Search

Abstract Background Racism contributes to health disparities and is a serious threat to public health. Teaching physicians about racism, how to address it in medical practice, and developing high quality and sustainable curricula are essential to combating racism. Objective This study aimed to (1) describe the experience of racism and anti-racism teaching in residency programs, and elicit recommendations from key informants, and (2) use these data and formative research to develop recommendations for other residencies creating, implementing, and evaluating anti-racism curricula in their own programs. Methods From May to July 2023, 20 faculty and residents were recruited via convenience sampling for key informant interviews conducted via Microsoft Teams. Interviews were audio recorded, transcribed, and coded. An initial list of themes was developed using theoretical frameworks, and then refined using a grounded-theory approach. A brief online optional anonymous demographic survey was sent to participants in August of 2023. Results Eighty percent (20/25) of participants approached were interviewed. Seventy-five percent (15/20) answered a brief optional demographic survey. Seven themes emerged: (1) Racism in medicine is ubiquitous; (2) Anti-racism teaching in medicine varies widely; (3) Sustainability strategies should be multifaceted and include recruitment, resource allocation, and outcome measures; (4) Resources are widely available and accessible if one knows where to look; (5) Outcomes and metrics of success should include resident- faculty-, patient- community-, and system-focused outcomes; (6) Curricular strategies should be multilayered, longitudinal, and woven into the curriculum; and (7) Self-reflection and discomfort are necessary parts of the process. Conclusions This study is one of the first to qualitatively examine perspectives of key stakeholders invested in anti-racism teaching for residents. The Support - Pipeline - Outcomes - Community (SPOC) Model, that was developed using information collected during this study, can be used in the future as a guide for others working to design and implement sustainable and high quality anti-racism curricula for residents.

BackgroundCardiac magnetic resonance is a useful clinical tool to identify late gadolinium enhancement in heart failure patients with implantable electronic devices. Identification of LGE in patients with CIED is limited by artifact, which can be improved with a wide band radiofrequency pulse sequence.ObjectiveThe authors hypothesize that image quality of LGE images produced using wide-band pulse sequence in patients with devices is comparable to image quality produced using standard LGE sequences in patients without devices.MethodsTwo independent readers reviewed LGE images of 16 patients with CIED and 7 patients without intracardiac devices to assess for image quality, device-related artifact, and presence of LGE using the American Society of Echocardiography/American Heart Association 17 segment model of the heart on a 4-point Likert scale. The mean and standard deviation for image quality and artifact rating were determined. Inter-observer reliability was determined by calculating Cohen's kappa coefficient. Statistical significance was determined by T-test as a p {less than or equal to} 0.05 with a 95% confidence interval.ResultsAll patients underwent CMR without any adverse events. Overall IQ of WB LGE images was significantly better in patients with devices compared to standard LGE in patients without devices (p = 0.001) with reduction in overall artifact rating (p = 0.05).ConclusionOur study suggests wide-band pulse sequence for LGE can be applied safely to heart failure patients with devices in detection of LV myocardial scar while maintaining image quality, reducing artifact, and following routine imaging protocol after intravenous gadolinium contrast administration.

Abstract. Objectives:. The objective of this study was to describe the relationship between positive toxicology screens and measures of preinjury mental health and physical function in an orthopaedic trauma population Design:. This was a cross-sectional study. Setting:. Urban Level 1 trauma center. Patients:. A total of 125 trauma patients gave written consent for this study. Main Outcome Measurements:. Questionnaires such as, Patient Health Questionnaire-9, General Anxiety Disorder-7, PCL-5, and Short Musculoskeletal Function Assessment, were used to survey patients after surgical intervention. Results:. Patient Health Questionnaire-9 (P = 0.05) and PCL-5 (P = 0.04) were not found to have significant differences between positive and negative toxicology screens. Both General Anxiety Disorder-7 (P = 0.004) and Short Musculoskeletal Function Assessment function (P = 0.006) were significantly higher in patients with positive toxicology screens. Conclusions:. Positive toxicology seems to be associated with preinjury anxiety. Patient reported preinjury function was not adversely affected by the presence of illicit substances or alcohol, nor were levels of post-traumatic stress disorder and depression found to be higher in patients with positive toxicology screens. Level of Evidence:. Level IV Cross-Sectional Study.

Abstract Background Over the last decade, the provision of online gambling has intensified with increased access, enhanced betting markets, a broader product range, and prolific marketing. However, little research has explored how this intensification is influencing contemporary gambling experiences. This study focused on two research questions: 1) What changes in online gambling have online gamblers observed over the past decade? 2) How have these changes influenced the online gambling experiences and behaviours reported by treatment-seeking and non-treatment-seeking gamblers? Methods Two samples of Australian adults were interviewed: 1) 19 people who had been gambling online for at least a decade and with no history of treatment-seeking for online gambling, and 2) 10 people who had recently sought professional help for an online gambling problem. Telephone interviews were semi-structured, with questions that encouraged participants to consider how their online gambling, including any harmful gambling, had been influenced by changes in operator practices and online gambling environments. Data were analysed using thematic analysis. Results Both treatment- and non-treatment-seekers noted the increased speed and ease of online gambling, which now enables instant access from anywhere at any time and increased their gambling opportunities. Both groups highlighted the continued proliferation of advertising and inducements for online gambling, particularly during televised sports and racing events, in social media, and through targeted push marketing. Many treatment- and non-treatment-seekers were aware of the vast range of recently introduced bet types, particularly multi-bets. Treatment-seekers disproportionately reported negative effects from these changes, and described how and why they fostered their increased gambling, impulsive gambling, persistence and loss-chasing. They reported limited uptake and effectiveness of current harm minimisation tools. Conclusions Counter to stated policy and practice objectives to minimise gambling harm, industry changes that have made online gambling easier, faster, and more heavily incentivised, and increased the array of complex bets with poorer odds, unduly affect addicted and harmed individuals – who are also the most profitable customers. Further consideration is needed to ensure gambling policy, industry practices and public health measures more effectively reduce gambling harm in contemporary settings. Inducements and the poor pricing of complex bets such as multi-bets, and their outsized attraction to players with problems, should be a key focus.

The development of the metropolis and the birth of photography are contemporary phenomena, but their relationship is not unidirectional; photography has not only represented the city, it has also suggested its best form and conditioned its ideology. In the dialectical opposition between decay and decorum, a powerful instrument of urban-social despotism, the photographers of the city have sometimes sided with the powers in place disciplining spaces and at other times with the critics of urbanism and its failures: but is a clear opposition between the two attitudes really possible? To what extent can showing the decay can incite the restoration of decorum, and how? Has the visual denouncement of urban social marginalization contributed to urge interventions of repression rather than rebalancing this situation? By quickly retracing the history of urban photography from the 19th century to the present day, this text tries to identify its ambiguities and highlight some attempts at apprehending an image of the urban environment that includes a redemption in terms of inclusion, justice, and citizenship.

Rheumatoid arthritis (RA) is an autoimmune disease marked by chronic synovial inflammation and both, genetic and environmental factors are involved in its pathogenesis. Human leukocyte antigen (HLA) DRB1*0401 is associated with susceptibility to develop RA, while cigarette smoke (CS) exposure promotes seropositive disease with increased severity in DRB1*0401+ individuals. Smokers have higher levels of antibodies against citrullinated peptides. In this study, we determined whether the response to a known autoantigen, Vimentin (Vim) is shared epitope specific and how CS influences this response using transgenic-mice carrying RA-susceptible,*0401, and -resistant, *0402, genes. Following relatively brief exposure to CS, peptidyl arginine deiminase (PAD) enzyme expression was increased in murine lungs. Cigarette smoking led to production of Interferon (IFN)-γ with reduced levels of Interleukin (IL)-10 by splenocytes of *0401 mice. In contrast, CS augmented Th2 cytokines along with T-regulatory cells in *0402 mice. An increase in levels of antibodies to native and citrullinated Vim was observed in naïve mice of both strains following CS exposure. Our data showed that both arthritis-susceptible and -resistant mice can generate cellular and humoral immunity to Vim; however CS-induced modulation of host immunity is dependent on the interaction with the host HLA genes.

As the life expectancy of the population continues to increase, more facial-rejuvenating procedures are sought. As the number of facelift procedures increases, it is mandatory to acknowledge, and most importantly prevent, any possible associated complications. One of the complications after rhytidectomy, and a sign of facelift, is the so-called "pixie ear deformity" or "bat ear." This is regarded as a telltale sign of a facelift procedure and appears to be identified in 5% of earlobe inset cases. The ear's location is a crucial hallmark of an aesthetically pleasing face, not only by itself but also in relation with other aesthetic units. When performing a facelift procedure, tension vectors of the rhytidectomy flap could cause alterations in ear's position and appearance: the ear loses its great mobility and becomes more fixed in its acquired position, resulting in a "stuck-on" appearance. The auricle is displaced following an anteroinferior direction, with the otobasion inferius (the most caudal anterior attachment of the earlobe to the cheek) being dislocated from its original more posterior and upper position to a new more anterior and caudal location. The displacement of the auricle is usually accompanied by distortion of the earlobe rotating forward and becoming more anterior than the rest of the ear. In recent decades, many techniques and procedures have been described to prevent and correct the pixie ear; in this review, we aim to analyze and describe them comprehensively., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ultrasound (US) has become a useful, bedside, noninvasive imaging technique in diagnosing pulmonary diseases, particularly in Neonatology, due to its non-invasive nature, lack of ionizing radiation, and high-quality imaging. This study explores current methodologies, applications, and benefits of thoracic US in neonatal care, highlighting its application in assessing pleural morphology, pulmonary consolidations, and diaphragmatic function. Key ultrasound findings, such as A-lines, B-lines, and the pleural sliding sign, are instrumental in diagnosing various lung conditions, including pneumothorax and respiratory distress syndrome. The present review emphasizes the growing importance of lung ultrasound (LUS) in predicting neonatal intensive care needs, reducing reliance on X-rays, and improving the early diagnosis of conditions like transient tachypnea of the newborn. The use of ultrasound scoring systems enhances diagnostic accuracy, making thoracic ultrasound a valuable addition to neonatal care protocols for real-time, radiation-free assessment from birth., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Carnazzo et al.)

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis, wherefore targeted therapies have experienced increasing interest. Zolbetuximab is a novel targeted therapy under investigation in patients with PDAC and targets Claudin 18.2 (CLDN18.2), which is a component of tight junctions and is of significance in various solid tumors. As its role in PDAC is not definitively elucidated, this study aims to clarify the significance of CLDN18.2 expression in PDAC in a real-world setting., Methods: All patients (n = 309) were recruited at one of the PANCALYZE study centers and received pancreatic resection with curative intention. Paraffin samples were analyzed using an antibody against CLDN18.2, which is known to be comparable to the antibody used by the SPOTLIGHT and GLOW studies., Results: 94 PDACs are positive for CLDN18.2 (30.4 %). Positive CLDN 18.2 expression was associated with significantly better cancer differentiation (p < 0.001). Patients with positive CLDN18.2 expression showed significantly better overall survival when compared to patients with negative expression (median OS: 30 versus 18 months, p = 0.003). Additionally, in multivariable analyses, CLDN18.2 expression was identified as an independent factor for better survival in patients with PDAC (HR = 0.686, 95 %CI = 0.492-0.956, p = 0.026)., Conclusion: Significant improvement in survival could be demonstrated by adding Zolbetuximab to known chemotherapy regimes in patients with gastro-esophageal junction adenocarcinoma with at least 75 % CLDN18.2 positive cancer cells. Our findings demonstrate, that 30.4 % of the included patients with PDAC would potentially be eligible for therapy with Zolbetuximab in a real-world patient cohort. Results of trials targeting Claudin 18.2 are pending in patients with PDAC., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background and Aim: Helicobacter pylori represents the major pathogen in the pathophysiology of diverse gastrointestinal conditions. This study sought to determine the endoscopic aspect of the gastric mucosa in relation to H. pylori infection in Cameroon., Methods: This study was conducted in three reference health facilities in Cameroon from October 2020 to October 2022. The study enrolled 494 consecutive volunteer dyspeptic patients attending to the gastroenterology department of the selected health facilities. A description of the aspect of gastric mucosa of all participants was performed during endoscopy examination, and biopsies were collected for H. pylori detection using rapid urease tests., Results: Gastritis, ulcerated lesions, duodenitis, esophagitis, normal mucosa aspect, bulbitis, and gastric neoplastic lesions were found in 40.1, 22.3, 10.9, 10.3, 9.7, 6.3, and 0.40% of biopsy samples, respectively. Erythematous/exudative (45.9%) and enterogastric reflux (12.2%) were the main gastritis types recorded. H. pylori was present in 58.1, 46.3, 87.1, 66.7, and 61.8% in gastritis, duodenitis, bulbitis, esophagitis, and ulcerated lesions, respectively. A positive relationship was noticed between the presence of H. pylori and gastritis (1.037 [0.720-1.493]; P  = 0.845), bulbitis (4.237 [1.602-11.235]; P  = 0.004), esophagitis (1.515 [0.822-2.793]; P  = 0.183), ulcerated lesions (1.233 [0.798-1.904]; P  = 0.345), erythematous/exudative gastritis (1.354 [0.768-2.389]; P  = 0.295), and enterogastric reflux gastritis (1.159 [0.492-2.733]; P  = 0.736)., Conclusion: Gastritis and erythematous/exudative gastritis are the most frequent gastrointestinal pathophysiology conditions in dyspeptic patient in our milieu. H. pylori infection is responsible for 94.8% of the gastrointestinal pathophysiology conditions with bulbitis as the condition is significantly associated with this bacterium infection., (© 2024 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) is a novel human coronavirus that was identified in 2019. SARS-CoV-2 infection results in an acute, severe respiratory disease called coronavirus disease 2019 (COVID-19). The emergence and rapid spread of SARS-CoV-2 has led to a global public health crisis, which continues to affect populations across the globe. Real time reverse transcription polymerase chain reaction (rRT-PCR) is the reference standard test for COVID-19 diagnosis. Serological tests are valuable tools for serosurveillance programs and establishing correlates of protection from disease. This study evaluated the performance of one in-house enzyme linked immunosorbent assay (ELISA) utilizing the pre-fusion stabilized ectodomain of SARS-CoV-2 spike (S), two commercially available chemiluminescence assays Ortho VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack and Abbott SARS-CoV-2 IgG assay and one commercially available Surrogate Virus Neutralization Test (sVNT), GenScript USA Inc., cPass SARS-CoV-2 Neutralization Antibody Detection Kit for the detection of SARS-CoV-2 specific antibodies. Using a panel of rRT-PCR confirmed COVID-19 patients' sera and a negative control group as a reference standard, all three immunoassays demonstrated high comparable positivity rates and low discordant rates. All three immunoassays were highly sensitive with estimated sensitivities ranging from 95.4-96.6 %. ROC curve analysis indicated that all three immunoassays had high diagnostic accuracies with area under the curve (AUC) values ranging from 0.9698 to 0.9807. High positive correlation was demonstrated among the conventional microneutralization test (MNT) titers and the sVNT inhibition percent values. Our study indicates that independent evaluations are necessary to optimize the overall utility and the interpretation of the results of serological tests. Overall, we demonstrate that all serological tests evaluated in this study are suitable for the detection of SARS-CoV-2 antibodies., Competing Interests: ‘The author(s) declare that there are no conflicts of interest’. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Names of specific vendors, manufacturers, or products are included for public health and informational purposes; inclusion does not imply endorsement of the vendors, manufacturers, or products by the Centers for Disease Control and Prevention or the US Department of Health and Human Services.

Background and Aim: There is an intimate relationship between oxidative stress and inflammation. Helicobacter pylori (H. pylori) infection leads to gastritis in almost all the hosts. So, we hypothesize that gastritis in H. pylori infection may be described as the accumulation of continuous oxidative damage., Methods: The study was conducted from October 2020 to October 2021 at three reference health facilities in Cameroon . A total of 266 participants (131 males and 135 females) ranging from 15 to 88 years old with 48.28 ± 17.29 years as mean age were enrolled. Each participant gave a written informed consent and ethical committees approved the protocol. Biopsies samples were collected for H. pylori detection using histological examination and rapid urease test. Malondialdehyde (MDA) and glutathione (GSH) content, and catalase (CAT) and superoxide dismutase (SOD) activities were evaluated in serum as biomarkers of oxidative stress., Results: Helicobacter pylori was detected in 71.80% of our sample population. Low income level was associated with higher GSH level ( P  = 0.0249) and having family history of gastric cancer to higher SOD activity ( P  = 0.0156). A significant higher MDA content ( P  < 0.0001) and SOD activity ( P  = 0.0235) was recorded among infected individuals compared with noninfected ones. A significantly higher MDA content and SOD activity was recorded among smokers ( P  = 0.0461) and participants older than 50 years old ( P  = 0.0491) with H. pylori positivity., Conclusion: Our findings showed that H. pylori infection is associated with overproduction of reactive oxygen species and oxidative stress. The presence of this pathogen in elderly individuals or in smokers increased their risk for oxidative stress., (© 2023 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Human immunodeficiency virus (HIV) self-testing has emerged as a tool to increase the proportion of people to know their status. Since the first HIV self-test was approved in 2012 by the US Food and Drug Administration (FDA), global access to HIV self-tests has been bolstered by public-private partnerships to ensure equitable access in low- and middle-income countries. However, no company has applied for FDA clearance in a decade. We highlight the potential benefits to reclassifying HIV self-tests from class III to class II., Competing Interests: Potential conflicts of interest. S. M. O. reports the following patent: Detection of HIV-1 nucleic acids by reverse-transcription loop-mediated isothermal amplification (patent no. 10697028; 30 June 2020); currently no money has been received for this patent, but it could be considered a diagnostic method. Y. C. M. reports consulting fees paid to the author from Abbott; a leadership or fiduciary role on the Infectious Diseases Institute board; and research grant support to Johns Hopkins University from Hologic, Cepheid, Roche, ChemBio, Becton Dickinson, and miDiagnostics. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The network structure of non-centrally cleared derivative markets, uncovered via the European Market Infrastructure Regulation, is investigated by reconstructing initial and variation margin networks to analyze channels of potential losses and liquidity dynamics. Despite the absence of central clearing, the derivative network is found to be ultra-small and a maximization-based filtering tool is proposed to identify channels in the network characterized by the highest exposures. I find these exposures to be mainly toward institutions outside the euro area, emphasizing the need for cooperation across different jurisdictions. Anomalous behavior in terms of diverging first and second moments of the degree and strength distributions are detected, signaling the presence of large exposures generating extreme liquidity outflows. A reference table of parameters' estimates based on real data is provided for different network sizes, with no break of confidentiality, making it possible to simulate in a realistic way the liquidity dynamic in global derivative markets even when access to supervisory data is not granted., Competing Interests: Conflict of interestThe author declares he has no conflict of interest., (© The Author(s) 2023.)

Introduction: This article analyzes experiences of antibiotic use and bacterial infections among Primary Health Care users of the Brazilian Unified Health System (SUS) and the possible implications for antimicrobial resistance (AMR). The aim is to map aspects that shape users' lay knowledge regarding antibiotics use and AMR., Methods: This is an exploratory study, which consists primarily of individual in-depth interviews with 19 respondents. Recurrent interview topics were coded and analysed according to thematic content analysis., Results: Our findings show users' lived experiences constitute three dimensions related to users' previous antibiotic use: (1) lay knowledge about medicines; (2) previous bacterial infections and (3) communication during the consultation. Lay knowledge encompasses the users' understanding of how antibiotics work in comparison to other drugs and experimentations they make with medication. Users' narratives about bacterial infections are divided into situations of urinary tract infections and antibiotic treatments for other conditions. Communication during the consultation is mainly characterized by a lack of shared knowledge and trust in the doctor-patient relationship., Discussion: Users bring together knowledge learned from their own experiences to create the rationale, which shapes how they understand antibiotic use, bacterial infections and medical advice. These experiences are interwoven with information received from healthcare professionals (HPs) on these topics, creating a scenario that goes beyond professional information about antibiotic use. Users have knowledge about medication, antibiotics use and bacterial infection but do not have room to share it with HP, allowing lived experiences to take precedence over professional information., Conclusion: Users ascribe symbolic meanings to antibiotics creating a lay knowledge frame, even if this knowledge is not scientifically correct. The personal experiences of bacterial infections and their treatment are also an important source of knowledge about antibiotic use and AMR among users. Users demand from their HPs both trust and willingness to listen to their health narratives and experiences. By considering lay knowledge as part of the assessment of a user's health condition, rather than dismissing it as erroneous and therefore unworthy of attention, HPs may enhance the compliance of users., Patient or Public Contribution: Patients or community members did not participate in the design stage of the study. Primary Care patients were invited to participate as respondents of in-depth interviews, which were carried out by the first author at a Primary Care Unit (PCU) in the suburb of Campo Limpo, Southern region of São Paulo, Brazil. Patients were interviewed after reading and signing a Free and Informed Consent Form, holding with them a copy of the Form. Among the final activities of the project, a feedback session at the same PCU is planned to report on the results of the study. All respondents will have the opportunity to contribute further information regarding their antibiotic use and exchange knowledge and experiences on antimicrobial resistance., (© 2022 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Antimicrobial resistance (AMR) is an increasing threat to global health. The risks and sanitary consequences of AMR are disproportionately experienced by those living in Low- and Middle-Income Countries (LMICs). While addressing antibiotic use has largely been documented in hospital settings, the understanding of social drivers affecting antibiotic prescribing and dispensing practices in the context of human and animal health in primary care (PC) in LMICs remains extremely limited. We seek to explore how in-locus and multi-level social factors influence antibiotic prescriptions and dispensing practices in the context of human and animal health in primary care in Brazil. This is a baseline qualitative One Health study; semi-structured interviews and field observations were undertaken in primary care sites located in a socioeconomically vulnerable area in the city of São Paulo, the most populated city of Brazil. Twenty-five human and animal healthcare professionals (HP) were purposely sampled. Interview data were subject to thematic analysis. Three overlapping social drivers were identified across HPs' discourses: individual and behavioral challenges; relational and contextual factors influencing the overprescription of antibiotics (AB); and structural barriers and systemic contradictions in the health system. As a result of the interaction between multilevel in-locus and structural and contextual factors, HPs experience contextual and territorial challenges that directly influence their risk perception, diagnosis, use of laboratorial and image exams, time and decision to undergo treatment, choice of AB and strategies in coping with AB prescriptions. Additionally, in-locus factors influencing antibiotic prescriptions and dispensing practices are intertwined with individual accounts of risk management, systemic contradictions and ambivalences in the national health system. Our findings suggest interventions tackling AB use and AMR in Brazil should consider the social context, the complex health system structure and current integrated programs and services in PC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 da Silva-Brandao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This article explores stakeholders' perceptions of the challenges for developing a One Health agenda to tackle antimicrobial resistance (AMR) in Brazil, including the development and implementation of the Brazilian National Action Plan (BR-NAP). The data originate from 27 interviews conducted with human, environmental, and animal health stakeholders, including academics, managers, and policymakers involved in developing the BR-NAP. Through thematic analysis, we identified three interconnected themes: governance, the health system, and technical and scientific challenges. The findings draw particular attention to failures in the agenda-setting process, revealed by interviewees strongly emphasising that AMR is not considered a policy priority in Brazil. The lack of political will and awareness of the clinical, social, and economic impacts of AMR are considered the main impediments to the agenda's progress. The joint work across disciplines and ministries must be reinforced through policymaker engagement and better environmental sector integration. The agenda must include sustainable governance structures less affected by political winds. Policies should be designed jointly with state and local governments to create strategies to engage communities and improve their translation into effective implementation.

Background: A doctor may recommend that a patient stop an antibiotic course before its scheduled completion time if further treatment may cause more harm than benefit., Objectives: This study explores general practitioners' (GP) opinions about the use of antibiotic deprescribing (AD) in general practice., Methods: A cross-sectional, questionnaire-based study answered from February to March 2022. GPs ( n  = 6,083) affiliated with the largest Spanish scientific society of primary care were invited to participate. The survey included two statements related to use and fourteen views about AD rated by GPs using a 5-item Likert scale., Results: Eleven hundred and seven doctors completed the surveys (18.2%), of whom 92.5% (95% confidence interval [CI] 90.8-94%) reported having used the AD strategy in their practice at least once. GPs felt very confident in using a deprescribing strategy in patients with common cold and influenza (97.6% and 93.5%, respectively) but less with acute bronchitis (45.5%); 12.1% (95% CI, 10.2-14.2%) considered this practice harmful to patients. Respondents reported using AD more frequently when they initiated the antibiotic course (96.8%; 95% CI, 95.5-97.7) than when the treatment was initiated by another doctor (52.3%; 95% CI, 49.3-55.3%). However, doctors aged >60 years were more prone to use AD compared with younger colleagues (64.5% vs. 50%; p  < 0.005)., Conclusion: The GPs in this study employ the strategy of AD. Nonetheless, essential differences lie in their views of the way the strategy is used. Further studies are warranted to explore the beliefs behind these perceptions and promote wider use of AD by GPs.

Background: Liver transplantation is a complex and valuable therapy. However, complications that burden postoperative quality of life, such as incisional hernia, are to be better elucidated, such as risk factors and prophylactic measures., Aim: This study aimed to define the rate of incisional hernia in patients who underwent liver transplantation in a population in southern Brazil and to assess the related risk factors in order to establish measures for prior optimization and specific prophylactic care in the future., Methods: Patients undergoing adult Liver transplantation from January 2004 to November 2020 were retrospectively analyzed, assessing demographic features, surgical outcomes, and predisposing factors., Results: Among 261 liver transplantation patients included, incisional hernia was diagnosed in 71 (27.2%). Of the 71 incisional hernia patients, 28 (39.4%) developed IH during the first post-transplant. Majority of the patients were male (52/71, 73.2%); of the 71 patients, 52 had hepatitis C virus (HCV) and 33 (46.5%) had hepatocellular carcinoma (HCC). Male gender (p=0.044), diabetes mellitus (p=0.008), and acute cellular rejection (p<0.001) were risk factors for IH. In all, 28 (39.4%) patients were submitted for hernia repair with mesh, with a recurrence rate of 17.8%., Conclusion: Incisional hernia after liver transplantation is a relatively common problem associated with male gender, diabetes, and acute cellular rejection. This is a problem that should not be trivialized in view of the complexity of liver transplantation, as it can lead to a reduction in quality of life as well as jeopardize late liver transplantation results and lead to incarceration and strangulation.

Serosurveillance can provide estimates of population-level exposure to infectious pathogens and has been used extensively during the COVID-19 pandemic. Simultaneous, serological testing for multiple pathogens can be done using bead-based immunoassays to add value to disease-specific serosurveys. We conducted a validation of four SARS-CoV-2 antigens-full-length spike protein, two receptor binding domain proteins, and the nucleocapsid protein-on our existing multiplex bead assay (MBA) for enteric diseases, malaria, and vaccine preventable diseases. After determining the optimal conditions for coupling the antigens to microsphere beads, the sensitivity and specificity of the assay were determined on two instruments (Luminex-200 and MAGPIX) when testing singly (monoplex) versus combined (multiplex). Sensitivity was assessed using plasma from 87 real-time reverse transcription polymerase chain reaction (rRT-PCR) positive persons collected in March-May of 2020 and ranged from 94.3% to 96.6% for the different testing conditions. Specificity was assessed using 98 plasma specimens collected prior to December 2019 and plasma from 19 rRT-PCR negative persons and ranged from 97.4% to 100%. The positive percent agreement was 93.8% to 97.9% using 48 specimens collected > 21 days post-symptom onset, while the negative percent agreement was ≥ 99% for all antigens. Test performance was similar using monoplex or multiplex testing. Integrating SARS-CoV-2 serology with other diseases of public health interest could add significant value to public health programs that have suffered severe programmatic setbacks during the COVID-19 pandemic.

Purpose: Patients with functional hypothalamic amenorrhea (FHA) could commonly have bone damage, often preceded by metabolic alterations due to a relative energy deficit state. To date, there are no markers capable of predicting osteopenia before it is manifested on DXA. Irisin is a myokine that promotes the differentiation of osteoblastic cells and appears to be inversely correlated with the incidence of bone fragility and fractures in postmenopausal women. The aim of this study was to measure irisin levels in FHA patients and to correlate it with bone density parameters., Methods: Thirty-two patients with FHA and 19 matched controls underwent the same clinical and laboratory evaluation., Results: Irisin and body mass index (BMI) were significantly lower in the case group than in healthy controls (2.03 ± 0.12 vs. 2.42 ± 0.09 p < 0.05 and 19.43 ± 2.26 vs. 22.72 ± 0.67 p < 0.05, respectively). Additionally, total body mass density (BMD g/cm 2 ) was significantly lower in the case group than in the healthy controls (1.09 ± 0.08 vs. 1.14 ± 0.05, p < 0.05), without signs of osteopenia., Conclusions: The FHA group showed lower irisin levels associated with significantly reduced BMD parameters that did not reach the severity of osteopenia. Therefore, we could speculate that irisin could predict DXA results in assessing modifications of body composition parameters. Future research is warranted to study these parameters in a larger population to confirm our results, so that irisin could be used as a predictor and screening method for bone deprivation. Furthermore, irisin is strictly related to energy metabolism and could be an indirect marker of nutritional status in FHA patients, identifying earlier states of energy deficit., (© 2022. The Author(s).)

Purpose: This retrospective study sought to identify predictors of metastatic site failure (MSF) at new and/or original (present at diagnosis) sites in high-risk neuroblastoma patients., Methods and Materials: Seventy-six high-risk neuroblastoma patients treated on four institutional prospective trials from 1997 to 2014 with induction chemotherapy, surgery, myeloablative chemotherapy, stem-cell rescue, and were eligible for consolidative primary and metastatic site (MS) radiotherapy were eligible for study inclusion. Computed-tomography and I-123 MIBG scans were used to assess disease response and Curie scores at diagnosis, post-induction, post-transplant, and treatment failure. Outcomes were described using the Kaplan-Meier estimator. Cox proportional hazards frailty (cphfR) and CPH regression (CPHr) were used to identify covariates predictive of MSF at a site identified either at diagnosis or later., Results: MSF occurred in 42 patients (55%). Consolidative MS RT was applied to 30 MSs in 10 patients. Original-MSF occurred in 146 of 383 (38%) non-irradiated and 18 of 30 (60%) irradiated MSs (p = 0.018). Original- MSF occurred in post-induction MIBG-avid MSs in 68 of 81 (84%) non-irradiated and 12 of 14 (85%) radiated MSs (p = 0.867). The median overall and progression-free survival rates were 61 months (95% CI 42.6-Not Reached) and 24.1 months (95% CI 16.5-38.7), respectively. Multivariate CPHr identified inability to undergo transplant (HR 32.4 95%CI 9.3-96.8, p < 0.001) and/or maintenance chemotherapy (HR 5.2, 95%CI 1.7-16.2, p = 0.005), and the presence of lung metastases at diagnosis (HR 4.4 95%CI 1.7-11.1, p = 0.002) as predictors of new MSF. The new MSF-free survival rate at 3 years was 25% and 87% in patients with and without high-risk factors., Conclusions: Incremental improvements in systemic therapy influence the patterns and type of metastatic site failure in neuroblastoma. Persistence of MIBG-avidity following induction chemotherapy and transplant at MSs increased the hazard for MSF., Competing Interests: 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., (© 2022 The Author(s).)

The emergence of SARS-CoV-2 created a crucial need for serology assays to detect anti-SARS-CoV-2 antibodies, which led to many serology assays entering the market. A trans-government collaboration was created in April 2020 to independently evaluate the performance of commercial SARS-CoV-2 serology assays and help inform U.S. Food and Drug Administration (FDA) regulatory decisions. To assess assay performance, three evaluation panels with similar antibody titer distributions were assembled. Each panel consisted of 110 samples with positive ( n = 30) serum samples with a wide range of anti-SARS-CoV-2 antibody titers and negative ( n = 80) plasma and/or serum samples that were collected before the start of the COVID-19 pandemic. Each sample was characterized for anti-SARS-CoV-2 antibodies against the spike protein using enzyme-linked immunosorbent assays (ELISA). Samples were selected for the panel when there was agreement on seropositivity by laboratories at National Cancer Institute's Frederick National Laboratory for Cancer Research (NCI-FNLCR) and Centers for Disease Control and Prevention (CDC). The sensitivity and specificity of each assay were assessed to determine Emergency Use Authorization (EUA) suitability. As of January 8, 2021, results from 91 evaluations were made publicly available (https://open.fda.gov/apis/device/covid19serology/, and https://www.cdc.gov/coronavirus/2019-ncov/covid-data/serology-surveillance/serology-test-evaluation.html). Sensitivity ranged from 27% to 100% for IgG ( n  = 81), from 10% to 100% for IgM ( n  = 74), and from 73% to 100% for total or pan-immunoglobulins ( n  = 5). The combined specificity ranged from 58% to 100% ( n  = 91). Approximately one-third ( n  = 27) of the assays evaluated are now authorized by FDA for emergency use. This collaboration established a framework for assay performance evaluation that could be used for future outbreaks and could serve as a model for other technologies. IMPORTANCE The SARS-CoV-2 pandemic created a crucial need for accurate serology assays to evaluate seroprevalence and antiviral immune responses. The initial flood of serology assays entering the market with inadequate performance emphasized the need for independent evaluation of commercial SARS-CoV-2 antibody assays using performance evaluation panels to determine suitability for use under EUA. Through a government-wide collaborative network, 91 commercial SARS-CoV-2 serology assay evaluations were performed. Three evaluation panels with similar overall antibody titer distributions were assembled to evaluate performance. Nearly one-third of the assays evaluated met acceptable performance recommendations, and two assays had EUAs revoked and were removed from the U.S. market based on inadequate performance. Data for all serology assays evaluated are available at the FDA and CDC websites (https://open.fda.gov/apis/device/covid19serology/, and https://www.cdc.gov/coronavirus/2019-ncov/covid-data/serology-surveillance/serology-test-evaluation.html).

We used diffusive gradients in thin films (DGT) to measure potentially bioavailable metals in coastal plain streams in the southeastern USA that exhibited strong to moderate blackwater characteristics. Metals were partitioned into particulate metals, DGT-inert metals (i.e., colloidal and refractory organic complexes not accumulated by DGT), and DGT-labile metals (i.e., free metal ions, small inorganic complexes, and labile organic complexes). We also examined the influence of different DGT deployment times using data collected from the field and a follow-up laboratory study. The DGT-measured fraction of dissolved metals in the streams was 15% for Cd, 21% for Zn, 33% for Cu, 37% for Pb, and 98% for Mn. Metals bound to particulates predominated only for Pb. Most of the Cd, Pb, Zn, and Cu were associated with colloids, refractory organic complexes, or particles. Relatively small amounts were in free ion or labile complexes likely to be bioavailable through respiratory surfaces. Modeled concentrations of free and inorganically bound Cu and Pb were lower than the DGT fraction indicating that DGT accumulated some organically bound Cu and Pb that might not have been bioavailable. DGT-exposure times in excess of 5 days may have contributed to the accumulation of partly labile organic-metal complexes and were associated with substantial biofouling that caused metal uptake by DGT to depart from linearity., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: a district health information system 2 tool with a customized routine immunization (RI) module and indicator dashboard was introduced in Kano State, Nigeria, in November 2014 to improve data management and analysis of RI services. We assessed the use of the module for program monitoring and decision-making, as well as the enabling factors and barriers to data collection and use., Methods: a mixed-methods approach was used to assess user experience with the RI data module and dashboard, including 1) a semi-structured survey questionnaire administered at 60 health facilities administering vaccinations and 2) focus group discussions and 16 in-depth interviews conducted with immunization program staff members at the local government area (LGA) and state levels., Results: in health facilities, a RI monitoring chart was used to review progress toward meeting vaccination coverage targets. At the LGA, staff members used RI dashboard data to prioritize health facilities for additional support. At the State level, immunization program staff members use RI data to make policy decisions. They viewed the provision of real-time data through the RI dashboard as a "game changer". Use of immunization data is facilitated through review meetings and supportive supervision visits. Barriers to data use among LGA staff members included inadequate understanding of the data collection tools and computer illiteracy., Conclusion: the routine immunization data dashboard facilitated access to and use of data for decision-making at the LGA, State and national levels, however, use at the health facility level remains limited. Ongoing data review meetings and training on computer skills and data collection tools are recommended., (©Dieula Delissaint Tchoualeu et al.)

Anticarsia gemmatalis is one of the main defoliating pests of soybeans in Brazil. In the current study, we characterized the histomorphology of the testes and the spermatogenesis process in A. gemmatalis. We also identified transcripts involved in the biosynthesis, metabolism, and signaling of juvenile and ecdysteroid hormones, in order to provide information about potential mechanisms of regulation of hormonal pathways in this species. Our analyses revealed that the A. gemmatalis larvae have a pair of kidney-shaped testicles. These are divided into four testicular follicles, where there are germ cell cysts at different stages of development. In the pupal stage, the testicles are fused, so adults have a single spherical testis, with a variable number of follicles. The A. gemmatalis has centripetal spermatogenesis and exhibits spermatic dimorphism. We identified 31 transcripts that encode proteins involved in juvenile hormone and ecdysteroid pathways, such as mevalonate kinase, CYP14A1, ecdysone receptor, among others. Our results on the morphology of the testes and spermatogenesis process, as well as identification of the genes involved in hormonal pathways in A. gemmatalis, provide important data for understanding the biology of this agricultural pest, which can be used as a basis for further research in other economically important lepidopterans., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Temperature and bioavailable energy control the distribution of life on Earth, and interact with each other due to the dependency of biological energy requirements on temperature. Here we analyze how temperature-energy interactions structure sediment microbial communities in two hydrothermally active areas of Guaymas Basin. Sites from one area experience advective input of thermogenically produced electron donors by seepage from deeper layers, whereas sites from the other area are diffusion-dominated and electron donor-depleted. In both locations, Archaea dominate at temperatures >45 °C and Bacteria at temperatures <10 °C. Yet, at the phylum level and below, there are clear differences. Hot seep sites have high proportions of typical hydrothermal vent and hot spring taxa. By contrast, high-temperature sites without seepage harbor mainly novel taxa belonging to phyla that are widespread in cold subseafloor sediment. Our results suggest that in hydrothermal sediments temperature determines domain-level dominance, whereas temperature-energy interactions structure microbial communities at the phylum-level and below., (© 2021. The Author(s).)

SARS-CoV-2 emerged in late 2019 and has since spread around the world, causing a pandemic of the respiratory disease COVID-19. Detecting antibodies against the virus is an essential tool for tracking infections and developing vaccines. Such tests, primarily utilizing the enzyme-linked immunosorbent assay (ELISA) principle, can be either qualitative (reporting positive/negative results) or quantitative (reporting a value representing the quantity of specific antibodies). Quantitation is vital for determining stability or decline of antibody titers in convalescence, efficacy of different vaccination regimens, and detection of asymptomatic infections. Quantitation typically requires two-step ELISA testing, in which samples are first screened in a qualitative assay and positive samples are subsequently analyzed as a dilution series. To overcome the throughput limitations of this approach, we developed a simpler and faster system that is highly automatable and achieves quantitation in a single-dilution screening format with sensitivity and specificity comparable to those of ELISA.

Background: In the US, one in six men who have sex with men (MSM) with HIV are unaware of their HIV infection. In certain circumstances, access to HIV testing and viral load (VL) monitoring is challenging. The objective of this study was to evaluate the feasibility of conducting laboratory-based HIV and antiretroviral (ARV) drug testing, and VL monitoring as part of two studies on self-collected dried blood spots (DBS)., Methods: Participants were instructed to collect DBS by self-fingerstick in studies that enrolled MSM online. DBS from the first study (N = 1444) were tested with HIV serological assays approved by the Food and Drug Administration (FDA). A subset was further tested with laboratory-modified serological and VL assays, and ARV levels were measured by mass spectrometry. DBS from the second study (N = 74) were only tested to assess VL monitoring., Results: In the first study, the mail back rate of self-collected DBS cards was 62.9%. Ninety percent of DBS cards were received at the laboratory within 2 weeks from the day of collection, and 98% of the cards had sufficient spots for one assay. Concordance between FDA-approved and laboratory-modified protocols was high. The samples with undetectable ARV had higher VL than samples with at least one ARV drug. In the second study, 70.3% participants returned self-collected DBS cards, and all had sufficient spots for VL assay. High VL was observed in samples from participants who reported low ARV adherence., Conclusions: In these studies, MSM were able to collect and provide adequate DBS for HIV testing. The FDA-approved and laboratory-modified testing algorithms performed similarly. DBS collected at home may be feasible for HIV testing, ARV measurement, and monitoring viral suppression.

Background: Currently, FDA-approved HIV-1 viral load (VL) assays use venipuncture-derived plasma. The Hologic Panther system uses 0.7 mL total volume for the Aptima HIV-1 Quant Assay standard (APT-Quant-std) and dilution (APT-Quant-dil) protocols. However, smaller plasma volumes from fingerstick whole blood (FSB) collected in EDTA-microtainer tubes (MCT) could provide an easier sample collection method for HIV-1 VL testing., Objectives: To evaluate the performance of the APT-Quant-std compared to the Roche CAP/CTM and Abbott m2000RT VL assays and an alternative APTQuant 1:7 dilution protocol, the latter using 100 μL of MCT-derived plasma from FSB., Study Design: Linearity was determined using commercial HIV-1 RNA plasma controls. Dilutions ranging 1.56-2.95 log10 copies/mL were prepared to determine the APT-Quant-dil Limit of Quantitation (LOQ) using Probit analysis. Specificity of APT-Quant-std was calculated using 326 HIVnegative samples. To evaluate agreement, 329 plasma specimens were tested with APT-Quant-std, CAP/CTM, and m2000RT. Forty-seven matched venipuncture and MCT-derived plasma specimens were tested with APT-Quant-std and APT-Quant-dil., Results: Among the RNA controls, specificity was 99.69 % for APT-Quant-std. The R2 values were 0.988 (APT-Quant-std/CAP/CTM), 0.980 (APT-Quant-std/ m2000RT), and 0.997 (APT-Quant-std/APT-Quant-dil). The APT-Quant-dil LOQ was estimated at 2.7 log10 copies/mL (500 copies/mL) (95 %CI 2.62-2.87). At 2.3 log10 copies/mL (200 copies/mL), the overall agreement was 91.0 % for APT-Quant-std/CAP/CTM, 85.7 % for APT-Quant-std/m2000RT, and 82.9 % for APT-Quant-std/APT-Quant-dil. Quantified APT-Quant-std results were on average 0.2 log10 copies/mL higher than CAP/CTM and m2000RT and 0.14 log10 copies/mL higher than APT-Quant-dil., Conclusion: APT-Quant showed similar performance compared to the CAP/CTM and m2000RT assays and remains sensitive and accurate using the dilution protocol., (Published by Elsevier B.V.)

Importance: Reported cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely underestimate the prevalence of infection in affected communities. Large-scale seroprevalence studies provide better estimates of the proportion of the population previously infected., Objective: To estimate prevalence of SARS-CoV-2 antibodies in convenience samples from several geographic sites in the US., Design, Setting, and Participants: This cross-sectional study performed serologic testing on a convenience sample of residual sera obtained from persons of all ages. The serum was collected from March 23 through May 12, 2020, for routine clinical testing by 2 commercial laboratory companies. Sites of collection were San Francisco Bay area, California; Connecticut; south Florida; Louisiana; Minneapolis-St Paul-St Cloud metro area, Minnesota; Missouri; New York City metro area, New York; Philadelphia metro area, Pennsylvania; Utah; and western Washington State., Exposures: Infection with SARS-CoV-2., Main Outcomes and Measures: The presence of antibodies to SARS-CoV-2 spike protein was estimated using an enzyme-linked immunosorbent assay, and estimates were standardized to the site populations by age and sex. Estimates were adjusted for test performance characteristics (96.0% sensitivity and 99.3% specificity). The number of infections in each site was estimated by extrapolating seroprevalence to site populations; estimated infections were compared with the number of reported coronavirus disease 2019 (COVID-19) cases as of last specimen collection date., Results: Serum samples were tested from 16 025 persons, 8853 (55.2%) of whom were women; 1205 (7.5%) were 18 years or younger and 5845 (36.2%) were 65 years or older. Most specimens from each site had no evidence of antibodies to SARS-CoV-2. Adjusted estimates of the proportion of persons seroreactive to the SARS-CoV-2 spike protein antibodies ranged from 1.0% in the San Francisco Bay area (collected April 23-27) to 6.9% of persons in New York City (collected March 23-April 1). The estimated number of infections ranged from 6 to 24 times the number of reported cases; for 7 sites (Connecticut, Florida, Louisiana, Missouri, New York City metro area, Utah, and western Washington State), an estimated greater than 10 times more SARS-CoV-2 infections occurred than the number of reported cases., Conclusions and Relevance: During March to early May 2020, most persons in 10 diverse geographic sites in the US had not been infected with SARS-CoV-2 virus. The estimated number of infections, however, was much greater than the number of reported cases in all sites. The findings may reflect the number of persons who had mild or no illness or who did not seek medical care or undergo testing but who still may have contributed to ongoing virus transmission in the population.

Through a process called "bioturbation," burrowing macrofauna have altered the seafloor habitat and modified global carbon cycling since the Cambrian. However, the impact of macrofauna on the community structure of microorganisms is poorly understood. Here, we show that microbial communities across bioturbated, but geochemically and sedimentologically divergent, continental margin sites are highly similar but differ clearly from those in nonbioturbated surface and underlying subsurface sediments. Solid- and solute-phase geochemical analyses combined with modeled bioturbation activities reveal that dissolved O 2 introduction by burrow ventilation is the major driver of archaeal community structure. By contrast, solid-phase reworking, which regulates the distribution of fresh, algal organic matter, is the main control of bacterial community structure. In nonbioturbated surface sediments and in subsurface sediments, bacterial and archaeal communities are more divergent between locations and appear mainly driven by site-specific differences in organic carbon sources., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Background: Since 2014, the recommended algorithm for laboratory diagnosis of HIV infection in the United States has consisted of an HIV-1/2 antigen/antibody (Ag/Ab) test followed by an HIV-1/2 antibody (Ab) differentiation test and, if necessary, a diagnostic HIV-1 nucleic acid test to resolve discordant or indeterminate results., Methods: Using stored specimens from persons seeking HIV testing who had not received a previous diagnosis or treatment, we compared the performance of a 3-step alternative algorithm consisting of an Ag/Ab test followed by a quantitative HIV-1 RNA viral load assay and, if viral load is not detected, an Ab differentiation test, to that of the recommended algorithm. We calculated the sensitivity and specificity of 5 Ag/Ab tests and the proportion of specimens correctly classified by the alternative algorithm compared with the recommended algorithm. Results were examined separately for specimens classified as early infection, established infection, and false-reactive screening., Results: Sensitivity and specificity were similar among all Ag/Ab tests. Viral load quantification correctly classified all specimens from early infection, all false-reactive screening specimens, and the majority of specimens from established infection., Conclusions: Although cost, regulatory barriers, test availability, and the ability to differentiate early from established infection must be considered, this alternative algorithm can potentially decrease the total number of tests performed and reduce turnaround time, thereby streamlining HIV diagnosis and initiation of treatment.

Background: There is benefit to early HIV-1 diagnosis and treatment, but there is no Food and Drug Administration-approved quantitative assay with a diagnostic claim. We compared the performance of the Hologic Aptima HIV-1 Quant (APT-Quant) and Aptima HIV-1 Qual (APT-Qual) assays for diagnostic use and the performance of a diagnostic algorithm consisting of Bio-Rad BioPlex 2200 HIV Ag-Ab assay (BPC) followed by APT-Quant (2-test) compared with BPC followed by Geenius HIV-1/2 supplemental assay (Geenius) with reflex to APT-Qual (3-test)., Methods: Five hundred twenty-four plasma, which included 419 longitudinal specimens from HIV-1 seroconverters (78 were after initiating antiretroviral therapy [ART]) and 105 from ART-naive persons with established HIV-1 infections, were used to evaluate APT-Quant performance for diagnostic use. Specimens from 200 HIV-negative persons were used to measure specificity. For the algorithm comparison, BPC-reactive specimens were evaluated with the 2-test or 3-test algorithm. McNemar's test was used to compare performance., Results: The APT-Quant detected more samples early in infection compared with APT-Qual. The APT-Quant specificity was 99.8%. Before ART initiation, the algorithms performed similarly among samples from different stages of infection. After ART initiation, the 3-test algorithm performed significantly better (P = 0.0233)., Conclusions: The APT-Quant has excellent performance for diagnostic use. The 2-test algorithm works well in ART-naive samples, but its performance decreases after the IgG response is elicited and with ART-induced suppressed viremia. Providing confirmation and viral load assay with 1 test result could be advantageous for patient care. However, additional factors and challenges associated with the implementation of this 2-test algorithm, such as cost, specimen type, and collection need further evaluation.

Since 2014, the recommended laboratory testing algorithm for diagnosing human immunodeficiency virus (HIV) infection has included a supplemental HIV-1/HIV-2 differentiation test to confirm infection type on the basis of the presence of type-specific antibodies (1). Correctly identifying HIV-1 and HIV-2 infections is vital because their epidemiology and clinical management differ. To describe the percentage of diagnoses for which an HIV-1/HIV-2 differentiation test result was reported and to categorize HIV type based on laboratory test results, 2010-2017 data from CDC's National HIV Surveillance System (NHSS) were analyzed. During 2010-2017, a substantial increase in the number of HIV-1/HIV-2 differentiation test results were reported to NHSS, consistent with implementation of the HIV laboratory-based testing algorithm recommended in 2014. However, >99.9% of all HIV infections identified in the United States were categorized as HIV-1, and the number of HIV-2 diagnoses (mono-infection or dual-infection) remained extremely low (<0.03% of all HIV infections). In addition, the overall number of false positive HIV-2 test results produced by the HIV-1/HIV-2 differentiation increased. The diagnostic value of a confirmatory antibody differentiation test in a setting with sensitive and specific screening tests and few HIV-2 infections might be limited. Evaluation and consideration of other HIV tests approved by the Food and Drug Administration (FDA) that might increase efficiencies in the CDC and Association of Public Health Laboratories-recommended HIV testing algorithm are warranted., 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.

Importance: Undiagnosed HIV infection results in delayed access to treatment and increased transmission. Self-tests for HIV may increase awareness of infection among men who have sex with men (MSM)., Objective: To evaluate the effect of providing HIV self-tests on frequency of testing, diagnoses of HIV infection, and sexual risk behaviors., Design, Setting, and Participants: This 12-month longitudinal, 2-group randomized clinical trial recruited MSM through online banner advertisements from March through August 2015. Those recruited were at least 18 years of age, reported engaging in anal sex with men in the past year, never tested positive for HIV, and were US residents with mailing addresses. Participants completed quarterly online surveys. Telephone call notes and laboratory test results were included in the analysis, which was completed from August 2017 through December 2018., Interventions: All participants had access to online web-based HIV testing resources and telephone counseling on request. Participants were randomized in a 1:1 ratio to the control group or a self-testing (ST) group, which received 4 HIV self-tests after completing the baseline survey with the option to replenish self-tests after completing quarterly surveys. At study completion, all participants were offered 2 self-tests and 1 dried blood spot collection kit., Main Outcomes and Measures: Primary outcomes were HIV testing frequency (tested ≥3 times during the trial) and number of newly identified HIV infections among participants in both groups and social network members who used the study HIV self-tests. Secondary outcomes included sex behaviors (eg, anal sex, serosorting)., Results: Of 2665 participants, the mean (SD) age was 30 (9.6) years, 1540 (57.8%) were white, and 443 (16.6%) had never tested for HIV before enrollment. Retention rates at each time point were more than 54%, and 1991 (74.7%) participants initiated 1 or more follow-up surveys. More ST participants reported testing 3 or more times during the trial than control participants (777 of 1014 [76.6%] vs 215 of 977 [22.0%]; P < .01). The cumulative number of newly identified infections during the trial was twice as high in the ST participants as the control participants (25 of 1325 [1.9%] vs 11 of 1340 [0.8%]; P = .02), with the largest difference in HIV infections identified in the first 3 months (12 of 1325 [0.9%] vs 2 of 1340 [0.1%]; P < .01). The ST participants reported 34 newly identified infections among social network members who used the self-tests., Conclusions and Relevance: Distribution of HIV self-tests provides a worthwhile mechanism to increase awareness of HIV infection and prevent transmission among MSM., Trial Registration: ClinicalTrials.gov identifier: NCT02067039.

Integrating behavioral health services into nurse-led primary care at one location ensures that individuals receive a comprehensive array of preventive and restorative services, based on their varying needs. A formative program evaluation of a federally funded behavioral health integration (BHI) project in a small nurse-led clinic used the Omaha System taxonomy to explore the changes in the documented practice of providers due to the BHI implementation. The evaluation provided evidence of the benefits of a collaborative care model to urban low-income, underserved, adults who were predominantly African American/Blacks.

Background: Cepheid's Xpert HIV-1 Viral Load (Xpert VL), a simplified, automated, single-use quantitative assay used with the GeneXpert System, is not FDA approved., Objectives: Using stored plasma, we conducted a study to assess the ability of Xpert VL to quantify viral load relative to the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 (Cobas VL) and to examine the use of the Xpert VL as a qualitative diagnostic test., Study Design: Following HIV-1 viral stock dilutions, we conducted a probit analysis to identify the concentration where 95 % of specimens had quantified VLs. We also examined Xpert and Cobas log VL correlation in linearity panels; compared the proportion of 220 seroconverter specimens with virus detected using McNemar's test; and tested specimens from persons with untreated, established HIV-1 infection (n=149) and uninfected persons (n=497). Furthermore, we examined Xpert VL as a qualitative test in seroconverter specimens with early (n=20) and later (n=68) acute infections., Results: At 1.80 log10 copies/mL, 95 % of specimens had quantifiable virus using Xpert VL. Xpert and Cobas VLs were highly correlated (R 2 =0.994). The proportion of seroconverter specimens with virus detected using Cobas and with Xpert VL was not statistically different (p=0.0578). Xpert VL detected 97.9 % of established infections, and specificity was 99.80 % (95 % CI 98.87%-99.99%). Xpert VL detected 90 % and 98.5 % of early and later acute infections, respectively., Conclusions: If approved, Xpert VL could allow U.S. laboratories that cannot bring on large, complex testing platforms to conduct HIV monitoring. An approval for diagnostic use may provide timely identification of HIV infections., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We evaluated the ability of diffusive gradients in thin films (DGT) to assess the effects of water hardness and dissolved organic carbon (DOC consisting of humic acids) on Cu and Zn toxicity (i.e., 48 h LC50s) to Ceriodaphnia dubia. When DOC was high, Cu concentrations measured by DGT (DGT Cu) were significantly lower than Cu concentrations in water (dissolved Cu), and DGT LC50s were significantly lower than LC50s based on dissolved concentrations. When DOC was low, differences between dissolved Cu and DGT Cu were small, as were differences between dissolved LC50s and DGT LC50s. Differences between DGT and dissolved measurements of Zn were small compared with the differences observed for Cu, and DGT Zn LC50s were relatively similar to dissolved Zn LC50s. Humic acids formed strong organic-Cu complexes that were both inaccessible for biological uptake and excluded by DGT, which selected for free or weakly bound Cu. In contrast, Zn did not form strong complexes with DOC that greatly affected either toxicity or the measurement of Zn by DGT. The effects of hardness on DGT measurements of Cu and Zn were smaller and more complex than the effects of DOC. Large, statistically significant differences between DGT measurements of Cu in low and high DOC water accurately reflected the strong effects of DOC on Cu toxicity. However, the effects of DOC were inconsistent for Zn, and DGT provided less information about the toxic fraction of this metal., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Congenital anomalies are the fifth leading cause of mortality in children under 5 years globally. The greatest burden is faced by those in developing countries, where over 95% of deaths occur. Many of these deaths may have been preventable through antenatal diagnosis and early intervention. This study aims to conduct a systematic review that investigates the use of antenatal ultrasound to diagnose congenital anomalies and improve the health outcomes of infants in low-income and middle-income countries (LMICs)., Methods and Analysis: A systematic literature review will be conducted using three search strings: (1) structural congenital anomalies, (2) LMICs and (3) antenatal diagnosis. Four electronic databases will be searched: MEDLINE, Embase, PubMed and the Cochrane Library. Title, abstract and full-text screening will be undertaken in duplicate by two reviewers independently using Covidence. Consensus will be sought from the wider authorship for discrepancies. Data extraction will be undertaken by the principal investigator. The primary analysis will focus on the availability and effectiveness of antenatal ultrasound for structural congenital anomalies. Secondary outcomes will include neonatal morbidity and mortality, termination rates and referral rates for further antenatal care. Descriptive statistics and a narrative synthesis will be included in the final report. The methodological quality of the included studies will be evaluated using the Cochrane-approved Risk of Bias for Non-Randomised Studies of Intervention and Risk of Bias in Randomised Trials V.2.0 tools., Ethics and Dissemination: Ethical approval is not required for conducting the systematic review as there will be no direct collection of data from individuals. The results will be submitted for publication in a scientific journal and presented internationally., Conclusion: This is the first study, to our knowledge, to systematically review current literature on the use of antenatal ultrasound for the detection of congenital anomalies in LMICs. This is vital to define current practice, highlight global disparities and evaluate effects on health outcomes for infants in low-resource settings., Prospero Registration Number: CRD42019105620., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Objective: To determine the precision of new and established methods for estimating duration of HIV infection., Design: A retrospective analysis of HIV testing results from serial samples in commercially available panels, taking advantage of extensive testing previously conducted on 53 seroconverters., Methods: We initially investigated four methods for estimating infection timing: method 1, 'Fiebig stages' based on test results from a single specimen; method 2, an updated '4th gen' method similar to Fiebig stages but using antigen/antibody tests in place of the p24 antigen test; method 3, modeling of 'viral ramp-up' dynamics using quantitative HIV-1 viral load data from antibody-negative specimens; and method 4, using detailed clinical testing history to define a plausible interval and best estimate of infection time. We then investigated a 'two-step method' using data from both methods 3 and 4, allowing for test results to have come from specimens collected on different days., Results: Fiebig and '4th gen' staging method estimates of time since detectable viremia had similar and modest correlation with observed data. Correlation of estimates from both new methods (3 and 4), and from a combination of these two ('two-step method') was markedly improved and variability significantly reduced when compared with Fiebig estimates on the same specimens., Conclusion: The new 'two-step' method more accurately estimates timing of infection and is intended to be generalizable to more situations in clinical medicine, research, and surveillance than previous methods. An online tool is now available that enables researchers/clinicians to input data related to method 4, and generate estimated dates of detectable infection.

Background: Serological assays to determine HIV incidence have contributed to estimates of HIV incidence, monitoring of HIV spread, and evaluation of prevention strategies. Two frequently used incidence assays are the Sedia HIV-1 LAg-Avidity EIA (LAg) and the Bio-Rad avidity incidence (BRAI) assays with a mean duration of recent infection (MDRI) of 130 and 240 days for subtype B infections, respectively. Little is known about how these assays perform with recombinant HIV-1 strains. We evaluated the concordance of these assays in a population infected mainly with HIV-1 CRF06&#95;cpx., Material/methods: Remnant serum samples (n = 288) collected from confirmed, newly-diagnosed HIV-positive persons from Estonia in 2013 were tested. Demographic and clinical data were extracted from clinical databases. LAg was performed according to the manufacturer's protocol and BRAI testing was done using a validated protocol. Samples with LAg-pending or BRAI-invalid results were reclassified as recent if they were from persons with viral loads <1000 copies/mL or were reclassified as long-term if presenting with AIDS., Results: In total 325 new HIV infections were diagnosed in 2013 in Estonia. Of those 276 persons were tested with both LAg and BRAI. Using assay results only, the recency rate was 44% and 70% by LAg and BRAI, respectively. The majority of samples (92%) recent by LAg were recent by BRAI. Similarly, 89% of samples long-term by BRAI were long-term by LAg. After clinical information was included in the analysis, the recency rate was 44% and 62% for LAg and BRAI, respectively. The majority of samples (86%) recent by LAg were recent by BRAI and 91% of long-term infections by BRAI were long-term by LAg., Conclusions: Comparison of LAg and BRAI results in this mostly CRF06&#95;cpx-infected population showed good concordance for incidence classification. Our finding of a higher recency rate with BRAI in this population is likely related to the longer MDRI for this assay., Competing Interests: The authors have declared that no competing interests exist.

The accuracy of flow cytometric (FCM) quantifications of microbial populations in sediments varies with FCM settings, cell extraction and staining protocols, as well as sample types. In the present study, we improve the accuracy of FCM for enumerating microorganisms inhabiting diverse lake and marine sediment types based on extensive tests with FCM settings, extraction buffer chemical compositions, cell separation methods, and staining procedures. Tests on the FCM settings, (e.g., acquisition time, rates of events) and salinity of extraction solutions show minor impacts on FCM enumerations and yields of cell extraction, respectively. Existing methods involving hydrofluoric acid (HF) treatment to release sediment-attached cells into solution prove effective on both marine and freshwater samples. Yet, different staining techniques (direct staining of cell extracts, staining of membrane-filtered cell extracts) produce clear differences in cell number estimates. We demonstrate that, while labor-intensive membrane-staining generates high cell staining efficiency and accurate cell counts that are consistent across FCM and epifluorescence microscopy-based (EFM) quantification methods, accurate cell counts determined by more time- and labor-efficient direct staining require consideration of dye concentration, sample dilution, and lithology. Yet, good agreement between the two staining methods can be achieved through sample-specific adjustments of dye concentrations and sample dilutions during direct staining. We thus present a complete protocol for FCM-based cell quantification, that includes all steps from the initial sample fixation to the final enumeration, with recommendations for buffer compositions, direct and membrane-based staining procedures, and the final FCM assay. This protocol is versatile, accurate, and reliable, as is evident from good agreement with cell quantifications by EFM and quantitative polymerase chain reaction (qPCR) of 16S rRNA genes across a wide range of sedimentary sample types.

Background: Laboratory assays for determining recent HIV-1 infection are an important public health tool for aiding in the estimation of HIV incidence. Some incidence assay analytes are remarkably predictive of time since seroconversion and may be useful for additional applications, such as predicting recent transmission events during HIV outbreaks and informing prevention strategies., Methods: Plasma samples (n = 154) from a recent HIV-1 outbreak in a rural community in Indiana were tested with the customized HIV-1 Multiplex assay, based on the Bio-Rad Bio-Plex platform, which measures antibody response to HIV envelope antigens, gp120, gp160, and gp41. Assay cutoffs for each analyte were established to determine whether an individual seroconverted within 30, 60, or 90 days of the sample collection date. In addition, a novel bioinformatics method was implemented to infer infection dates of persons newly diagnosed with HIV during the outbreak., Results: Sensitivity/specificity of the HIV-1 Multiplex assay for predicting seroconversion within 30, 60, and 90 days, based on a training data set, was 90.5%/95.4%, 94.1%/90%, and 89.4%/82.9%, respectively. Of 154 new diagnoses in Indiana between December 2014 and August 2016, the majority (71%) of recent infections (≤3 months since seroconversion) were identified between February and May 2016. The epidemiologic curve derived from the bioinformatics analysis indicated HIV transmission began as early as 2010, grew exponentially in 2014, and leveled off in April 2015., Conclusions: The HIV-1 Multiplex assay has the potential to identify and monitor trends in recent infection during an epidemic to assess the efficacy of programmatic or treatment interventions.

Background: In the US, the HIV diagnostic algorithm for laboratory settings recommends the use of an HIV-1/HIV-2 differentiation supplemental assay after an initial reactive antigen/antibody (Ag/Ab) assay result. Since the discontinuation of the Multispot HIV-1/HIV-2 Rapid Test (MS), the Geenius HIV-1/2 Supplemental assay (Geenius) is the only FDA-approved supplemental differentiation test., Objective: We compared the performance of Geenius to MS and Western Blot (WB)., Study Design: The relative seroconversion plasma reactivity of Geenius and MS was assessed using a 50% cumulative frequency analysis from 17 HIV-1 seroconverters. In addition, previously characterized plasma specimens, 186 HIV-1 positive, 100 HIV-2 positive, and 93 Ag/Ab-positive/HIV-1 RNA-negative, were tested with Geenius v1.1 software. McNemar's test was used for paired comparison analysis. A subset of 48 specimens were retested with the upgraded Geenius v1.3 software., Results: In HIV-1 seroconverters, the relative seroconversion reactivity was 2.5 and 2 days before the first positive HIV-1 WB for Geenius and MS, respectively. In HIV-1 positive samples, Geenius performed similarly to HIV-1 WB (p=0.1687) and MS (p=0.8312). In HIV-2 positive samples, Geenius underperformed compared to HIV-2 WB (p=0.0005) and MS (p=0.0012). When using the upgraded software among the HIV-1 positive and Ag/Ab-reactive/HIV-1 RNA-negative samples, gp140 reactivity decreased without affecting characterization of HIV-2 samples., Conclusions: With HIV-1 samples, Geenius, WB and MS performance was similar as supplemental tests. The updated Geenius software reduced false gp140 reactivity, but had no impact on identifying true HIV-2 infections. Further evaluation will assess the impact of the Geenius software update on final diagnostic interpretations., (Copyright © 2018 Elsevier B.V. All rights reserved.)