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Background: Chlamydia and gonorrhea are two of the most common sexually transmitted infections (STIs) worldwide, presenting major public health challenges and resulting in billions of dollars in direct medical costs in the U.S. Incarcerated females have a particularly elevated risk of these infections, which can result in serious sequelae if left untreated. On December 13, 2021, the Los Angeles County Jail system began offering opt-out urogenital chlamydia and gonorrhea screening to all newly incarcerated females., Methods: We retrospectively analyzed electronic health record data for completed urogenital chlamydia/gonorrhea screening among newly incarcerated females between December 13, 2021, and May 31, 2023. We used multivariable logistic regression to examine the association of STIs and treatment non-initiation outcomes with various demographic and self-reported variables., Results: Of the 13,739 female entrants offered STI testing, 10,717 (78%) completed screening, with 1151 (11%) having a chlamydial infection, 788 (7%) having a gonococcal infection, and 1626 (15%) having >1 infection. STI positivity was associated with age 18-34, reported houselessness, amphetamine use, and history of a positive prior treponemal antibody test. STI treatment non-initiation was associated with shorter jail stay for both chlamydial ([aOR] = 87.4, 95% CI (34.2, 223.2)) and gonococcal ([aOR] = 9.0, 95% CI (5.2, 15.7)) infections., Conclusion: The STI prevalence among female detainees tested was manyfold higher than that of the general population. The implementation of routine opt-out STI screening in carceral settings provides a unique opportunity to benefit the health of both the correctional population and potentially that of the surrounding community., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article, (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

Correctional settings provide a high-risk environment for hepatitis A transmission because of the high proportion of homelessness and injection drug use among persons who are incarcerated. On May 30, 2023, Los Angeles County Department of Public Health informed the Communicable Disease Surveillance and Control (CDSC) unit of the Los Angeles County Jail system that a symptomatic incarcerated person had received a positive test result for acute hepatitis A. Upon learning the next day that the patient was a food handler, CDSC staff members identified 5,830 potential contacts of the index patient, 1,702 of whom had been released from the jail. During June 1-12, a total of 2,766 contacts who did not have a documented history of hepatitis A serology or vaccination that could be confirmed from the electronic health record or state immunization registry were identified. These persons were offered hepatitis A vaccination as postexposure prophylaxis; 1,510 (54.6%) accepted vaccination. Contacts who were food handlers without confirmed evidence of immunity and who declined vaccination were removed from food-handling duties for the duration of their potential incubation period. No additional cases were identified. Identifying contacts promptly and using immunization and serology records to ensure rapid delivery of postexposure prophylactic vaccine can help prevent hepatitis A transmission during exposures among incarcerated populations., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Correctional populations have been disproportionately affected by COVID-19, and many large outbreaks have occurred in jails and prisons. Vaccination is a key strategy to reduce the SARS-CoV-2 transmission in carceral settings. Although implementation can be challenging due to vaccine hesitancy and medical mistrust, correctional settings provide largely equitable healthcare access and present a unique opportunity to identify potential predictors of vaccine hesitancy independent of access issues., Methods: We retrospectively analyzed electronic health record data for individuals offered COVID-19 vaccination at the Los Angeles County Jail between January 19, 2021, and January 31, 2023, and used multivariable logistic regression to determine predictors of COVID-19 vaccine refusal., Results: Of the 21,424 individuals offered COVID-19 vaccination, 2,060 (9.6 %) refused. Refusal was associated with male sex ([aOR] = 2.3, 95 % CI (1.9, 2.8)), age 18-34 ([aOR] = 1.2, 95 % CI (1.1, 1.4), referent group: age 45-54), Black race ([aOR] = 1.2, 95 % CI (1.1, 1.4)), reporting ever being houseless ([aOR] = 1.2, 95 % CI (1.1, 1.3)), and having a history of not receiving influenza vaccination while incarcerated ([aOR] = 2.4, 95 % CI (2.0, 2.8)). When analyzing male and female populations separately, male-specific trends reflected those seen in the overall population, whereas the only significant predictor of vaccine refusal in the female population was not receiving influenza vaccination while in custody ([aOR] = 6.5, 95 % CI (2.4, 17.6))., Conclusion: Identifying predictors of vaccine refusal in correctional populations is an essential first step in the development and implementation of targeted interventions to mitigate vaccine hesitancy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

For diverse procedures, sizable geographic variation exists in rates and outcomes of surgery, including for degenerative lumbar spine conditions. Little is known about how surgeon training and experience are associated with surgeon-level variations in spine surgery practice and short-term outcomes. This retrospective observational analysis characterized variations in surgical operations for degenerative lumbar scoliosis or spondylolisthesis, two common age-related conditions. The study setting was two large spine surgery centers in one region during 2017-19. Using data (International Classification of Diseases-10th edition and current procedural terminology codes) extracted from electronic health record systems, we characterized surgeon-level variations in practice (use of instrumented fusion - a more extensive procedure that involves device-related risks) and short-term postoperative outcomes (major in-hospital complications and readmissions). Next, we tested for associations between surgeon training (specialty and spine fellowship) and experience (career stage and operative volume) and use of instrumented fusion as well as outcomes. Eighty-nine surgeons performed 2481 eligible operations. For the study diagnoses, spine surgeons exhibited substantial variation in operative volume, use of instrumented fusion, and postoperative outcomes. Among surgeons above the median operative volume, use of instrumented fusion ranged from 0% to >90% for scoliosis and 9% to 100% for spondylolisthesis, while rates of major in-hospital complications ranged from 0% to 25% for scoliosis and from 0% to 14% for spondylolisthesis. For scoliosis, orthopedic surgeons were more likely than neurosurgeons to perform instrumented fusion for scoliosis [49% vs. 33%, odds ratio (OR) = 2.3, 95% confidence interval (95% CI) 1.3-4.2, P-value = .006] as were fellowship-trained surgeons (49% vs. 25%, OR = 3.0, 95% CI 1.6-5.8; P = .001). Fellowship-trained surgeons had lower readmission rates. Surgeons with higher operative volumes used instrumented fusion more often (OR = 1.1, 95% CI 1.0-1.2, P < .05 for both diagnoses) and had lower rates of major in-hospital complications (OR = 0.91, 95% CI 0.85-0.97; P = .006). Surgical practice can vary greatly for degenerative spine conditions, even within the same region and among colleagues at the same institution. Surgical specialty and subspecialty, in addition to recent operative volume, can be linked to variations in spine surgeons' practice patterns and outcomes. These findings reinforce the notion that residency and fellowship training may contribute to variation and present important opportunities to optimize surgical practice over the course of surgeons' careers. Future efforts to reduce unexplained variation in surgical practice could test interventions focused on graduate medical education. Graphical Abstract., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Quality in Health Care.)

This graphical review provides a mechanistic overview of different molecular processes that are tightly coupled and cooperate to achieve efficient and spatial-temporally regulated co-transcriptional protein-RNA complex assembly, including co-transcriptional RNA folding, processing, modification and the assembly in context of biomolecular condensates., (© 2023 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Cell-free protein synthesis assays have become a valuable tool to understand transcriptional and translational processes. Here, we established a fluorescence-based coupled in vitro transcription-translation assay as a read-out system to simultaneously quantify mRNA and protein levels. We utilized the well-established quantification of the expression of shifted green fluorescent protein (sGFP) as a read-out of protein levels. In addition, we determined mRNA quantities using a fluorogenic Mango-(IV) RNA aptamer that becomes fluorescent upon binding to the fluorophore thiazole orange (TO). We utilized a Mango-(IV) RNA aptamer system comprising four subsequent Mango-(IV) RNA aptamer elements with improved sensitivity by building Mango arrays. The design of this reporter assay resulted in a sensitive read-out with a high signal-to-noise ratio, allowing us to monitor transcription and translation time courses in cell-free assays with continuous monitoring of fluorescence changes as well as snapshots of the reaction. Furthermore, we applied this dual read-out assay to investigate the function of thiamine-sensing riboswitches thiM and thiC from Escherichia coli and the adenine-sensing riboswitch ASW from Vibrio vulnificus and pbuE from Bacillus subtilis, which represent transcriptional and translational on- and off-riboswitches, respectively. This approach enabled a microplate-based application, a valuable addition to the toolbox for high-throughput screening of riboswitch function., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The ongoing pandemic of the respiratory disease COVID-19 is caused by the SARS-CoV-2 (SCoV2) virus. SCoV2 is a member of the Betacoronavirus genus. The 30 kb positive sense, single stranded RNA genome of SCoV2 features 5'- and 3'-genomic ends that are highly conserved among Betacoronaviruses. These genomic ends contain structured cis-acting RNA elements, which are involved in the regulation of viral replication and translation. Structural information about these potential antiviral drug targets supports the development of novel classes of therapeutics against COVID-19. The highly conserved branched stem-loop 5 (SL5) found within the 5'-untranslated region (5'-UTR) consists of a basal stem and three stem-loops, namely SL5a, SL5b and SL5c. Both, SL5a and SL5b feature a 5'-UUUCGU-3' hexaloop that is also found among Alphacoronaviruses. Here, we report the extensive 1 H, 13 C and 15 N resonance assignment of the 37 nucleotides (nts) long sequence spanning SL5b and SL5c (SL5b + c), as basis for further in-depth structural studies by solution NMR spectroscopy., (© 2022. The Author(s).)

The SARS-CoV-2 virus is the cause of the respiratory disease COVID-19. As of today, therapeutic interventions in severe COVID-19 cases are still not available as no effective therapeutics have been developed so far. Despite the ongoing development of a number of effective vaccines, therapeutics to fight the disease once it has been contracted will still be required. Promising targets for the development of antiviral agents against SARS-CoV-2 can be found in the viral RNA genome. The 5'- and 3'-genomic ends of the 30 kb SCoV-2 genome are highly conserved among Betacoronaviruses and contain structured RNA elements involved in the translation and replication of the viral genome. The 40 nucleotides (nt) long highly conserved stem-loop 4 (5&#95;SL4) is located within the 5'-untranslated region (5'-UTR) important for viral replication. 5&#95;SL4 features an extended stem structure disrupted by several pyrimidine mismatches and is capped by a pentaloop. Here, we report extensive 1 H, 13 C, 15 N and 31 P resonance assignments of 5&#95;SL4 as the basis for in-depth structural and ligand screening studies by solution NMR spectroscopy., (© 2021. The Author(s).)

The stem-loop (SL1) is the 5'-terminal structural element within the single-stranded SARS-CoV-2 RNA genome. It is formed by nucleotides 7-33 and consists of two short helical segments interrupted by an asymmetric internal loop. This architecture is conserved among Betacoronaviruses. SL1 is present in genomic SARS-CoV-2 RNA as well as in all subgenomic mRNA species produced by the virus during replication, thus representing a ubiquitous cis-regulatory RNA with potential functions at all stages of the viral life cycle. We present here the 1 H, 13 C and 15 N chemical shift assignment of the 29 nucleotides-RNA construct 5&#95;SL1, which denotes the native 27mer SL1 stabilized by an additional terminal G-C base-pair., (© 2021. The Author(s).)

SARS-CoV-2 contains a positive single-stranded RNA genome of approximately 30 000 nucleotides. Within this genome, 15 RNA elements were identified as conserved between SARS-CoV and SARS-CoV-2. By nuclear magnetic resonance (NMR) spectroscopy, we previously determined that these elements fold independently, in line with data from in vivo and ex-vivo structural probing experiments. These elements contain non-base-paired regions that potentially harbor ligand-binding pockets. Here, we performed an NMR-based screening of a poised fragment library of 768 compounds for binding to these RNAs, employing three different 1 H-based 1D NMR binding assays. The screening identified common as well as RNA-element specific hits. The results allow selection of the most promising of the 15 RNA elements as putative drug targets. Based on the identified hits, we derive key functional units and groups in ligands for effective targeting of the RNA of SARS-CoV-2., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Translational riboswitches are cis-acting RNA regulators that modulate the expression of genes during translation initiation. Their mechanism is considered as an RNA-only gene-regulatory system inducing a ligand-dependent shift of the population of functional ON- and OFF-states. The interaction of riboswitches with the translation machinery remained unexplored. For the adenine-sensing riboswitch from Vibrio vulnificus we show that ligand binding alone is not sufficient for switching to a translational ON-state but the interaction of the riboswitch with the 30S ribosome is indispensable. Only the synergy of binding of adenine and of 30S ribosome, in particular protein rS1, induces complete opening of the translation initiation region. Our investigation thus unravels the intricate dynamic network involving RNA regulator, ligand inducer and ribosome protein modulator during translation initiation., (© 2021. The Author(s).)

The ribosomal S1 protein (rS1) is indispensable for translation initiation in Gram-negative bacteria. rS1 is a multidomain protein that acts as an RNA chaperone and ensures that mRNAs can bind the ribosome in a single-stranded conformation, which could be related to fast recognition. Although many ribosome structures were solved in recent years, a high-resolution structure of a two-domain mRNA-binding competent rS1 construct is not yet available. Here, we present the NMR solution structure of the minimal mRNA-binding fragment of Vibrio Vulnificus rS1 containing the domains D3 and D4. Both domains are homologues and adapt an oligonucleotide-binding fold (OB fold) motif. NMR titration experiments reveal that recognition of miscellaneous mRNAs occurs via a continuous interaction surface to one side of these structurally linked domains. Using a novel paramagnetic relaxation enhancement (PRE) approach and exploring different spin-labeling positions within RNA, we were able to track the location and determine the orientation of the RNA in the rS1-D34 bound form. Our investigations show that paramagnetically labeled RNAs, spiked into unmodified RNA, can be used as a molecular ruler to provide structural information on protein-RNA complexes. The dynamic interaction occurs on a defined binding groove spanning both domains with identical β2-β3-β5 interfaces. Evidently, the 3'-ends of the cis-acting RNAs are positioned in the direction of the N-terminus of the rS1 protein, thus towards the 30S binding site and adopt a conformation required for translation initiation., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium's collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com , we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form., Competing Interests: CH was employed by Signals GmbH & Co. KG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Altincekic, Korn, Qureshi, Dujardin, Ninot-Pedrosa, Abele, Abi Saad, Alfano, Almeida, Alshamleh, de Amorim, Anderson, Anobom, Anorma, Bains, Bax, Blackledge, Blechar, Böckmann, Brigandat, Bula, Bütikofer, Camacho-Zarco, Carlomagno, Caruso, Ceylan, Chaikuad, Chu, Cole, Crosby, de Jesus, Dhamotharan, Felli, Ferner, Fleischmann, Fogeron, Fourkiotis, Fuks, Fürtig, Gallo, Gande, Gerez, Ghosh, Gomes-Neto, Gorbatyuk, Guseva, Hacker, Häfner, Hao, Hargittay, Henzler-Wildman, Hoch, Hohmann, Hutchison, Jaudzems, Jović, Kaderli, Kalniņš, Kaņepe, Kirchdoerfer, Kirkpatrick, Knapp, Krishnathas, Kutz, zur Lage, Lambertz, Lang, Laurents, Lecoq, Linhard, Löhr, Malki, Bessa, Martin, Matzel, Maurin, McNutt, Mebus-Antunes, Meier, Meiser, Mompeán, Monaca, Montserret, Mariño Perez, Moser, Muhle-Goll, Neves-Martins, Ni, Norton-Baker, Pierattelli, Pontoriero, Pustovalova, Ohlenschläger, Orts, Da Poian, Pyper, Richter, Riek, Rienstra, Robertson, Pinheiro, Sabbatella, Salvi, Saxena, Schulte, Schiavina, Schwalbe, Silber, Almeida, Sprague-Piercy, Spyroulias, Sreeramulu, Tants, Tārs, Torres, Töws, Treviño, Trucks, Tsika, Varga, Wang, Weber, Weigand, Wiedemann, Wirmer-Bartoschek, Wirtz Martin, Zehnder, Hengesbach and Schlundt.)

The SARS-CoV-2 (SCoV-2) virus is the causative agent of the ongoing COVID-19 pandemic. It contains a positive sense single-stranded RNA genome and belongs to the genus of Betacoronaviruses. The 5'- and 3'-genomic ends of the 30 kb SCoV-2 genome are potential antiviral drug targets. Major parts of these sequences are highly conserved among Betacoronaviruses and contain cis-acting RNA elements that affect RNA translation and replication. The 31 nucleotide (nt) long highly conserved stem-loop 5a (SL5a) is located within the 5'-untranslated region (5'-UTR) important for viral replication. SL5a features a U-rich asymmetric bulge and is capped with a 5'-UUUCGU-3' hexaloop, which is also found in stem-loop 5b (SL5b). We herein report the extensive 1 H, 13 C and 15 N resonance assignment of SL5a as basis for in-depth structural studies by solution NMR spectroscopy.

The international Covid19-NMR consortium aims at the comprehensive spectroscopic characterization of SARS-CoV-2 RNA elements and proteins and will provide NMR chemical shift assignments of the molecular components of this virus. The SARS-CoV-2 genome encodes approximately 30 different proteins. Four of these proteins are involved in forming the viral envelope or in the packaging of the RNA genome and are therefore called structural proteins. The other proteins fulfill a variety of functions during the viral life cycle and comprise the so-called non-structural proteins (nsps). Here, we report the near-complete NMR resonance assignment for the backbone chemical shifts of the non-structural protein 10 (nsp10). Nsp10 is part of the viral replication-transcription complex (RTC). It aids in synthesizing and modifying the genomic and subgenomic RNAs. Via its interaction with nsp14, it ensures transcriptional fidelity of the RNA-dependent RNA polymerase, and through its stimulation of the methyltransferase activity of nsp16, it aids in synthesizing the RNA cap structures which protect the viral RNAs from being recognized by the innate immune system. Both of these functions can be potentially targeted by drugs. Our data will aid in performing additional NMR-based characterizations, and provide a basis for the identification of possible small molecule ligands interfering with nsp10 exerting its essential role in viral replication.

The current pandemic situation caused by the Betacoronavirus SARS-CoV-2 (SCoV2) highlights the need for coordinated research to combat COVID-19. A particularly important aspect is the development of medication. In addition to viral proteins, structured RNA elements represent a potent alternative as drug targets. The search for drugs that target RNA requires their high-resolution structural characterization. Using nuclear magnetic resonance (NMR) spectroscopy, a worldwide consortium of NMR researchers aims to characterize potential RNA drug targets of SCoV2. Here, we report the characterization of 15 conserved RNA elements located at the 5' end, the ribosomal frameshift segment and the 3'-untranslated region (3'-UTR) of the SCoV2 genome, their large-scale production and NMR-based secondary structure determination. The NMR data are corroborated with secondary structure probing by DMS footprinting experiments. The close agreement of NMR secondary structure determination of isolated RNA elements with DMS footprinting and NMR performed on larger RNA regions shows that the secondary structure elements fold independently. The NMR data reported here provide the basis for NMR investigations of RNA function, RNA interactions with viral and host proteins and screening campaigns to identify potential RNA binders for pharmaceutical intervention., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The SARS-CoV-2 genome encodes for approximately 30 proteins. Within the international project COVID19-NMR, we distribute the spectroscopic analysis of the viral proteins and RNA. Here, we report NMR chemical shift assignments for the protein Nsp3b, a domain of Nsp3. The 217-kDa large Nsp3 protein contains multiple structurally independent, yet functionally related domains including the viral papain-like protease and Nsp3b, a macrodomain (MD). In general, the MDs of SARS-CoV and MERS-CoV were suggested to play a key role in viral replication by modulating the immune response of the host. The MDs are structurally conserved. They most likely remove ADP-ribose, a common posttranslational modification, from protein side chains. This de-ADP ribosylating function has potentially evolved to protect the virus from the anti-viral ADP-ribosylation catalyzed by poly-ADP-ribose polymerases (PARPs), which in turn are triggered by pathogen-associated sensing of the host immune system. This renders the SARS-CoV-2 Nsp3b a highly relevant drug target in the viral replication process. We here report the near-complete NMR backbone resonance assignment ( 1 H, 13 C, 15 N) of the putative Nsp3b MD in its apo form and in complex with ADP-ribose. Furthermore, we derive the secondary structure of Nsp3b in solution. In addition, 15 N-relaxation data suggest an ordered, rigid core of the MD structure. These data will provide a basis for NMR investigations targeted at obtaining small-molecule inhibitors interfering with the catalytic activity of Nsp3b.

The ongoing pandemic caused by the Betacoronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) demonstrates the urgent need of coordinated and rapid research towards inhibitors of the COVID-19 lung disease. The covid19-nmr consortium seeks to support drug development by providing publicly accessible NMR data on the viral RNA elements and proteins. The SARS-CoV-2 genome encodes for approximately 30 proteins, among them are the 16 so-called non-structural proteins (Nsps) of the replication/transcription complex. The 217-kDa large Nsp3 spans one polypeptide chain, but comprises multiple independent, yet functionally related domains including the viral papain-like protease. The Nsp3e sub-moiety contains a putative nucleic acid-binding domain (NAB) with so far unknown function and consensus target sequences, which are conceived to be both viral and host RNAs and DNAs, as well as protein-protein interactions. Its NMR-suitable size renders it an attractive object to study, both for understanding the SARS-CoV-2 architecture and drugability besides the classical virus' proteases. We here report the near-complete NMR backbone chemical shifts of the putative Nsp3e NAB that reveal the secondary structure and compactness of the domain, and provide a basis for NMR-based investigations towards understanding and interfering with RNA- and small-molecule-binding by Nsp3e.

Through the Comprehensive Primary Care (CPC) and Comprehensive Primary Care Plus (CPC+) programs, the Centers for Medicare & Medicaid Services (CMS) has encouraged primary care practices to invest in "comprehensive primary care" capabilities. Empirical evidence suggests these capabilities are under-reimbursed or not reimbursed under prevailing fee-for-service payment models. To help CMS design alternative payment models (APMs) that reimburse the costs of these capabilities, the authors developed a method for estimating related practice expenses. Fifty practices, sampled for diversity across CPC+ participation status, geographic region, rural status, size, and parent-organization affiliation, completed the study. Researchers developed a mixed-methods strategy, beginning with interviews of practice leaders to identify their capabilities and the types of costs incurred. This was followed by researcher-assisted completion of a workbook tailored to each practice, which gathered related labor and nonlabor costs. In a final interview, practice leaders reviewed cost estimates and made any needed corrections before approval. A main goal was to address a persistent question faced by CMS: When practices reported widely divergent costs for a given capability, was that divergence due to practices having different prices for the same capability or from their having substantially different capabilities? The cost estimation method developed in this project collected detailed data on practice capabilities and their costs. However, the small sample did not allow quantitative estimation of the contributions of service level and pricing to the variation in overall costs. This cost estimation method, deployed on a larger scale, could generate robust data to inform new payment models aimed at incentivizing and sustaining comprehensive primary care., (Copyright © 2020 RAND Corporation.)

Despite widespread adoption of electronic health records and increasing exchange of health care data, the benefits of interoperability and health information technology have been hampered by the inability to reliably match patients and their records. The Pew Charitable Trusts contracted with the RAND Corporation to investigate "patient-empowered" approaches to record matching-solutions that have some additional, voluntary role for patients beyond simply supplying demographics to their health care providers-and to select a promising solution for further development and pilot testing. After extensive consultation with a variety of experts, researchers did not identify a "silver bullet" or achieve consensus on a single solution. Instead, this study recommends adopting a three-stage approach that aims to improve the quality of identity information, establish new smartphone app functionality to facilitate bidirectional exchange of identity information and health care data between patients and providers, and create advanced functionality to further improve value. The study also suggests that because the solution contains multiple components involving diverse stakeholders, a governance mechanism likely will be needed to provide leadership, track pilot tests, and evaluation, as well as to convene key stakeholders to build consensus where consensus is needed.

Background: The reduction and control over neonatal, infant, and maternal mortality is a collective mission of the World Health Organization under United Nations., Methods: This article summarizes the automation of verbal autopsy reporting for neonatal, infant, and maternal mortality with primary focus on user-centered design for technologically illiterate workforce with minimum available resources. The diminution in neonatal, infant, and maternal deaths is not possible until grassroot level quality data are available for mortality. The estimated data are less effective for developing countries like Pakistan because it has heterogeneous demographic pockets with respect to mortality causes. The Neonatal, Infant, and Maternal Death E-surveillance System is a project in which a real-time reporting system is innovated that is useful in detecting the causes of mortality and effective in adopting appropriate countermeasure policies. In a pilot study, the system was implemented initially in nine districts of Punjab, Pakistan. The initial system was refined after getting detailed feedback from district management staff including Lady Health Workers and Lady Health Supervisors. The refined surveillance system was finally implemented in all 36 districts of Punjab, Pakistan., Results: The results exhibited 31% improvement in infant data collection and 6% improvement in maternal data collection regarding mortality., Conclusion: This research will be helpful in achieving the milestone of gathering real-time mortality data from grassroot level using user-centered design methodology., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Initiation of bacterial translation requires that the ribosome-binding site in mRNAs adopts single-stranded conformations. In Gram-negative bacteria the ribosomal protein S1 (rS1) is a key player in resolving of structured elements in mRNAs. However, the exact mechanism of how rS1 unfolds persistent secondary structures in the translation initiation region (TIR) is still unknown. Here, we show by NMR spectroscopy that Vibrio vulnificus rS1 displays a unique architecture of its mRNA-binding domains, where domains D3 and D4 provide the mRNA-binding platform and cover the nucleotide binding length of the full-length rS1. D5 significantly increases rS1's chaperone activity, although it displays structural heterogeneity both in isolation and in presence of the other domains, albeit to varying degrees. The heterogeneity is induced by the switch between the two equilibrium conformations and is triggered by an order-to-order transition of two mutually exclusive secondary structures (β-strand-to-α-helix) of the 'AERERI' sequence. The conformational switching is exploited for melting of structured 5'-UTR's, as the conformational heterogeneity of D5 can compensate the entropic penalty of complex formation. Our data thus provides a detailed understanding of the intricate coupling of protein and RNA folding dynamics enabling translation initiation of structured mRNAs.

Objective: The aim of the study was twofold: 1. To assess the acceptance for HIV screening in women attending Colposcopy clinic 2. To determine the prevalence of HIV in women presenting with high-grade cervical smear abnormalities., Design: A prospective study., Setting: Colposcopy clinic, Birmingham Women's Hospital, UK., Population: Patients attending colposcopy clinic., Main Outcome Measures: To determine acceptance of HIV testing and prevalence in colposcopy patients with High-grade cervical smear abnormalities., Results: Of the 252 patients who were offered the HIV test, 244(96.5%) accepted the test. None of 244 cases tested for HIV were found positive., Conclusions: HIV testing is feasible and acceptable in colposcopy clinics., (Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.)

Paramagnetic relaxation enhancement (PRE) is a versatile tool for NMR spectroscopic structural and kinetic studies in biological macromolecules. Here, we compare the quality of PRE data derived from two spin labels with markedly different dynamic properties for large RNAs using the I-A riboswitch aptamer domain (78 nt) from Mesoplamsa florum as model system. We designed two I-A aptamer constructs that were spin-labeled by noncovalent hybridization of short spin-labeled oligomer fragments. As an example of a flexible spin label, Ureido U-TEMPO was incorporated into the 3' terminal end of helix P1 while, the recently developed rigid spin-label Çm was incorporated in the 5' terminal end of helix P1. We determined PRE rates obtained from aromatic 13 C bound proton intensities and compared these rates to PREs derived from imino proton intensities in this sizeable RNA (~78 nt). PRE restraints derived from both imino and aromatic protons yielded similar data quality, and hence can both be reliably used for PRE determination. For NMR, the data quality derived from the rigid spin label Çm is slightly better than the data quality for the flexible Ureido TEMPO as judged by comparison of the structural agreement with the I-A aptamer crystal structure (3SKI).

Certification in Colposcopy by the British Society for Colposcopy and Cervical Pathology (BSCCP) and the Royal College of Obstetricians and Gynaecologists is a formal pre- requisite to the practice of colposcopy within the UK. This certification is awarded after passing an Objective Structured Clinical Examination (OSCE). The aim of the project is to explore examiners' perceptions of the OSCE examination in colposcopy and consider whether it is the right tool to differentiate between safe and unsafe practice in colposcopy. A case study research methodology was employed for the project, and questionnaires were sent to 30 examiners for OSCE in Colposcopy. The project also included conducting semi-structured interviews with two examiners, two trainees and a senior manager of the BSCCP. The questionnaire had a response rate of 28 (94%). The satisfaction rate among the examiners about the standard of questions in OSCE in Colposcopy was 93%, and 89% of the examiners would allow a candidate passing the examination to carry out a clinic in their absence. A total of 26 (94%) examiners thought that the examination was fit for purpose. It was suggested that testing of practical skills should also be made part of the examination. It seems OSCE in Colposcopy is perceived well both by the examiners and the candidates.

Threatened miscarriage, as demonstrated by vaginal bleeding with or without abdominal cramps, is a common complication of pregnancy. It occurs in about 20% of recognised pregnancies. Risk of miscarriage is increased in older women and those with a history of miscarriage. Low serum levels of progesterone or human chorionic gonadotrophin (hCG) are a risk factor for miscarriage. Other risk factors include heavy bleeding, early gestational age and an empty gestational sac of >15-17 mm diameter. Clinical history and examination, maternal serum biochemistry and ultrasound findings provide valuable information about the prognosis and are important to establish in order to determine potential treatment options. Although bed rest is the most common choice of treatment, there is little evidence of its value. Other options include luteal support with progesterone, dydrogesterone or hCG. There is some evidence from clinical studies indicating that progesterone or dydrogesterone may reduce the rate of miscarriage, although further data from double-blind, randomised-controlled trials are necessary to confirm efficacy., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Ward rounds have been regarded as a traditional forum for the teaching and training of trainees. The aim of this research project was to look at what role ward rounds play in the medical education of trainees in obstetrics and gynaecology. A questionnaire comprising 10 statements devised around the theme of quality of medical education and the overall experience of ward rounds was distributed at the Specialist Registrars monthly training days. A total of 46 completed questionnaires were received. The ward rounds took place at least twice weekly at the Welsh Deanery hospitals, however, none of the trainees regarded these ward rounds as 'teaching' ward rounds. A total of 32 (70%) of the trainees disagreed or were uncertain that they learnt something new on ward rounds each day and 34 (74%) of trainees agreed or strongly agreed that in the presence of a consultant, SpRs are not given a chance to lead a ward round. The educational role of the ward rounds does not seem fully utilised in the Welsh Deanery Hospitals and needs to be developed further to suit the needs of junior doctors.

Objective: To determine whether administration of exogenous human chorionic gonadotrophin (hCG) treatment improve the pregnancy outcome in first trimester threatened miscarriages., Design: A prospective, double blind, randomised, placebo-controlled trial., Setting: The Early Pregnancy Assessment Unit, Royal Bolton Hospital, Bolton, United Kingdom., Population: One hundred and eighty-three women with vaginal bleeding and a viable fetus seen on ultrasound scan (USS) in the first 12 weeks of pregnancy., Methods: The patients were randomised to receive either hCG or placebo treatment until 14 weeks of gestation., Main Outcome Measures: The primary objective of the trial was to determine the miscarriage rate in the hCG arm compared from the placebo arm., Results: Of the 183 cases, 87 were randomised to treatment with hCG while 96 were randomised to receive a placebo. Forty-seven (25%) did not comply with the study protocol. The mean [SD] gestational age at presentation was 7 [1.33] weeks. The mean [SD] age of women in study was 27 [5] years in the placebo and 28 [5] in the hCG group. The mean body mass index (kg/m(2)) was 25 [5] in the study. The number of patients actively bleeding per vaginum at presentation was 85 (93%) in placebo group and 79 (96%) in the hCG group. The median number of hCG or placebo injections for both groups was 7. Ten women (11%) in the placebo group proceeded to have a complete miscarriage, as did 10 women (12%) in the hCG group, relative risk (RR) [95% confidence interval (CI)] of 1.1 (0.63-1.6)., Conclusion: Our study showed no evidence of a difference in the outcome of threatened miscarriages when treated with hCG in the first trimester, this may be because our study sample size was small and follow up was suboptimal. A large, randomised, multicentre trial is still needed to establish the usefulness of hCG treatment in cases of threatened miscarriage.

Background: Early preterm onset of elevated liver enzymes/low platelet count (ELLP) syndrome poses a significant management problem., Case: Antepartum methylprednisolone, 40 mg/d intravenously was employed to stabilize ELLP syndrome, to achieve fetal lung maturity and to postpone delivery at 25 weeks and 5 days' gestation. Normalization of the liver transaminases and platelet count occurred with the use of corticosteroids, but sudden fetal death occurred at 28 weeks and 2 days' gestation., Conclusion: Prenatal corticosteroids may improve the biochemical and hematologic parameters of ELLP syndrome but may result in intrauterine death.

Transport in vitro fertilisation (IVF) is an important development in assisted conception. We report our experience of transport IVF treatment from May 1993 to April 1996 at Arrowe Park Fertility Centre. A total of 74 patients were treated during this period. The main indications of treatment were tubal damage, unexplained infertility of more than 3 years duration, polycystic ovarian disease and endometriosis. Total number of simulated ovarian cycles were 101. Thirteen cycles were abandoned. Eighty-eight transport IVF cycles led to 29 pregnancies, giving a live birth rate and on-going pregnancy rate per patient of 31% and per cycle rate of 23%. There was one case of severe ovarian hyperstimulation syndrome. Of the 74 patients, 70 (95%) patients preferred to have treatment at the local hospital. Transport IVF is an effective, efficient and economic way of providing assisted conception at district general hospital. The success rate and safety of transport IVF are comparable with conventional IVF treatment.