
Source:Acta Histochemica
Author(s): Maria Luiza S. Mello, Benedicto de Campos Vidal
The Feulgen reaction has been proposed by Robert Feulgen and Heinrich Rossenbeck for the identification of DNA nearly a hundred years ago. Since then, many other applications of this cytochemical/topochemical procedure at qualitative and quantitative level have been proposed in relation to DNA and its role in chromatin in human, animal and plant cells. In this article, we briefly review some fundamental aspects of the Feulgen reaction and current applications of such a method in studies of altered chromatin texture, including its association with or preceding changes in transcriptional activities and effect on epigenetic marks. Further perspectives on the use of the Feulgen reaction will depend of the proposal of innovative biological questions in which its reveals appropriate.



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Clinicopathological and immunohistochemical analysis of epithelial-lined (true) cysts of the adrenal gland with proposal of a new histogenetic categorization

Publication date: Available online 21 July 2017
Source:Pathology - Research and Practice
Author(s): Łukasz Koperski, Paweł Pihowicz, Benedykt Szczepankiewicz, Łukasz Fus, Agata Cyran, Magdalena Bogdańska, Barbara Górnicka
Epithelial- lined (true) cysts are rare lesions and until now the only information we had about their histogenesis was based on the analysis of a few cases. We retrospectively reviewed 8 cases of cysts with a true epithelial lining (confirmed immunohistochemically). The pathological findings and immunohistochemical analysis of the epithelial linings allowed for categorization of the cysts into 3 groups. Five cysts had pure mesothelial lining, which was flattened to cuboidal, and demonstrated a positive reaction for mesothelial markers (eg. calretinin, WT1), and a negative reaction for EpCAM, EMA, PAX8 and ER. Two cysts had cuboidal to flattened lining, the cells of which were diffusely or focally positive for mesothelial markers, for some epithelial markers (eg. EpCAM and EMA) and despite a lack of müllerian-type epithelium demonstrated a positive reaction for PAX8 and focally for ER. A cyst derived from adreno-hepatic fusion (AHF)-related intra-adrenal bile ductules was diagnosed in a right adrenal gland which was directly adherent to the liver, microscopically features of AHF were visible with intermingling of adrenal and liver parenchymal cells. The immunoreactivity pattern was similar among the preserved cells of the cyst-lining, the intra-adrenal bile ductules and the normal bile ductules in the adjoining liver parenchyma. On the basis of this case series from a single institution (8 presented now and 1 reported before) we propose a new histogenetic categorization of adrenal epithelial cysts into: 1. pure mesothelial cysts (the most common type), 2. mesothelial cysts with incomplete or complete müllerian metaplasia 3. AHF-related cysts.



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Large-volume breast fat transfer: technical evolutions and safety aspects based on over 800 cases and 26 years of follow-up

Abstract

Current techniques for augmentation mammoplasty involve the use of alloplastic materials and an open approach. The former may not be well tolerated and often can be the origin of undesirable effects such as capsule contracture. The latter implies residual scars, which can sometimes be less than satisfactory from an esthetic point of view. Considering all the problems mentioned above and seeking to find safe and reliable alternatives to implants, we focused our attention on the possibility of using fat tissue as filling material for breast augmentation. Autologous adipose tissue has been used to correct soft tissue defects for more than a century. Its soft and natural texture, the absence of a line, and its versatility have always made adipose tissue the ideal physiologic filling material. The author describes his surgical experience with breast fat transfer. The clinical outcome described in this Article is based on over 800 patients with a follow-up period of over than 26 years. The surgical techniques described by the author evolved constantly and steadily aiming to achieve more consistent results and trying to increase at the same time patient safety and satisfaction. Analyzing the clinical data clearly appears that complications are strictly related to the oily content of the transplanted tissue, where more TGs in the recipient site is clearly at the origin of a higher level of complications. In order to improve patient's safety and to limit risk of side effects, the author developed a new "oil-free" fat transfer technique. All the technical steps are described in details. An important part of this work is dedicated to a careful evaluation of safety aspects and oncologic concerns. The total oncologic safety of fat transfer in breast reconstruction and in esthetic augmentation has been clearly proved and confirmed.

Level of Evidence: Level IV, therapeutic study.

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Treatment with Chemotherapy and Cognitive Functioning Among Older Adult Cancer Survivors

Publication date: Available online 20 July 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Ruth T. Morin, Elizabeth Midlarsky
ObjectiveTo investigate whether treatment of cancer with chemotherapy, when compared to surgery and radiation, differentially affects cognitive functioning among older adults.DesignData were examined prospectively from two years prior to cancer diagnosis to four years after cancer diagnosis. Distinct classes of cognitive functioning were identified using latent class growth analysis techniques (LCGA). Treatment type was assessed as a predictor of class membership.SettingData were collected from a large population-based cohort in the context of the Health and Retirement Study.Participants403 older adults with a new diagnosis of cancer, who were still alive 4 years after their diagnosis. Participants had provided informed consent for the data collection, and the use of the data was approved by the Institutional Review Board of Columbia University, Teachers College.InterventionsNot applicable.Main Outcome MeasureCognition (degree of immediate recall and delayed recall of a word list).ResultsFindings indicated that three classes of cognitive functioning best fit the data, specifically High, Middle, and Low Recall classes. Individuals treated with chemotherapy were significantly more likely to be in the High Recall class, with no effect of receiving surgery or radiation. When interactions with demographic predictors were entered into the model, an age x treatment interaction was present, such that individuals under 80 were more likely to both receive chemotherapy and have high recall cognition.ConclusionsThree distinct classes of cognitive functioning emerged among older adults with cancer. Treatment with chemotherapy predicted likely membership in the High Recall class in this sample of cancer survivors, however this was due to an age by treatment interaction. Implications for understanding cognitive sequelae of cancer in late life are discussed.



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Prevalence and characteristics of work-anxiety in medical rehabilitation patients – a cross-sectional observation study

Publication date: Available online 20 July 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Beate Muschalla, Michael Jöbges
ObjectiveTo investigate frequency, type and characteristics of work-anxieties in somatic rehabilitation inpatients. Work-anxieties are serious disorders which affect occupational functioning and often go along with long-term sick leave. Somatic patients may suffer from work-related participation problems due to their chronic health condition. Work-anxieties need specific diagnostic and treatment.DesignThis is a cross-sectional observation study.SettingWe investigated inpatients from a neurological, orthopedic and cardiologic rehabilitation clinic.Participants1610 patients (18-65 years) were investigated for work-anxieties in a short structured interview.Main outcome measuresPatients who scored high in at least two out of nine work-anxiety leading symptoms and reported impairment were investigated with a differential-diagnostic interview on work-anxieties, and with the MINI interview on non-work-related common mental disorders. Patients also filled in a self-rating on their subjective symptom load and sociodemographic data.ResultsAbout 20-27% of the investigated somatic rehabilitation inpatients (altogether n=393) got a work-anxiety diagnosis. Orthopaedic patients report highest work-anxiety and have longest preceding sick leave (20.6 weeks in past 12 months). Orthopaedic patients suffer from work-related adjustment anxieties, social anxieties, and workplace phobia, while cardiology patients are more often affected from hypochondriac anxieties. Anxieties of insufficiency and worrying occur equally in all indications.ConclusionsAbout one quarter of somatic rehabilitation patients is in need of additional diagnostic attention due to work-anxieties. Differential diagnostic of work-anxiety is needed for initiating adequate therapeutic action. Somatic rehabilitation physicians should be aware of work-anxieties in their patients, especially in orthopaedic patients with preceding long-term sick leave.



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Successful outcome of musculoskeletal injury leads to a reduction in chronic fatigue: A case report

Publication date: Available online 21 July 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Carl Todd DO
BackgroundChronic fatigue syndrome (CFS) is a general term used to describe a number of medical conditions that lead to persistent levels of fatigue and distress.ObjectivesOsteopathic manipulative treatment (OMT) combined with shoulder exercises to resolve musculoskeletal sports injury may have also led to a reduction in pain and improved strength with the patient reporting a change in CFS levels.Clinical features19-year-old male student, (statue 194cm and mass 80kg) who had played county level cricket and hockey. Presented with a two-year history of left shoulder pain (VAS 8/10) and a diagnosis of chronic fatigue syndrome.Intervention and outcomesOMT was performed over four clinical visits throughout a four a month period. Management goal was pain reduction, neural regulation, and facilitation of breathing mechanics to improve lymphatic drainage and restoration of shoulder strength and control.ConclusionClinically a reduction in pain (VAS 8/10–0/10) over four treatments appeared to correlate with improved shoulder strength. It was also reported that due to pain reduction, CFS might have improved.



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A comparison of lower limb muscle activation pattern using voluntary response index between pronated and normal foot structures during forward jump landing

Publication date: Available online 21 July 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Hosein Kouhzad Mohammadi, Mohammad Mehravar, Khosro Khademi Kalantari, Sedighe Sadat Naimi, Alireza Akbarzadeh Baghban, Farshad Okhovatian, Asghar rezasoltani, Mohammad Ali Mohseni Bandpei, Navid Taheri
BackgroundPronated foot is one of the important factors contributing to the musculoskeletal problems of the lower extremities. It is known that in pronated foot, excessive mechanical load is applied to the lower limb structures which may result in altered biomechanics and muscle activation patterns. The aim of this study was to determine changes in the muscle activation pattern of the lower extremities in the pronated compared to normal foot individuals, using the voluntary response index (VRI).MethodsIn this cross sectional study, 15 asymptomatic pronated foot individuals (mean age 23.27 ± 3.28 years) and 15 normal subjects (mean age 23.40 ± 3.11 years) were recruited by simple non-random sampling. Electrical activities of gluteus medius (GM), vastus lateralis (VL), vastus medialis (VM), biceps femoris, semitendinosus (ST), and medial gastrocnemius (MG) muscles were recorded during a forward jump landing task. Voluntary response index (VRI) variables, included similarity index (SI) and magnitude (Mag) were also evaluated.ResultsMuscle activity of VM (p < 0.001) and ST (p = 0.010) were significantly higher but VL (p = 0.039) and MG (p = 0.001) were significantly lower in pronated foot, compared to normal subjects. Similarity index was found to be different (p < 0.001) between pronated foot and healthy individuals. No significant difference was found in terms of Mag between the two groups (p = 0.576).ConclusionThe altered pattern of lower limb muscle activation identified in the pronated foot during landing may be attributed to the different activation in VL, VM, MG and ST muscles. Adaptations to the biomechanical effects due to the pronated foot causing altered activation of VL, VM, MG, and ST muscles, resulting in an altered pattern of muscle activation. This change in activation pattern may harm the effectiveness of movement control processes; and might also predispose individuals with pronated foot to injuries. It seems that an altered motor strategy with the aim of minimizing biomechanical changes, predisposes individuals to injuries. However, further large scale studies are needed to support the findings of the present study.



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An attempt to explain the Vojta therapy mechanism of action using the surface polyelectromyography in healthy subjects: A pilot study

Publication date: Available online 21 July 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Ewa Gajewska, Juliusz Huber, Aleksandra Kulczyk, Joanna Lipiec, Magdalena Sobieska
BackgroundRehabilitation according to Vojta is a neurophysiological method used to obtain reflex responses in muscles following stimulation of particular activation zones.Objectives: This study aims to objectively evaluate the muscular responses following stimulation according to Vojta's method. The possible routes of spinal transmission responsible for the phenomenon of muscle activation in upper and lower extremities are considered.MethodsPolyelectromyographic (pEMG) recordings in the upper and lower extremities in healthy volunteers (N = 25; aged 24 ± 1 year) were performed to find out the possible routes of spinal transmission, responsible for muscle activation. The left acromion and right femoral epicondyle were stimulated by a Vojta therapist; pEMG recordings were made including the bilateral deltoid and rectus femoris muscles.Resultsand Discussion: Following acromion stimulation, muscle activation was mostly expressed in the contralateral rectus femoris, rather than the contralateral deltoid and the ipsilateral rectus femoris muscles. After stimulation of the lower femoral epicondyle, the following order was observed: contra lateral deltoid, ipsilateral deltoid and the contra lateral rectus femoris muscle.One of the candidates responsible for the main crossed neural transmission involved in the Vojta therapy mechanism would be the long propriospinal tract neurons.



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A review study to evaluate holmium:YAG laser lithotripsy with flexible ureteroscopy in patients on ongoing oral anticoagulant therapy

Abstract

The objective of this study was to evaluate the safety and efficacy of flexible ureteroscopy (FURS) and holmium:YAG laser lithotripsy for the treatment of upper urinary tract stones in patients on active oral anticoagulants. The records of 1081 patients who underwent flexible ureteroscopic holmium:YAG (Ho:YAG) laser lithotripsy for upper ureteral and renal calculi from 1999 to 2015 were retrospectively reviewed. A total of 84 patients on continuous oral anticoagulation or antiplatelet therapy (warfarin, aspirin, or clopidogrel) were identified. Of these patients, 40 were on warfarin, 25 on aspirin, 11 on clopidogrel, and 8 on both aspirin and clopidogrel. The drugs were not discontinued. The baseline characteristics, indications for anticoagulation therapy, perioperative data, stone-free rate, and complications were documented. Evaluation of outcomes was assessed at 1-, 3-, and 6-month follow-up postoperatively. Mean stone size was 19.7 ± 9.4 (range 8 to 31 mm). Twenty patients had upper ureteral and 64 patients had intrarenal calculi. Two patients had bilateral renal calculi. Mean operation time was 78.2 ± 23.8 min (range 17 to 144 min). Two procedures (2.3%) in warfarin group were terminated due to persistent bleeding causing visual impairment. No transfusions were required. The mean serum hemoglobin levels did not change significantly (12.9 ± 3.7 to 12.2 ± 3.3 g/dL). No thromboembolic or cardiac adverse events were observed perioperatively. The double-j (DJ) ureteral catheterization time was 29.6 ± 9.3 days (range 14 to 68 days) and the hospital stay was 1.6 ± 0.6 days (range 1 to 4). The stone-free rate was 95.2% (80 patients) at 6 months. Flexible ureteroscopic Ho:YAG laser lithotripsy in patients requiring long-term anticoagulation therapy seems to be a safe and effective procedure and should be considered as a first-line treatment option in such patients for the surgical management of upper urinary tract stones.

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To4, the first Tityus obscurus β-toxin fully electrophysiologically characterized on human sodium channel isoforms

Publication date: Available online 21 July 2017
Source:Peptides
Author(s): Harry Morales Duque, Caroline Barbosa Farias Mourão, Diogo Vieira Tibery, Eder Alves Barbosa, Leandro Ambrósio Campos, Elisabeth Ferroni Schwartz
Many scorpion toxins that act on sodium channels (NaScTxs) have been characterized till date. These toxins may act modulating the inactivation or the activation of sodium channels and are named α- or β-types, respectively. Some venom toxins from Tityus obscurus (Buthidae), a scorpion widely distributed in the Brazilian Amazon, have been partially characterized in previous studies; however, little information about their electrophysiological role on sodium ion channels has been published. In the present study, we describe the purification, identification and electrophysiological characterization of a NaScTx, which was first described as Tc54 and further fully sequenced and renamed To4. This toxin shows a marked β-type effect on different sodium channel subtypes (hNav1.1–hNav1.7) at low concentrations, and has more pronounced activity on hNav1.1, hNav1.2 and hNav1.4. By comparing To4 primary structure with other Tityus β-toxins which have already been electrophysiologically tested, it is possible to establish some key amino acid residues for the sodium channel activity. Thus, To4 is the first toxin from T. obscurus fully electrophysiologically characterized on different human sodium channel isoforms.



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Managing metastatic bone pain: New perspectives, different solutions

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Iwona Zaporowska-Stachowiak, Jacek Łuczak, Karolina Hoffmann, Katarzyna Stachowiak, Wiesław Bryl, Maciej Sopata
Bone metastases are the most frequent cause of cancer-induced bone pain (CIBP). Although palliative radiotherapy and pharmacotherapy conducted according to World Health Organization (WHO) analgesic ladder are the treatment of choice for CIBP reduction, these methods are not always successful, especially with regard to alleviation of incidental pain. Antiresorptive drugs (bisphosphonates) are able to inhibit bone destruction (loss), proliferation of cancer cells and angiogenesis, but their prolonged use may lead to a spectrum of adverse effects. In this paper, types of bone metastases, their complications, as well as diagnostic and therapeutic implications are presented. Moreover, the paper discusses presently used CIBP treatment methods and research directions for future methods, with special focus on bone metastases.



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Proteomic analysis of the secretome of human bone marrow-derived mesenchymal stem cells primed by pro-inflammatory cytokines

Publication date: Available online 21 July 2017
Source:Journal of Proteomics
Author(s): Elisa Maffioli, Nonnis Simona, Roberta Angioni, Fabiana Santagata, Bianca Calì, Lucia Zanotti, Armando Negri, Antonella Viola, Gabriella Tedeschi
Mesenchymal stem cells (MSC) represent an impressive opportunity in term of regenerative medicine and immunosuppressive therapy. Although it is clear that upon transplantation MSC exert most of their therapeutic effects through the secretion of bioactive molecules, the effects of a pro-inflammatory recipient environment on MSC secretome have not been characterized. In this study, we used a label free mass spectrometry based quantitative proteomic approach to analyze how pro-inflammatory cytokines modulate the composition of the human MSC secretome. We found that pro-inflammatory cytokines have a strong impact on the secretome of human bone marrow-derived MSC and that the large majority of cytokine-induced proteins are involved in inflammation and/or angiogenesis. Comparative analyses with results recently obtained on mouse MSC secretome stimulated under the same conditions reveals both analogies and differences in the effect of pro-inflammatory cytokines on MSC secretome in the two organisms. In particular, functional analyses confirmed that tissue inhibitor of metalloproteinase-1 (TIMP1) is a key effector molecule responsible for the anti-angiogenic properties of both human and mouse MSC within an inflammatory microenvironment. Mass spectrometry data are available via ProteomeXchange with identifier PXD005746SignificanceThe secretion of a broad range of bioactive molecules is believed to be the main mechanism by which MSC exert specific therapeutic effects. MSC are very versatile and respond to specific environments by producing and releasing a variety of effector molecules. To the best of our knowledge this is the first study aimed at describing the secretome of human MSC primed using a mixture of cytokines, to mimic pro-inflammatory conditions encountered in vivo, by a quantitative high-resolution mass spectrometry based approach. The main output of the study concerns the identification of a list of specific proteins involved in inflammation and angiogenesis which are overrepresented in stimulated MSC secretome. The data complement a previous study on the secretome of mouse MSC stimulated under the same conditions. Comparative analyses reveal analogies and differences in the biological processes affected by overrepresented proteins in the two organisms. In particular, the key role of TIMP-1 for the anti-angiogenic properties of stimulated MSC secretome already observed in mouse is confirmed in human. Overall, these studies represent key steps necessary to characterize the different biology of MSC in the two organisms and design successful pre-clinical experiments as well as clinical trials.

Graphical abstract

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Revisiting venom of the sea anemone Stichodactyla haddoni: Omics techniques reveal the complete toxin arsenal of a well-studied sea anemone genus

Publication date: Available online 21 July 2017
Source:Journal of Proteomics
Author(s): Bruno Madio, Eivind A.B. Undheim, Glenn F. King
More than a century of research on sea anemone venoms has shown that they contain a diversity of biologically active proteins and peptides. However, recent omics studies have revealed that much of the venom proteome remains unexplored. We used, for the first time, a combination of proteomic and transcriptomic techniques to obtain a holistic overview of the venom arsenal of the well-studied sea anemone Stichodactyla haddoni. A purely search-based approach to identify putative toxins in a transcriptome from tentacles regenerating after venom extraction identified 508 unique toxin-like transcripts grouped into 63 families. However, proteomic analysis of venom revealed that 52 of these toxin families are likely false positives. In contrast, the combination of transcriptomic and proteomic data enabled positive identification of 23 families of putative toxins, 12 of which have no homology known proteins or peptides. Our data highlight the importance of using proteomics of milked venom to correctly identify venom proteins/peptides, both known and novel, while minimizing false positive identifications from non-toxin homologues identified in transcriptomes of venom-producing tissues. This work lays the foundation for uncovering the role of individual toxins in sea anemone venom and how they contribute to the envenomation of prey, predators, and competitors.Biological significanceProteomic analysis of milked venom combined with analysis of a tentacle transcriptome revealed the full extent of the venom arsenal of the sea anemone Stichodactyla haddoni. This combined approach led to the discovery of 12 entirely new families of disulfide-rich peptides and proteins in a genus of anemones that have been studied for over a century.

Graphical abstract

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Predation by female chimpanzees: Toward an understanding of sex differences in meat acquisition in the last common ancestor of Pan and Homo

Publication date: September 2017
Source:Journal of Human Evolution, Volume 110
Author(s): Ian C. Gilby, Zarin P. Machanda, Robert C. O'Malley, Carson M. Murray, Elizabeth V. Lonsdorf, Kara Walker, Deus C. Mjungu, Emily Otali, Martin N. Muller, Melissa Emery Thompson, Anne E. Pusey, Richard W. Wrangham
Among modern foraging societies, men hunt more than women, who mostly target relatively low-quality, reliable resources (i.e., plants). This difference has long been assumed to reflect human female reproductive constraints, particularly caring for and provisioning mates and offspring. Long-term studies of chimpanzees (Pan troglodytes) enable tests of hypotheses about the possible origins of human sex differences in hunting, prior to pair-bonding and regular provisioning. We studied two eastern chimpanzee communities (Kasekela, Mitumba) in Gombe, Tanzania and one (Kanyawara) in Kibale, Uganda. Relative to males, females had low hunting rates in all three communities, even where they encountered red colobus monkeys (the primary prey of chimpanzees) as often as males did. There was no evidence that clinging offspring hampered female hunting. Instead, consistent with the hypothesis that females should be more risk-averse than males, females at all three sites specialized in low-cost prey (terrestrial/sedentary prey at Gombe; black and white colobus monkeys at Kanyawara). Female dominance rank was positively correlated with red colobus hunting probability only at Kasekela, suggesting that those in good physical condition were less sensitive to the costs of possible failure. Finally, the potential for carcass appropriation by males deterred females at Kasekela (but not Kanyawara or Mitumba) from hunting in parties containing many adult males. Although chimpanzees are not direct analogs of the last common ancestor (LCA) of Pan and Homo, these results suggest that before the emergence of social obligations regarding sharing and provisioning, constraints on hunting by LCA females did not necessarily stem from maternal care. Instead, they suggest that a risk-averse foraging strategy and the potential for losing prey to males limited female predation on vertebrates. Sex differences in hunting behavior would likely have preceded the evolution of the sexual division of labor among modern humans.



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Hand rejuvenation with fat grafting: A 12-year single-surgeon experience

Abstract

Background

Fat grafting has been successfully used for reconstructive and esthetic surgery of the breast, face, and other body parts. In this article, we present our protocol for hand fat grafting and over a decade of clinical experience.

Methods

Fat tissue is obtained from the flanks, peri-umbilical region, or internal side of the thigh or knee. No centrifuge machine is used to prevent fat damage. After decantation, fat is injected into the dorsum of the hand using a cannula from the wrist and not from the fingers. Fat is distributed gently above the dorsal deep fascia to avoid perforation of the vessels.

Results

The proposed technique was applied to 65 patients. The amount of fat injected ranged from 10 to 30 cm³. No allergic reactions were noticed. Each patient's progress was followed-up for a minimum of 12 months. Over this period, contour changes and the effects of the procedure(s) on the skin were analyzed. Fifty-six patients (84%) were satisfied with the results during the observation period, 7 patients (12%) were somewhat satisfied and needed one more fat grafting procedure to achieve complete satisfaction, and 2 patients (4%) were dissatisfied with the results. Three cases of temporary swelling of the hands resolved naturally. No long-term complications were seen.

Conclusions

This study covers over a decade of practical experience in applying fat grafts to hands. The procedure is effective in reshaping and rejuvenating the hand as it shows long-lasting results after 1-year follow-up.

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Types of strain among family members of individuals with autism spectrum disorder across the lifespan

Publication date: September 2017
Source:Research in Developmental Disabilities, Volume 68
Author(s): Carolyn M. Shivers, Katarina Krizova, Gloria K. Lee
BackgroundAlthough increased caregiver strain is often found among family caregivers of individuals with autism spectrum disorder, it is still unclear as to how different types of strain relate to amount and types of caregiving across the lifespan.AimsThe present study examined different types of strain (i.e. subjective internalized strain, subjective externalized strain, and objective strain) and how such strain relates to the amount of caregiving responsibilities.MethodsData was collected via online survey from a sample of 193 family caregivers of individuals with ASD from the United States, Canada, and the Republic of Ireland. Participants completed measures of strain and caregiving responsibilities, as well as coping, demographics, and services needed and received by the individual with ASD.ResultsCaregivers reported higher levels of objective strain than subjective, and caregiving responsibility was related to objective and subjective internalized strain. Coping style was strongly correlated with all types of strain, and unmet service needs were significantly related to objective and subjective internalized strain. Caregiving behaviors were only related to objective strain.ConclusionThe present results indicate that, although caregiving responsibility is related to objective and subjective internalized strain, the relationship is perhaps not as strong as the relationship between coping mechanisms and strain. Future research is needed to understand different types of strain and develop strategies to help caregivers.



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Self-efficacy of physical education teachers in including students with cerebral palsy in their classes

Publication date: September 2017
Source:Research in Developmental Disabilities, Volume 68
Author(s): Yeshayahu Hutzler, Sharon Barak
Children with cerebral palsy (CP) are often mainstreamed into the general education system, but are likely to be excluded from physical education (PE) classes. A questionnaire was constructed and utilized to measure PE teachers' self-efficacy (SE) toward inclusion of students with CP in each of three mobility categories (independent, using assistive devices, using wheelchair mobility) and the impact of experience and training on teachers' SE. Participants in the study were 121 PE teachers from different parts of Israel (mean age: 41.02±9.33 years; range: 25.00–59.00 years). Exploratory factor analysis was used to determine the structure of the sub-scales' factors' structure and Cronbach's Alpha reliability was satisfactory (range 0.872–0.941). Independent t-tests were calculated in order to compare the SE of teachers with and without adapted PE experience. Repeated Analysis of Variance was performed to measure within-group differences in SE. Results revealed that the PE teachers' SE in teaching students who use mobility assistive devices or wheelchairs was significantly lower compared to teaching those who walk and run unaided (F=19.11; p<0.001). The teachers' SE towards including CP children who independently ambulate was influenced (p<0.05; d=0.94) by the teacher's experience (elementary school practicum). SE in the mobility with assistive device group was also significantly influenced (p<0.05; d=0.1) by teaching experience (previous experience and having a specialization in adapted PE). Finally, SE when teaching the wheelchair mobility group was influenced by having an adapted PE specialization (p<0.05; d=0.82). Specialized training in this particular area should be enhanced to increase teachers' SE and enable greater participation of children with CP in general physical education classes



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Thinking inside the box: Spatial frames of reference for drawing in Williams syndrome and typical development

Publication date: September 2017
Source:Research in Developmental Disabilities, Volume 68
Author(s): Kerry D. Hudson, Emily K. Farran
BackgroundSuccessfully completing a drawing relies on the ability to accurately impose and manipulate spatial frames of reference for the object that is being drawn and for the drawing space. Typically developing (TD) children use cues such as the page boundary as a frame of reference to guide the orientation of drawn lines. Individuals with Williams syndrome (WS) typically produce incohesive drawings; this is proposed to reflect a local processing bias.AimsAcross two studies, we provide the first investigation of the effect of using a frame of reference when drawing simple lines and shapes in WS and TD groups (matched for non-verbal ability).Methods and proceduresIndividuals with WS (N=17 Experiment 1; N=18 Experiment 2) and TD children matched by non-verbal ability drew single lines (Experiment One) and whole shapes (Experiment Two) within a neutral, incongruent or congruent frame. The angular deviation of the drawn line/shape, relative to the model line/shape, was measured.Outcomes and resultsBoth groups were sensitive to spatial frames of reference when drawing single lines and whole shapes, imposed by a frame around the drawing space.Conclusions and implicationsA local processing bias in WS cannot explain poor drawing performance in WS.



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Bioaccumulation kinetics of arsenite and arsenate in Dunaliella salina under different phosphate regimes

Abstract

Dunaliella salina is a potential candidate for the phycoremediation of saline water contaminated with arsenic (As) due to its strong tolerance of salt and this toxic metalloid. However, the efficiency of As removal by this microalga varies under different phosphate regimes and the underlying mechanisms remain unresolved. Therefore, more detailed studies are needed to optimize As remediation using D. salina. Here, we investigated the dynamic processes of arsenite (As(III)) and arsenate (As(V)) uptake, transformation, and excretion by D. salina under phosphate-deficient (−P) and phosphate-enriched (+P) conditions through short-term and long-term uptake experiments. In the short-term uptake experiment, the absorption of As(III) or As(V) by D. salina was significantly suppressed by an increased phosphate supply. The V _max values for As(III) and As(V) decreased by 2- and 2.5-fold, respectively, under +P conditions, although the Michaelis constants (K _m ) were similar irrespective of the phosphate supply. Long-term uptake experiments also revealed enhanced As(III)/As(V) absorption and efflux rates and As(V) reduction by D. salina under −P conditions. This study quantified the kinetic processes of As metabolism in D. salina. More importantly, the results imply that the optimal As remediation by this microalga may be achieved by regulating the phosphate level in the culture.

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Concentrations and inhalation risk assessment of short-chain polychlorinated paraffins in the urban air of Dalian, China

Abstract

The concentrations of short-chain polychlorinated paraffins (SCCPs) in the urban air of Dalian, China, were monitored from March to October 2010 and from September to October 2016 with active high-volume sampler. The total concentration of SCCPs (particulate phase + gas phase) ranged from 15.12 to 66.44 ng m⁻³, with an average of 30.26 ng m⁻³ in 2010, and 65.30 to 91.00 ng m⁻³, with an average of 78.15 ng m⁻³ in 2016. Hexa-chlorinated dodecane and hexa-chlorinated undecane are the predominant components in the gas phase, while octa-chlorinated undecane and hepta-chlorinated tridecane are dominant in the particulate phase. In 2010, 82.57–97.16% of the total SCCPs were found in the gas phase, except that in winter, where 63.11% of the total SCCPs were in the particulate phase; the air concentrations of SCCPs in gas phase were summer > autumn > spring > winter, which was positively correlated with the change of the average ambient temperature, while it was the contrary in particulate phase. In autumn, the gas phase and the total air concentration of SCCPs in 2016 were 2.57 times more than that in 2010, while the congener group patterns of SCCPs were similar. Spearman's rank correlation analysis between the concentrations of SCCPs with meteorological parameters was conducted. The gas-particle distribution was examined through the relationship of the logarithm of the gas-particle partition coefficient with that of the subcooled vapor pressure and the octanol-air partitioning coefficient of SCCPs. Results indicated that the absorption mechanisms contributed more to the partitioning process. The exposure risk of SCCPs was evaluated, which illustrated that the estimated exposure of SCCPs via the outdoor environment in Dalian did not exceed the health concern threshold of the European risk assessment.

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Zero-valent iron particles for PCB degradation and an evaluation of their effects on bacteria, plants, and soil organisms

Abstract

Two types of nano-scale zero-valent iron (nZVI-B prepared by borohydride reduction and nZVI-T produced by thermal reduction of iron oxide nanoparticles in H₂) and a micro-scale ZVI (mZVI) were compared for PCB degradation efficiency in water and soil. In addition, the ecotoxicity of nZVI-B and nZVI-T particles in treated water and soil was evaluated on bacteria, plants, earthworms, and ostracods. All types of nZVI and mZVI were highly efficient in degradation of PCBs in water, but had little degradation effect on PCBs in soil. Although nZVI-B had a significant negative impact on the organisms tested, treatment with nZVI-T showed no negative effect, probably due to surface passivation through controlled oxidation of the nanoparticles.

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Thoracic paravertebral block for postoperative pain management after renal surgery: A randomised controlled trial.

BACKGROUND: Thoracic paravertebral block (ThPVB) combined with general anaesthesia is used in thoracic and general surgery. It provides effective analgesia, reduces surgical stress response and the incidence of chronic postoperative pain. OBJECTIVE: To assess the efficacy of ThPVB in reducing opioid requirements and decreasing the intensity of pain after renal surgery. DESIGN: A prospective, randomised, open label study. SETTING: A single university hospital. Study conducted from August 2013 to February 2014. PARTICIPANTS: In total, 68 patients scheduled for elective renal surgery (open nephrectomy or open nephron-sparing surgery). INTERVENTIONS: Preoperative ThPVB with 0.5% bupivacaine combined with general anaesthesia, followed by postoperative oxycodone combined with nonopioid analgesics as rescue drugs. Follow-up period: 48 h. MAIN OUTCOME MEASURES: Total dose of postoperative oxycodone required, pain intensity, occurrence of opioid related adverse events, ThPVB-related adverse events and patient satisfaction. RESULTS: A total of 68 patients were randomised into two groups and, of these, 10 were subsequently excluded from analysis. Patients in group paravertebral block (PVB; n = 27) had general anaesthesia and ThPVB, and those in group general (anaesthesia) (GEN) (n = 31) formed a control group receiving general anaesthesia only. Compared with patients in group GEN, patients who received ThPVB required 39% less i.v. oxycodone over the first 48 h and had less pain at rest (P

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Injectate spread following anterior sub-costal and posterior approaches to the quadratus lumborum block: A comparative cadaveric study.

BACKGROUND: The dermatomal level of analgesia achieved with quadratus lumborum blocks varies according to the location of injection. The most commonly used approaches are either at the postero-lateral aspect or anterior to the quadratus lumborum muscle. The aim of the study was to determine whether the site of injection of contrast dye around the quadratus lumborum muscle of cadavers affects the extent and mechanism of dye spread. METHODS: Six fresh human cadavers received either a posterior quadratus lumborum block or an anterior sub-costal quadratus lumborum block on each side. Cadavers were then dissected to determine the extent of dye spread. RESULTS: The posterior quadratus lumborum block approach revealed consistently deep staining of the iliohypogastric, ilioinguinal, subcostal nerve, T11 to 12 and L1 nerve roots. In addition, staining of the middle thoracolumbar fascia was seen in all specimens but only variable staining of T10 nerve roots. The anterior subcostal quadratus lumborum block approach in all specimens demonstrated predictable deep staining of the iliohypogastric and ilioinguinal nerves, subcostal nerves, T11 to 12 and L1 nerve roots, and in addition traversing the arcuate ligaments to involve T9 to 12 nerve roots with variable staining of higher thoracic nerve roots. CONCLUSION: Our cadaveric study demonstrates that injection of dye on the posterior aspect of quadratus lumborum muscle led to injectate spread through the lateral and posterior abdominal wall but with limited cranial spread, whereas the anterior approach produced broader coverage of the lower to mid-thoracic region. Clinical translation of these findings to determine the practical significance is warranted. (C) 2017 European Society of Anaesthesiology

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Serious game versus online course for pretraining medical students before a simulation-based mastery learning course on cardiopulmonary resuscitation: A randomised controlled study.

BACKGROUND: Although both recorded lectures and serious games have been used to pretrain health professionals before simulation training on cardiopulmonary resuscitation, they have never been compared. OBJECTIVE: The aim of this study was to compare an online course and a serious game for pretraining medical students before simulation-based mastery learning on the management of sudden cardiac arrest. DESIGN: A randomised controlled trial. Participants were pretrained using the online course or the serious game on day 1 and day 7. On day 8, each participant was evaluated repeatedly on a scenario of cardiac arrest until reaching a minimum passing score. SETTING: Department of Simulation in Healthcare in a French medical faculty. PARTICIPANTS: Eighty-two volunteer second-year medical students participated between June and October 2016 and 79 were assessed for primary outcome. INTERVENTIONS: The serious game used was Staying Alive, which involved a 3D realistic environment, and the online course involved a PowerPoint lecture. MAIN OUTCOME MEASURES: The median total training time needed for students to reach the minimum passing score on day 8. This same outcome was also assessed 4 months later. RESULTS: The median training time (interquartile range) necessary for students to reach the minimum passing score was similar between the two groups: 20.5 (15.8 to 30.3) minutes in the serious game group versus 23 (15 to 32) minutes in the online course group, P = 0.51. Achieving an appropriate degree of chest compression was the most difficult requirement to fulfil for students in both groups. Four months later, the median training time decreased significantly in both groups, but no correlation was found at an individual level with the training times observed on day 8. CONCLUSION: The serious game used in this study was not superior to an online course to pretrain medical students in the management of a cardiac arrest. The absence of any correlation between the performances of students evaluated during two training sessions separated by 4 months suggests that elements such as chest compression can only be learned by simulation-based training. TRIAL REGISTRATION: ClinicalTrials.gov-NCT02758119. (C) 2017 European Society of Anaesthesiology

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Crocin modulates IL-4/IL-13 signaling and ameliorates experimentally induced allergic airway asthma in a murine model

Publication date: September 2017
Source:International Immunopharmacology, Volume 50
Author(s): Haidy Yosri, Wagdi F. Elkashef, Eman Said, Nariman M. Gameil
Allergic asthma is a chronic respiratory disease with a prevalent T helper (Th2)-mediated immune reaction. Crocin, the major bioactive constituent of saffron, has been reported in multiple studies to have numerous pharmacological activities, including prominent anti-oxidant activities. In the current study, the anti-asthmatic potential of crocin was evaluated. Adult male Swiss Albino mice were administered 10mg of ovalbumin (OVA) mixed with 1mg of aluminum hydroxide intraperitoneally on days 0 and 7 and were administered crocin (25mg/kg) orally daily for 16days. Asthma progression was associated with significant increase in the lung/body weight index, inflammatory cell counts in bronchoalveolar lavage fluid (BALF), lung total protein content, and serious index of lung permeability, indicating pulmonary edema with accumulation of serous fluids within the lungs. Serum lactate dehydrogenase (LDH) activity and lung malondialdehyde (MDA) content were significantly increased, while lung superoxide dismutase (SOD) activity, reduced glutathione (GSH) levels, and serum and lung catalase activities were significantly decreased. These changes reflect significant pulmonary inflammation with concomitant disturbance of oxidant/antioxidant homeostasis. Moreover, tumor necrosis factor (TNF)-α, interleukin (IL)-4, and IL-13 contents in the lung were also significantly high after OVA sensitization. Crocin treatment significantly alleviated the OVA-induced allergic asthma-associated alterations in inflammatory and oxidative stress biomarkers. Crocin enhanced anti-oxidant defenses, reduced the incidence of oxidative stress, and restored pro-inflammatory cytokines to normal levels. Histopathological analysis showed significant lung improvement in crocin-treated mice. In conclusion, crocin showed a significant protective effect against allergic asthma progression, which was associated with down-regulation of inflammatory cytokine expression and restoration of oxidant/antioxidant homeostasis.



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Asiatic acid inhibits LPS-induced inflammatory response in human gingival fibroblasts

Publication date: September 2017
Source:International Immunopharmacology, Volume 50
Author(s): Chunbo Hao, Buling Wu, Zhiming Hou, Qi Xie, Tianan Liao, Tao Wang, Dandan Ma
Asiatic acid, a triterpenoid component isolated from Centella asiatica (L.) Urban, possesses antioxidative and anti-inflammatory activities. In this study, we aimed to investigate the anti-inflammatory effects of asiatic acid both in vivo and in vitro. HGFs or RAW264.7 cells were treated with asiatic acid 1h before LPS treatment. Cell viability was measured by MTT assay. The levels of PGE2, NO, IL-6, and IL-8 were detected by ELISA. Protein expression levels were detected by western blot analysis. In vivo, asiatic acid significantly inhibited LPS-induced IL-6 and IL-8 expression levels in gingival tissues. In vitro, LPS-induced PGE2, NO, IL-6, and IL-8 production was significantly attenuated by asiatic acid. Asiatic acid also inhibited p65 NF-κB phosphorylation induced by LPS in HGFs. The expression of PPAR-γ was up-regulated by asiatic acid. Furthermore, GW9662, a PPAR-γ inhibitor, attenuated the inhibitory effect of asiatic acid on PGE2, NO, IL-6, and IL-8 production. Our results suggest that asiatic acid activates PPAR-γ, which subsequently inhibits LPS-induced NF-κB activation and inflammatory mediators production. Asiatic acid may offer therapeutic potential for the treatment of periodontitis.



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Large improvement of RF transmission efficiency and reception sensitivity for human in vivo 31P MRS imaging using ultrahigh dielectric constant materials at 7T

Publication date: Available online 21 July 2017
Source:Magnetic Resonance Imaging
Author(s): Byeong-Yeul Lee, Xiao-Hong Zhu, Sebastian Rupprecht, Michael T. Lanagan, Qing X. Yang, Wei Chen
In vivo³¹P MRS provides a unique and important imaging tool for studying high-energy phosphate metabolism and bioenergetics noninvasively. However, compared to ¹H MRS, ³¹P MRS with a relatively low gyromagnetic ratio (γ) has a lower and limited sensitivity even at ultrahigh field. The proof of concept has been recently demonstrated that the use of high dielectric constant (HDC) materials between RF coil and object sample could increase MRI signal and reduce required RF transmission power for reaching the same RF pulse flip angle in the region of interest. For low-γ MRS applications operated at relatively lower frequency, however, it demands the dielectric materials with a much higher permittivity for achieving optimal performance. We conducted a ³¹P MRS imaging study using ultra-HDC (uHDC; with a relative permittivity of ~1200) material blocks incorporated with an RF volume coil at ultrahigh field of 7.0T. The experimental results from phantom and human calf muscle demonstrate that the uHDC technique significantly enhanced RF magnetic transmit field (B1⁺) and reception field (B1⁻) and the gain could reach up to two folds in the tissue near the uHDC blocks. The overall results indicate that the incorporation of the uHDC materials having an appropriate permittivity value with a RF coil can significantly increase detection sensitivity and reduces RF transmission power for X-nuclei MRS applications at ultrahigh field. The uHDC technology could provide an efficient, cost-effective engineering solution for achieving high detection sensitivity and concurrently minimizing tissue heating concern for human MRS and MRI applications.



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Rat brain digital stereotaxic white matter atlas with fine tract delineation in Paxinos space and its automated applications in DTI data analysis

Publication date: Available online 21 July 2017
Source:Magnetic Resonance Imaging
Author(s): Shengxiang Liang, Shang Wu, Qi Huang, Shaofeng Duan, Hua Liu, Yuxiao Li, Shujun Zhao, Binbin Nie, Baoci Shan
PurposeTo automatically analyze diffusion tensor images of the rat brain via both voxel-based and ROI-based approaches, we constructed a new white matter atlas of the rat brain with fine tracts delineation in the Paxinos and Watson space.Materials and methodsUnlike in previous studies, we constructed a digital atlas image from the latest edition of the Paxinos and Watson. This atlas contains 111 carefully delineated white matter fibers. A white matter network of rat brain based on anatomy was constructed by locating the intersection of all these tracts and recording the nuclei on the pathway of each white matter tract. Moreover, a compatible rat brain template from DTI images was created and standardized into the atlas space. To evaluate the automated application of the atlas in DTI data analysis, a group of rats with right-side middle cerebral artery occlusion (MCAO) and those without were enrolled in this study.ResultsThe voxel-based analysis result shows that the brain region showing significant declines in signal in the MCAO rats was consistent with the occlusion position.ConclusionWe constructed a stereotaxic white matter atlas of the rat brain with fine tract delineation and a compatible template for the data analysis of DTI images of the rat brain.



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Biological effects of citalopram in a suspended sediment-water system on Daphnia magna

Abstract

Suspended sediment (SPS) plays an important role in the aquatic ecosystems. Selective serotonin uptake inhibitors (SSRIs) are commonly used antidepressants and are frequently detected in aquatic environments. However, the biological effects of SSRIs in the presence of SPS are not well understood. To fill this gap, an SPS-water system was constructed to investigate the effects of citalopram (CIT) on Daphnia magna in the presence of SPS with different concentrations (0.1, 0.5, 1 g l⁻¹) and organic carbon contents (0.5, 1, 1.5, 2%). A dialysis bag was applied in the exposure system to control the same dissolved concentration of CIT and prevent SPS from entering into the bag. The dissolved CIT concentration obviously decreased in the SPS-water system during the exposure period. The presence of SPS significantly increased the immobilization of D. magna, and the immobilization rates were positively correlated with the SPS concentration and negatively correlated with the organic carbon content in SPS. For a single exposure, CIT significantly increased superoxide dismutase (SOD) activity and inhibited acetylcholinesterase (AChE) activity in D. magna, while SPS itself did not change the SOD and AChE activities. In the SPS-water system, SOD activity was significantly suppressed, indicating that the SPS-CIT combination could result in oxidative damage. However, SPS did not enhance the neurotoxicity of D. magna that was induced by CIT. These results suggest that SPS exerts a vital role on the biological effects of CIT and the contaminants sorbed on SPS should be taken into consideration.

http://ift.tt/2uIAIOq

Gaining ethnoarchaeological insight into prehistoric southern African pigment mining practices

Publication date: December 2017
Source:Journal of Anthropological Archaeology, Volume 48
Author(s): Riaan F. Rifkin
Although the exploitation of ochre and its role in the emergence of modern human behaviour has been afforded substantial academic consideration, inquiries into ochre procurement strategies remain limited. Since the systematic exploitation of red ochre is widely viewed as symptomatic of increasing cognitive complexity, the persistence of this behaviour amongst extant sub-Saharan African groups is significant in terms of human behavioural aspects observed in the archaeological record. The aim of this paper is to provide insight into prehistoric ochre procurement strategies by presenting an account of the methods implicated in the extraction of red ochre by the Ovahimba of the Kunene Region, north-western Namibia. I draw correlations between prehistoric and modern traditional mining practices and show that ethnoarchaeological research provides a basis for the formulation and assessment of archaeological research questions. I focus on the primary source of red ochre in the Kunene Region, the Ombumbuu ochre quarries, and employ visible spectroscopy, energy-dispersive X-ray fluorescence (ED-XRF), X-ray diffraction (XRD) and scanning electron microscopy and energy dispersive X-ray spectrometry (SEM-EDS) to characterise ochre from this resource. I also explore the evolutionary impact that the habitual exploitation of red ochre might have had on prehistoric human adaptive strategies and assert that these played an important role in increasing human survivability and cumulative cultural capacity.



http://ift.tt/2uhxK2s

Primary Signet Ring Stromal Tumor of the Testis: A Study of 13 Cases Indicating Their Phenotypic and Genotypic Analogy to Pancreatic Solid Pseudopapillary Neoplasm

Publication date: Available online 21 July 2017
Source:Human Pathology
Author(s): Kvetoslava Michalova, Michael Michal, Dmitry V. Kazakov, Monika Sedivcova, Ondrej Hes, Ladislav Hadravsky, Abbas Agaimy, Maria Tretiakova, Carlos Bacchi, Arndt Hartmann, Naoto Kuroda, Stela Bulimbasic, Marijana Coric, Tatjana Antic, Michal Michal
Primary signet ring stromal tumor of the testis (PSRSTT) is an extremely rare tumor described only twice in the literature. Pancreatic-analogue solid pseudopapillary neoplasm (SPN) of the testis is a recently reported entity with morphological overlap with PSRSTT. We reviewed our files to find all cases of PSRSTT in order to better characterize this entity. We studied 13 cases of PSRSTTs using histological, immunohistochemical (IHC) and molecular genetic methods and compared the results with pancreatic SPN. Grossly, the size of PSRSTTs ranged from 0.5 to 2 cm (mean 1.1). Microscopically, PSRSTTs predominantly showed a proliferation of low-grade epithelioid cells containing characteristic cytoplasmic vacuole dislodging the nucleus (signet ring cells) separated by fibrous septa into trabeculae and nests. The immunoprofile was characterized by immunoreactivity for β-catenin, cyclin D1 (nuclear positivity for both antibodies), CD10, vimentin, galectin 3, claudin7, α-1-antitrypsin, CD56, NSE and negativity with chromogranin, inhibin, calretinin, SF-1, NANOG, OCT3/4 and SALL4. In some cases, the IHC panel was restricted due to a limited amount of tissue. Molecular genetic analysis revealed mutations within exon 3 of the CTNNB1 encoding β-catenin in all analyzable cases. Based on histological similarities between pancreatic SPN and PSRSTT and their identical IHC and molecular genetic features, we assume that both neoplasms share the same pathogenesis and thus PSRSTT can be considered as a testicular analogue of pancreatic SPN.



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Increased Expression of EZH2 in Merkel Cell Carcinoma Is Associated with Disease Progression and Poorer Prognosis

Publication date: Available online 21 July 2017
Source:Human Pathology
Author(s): Kelly L. Harms, Heather Chubb, Lili Zhao, Douglas R. Fullen, Christopher K. Bichakjian, Timothy M. Johnson, Shannon Carskadon, Nallasivam Palanisamy, Paul W. Harms
Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that affects tumorigenesis by epigenetic gene silencing. Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine carcinoma that has a high risk of disease progression with nodal and distant metastases. Here, we evaluated EZH2 expression by immunohistochemistry in a cohort of 85 MCC tumors (29 primary tumors, 41 lymph node metastases, 13 in-transit metastases, and 2 distant metastases) with clinical follow-up. We show strong/moderate EZH2 expression in 54% of tumors. Importantly, weak expression of EZH2 in the primary tumor, but not nodal metastases, correlated with improved prognosis compared to moderate/strong EZH2 expression (5-year MCC-specific survival of 68% versus 22%, respectively, P=.024). In addition, EZH2 was expressed at higher levels in nodal metastases compared to primary tumors (P=.005). Our data demonstrate that EZH2 has prognostic value and may play an oncogenic role in MCC.



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Salivary Gland Epithelial Neoplasms in Pediatric Population: a Single Institute Experience with a Focus on the Histologic Spectrum and Clinical Outcome

Publication date: Available online 21 July 2017
Source:Human Pathology
Author(s): Bin Xu, Amandeep Aneja, Ronald Ghossein, Nora Katabi
Salivary gland epithelial neoplasms are rare in children and adolescents with only a handful of large series have been published. A retrospective study was conducted for 57 cases in patients 20years or younger. The tumors were located in the parotid (n=36), submandibular gland (n=7), and minor salivary glands (n=14). 19 (33%) tumors were pleomorphic adenoma, while the remaining (67%) were malignant. The histologic types of carcinomas were mucoepidermoid carcinoma (MEC, n=19, 33%), acinic cell carcinoma (n=7, 12%), adenoid cystic carcinoma (n=6, 11%), secretory carcinoma (mammary analogue) (SC, n=4, 7%), and myoepithelial carcinoma (n=2, 4%). 93% (13/14) of the minor and 58% (25/43) of the major salivary gland tumors were malignant. A seven-year-old girl (2%) with a high grade MEC died from her disease due to uncontrollable locoregional recurrence. Seven patients (16%) developed recurrence including 2 distant metastases from adenoid cystic carcinoma and 6 locoregional recurrences (2 pleomorphic adenomas, 1 SC, 1 myoepithelial carcinoma, 1 adenoid cystic carcinoma, and 1 MEC). The following parameters were associated with decreased disease free survival in malignant tumors: elevated mitotic index of >4/10 HPFs (log rank test, P<.001), advanced AJCC pT (P=.029) and pN stage (P<.001). In conclusion, myoepithelial carcinoma and SC can occur in the pediatric population and should be considered in the differential diagnosis. Salivary gland malignancies in children appear to have better clinical outcome, associated with a 10-year recurrence free survival rate of 74%, and a 10-year disease specific survival of 94%.



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Overexpression of Rabl3 and Cullin7 is associated with pathogenesis and poor prognosis in hepatocellular carcinoma

Publication date: Available online 21 July 2017
Source:Human Pathology
Author(s): Jun An, Zhiyong Liu, Qiong Liang, Yuhang Pan, Haifeng Li, Ruizhi Wang, Yi Jin
The expression of Rabl3 and Cullin7 is relevant to the carcinogenesis of certain cancers. However, the relationship of this expression with hepatocellular carcinoma remains unclear. To study the protein expression of Rabl3 and Cullin7 and to evaluate their role in hepatocarcinogenesis, in 162 cases of hepatocellular carcinoma, we used immunohistochemistry to investigate the expression of Rabl3 and Cullin7 in both the cancer tissues and the normal hepatic tissues around the hepatocellular carcinoma. The results demonstrated that the rates of positive Rabl3 and Cullin7 expression were 80.2% and 69.1%, respectively, in hepatocellular carcinoma tissues. However, the rates of positive Rabl3 and Cullin7 expression were 31.5% and 29.0%, respectively, in adjacent normal hepatic tissues. Rabl3 and Cullin7 were expressed at significantly higher rates in hepatocellular carcinoma compared with adjacent normal hepatic tissues (P<.01). The rates of positive Rabl3 and Cullin7 expression were higher in the hepatocellular carcinoma tissues of patients with lymph node metastasis, tumor thrombi in the portal vein and an advanced clinical stage (P<.05). A positive correlation between the expression of Rabl3 and the expression of Cullin7 (r=0.27, P<.001) was also observed in our hepatocellular carcinoma cohort. Moreover, patients with positive expression for both Rabl3 and Cullin7 had a remarkably shorter survival time compared with patients with negative expression for both proteins (P<.05). Therefore, the expression of the Rabl3 and Cullin7 proteins may play an important role in the pathogenesis and progression of hepatocellular carcinoma and could be used as a prognostic indicator in patients with hepatocellular carcinoma.



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Let’s Make Academic Radiology Great Again

Publication date: September–October 2017
Source:Current Problems in Diagnostic Radiology, Volume 46, Issue 5
Author(s): Michael N. Patlas, Nataly Farshait, Jason N. Itri




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Rapid decay of transthoracic echocardiography skills at 1 month: A prospective observational study

Publication date: Available online 21 July 2017
Source:Journal of Surgical Education
Author(s): Ryo Yamamoto, David Clanton, Ross E. Willis, Rachelle Babbitt Jonas, Ramon F. Cestero
ObjectiveFocused transthoracic echocardiography (FTTE) is an emerging tool in the management of critically ill patients, but the lack of adequate training models has limited the expansion of this technology. Although basic FTTE training courses have been shown to be sufficient in developing echocardiography skills, limited data exist regarding skill retention. In an effort to develop an adequate FTTE training model, we sought to determine the degree of skill retention after FTTE training.DesignA prospective, observational study.SettingAn academic center.ParticipantsSurgical residents and medical students: 31 subjects were enrolled from February to June 2016.ResultsParticipants underwent a 2-hour FTTE course including didactics and a hands-on session measuring ejection fraction of left ventricle (LV) and inferior vena cava (IVC) diameter. Written knowledge and performance examinations applying FTTE were conducted before the course, immediately after, and at 1- and 3-month intervals, which were evaluated on a 0 to 9 scale and analyzed with paired t-tests. Performance examination scores obtaining the LV and IVC views preinitial and postinitial training increased from 1.7 to 6.5 (LV) and from 2.0 to 6.8 (IVC) (p < 0.01), decreased to 5.0 and 4.8, respectively, at 1 month (posttraining vs 1 month, p < 0.01), and did not significantly change at 3 months (5.4 and 5.0, respectively). Written examination scores increased from 42% to 62% (pretraining vs posttraining, p < 0.01), decreased to 48% in 1 month (posttraining vs 1 month, p < 0.01), and further decreased to 34% at 3 months (1 month vs 3 month, p < 0.01).ConclusionsAlthough a short training course appears sufficient to impart basic FTTE skills and knowledge, skills are significantly decayed at 1 month and knowledge continually decreases at 1 and 3 months. Future FTTE training models should consider the rapid degradation of knowledge and skills in determining frequency of refresher training and ongoing evaluation.



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Decreased mortality in patients prescribed vancomycin after implementation of antimicrobial stewardship program

Publication date: Available online 21 July 2017
Source:American Journal of Infection Control
Author(s): Erin L. Conway, John A. Sellick, Amy Horey, Kristen Fodero, Michael C. Ott, Michael P. Krajewski, Kari A. Mergenhagen
BackgroundThe impact of an antimicrobial stewardship program (ASP) on 30-day mortality rates was evaluated in patients prescribed vancomycin in a Veterans Affairs hospital.MethodsA retrospective chart review of patients receiving a minimum of 48 hours of vancomycin during October 2006-July 2014. A multivariate logistic regression analysis was used to determine predictors of mortality. Interventions of the ASP consist of appropriate antibiotic selection, dosing, microbiology, and treatment duration.ResultsDeath occurred in 12.4% of 453 patients. Of the 56 deaths, 64.3% occurred during prestewardship versus 35.7% during stewardship (P = .021). Increased mortality was associated with pre-ASP (odds ratio [OR], 2.17; 95% confidence interval [CI], 1.13-4.27), age (unit OR, 1.08; 95% CI, 1.05-1.12), nephrotoxicity (OR, 3.24; 95% CI, 1.27-8.01), and hypotension (OR, 3.28; 95% CI, 1.42-7.44). Patients treated in the intensive care unit were associated with increased mortality. Patients in the stewardship group experienced lower rates of mortality, which may be caused by interventions initiated by the stewardship team, including minimizing nephrotoxicity and individualized chart review.ConclusionsMortality in patients treated with vancomycin was decreased after antimicrobial stewardship was implemented. As anticipated, older age, hypotension, nephrotoxicity, and intensive care unit admission were associated with an increased incidence of mortality.



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An optimized non-destructive protocol for testing mechanical properties in decellularized rabbit trachea

Publication date: Available online 21 July 2017
Source:Acta Biomaterialia
Author(s): M Den Hondt, BM Vanaudenaerde, EF Maughan, CR Butler, C Crowley, EK Verbeken, SE Verleden, JJ Vranckx
Successful tissue-engineered tracheal transplantation relies on the use of non-immunogenic constructs, which can vascularize rapidly, support epithelial growth, and retain mechanical properties to that of native trachea. Current strategies to assess mechanical properties fail to evaluate the trachea to its physiological limits, and lead to irreversible destruction of the construct. Our aim was to develop and evaluate a novel non-destructive method for biomechanical testing of tracheae in a rabbit decellularization model. To validate the performance of this method, we simultaneously analyzed quantitative and qualitative graft changes in response to decellularization, as well as in-vivo biocompatibility of implanted scaffolds.Rabbit tracheae underwent two, four and eight cycles of detergent-enzymatic decellularization. Biomechanical properties were analyzed by calculating luminal volume of progressively inflated and deflated tracheae with microCT. DNA, glycosaminoglycan and collagen contents were compared to native trachea. Scaffolds were prelaminated in vivo.Native, two- and four-cycle tracheae showed equal mechanical properties. Collapsibility of eight-cycle tracheae was significantly increased from -40 cmH2O (-3.9 kPa). Implantation of two- and four-cycle decellularized scaffolds resulted in favorable flap-ingrowth; eight-cycle tracheae showed inadequate integration.We showed a more limited detergent-enzymatic decellularization successfully removing non-cartilaginous immunogenic matter without compromising extracellular matrix content or mechanical stability. With progressive cycles of decellularization, important loss of functional integrity was detected upon mechanical testing and in-vivo implantation. This instability was not revealed by conventional quantitative nor qualitative architectural analyses. These experiments suggest that non-destructive, functional evaluation, e.g. by microCT, may serve as an important tool for mechanical screening of scaffolds before clinical implementation.

Graphical abstract

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In-situ tissue regeneration through SDF-1α driven cell recruitment and stiffness-mediated bone regeneration in a critical-sized segmental femoral defect

Publication date: Available online 21 July 2017
Source:Acta Biomaterialia
Author(s): Amaia Cipitria, Kathrin Boettcher, Sophia Schoenhals, Daniela S. Garske, Katharina Schmidt-Bleek, Agnes Ellinghaus, Anke Dienelt, Anja Peters, Manav Mehta, Christopher M. Madl, Nathaniel Huebsch, David J. Mooney, Georg N. Duda
In-situ tissue regeneration aims to utilize the body's endogenous healing capacity through the recruitment of host stem or progenitor cells to an injury site. Stromal cell-derived factor-1 α (SDF-1 α) is widely discussed as a potent chemoattractant. Here we use a cell-free biomaterial-based approach to (i) deliver SDF-1 α for the recruitment of endogenous bone marrow-derived stromal cells (BMSC) into a critical-sized segmental femoral defect in rats and to (ii) induce hydrogel stiffness-mediated osteogenic differentiation in-vivo. Ionically crosslinked alginate hydrogels with a stiffness optimized for osteogenic differentiation were used. Fast-degrading porogens were incorporated to impart a macroporous architecture that facilitates host cell invasion. Endogenous cell recruitment to the defect site was successfully triggered through the controlled release of SDF-1 α. A trend for increased bone volume fraction (BV/TV) and a significantly higher bone mineral density (BMD) were observed for gels loaded with SDF-1 α, compared to empty gels at two weeks. A trend was also observed, albeit not statistically significant, towards matrix stiffness influencing BV/TV and BMD at two weeks. However, over a six week time-frame, these effects were insufficient for bone bridging of a segmental femoral defect. While mechanical cues combined with ex-vivo cell encapsulation have been shown to have an effect in the regeneration of less demanding in-vivo models, such as cranial defects of nude rats, they are not sufficient for a SDF-1 α mediated in-situ regeneration approach in segmental femoral defects of immunocompetent rats, suggesting that additional osteogenic cues may also be required.Statement of SignificanceStromal cell-derived factor-1 α (SDF-1 α) is a chemoattractant used to recruit host cells for tissue regeneration. The concept that matrix stiffness can direct mesenchymal stromal cell (MSC) differentiation into various lineages was described a decade ago using in-vitro experiments. Recently, alginate hydrogels with an optimized stiffness and ex-vivo encapsulated MSCs were shown to have an effect in the regeneration of skull defects of nude rats. Here, we apply this material system, loaded with SDF-1 α and without encapsulated MSCs, to (i) recruit endogenous cells and (ii) induce stiffness-mediated osteogenic differentiation in-vivo, using as model system a load-bearing femoral defect in immunocompetent rats. While a cell-free approach is of great interest from a translational perspective, the current limitations are described.

Graphical abstract

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Manufacturing of hydrogel biomaterials with controlled mechanical properties for tissue engineering applications

Publication date: Available online 20 July 2017
Source:Acta Biomaterialia
Author(s): Armin Vedadghavami, Farnaz Minooei, Mohammad Hossein Mohammadi, Sultan Khetani, Ahmad Rezaei, Shohreh Mashayekhan, Amir Sanati-Nezhad
Hydrogels have been recognized as crucial biomaterials in the field of tissue engineering, regenerative medicine, and drug delivery applications due to their specific characteristics. These biomaterials benefit from retaining a large amount of water, effective mass transfer, similarity to natural tissues and the ability to form different shapes. However, having relatively poor mechanical properties is a limiting factor associated with hydrogel biomaterials. Controlling the biomechanical properties of hydrogels is of paramount importance. In this work, firstly, mechanical characteristics of hydrogels and methods employed for characterizing these properties are explored. Subsequently, the most common approaches used for tuning mechanical properties of hydrogels including but are not limited to, interpenetrating polymer networks, nanocomposites, self-assembly techniques, and co-polymerization are discussed. The performance of different techniques used for tuning biomechanical properties of hydrogels is further compared. Such techniques involve lithography techniques for replication of tissues with complex mechanical profiles; microfluidic techniques applicable for generating gradients of mechanical properties in hydrogel biomaterials for engineering complex human tissues like intervertebral discs, osteochondral tissues, blood vessels and skin layers; and electrospinning techniques for synthesis of hybrid hydrogels and highly ordered fibers with tunable mechanical and biological properties. We finally discuss future perspectives and challenges for controlling biomimetic hydrogel materials possessing proper biomechanical properties.Statement of SignificanceHydrogels biomaterials are essential constituting components of engineered tissues with the applications in regenerative medicine and drug delivery. The mechanical properties of hydrogels play crucial roles in regulating the interactions between cells and extracellular matrix and directing the cells phenotype and genotype. Despite significant advances in developing methods and techniques with the ability of tuning the biomechanical properties of hydrogels, there are still challenges regarding the synthesis of hydrogels with complex mechanical profiles as well as limitations in vascularization and patterning of complex structures of natural tissues which barricade the production of sophisticated organs. Therefore, in addition to a review on advanced methods and techniques for measuring a variety of different biomechanical characteristics of hydrogels, the new techniques for enhancing the biomechanics of hydrogels are presented. It is expected that this review will profit future works for regulating the biomechanical properties of hydrogel biomaterials to satisfy the demands of a variety of different human tissues.

Graphical abstract

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Scaffold curvature-mediated novel biomineralization process originates a continuous soft tissue-to-bone interface

Publication date: Available online 20 July 2017
Source:Acta Biomaterialia
Author(s): Michael Paris, Andreas Götz, Inga Hettrich, Cécile M. Bidan, John W.C. Dunlop, Hajar Razi, Ivo Zizak, Dietmar W. Hutmacher, Peter Fratzl, Georg N. Duda, Wolfgang Wagermaier, Amaia Cipitria
A myriad of shapes are found in biological tissues, often naturally evolved to fulfill a particular function. In the field of tissue engineering, substrate geometry influences cell behavior and tissue formation in-vitro, yet little is known how this translates to an in-vivo scenario. Here we investigate scaffold curvature-induced tissue growth, without additional growth factors or cells, in an ovine animal model. We show that soft tissue formation follows a curvature-driven tissue growth model. The highly organized endogenous soft matrix, potentially under mechanical strain, leads to a non-standard form of biomineralization, whereby the pre-existing organic matrix is mineralized without collagen remodeling and without an intermediate cartilage ossification phase. Micro- and nanoscale characterization of the tissue microstructure using histology, backscattered electron (BSE) and second-harmonic generation (SHG) imaging and synchrotron small angle X-ray scattering (SAXS) revealed (i) continuous collagen fibers across the soft-hard tissue interface on the tip of mineralized cones, and (ii) bone remodeling by basic multicellular units (BMUs) in regions adjacent to the native cortical bone. Thus, features of soft tissue-to-bone interface resembling the insertion sites of ligaments and tendons into bone were created, using a scaffold that did not mimic the structural or biological gradients across such a complex interface at its mature state. This study provides fundamental knowledge for biomimetic scaffold design in the fields of bone regeneration and soft tissue-to-bone interface tissue engineering.Statement of significanceGeometry influences cell behavior and tissue formation in-vitro. However, little is known how this translates to an in-vivo scenario. Here we investigate the influence of scaffold mean surface curvature on in-vivo tissue growth using an ovine animal model. Based on a multiscale tissue microstructure characterization, we show a seamless integration of soft tissue into newly formed bone, resembling the insertion sites of ligaments and tendons into bone. This interface was created using a scaffold without additional growth factors or cells that did not recapitulate the structural or biological gradients across such a complex tissue interface at its mature state. These findings have important implications for biomimetic scaffold design for bone regeneration and soft tissue-to-bone interface tissue engineering.

Graphical abstract

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Peptide Modification of Polyimide-Insulated Microwires: Towards Improved Biocompatibility through Reduced Glial Scarring

Publication date: Available online 19 July 2017
Source:Acta Biomaterialia
Author(s): Sangita Sridar, Matthew A. Churchward, Vivian K. Mushahwar, Kathryn G. Todd, Anastasia L. Elias
The goal of this study is to improve the integration of implanted microdevices with tissue in the central nervous system (CNS). The long-term utility of neuroprosthetic devices implanted in the CNS is affected by the formation of a scar by resident glial cells (astrocytes and microglia), limiting the viability and functional stability of the devices. Reduction in the proliferation of glial cells is expected to enhance the biocompatibility of devices. We demonstrate the modification of polyimide-insulated microelectrodes with a bioactive peptide KHIFSDDSSE. Microelectrode wires were functionalized with (3-aminopropyl) triethoxy silane (APTES); the peptide was then covalently bonded to the APTES. The soluble peptide was tested in 2D mixed cultures of astrocytes and microglia, and reduced the proliferation of both cell types. The interactions of glial cells with the peptide-modified wires was then examined in 3D cell-laden hydrogels by immunofluorescence microscopy. As expected for uncoated wires, the microglia were first attracted to the wire (7 days) followed by astrocyte recruitment and hypertrophy (14 days). For the peptide-treated wires, astrocytes coated the wires directly (24 hours), and formed a thin, stable coating without evidence of hypertrophy, and the attraction of microglia to the wire was significantly reduced. The results suggest a mechanism to improve tissue integration by promoting uniform coating of astrocytes on a foreign body while lessening the reactive response of microglia. We conclude that the bioactive peptide KHIFSDDSSE may be effective in improving the biocompatibility of neural interfaces by both reducing acute glial reactivity and generating stable integration with tissue.Statement of SignificanceThe peptide KHIFSDDSSE has previously been shown in vitro to both reduce the proliferation of astrocytes, and to increase the adhesion of astrocyte to glass substrates. Here, we demonstrate a method to apply uniform coatings of peptides to microwires, which could readily be generalized to other peptides and surfaces. We then show that when peptide-modified wires are inserted into 3D cell-laden hydrogels, the normal cellular reaction (microglial activation followed by astrocyte recruitment and hypertrophy) does not occur, rather astrocytes are attracted directly to the surface of the wire, forming a relatively thin and uniform coating. This suggests a method to improve tissue integration of implanted devices to reduce glial scarring and ultimately reduce failure of neural interfaces.

Graphical abstract

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In vitro degradation of calcium phosphates: effect of multiscale porosity, textural properties and composition

Publication date: Available online 21 July 2017
Source:Acta Biomaterialia
Author(s): A. Díez-Escudero, M. Espanol, S. Beats, M.P. Ginebra
The capacity of calcium phosphates to be replaced by bone is tightly linked to their resorbability. However, the relative importance of some textural parameters on their degradation behaviour is still unclear. The present study aims to quantify the effect of composition, specific surface area (SSA), and porosity at various length scales (nano-, micro- and macroporosity) on the in vitro degradation of different calcium phosphates. Degradation studies were performed in an acidic medium to mimic the osteoclastic environment. Small degradations were found in samples with interconnected nano- and micropores with sizes below 3 µm although they were highly porous (35-65%), with maximum weight loss of 8 wt%. Biomimetic calcium deficient hydroxyapatite, with high SSA and low crystallinity, presented the highest degradation rates exceeding even the more soluble β-TCP. A dependence of degradation on SSA was indisputable when porosity and pore sizes were increased. The introduction of additional macroporosity with pore interconnections above 20 µm significantly impacted degradation, more markedly in the substrates with high SSA (>15 m²/g), whereas in sintered substrates with low SSA (<1 m²/g) it resulted just in a linear increase of degradation. Up to 30% of degradation was registered in biomimetic substrates, compared to 15% in β-TCP or 8% in sintered hydroxyapatite. The incorporation of carbonate in calcium deficient hydroxyapatite did not increase its degradation rate. Overall, the study highlights the importance of textural properties, which can modulate or even outweigh the effect of other features such as the solubility of the compounds.Statement of SignificanceThe physicochemical features of calcium phosphates are crucial to tune biological events like resorption during bone remodeling. Understanding in vitro resorption can help to predict the in vivo behavior. Besides chemical composition, other parameters such as porosity and specific surface area have a strong influence on resorption. The complexity of isolating the contribution of each parameter lies in the close interrelation between them. In this work, a multiscale study was proposed to discern the extent to which each parameter influences degradation in a variety of calcium phosphates, using an acidic medium to resemble the osteoclastic environment. The results emphasize the importance of textural properties, which can modulate or even outweigh the effect of the intrinsic solubility of the compounds.

Graphical abstract

http://ift.tt/2uiBReC