Towards Identifying Protective B-Cell Epitopes: The PspA Story

Pneumococcal Surface Protein A (PspA) is one of the most abundant surface molecules of Streptococcus pneumoniae (or pneumococcus). As an important structural and serological variable cell surface virulence factor, it evades complement-mediated phagocytosis of pneumococcus essential for its survival in the host. The cross-protection eliciting regions in the structure of PspA have been localized in the α-helical and proline rich regions of PspA. Recent data indicate significant variation in the ability of antibodies induced against different recombinant PspAs to recognize S. pneumoniae strains expressing distinct PspAs. Identification of topographical repertoire of B-cell epitopes that elicit a protective immune response seems essential in the engineering of a superior PspA based vaccine. Herein, we revisited the epitope identification in PspA and the advent of hybridoma technology in directing identification of protective epitopic regions of PspA, having potential to be exploited in the generation of potent vaccine

Community pharmacies, drug stores, and antibiotic dispensing in Indonesia: a qualitative study

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The response to COVID-19 among drug retail outlets in Indonesia: A cross-sectional survey of knowledge, attitudes, and practices

Background: Pharmacists have been at the frontline of the COVID-19 response in Indonesia, providing medicines, advice, and referral services often in areas with limited healthcare access. This study aimed to explore their knowledge, attitudes, and practices during the pandemic, so that we can be better prepared for future emergencies. / Methods: A cross-sectional online survey of community pharmacists and pharmacy technicians in Indonesia was conducted between July and August 2020. The dataset was analysed descriptively, and logistic regression was used to explore willingness to participate in COVID-19 interventions. / Findings: 4716 respondents participated in the survey. Two-thirds (66·7%) reported knowing only “a little” about COVID-19 and around a quarter (26·6%) said they had not received any COVID-19 guidelines. Almost all were concerned about being infected (97·2%) and regularly took steps to protect themselves and their clients (87·2%). Stock-outs of Personal Protective Equipment (PPE) and other products (32·3%) was the main reason for not taking any precautions. Around a third (37·7%) mentioned having dispensed antibiotics to clients suspected of having COVID-19. To support COVID-19 response efforts, most respondents were willing to provide verbal advice to clients (97·8%), distribute leaflets to clients (97·7%), and participate in surveillance activities (88·8%). Older respondents, those identifying as male, and those working in smaller outlets were more willing to provide information leaflets. Those working in smaller outlets were also more willing to engage in outbreak surveillance. / Interpretation: Drug retail outlets continue to operate at the frontline of disease outbreaks and pandemics around the world. These providers have an important role to play by helping to reduce the burden on facilities and providing advice and treatment. To fulfil this role, drug retail outlets require regular access to accurate guidelines and steady supplies of PPE. Calls for drug retail outlet staff to plat in response efforts including the provision of information to clients and surveillance could ease escalating pressures on the health system during future outbreaks. / Funding: This study was funded by a grant from the Department of Foreign Affairs and Trade, Australia, under the Stronger Health Systems for Health Security Scheme

LONGITUDINAL STUDY OFRPE65-ASSOCIATED INHERITED RETINAL DEGENERATIONS

Purpose: To study the disease course ofRPE65-associated inherited retinal degenerations (IRDs) as a function of the genotype, define a critical age for blindness, and identify potential modifiers. Methods: Forty-five patients with IRD from 33 families with biallelicRPE65mutations, 28 stemming from a genetic isolate. We collected retrospective data from medical charts. Coexisting variants in 108 IRD-associated genes were identified with Molecular Inversion Probe analysis. Results: Most patients were diagnosed within the first years of life. Daytime visual function ranged from near-normal to blindness in the first four decades and met WHO criteria for blindness for visual acuity and visual field in the fifth decade. p.(Thr368His) was the most common variant (54%). Intrafamilial variability and interfamilial variability in disease severity and progression were observed. Molecular Inversion Probe analysis confirmed allRPE65variants and identified one additional variant inLRATand one inEYSin two separate patients. Conclusion: All patients withRPE65-associated IRDs developed symptoms within the first year of life. Visual function in childhood and adolescence varied but deteriorated inevitably toward blindness after age 40. In this study, genotype was not predictive of clinical course. The variance in severity of disease could not be explained by double hits in other IRD genes

Osteonecrosis following resurfacing arthroplasty: A clinical positron emission tomography study of 14 cases

Background and purpose One of the main concerns regarding resurfacing arthroplasty is the viability of the remaining part of the femoral head, and the postoperative risk of a femoral neck fracture or collapse. In contrast to radiographic methods, positron emission tomography using the radiotracer [18F]-fluoride (Fluoride-PET) enables us to visualize the viability of bone in the remaining part of the head, despite the presence of the covering metal component

IL-22 mediates goblet cell hyperplasia and worm expulsion in intestinal helminth infection.

Type 2 immune responses are essential in protection against intestinal helminth infections. In this study we show that IL-22, a cytokine important in defence against bacterial infections in the intestinal tract, is also a critical mediator of anti-helminth immunity. After infection with Nippostrongylus brasiliensis, a rodent hookworm, IL-22-deficient mice showed impaired worm expulsion despite normal levels of type 2 cytokine production. The impaired worm expulsion correlated with reduced goblet cell hyperplasia and reduced expression of goblet cell markers. We further confirmed our findings in a second nematode model, the murine whipworm Trichuris muris. T.muris infected IL-22-deficient mice had a similar phenotype to that seen in N.brasiliensis infection, with impaired worm expulsion and reduced goblet cell hyperplasia. Ex vivo and in vitro analysis demonstrated that IL-22 is able to directly induce the expression of several goblet cell markers, including mucins. Taken together, our findings reveal that IL-22 plays an important role in goblet cell activation, and thus, a key role in anti-helminth immunity

Cortical depth dependent functional responses in humans at 7T: improved specificity with 3D GRASE

Ultra high fields (7T and above) allow functional imaging with high contrast-to-noise ratios and improved spatial resolution. This, along with improved hardware and imaging techniques, allow investigating columnar and laminar functional responses. Using gradient-echo (GE) (T2* weighted) based sequences, layer specific responses have been recorded from human (and animal) primary visual areas. However, their increased sensitivity to large surface veins potentially clouds detecting and interpreting layer specific responses. Conversely, spin-echo (SE) (T2 weighted) sequences are less sensitive to large veins and have been used to map cortical columns in humans. T2 weighted 3D GRASE with inner volume selection provides high isotropic resolution over extended volumes, overcoming some of the many technical limitations of conventional 2D SE-EPI, whereby making layer specific investigations feasible. Further, the demonstration of columnar level specificity with 3D GRASE, despite contributions from both stimulated echoes and conventional T2 contrast, has made it an attractive alternative over 2D SE-EPI. Here, we assess the spatial specificity of cortical depth dependent 3D GRASE functional responses in human V1 and hMT by comparing it to GE responses. In doing so we demonstrate that 3D GRASE is less sensitive to contributions from large veins in superficial layers, while showing increased specificity (functional tuning) throughout the cortex compared to GE

Nucleon-Gold Collisions at 200 AGeV Using Tagged d+Au Interactions in PHOBOS

Forward calorimetry in the PHOBOS detector has been used to study charged hadron production in d+Au, p+Au and n+Au collisions at sqrt(s_nn) = 200 GeV. The forward proton calorimeter detectors are described and a procedure for determining collision centrality with these detectors is detailed. The deposition of energy by deuteron spectator nucleons in the forward calorimeters is used to identify p+Au and n+Au collisions in the data. A weighted combination of the yield of p+Au and n+Au is constructed to build a reference for Au+Au collisions that better matches the isospin composition of the gold nucleus. The p_T and centrality dependence of the yield of this improved reference system is found to match that of d+Au. The shape of the charged particle transverse momentum distribution is observed to extrapolate smoothly from pbar+p to central d+Au as a function of the charged particle pseudorapidity density. The asymmetry of positively- and negatively-charged hadron production in p+Au is compared to that of n+Au. No significant asymmetry is observed at mid-rapidity. These studies augment recent results from experiments at the LHC and RHIC facilities to give a more complete description of particle production in p+A and d+A collisions, essential for the understanding the medium produced in high energy nucleus-nucleus collisions.Comment: 17 pages, 18 figure

Substantial and sustained reduction in under-5 mortality, diarrhea, and pneumonia in Oshikhandass, Pakistan : Evidence from two longitudinal cohort studies 15 years apart

Funding Information: Study 1 was funded through the Applied Diarrheal Disease Research Program at Harvard Institute for International Development with a grant from USAID (Project 936–5952, Cooperative Agreement # DPE-5952-A-00-5073-00), and the Aga Khan Health Service, Northern Areas and Chitral, Pakistan. Study 2 was funded by the Pakistan US S&T Cooperative Agreement between the Pakistan Higher Education Commission (HEC) (No.4–421/PAK-US/HEC/2010/955, grant to the Karakoram International University) and US National Academies of Science (Grant Number PGA-P211012 from NAS to the Fogarty International Center). The funding bodies had no role in the design of the study, data collection, analysis, interpretation, or writing of the manuscript. Publisher Copyright: © 2020 The Author(s).Peer reviewedPublisher PD