Comparative Study of Bioactive Compounds in Different Varieties of Pears in Nepal

This study was conducted to evaluate the physicochemical parameters, perform qualitative tests (for sugars and phytochemicals), and quantitative tests (phenolics, antioxidants, anthocyanins, tannins, vitamin C) of six different varieties of pears i.e. Bartlette, Chinese pears, Chojuro, Kosui, Pharping local, and Yakumo. The juices extracted from respective pears were used for the analysis. The phenols were determined by the Folin-Ciocalteu method, antioxidants by the DPPH scavenging activity, and anthocyanins by a SO2 bleaching technique. The Pharping local pears were found to have the highest anthocyanins (85.95±0.1 mg/l), total phenolic content (600±0.01 mg GAE/l), antioxidants (IC50 value 250±0.00 mg of phenol/l) and vitamin C content (12.2±0.01 mg/100 ml) and tannins were observed to be highest in Yakumo pears (0.93±0.01 g/l). Likewise, the highest clarity i.e. 1.960±0.00 was observed in Bartlette pears and the highest acidity (2.01±0.01%) in  Chojuro pears. Various sugar/carbohydrate tests like Molisch’s test, Benedict’s test, Barfoed test, Bial’s test, Seliwanoff test, Fehling’s test and Iodine test were performed for the pear varieties. All the pears gave positive results for all the sugar tests except Iodine test. The positive results for sugar/carbohydrate signifies the presence of various sugars that help for the better taste, texture, and aroma of pear. The pear varieties showed the presence of phytochemicals like flavonoids, terpenoids, catechins, cyclic glycosides, and proteins. The phytochemicals are responsible for fruit preservation and act as anti-carcinogenic components. Among the varieties of pears, Pharping local pears were observed to be most nutritional because of high antioxidants, phenols, anthocyanins, and vitamin C

Evaluation of Phytochemical, Antimicrobial, Antioxidant Activity and Cytotoxic Potentials of Agave americana

Ethnomedicinal plants are being used as a source of medicine from ancient time but they lack the proof of modern scientific evidence for their effectiveness. This study focuses on the evaluation of phytochemical, antimicrobial, antioxidant properties of one of the ethnomedicinal plant Agave americana from Dhulikhel region of Nepal. The plant extract was prepared using solvent-based warm soxhlet extraction from the leaves of the plant and antimicrobial activity against six different non-resistant clinical isolates of bacteria (Staphylococcus aureus, Shigella, Klebsiella pneumoniae, Escherichia coli, Bacillus thuringiensis, and Salmonella paratyphi) was evaluated using agar disc diffusion method along with qualitative analysis for presence/absence of phytochemicals. Antioxidant activity was measured by DPPH assay and the cytotoxicity was evaluated using MCF-7 (human breast adenocarcinoma) cancer cell. Presence of phytochemicals like alkaloids, flavonoids, reducing sugars and saponins were detected in the plant extract. The extract was found to show some level of antimicrobial activity against Staphylococcus aureus, Escherichia coli and Bacillus thuringiensis at 50, 100 and 200 mg/ml. The IC50 value of the extract was found to be 7.68 μg/ml. The extracts of Agave americana showed 50 % cell-death of MCF-7 in 12 h at 5 μg/ml. Although this study provided some scientific evidence for the medicinal value of Agave americana, further studies are still needed for the detailed evaluations of every molecule present in this plant along with screening in larger geographical area of Nepal

Cost-Effectiveness of Newborn Circumcision in Reducing Lifetime HIV Risk among U.S. Males

BACKGROUND: HIV incidence was substantially lower among circumcised versus uncircumcised heterosexual African men in three clinical trials. Based on those findings, we modeled the potential effect of newborn male circumcision on a U.S. male's lifetime risk of HIV, including associated costs and quality-adjusted life-years saved. METHODOLOGY/PRINCIPAL FINDINGS: Given published estimates of U.S. males' lifetime HIV risk, we calculated the fraction of lifetime risk attributable to heterosexual behavior from 2005-2006 HIV surveillance data. We assumed 60% efficacy of circumcision in reducing heterosexually-acquired HIV over a lifetime, and varied efficacy in sensitivity analyses. We calculated differences in lifetime HIV risk, expected HIV treatment costs and quality-adjusted life years (QALYs) among circumcised versus uncircumcised males. The main outcome measure was cost per HIV-related QALY saved. Circumcision reduced the lifetime HIV risk among all males by 15.7% in the base case analysis, ranging from 7.9% for white males to 20.9% for black males. Newborn circumcision was a cost-saving HIV prevention intervention for all, black and Hispanic males. The net cost of newborn circumcision per QALY saved was $87,792 for white males. Results were most sensitive to the discount rate, and circumcision efficacy and cost. CONCLUSIONS/SIGNIFICANCE: Newborn circumcision resulted in lower expected HIV-related treatment costs and a slight increase in QALYs. It reduced the 1.87% lifetime risk of HIV among all males by about 16%. The effect varied substantially by race and ethnicity. Racial and ethnic groups who could benefit the most from circumcision may have least access to it due to insurance coverage and state Medicaid policies, and these financial barriers should be addressed. More data on the long-term protective effect of circumcision on heterosexual males as well as on its efficacy in preventing HIV among MSM would be useful

EN-BIRTH Data Collector Training - Handbook and Manual

The EN-BIRTH study aims to validate selected newborn and maternal indicators for routine facility-based tracking of coverage and quality of care for use at district, national and global levels. The item contains the EN-BIRTH_Trainer's Manual (14 June 2017) and EN-BIRTH_Training Handbook (23 May 2017)

EN-BIRTH Data Collector Training - Supporting Annexes

The EN-BIRTH study aims to validate selected newborn and maternal indicators for routine facility-based tracking of coverage and quality of care for use at district, national and global levels. The item contains consent forms and participant information, in addition to standard operating procedures (SOP) for adverse clinical events, and managing distress in interviews. The full complement of annex files used during the training can be requested via this site if required

The mammalian LINC complex regulates genome transcriptional responses to substrate rigidity

Mechanical integration of the nucleus with the extracellular matrix (ECM) is established by linkage between the cytoskeleton and the nucleus. This integration is hypothesized to mediate sensing of ECM rigidity, but parsing the function of nucleus-cytoskeleton linkage from other mechanisms has remained a central challenge. Here we took advantage of the fact that the LINC (linker of nucleoskeleton and cytoskeleton) complex is a known molecular linker of the nucleus to the cytoskeleton, and asked how it regulates the sensitivity of genome-wide transcription to substratum rigidity. We show that gene mechanosensitivity is preserved after LINC disruption, but reversed in direction. Combined with myosin inhibition studies, we identify genes that depend on nuclear tension for their regulation. We also show that LINC disruption does not attenuate nuclear shape sensitivity to substrate rigidity. Our results show for the first time that the LINC complex facilitates mechano-regulation of expression across the genome

Floristic quality assessment for Orchis Fen Preserve, Emmet County, Michigan

Field Biology of PlantsThe Michigan Floristic Quality Assessment (FQA) is a tool used to evaluate the natural significance and floristic quality of a given locality. We evaluated the plant community at Orchis Fen, a 35-acre preserve in Emmet County, Michigan owned by the Little Traverse Conservancy and Nature Conservancy. The purpose of our study was to use the Floristic Quality Index (FQI), Wetness Index, and the mean coefficient of conservatism (C) to provide the Little Traverse Conservancy and Nature Conservancy with information to aid in their preservation and management strategies. We set up a diagonal transect and identified plants across the site, passing through three interconnected habitats: cedar swamp, fen, and hardwood forest (Figure 1). We found that the mean C was 5.14 for native species and 4.42 when invasive species were taken into account. The FQI for native species was 53.14 and 49.60 including invasive species. The native wetness coefficient (W) was -1.96 for the entire transect and changed to -1.75 with adventives. These values indicate that Orchis Fen is a high quality natural area with an above-average representation of plant species associated with pre-settlement conditions. Our study reinforces the importance of continuing to focus on preservation efforts in this area.http://deepblue.lib.umich.edu/bitstream/2027.42/61466/3/Falk_et_al_2008.pd

Proactive prevention: Act now to disrupt the impending non-communicable disease crisis in low-burden populations

Non-communicable disease (NCD) prevention efforts have traditionally targeted high-risk and high-burden populations. We propose an alteration in prevention efforts to also include emphasis and focus on low-risk populations, predominantly younger individuals and low-prevalence populations. We refer to this approach as “proactive prevention.” This emphasis is based on the priority to put in place policies, programs, and infrastructure that can disrupt the epidemiological transition to develop NCDs among these groups, thereby averting future NCD crises. Proactive prevention strategies can be classified, and their implementation prioritized, based on a 2-dimensional assessment: impact and feasibility. Thus, potential interventions can be categorized into a 2-by-2 matrix: high impact/high feasibility, high impact/ low feasibility, low impact/high feasibility, and low impact/low feasibility. We propose that high impact/high feasibility interventions are ready to be implemented (act), while high impact/low feasibility interventions require efforts to foster buy-in first. Low impact/high feasibility interventions need to be changed to improve their impact while low impact/low feasibility might be best re-designed in the context of limited resources. Using this framework, policy makers, public health experts, and other stakeholders can more effectively prioritize and leverage limited resources in an effort to slow or prevent the evolving global NCD crisis.Fil: Njuguna, Benson. Moi Teaching & Referral Hospital; KeniaFil: Fletcher, Sara L.. State University of Oregon; Estados UnidosFil: Akwanalo, Constantine. Moi Teaching & Referral Hospital; KeniaFil: Asante, Kwaku Poku. Kintampo Health Research Centre; GhanaFil: Baumann, Ana. Washington University in St. Louis; Estados UnidosFil: Brown, Angela. Washington University in St. Louis; Estados UnidosFil: Davila Roman, Victor G.. Washington University in St. Louis; Estados UnidosFil: Dickhaus, Julia. New York University Grossman School of Medicine; Estados UnidosFil: Fort, Meredith. Colorado School Of Public Health; Estados UnidosFil: Iwelunmor, Juliet. Saint Louis University; Estados UnidosFil: Irazola, Vilma. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Mohan, Sailesh. Centre For Chronic Disease Control; India. Public Health Foundation Of India; IndiaFil: Mutabazi, Vincent. Regional Alliance For Sustainable Development; RuandaFil: Newsome, Brad. Center for Translation Research and Implementation Science; Estados UnidosFil: Ogedegbe, Olugbenga. New York University Grossman School of Medicine; Estados UnidosFil: Pastakia, Sonak D.. Purdue University College Of Pharmacy; Estados UnidosFil: Peprah, Emmanuel K.. University of New York; Estados UnidosFil: Plange Rhule, Jacob. Ghana College Of Physicians And Surgeons; GhanaFil: Roth, Gregory. University of Washington; Estados UnidosFil: Shrestha, Archana. Kathmandu University School Of Medical Sciences; NepalFil: Watkins, David A.. University of Washington; Estados UnidosFil: Vedanthan, Rajesh. New York University Grossman School of Medicine; Estados Unido

EN-BIRTH Data Collection Tools

The EN-BIRTH study aims to validate selected newborn and maternal indicators for routine facility-based tracking of coverage and quality of care for use at district, national and global levels. The item contains the following data collection tools: Register data extraction, Observation checklist (labour and delivery ward), Observation checklist (kangaroo mother care), Patient record verification tools for antenatal corticosteroid administration, Patient record verification tools for antibiotic administration, and the Maternal recall survey

Combination Therapies Targeting ALK-aberrant Neuroblastoma in Preclinical Models

PURPOSE ALK-activating mutations are identified in approximately 10% of newly diagnosed neuroblastomas and ALK amplifications in a further 1%-2% of cases. Lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) inhibitor, will soon be given alongside induction chemotherapy for children with ALK-aberrant neuroblastoma. However, resistance to single-agent treatment has been reported and therapies that improve the response duration are urgently required. We studied the preclinical combination of lorlatinib with chemotherapy, or with the MDM2 inhibitor, idasanutlin, as recent data have suggested that ALK inhibitor resistance can be overcome through activation of the p53-MDM2 pathway. EXPERIMENTAL DESIGN We compared different ALK inhibitors in preclinical models prior to evaluating lorlatinib in combination with chemotherapy or idasanutlin. We developed a triple chemotherapy (CAV: cyclophosphamide, doxorubicin, and vincristine) in vivo dosing schedule and applied this to both neuroblastoma genetically engineered mouse models (GEMM) and patient-derived xenografts (PDX). RESULTS Lorlatinib in combination with chemotherapy was synergistic in immunocompetent neuroblastoma GEMM. Significant growth inhibition in response to lorlatinib was only observed in the ALK-amplified PDX model with high ALK expression. In this PDX, lorlatinib combined with idasanutlin resulted in complete tumor regression and significantly delayed tumor regrowth. CONCLUSIONS In our preclinical neuroblastoma models, high ALK expression was associated with lorlatinib response alone or in combination with either chemotherapy or idasanutlin. The synergy between MDM2 and ALK inhibition warrants further evaluation of this combination as a potential clinical approach for children with neuroblastoma