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Partnership for the implementation of mental health policy in Nigeria: a case study of the Comprehensive Community Mental Health Programme in Benue State.

BACKGROUND: 71% of countries in the World Health Organisation's (WHO's) African Region have a stand-alone mental health policy or plan, but only 14% have fully implemented it. In Nigeria, integration of mental health into primary care has been a stumbling block to the implementation of the 1991 National Mental Health Policy, 2013 Policy on Mental Health Services Delivery and the National Mental, Neurological and Substance Use Programme and Action Plan. A partnership between public and private not-for-profits in Benue State, the Comprehensive Community Mental Health Programme (CCMHP) has successfully integrated mental health into primary care in alignment with the national mental health policy and the WHO's mental health Gap Action Programme Intervention Guide (mhGAP-IG). There is a need to document such examples in order to inform policy implementation in Nigeria and other low- and middle-income countries (LMICs). METHODS: We followed the Case Study Methodology to Monitor and Evaluate Community Mental Health Programmes in LMICs. Four field visits were conducted between 2013 and 2017 to document the first phase of activities of CCMHP, covering the period of January 2011 through June 2016. RESULTS: In its first phase, CCMHP trained 19 community psychiatric nurses and 48 community health extension workers in mhGAP-IG, establishing 45 new mental health clinics in primary care facilities across Benue, a state more populous than many countries. As a result, 13,785 clients (55% male, 45% female) were enrolled in mental health services either in primary care or in one of two pre-existing community-based rehabilitation facilities. Most are adults over age 18 (82.75%), and present to services with epilepsy (52.38%) or psychosis (38.41%). CONCLUSION: The case of CCMHP demonstrates it is possible to rapidly scale-up mental health services in line with national mental health policy using the mhGAP-IG, even in a challenging, low-resource setting. Multi-sectoral partnerships may help to overcome some of the barriers to successful integration of mental health into general healthcare by capitalising on the resources and expertise of both state and non-state actors. However, a difficult political context could threaten the sustainability of the programme if funder requirements force a rapid transition to full government ownership

Ultrastructural and functional fate of recycled vesicles in hippocampal synapses

Efficient recycling of synaptic vesicles is thought to be critical for sustained information transfer at central terminals. However, the specific contribution that retrieved vesicles make to future transmission events remains unclear. Here we exploit fluorescence and time-stamped electron microscopy to track the functional and positional fate of vesicles endocytosed after readily releasable pool (RRP) stimulation in rat hippocampal synapses. We show that most vesicles are recovered near the active zone but subsequently take up random positions in the cluster, without preferential bias for future use. These vesicles non-selectively queue, advancing towards the release site with further stimulation in an actin-dependent manner. Nonetheless, the small subset of vesicles retrieved recently in the stimulus train persist nearer the active zone and exhibit more privileged use in the next RRP. Our findings reveal heterogeneity in vesicle fate based on nanoscale position and timing rules, providing new insights into the origins of future pool constitution

Comparison of SPECT bone scintigraphy with MRI for diagnosis of meniscal tears

BACKGROUND: Scintigraphy has been considered as competitive to MRI, but limited data are available on the accuracy of single photon emission tomography (SPECT) compared with MRI for the assessment of meniscal tears. Our objective was to assess the value of SPECT in comparison to MRI. METHODS: Between January 2003 and March 2004, sixteen patients were studied with both modalities and the accuracy rates of SPECT scan results, and MRI findings in the diagnosis of meniscal tears were compared. Arthroscopy was the gold standard. RESULTS: The respective sensitivity rate, specificity rate, and positive and negative predictive accuracies of MRI were 89%, 94%, 93%, and 79% and for SPECT those were 78%, 94%, 94%, and 88%. There was good agreement on the presence or absence of tears between two modalities (κ statistic = 0.699). CONCLUSION: SPECT and MRI are both valuable imaging techniques. SPECT is a useful alternative when MRI is unavailable or unsuitable and it is beneficial when more possible accuracy is desired (such as when MRI results are either inconclusive or conflict with other clinical data)

Percent body fat estimations in college women using field and laboratory methods: a three-compartment model approach

This is the publisher's version, also available electronically from http://www.jissn.com/content/4/1/16.Background Methods used to estimate percent body fat can be classified as a laboratory or field technique. However, the validity of these methods compared to multiple-compartment models has not been fully established. This investigation sought to determine the validity of field and laboratory methods for estimating percent fat (%fat) in healthy college-age women compared to the Siri three-compartment model (3C). Methods Thirty Caucasian women (21.1 ± 1.5 yrs; 164.8 ± 4.7 cm; 61.2 ± 6.8 kg) had their %fat estimated by BIA using the BodyGram™ computer program (BIA-AK) and population-specific equation (BIA-Lohman), NIR (Futrex® 6100/XL), a quadratic (SF3JPW) and linear (SF3WB) skinfold equation, air-displacement plethysmography (BP), and hydrostatic weighing (HW). Results All methods produced acceptable total error (TE) values compared to the 3C model. Both laboratory methods produced similar TE values (HW, TE = 2.4%fat; BP, TE = 2.3%fat) when compared to the 3C model, though a significant constant error (CE) was detected for HW (1.5%fat, p ≤ 0.006). The field methods produced acceptable TE values ranging from 1.8 – 3.8 %fat. BIA-AK (TE = 1.8%fat) yielded the lowest TE among the field methods, while BIA-Lohman (TE = 2.1%fat) and NIR (TE = 2.7%fat) produced lower TE values than both skinfold equations (TE > 2.7%fat) compared to the 3C model. Additionally, the SF3JPW %fat estimation equation resulted in a significant CE (2.6%fat, p ≤ 0.007). Conclusion Data suggest that the BP and HW are valid laboratory methods when compared to the 3C model to estimate %fat in college-age Caucasian women. When the use of a laboratory method is not feasible, NIR, BIA-AK, BIA-Lohman, SF3JPW, and SF3WB are acceptable field methods to estimate %fat in this population

Human α2β1HI CD133+VE epithelial prostate stem cells express low levels of active androgen receptor

Stem cells are thought to be the cell of origin in malignant transformation in many tissues, but their role in human prostate carcinogenesis continues to be debated. One of the conflicts with this model is that cancer stem cells have been described to lack androgen receptor (AR) expression, which is of established importance in prostate cancer initiation and progression. We re-examined the expression patterns of AR within adult prostate epithelial differentiation using an optimised sensitive and specific approach examining transcript, protein and AR regulated gene expression. Highly enriched populations were isolated consisting of stem (α(2)β(1)(HI) CD133(+VE)), transiently amplifying (α(2)β(1)(HI) CD133(-VE)) and terminally differentiated (α(2)β(1)(LOW) CD133(-VE)) cells. AR transcript and protein expression was confirmed in α(2)β(1)(HI) CD133(+VE) and CD133(-VE) progenitor cells. Flow cytometry confirmed that median (±SD) fraction of cells expressing AR were 77% (±6%) in α(2)β(1)(HI) CD133(+VE) stem cells and 68% (±12%) in α(2)β(1)(HI) CD133(-VE) transiently amplifying cells. However, 3-fold lower levels of total AR protein expression (peak and median immunofluorescence) were present in α(2)β(1)(HI) CD133(+VE) stem cells compared with differentiated cells. This finding was confirmed with dual immunostaining of prostate sections for AR and CD133, which again demonstrated low levels of AR within basal CD133(+VE) cells. Activity of the AR was confirmed in prostate progenitor cells by the expression of low levels of the AR regulated genes PSA, KLK2 and TMPRSS2. The confirmation of AR expression in prostate progenitor cells allows integration of the cancer stem cell theory with the established models of prostate cancer initiation based on a functional AR. Further study of specific AR functions in prostate stem and differentiated cells may highlight novel mechanisms of prostate homeostasis and insights into tumourigenesis

In Vivo Anti-Tumor Activity of Polypeptide HM-3 Modified by Different Polyethylene Glycols (PEG)

HM-3, designed by our laboratory, is a polypeptide composed of 18 amino acids. Pharmacodynamic studies in vivo and in vitro indicated that HM-3 could inhibit endothelial cell migration and angiogenesis, thereby inhibiting tumor growth. However, the half-life of HM-3 is short. In this study, we modified HM-3 with different polyethylene glycols (PEG) in order to reduce the plasma clearance rate, extend the half-life in the body, maintain a high concentration of HM-3 in the blood and increase the therapeutic efficiency. HM-3 was modified with four different types of PEG with different molecular weights (ALD-mPEG5k, ALD-mPEG10k, SC-mPEG10k and SC-mPEG20k), resulting in four modified products (ALD-mPEG5k-HM-3, ALD-mPEG10k-HM-3, SC-mPEG10k-HM-3 and SC-mPEG20k-HM-3, respectively). Anti-tumor activity of these four modified HM-3 was determined in BALB/c mice with Taxol as a positive control and normal saline as a negative control. Tumor weight inhibition rates of mice treated with Taxol, HM-3, ALD-mPEG5k-HM-3, ALD-mPEG10k-HM-3, SC-mPEG10k-HM-3 and SC-mPEG20k-HM-3 were 44.50%, 43.92%, 37.95%, 31.64%, 20.27% and 50.23%, respectively. Tumor inhibition rates in the Taxol, HM-3 and SC-mPEG20k-HM-3 groups were significantly higher than that in the negative control group. The efficiency of tumor inhibition in the SC-mPEG20k-HM-3 group (drug treatment frequency: once per two days) was better than that in the HM-3 group (drug treatment frequency: twice per day). In addition, tumor inhibition rate in the SC-mPEG20k-HM-3 group was higher than that in the taxol group. We conclude that SC-mPEG20k-HM-3 had a low plasma clearance rate and long half-life, resulting in high anti-tumor therapeutic efficacy in vivo. Therefore, SC-mPEG20k-HM-3 could be potentially developed as new anti-tumor drugs

Peptide exchange on MHC-I by TAPBPR is driven by a negative allostery release cycle.

Chaperones TAPBPR and tapasin associate with class I major histocompatibility complexes (MHC-I) to promote optimization (editing) of peptide cargo. Here, we use solution NMR to investigate the mechanism of peptide exchange. We identify TAPBPR-induced conformational changes on conserved MHC-I molecular surfaces, consistent with our independently determined X-ray structure of the complex. Dynamics present in the empty MHC-I are stabilized by TAPBPR and become progressively dampened with increasing peptide occupancy. Incoming peptides are recognized according to the global stability of the final pMHC-I product and anneal in a native-like conformation to be edited by TAPBPR. Our results demonstrate an inverse relationship between MHC-I peptide occupancy and TAPBPR binding affinity, wherein the lifetime and structural features of transiently bound peptides control the regulation of a conformational switch located near the TAPBPR binding site, which triggers TAPBPR release. These results suggest a similar mechanism for the function of tapasin in the peptide-loading complex

MicroRNA-125b Potentiates Macrophage Activation

MicroRNA (miR)-125b expression is modulated in macrophages in response to stimulatory cues. In this study, we report a functional role of miR-125b in macrophages. We found that miR-125b is enriched in macrophages compared with lymphoid cells and whole immune tissues. Enforced expression of miR-125b drives macrophages to adapt an activated morphology that is accompanied by increased costimulatory factor expression and elevated responsiveness to IFN-y, whereas anti–miR-125b treatment decreases CD80 surface expression. To determine whether these alterations in cell signaling, gene expression, and morphology have functional consequences, we examined the ability of macrophages with enhanced miR-125b expression to present Ags and found that they better stimulate T cell activation than control macrophages. Further indicating increased function, these macrophages were more effective at killing EL4 tumor cells in vitro and in vivo. Moreover, miR-125b repressed IFN regulatory factor 4 (IRF4), and IRF4 knockdown in macrophages mimicked the miR-125b overexpression phenotype. In summary, our evidence suggests that miR-125b is at least partly responsible for generating the activated nature of macrophages, at least partially by reducing IRF4 levels, and potentiates the functional role of macrophages in inducing immune responses