Unravelling the multiple functions of the architecturally intricate Streptococcus pneumoniae ß-galactosidase, BgaA.

Bacterial cell-surface proteins play integral roles in host-pathogen interactions. These proteins are often architecturally and functionally sophisticated and yet few studies of such proteins involved in host-pathogen interactions have defined the domains or modules required for specific functions. Streptococcus pneumoniae (pneumococcus), an opportunistic pathogen that is a leading cause of community acquired pneumonia, otitis media and bacteremia, is decorated with many complex surface proteins. These include ß-galactosidase BgaA, which is specific for terminal galactose residues ß-1-4 linked to glucose or N-acetylglucosamine and known to play a role in pneumococcal growth, resistance to opsonophagocytic killing, and adherence. This study defines the domains and modules of BgaA that are required for these distinct contributions to pneumococcal pathogenesis. Inhibitors of ß-galactosidase activity reduced pneumococcal growth and increased opsonophagocytic killing in a BgaA dependent manner, indicating these functions require BgaA enzymatic activity. In contrast, inhibitors increased pneumococcal adherence suggesting that BgaA bound a substrate of the enzyme through a distinct module or domain. Extensive biochemical, structural and cell based studies revealed two newly identified non-enzymatic carbohydrate-binding modules (CBMs) mediate adherence to the host cell surface displayed lactose or N-acetyllactosamine. This finding is important to pneumococcal biology as it is the first adhesin-carbohydrate receptor pair identified, supporting the widely held belief that initial pneumococcal attachment is to a glycoconjugate. Perhaps more importantly, this is the first demonstration that a CBM within a carbohydrate-active enzyme can mediate adherence to host cells and thus this study identifies a new class of carbohydrate-binding adhesins and extends the paradigm of CBM function. As other bacterial species express surface-associated carbohydrate-active enzymes containing CBMs these findings have broad implications for bacterial adherence. Together, these data illustrate that comprehending the architectural sophistication of surface-attached proteins can increase our understanding of the different mechanisms by which these proteins can contribute to bacterial pathogenesis.

Macrophage migration inhibitory factor acts as a neurotrophin in the developing inner ear.

This study is the first to demonstrate that macrophage migration inhibitory factor (MIF), an immune system 'inflammatory' cytokine that is released by the developing otocyst, plays a role in regulating early innervation of the mouse and chick inner ear. We demonstrate that MIF is a major bioactive component of the previously uncharacterized otocyst-derived factor, which directs initial neurite outgrowth from the statoacoustic ganglion (SAG) to the developing inner ear. Recombinant MIF acts as a neurotrophin in promoting both SAG directional neurite outgrowth and neuronal survival and is expressed in both the developing and mature inner ear of chick and mouse. A MIF receptor, CD74, is found on both embryonic SAG neurons and adult mouse spiral ganglion neurons. Mif knockout mice are hearing impaired and demonstrate altered innervation to the organ of Corti, as well as fewer sensory hair cells. Furthermore, mouse embryonic stem cells become neuron-like when exposed to picomolar levels of MIF, suggesting the general importance of this cytokine in neural development.

A Survey of Texas HIV, Sexually Transmitted Disease, Tuberculosis, and Viral Hepatitis Providers' Billing and Reimbursement Capabilities.

The Affordable Care Act presents financial challenges and opportunities for publicly funded service providers. We assessed billing practices and anticipated barriers to third-party billing among organizations in Texas that provide publicly funded HIV, sexually transmitted diseases, tuberculosis, and viral hepatitis services. One third to one half of the organizations did not bill for medical services. The most common barrier to third-party billing was lack of staff knowledge about billing and coding. Future research must evaluate options for organizations and communities to maintain access to infectious disease services for vulnerable populations.

Capitalizing on Hope: Questionable Marketing Approval and Pricing of a New ALS Drug.

Regulatory agencies must balance patient demands to access new treatments for fatal diseases with limited treatment options while ensuring drug safety and efficacy. However, questionable U.S. regulatory actions resulted in the early approval of AMX0035 to treat amyotrophic lateral sclerosis (ALS) by reconvening advisory commissions to obtain positive decisions and designating the drug as a new molecular entity. Data from one randomized clinical trial suggests minimal delays in disease progression and longer survivability, but debate remains about the lack of confirmatory evidence of effectiveness owing to study limitations. A patient's decision-making process details the experience of using the drug, including perspectives on access, cost, effectiveness, and adverse effects. In line with the "nichebuster" business model, the drugmaker, Amylyx Pharmaceuticals, is charging US$158,000/year/patient and thus forecast to turn a profit on a drug with debatable clinical effectiveness prior to completing a Phase 3 trial. Early marketing approval, despite community demands, is unnecessary and may have reduced access because of the end of a compassionate use program, and the high price tag results in restricted coverage and high out-of-pocket costs. Also, the drug's key ingredients are available as a generic and a supplement.

#Anatomynotes: A temporal content analysis of anatomy education posts on Instagram.

Social media platforms such as Instagram are becoming increasingly popular sources for students to access anatomy educational resources. This review used content analysis to examine posts under the hashtag #anatomynotes and is the first to map the characteristics of anatomy education posts on Instagram and determine any temporal changes. Sample posts were gathered from April 2019 and April 2021 and categorized according to the technical format, purpose and author credentials. Engagement was recorded in the form of likes and comments. Overall, posts depicting illustrations remained the most popular format within both time periods. Three-dimensional models saw an increase in popularity with a 62.5% rise. Students remained the most common author type throughout and increased further in 2021 by 25%. Clinician authors and posts focusing on clinical education also increased in 2021 by 17.9% and 227%, respectively. Humor-based posts saw the greatest increase among the post purposes, with 1000% more recorded in 2021. Engagement overall saw a decline with notably significant reductions in average likes per post among all text-based posts (-72%, p < 0.0001), all illustrative posts (-51%, p = 0.0013), and a decline in the presence of comments among all text-based posts (-65.1%, p = 0.0158). These findings highlight that Instagram is a popular platform for facilitating near-peer teaching while increasingly providing a space where students and clinicians can interact. Additionally, it highlights the benefits of the platform for visually focused learners. However, future research should seek to determine whether Instagram can facilitate deeper learning and have an impact on academic and clinical performance.

Brazilian pharmaceutical diplomacy: social democratic principles versus soft power interests.

Current debates concerning the rise of health diplomacy are polarized between competing international relations theories of realism, based on power politics, and constructivist approaches, which emphasize the norms, values, and identities shaping foreign policies. A case study of Brazil's health diplomacy over the past 10 years, focusing on issues related to pharmaceuticals, seeks to provide data to assess these theories. The country's intellectual property disputes, multilateral lobbying efforts, and foreign assistance programs are contrasted with those of the United States, Mexico, and other countries. Instead of viewing Brazilian efforts as a form of soft power, the evidence suggests that the origins of Brazil's involvement and continued efforts in this arena stem more from values based on human rights and social democratic principles. A close examination of domestic political considerations leads to a more nuanced understanding of the drivers behind a country's health diplomacy.

The evil corporation master frame: The cases of vaccines and genetic modification.

Employing a qualitative content analysis of online comments made on YouTube and letters to the editor published in US newspapers, we examine the deployment and neutralization of the evil corporation master frame in debates on two distinct biotechnologies, vaccines and genetically modified organisms. This study builds on previous research by outlining three diagnostic components of the evil corporation master frame: dishonesty, greed, and the contamination of authority. It also finds that supporters of vaccines and genetically modified organisms seek to neutralize the evil corporation master frame through aggressive, defensive, endurance, and redemptive framings. This study provides ideational detail for the ways that controversial biotechnology is constructed. The particularly vexing anti-vaccine movement is not dissimilar from other challenges to mainstream science as disparate movements draw on the same master frame. It also demonstrates how defenses of genetically modified organisms and vaccines tend to reify the anti-corporate stigma that sustains challenges to scientific authority.

Glycolaldehyde as a Bio-Based C1 Building Block for Selective N-Formylation of Secondary Amines.

Biomass derived glycolaldehyde was employed as C1 building block for the N-formylation of secondary amines using air as oxidant. The reaction is atom economic, highly selective and proceeds under catalyst free conditions. This strategy can be used for the synthesis of cyclic and acyclic formylamines, including DMF. Mechanistic studies suggest a radical oxidation pathway.

Children Receiving a Nutrition and High-Quality Early Childhood Education Intervention Are Associated with Greater Math and Fluid Intelligence Scores: The Guatemala City Municipal Nurseries.

Background: About 47% of children < 5 years of age are stunted in Guatemala. In this study, the investigators aimed to compare growth and cognitive outcomes between children in second grade that attended five Guatemala City Municipal Nurseries (GCMN) vs. same sex, grade, and age-matched children. Methods: A cross-sectional design nested in a retrospective cohort was implemented between 2015 and 2019. Children that attended the GCMN and matched controls completed a math test and validated receptive language and fluid intelligence tests. The primary caregivers completed a sociodemographic survey. General and generalized linear mixed effect models were used to compare children that attended the GCMN vs. controls. The models were adjusted by maternal education, sex, asset score, and other relevant covariates. Results: Children that attended the GCMN exhibited greater math and fluid intelligence scores relative to the controls in the adjusted models (ß = 6.48; 95% CI (2.35−10.61)) and (ß = 1.20; 95% CI (0.12−2.29)), respectively. Lower odds of stunting were significant for children who went to any early childcare institution (AOR = 0.28; 95% CI (0.09−0.89)). Conclusions: The importance of integrating nutrition and high-quality early childhood education interventions in cognitive and growth outcomes is highlighted in this study. The GCMN model may be a scalable model in similar low-resource settings.

Interactions of the bacteriome, virome, and immune system in the nose.

Emerging evidence suggests that the nasal microbiome may influence host susceptibility to initial development and severity of respiratory viral infections. While not as extensively studied as the microbiota of the alimentary tract, it is now clearly established that the microbial composition of this niche is influenced by medical, social and pharmacological influences, predisposing some sub-populations to respiratory infections. The resulting specific microbial profiles may explain variance in susceptibility to viral infection. This review summaries the evolution and constituents of the commensal nasal microbiome; the bacterial-virus, bacterial-host and interbacterial interactions which potentiate disease; and considers the effects of interventions such as vaccination and probiotics.

Developing critical appraisal and evidence synthesis skills in future microbiologists.

The Covid-19 pandemic has demanded modifications to undergraduates' learning experiences and promised a more challenging scientific world in which they will live. Bespoke evidence synthesis and critical appraisal skills modules are an opportunity to utilize our information-saturated world to our advantage. This program of study made use of a virtual journal club, structured literature searches, scoping review methods and a variety of online research tools to navigate and critique the literature. The program design is here outlined with sample learning objectives and reference to the resources used.

Global capitalism as a societal determinant of health: A conceptual framework.

Recent scholarship has sought to distinguish between the deeper societal factors that shape the more proximate social determinants of health. One of these socio-structural institutions is global capitalism. While critical scholarship has advanced our understanding of the relationships between capitalist globalization and health, more work is needed to understand the transnational economic, political, and cultural practices that affect various global health issues. This paper argues that the theory of global capitalism provides an important, critical perspective for understanding different phenomena associated with global health. The theory's key concepts of transnational corporations, financialization, consumerism, transnational social classes, and transnational state comprise the conceptual framework. When applied to various global health topics, the theory advances our understanding of the health-related institutional structures of today's global economy, provides a holistic view that integrates various strands of health research, highlights various forms of health activism, and offers new questions for addressing persistent health injustice across the world.

The microbiome of the nasopharynx.

The nasopharyngeal microbiome is a dynamic microbial interface of the aerodigestive tract, and a diagnostic window in the fight against respiratory infections and antimicrobial resistance. As its constituent bacteria, viruses and mycobacteria become better understood and sampling accuracy improves, diagnostics of the nasopharynx could guide more personalized care of infections of surrounding areas including the lungs, ears and sinuses. This review will summarize the current literature from a clinical perspective and highlight its growing importance in diagnostics and infectious disease management.

Framing access to medicines during COVID-19: A qualitative content analysis of Gilead's Remdesivir.

The COVID-19 pandemic calls into question the institutional structure underlying the pharmaceutical industry. While some have called for medical technologies to be global public goods and patent waivers on pharmaceuticals, much of the industry has pushed back against any attempts that might threaten their monopoly power to set prices. Public acceptance of the role of private companies to control life-saving drugs, as well as of the intellectual property system, informs campaigns guaranteeing universal access to medicines and corporate strategies to shape policy. This study consists of a qualitative content analysis of online comments about news reports of Gilead Science's pricing of remdesivir, a re-purposed drug that shows some positive efficacy against COVID-19 in clinical trials. Analysing elite and public framing about medicine pricing informs our understanding of the social construction of markets. The findings identify hegemonic and counter-hegemonic discourse about innovation, affordability, saving lives, health care savings and international comparisons that stimulate debate and potentially advocacy. As such, the discursive context delineates the possibilities for remediating the normative and material structure of a pharmaceutical system currently geared towards private profit instead of public health needs.

Nasopharyngeal Swabs vs. Nasal Aspirates for Respiratory Virus Detection: A Systematic Review.

Nasal pathogen detection sensitivities can be as low as 70% despite advances in molecular diagnostics. This may be linked to the choice of sampling method. A diagnostic test accuracy review for sensitivity was undertaken to compare sensitivity of swabbing to the nasopharynx and extracting nasal aspirates, using the PRISMA protocol, Cochrane rapid review methodology, and QUADAS-2 risk of bias tools, with meta-analysis of included studies. Sensitivities were calculated by a consensus standard of positivity by either method as the 'gold standard.' Insufficient sampling methodology, cross sectional study designs, and studies pooling samples across anatomical sites were excluded. Of 13 subsequently eligible studies, 8 had 'high' risk of bias, and 5 had 'high' applicability concerns. There were no statistical differences in overall sensitivities between collection methods for eight different viruses, and this did not differ with use of PCR, immunofluorescence, or culture. In one study alone, Influenza H1N1(2009) favored nasopharyngeal swabs, with aspirates having 93.3% of the sensitivity of swabs (p > 0.001). Similarly equivocal sensitivities were noted in reports detecting bacteria. The chain of sampling, from anatomical site to laboratory results, features different potential foci along which sensitivity may be lost. A fair body of evidence exists that use of a different sampling method will not yield more respiratory pathogens.

On the activation of PhICl2 with pyridine.

It has been previously proposed that pyridines can activate PhICl2 by displacing a chloride and forming the [PhI(Pyr)(Cl)]+ cation as a reactive intermediate. Here we show that pyridine does not displace chloride, but rather forms a weak complex with the iodine via halogen bonding along the C-I bond axis. This interaction is interrogated by NMR, structural, charge density, and theoretical investigations, which all indicate that pyridine does not activate PhICl2 as proposed.

Isomers of Alkali Metal (Methylbenzyl)allylamides: A Theoretical Perspective.

Recent studies of alkali metal N-(α-methylbenzyl)allylamides containing lithium, sodium, and potassium have shown unique rearrangements in NMR experiments. It was found that lithium isomers favored the formation of aza-allyl and aza-enolate complexes that could exist in a solution for a substantial amount of time. As the radius of the metal ion increases going from lithium to potassium, so does the preference for the formation of the imine structure. For sodium, the aza-allyl complex could still be isolated, whereas the imine structure was only found to be stable on the scale of several hours for potassium. In this work, ab initio calculations were used to shed light on this phenomenon. Decomposition of intermolecular interaction energies of the aza-allyl, aza-enolate, and imine complexes showed that for lithium, the formation of aza-allyl and aza-enolate complexes was driven by electrostatic interactions. For potassium, the dispersion component of the metal interaction with the ligand proved to be more important for the stability of the imine structure. The presence of the imine formation in potassium and partially in sodium was found to be due to the reduced electrostatic nature of these larger metals. The assignment of the experimental NMR spectra was further confirmed with the natural bond order (NBO) analysis as well as the partial charge calculations. Analysis of orbital energies, specifically those of the highest occupied molecular orbitals (HOMOs), as well as the deformation energies of each of the ligands, were also considered. Through these procedures, an understanding of the tendency for each metal to have a unique isomerization pathway was gained.

Acceptability of the Predicting Abusive Head Trauma (PredAHT) clinical prediction tool: A qualitative study with child protection professionals.

The validated Predicting Abusive Head Trauma (PredAHT) tool estimates the probability of abusive head trauma (AHT) based on combinations of six clinical features: head/neck bruising; apnea; seizures; rib/long-bone fractures; retinal hemorrhages. We aimed to determine the acceptability of PredAHT to child protection professionals. We conducted qualitative semi-structured interviews with 56 participants: clinicians (25), child protection social workers (10), legal practitioners (9, including 4 judges), police officers (8), and pathologists (4), purposively sampled across southwest United Kingdom. Interviews were recorded, transcribed and imported into NVivo for thematic analysis (38% double-coded). We explored participants' evaluations of PredAHT, their opinions about the optimal way to present the calculated probabilities, and their interpretation of probabilities in the context of suspected AHT. Clinicians, child protection social workers and police thought PredAHT would be beneficial as an objective adjunct to their professional judgment, to give them greater confidence in their decisions. Lawyers and pathologists appreciated its value for prompting multidisciplinary investigations, but were uncertain of its usefulness in court. Perceived disadvantages included: possible over-reliance and false reassurance from a low score. Interpretations regarding which percentages equate to 'low', 'medium' or 'high' likelihood of AHT varied; participants preferred a precise % probability over these general terms. Participants would use PredAHT with provisos: if they received multi-agency training to define accepted risk thresholds for consistent interpretation; with knowledge of its development; if it was accepted by colleagues. PredAHT may therefore increase professionals' confidence in their decision-making when investigating suspected AHT, but may be of less value in court.

Factors influencing child protection professionals' decision-making and multidisciplinary collaboration in suspected abusive head trauma cases: A qualitative study.

Clinicians face unique challenges when assessing suspected child abuse cases. The majority of the literature exploring diagnostic decision-making in this field is anecdotal or survey-based and there is a lack of studies exploring decision-making around suspected abusive head trauma (AHT). We aimed to determine factors influencing decision-making and multidisciplinary collaboration in suspected AHT cases, amongst 56 child protection professionals. Semi-structured interviews were conducted with clinicians (25), child protection social workers (10), legal practitioners (9, including 4 judges), police officers (8), and pathologists (4), purposively sampled across southwest United Kingdom. Interviews were recorded, transcribed and imported into NVivo for thematic analysis (38% double-coded). We identified six themes influencing decision-making: 'professional', 'medical', 'circumstantial', 'family', 'psychological' and 'legal' factors. Participants diagnose AHT based on clinical features, the history, and the social history, after excluding potential differential diagnoses. Participants find these cases emotionally challenging but are aware of potential biases in their evaluations and strive to overcome these. Barriers to decision-making include lack of experience, uncertainty, the impact on the family, the pressure of making the correct diagnosis, and disagreements between professionals. Legal barriers include alternative theories of causation proposed in court. Facilitators include support from colleagues and knowledge of the evidence-base. Participants' experiences with multidisciplinary collaboration are generally positive, however child protection social workers and police officers are heavily reliant on clinicians to guide their decision-making, suggesting the need for training on the medical aspects of physical abuse for these professionals and multidisciplinary training that provides knowledge about the roles of each agency.