Publication date: Available online 21 December 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Elisa Cançado Porto-Mascarenhas, Daniele Xavier Assad, Hélène Chardin, David Gozal, Graziela De Luca Canto, Ana Carolina Acevedo, Eliete Neves Silva Guerra
Salivary biomarkers could be helpful to characterize breast cancer. Therefore, this review was performed to evaluate the capability of salivary biological markers in the diagnosis and monitoring of breast cancer. Studies were eligible for inclusion if they assessed the potential diagnostic value or other discriminatory properties of biological markers in saliva of patients with breast cancer. The search was performed in six electronic databases (Cochrane, LILACS, PubMed, Science Direct, Scopus, Web of Science). In addition the biomarkers were classified according to their potential clinical application. We identified 567 pertinent studies, of which 13 met the inclusion criteria. Combined biomarker approaches demonstrated better ability to predict breast cancer patients than individual biomarkers. As single biomarker, namely proline, reported great capacity in both early and late stage breast cancer diagnosis. Taurine showed interesting capability to identify early breast cancer individuals. Furthermore, valine also demonstrated excellent diagnostic test accuracy for advanced stages of breast cancer. Only seven studies reported sensitivity and specificity (Zhang et al., 2010; Streckfus et al., 2000a; Brooks et al., 2008; Cheng et al., 2015; Bigler et al., 2002; Zhong et al., 2016; Streckfus, 2009), which varied considerably from 50% to 100%, and from 51% to 97%, respectively. In general, salivary biomarkers identified advanced stages of breast cancer better than early stages. There is currently limited evidence to confirm the putative implementation of salivary biomarkers as diagnostic tools for breast cancer. However, current review provides new research directions.
http://ift.tt/2ibBfTc
Τετάρτη 21 Δεκεμβρίου 2016
Salivary Biomarkers in the Diagnosis of Breast Cancer: A Review
Literature Review of Cosmetic Procedures in Men: Approaches and Techniques are Gender Specific
Abstract
The proportion of men receiving non-surgical cosmetic procedures has risen substantially in recent years. Various physiologic, anatomic, and motivational considerations differentiate the treatments for male and female patients. Nevertheless, research regarding approaches to the male cosmetic patient is scarce. We sought to provide an overview and sex-specific discussion of the most popular cosmetic dermatologic procedures pursued by men by conducting a comprehensive literature review pertaining to non-surgical cosmetic procedures in male patients. The most common and rapidly expanding non-surgical interventions in men include botulinum toxin, filler injection, chemical peels, microdermabrasion, laser resurfacing, laser hair removal, hair transplantation, and minimally invasive techniques for adipose tissue reduction. Important sex-specific factors associated with each of these procedures should be considered to best serve the male cosmetic patient.
http://ift.tt/2h2Rih0
Biomarkers associated with disease severity in allergic and nonallergic asthma
Source:Molecular Immunology, Volume 82
Author(s): Selene Baos, David Calzada, Lucía Cremades, Joaquín Sastre, Joaquín Quiralte, Fernando Florido, Carlos Lahoz, Blanca Cárdaba
Asthma is a complex, chronic respiratory disease with a wide clinical spectrum. Use of high-throughput technologies has generated a great deal of data that require validation. In this work the objective was to validate molecular biomarkers related to asthmatic disease types in peripheral blood samples and define their relationship with disease severity. With this purpose, ninety-four previously described genes were analyzed by qRT-PCR in 30 healthy control (HC) subjects, 30 patients with nonallergic asthma (NA), 30 with allergic asthma (AA), and 14 patients with allergy (rhinitis) but without asthma (AR). RNA was extracted from peripheral blood mononuclear cells (PBMCs) using the TRIzol method. After data normalization, principal component analysis (PCA) was performed, and multiple approaches were used to test for differential gene expression. Relevance was defined by RQ (relative quantification) and corrected P value (<0.05). Protein levels of IL-8 and MSR1 were determined by ELISA and Western blot, respectively.PCA showed 4 gene expression clusters that correlated with the 4 clinical phenotypes. Analysis of differential gene expression between clinical groups and HCs revealed 26 statistically relevant genes in NA and 69 in AA. Protein interaction analysis revealed IL-8 to be a central protein. Average levels of IL-8 were higher in the asthma patients' sera (NA: 452.28±357.72, AA: 327.46±377pg/ml) than in HCs (286.09±179.10), but without reaching statistical significance. Nine genes, especially MSR1, were strongly associated with severe NA.In conclusion, several molecular biomarkers of asthma have been defined, some of which could be useful for the diagnosis or prognosis of disease severity.
http://ift.tt/2haR9LD
Vascular alterations after photodynamic therapy mediated by 5-aminolevulinic acid in oral leukoplakia
Abstract
Impairment of vascular functions after photodynamic therapy (PDT) is frequently associated with tumor remission and is considered one of the main antineoplastic PDT effects. Vascular alterations in oral leukoplakia (OL) treated with PDT have not yet been described. The aim of this study was to evaluate the effect of topical 5-ALA-mediated PDT on the vascular network of 4NQO-induced OL in rats. After applying 4NQO topically on the tongue during 16 weeks, there was induction of dysplastic lesions, which were treated with two PDT sessions (with an interval of 72 h between them), using topical application of 5-ALA and posterior irradiation with a laser (90 J/cm2 fluency). Histological sections of the tongues were obtained and analyzed concerning plasmatic exudation and microvessel density after immunolabeling with CD31 and CD34 vessel markers. There was intense plasmatic exudation after 6 h of the first PDT session; at 6 h of the second PDT session, there was a significant reduction in the density of CD31- and CD34-positive microvessels in comparison to controls (p < 0.05). In the PDT intervals, there was an increase in the density of CD31 and CD34 microvessels, suggesting angiogenesis. Topical application of 5-ALA-mediated PDT caused an immediate deleterious effect on the vascular network, increasing vessel permeability and reducing vessel density, mainly after two sessions of the treatment. However, secondary angiogenesis emerged in these lesions during intervals of the PDT session. This fact may be considered during the adoption of a PDT protocol, to avoid OL resistance and recurrence after the treatment.
http://ift.tt/2igipGv
Curcumin inhibits growth potential by G1 cell cycle arrest and induces apoptosis in p53-mutated COLO 320DM human colon adenocarcinoma cells
Publication date: February 2017
Source:Biomedicine & Pharmacotherapy, Volume 86
Author(s): Jade Dhananjay Dasiram, Ramamoorthi Ganesan, Janani Kannan, Venkatesan Kotteeswaran, Nageswaran Sivalingam
Curcumin, a natural polyphenolic compound and it is isolated from the rhizome of Curcuma longa, have been reported to possess anticancer effect against stage I and II colon cancer. However, the effect of curcumin on colon cancer at Dukes' type C metastatic stage III remains still unclear. In the present study, we have investigated the anticancer effects of curcumin on p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes' type C metastatic stage. The cellular viability and proliferation were assessed by trypan blue exclusion assay and MTT assay, respectively. The cytotoxicity effect was examined by lactate dehydrogenase (LDH) cytotoxicity assay. Apoptosis was analyzed by DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis. Cell cycle distribution was performed by flow cytometry analysis. Here we have observed that curcumin treatment significantly inhibited the cellular viability and proliferation potential of p53 mutated COLO 320DM cells in a dose- and time-dependent manner. In addition, curcumin treatment showed no cytotoxic effects to the COLO 320DM cells. DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis revealed that curcumin treatment induced apoptosis in COLO 320DM cells. Furthermore, curcumin caused cell cycle arrest at the G1 phase, decreased the cell population in the S phase and induced apoptosis in COLO 320DM colon adenocarcinoma cells. Together, these data suggest that curcumin exerts anticancer effects and induces apoptosis in p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes' type C metastatic stage.
http://ift.tt/2i1sVC5
Grape seed procyanidin B2 inhibits adipogenesis of 3T3-L1 cells by targeting peroxisome proliferator-activated receptor γ with miR-483-5p involved mechanism
Publication date: February 2017
Source:Biomedicine & Pharmacotherapy, Volume 86
Author(s): Jun Zhang, Yazeng Huang, Haiyu Shao, Qing Bi, Jinping Chen, Zhaoming Ye
Procyanidins have lipolysis effect on adipose metabolism, but the underlying mechanism is not fully understood. The aim of present study was to examine the effect of grape seed procyanidin B2 (GSP) on the adipogenic differentiation of 3T3-L1 preadipocyte cell line and investigate the underlying mechanism. The results showed that GSP treatment significantly reduced the intracellular lipid accumulation in induced 3T3-L1 cells by targeting miR-483-5p as well as peroxisome proliferator-activated receptor γ (PPARγ). In addition, our results revealed that overexpression of miR-483-5p increased adipogenic differentiation, while inhibition of miR-483-5p reduced the lipid accumulation by suppressing the adipogenic differentiation. Moreover, overexpression of miR-483-5p could reverse GSP's inhibition of adipocyte differentiation as well as increase the level of PPARγ. These results demonstrate that GSP inhibits adipogenesis by targeting PPARγ and suggest this effect might be mediated by miR-483-5p.
http://ift.tt/2hVJwtE
Induction of G2/M phase arrest and apoptosis by a new tetrahydroingenol diterpenoid from Euphorbia erythradenia Bioss. in melanoma cancer cells
Publication date: February 2017
Source:Biomedicine & Pharmacotherapy, Volume 86
Author(s): Faranak Fallahian, Mustafa Ghanadian, Mahmoud Aghaei, Seyed Mohammad Zarei
In the current study, a new tetrahydroingenol diterpene isolated from Euphorbia erythradenia, 7,13-diacetyl-5-angeloyl-20-nicotinyl-3-propionyl-1,2,6,7-tetrahydroingenol (DANPT), were tested for the molecular mechanism of its anti-cancer activity in two human melanoma cancer cell lines, A375 and HMCB. DANPT was found cytotoxic against A375 and HMCB cells with IC50 value of 15.37±2.6μM and 15.62±1.89μM, respectively. Flow cytometric analysis showed that DANPT halted the A375 and HMCB cells in G2/M phase and induced apoptosis in a dose-dependent manner. Cell cycle arrest was associated with down-regulation of cyclin B and Cdk-1 and subsequent up-regulation of p53 and p21. Moreover, DANPT induced Bax and inhibited Bcl-2 expression, which results in increasing Bax/Bcl-2 ratio and activation of caspase-3. Furthermore, the apoptotic effect of DANPT was also related to ROS production and loss of mitochondrial membrane potential (ΔYm). Overall, our results suggest that DANPT can inhibit proliferation of human melanoma cancer cells by promoting apoptosis and inducing cell cycle arrest and therefore, it can be a promising natural agent for the treatment of melanoma cancer.
http://ift.tt/2hazh3E
Heart targeted nanoliposomal/nanoparticles drug delivery: An updated review
Publication date: February 2017
Source:Biomedicine & Pharmacotherapy, Volume 86
Author(s): Mostafa Cheraghi, Babak Negahdari, Hadis Daraee, Ali Eatemadi
Nanoliposomes are type of nano-sized vesicles made of bi-layered phospholipid membranes with an aqueous interior. They have been demonstrated to deliver several materials like low molecular weight drugs, imaging agents, peptides, proteins, and nucleic acids. Nanoliposomes have been demonstrated to slowly release an encapsulated drug, thereby leading to sustained exposure to target region and improved efficacy. This ability of nano-liposomes can be harnessed to deliver therapeutic agents precisely to the infarcted heart. Accordingly, this article will review recent developments in the application of nano liposomes and nanoparticles as drug delivery systems to treat cardiovascular related disorders such as atherosclerosis, restenosis and myocardial infarction.
http://ift.tt/2i1wR5J
Multiple sclerosis: Therapeutic applications of advancing drug delivery systems
Publication date: February 2017
Source:Biomedicine & Pharmacotherapy, Volume 86
Author(s): Sanam Dolati, Zohreh Babaloo, Farhad Jadidi-Niaragh, Hormoz Ayromlou, Sanam Sadreddini, Mehdi Yousefi
Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system, which is accompanying with demyelination, neurodegeneration and sensibility to oxidative stress. In MS, auto-reactive lymphocytes cross the blood–brain barrier (BBB) and reside in the perivenous demyelinating lesions which create various distinct inflammatory demyelinated plaques situated predominantly in the white matter. The current MS-related therapeutic approaches can be classified into disease-modifying therapies (DMTs) and symptomatic therapy. DMTs suppress circulating immune cells, inhibit passing the BBB and decrease the inflammatory responses. Recent advances have remarkably delayed disease development and improved the quality of life for numerous patients. In spite of major improvements in therapeutic options, there are some limitations regarding the routes of administration and the necessity for repeated and long-term dosing in which cause to systemic disadvantageous consequences and patient non-compliance. Nanotechnology presents promising approaches to improve autoimmune disease treatment with the capability to overcome many of the limitations common to the current immunosuppressive and biological therapies. Here we emphasis on nanomedicine-based drug delivery approaches of biological immunomodulatory mediators for the treatment of multiple sclerosis. This comprehensive review details the most successful drugs in MS therapy and also focuses on conceptions and clinical potential of novel nanomedicine attitudes for inducing immunosuppression and immunological tolerance in MS to modulate abnormal and pathologic immune responses.
http://ift.tt/2hVSUO9
Anti-diabetic effect of the ethyl acetate fraction of Clerodendrum volubile: protocatechuic acid suppresses phagocytic oxidative burst and modulates inflammatory cytokines
Publication date: February 2017
Source:Biomedicine & Pharmacotherapy, Volume 86
Author(s): Ochuko L. Erukainure, Rahman M. Hafizur, M. Iqbal Choudhary, Achyut Adhikari, Ahmed M. Mesaik, Olubunmi Atolani, Priyanka Banerjee, Robert Preissner, Aliyu Muhammad, Md. Shahidul Islam
The antidiabetic effects of the ethyl acetate (EtOAc) fraction of Clerodendrum volubile leaves was investigated in this study. EtOAc was also fractionated to isolate the active compounds. The structure of the isolated compound (Protocatechuic acid) was established using 1H and 13C NMR spectroscopies and mass spectrometry. Protocatechuic acid was investigated for its anti-oxidative burst in polymorphonuclear neutrophils (PMNs) and macrophages. It was also docked with α–glucosidase and TNF-α. Acute treatment with EtOAc fraction of Clerodendrum volubile leaves significantly (p<0.05) decreased blood glucose level and hepatic biomarkers, and significantly (p<0.05) increased serum insulin level and β–cell function. It had little or no effect on serum lipid profile and atherogenic indices. Protocatechuic acid significantly (p<0.05) suppressed phagocytic oxidative burst and docked well with α–glucosidase and TNF-α. These results indicate the therapeutic effect of EtOAc fraction of C. volubile on type 2 diabetes and its complications, which can be attributed to the main bioactive compound, protocatechuic acid.
http://ift.tt/2i1rTWM
Effect of hydroalcoholic Allium ampeloprasum extract on oxidative stress, diabetes mellitus and dyslipidemia in alloxan-induced diabetic rats
Publication date: February 2017
Source:Biomedicine & Pharmacotherapy, Volume 86
Author(s): Mohammad Rahimi-Madiseh, Esfandiar Heidarian, Soleiman Kheiri, Mahmoud Rafieian-Kopaei
Allium ampeloprasum (AA) is a medicinal plant which is used in Iranian traditional medicine to treat or prevent different diseases. The aim of this study is to investigate the effect of AA extract on oxidative stress and dyslipidemia in diabetic rats induced by alloxan. In this experimental study, 60 male Wistar rats weighing 200–250gr were randomly divided to five groups of 12 each including healthy control (group I), diabetic control (group II), metformin-treated diabetic positive control (group III) and two groups treated with doses 400 (group IV) and 800 (groupV) mg/kg/BW of AA extracts. Diabetes mellitus was experimentally induced by injection of two doses of alloxan-120 and 65mg/kg-within two consecutive days. Alloxan-induced diabetes caused significant increase in serum glucose, triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), very low density lipoprotein (VLDL) and high density lipoprotein (HDL) levels in group II (p<0.05). Furthermore, serum malondialdehyde (MDA) levels increased significantly and liver catalase activity decreased significantly in the 2nd group compared to 1st control; respectively p=0.0001 and p=0.009. In the group IV has seen a significant decrease in serum TG (p=0.01), TC (p=0.0001), VLDL (p=0.01), and MDA (p=0.0001) levels and significant increase in the liver and kidney catalase activities of the rats compared to the group II; respectively p=0.0001 and p=0.0001. In Conclusion our results highlight potentially relevant health beneficial effects of AA extract which exerts hypoglycemic, hypolipidemic, and anti-oxidative stress effects in rats with alloxan-induced diabetes. Therefore, it may be considered as useful dietary supplements in diabetic patients.
http://ift.tt/2hVPNWn
Acute, 28days sub acute and genotoxic profiling of Quercetin-Magnesium complex in Swiss albino mice
Publication date: February 2017
Source:Biomedicine & Pharmacotherapy, Volume 86
Author(s): Nilanjan Ghosh, Rajendra Sandur, Deepanwita Ghosh, Souvik Roy, Suresh Janadri
Quercetin-Magnesium complex is one of the youngest alkaline rare earth metal (Magnesium) complexes with flavonoids (Quercetin) in organo-metalic family. Earlier studies describe the details of the complex formation, characterization and antioxidant study of the complex but toxicity profile is still under darkness. The present study was taken up to investigate the oral acute toxicity, 28days repeated oral sub-acute toxicity study and genotoxicity study of Quercetin-Magnesium complex in Swiss albino mice. Quercetin-Magnesium complex showed mortality at a dose of 185mg/kg in the Swiss albino mice. In 28days repeated oral toxicity study, Quercetin-Magnesium complex was administered to both sex of Swiss albino mice at dose levels of 150, 130 and 100mg/kg body weight respectively. Where 150mg/kg dose shows increased levels of white blood cells and changes in total protein, serum creatinine and blood urea nitrogen. Histopathological study of Quercetin-Magnesium complex shows minor structural alteration in kidney at 150mg/kg dose. No observed toxic level found in 130mg/kg or below doses. No genotoxic effect found in any doses of the complex. Therefore 130mg/kg or below dose level could be better for further study.
http://ift.tt/2i1rXG5
Possible involvement of Nrf2 and PPARγ up-regulation in the protective effect of umbelliferone against cyclophosphamide-induced hepatotoxicity
Publication date: February 2017
Source:Biomedicine & Pharmacotherapy, Volume 86
Author(s): Ayman M. Mahmoud, Mousa O. Germoush, Mohammed F. Alotaibi, Omnia E. Hussein
Umbelliferone (UMB) is a coumarin derivative with promising hepatoprotective effects. In this study, we examined the possible protective effects of UMB against cyclophosphamide (CP)-induced hepatotoxicity, addressing the question of the possible role of nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator activated receptor gamma (PPARγ). Wistar rats were orally administered UMB at doses 50 and 100mg/kg two weeks prior to CP injection. Five days after CP administration, the rats were sacrificed and samples were collected for analyses. CP induced a significant increase in circulating liver marker enzymes and pro-inflammatory cytokines. Hepatic lipid peroxidation and nitric oxide levels, and nuclear factor-kappaB (NF-κB) and inducible nitric oxide synthase (iNOS) expression were significantly increased following CP administration. UMB supplementation attenuated CP-induced inflammation and oxidative stress as assessed by restoration of the activity and expression of the antioxidant defenses, and suppression of pro-inflammatory cytokines. Histological examination also showed that UMB could significantly reduce CP-induced alterations. CP-induced rats showed significant down-regulation of Nrf2, HO-1 and PPARγ, an effect that was markedly reversed by UMB. In conclusion, the hepatoprotective effects of UMB appear to depend on co-activation of PPARγ and Nrf2, and subsequent suppression of oxidative stress and inflammation.
http://ift.tt/2hVQdMy
Propofol enhances the cisplatin-induced apoptosis on cervical cancer cells via EGFR/JAK2/STAT3 pathway
Publication date: February 2017
Source:Biomedicine & Pharmacotherapy, Volume 86
Author(s): Haoran Li, Yan Lu, Yangyang Pang, Mengjiao Li, Xi Cheng, Jiawei Chen
ObjectiveThe main purpose of this study was to evaluate propofol and its combined effect with cisplatin on apoptosis of cervical cancer cells and molecular mechanisms of this phenomenon.MethodsThe effects of propofol and cisplatin on cell viability and apoptosis were detected by cell counting kit-8 (CCK-8) assay, colony formation assay and flow cytometry assay. Besides, protein expression of EGFR/JAK2/STAT3 pathway was determined by western blot. STAT3 was over-expressed in cervical cancer cells by STAT3 cDNA. Expression of EGFR and STAT3 protein of human tissues was evaluated by immunohistochemistry (IHC) assay.ResultsIn this study, we found that not only propofol alone could inhibit cervical cancer cells viability but also could increase the inhibitory effect of cisplatin on cervical cancer cells growth. Meanwhile, propofol sensitized cervical cancer cells to cisplatin-induced apoptosis but not affected normal cervical cells. In genetic level, propofol could enhance the anti-tumor effect of cisplatin through EGFR/JAK2/STAT3 pathway. Further studies indicated that overexpression of EGFR and STAT3 is related to poor prognoses in cervical cancer patients, which contributed to confirm the clinical role of combined application of propofol and cisplatin.ConclusionPropofol enhances the cisplatin-induced cell apoptosis cervical cancer cells via EGFR/JAK2/STAT3 pathway and may be developed as a potential therapeutic agent to treat cervical cancer.
http://ift.tt/2i1rSlG
The combination of db-cAMP and ChABC with poly(propylene carbonate) microfibers promote axonal regenerative sprouting and functional recovery after spinal cord hemisection injury
Publication date: February 2017
Source:Biomedicine & Pharmacotherapy, Volume 86
Author(s): Tongliang Xia, Bin Huang, Shilei Ni, Lei Gao, Jiangang Wang, Jian Wang, Anjing Chen, Shaowei Zhu, Benlin Wang, Gang Li, Shugan Zhu, Xingang Li
This study describes the use of poly(propylene carbonate) (PPC) electrospun microfibres impregnated with a combination of dibutyryl cyclic adenosine monophosphate (db-cAMP) and chondroitinase ABC (ChABC) in the treatment of right-side hemisected spinal cord injury (SCI). Release of db-cAMP and/or ChABC from the microfibres was assessed in vitro using high-performance liquid chromatography (HPLC). Drug-impregnated microfibres were implanted into the hemisected thoracic spinal cord of rats, and treatment was evaluated using functional recovery examinations and immunohistochemistry. Our results demonstrated that the microfibres containing db-cAMP and/or ChABC displayed a stable and prolonged release of each agent. Sustained delivery of db-cAMP and/or ChABC was found to promote axonal regenerative sprouting, functional recovery, and reduced glial scar formation when compared to untreated control animals. The combination of both db-cAMP and ChABC was determined to be more effective than using either drug alone in the treatment of SCI. These findings demonstrate the feasibility of using PPC electrospun microfibres for multi-drug combination therapy in SCI.
http://ift.tt/2hVPLxJ
The effect of Searsia chirindensis stem-bark extract on renal and liver function in a rat model of neurotoxicity
Publication date: February 2017
Source:Biomedicine & Pharmacotherapy, Volume 86
Author(s): Zulfiah Mohamed Moosa, Musa Mabandla
Searsia chirindensis (SC) (Baker F.) (Anacardiaceae) has shown potential for the treatment of many neurological diseases however its effect on other bodily systems in neurotoxic models is not well-documented. In this study we investigated the effects of SC on blood glucose homeostasis, as well as its effect on liver and kidney function by assessing lipid peroxidation using the TBARS assay and measuring plasma and urinary electrolyte concentrations in a 6-hydroxydopamine parkinsonian model. The relative levels of phytochemicals were also quantified, along with testing free radical scavenging activity via the DPPH assay. Our results showed that SC decreases blood glucose levels but did not alter the liver and kidney function as reflected by the absence of electrolyte imbalances and lipid peroxidation damage. We also found that SC comprises primarily phenolic acids (945.73±154.01mg GA/g SC) and triterpenoids (1997.21±404.04mg OA/g SC) with minimal flavonoid content (12.98±2.75mg Q/g SC) and exhibited strong free radical scavenging activity (≈80%). In conclusion, these results suggest that SC does not alter the renal and liver function at least in the different parameters studied.
http://ift.tt/2i1uwrG
Radiosurgery for liver metastases. A single institution experience
Publication date: Available online 21 December 2016
Source:Reports of Practical Oncology & Radiotherapy
Author(s): Beatriz Amendola, Marco Amendola, Jesús M. Blanco, Naipy Perez, Xiaodong Wu
AimTo report our initial results on the use of radiosurgery for treatment of liver metastases.BackgroundIn recent years there has been increasing interest in the use of stereotactic body radiation therapy to treat metastatic disease to the liver as an alternative to interventional procedures.Materials and methodsBetween November 2008 and June 2015 a total of 36 LINAC-based radiosurgeries using VMAT were performed in 27 patients with liver metastases from 10 different primary sites. Doses ranged from 21Gy to 60Gy in 1 to 5 fractions. In all patients the volume of liver receiving less than 15Gy was more than 700cc. The volume treated with the prescription dose ranged from 1cc to 407cc with a median of 58cc. All patients but one received systemic treatment.ResultsOverall median survival for the entire group is 9 months (ranging from 1 to 67 months). Local recurrence free survival ranged from 4 to 67 months with a median of 14 months.Twenty patients (80%) survived more than six months. Three patients treated for oligometastases were alive after 3 years. Grade 0 toxicity was encountered in 22/27 patients, Grade 1 toxicity in 5/27 and only 1/27 patient experienced Grade 2 toxicity. No patient experienced grade 3–4 toxicity.ConclusionBased on these initial results we conclude that SBRT for treating liver metastases with radiosurgery is safe and effective for treating one or multiple lesions as long as normal tissue constraints for liver are respected.
http://ift.tt/2hTYZIg
Sanggenol F exerts anti-diabetic effects via promoting adipocyte differentiation and modifying adipokines expression
Abstract
Adipose tissue is not only a lipid storage site, but also a well-known endocrine organ. Dysfunction of adipose tissue is associated with irregular lipid metabolism, ectopic lipid accumulation and insulin resistance. It is proposed that modulating on adipose tissue is a reasonable way to ameliorate glucose and lipid metabolism. (±)-sanggenol F (SGF, purity >98.5%) was synthesized as a racemic mixture of natural (+)-sanggenol F. In this study, SGF was found to promote adipocyte differentiation, enhance insulin sensitivity, and upregulate beneficial adipokines expression in 3T3-L1 cells. Furthermore, in vivo study showed that treatment with SGF for 4 weeks improved glucose metabolism, by decreasing fasting blood glucose and enhancing insulin sensitivity. It also improved lipid metabolism, with reduced serum lipid level and ameliorated hepatic steatosis in db/db mice. During the process of target finding, we found that SGF had multiple activities of protein tyrosine phosphatase 1B inhibition, peroxisome proliferator-activated receptor γ and peroxisome proliferator-activated receptor α agonism. These results showed the potential of SGF as a candidate for the therapy of type 2 diabetes.
http://ift.tt/2hrTFuT
Ghrelin is independently associated with anti-mullerian hormone levels in obese but not non-obese women with polycystic ovary syndrome
Abstract
Ghrelin is an endogenous appetite stimulant that may have a role in ovarian function. Women with polycystic ovary syndrome have anovulation and frequently weight management issues; however the associations between ghrelin and hormonal markers in polycystic ovary syndrome have not been well studied. In order to characterize the association between total ghrelin levels and ovarian function and the possible modification of this relationship by obesity, we examined total ghrelin levels and anti-mullerian hormone, total testosterone, and insulin in obese and non-obese women with and without polycystic ovary syndrome. Total ghrelin levels were lower in obese women with polycystic ovary syndrome (n = 45) compared to obese controls (n = 33) (p = 0.005), but similar in non-obese women with polycystic ovary syndrome (n = 20) compared to non-obese controls (n = 21) (p = NS). In the obese polycystic ovary syndrome group, anti-mullerian hormone was associated with ghrelin levels independent of age, insulin, and total testosterone (p = 0.008). There was no association between total ghrelin and anti-mullerian hormone levels in non-obese women with polycystic ovary syndrome, non-obese controls, or obese controls (p = NS). Our results provide evidence for a potential relationship between ghrelin and ovarian function in obese women with polycystic ovary syndrome that was not observed in non-obese women with polycystic ovary syndrome or controls.
http://ift.tt/2hdbB0c
Reconstructions Following Graft Infection: An Unsolved Challenge
Publication date: Available online 20 December 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): E.S. Debus, H. Diener
http://ift.tt/2hI5DDH
Enhancement of Cd phytoextraction by hyperaccumulator Sedum alfredii using electrical field and organic amendments
Abstract
The combined use of organic amendment-assisted phytoextraction and electrokinetic remediation to decontaminate Cd-polluted soil was demonstrated in a laboratory-scale experiment. The plant species selected was the hyperaccumulator Sedum alfredii. Prior to the pot experiment, the loamy soil was treated with 15 g kg−1 of pig manure compost, 10 g kg−1 of humic acid, or 5 mmol kg−1 of EDTA, and untreated soil without application of any amendment was the control. Two conditions were applied to each treatment: no voltage (without an electrical field) and a direct current (DC) electrical field (1 V cm−1 with switching polarity every day). Results indicated that Cd concentrations in S. alfredii were significantly (p < 0.05) increased by application of the electrical field and soil amendments (pig manure compost, humic acid, and EDTA). By switching the polarity of the DC electrical field, significant pH variation from anode to cathode can be avoided, and no significant impact was observed on shoot biomass production. Electrical field application increased DTPA-extractable Cd in soils and the Cd accumulation in shoots by 6.06–15.64 and 24.53–52.31%, respectively. The addition of pig manure compost and humic acid enhanced shoot Cd accumulation by 1.54- to 1.92- and 1.38- to 1.64-fold because of their simultaneous enhancement of Cd concentration in shoots and biomass production. However, no enhancement of Cd accumulation was found in the EDTA treatment, which can be ascribed to the inhibition of plant growth caused by EDTA. In conclusion, pig manure compost or humic acid addition in combination with the application of a switched-polarity DC electrical field could significantly enhance Cd phytoextraction by hyperaccumulator S. alfredii.
http://ift.tt/2hTHkAy
Maladie de Hailey-Hailey : efficacité de l’association doxycycline et vitamine PP
Source:Annales de Dermatologie et de Vénéréologie
Author(s): F.Z. Elfatoifi, F. Fanian, S. Chiheb, P. Humbert
http://ift.tt/2hVyzs6
Recommandations pour la prise en charge buccodentaire des patients atteints de maladies bulleuses auto-immunes avec atteinte buccale
Publication date: Available online 20 December 2016
Source:Annales de Dermatologie et de Vénéréologie
Author(s): V. Sobocinski, S.-M. Dridi, C. Bisson, S. Jeanne, F. Gaultier, C. Prost-Squarcioni, P. Bernard, F. Pascal, B. Lefevre, P. Weber, C. Abasq, S. Agbo-Godeau, P. Joly, S. Ingen-Housz-Oro, S. Duvert-Lehembre
IntroductionLes maladies bulleuses auto-immunes (MBAI) peuvent occasionner des lésions buccales d'évolution chronique et insidieuse.ObjectifÉlaborer des recommandations permettant une prise en charge buccodentaire optimale des patients atteints de MBAI avec atteinte buccale.MéthodesEn l'absence d'études scientifiques de niveau de preuve élevé, ces recommandations ont été élaborées lors de deux réunions par un comité d'experts en MBAI composé de 7 dermatologues, 1 stomatologue, 1 chirurgien maxillo-facial, 2 odontologistes et 4 parodontologistes.RésultatsLes lésions buccales des MBAI peuvent être classées en trois grades de sévérité : atteinte sévère (gingivite érosive généralisée touchant au minimum 30 % des sites dentaires), atteinte modérée (gingivite érosive localisée touchant moins de 30 % des sites dentaires), ou maladie contrôlée (absence de lésion érosive buccale). Une bonne hygiène buccodentaire, adaptée à la sévérité des lésions buccales, doit absolument être maintenue chez ces patients, afin d'éviter la formation de plaque dentaire aggravant la symptomatologie. La réalisation de soins dentaires et parodontaux doit être discutée en fonction du grade de sévérité des lésions buccales : en cas d'atteinte sévère, la plaque dentaire doit être éliminée manuellement à la curette, mais plusieurs soins (détartrage, traitement des caries, extractions dentaires non urgentes…) doivent être proscrits jusqu'à ce que l'atteinte buccale soit modérée ou que la maladie soit stabilisée.ConclusionLes dermatologues, médecins référents des patients atteints de MBAI, doivent donner à leurs patients des conseils d'hygiène buccodentaire adaptés en cas de lésions buccales, et collaborer étroitement avec les odontologistes et stomatologues pour ces patients.BackgroundAutoimmune bullous diseases (AIBD) may cause chronic oral lesions that progress insidiously.AimsTo provide recommendations for optimal oral-dental management of patients presenting AIBD with oral involvement.Patients and methodsIn the absence of scientific studies with high levels of proof, these recommendations have been drawn up at two meetings by a committee of experts on AIBD comprising 7 dermatologists, 1 stomatologist, 1 maxillofacial surgeon, 2 odontologists and 4 parodontologists.ResultsThe oral lesions associated with AIBD may be classified into three grades of severity: severe (generalised erosive gingivitis affecting at least 30% of dental sites), moderate (localised erosive gingivitis affecting less than 30% of dental sites) and controlled (no erosive oral lesions). Good oral-dental hygiene suited to the severity of the oral lesions, must be practised continually by these patients so as to avoid the formation of dental plaque, which aggravates symptoms. Dental and parodontal care must be considered in accordance with the severity grade of the oral lesions: in severe cases, the dental plaque must be eliminated manually with a curette, but several types of care (descaling, treatment for tooth decay, non-urgent extractions, etc.) must be suspended until the grade of severity is moderate or until the disease is stabilised.
http://ift.tt/2i1blhn
Syndrome de Lyell aux anti-PD1 d’évolution fatale
Source:Annales de Dermatologie et de Vénéréologie
Author(s): S. Demirtas, L. El Aridi, M. Acquitter, C. Fleuret, P. Plantin
http://ift.tt/2hVlHT4
Repair, Reuse, Recycle: The Expanding Role of Autophagy in Genome Maintenance
Publication date: Available online 21 December 2016
Source:Trends in Cell Biology
Author(s): Graeme Hewitt, Viktor I. Korolchuk
(Macro)Autophagy is a catabolic pathway that delivers excess, aggregated, or damaged proteins and organelles to lysosomes for degradation. Autophagy is activated in response to numerous cellular stressors such as increased levels of reactive oxygen species (ROS) and low levels of cellular nutrients as well as DNA damage. Although autophagy occurs in the cytoplasm, its inhibition leads to accumulation of DNA damage and genomic instability. In the past few years, our understanding of the interplay between autophagy and genomic stability has greatly increased. In this review we summarize these recent advances in understanding the molecular mechanisms linking autophagy to DNA repair.
http://ift.tt/2ift0Bg
Ensuring access to oral cholera vaccine to those who need them most
Source:Vaccine, Volume 35, Issue 3
Author(s): Francisco J. Luquero, Anne Ballard, David A. Sack
http://ift.tt/2iaEN8d
A phase III observer-blind randomized, controlled study to evaluate the immune response and the correlation with nasopharyngeal carriage after immunization of university students with a quadrivalent meningococcal ACWY glycoconjugate or serogroup B meningococcal vaccine
Publication date: 11 January 2017
Source:Vaccine, Volume 35, Issue 3
Author(s): Robert C. Read, Peter Dull, Xilian Bai, Kate Nolan, Jamie Findlow, Rohit Bazaz, Annett Kleinschmidt, Maggie McCarthy, Huajun Wang, Daniela Toneatto, Ray Borrow
BackgroundUniversity students have high rates of pharyngeal carriage of Neisseria meningitidis. Interruption of carriage acquisition is an important mechanism of vaccines for inducing herd protection. 4CMenB and MenACWY-CRM vaccines have been shown to be immunogenic against meningococcal serogroups B and ACWY respectively in younger age groups, and also to elicit a modest impact on meningococcal carriage in vaccinated students. However, vaccine responses in university students and the impact of serum bactericidal antibody (SBA) titers on meningococcal carriage are undetermined.MethodsImmunogenicity of two 4CMenB doses or one MenACWY-CRM dose was measured in university students at Months 2, 4, 6 and 12 post-first vaccination. Immunogenicity of one MenACWY-CRM dose in students with previous meningococcal serogroup C conjugate vaccination was also assessed. Immune responses were measured with an SBA assay using human complement (hSBA) against three reference strains for serogroup B and against one strain for each for serogroups C and Y. Correlations between hSBA titers and meningococcal carriage were analyzed.ResultsAll subjects demonstrated robust functional antibody responses to both vaccines at Month 2 and a high proportion maintained protective hSBA titers up to Month 12. At baseline, carriage of disease-associated serogroup B strains and serogroups C and Y were higher in subjects with already-protective hSBA titers. Post-vaccination, while both 4CMenB and MenACWY-CRM elicited robust immunogenicity in students, significant correlations between post-vaccination hSBA titers and carriage of disease-associated serogroups were not observed.Conclusions4CMenB and MenACWY-CRM were both highly immunogenic. There was no correlation between carriage and post-vaccination hSBA titers.
http://ift.tt/2h1YhHa
Editorial Board/Aims and Scope
Source:Vaccine, Volume 35, Issue 3
http://ift.tt/2iaLuak
Concomitant administration of a fully liquid, ready-to-use DTaP-IPV-HB-PRP-T hexavalent vaccine with a meningococcal serogroup C conjugate vaccine in infants
Source:Vaccine, Volume 35, Issue 3
Author(s): Timo Vesikari, Ray Borrow, Xavier Da Costa, Patrick Richard, Cécile Eymin, Florence Boisnard, Stephen Lockhart
DTaP-IPV-HB-PRP-T or hexavalent vaccines are indicated for primary and booster vaccination of infants and toddlers against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive diseases caused by Haemophilus influenzae type b (Hib). The present study evaluates the safety and immunogenicity of a ready-to-use hexavalent vaccine when co-administered with a meningococcal serogroup C conjugate (MenC) vaccine in infants.This was a phase III, open-label, randomised, multicentre study conducted in Finland. Healthy infants, aged 46–74days (n=350), were randomised in a ratio of 1:1 to receive DTaP-IPV-HB-PRP-T vaccine at two, three and four months, either with a MenC vaccine co-administered at two and four months (Group 1; n=175) or without MenC vaccine (Group 2; n=175). All infants also received routine rotavirus and 13-valent pneumococcal conjugate vaccines.The proportion of participants with an anti-HBs concentration ⩾10mIU/mL assessed one month after the third dose of DTaP-IPV-HB-PRP-T vaccine was 97.5% [95%CI: 93.1–99.3] in the coadministration group and 96.1% [95%CI: 91.8–98.6] in the group without MenC vaccine. The proportion of participants with an anti-MenC SBA titre ⩾8 assessed one month after the second dose of MenC vaccine was 100% in the coadministration group. Both primary objectives were achieved.Secondary immunogenicity and safety analyses showed that co-administration of DTaP-IPV-HB-PRP-T and MenC vaccines did not impact the immune response to the antigens of each of the two vaccines. All vaccines were well tolerated and the safety profile of DTaP-IPV-HB-PRP-T vaccine was similar in both groups.ClinicalTrials.gov identifier: NCT01839175; EudraCT number: 2012-005547-24.
http://ift.tt/2h1WsKc
Animal models of respiratory syncytial virus infection
Publication date: 11 January 2017
Source:Vaccine, Volume 35, Issue 3
Author(s): Geraldine Taylor
Human respiratory syncytial virus (hRSV) is a major cause of respiratory disease and hospitalisation of infants, worldwide, and is also responsible for significant morbidity in adults and excess deaths in the elderly. There is no licensed hRSV vaccine or effective therapeutic agent. However, there are a growing number of hRSV vaccine candidates that have been developed targeting different populations at risk of hRSV infection. Animal models of hRSV play an important role in the preclinical testing of hRSV vaccine candidates and although many have shown efficacy in preclinical studies, few have progressed to clinical trials or they have had only limited success. This is, at least in part, due to the lack of animal models that fully recapitulate the pathogenesis of hRSV infection in humans. This review summarises the strengths and limitations of animal models of hRSV, which include those in which hRSV is used to infect non-human mammalian hosts, and those in which non-human pneumoviruses, such as bovine (b)RSV and pneumonia virus of mice (PVM) are studied in their natural host.Apart from chimpanzees, other non-human primates (NHP) are only semi-permissive for hRSV replication and experimental infection with large doses of virus result in little or no clinical signs of disease, and generally only mild pulmonary pathology. Other animal models such as cotton rats, mice, ferrets, guinea pigs, hamsters, chinchillas, and neonatal lambs are also only semi-permissive for hRSV. Nevertheless, mice and cotton rats have been of value in the development of monoclonal antibody prophylaxis for infants at high risk of severe hRSV infection and have provided insights into mechanisms of immunity to and pathogenesis of hRSV. However, the extent to which they predict hRSV vaccine efficacy and safety is unclear and several hRSV vaccine candidates that are completely protective in rodent models are poorly effective in chimpanzees and other NHP, such as African Green monkeys. Furthermore, interpretation of findings from many rodent and NHP models of vaccine-enhanced hRSV disease has been confounded by sensitisation to non-viral antigens present in the vaccine and challenge virus.Studies of non-human pneumoviruses in their native hosts are more likely to reflect the pathogenesis of natural hRSV infection, and experimental infection of calves with bRSV and of mice with PVM result in clinical disease and extensive pulmonary pathology. These animal models have not only been of value in studies on mechanisms of immunity to and the pathogenesis of pneumovirus infections but have also been used to evaluate hRSV vaccine concepts. Furthermore, the similarities between the epidemiology of bRSV in calves and hRSV in infants and the high level of genetic and antigenic similarity between bRSV and hRSV, make the calf model of bRSV infection a relevant model for preclinical evaluation of hRSV vaccine candidates which contain proteins that are conserved between hRSV and bRSV.
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Training Tools for Nontechnical Skills for Surgeons—A Systematic Review
Publication date: Available online 20 December 2016
Source:Journal of Surgical Education
Author(s): Thomas Charles Wood, Nicholas Raison, Shreya Haldar, Oliver Brunckhorst, Craig McIlhenny, Prokar Dasgupta, Kamran Ahmed
ObjectiveDevelopment of nontechnical skills for surgeons has been recognized as an important factor in surgical care. Training tools for this specific domain are being created and validated to maximize the surgeon's nontechnical ability. This systematic review aims to outline, address, and recommend these training tools.DesignA full and comprehensive literature search, using a systematic format, was performed on ScienceDirect and PubMed, with data extraction occurring in line with specified inclusion criteria.SettingSystematic review was performed fully at King's College London.ResultsA total of 84 heterogeneous articles were used in this review. Further, 23 training tools including scoring systems, training programs, and mixtures of the two for a range of specialities were identified in the literature. Most can be applied to surgery overall, although some tools target specific specialities (such as neurosurgery). Interrater reliability, construct, content, and face validation statuses were variable according to the specific tool in question.ConclusionsStudy results pertaining to nontechnical skill training tools have thus far been universally positive, but further studies are required for those more recently developed and less extensively used tools. Recommendations can be made for individual training tools based on their level of validation and for their target audience. Based on the number of studies performed and their status of validity, NOTSS and Oxford NOTECHS II can be considered the gold standard for individual- and team-based nontechnical skills training, respectively, especially when used in conjunction with a training program.
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Cost Comparison of Fundamentals of Laparoscopic Surgery Training Completed With Standard Fundamentals of Laparoscopic Surgery Equipment versus Low-Cost Equipment
Publication date: Available online 20 December 2016
Source:Journal of Surgical Education
Author(s): Brenton R. Franklin, Sarah B. Placek, Mercy D. Wagner, Sarah M. Haviland, Mary T. O'Donnell, E. Matthew Ritter
ObjectiveTraining for the Fundamentals of Laparoscopic Surgery (FLS) skills test can be expensive. Previous work demonstrated that training on an ergonomically different, low-cost platform does not affect FLS skills test outcomes. This study compares the average training cost with standard FLS equipment and medical-grade consumables versus training on a lower cost platform with non–medical-grade consumables.DesignSubjects were prospectively randomized to either the standard FLS training platform (n = 19) with medical-grade consumables (S-FLS), or the low-cost platform (n = 20) with training-grade products (LC-FLS). Both groups trained to proficiency using previously established mastery learning standards on the 5 FLS tasks. The fixed and consumable cost differences were compared.SettingTraining occurred in a surgical simulation center.ParticipantsLaparoscopic novice medical student and resident physician health care professionals who had not completed the national FLS proficiency curriculum and who had performed less than 10 laparoscopic cases.ResultsThe fixed cost of the platform was considerably higher in the S-FLS group (S-FLS, $3360; LC-FLS, $879), and the average consumable training cost was significantly higher for the S-FLS group (S-FLS, $1384.52; LC-FLS, $153.79; p < 0.001). The LC-FLS group had a statistically discernable cost reduction for each consumable (Gauze $9.24 vs. $0.39, p = 0.002; EndoLoop $540.00 vs. $40.60, p < 0.001; extracorporeal suture $216.45 vs. $25.20, p < 0.001; intracorporeal suture $618.83 vs. $87.60, p < 0.001). The annual fixed and consumable cost to train 5 residents is $10,282.60 in the S-FLS group versus $1647.95 in the LC-FLS group.ConclusionsThis study shows that the average cost to train a single trainee to proficiency using a lower fixed-cost platform and non–medical-grade equipment results in significant financial savings. A 5-resident program will save approximately $8500 annually. Residency programs should consider adopting this strategy to reduce the cost of FLS training.
http://ift.tt/2h1WUrV
Common Femoral Artery Access on YouTube: What Practices are Being Shown and Who is Delivering the Message?
Publication date: Available online 20 December 2016
Source:Journal of Surgical Education
Author(s): Grayson S. Pitcher, Daniel H. Newton, Michael F. Amendola
ObjectivesNovice learners are increasingly turning to YouTube as a learning resource for surgical procedures. One example of such a procedure is common femoral artery puncture and sheath placement. Practitioners in several specialties perform this procedure to access the arterial system for angiography and intervention. We set forth to compare the techniques demonstrated on YouTube by the various specialists, as well as compare each specialty׳s prevalence on this website.MethodsYouTube (www.youtube.com) was accessed in December 2015 at multiple time points with a cleared-cache web browser for the keyword search categories: "femoral artery access," "femoral access," and "angiography access." The top 500 videos from each of these keyword searches were analyzed. Videos were categorized by practitioner specialty, technique, duration of video, age of video, and total views. Videos with clear demonstration of femoral artery access were included in the analysis. All industry videos were excluded from the analysis. Categorical variables were compared using Fisher׳s exact test, and continuous variables were compared with the Student׳s t-test.ResultsA total of 2460, 4680 and 1800 videos were found for each keyword search, respectively. Of these, 33 videos clearly demonstrated femoral artery access technique. Vascular specialists, compared to interventional cardiology and radiology, had fewer videos (n = 4 vs. 14) and older videos (3.5 ± 2.1y vs. 2.25 ± 0.5y, p < 0.05). The vascular specialists demonstrated ultrasound-guided access, while interventional cardiology predominantly demonstrated landmark-guided access (p < 0.05).ConclusionsAlthough YouTube and other online resources are being used by novice learners, vascular specialists are underrepresented for femoral artery access, a foundational vascular procedure. Other practitioners demonstrate videos with landmark-guided access and rarely demonstrate ultrasound use. As recognized vascular experts, vascular surgeons should improve their visibility in online learning resources.
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Costs and Resource Use following Defunctioning Stoma in Low Anterior Resection for Cancer-A long-term analysis of a randomized multicenter trial
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Hannah Floodeen, Olof Hallböök, Lars A. Hagberg, Peter Matthiessen
BackgroundDefunctioning stoma in low anterior resection (LAR) for rectal cancer can prevent major complications, but overall cost-effectiveness for the healthcare provider is unknown. This study compared inpatient healthcare resources and costs within 5 years of LAR between two randomized groups of patients undergoing LAR with and without defunctioning stoma.MethodFive-year follow-up of a randomized, multicenter trial on LAR (NCT 00636948) with (stoma; n=116) or without (no stoma; n=118) defunctioning stoma comparing inpatient healthcare resources and costs. Unplanned stoma formation, days with stoma, length of hospital stay, reoperations, and total associated inpatient costs were analyzed.ResultsAverage costs were € 21.663 per patient with defunctioning stoma and € 15.922 per patient without defunctioning stoma within 5 years of LAR, resulting in an average cost-saving of € 5.741. There was no difference between groups regarding the total number of days with any stoma (stoma=33398 vs. no stoma=34068). The total number of unplanned reoperations were 70 (no stoma) and 32 (stoma); p<0.001. In the group randomized to no stoma at LAR, 30.5% (36/118) required an unplanned stoma later.ConclusionRandomization to defunctioning stoma in LAR was more expensive than no stoma, despite the cost-savings associated with a reduced frequency of anastomotic leakage. Both groups required the same total number of days with a stoma within five years of LAR.
http://ift.tt/2i0NkqP
Some Chemicals that Cause Tumours of the Kidney or Urinary Bladder in Rodents and Some Other Substances.
This monograph evaluates the carcinogenic risk to humans posed by 20 individual compounds and three groups of compounds (cyclamates, saccharin and its salts, and nitrilotriacetic acid and its salts) that are known to induce tumours of the kidney or urinary bladder in rodents. As data on cancer in humans were judged inadequate for all compounds and groups of compounds, the evaluations draw on recent guidelines for determining whether the mechanisms by which a chemical exerts its carcinogenic effects in rodents are relevant to humans. Evaluations also draw on findings from studies of metabolic fate, toxic effects, reproductive and developmental effects, and genetic and related effects. Some of the compounds covered in the volume are widely used as chemical intermediates, pesticides, artificial sweeteners, and food additives. The volume also includes evaluations of the analgesic and antipyretic, paracetamol, and several naturally occurring substances in food. All but two of the compounds (meta-dichlorobenzene and methyl tert-butyl ether) were evaluated in previous IARC Monographs. Re-evaluations were made in the light of both new studies of the compounds and a growing body of evidence concerning certain pathological processes that lead to tumour development in the kidney and urinary bladder of rats exposed to some chemicals. Eight compounds were classified as possibly carcinogenic to humans: ortho-anisidine, chloroform, chlorothalonil, para-dichlorobenzene, hexachloroethane, nitrilotriacetic acid and its salts, sodium ortho-phenylphenate, and potassium bromate. The remaining substances could not be classified on the basis of available data.
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Coercion in mental health: a trial of the effectiveness of community treatment orders and an investigation of informal coercion in community mental health care.
The OCTET RCT showed no effect of community treatment orders for patients with psychosis on hospital readmissions or on clinical or social functioning.
http://ift.tt/2iawpp6
Parenting Matters: Supporting Parents of Children Ages 0-8.
Decades of research have demonstrated that the parent-child dyad and the environment of the family—which includes all primary caregivers—are at the foundation of children's well-being and healthy development. From birth, children are learning and rely on parents and the other caregivers in their lives to protect and care for them. The impact of parents may never be greater than during the earliest years of life, when a child's brain is rapidly developing and when nearly all of her or his experiences are created and shaped by parents and the family environment. Parents help children build and refine their knowledge and skills, charting a trajectory for their health and well-being during childhood and beyond. The experience of parenting also impacts parents themselves. For instance, parenting can enrich and give focus to parents' lives; generate stress or calm; and create any number of emotions, including feelings of happiness, sadness, fulfillment, and anger.
http://ift.tt/2h1OReJ
Synthetic peptide antigens derived from long-chain alpha-neurotoxins: immunogenicity effect against elapid venoms
Source:Peptides
Author(s): Guillermo de la Rosa, Nina Pastor, Alejandro Alagón, Gerardo Corzo
Three-finger toxins (3FTXs), especially α-neurotoxins, are the most poorly neutralized elapid snake toxins by current antivenoms. In this work, the conserved structural similarity and motif arrangements of long-chain α-neurotoxins led us to design peptides with consensus sequences. Eight long-chain α-neurotoxins (also known as Type II) were used to generate a consensus sequence from which two peptides were chemically synthesized, LCP1 and LCP2. Rabbit sera raised against them were able to generate partially-neutralizing antibodies, which delayed mice mortality in neutralization assays against Naja haje, Dendrospis polylepis and Ophiophagus hannah venoms.
http://ift.tt/2i0JLAO
Impairment of the visuo-spatial sketch pad by left prefrontal transcranial direct current stimulation
Source:Brain Stimulation
Author(s): A.S. Alencastro, E.M. Borigato, I.B. Rios, M.O. Santos, R.C.A. Melo, R.E. Torres, V.M.S. Moraes, S.L. Sá, A. Iannone, A. Garcia, C. Satler, M.C.H. Tavares, J.P. Brasil-Neto
http://ift.tt/2ifleaB
Pathological changes of adipose tissue in secondary lymphedema
Abstract
Background
The pathophysiology of lymphedema is poorly understood. Current treatment options include compression therapy, resection, liposuction, and lymphatic microsurgery, but determining the optimal treatment approach for each patient remains challenging.
Objectives
We characterized skin and adipose tissue alterations in the setting of secondary lymphedema.
Methods
Morphologic and histopathologic evaluations were conducted for 70 specimens collected from 26 female patients with lower extremity secondary lymphedema following surgical intervention for gynecologic cancers. Indocyanine green lymphography was performed for each patient to assess lymphedema severity.
Results
Macroscopic and ultrasound findings revealed that lymphedema adipose tissue had larger lobules of adipose tissue, with these lobules surrounded by thick collagen fibers and interstitial lymphatic fluid. In lymphedema specimens, adipocytes displayed hypertrophic changes and more collagen fiber deposits when examined using electromicroscopy, whole mount staining, and immunohistochemistry. The number of capillary lymphatic channels was also found to be increased in the dermis of lymphedema limbs. Crown-like structures (dead adipocytes surrounded by M1 macrophages) were less frequently seen in lymphedema samples. Flow cytometry revealed that, among the cellular components of adipose tissue, adipose-derived stem/stromal cells (ASCs) and M2 macrophages were decreased in number in lymphedema adipose tissue compared to normal controls.
Conclusions
These findings suggest that long-term lymphatic volume overload can induce chronic tissue inflammation, progressive fibrosis, impaired homeostasis, altered remodeling of adipose tissue, impaired regenerative capacity, and immunologic dysfunction. Further elucidation of the pathophysiologic mechanisms underlying lymphedema will lead to more reliable therapeutic strategies.
This article is protected by copyright. All rights reserved.
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Disfluency characteristics of children with attention-deficit/hyperactivity disorder symptoms
Source:Journal of Communication Disorders
Author(s): Hyunkyung Lee, Hyunsub Sim, Eunju Lee, Dahye Choi
The purpose of the current study was to investigate the characteristics of speech disfluency in 15 children with attention-deficit/hyperactivity disorder (ADHD) symptoms and 15 age-matched control children. Reading, story retelling, and picture description tasks were used to elicit utterances from the participants. The findings indicated that children with ADHD symptoms produced significantly more stuttering-like disfluencies (SLD) and other disfluencies (OD) when compared to the control group during all three tasks. Further statistical analysis showed that children with ADHD symptoms produced more OD during the story retelling task than the other two tasks, whereas no significant differences in OD were observed among the three tasks in the control children. Finally, children with ADHD symptoms exhibited a higher proportion of SLD in total disfluencies (TD) than the control children. These results are consistent with previous studies that children with ADHD are disfluent in their verbal production. Furthermore, children with ADHD symptoms seem to be more vulnerable to a speaking task that places greater demands on their attentional resources for language production, resulting in increased speech disfluencies.
http://ift.tt/2hUTuM8
Personalized and Cell-based Antitumor Immunization MVX-ONCO-1 in Advanced HNSCC
Intervention: Other: MVX-ONCO-1
Sponsor: Swiss Group for Clinical Cancer Research
Not yet recruiting - verified December 2016
http://ift.tt/2hHzPP1
Randomized Trial of Avelumab-cetuximab-radiotherapy Versus SOCs in LA SCCHN (REACH)
Interventions: Drug: Cetuximab; Drug: avelumab; Drug: Cisplatin; Radiation: IMRT
Sponsors: Groupe Oncologie Radiotherapie Tete et Cou; Merck Sharp & Dohme Corp.; Pfizer
Not yet recruiting - verified December 2016
http://ift.tt/2hTfzrQ
A Study of APR-246 in Oesophageal Cancer
Intervention: Drug: APR-246
Sponsor: Peter MacCallum Cancer Centre, Australia
Not yet recruiting - verified November 2016
http://ift.tt/2hHtBi2
Primary hyperparathyroidism regression associated to cinacalcet therapy proved by 99mTc-MIBI scintigraphy
Publication date: Available online 20 December 2016
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): A. Coloma, S. Hernández-Estrada, H. Bowles, N. Sánchez, D. Fuster, J. Torregrosa
http://ift.tt/2hTlPzU
Tumor-derived CD4+CD25+regulatory T cells inhibit dendritic cells function by CTLA-4
Publication date: Available online 21 December 2016
Source:Pathology - Research and Practice
Author(s): Xin Chen, Yong Du, Qingqing Hu, ZhiMing Huang
PurposeCD4+CD25+regulatoryT cells (Tregs) play an important role in anti-tumor immune responses. Poor prognosis and declining survival rates have intimate connection with high Treg expression in cancer patients. Cytotoxic T Lymphocyte-associated protein (CTLA-4) is one of the most prominent molecules on Treg. In our previous research, we have demonstrated that HCC-derived Tregs can interfere with Dendritic cells (DCs) function and down-modulate CD80/CD86 on DCs in vitro in a cell-contact dependent way. However the mechanism of how HCC-derived Treg affect DC phenotype are not very clear. Therefore, we investigated the function of CTLA-4 in anti-tumor immune responses.Materials and methodsWe established BABL/C mouse with hepatocellular carcinoma model, and tumor-derived Tregs were purified by magnetic cell sorting using mouse CD4+CD25+regulatoryT cell isolation kit. Splenic DCs were enriched using CD11c-conjugated microbeads. Then splenic DCs co-cultured with tumor-derived Tregs and antibody-blocking experiments was performed.ResultsIn our research, we found the down-modulation of CD80/CD86 on DCs was inhibited by blocking CTLA-4. HCC-derived Tregs down-modulated CD80/CD86 on DCs in a CTLA-4-dependent way. Blockade of CTLA-4 can lead to increase DC-mediated immunity.ConclusionCTLA-4 play a vital role in Treg-mediated immnue inhibition and this discovery can open up new ideas for the development of therapeutic strategies.
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Pathologic features of colorectal carcinomas associated with Crohn’s disease in Korean population
Publication date: Available online 21 December 2016
Source:Pathology - Research and Practice
Author(s): Jiyoon Kim, Ho-Su Lee, Sang Hyoung Park, Suk-Kyun Yang, Byong Duk Ye, Dong-Hoon Yang, Kyung-Jo Kim, Jeong-Sik Byeon, Yong Sik Yoon, Chang Sik Yu, Jihun Kim
BackgroundColorectal cancer (CRC) has been known to complicate Crohn's disease (CD). Several reports in Western population revealed that CRC in CD were characterized by much younger onset and equal distribution of tumors along the entire colon. However, clinicopathologic features of CD-associated CRC in Korean population have not been well documented yet.MethodsAmong 2968 Korean CD patients, 16 patients (0.54%) were found to develop CRC during follow up. We reviewed clinicopathologic features of the 16 CRC patients.ResultsThe mean age at the time of CRC diagnosis was 39.3 years (range 18–59 years) and 14 of the 16 CRCs (87.5%) occurred in anorectal region. Mucinous adenocarcinoma was strikingly frequent (9/16, 56.3%) and eight cases (8/9) of the mucinous adenocarcinoma cases were located at anorectal area. The other cases consisted of 4 tubular adenocarcinomas, 2 signet ring cell carcinomas and 1 neuroendocrine tumor. Thirteen patients (81.3%) had a history of perianal fistula and 8 of them had a histological association between the CRC and the perianal fistula.ConclusionsCD-associated CRC was characterized by young age at diagnosis, mucinous histology and association with perianal fistula in Korean patients.
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Stereotactic precision and conventional radiotherapy evaluation (SPACE)-Trial for medically inoperable Stage I NSCLC: A lost opportunity?
Publication date: Available online 20 December 2016
Source:Radiotherapy and Oncology
Author(s): Filippo Alongi, Umberto Tebano, Rosario Mazzola
http://ift.tt/2i098mp
Anxiety Sensitivity Explains Associations between Anxious Arousal Symptoms and Smoking Abstinence Expectancies, Perceived Barriers to Cessation, and Problems Experienced during Past Quit Attempts among Low-Income Smokers
Source:Journal of Anxiety Disorders
Author(s): Michael J. Zvolensky, Daniel J. Paulus, Kirsten J. Langdon, Zuzuky Robles, Lorra Garey, Peter J. Norton, Michael S. Businelle
Disproportionately more smokers report low-income and mental health problems relative to non-smokers. Low-income smokers may use smoking to alleviate negative emotional states resulting from exposure to multiple stressors. Yet, little work has been devoted to elucidating mechanisms that may explain the association between negative emotional states and smoking-related processes among low-income smokers. The present study sought to address this gap by examining anxiety sensitivity, a transdiagnostic factor related to both anxiety and smoking, as a potential mediator for the influence of anxiety symptoms on smoking-related processes, including threat-related smoking abstinence expectancies (somatic symptoms and harmful consequences), perceived barriers for cessation, and problems experienced during past quit attempts. Participants included treatment-seeking daily cigarette smokers (n=101; 68.3% male; Mage=47.1; SD=10.2). Results indicated that anxiety symptoms exerted a significant indirect effect through anxiety sensitivity for threat-related smoking abstinence expectancies (somatic symptoms and harmful consequences), perceived barriers for cessation, and problems experienced during past quit attempts. The present results provide empirical support that anxiety sensitivity may be an underlying mechanism that partially explains the relation between anxiety symptoms and smoking processes among low-income treatment-seeking smokers. Findings broaden current theoretical understanding of pathways through which anxiety symptoms contribute to maladaptive smoking processes and cognitions among socioeconomically disadvantaged smokers.
http://ift.tt/2hT9CuQ
All-or-Nothing Thinking: The Processing of Emotional Expressions in Traumatized Post-Deployment Soldiers
Source:Journal of Anxiety Disorders
Author(s): Claudia Gebhardt, Christina Alliger-Horn, Kristin Mitte, Heide Glaesmer
The exposure to trauma is a dramatic life event with complex consequences among those like changes in information processing. Dysfunctional cognitions like a negative interpretation of information are a risk factor for the development of trauma-related disorders. The aim of the present study was to test whether post-deployment soldiers with trauma differ in their interpretation of emotional expressions from member of a control group. Interpretation of emotional expressions was assessed in a sample of 106 males (n=53 soldiers, n=53 controls) with the Similarity Rating Task (simtask) and analyzed with a multidimensional scaling (MDS) approach. The findings suggest that individuals with war-related trauma tend to show a negative interpretation bias. Furthermore, traumatized individuals did not discriminate between different intensities of emotional expressions the way controls did. The findings are discussed in terms of the role of dysfunctional cognitions in the development and treatment of mental disorders.
http://ift.tt/2hHmeYd
Msx1-Positive Progenitors in the Retinal Ciliary Margin Give Rise to Both Neural and Non-neural Progenies in Mammals
Publication date: Available online 20 December 2016
Source:Developmental Cell
Author(s): Marie-Claude Bélanger, Benoit Robert, Michel Cayouette
In lower vertebrates, stem/progenitor cells located in a peripheral domain of the retina, called the ciliary margin zone (CMZ), cooperate with retinal domain progenitors to build the mature neural retina. In mammals, it is believed that the CMZ lacks neurogenic potential and that the retina develops from one pool of multipotent retinal progenitor cells (RPCs). Here we identify a population of Msx1-expressing progenitors in the mouse CMZ that is both molecularly and functionally distinct from RPCs. Using genetic lineage tracing, we report that Msx1 progenitors have unique developmental properties compared with RPCs. Msx1 lineages contain both neural retina and non-neural ciliary epithelial progenies and overall generate fewer photoreceptors than classical RPC lineages. Furthermore, we show that the endocytic adaptor protein Numb regulates the balance between neural and non-neural fates in Msx1 progenitors. These results uncover a population of CMZ progenitors, distinct from classical RPCs, that also contributes to mammalian retinogenesis.
Graphical abstract
Teaser
The mammalian retina was thought to develop from a single pool of multipotent retinal progenitor cells (RPCs), but Bélanger et al. now identify a distinct progenitor population in the mouse retinal periphery that also contributes to retinogenesis in addition to producing non-neural ciliary epithelium.http://ift.tt/2ieKmhM
Editorial board
Publication date: February 2017
Source:Atmospheric Environment, Volume 151
http://ift.tt/2hU80U6
The impact of the appetite-regulating, orexigenic peptide ghrelin on alcohol use disorders: a systematic review of preclinical and clinical data
Source:Biological Psychology
Author(s): Anne Koopmann, Rilana Schuster, Falk Kiefer
Ghrelin, which is mainly released from the stomach, is the most important orexigenic regulator of food intake, inducing appetite, enhancing adiposity and releasing growth hormone. Besides the hypothalamus, ghrelin receptors (GHS-R1A) are also expressed in the mesolimbic dopaminergic system, which increases the possibility that ghrelin plays an important role in reward regulation for substance use disorders such as alcohol addiction, especially through activating the cholinergic-dopaminergic reward link. In this review we focus on the impact of ghrelin on the development and maintenance of alcohol addiction/dependence, alcohol consumption, alcohol craving and alcohol withdrawal, attempting to integrate preclinical and clinical studies concerning the intriguing relationship between appetite regulation, reward and alcohol addiction.Integrating the existing preclinical and clinical data on ghrelin antagonism, specifically at the GHS-R1A receptor in mesolimbic dopaminergic pathways, may reveal a new and innovative target for the treatment of alcohol dependence in the future.
http://ift.tt/2hSLxEP
The Role of Reward Circuitry and Food Addiction in the Obesity Epidemic: An Update
Source:Biological Psychology
Author(s): Sarah-Jane Leigh, Margaret J. Morris
The increasing worldwide prevalence of obesity is partially related to the ready availability of highly palatable foods which increases the incidence of hedonic, non-homeostatic feeding. The "food addiction" hypothesis postulates that exposure to these foods alters the brain's reward circuitry, driving an addiction-like behavioural phenotype of compulsive overeating. This review highlights recent evidence that examines changes in the mesolimbic dopaminergic circuit, the primary component of the reward system, associated with exposure to highly palatable foods and obesity. The majority of obesity studies in animals have not measured addictive-like behaviours, but reports of such behaviours have been restricted to experiments using models of binge eating. Where examined, the prevalence of addiction-like behaviour in overweight and obese subjects indicates that 10-25% of the population meets the Yale Food Addiction Score criteria. There is considerable overlap in the behaviours ascribed to food addiction and binge eating disorder, and food addiction scores correlate highly with measures of binge eating. We feel that more research is required in humans to determine whether food addiction is both behaviourally and neurobiologically distinct from binge eating disorder. While the reward circuitry is clearly affected by both highly palatable foods and diet-induced obesity in a similar manner to short and long exposure to drugs of abuse, the challenge for the future is to show that these neurobiological changes are associated with addiction-like behaviour.
http://ift.tt/2hGXFdH
Health Status of Patients with Moderate to Severe COPD after Treatment with Nebulized Arformoterol Tartrate or Placebo for 1 Year
Source:Clinical Therapeutics
Author(s): James F. Donohue, Vaidyanathan Ganapathy, Vamsi Bollu, Michael D. Stensland, Lauren M. Nelson
PurposeChronic obstructive pulmonary disease (COPD) is a progressive disease that impairs both objectively measured lung function and patient-reported health status. In a randomized clinical trial of patients with moderate to severe COPD, we compared changes in health status after adding arformoterol tartrate or placebo to patients' treatment regimens.MethodsIn this multicenter, double-blind trial, patients were randomized to receive nebulized arformoterol 15 µg BID (n = 420) or matched placebo (n = 421). Treatment with other COPD medications was permitted, except for long-acting β2-agonists. Inclusion criteria were a forced expiratory volume in 1 second (FEV1) ≤65% of predicted, FEV1 >0.50 L, age ≥40 years, smoking history ≥15 pack-years, and a baseline breathlessness severity grade ≥2. The Clinical COPD Questionnaire (CCQ) was used to measure health status at randomization and at months 3, 6, and 12. CCQ scores range from 0 to 6, with higher scores indicating worse health status, and a decrease from baseline in total score by 0.4 point is considered clinically significant. Outcomes were analyzed by using mixed models for repeated measures.FindingsAt baseline, patients' mean age was 63.8 years; 42.9% of patients were female, and 51.4% were current smokers. The mean baseline CCQ total scores were 2.88 and 2.91 for the arformoterol and placebo groups, respectively. A total of 841 patients were randomized to receive either arformoterol (n = 420) or placebo (n = 421); among them, 211 (50.1%) who received placebo and 255 (60.7%) who received arformoterol completed the trial. Arformoterol-treated patients had greater mean improvement from baseline in CCQ total score (−0.18 vs 0.02; P = 0.001), symptoms (−0.21 vs 0.01; P = 0.002), functional state (−0.15 vs 0.02; P = 0.018), and mental state (−0.18 vs 0.02; P = 0.023) than patients receiving placebo. At study end, 38.3% of the arformoterol-treated patients and 30.8% of patients receiving placebo reported clinically significant improvements on the CCQ (P = 0.026). These improvements were only modestly correlated with improvements in FEV1 (r = −0.15; P < 0.01).ImplicationsIn this 52-week trial, arformoterol-treated patients had greater improvements in health status than patients receiving placebo. Assessing health status along with lung function seems to provide additional information regarding the effectiveness of COPD maintenance treatments. ClinicalTrials.gov identifier: NCT00909779.
http://ift.tt/2i9B8aN
Different Disclosed Probabilities to Receive an Antiemetic Equally Decrease Subjective Symptoms in an Experimental Placebo Study: To Be or Not to Be Sure
Source:Clinical Therapeutics
Author(s): Katja Weimer, Björn Horing, Eric R. Muth, Jenna L. Scisco, Sibylle Klosterhalfen, Paul Enck
PurposeThe purpose of this study was to examine whether the disclosed probability of receiving an antiemetic affects nausea.MethodsForty-eight healthy participants (mean [SD] age, 26.8 [5.4] years; 50% female) were exposed to 5 × 2 minutes of nauseogenic body rotations on 2 days. On day 2, participants were randomized to 3 experimental groups that were given different instructions concerning the probability of receiving an antiemetic remedy (100%, 50%, or 0% probability), whereas all received an inert substance. Subjective symptoms, behavioral (rotation tolerance) measures, and physiologic (electrogastrogram) measures of nausea were assessed and mediator and moderator analyses performed for effects of expectations and psychological characteristics on outcomes.FindingsDisclosed probabilities of both 100% and 50% significantly reduced subjective symptoms of nausea in an equal manner compared with the 0% probability group from day 1 to day 2. This effect was found for neither rotation tolerance nor myoelectric gastric activity. Expectations and psychological characteristics did not affect the results found. Post hoc analyses revealed that women only seem to be susceptible to this placebo effect.ImplicationsNausea is susceptible to placebo effects independent of the disclosed probability of receiving a drug and of explicit expectations. In line with placebo research, this effect is probably attributable to central mechanisms, and it is speculated that it could be related to the reward circuitry and social interactions.
http://ift.tt/2h10wug
Subcutaneous Dirofilariasis: A Masquerade of a Palisaded Granulomatous Dermatitis
Abstract
Dirofilaria species are roundworms responsible for "heartworm" in canines. On occasion, humans are an accidental host, resulting in pulmonary (D. immitis) or extrapulmonary (D. repens) manifestations. Of the extrapulmonary sites of involvement, subcutaneous involvement is particularly common. We report a case of a 49 year-old female who presented with an erythematous nodule on her shin, which closely resembled necrobiosis lipoidica on histopathologic examination. On closer examination, there were foci of necrosis which harbored segments of the nematode, diagnostic of dirofiliarisis. We present this case to highlight the histopathologic similarities and differences between palisaded necrobiotic conditions and this potentially under-recognized entity.
http://ift.tt/2hqi0Bf
Eruptive xanthogranuloma in a healthy adult male
Abstract
Xanthogranuloma is a benign, non-Langerhans cell histiocytosis primarily diagnosed in infants and children, although a subset occurs in adults. Multifocal eruptive presentation of xanthogranuloma is very rare with only four previous cases reported in the literature to our knowledge. We describe a case of eruptive xanthogranuloma in a 49-year-old man who presented with sudden onset of numerous asymptomatic, red-yellow to orange papules on the face, scalp, axilla, flank, and scrotum. Histologic features were consistent with xanthogranuloma with diffuse mixed infiltrate of foamy histiocytes, Touton giant cells, and lymphocytes. Other than temporarily elevated non-fasting triglycerides, lab values have been unremarkable including serum plasma electrophoresis; however, the patient will continue to be monitored for ocular and other extracutaneous involvement and hematologic malignancies.
http://ift.tt/2hbtZ9J
Amicrobial Pustulosis of the Folds: Report of 4 Cases
Abstract
Amicrobial pustulosis of the folds (APF) is a rare disease characterized by aseptic pustular lesions involving cutaneous folds, typically occurring in the context of an autoimmune disorder. We present 4 patients with APF, focusing on clinical and histopathologic characteristics to improve the recognition of this entity. All 4 patients had intertriginous and extra-intertriginous involvement. Common histopathologic features of skin biopsies in these patients were intracorneal, subcorneal, intraepidermal, perivascular, perifollicular, and interstitial neutrophilic inflammation. Pustules overlying adnexal ostium and papillary dermal edema were consistently observed. The pustules were negative for microorganisms on stain testing. In these cases, associated conditions were undifferentiated connective tissue disease, systemic lupus erythematosus, antiphospholipid syndrome, Crohn disease, and Hashimoto thyroiditis. The aforementioned clinical and histopathologic characteristics of patients with suspected or diagnosed connective tissue disorders should lead to suspicion for APF.
http://ift.tt/2hqaHJW
Epidermal Anti-Programmed Cell Death-Ligand 1 Expression in TEN Associated with Nivolumab Therapy
Abstract
Background
Nivolumab is an anti-programmed cell death receptor-1 (PD-1) antibody used in the treatment of metastatic or unresectable melanoma. Cutaneous reactions are the most common adverse events reported with these agents and are rarely severe or life-threatening.
Methods
Case report describing the clinicopathological findings of a patient with a fatal toxic epidermal necrolysis (TEN) eruption associated with use of nivolumab for treatment of metastatic melanoma.
Results
The patient developed a pruritic, morbiliform eruption, which slowly progressed over 3 months to a tender, exfoliative dermatosis. Histology initially demonstrated interface dermatitis and subsequently revealed full thickness epidermal necrosis. The diagnosis of TEN was made. From initial biopsy to TEN presentation, there was an increase in the number of CD8+ lymphocytes within the dermal-epidermal junction and programmed death ligand 1 (PD-L1) expression increased in both lymphocytes and keratinocytes. Despite treatment with infliximab, high dose steroids, and intravenous immunoglobulin, the patient expired.
Conclusions
Herein we describe what we believe is the 2nd case of TEN associated with anti-PD1 therapy reported in the literature. Increased expression of PD-L1 by immunohistochemistry was observed as the eruption progressed to TEN. Early diagnosis and treatment is necessary in these fatal TEN reactions secondary to the anti-PD-1 antibody therapies.
http://ift.tt/2hbFzBB
Primary cutaneous histiocytoid carcinoma with distant metastasis
Abstract
Distinguishing primary cutaneous adnexal carcinoma from metastatic carcinoma of unknown primary can be a diagnostic challenge due to the frequent overlap of histologic and immunohistochemical features. A 58-year-old man presented with a tender, indurated plaque on axillary skin. Biopsy revealed infiltrating atypical cells throughout the dermis, without connection to the epidermis. Tumor cells had a histiocytoid appearance and displayed mild pleomorphism. The tumor was discohesive and had areas with a single file pattern. Signet ring cells were also present. Cells were reactive with CK7, CK5/6, p63, GATA3, GCDFP-15 and Her 2-neu. Additional studies were negative, including TTF-1, CDX2, E-cadherin, mammaglobin, ER and PR. Thorough clinical and radiologic evaluation failed to identify an occult primary extracutaneous malignancy; however, regional lymphadenopathy, widespread osteoblastic lesions and multiple subcentimeter liver hypodensities were noted. Considering the clinical and histopathologic features, the diagnosis of primary cutaneous histiocytoid carcinoma with distant metastasis was favored.
http://ift.tt/2hqkxeu
Static Otolithic Drive Alters Presynaptic Inhibition in Soleus Motor Pool
Publication date: Available online 20 December 2016
Source:Journal of Electromyography and Kinesiology
Author(s): Apollonia Fox, David Koceja
The vestibular system has both direct and indirect connections to the soleus motor pool via the vestibulospinal and reticulospinal tracts. The exact nature of how this vestibular information is integrated within the spinal cord is largely unknown. The purpose of this study was to identify whether changes in static otolithic drive altered the amount of presynaptic inhibition in the soleus H-reflex pathway. Changes in static otolithic drive were investigated in sixteen healthy participants using a tilt table. Two presynaptic pathways (common peroneal and femoral) to the soleus H-reflex were tested in three weight conditions (supine, non-weight bearing, and weight bearing). The dependent variable was the peak-to-peak amplitude of the soleus H-reflex. Inhibition to the soleus motor pool through the common peroneal nerve pathway differed significantly during weight conditions and tilt. During tilt and non-weight bearing there was greater inhibition of the soleus H-reflex compared to supine, however, this effect was reversed during tilt and weight bearing. Facilitation from the femoral nerve pathway was reduced by tilt compared to supine, but this reduction was unaffected by weight condition. This supports a role of the vestibular system as providing complex, task-dependent presynaptic input to motoneurons in the lower limbs.
http://ift.tt/2hGPGxy
Postural Response Characterization of Standing Humans to Multi-directional, Predictable and Unpredictable Perturbations to the Arm
Publication date: Available online 20 December 2016
Source:Journal of Electromyography and Kinesiology
Author(s): Ali Forghani, Richard Preuss, Theodore Milner
When the arm of a standing human is perturbed in an unpredictable direction, postural muscles are activated at latencies as short as 50-110 ms. While the motion of the body clearly progresses in hand-to-leg sequence, there is no systematic muscle activation sequence from the arm to the leg muscles, suggesting that the activation of the muscles is not likely the result of local stretch reflexes. In fact, the lower limb muscles are activated before the upright posture is significantly disturbed. The short-latency activation amplitude and the activation probability are clearly tuned to the direction of the arm perturbation for both rostral and caudal muscles. The effect of central set on the short-latency response has been investigated by manipulating the predictability of the perturbations. Possible underlying neural mechanisms have been discussed.
http://ift.tt/2hSEzzn
Analysis of three-dimensional knee kinematics during stair descent two decades post-ACL rupture - data revisited using Statistical Parametric Mapping
Publication date: Available online 20 December 2016
Source:Journal of Electromyography and Kinesiology
Author(s): Gisela Sole, Todd Pataky, Eva Tengman, Charlotte Häger
Changes in movement patterns following knee injuries have generally used analyses of pre-defined discrete event-related variables, whereas statistical parametric mapping (SPM) assesses continuous data over time. We applied SPM to test differences for knee trajectories during stair descent between participants with past anterior cruciate ligament (ACL) rupture who underwent reconstruction or only physical therapy compared to healthy controls. Three-dimensional knee joint kinematics during stair descent were registered for 31 subjects with ACL reconstruction (ACLR), 36 subjects with ACL rupture managed with physical therapy only (ACLPT) (∼23 years post-injury), and 32 uninjured controls. SPM was used to assess differences between groups for the entire three-component knee trajectory. A significant difference between the three groups was found for the first ∼10% of stance phase. Post-hoc analyses showed between-group differences when comparing the ACLPT to the control groups. Analyses of ACLPT versus control groups for individual vector components suggested a combination of less flexion at initial foot contact, and less adduction during weight acceptance (∼40% of stance). Altered knee kinematics were confirmed during weight acceptance of stair descent for the ACLPT group compared to controls, but not for ACLR group. Further exploration of the use of SPM and agreement with clinical gait assessment is warranted.
http://ift.tt/2hGSPgE
Effects of age and sex on fatigability and recovery from a sustained maximal isometric voluntary contraction
Publication date: Available online 20 December 2016
Source:Journal of Electromyography and Kinesiology
Author(s): Rima Solianik, Lina Kreivėnaitė, Vytautas Streckis, Dalia Mickevičienė, Albertas Skurvydas
The aim was to assess the effects of sex and age on fatigability and recovery from sustained maximal voluntary contraction (MVC) of the knee extensor muscles. The central (central activation ratio (CAR) and electrical activity amplitude) and peripheral (electrically evoked torque and muscle contractile properties) factors contributing to fatigue and recovery of 24 young adults (12 males) aged 23.2 ± 3.6 years and 20 older adults (12 males) aged 70.6 ± 4.4 years were compared. The increase in central and peripheral fatigue was greater (p ⩽ 0.01) in the young adults vs the older adults. Sex differences (p = 0.002) regarding MVC were attributed to the greater (p < 0.01) peripheral fatigue of males vs females. The recovery rate of MVC was greater (p < 0.001) in the young adults vs the older adults, with no sex effect. The recovery of MVC was correlated with the CAR in older adults (p = 0.001). Thus, the greater endurance observed with age is caused by differences in central and peripheral mechanisms, whereas the greater endurance in females is caused by a difference in a mechanism located within the muscle. The impaired recovery from fatigue in older adults relied more on the recovery of central factors.
http://ift.tt/2hSIEUf
A review of methods to assess coactivation in the Spine
Publication date: Available online 20 December 2016
Source:Journal of Electromyography and Kinesiology
Author(s): Peter Le, Thomas M. Best, Safdar N. Khan, Ehud Mendel, William S. Marras
Coactivation is an important component for understanding the physiological cost of muscular and spinal loads and their associations with spinal pathology and potentially myofascial pain. However, due to the complex and dynamic nature of most activities of daily living, it can be difficult to capture a quantifiable measure of coactivation. Many methods exist to assess coactivation, but most are limited to two-muscle systems, isometric/complex analyses, or dynamic/uniplanar analyses. Hence, a void exists in that coactivation has not been documented or assessed as a multiple-muscle system under realistic complex dynamic loading. Overall, no coactivation index has been capable of assessing coactivation during complex dynamic exertions. The aim of this review is to provide an understanding of the factors that may influence coactivation, document the metrics used to assess coactivity, assess the feasibility of those metrics, and define the necessary variables for a coactivation index that can be used for a variety of tasks. It may also be clinically and practically relevant in the understanding of rehabilitation effectiveness, efficiency during task performance, human-task interactions, and possibly the etiology for a multitude of musculoskeletal conditions.
http://ift.tt/2hSIDzF
ADAMTS-3, -13, -16, and -19 levels in patients with habitual abortion
Publication date: Available online 20 December 2016
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Meryem Kuru Pekcan, Esma Sarıkaya, Aytekin Tokmak, Murat Alışık, Afra Alkan, Gülnur Özakşit, Özcan Erel
A disintegrin-like and metalloproteinase domain with thrombospondin-type 1 motifs (ADAMTS) protein superfamily includes 19 secreted metalloproteases. Proteolytic substrates of ADAMTS enzymes have been linked to reproductive function. The aim of this study was to investigate serum ADAMTS-3, -13, -16, and -19 levels in women with habitual abortions compared with those in healthy controls. A total of 86 women were enrolled in this prospective case-control study. ADAMTS-3, -13, -16, and -19 values were recorded and analyzed in association with demographic and clinical parameters. There were no statistically significant differences between the two groups in terms of demographics. No statistically significant differences were observed between the groups with regard to ADAMTS-13 and -19 levels (p>0.05). However, ADAMTS-3 and -16 were significantly higher in the study group than in the control group (p=0.004 and p=0.005, respectively). To estimate habitual abortions using an area under receiver operating characteristic curve analysis, the cutoff values for ADAMTS-3 and -16 were found to be 87.28 ng/mL (sensitivity, 64.44%; specificity 68.29%) and 15.75 ng/mL (sensitivity, 66.67%; specificity 68.29%), respectively. In conclusion, the pregnancy-loss rate seems to be affected by both ADAMTS-3 and -16.
http://ift.tt/2h9aME1
Impaired ApoB-Lipoprotein and Triglyceride Metabolism in Obese Adolescents with Polycystic Ovary Syndrome.
The Journal of Clinical Endocrinology &Metabolism, Early Release.
http://ift.tt/2hGC4Cf
Progesterone receptors and proliferation of the endometrium in obese women with polycystic ovary syndrome – a lifestyle intervention study
The Journal of Clinical Endocrinology &Metabolism, Early Release.
http://ift.tt/2hSw4Ey
Editorial Board and Contents
Publication date: January 2017
Source:Trends in Endocrinology & Metabolism, Volume 28, Issue 1
http://ift.tt/2iekKSf
Assessment of a smartphone app (Capstesia) for measuring pulse pressure variation: agreement between two methods: A Cross-sectional study.
http://ift.tt/2hTPXNP
Achille Civatte: A Master of the Microscope.
http://ift.tt/2i9cl6s
Superficial Acral Fibromyxoma of the Toe: Unusual Location of the Mixoid Variant.
http://ift.tt/2i9eD5K
Τρίτη 20 Δεκεμβρίου 2016
Transcription Factor EB Controls Metabolic Flexibility during Exercise
Publication date: Available online 20 December 2016
Source:Cell Metabolism
Author(s): Gelsomina Mansueto, Andrea Armani, Carlo Viscomi, Luca D'Orsi, Rossella De Cegli, Elena V. Polishchuk, Costanza Lamperti, Ivano Di Meo, Vanina Romanello, Silvia Marchet, Pradip K. Saha, Haihong Zong, Bert Blaauw, Francesca Solagna, Caterina Tezze, Paolo Grumati, Paolo Bonaldo, Jeffrey E. Pessin, Massimo Zeviani, Marco Sandri, Andrea Ballabio
The transcription factor EB (TFEB) is an essential component of lysosomal biogenesis and autophagy for the adaptive response to food deprivation. To address the physiological function of TFEB in skeletal muscle, we have used muscle-specific gain- and loss-of-function approaches. Here, we show that TFEB controls metabolic flexibility in muscle during exercise and that this action is independent of peroxisome proliferator-activated receptor-γ coactivator1α (PGC1α). Indeed, TFEB translocates into the myonuclei during physical activity and regulates glucose uptake and glycogen content by controlling expression of glucose transporters, glycolytic enzymes, and pathways related to glucose homeostasis. In addition, TFEB induces the expression of genes involved in mitochondrial biogenesis, fatty acid oxidation, and oxidative phosphorylation. This coordinated action optimizes mitochondrial substrate utilization, thus enhancing ATP production and exercise capacity. These findings identify TFEB as a critical mediator of the beneficial effects of exercise on metabolism.
Graphical abstract
Teaser
Mansueto et al. show that TFEB acts as a central coordinator of skeletal muscle insulin sensitivity, glucose homeostasis, lipid oxidation, and mitochondrial function in the adaptive metabolic response to physical exercise in a PGC1α-independent manner.http://ift.tt/2hTBm56
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Publication date: September 2017 Source: Free Radical Biology and Medicine, Volume 110 Author(s): Lucía Fernández-del-Río, Anish Nag, Elen...
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Abstract Noise pollution is a major factor of environmental complaints in many cities, which has significant impacts on human health. As a...
