Ιατρικά Άρθρα: 09/22/17

Παρασκευή 22 Σεπτεμβρίου 2017

A minimum-phase Shinnar-Le Roux spectral-spatial excitation RF pulse for simultaneous water and lipid suppression in 1H-MRSI of body extremities

Publication date: January 2018
Source:Magnetic Resonance Imaging, Volume 45
Author(s): Paul Kyu Han, Chao Ma, Kexin Deng, Shuang Hu, Kyung-Wook Jee, Kui Ying, Yen-Lin Chen, Georges El Fakhri
PurposeTo develop a spectral-spatial (SPSP) excitation RF pulse for simultaneous water and lipid suppression in proton (¹H) magnetic resonance spectroscopic imaging (MRSI) of body extremities.MethodsAn SPSP excitation pulse is designed to excite Creatine (Cr) and Choline (Cho) metabolite signals while suppressing the overwhelming water and lipid signals. The SPSP pulse is designed using a recently proposed multidimensional Shinnar-Le Roux (SLR) RF pulse design method. A minimum-phase spectral selectivity profile is used to minimize signal loss from T2^⁎ decay.ResultsThe performance of the SPSP pulse is evaluated via Bloch equation simulations and phantom experiments. The feasibility of the proposed method is demonstrated using three-dimensional, short repetition-time, free induction decay-based ¹H-MRSI in the thigh muscle at 3T.ConclusionThe proposed SPSP excitation pulse is useful for simultaneous water and lipid suppression. The proposed method enables new applications of high-resolution ¹H-MRSI in body extremities.

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Test-retest reliability of cerebral blood flow in healthy individuals using arterial spin labeling: Findings from the EMBARC study

Publication date: January 2018
Source:Magnetic Resonance Imaging, Volume 45
Author(s): Jorge R.C. Almeida, Tsafrir Greenberg, Hanzhang Lu, Henry W. Chase, Jay Fournier, Crystal M. Cooper, Thilo Deckersbach, Phil Adams, Thomas Carmody, Mauricio Fava, Benji Kurian, Patrick J. McGrath, Melvin G. McInnis, Maria A. Oquendo, Ramin Parsey, Myrna Weissman, Madhukar Trivedi, Mary L. Phillips
IntroductionPrevious investigations of test-retest reliability of cerebral blood flow (CBF) at rest measured with pseudo-continuous Arterial Spin Labeling (pCASL) demonstrated good reliability, but are limited by the use of similar scanner platforms. In the present study we examined test-retest reliability of CBF in regions implicated in emotion and the default mode network.Material and methodsWe measured absolute and relative CBF at rest in thirty-one healthy subjects in two scan sessions, one week apart, at four different sites and three different scan platforms. We derived CBF from pCASL images with an automated algorithm and calculated intra-class correlation coefficients (ICCs) across sessions for regions of interest. In addition, we investigated site effects.ResultsFor both absolute and relative CBF measures, ICCs were good to excellent (i.e. >0.6) in most brain regions, with highest values observed for the subgenual anterior cingulate cortex and ventral striatum. A leave-one-site-out cross validation analysis did not show a significant effect for site on whole brain CBF and there was no proportional bias across sites. However, a significant site effect was present in the repeated measures ANOVA.ConclusionsThe high test-retest reliability of CBF measured with pCASL in a range of brain regions implicated in emotion and salience processing, emotion regulation, and the default mode network, which have been previously linked to depression symptomatology supports its use in studies that aim to identify neuroimaging biomarkers of treatment response.

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Cost evaluation to optimise radiation therapy implementation in different income settings: A time-driven activity-based analysis

Publication date: Available online 22 September 2017
Source:Radiotherapy and Oncology
Author(s): Jacob Van Dyk, Eduardo Zubizarreta, Yolande Lievens
BackgroundWith increasing recognition of growing cancer incidence globally, efficient means of expanding radiotherapy capacity is imperative, and understanding the factors impacting human and financial needs is valuable.Materials and methodsA time-driven activity-based costing analysis was performed, using a base case of 2-machine departments, with defined cost inputs and operating parameters. Four income groups were analysed, ranging from low to high income. Scenario analyses included department size, operating hours, fractionation, treatment complexity, efficiency, and centralised versus decentralised care.ResultsThe base case cost/course is US$5,368 in HICs, US$2,028 in LICs; the annual operating cost is US$4,595,000 and US$1,736,000, respectively. Economies of scale show cost/course decreasing with increasing department size, mainly related to the equipment cost and most prominent up to 3 linacs. The cost in HICs is two or three times as high as in U-MICs or LICs, respectively. Decreasing operating hours below 8h/day has a dramatic impact on the cost/course. IMRT increases the cost/course by 22%. Centralising preparatory activities has a moderate impact on the costs.ConclusionsThe results indicate trends that are useful for optimising local and regional circumstances. This methodology can provide input into a uniform and accepted approach to evaluating the cost of radiotherapy.

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Sappanone A inhibits RANKL-induced osteoclastogenesis in BMMs and prevents inflammation-mediated bone loss

Publication date: November 2017
Source:International Immunopharmacology, Volume 52
Author(s): Young-Yeon Choo, Phuong Thao Tran, Byung-Sun Min, Okwha Kim, Hai Dang Nguyen, Seung-Hae Kwon, Jeong-Hyung Lee
Receptor activator of nuclear factor-kB ligand (RANKL) is a key factor in the differentiation and activation of osteoclasts. Suppressing osteoclastogenesis is considered an effective therapeutic approach for bone-destructive diseases, such as osteoporosis and rheumatoid arthritis. Sappanone A (SPNA), a homoisoflavanone compound isolated from the heartwood of Caesalpinia sappan, has been reported to exert anti-inflammatory effects; however, the effects of SPNA on osteoclastogenesis have not been investigated. In the present study, we describe for the first time that SPNA inhibits RANKL-induced osteoclastogenesis in mouse bone marrow macrophages (BMMs) and suppresses inflammation-induced bone loss in a mouse model. SPNA inhibited the formation of osteoclasts from BMMs, osteoclast actin-ring formation, and bone resorption in a concentration-dependent manner. At the molecular level, SPNA significantly inhibited RANKL-induced activation of the AKT/glycogen synthase kinase-3β (GSK-3β) signaling pathway without affecting its activation of the mitogen-activated protein kinases (MAPKs) JNK, p38, and ERK. In addition, SPNA suppressed the induction of nuclear factor of activated T cells cytoplasmic 1 (NFATc1), which is a crucial transcription factor in osteoclast differentiation. As a result, SPNA decreased osteoclastogenesis-related marker gene expression, including CtsK, TRAP, dendritic cell-specific transmembrane protein (DC-STAMP), MMP-9 and osteoclast-associated receptor (OSCAR). In a mouse inflammatory bone loss model, SPNA significantly inhibited lipopolysaccharide (LPS)-induced bone loss by suppressing the number of osteoclasts. Taken together, these findings suggest that SPNA inhibits osteoclastogenesis and bone resorption by inhibiting the AKT/GSK-3β signaling pathway and may be a potential candidate compound for the prevention and/or treatment of inflammatory bone loss.

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Baicalin suppresses IL-1β-induced expression of inflammatory cytokines via blocking NF-κB in human osteoarthritis chondrocytes and shows protective effect in mice osteoarthritis models

Publication date: November 2017
Source:International Immunopharmacology, Volume 52
Author(s): Chunhui Chen, Chuanxu Zhang, Leyi Cai, Huanguang Xie, Wei Hu, Te Wang, Di Lu, Hua Chen
Osteoarthritis (OA) is a degenerative joint disease with an inflammatory component that drives the degradation of cartilage extracellular matrix. Baicalin, a predominant flavonoid isolated from the dry root of Scutellaria baicalensis Georgi, has been reported to have anti-inflammatory effects. However, the anti-inflammatory effects of baicalin on OA have not been reported. Our study aimed to investigate the effect of baicalin on OA both in vitro and in vivo. In vitro, human OA chondrocytes were pretreated with baicalin (10, 50, 100μM) for 2h and subsequently stimulated with IL-1β for 24h. Production of NO and PGE2 were evaluated by the Griess reaction and ELISAs. The mRNA expression of COX-2, iNOS, MMP-3, MMP-13, ADAMTS-5, aggrecan and collagen-II were measured by real-time PCR. The protein expression of COX-2, iNOS, MMP-3, MMP-13, ADAMTS-5, p65, p-p65, IκBα and p-IκBα was detected by Western blot. The protein expression of collagen-II was evaluated by immunofluorescence. Luciferase activity assay was used to assess the relative activity of NF-kB. In vivo, the severity of OA was determined by histological analysis. We found that baicalin significantly inhibited the IL-1β-induced production of NO and PGE2, expression of COX-2, iNOS, MMP-3, MMP-13 and ADAMTS-5 and degradation of aggrecan and collagen-II. Furthermore, baicalin dramatically suppressed IL-1β-stimulated NF-κB activation. In vivo, treatment of baicalin not only prevented the destruction of cartilage but also relieved synovitis in mice OA models. Taken together, these results suggest that baicalin may be a potential agent in the treatment of OA.

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Polyvalent immunoglobulin binding is an obstacle to accurate measurement of specific antibodies with ELISA despite inclusion of blocking agents

Publication date: November 2017
Source:International Immunopharmacology, Volume 52
Author(s): David A. Loeffler, Andrea C. Klaver
Specific antibody concentrations are frequently measured in serum (and plasma and intravenous immunoglobulin) samples by enzyme-linked immunosorbent assay (ELISA). The standard negative control involves incubation of buffer alone on antigen-coated wells. The immunoreactivity that develops in antigen-coated wells in which diluted serum has been incubated is assumed to represent specific antibody binding. This approach can result in marked overestimation of specific antibody levels, because serum contains specific polyvalent antibodies which bind, primarily with low affinity, to multiple antigens (including those on ELISA plates) despite the use of blocking agents. Non-denaturing purification of serum IgG, followed by assessment of the antigen binding or antigen-binding affinity of this purified IgG, can reduce but not eliminate the problem of polyvalent antibody binding in indirect ELISAs. Alternatively, polyvalent antibody binding can be estimated by incubating a diluted serum sample on wells coated with an irrelevant protein (such as bovine serum albumin or a scrambled peptide sequence) or buffer alone, then subtracting this reactivity from the sample's binding to wells coated with the antigen of interest. Polyvalent binding of immunoglobulins must be accounted for in order to obtain accurate ELISA measurements of serum, plasma, or intravenous immunoglobulin antibodies.

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Rapid development of cutaneous melanoma metastases after herpes zoster infection in a radiotherapy field

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Association between circulating prolactin levels and psoriasis and its correlation with disease severity: a meta-analysis

Summary

Background

Studies that have compared circulating prolactin (PRL) levels in patients with psoriasis and healthy controls (HCs) and determined the relation between PRL levels and psoriasis severity have shown mixed results.

Aim

To evaluate the association between circulating PRL levels and psoriasis, and between serum/plasma PRL levels and psoriasis severity.

Methods

We performed a meta-analysis comparing serum/plasma PRL levels in patients with psoriasis with those of HCs, and examined the correlation coefficients for circulating PRL levels and psoriasis severity based on Psoriasis Area and Severity Index (PASI).

Results

In total, 12 studies assessing 446 patients with psoriasis and 401 HCs were included. PRL levels were significantly higher in the psoriasis group than in the HC group [standardized mean difference (SMD) 0.54; 95% CI = 0.18–090; P < 0.01). Stratification by age and sex revealed a significantly higher PRL level in the psoriasis group (SMD = 0.53; 95% CI = 0.15–0.91; P < 0.01). Subgroup analysis by sample size showed a significantly higher PRL level with larger sample sizes (n ≥ 80) (SMD = 0.51, 95% CI = 0.07–0.95, P = 0.02), but not with smaller sample sizes (n < 80) in the psoriasis group. Stratification by sample type revealed a significantly higher level of PRL in the sera, but not plasma of the psoriasis group. Meta-analysis of the correlation coefficients showed a positive, although not statistically significant, correlation between circulating PRL levels and PASI (correlation coefficient = 0.48, 95% CI = −0.05 to 0.80, P = 0.08).

Conclusion

Circulating PRL levels are higher in patients with psoriasis, and PRL levels may correlate with psoriasis severity.

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T-helper immune phenotype may underlie ‘paradoxical’ tumour necrosis factor-α inhibitor therapy-related psoriasiform dermatitis

Summary

Background

Therapeutics targeting tumour necrosis factor (TNF)-α are effective for psoriasis; however, in patients treated for other disorders, psoriasis may worsen and psoriasiform dermatitis (PsoD) may arise. T helper (Th) cytokines in psoriasis upregulate keratin (K)17, which modulates TNF-α transduction, leading to vascular adhesion molecule upregulation and lymphocytic extravasation.

Aim

We investigated Th phenotype and expression of K17, intercellular adhesion molecule (ICAM)-1 and vascular adhesion molecule (VCAM)-1 in psoriasis and anti-TNF-α-related PsoD.

Methods

Skin biopsies from patients with psoriasis unresponsive to TNF-α inhibitor therapy (n = 11), PsoD-related to TNF-α inhibition (n = 9), untreated psoriasis (n = 9) or atopic dermatitis (AD; n = 9) were immunohistochemically analysed for Th1, Th2, Th17 and Th22. Expression of K17, ICAM-1 and VCAM-1 was also examined.

Results

Anti-TNF-α-unresponsive psoriasis and anti-TNF-α-related PsoD showed decreased Th1 : Th2 raio and increased Th17 : Th1 ratio compared with untreated psoriasis. Anti-TNF-α-unresponsive psoriasis had significantly fewer Th1 (4% vs. 12%) and more Th17 (51% vs. 20%) cells than untreated psoriasis. No difference in Th22 cells was identified. K17 was present in all cases of untreated psoriasis and anti-TNF-α-related PsoD, 91% of anti-TNF-α-unresponsive psoriasis, and only 22% of AD. VCAM-1 and ICAM-1 in anti-TNF-α-related PsoD was akin to untreated psoriasis, but decreased in anti-TNF-α-unresponsive psoriasis.

Conclusions

These findings further the current understanding of the anti-TNF-α-related psoriasiform phenotype and support a rationale for therapeutic targeting of interleukin-17 and TNF-α in combination.

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The clinicoaetiological, hormonal and histopathological characteristics of melasma in men

Summary

Background

Melasma is relatively uncommon in males, and there is a paucity of data on male melasma, including its clinical pattern, triggering factors, endocrine profile and histopathological findings.

Aim

To characterize the clinical findings and aetiological factors, including hormonal and histopathological features, of male melasma.

Methods

Male patients with melasma and age- and sex-matched healthy controls (HCs) were recruited. Demographic profile, risk factors, clinical pattern and Wood lamp findings of patients were recorded. Sera were obtained from patients and HCs to determine hormone levels. Biopsy specimens were obtained from lesional and adjacent nonlesional skin.

Results

In total, 50 male patients with melasma and 20 HCs were recruited into the study. Mean age of patients was 27.58 ± 4.51 years. The most common clinical pattern of melasma was malar, which occurred in 52% of cases. Positive family history was present in 16% of patients, while 34% had disease aggravation with sun exposure and 62% used mustard oil for hair growth and/or as an emollient. Wood lamp examination revealed epidermal-type melasma in 54% of patients. There were no significant differences in hormone levels between patients and HCs. Histologically, epidermal melanin, elastotic degeneration, vascular proliferation and mast cells were more pronounced in lesional compared with nonlesional skin. Absent to weak expression of oestrogen receptors, progesterone receptors and stem cell factor was observed in lesional skin.

Conclusion

Ultraviolet light and mustard oil are important causative factors in male melasma. Although stress and family history may contribute, hormonal factors possibly have no role. Quantitative analysis of immunohistochemical markers would provide insight in understanding the pathogenesis of melasma.

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Systemic photodynamic therapy in folliculitis decalvans

Summary

Folliculitis decalvans (FD) is classified as a primary neutrophilic cicatricial alopecia, and is estimated to account for approximately 10% of all cases of primary cicatricial alopecia. The role of dysfunctional immune activity and the presence of bacteria, particularly Staphylococcus aureus, appear pivotal. We describe a 26-year-old man with a 4-year history of FD that was recalcitrant to numerous systemic and topical therapies, whose disease was virtually cleared during a follow-up of 25 months following a course of treatment with systemic photodynamic therapy (PDT) using ultraviolet light (100–140 J/cm²) with porfimer sodium 1 mg/kg as monotherapy. This is the first report of the use of systemic PDT as a treatment for FD. Systemic PDT has potent antibacterial effects with little or no resistance. In addition, systemic PDT provides local immunomodulation and improved scar healing. Significant adverse effects following systemic PDT with appropriate aftercare are rare. This case demonstrates that systemic PDT is a useful therapy option in the treatment of recalcitrant FD.

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Periocular cutaneous oncocytoma

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Complete resolution of extensive xanthomas associated with primary sclerosing cholangitis following liver transplantation

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Acral melanoma foot lesions. Part 1: epidemiology, aetiology, and molecular pathology

Summary

Acral melanoma (AM) is a rare subtype of cutaneous malignant melanoma (MM) found on acral skin, primarily on the soles of the feet. Although rare, it is the most common subtype of MM found in patients of African or East Asian ethnicity and has a poor prognosis, often because of the more advanced stage of presentation at diagnosis. The pathogenesis of AM is unclear, but genetic alterations, including mutations in BRAF, NRAS, and KIT have been implicated. Early diagnosis of AM is important for a better prognosis, but its identification is often challenging, leading to easy misdiagnosis. In the first of this two-part review, we review the history, epidemiology, aetiology and molecular pathology of AM; in part 2 we will review diagnosis and management.

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A novel 1-bp deletion mutation and extremely skewed X-chromosome inactivation causing severe X-linked hypohidrotic ectodermal dysplasia in a Chinese girl

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Allergic contact dermatitis caused by a moisturizer containing iodopropynyl butylcarbamate

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MicroRNAs in cutaneous lichen planus

Summary

Lichen planus (LP) is a chronic, inflammatory, papulosquamous, autoimmune disease. The pathogenesis of LP appears to be complex, with interactions between genetic, environmental and lifestyle factors. MicroRNAs (miRNAs) are short RNAs encoded in both protein coding and noncoding areas of the genome, and have been found to be involved in the pathogenesis of some inflammatory skin diseases. The aim of this study was to map the levels of miRNA (miR-)-203 and miR-125b in cutaneous LP to evaluate their possible role in the pathogenesis of the disease. In total, 40 patients with classic cutaneous LP and 40 age- and sex- matched healthy controls (HCs) were enrolled in this study. Punch biopsies (4 mm) were taken from cutaneous LP lesions of patients and from normal skin of HCs. miRNA-203 and miRNA-125b mRNA expression was estimated by reverse transcription PCR. Our analysis revealed a significantly (P < 0.001 for both) lower expression of both miR-203 and miR-125b mRNA in the LP than in the HC biopsies. No relationship was found between expression of miR-203 or miR-125b and either age, sex, presence of mucosal lesions or positivity for HCV antibodies. miR-125b and miR-203 could be involved in the pathogenesis of cutaneous LP.

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Dermoscopic features of pigmented vulvar intraepithelial neoplasia

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Optogenetic Activation of the Sensorimotor Cortex Reveals “Local Inhibitory and Global Excitatory” Inputs to the Basal Ganglia

Abstract

To understand how information from different cortical areas is integrated and processed through the cortico-basal ganglia pathways, we used optogenetics to systematically stimulate the sensorimotor cortex and examined basal ganglia activity. We utilized Thy1-ChR2-YFP transgenic mice, in which channelrhodopsin 2 is robustly expressed in layer V pyramidal neurons. We applied light spots to the sensorimotor cortex in a grid pattern and examined neuronal responses in the globus pallidus (GP) and entopeduncular nucleus (EPN), which are the relay and output nuclei of the basal ganglia, respectively. Light stimulation typically induced a triphasic response composed of early excitation, inhibition, and late excitation in GP/EPN neurons. Other response patterns lacking 1 or 2 of the components were also observed. The distribution of the cortical sites whose stimulation induced a triphasic response was confined, whereas stimulation of the large surrounding areas induced early and late excitation without inhibition. Our results suggest that cortical inputs to the GP/EPN are organized in a "local inhibitory and global excitatory" manner. Such organization seems to be the neuronal basis for information processing through the cortico-basal ganglia pathways, that is, releasing and terminating necessary information at an appropriate timing, while simultaneously suppressing other unnecessary information.

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Vascular smooth muscle cells derived from inbred swine induced pluripotent stem cells for vascular tissue engineering

Publication date: December 2017
Source:Biomaterials, Volume 147
Author(s): Jiesi Luo, Lingfeng Qin, Mehmet H. Kural, Jonas Schwan, Xia Li, Oscar Bartulos, Xiao-qiang Cong, Yongming Ren, Liqiong Gui, Guangxin Li, Matthew W. Ellis, Peining Li, Darrell N. Kotton, Alan Dardik, Jordan S. Pober, George Tellides, Marsha Rolle, Stuart Campbell, Robert J. Hawley, David H. Sachs, Laura E. Niklason, Yibing Qyang
Development of autologous tissue-engineered vascular constructs using vascular smooth muscle cells (VSMCs) derived from human induced pluripotent stem cells (iPSCs) holds great potential in treating patients with vascular disease. However, preclinical, large animal iPSC-based cellular and tissue models are required to evaluate safety and efficacy prior to clinical application. Herein, swine iPSC (siPSC) lines were established by introducing doxycycline-inducible reprogramming factors into fetal fibroblasts from a line of inbred Massachusetts General Hospital miniature swine that accept tissue and organ transplants without immunosuppression within the line. Highly enriched, functional VSMCs were derived from siPSCs based on addition of ascorbic acid and inactivation of reprogramming factor via doxycycline withdrawal. Moreover, siPSC-VSMCs seeded onto biodegradable polyglycolic acid (PGA) scaffolds readily formed vascular tissues, which were implanted subcutaneously into immunodeficient mice and showed further maturation revealed by expression of the mature VSMC marker, smooth muscle myosin heavy chain. Finally, using a robust cellular self-assembly approach, we developed 3D scaffold-free tissue rings from siPSC-VSMCs that showed comparable mechanical properties and contractile function to those developed from swine primary VSMCs. These engineered vascular constructs, prepared from doxycycline-inducible inbred siPSCs, offer new opportunities for preclinical investigation of autologous human iPSC-based vascular tissues for patient treatment.

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Bone regeneration with micro/nano hybrid-structured biphasic calcium phosphate bioceramics at segmental bone defect and the induced immunoregulation of MSCs

Publication date: December 2017
Source:Biomaterials, Volume 147
Author(s): Yu Zhu, Kun Zhang, Rui Zhao, Xingjiang Ye, Xuening Chen, Zhanwen Xiao, Xiao Yang, Xiangdong Zhu, Kai Zhang, Yujiang Fan, Xingdong Zhang
Adequate bone regeneration has been difficult to achieve at segmental bone defects caused by disease. The surface structure and phase composition of calcium phosphate bioceramic are crucial for its bioactivity and osteoinductivity. In the present study, biphasic calcium phosphate (BCP) bioceramics composed of micro-whiskers and nanoparticles hybrid-structured surface (hBCP) were fabricated via a hydrothermal reaction. The in vivo long bone defect model of beagle dogs implanted with hBCP bioceramics achieved a higher quality regenerated bone as compared to the traditional smooth-surface BCP control group. After a 12-week implantation period, more new bone formation within the implanted material and a higher fracture load were observed in the hBCP group (p < 0.05 vs. control). In addition, the local bone integration efficacy, as determined by nanoindentation, showed a significantly closer elastic modulus of the implanted hBCP bioceramics to that of the natural bone adjacent. Finally, in vitro gene microarray analysis of the mesenchymal stem cells (MSCs) co-cultured with two bioceramics showed that the hBCP group induced a drastic downregulation of the genes associated with inflammatory response, which was never documented in previous studies regarding biomaterials with a micro/nano hybrid structure. The tumor necrosis factor (TNF) signalling pathway was the most involved and preferentially inhibited by the hBCP material. Collectively, the findings suggested that the micro/nano hybrid-structured bioceramics augmented local bone regeneration at segmental bone defects and presented a potential alternative to autologous bone grafts.

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Bio-inspired engineering of cell- and virus-like nanoparticles for drug delivery

Publication date: December 2017
Source:Biomaterials, Volume 147
Author(s): Alessandro Parodi, Roberto Molinaro, Manuela Sushnitha, Michael Evangelopoulos, Jonathan O. Martinez, Noemi Arrighetti, Claudia Corbo, Ennio Tasciotti
The engineering of future generations of nanodelivery systems aims at the creation of multifunctional vectors endowed with improved circulation, enhanced targeting and responsiveness to the biological environment. Moving past purely bio-inert systems, researchers have begun to create nanoparticles capable of proactively interacting with the biology of the body. Nature offers a wide-range of sources of inspiration for the synthesis of more effective drug delivery platforms. Because the nano-bio-interface is the key driver of nanoparticle behavior and function, the modification of nanoparticles' surfaces allows the transfer of biological properties to synthetic carriers by imparting them with a biological identity. Modulation of these surface characteristics governs nanoparticle interactions with the biological barriers they encounter. Building off these observations, we provide here an overview of virus- and cell-derived biomimetic delivery systems that combine the intrinsic hallmarks of biological membranes with the delivery capabilities of synthetic carriers. We describe the features and properties of biomimetic delivery systems, recapitulating the distinctive traits and functions of viruses, exosomes, platelets, red and white blood cells. By mimicking these biological entities, we will learn how to more efficiently interact with the human body and refine our ability to negotiate with the biological barriers that impair the therapeutic efficacy of nanoparticles.

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Bile acid transporter mediated endocytosis of oral bile acid conjugated nanocomplex

Publication date: December 2017
Source:Biomaterials, Volume 147
Author(s): Jooho Park, Jeong Uk Choi, Kwangmeyung Kim, Youngro Byun
The development of highly funtional and orally available nanoparticles is the ultimate goal in nanoparticle delivery. Various functional nanoparticles have been studied to that end but there has yet to be an oral nanoparticle that can be successfully applied. Here, we describe for the first time a novel bile acid conjugated nanoparticle that can be selectively absorbed by bile acid transporters in the small intestine. The bile acid conjugate nanoparticles that were first treated with enterocytes were successfully attached to the cell surface and then internalized inside the cells. We show that bile acid based interaction between a nanoparticle and its transporter induces its endocytosis and cellular uptake. This feature of cellular activity, described here for the first time, could be well utilized in the uptake of nanoparticles or macromolecules inside epithelial cells for oral delivery. In animal studies, bile acid conjugated self-assembling nanocomplexes successfully interacted with bile acid transporters in the ileum and were subsequently taken up into the epithelial cells. Considering the importance of orally deliverable nanoparticles, this nanotechnology using bile acid conjugation and transporter mediated endocytosis could be a crucial method for the successful application of various nanoparticles.

Graphical abstract

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Validation of salivary oxytocin and vasopressin as biomarkers in domestic dogs

Publication date: 1 January 2018
Source:Journal of Neuroscience Methods, Volume 293
Author(s): Evan L. MacLean, Laurence R. Gesquiere, Nancy Gee, Kerinne Levy, W. Lance Martin, C. Sue Carter
BackgroundOxytocin (OT) and Vasopressin (AVP) are phylogenetically conserved neuropeptides with effects on social behavior, cognition and stress responses. Although OT and AVP are most commonly measured in blood, urine and cerebrospinal fluid (CSF), these approaches present an array of challenges including concerns related to the invasiveness of sample collection, the potential for matrix interference in immunoassays, and whether samples can be collected at precise time points to assess event-linked endocrine responses.New methodWe validated enzyme-linked immunosorbent assays (ELISAs) for the measurement of salivary OT and AVP in domestic dogs.ResultsBoth OT and AVP were present in dog saliva and detectable by ELISA and high performance liquid chromatography – mass spectrometry (HPLC–MS). OT concentrations in dog saliva were much higher than those typically detected in humans. OT concentrations in the same samples analyzed with and without sample extraction were highly correlated, but this was not true for AVP. ELISA validation studies revealed good accuracy and parallelism, both with and without solid phase extraction. Collection of salivary samples with different synthetic swabs, or following salivary stimulation or the consumption of food led to variance in results. However, samples collected from the same dogs using different techniques tended to be positively correlated. We detected concurrent elevations in salivary and plasma OT during nursing.Comparison with existing methodsThere are currently no other validated methods for measuring OT/AVP in dog saliva.ConclusionsOT and AVP are present in dog saliva, and ELISAs for their detection are methodologically valid.

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Patterns of care and impact of brachytherapy boost utilization for squamous cell carcinoma of the base of tongue in a large, national cohort

Publication date: Available online 22 September 2017
Source:Brachytherapy
Author(s): Anna Lee, Babak Givi, S. Peter Wu, Moses M. Tam, Naamit K. Gerber, Kenneth S. Hu, Peter Han, David Schreiber
PurposeThe National Cancer Data Base was analyzed to evaluate the patterns of care and impact of brachytherapy (BT) boost on overall survival (OS) for patients with squamous cell carcinoma of the base of tongue.Methods and MaterialsPatients with nonmetastatic squamous cell carcinoma of the base of tongue between 2004 and 2012 who received concurrent external beam radiation therapy (EBRT) and chemotherapy with or without BT boost in the definitive setting were queried. Overall survival was assessed by the Kaplan-Meier method. Cox regression analysis was used to identify covariates that affected OS.ResultsThere were 15,934 patients included in this study; 137 (0.9%) received EBRT + BT and the remaining received EBRT only. Median followup was 41.2 months. The utilization of BT boost declined from 2.1% in 2004 to 0.2% in 2012 (p < 0.0001), whereas intensity-modulated radiation therapy use increased from 22.8% in 2004 to 69.2% in 2012 (p < 0.0001). The three- and 5-year OS was 83.2% and 78.3% for patients receiving EBRT + BT compared with 77.4% and 69.0% for those receiving EBRT only (p = 0.03). The difference in survival was significantly better among patients with T3-4 tumors with EBRT + BT boost (p = 0.009) however, there was no survival benefit among patients with T1-2 tumors (p = 0.72). The analysis was repeated with patients who received intensity-modulated radiation therapy vs. EBRT with BT boost and the survival difference was sustained only for those with T3-4 tumors (p = 0.02).ConclusionsBrachytherapy boost has decreased in its utilization even though it was associated with favorable survival outcomes particularly among patients with higher T-stage tumors.

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An integrated system for clinical treatment verification of HDR prostate brachytherapy combining source tracking with pretreatment imaging

Publication date: Available online 22 September 2017
Source:Brachytherapy
Author(s): Ryan L. Smith, Max Hanlon, Vanessa Panettieri, Jeremy L. Millar, Bronwyn Matheson, Annette Haworth, Rick D. Franich
PurposeHigh-dose-rate (HDR) prostate brachytherapy treatment is usually delivered in one or a few large dose fractions. Poor execution of a planned treatment could have significant clinical impact, as high doses are delivered in seconds, and mistakes in an individual fraction cannot be easily rectified. Given that most potential errors in HDR brachytherapy ultimately lead to a geographical miss, a more direct approach to verification of correct treatment delivery is to directly monitor the position of the source throughout the treatment. In this work, we report on the clinical implementation of our treatment verification system that uniquely combines the 2D source-tracking capability with 2D pretreatment imaging, using a single flat panel detector (FPD).Methods and MaterialsThe clinical brachytherapy treatment couch was modified to allow integration of the FPD into the couch. This enabled the patient to be set up in the brachytherapy bunker in a position that closely matched that at treatment planning imaging. An anteroposterior image was acquired of the patient immediately before treatment delivery and was assessed by the Radiation Oncologist online, to reestablish the positions of the catheters relative to the prostate. Assessment of catheter positions was performed in the left-right and superior-inferior directions along the entire catheter length and throughout the treatment volume. Source tracking was then performed during treatment delivery, and the measured position of the source dwells were directly compared to the treatment plan for verification.ResultsThe treatment verification system was integrated into the clinical environment without significant change to workflow. Two patient cases are presented in this work to provide clinical examples of this system, which is now in routine use for all patient treatments in our clinic. The catheter positions were visualized relative to the prostate, immediately before treatment delivery. For one of the patient cases presented in this work, they agreed with the treatment plan on average by 1.5 mm and were identifiable as a predominantly inferior shift. The source tracking was performed during treatment delivery, and for the same case, the mean deviation from the planned dwell positions was 1.9 mm (max = 4.9 mm) for 280 positions across all catheters.ConclusionWe have implemented our noninvasive treatment verification system based on an FPD in the clinical environment. The device is integrated into a patient treatment couch, and the process is now included in the routine clinical treatment procedure with minor impact on workflow. The system which combines both 2D pretreatment imaging and HDR 2D source tracking provides a range of information that can be used for comprehensive treatment verification. The system has the potential to meaningfully improve safety standards by allowing widespread adoption of routine treatment verification in HDR brachytherapy.

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Time-resolved in vivo dosimetry for source tracking in brachytherapy

Publication date: Available online 22 September 2017
Source:Brachytherapy
Author(s): Jacob Graversen Johansen, Susanne Rylander, Simon Buus, Lise Bentzen, Steffen Bjerre Hokland, Christian Skou Søndergaard, Anders Karl Mikael With, Gustavo Kertzscher, Kari Tanderup
PurposeThe purpose of this article is to demonstrate that brachytherapy source tracking can be realized with in vivo dosimetry. This concept could enable real-time treatment monitoring.MethodsIn vivo dosimetry was incorporated in the clinical routine during high-dose-rate prostate brachytherapy at Aarhus University Hospital. The dosimetry was performed with a radioluminescent crystal positioned in a dedicated brachytherapy needle in the prostate. The dose rate was recorded every 50–100 ms during treatment and analyzed retrospectively. The measured total delivered dose and dose rates for each dwell position with dwell times >0.7 s were compared with expected values. Furthermore, the distance between the source and dosimeter, which was derived from the measured dose rates, was compared with expected values. The measured dose rate pattern in each needle was used to determine the most likely position of the needle relative to the dosimeter.ResultsIn total, 305 needles and 3239 dwell positions were analyzed based on 20 treatments. The measured total doses differed from the expected values by −4.7 ± 8.4% (1SD) with range (−17% to 12%). It was possible to determine needle shifts for 304 out of 305 needles. The mean radial needle shift between imaging and treatment was 0.2 ± 1.1 mm (1SD), and the mean longitudinal shift was 0.3 ± 2.0 mm (1SD).ConclusionTime-resolved in vivo dosimetry can be used to provide geometric information about the treatment progression of afterloading brachytherapy. This information may provide a clear indication of errors and uncertainties during a treatment and, therefore, enables real-time treatment monitoring.

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Image-guided high-dose-rate intracavitary brachytherapy in the treatment of medically inoperable early-stage endometrioid type endometrial adenocarcinoma

Publication date: Available online 22 September 2017
Source:Brachytherapy
Author(s): Scott E. Jordan, Ida Micaily, Enrique Hernandez, J. Stuart Ferriss, Curtis T. Miyamoto, Shidong Li, Bizhan Micaily
PurposeThe purpose of this case series is to describe the treatment and outcomes of a cohort of patients with inoperable early-stage endometrioid endometrial cancer with 3D image-guided high-dose-rate (HDR) intracavitary brachytherapy.MATERIALS AND METHODSA review was performed of patients with early-stage endometrial cancer who underwent primary radiation treatment between 2010 and 2016. Staging and treatment planning were performed CT, pelvic ultrasound, and pelvic MRI. Gross tumor volume (GTV) was defined as the MRI or ultrasound demonstrated endometrial stripe width, with the entire uterine corpus, cervix, and proximal vagina representing the clinical target volume (CTV). Dosimetry calculations were performed in each fraction of HDR brachytherapy.RESULTSEight patients received external beam radiation therapy followed by intracavitary HDR brachytherapy. Seven patients underwent intracavitary HDR brachytherapy alone. In all patients, mean cumulative dose to 90% (D90) of GTV was 95.99 Gy in equivalent dose in 2 Gy fractions (EQD2, α/β = 10). Mean cumulative D90 EQD2 to CTV was 51.64 Gy. Average follow-up was 29 months. Four patients died from concurrent disease(s) at an average of 2.83 years after completion of treatment. Except for 1 (6.6%) patient who recurred at 9 months following completion of treatment, all patients remained disease-free for the remainder of follow-up.ConclusionsIn patients who are poor surgical candidates and have early-stage endometrioid type endometrial carcinoma, image-guided HDR intracavitary brachytherapy carries minimal side effects and a high response rate.

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Oil shale powders and their interactions with ciprofloxacin, ofloxacin, and oxytetracycline antibiotics

Abstract

The interaction of oil shale, as a widespread sedimentary rock, with common antibiotics ofloxacine, oxytetracycline, and ciprofloxacine was studied. The selected Moroccan deposit and its thermally treated forms were fully characterized from a chemical and structural point of view, indicating the prevalence of quartz as a mineral component together with aluminum- and iron-rich phase that are converted into Al-doped iron oxide phases upon heating. The presence of 4 wt% organics was also detected, which was removed at 550 °C without significant loss of specific surface area. The pseudo-second-order kinetic model and Langmuir equation were found the most adequate to reproduce the kinetics and isothermal sorption experiments. These analyses enlighten the contribution of the organic matter on antibiotic retention as well as the key role of hydrophobic interactions on the molecule-mineral surface interactions. Our results emphasize the possible contribution of raw oil shale in the accumulation of antibiotics in soils and suggest that thermally treated oil shell powders can constitute cheap mineral sorbents for environmental cleaning.

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Rapid quantification of persulfate in aqueous systems using a modified HPLC unit

Publication date: 1 February 2018
Source:Talanta, Volume 178
Author(s): Abbas Baalbaki, Nagham Zein Eddine, Saly Jaber, Maya Amasha, Antoine Ghauch
Existing analytical techniques used for the quantification of persulfate (PS) in water mostly rely on polarography, reductometry or spectrophotometry. Although acceptable to a certain extent, these methods did not satisfy environmental chemists seeking rapid, reproducible and accurate quantification of PS upon the application of ISCO and AOPs technologies. Accordingly, a novel flow injection/spectroscopy analytical technique is developed via the use of an HPLC coupled to bypass capillary columns and a DAD detector. Special HPLC configuration uses concentrated KI solution as mobile phase to readily reduce PS present in the sample. The reaction takes place inside the capillary columns, under moderate pressure facilitating the production of Iodine suspension (I2), to yield finally the formation of the Triiodide anion (I3−) in the presence of an excess of I−. Triiodide absorbs at 352nm which minimizes interferences from other organic contaminants (OCs). The method was validated by comparison to traditional PS quantification methods and tested on several environmental samples. The new method proved its superiority in terms of time requirement, labor need, material consumption, sample volume and simplicity. It eliminates the inconsistency present in other idiometric methods which is caused by the delay between the PS/I− reaction and I3− measurement. The obtained LDR extends from 0.075 to 300mmolL⁻¹ with a LOD of 6.6 × 10⁻³mmol L⁻¹ and a LOQ of 2.20 × 10⁻²mmolL⁻¹. The method is successfully implemented in our laboratory to rapidly and automatically monitor the variation in the concentration of PS used in different projects, which facilitates the rapid determination of the reaction stoichiometric efficiency (RSE) of the oxidation reaction, a key factor toward the optimization of the mineralization process and its sustainability.

Graphical abstract

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Alteration in the liver metabolome of rats with metabolic syndrome after treatment with Hydroxytyrosol. A Mass Spectrometry And Nuclear Magnetic Resonance - based metabolomics study

Publication date: 1 February 2018
Source:Talanta, Volume 178
Author(s): Ioanna Dagla, Dimitra Benaki, Eirini Baira, Nikolaos Lemonakis, Hemant Poudyal, Lindsay Brown, Anthony Tsarbopoulos, Alexios-Leandros Skaltsounis, Emmanouel Mikros, Evagelos Gikas
Metabolic syndrome (MetS) represents a group of abnormalities that enhances the risk for cardiovascular disease, diabetes and stroke. The Mediterranean diet seems to be an important dietary pattern, which reduces the incidence of MetS. Hydroxytyrosol (HT) - a simple phenol found in olive oil - has received increased attention for its antioxidant activity. Recently, the European Foods Safety Authority (EFSA) claimed that dietary consumption of HT exhibits a protective role against cardiovascular disease. In this study, an experimental protocol has been setup, including isolated HT administration in a diet induced model of MetS in young Wistar rats, in order to find out whether HT has a protective effect against MetS. Rats were randomly divided into two groups nurtured by high-carbohydrate high-fat (H) (MetS inducing diet) and high-carbohydrate high-fat + HT (HHT). HT (20mg/kg/d oral gavage, water vehicle) was administered for 8 weeks on the basal diet. Previous pharmacological evaluation of HT showed that hepatic steatosis was reduced and the inflammatory cells into the liver were infiltrated. These indicate that HT shows bioactivity against metabolic syndrome. Therefore, the metabolomics evaluation of liver extracts would indicate the putative biochemical mechanisms of HT activity. Thus, the extracts of liver tissues were analyzed using Ultra Performance Liquid Chromatography – High Resolution Mass Spectrometry (UPLC-HRMS, Orbitrap Discovery) and Nuclear Magnetic Resonance (NMR) spectroscopy (Bruker Avance III 600MHz). Multivariate analysis was performed in order to gain insight on the metabolic effects of HT administration on the liver metabolome. Normalization employing multiple internal standards and Quality Control–based Robust LOESS (LOcally Estimated Scatterplot Smoothing) Signal Correction algorithm (QC-RLSC) was added in the processing pipeline to enhance the reliability of metabolomic analysis by reducing unwanted information. Experimentally, HHT rats were clearly distinguished from H in PLS-DA, showing differences in the liver metabolome between the groups and specific biomarkers were determined supporting the pharmacological findings. More specifically, HT has shown to be effective towards the mobilization of lipids as various lipid classes being differentially regulated between the H and HHT groups. Interestingly branched fatty acid esters of hydroxy oleic acids (OAHSA) lipids have been shown to be up regulated to the HHT group, denoting the alleviation of the MetS to the animals administered with HT.

Graphical abstract

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The Role of US in Breast Cancer Screening: The Case For and Against Ultrasound

Publication date: Available online 22 September 2017
Source:Seminars in Ultrasound, CT and MRI
Author(s): Jaime Geisel, Madhavi Raghu, Regina Hooley
Mammography is the gold standard for breast cancer screening. However, with increasing awareness among patients and health care providers of mammography limitations especially in dense breasts, supplemental screening for breast cancer with ultrasound and MRI has been expanding. The roles of both in screening need to be reexamined. This article reviews the efficacy, utility and feasibility of ultrasound as a screening tool for the early detection of occult breast cancer.

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How thoughts arise from sights: inferotemporal and prefrontal contributions to vision

Publication date: October 2017
Source:Current Opinion in Neurobiology, Volume 46
Author(s): Simon Kornblith, Doris Y Tsao
We are rapidly approaching a comprehensive understanding of the neural mechanisms behind object recognition. How we use this knowledge of the visual world to plan and act is comparatively mysterious. To fill this gap, we must understand how visual representations are transformed within cognitive regions, and how these cognitive representations of visual information act back upon earlier sensory representations. Here, we summarize our current understanding of visual representation in inferotemporal cortex (IT) and prefrontal cortex (PFC), and the interactions between them. We emphasize the apparent consistency of visual representation in PFC across tasks, and suggest ways to leverage advances in our understanding of high-level vision to better understand cognitive processing.

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Spatial distribution of metals within the liver acinus and their perturbation by PCB126

Abstract

Animal studies show that exposure to the environmental pollutant 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) causes alterations in hepatic metals as measured in acid-digested volume-adjusted tissue. These studies lack the detail of the spatial distribution within the liver. Here we use X-ray fluorescence microscopy (XFM) to assess the spatial distribution of trace elements within liver tissue. Liver samples from male Sprague Dawley rats, treated either with vehicle or PCB126, were formalin fixed and paraffin embedded. Serial sections were prepared for traditional H&E staining or placed on silicon nitride windows for XFM. With XFM, metal gradients between the portal triad and the central vein were seen, especially with copper and iron. These gradients change with exposure to PCB126, even reverse. This is the first report of how micronutrients vary spatially within the liver and how they change in response to toxicant exposure. In addition, high concentrations of zinc clusters were discovered in the extracellular space. PCB126 treatment did not affect their presence, but did alter their elemental makeup suggesting a more general biological function. Further work is needed to properly evaluate the gradients and their alterations as well as classify the zinc clusters to determine their role in liver function and zinc homeostasis.

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Applicability and efficacy of diatom indices in water quality evaluation of the Chambal River in Central India

Abstract

Diatom indices have gained considerable popularity in estimation of the trophic state and degree of pollution in lotic ecosystems. However, their applicability and efficacy have rarely been tested in Indian streams and rivers. In the present study, benthic diatom assemblages were sampled at 27 sites along the Chambal River in Central India. PCA revealed three groups of sites, namely, heavily polluted (HVPL), moderately polluted (MDPL), and least polluted (SANT). A total of 100 diatom taxa belonging to 40 genera were identified. Brachysira vitrea (Grunow) was the most abundant species recorded from the least polluted sites with an average relative abundance of 29.52. Nitzschia amphibia (Grunow) was representative of heavily polluted sites (average relative abundance 31.71) whereas moderately polluted sites displayed a dominance of Achnanthidium minutissimum (Kϋtzing) with an average relative abundance of 26.33. CCA was used to explore the relationship between diatom assemblage composition and environmental variables. Seventeen different diatom indices were calculated using diatom assemblage data. The relationship between measured water quality variables and index scores was also investigated. Most of the diatom indices exhibited strong correlations with water quality variables including BOD, COD, conductivity, and nutrients, particularly phosphate. Best results were obtained for TDI and IPS indices which showed a high level of resolution with respect to discrimination of sites on the basis of pollution gradients. Water quality maps for the Chambal River were hence prepared in accordance with these two indices. However, satisfactory results with respect to water quality evaluation were also obtained by the application of EPI-D and IGD indices. The present study suggests that TDI and IPS are applicable for biomonitoring of rivers of Central India. Diatom indices, which are simpler to use such as IGD, may be considered, at least for a coarser evaluation of water quality.

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An investigation of the health effects caused by exposure to arsenic from drinking water and coal combustion: arsenic exposure and metabolism

Abstract

Few studies have been conducted to compare arsenic exposure, metabolism, and methylation in populations exposed to arsenic in drinking water and from coal combustion. Therefore, arsenic concentrations in the environment and arsenic speciation in the urine of subjects exposed to arsenic as a consequence of coal combustion in a rural area in Shaanxi province (CCA) and in drinking water in a rural area in Inner Mongolia (DWA) were investigated. The mean arsenic concentrations in drinking water, indoor air, and soil in CCA were 4.52 μg/L, 0.03 mg/m³, and 14.93 mg/kg, respectively. The mean arsenic concentrations in drinking water and soil in DWA were 144.71 μg/L and 10.19 mg/kg, respectively, while the level in indoor air was lower than the limit of detection. The total daily intakes of arsenic in DWA and CCA were 4.47 and 3.13 μg/day·kg, respectively. The mean urinary concentrations of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsenic acid (DMA), and total arsenic (TAs) for subjects with skin lesions in DWA were 50.41, 47.01, 202.66, and 300.08 μg/L. The concentrations for subjects without skin lesions were 49.76, 44.20, 195.60, and 289.56 μg/L, respectively. The %iAs, %MMA, and %DMA in the TAs in the urine of subjects from CCA were 12.24, 14.73, and 73.03%, while the corresponding values from DWA were 17.54, 15.57, and 66.89%, respectively. The subjects in DWA typically had a higher %iAs and %MMA, and a lower %DMA, and primary and secondary methylation index (PMI and SMI) than the subjects in CCA. It was concluded that the arsenic methylation efficiency of subjects in DWA and CCA was significantly influenced by chronic exposure to high levels of arsenic in the environment. The lower PMI and SMI values in DWA revealed lower arsenic methylation capacity due to ingestion of arsenic in drinking water. However, it remained unclear if the differences in arsenic metabolism between the two groups were due to differences in exposure levels or in exposure route.

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Interpreting long-term trends in bushmeat harvest in southeast Cameroon

Publication date: Available online 22 September 2017
Source:Acta Oecologica
Author(s): Eva Ávila, Nikki Tagg, Jacob Willie, Donald Mbohli, Miguel Ángel Farfán, J. Mario Vargas, Wagner H. Bonat, Jef Dupain, Manfred A. Epanda, Inge Luyten, Luc Tedonzong, Martine Peeters, John E. Fa
Measuring hunting sustainability across West/Central African forests remains a challenge. Long-term assessment of trends is crucial. Via hunter-reported surveys we collected offtake data in three villages near the Dja Biosphere Reserve (southeast Cameroon). During four months (March–June) in 2003, 2009 and 2016, we gathered information on hunters, prey species and number of carcasses brought to the three settlements. Because it was not possible to record hunter effort i.e. the time a hunter spent pursuing animals or setting traps, to calculate catch per unit effort (CPUE), we used catch per hunter per day (CPHD) to document hunter returns. We then used the changes in the mean body mass indicator (MBMI) throughout the study period to test for defaunation in the three villages. Differences in CPHD and MBMI by month and year, between villages and hunting method, were investigated using Tweedie regression models. For all species pooled, we found that the mean CPHD remained relatively constant between 2003 and 2016. There was an observed shift from traps to firearms during the study period. CPHD for each of the seven most hunted species did not vary significantly during the entire study period, and a similar change from traps to firearms was observed. MBMI also remained stable for all species pooled, but significantly declined in the remotest village. Starting MBMI values for this village were higher than for the other two settlements perhaps because wildlife here is less depleted. Although hunter effort data may be difficult to obtain over long time periods, CPHD and MBMI may be useful tools as a measure of impact of hunters on prey populations.

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