Search

Abstract Background Sexually transmitted infections (STIs) such as syphilis and HIV remain to be a significant public health issue worldwide. Dual rapid point-of-care tests (POCTs) have shown promise for detecting antibodies to HIV and syphilis but have not been fully evaluated in the field. Our study supported the WHO ProSPeRo study on Sexually Transmitted Infection Point-of-Care Testing (STI POCT) by providing external quality assessment (EQA) for HIV and syphilis testing in reference laboratories and their associated clinical sites in seven countries. Methods HIV/syphilis serum liquid and dried tube specimen (DTS) panels were prepared by CDC. Liquid panels were distributed to the reference laboratories for three rounds of testing using commercially and locally available laboratory-based serological tests. DTS panels were sent to the clinical testing sites for 8 rounds of POC testing using the Abbott SD BIOLINE HIV/Syphilis Duo test (hereafter referred to as SD BIOLINE) and the Chembio Dual Path Platform (DPP) HIV-Syphilis assay. EQA panels were tested at CDC using the Rapid Plasma Reagin (RPR) test and the Treponema pallidum Particle Agglutination assay (TP-PA) for syphilis antibodies. Genetic Systems HIV-1/HIV-2 Plus O EIA, Geenius HIV Supplemental Assay and the Oraquick Advance HIV test were used to detect HIV antibodies in the EQA panels. Results from the reference laboratories and POCT sites were compared to those obtained at the CDC and a percentage agreement was calculated. Results Qualitative RPR and TP-PA performed at the reference laboratories demonstrated 95.4–100% agreement with CDC results while quantitative RPR and TP-PA tests demonstrated 87.7% and 89.2% agreement, respectively. A 93.8% concordance rate was observed for qualitative HIV testing in laboratories. EQA testing at clinical sites using dual tests showed 98.7% and 99.1% agreement for detection of HIV antibodies and eight out of 10 sites had > 95.8% agreement for syphilis testing. However, two clinical sites showed only 65.0–66.7% agreement for SD BIOLINE and 84.0–86.7% for DPP, respectively, for syphilis testing. Conclusions Overall, laboratories demonstrated high EQA performance in this study. Both HIV/syphilis POCTs gave expected results in the clinic-based evaluations using DTS. However, testing errors were identified in a few testing sites suggesting the necessity for continuous training and monitoring the quality of POC testing.

ABSTRACT Objective: To describe the clinical features and outcomes of patients with uveitis associated with juvenile idiopathic arthritis (JIA) and idiopathic uveitis. Methods: This was an observational, retrospective study, conducted in a tertiary center. Patients under 18 years old who experienced at least one episode of uveitis and followed between 2000 and 2019 were included. Results: A total of 82 patients were included, of whom 43 had idiopathic uveitis and 39 had uveitis associated with JIA. Anterior uveitis was the primary site of ocular inflammation (76.8%) and occurred in 24 and 39 patients with idiopathic uveitis and uveitis associated with JIA arthritis, respectively (p=0.02). The complete response to corticotherapy was more frequent in uveitis associated with JIA (p=0.001). Total and partial responses to biological disease modifying antirheumatic drugs were more frequent in uveitis associated with JIA (p=0.025) and idiopathic uveitis (p=0.045), respectively. There were 203 complications: cataracts were more frequently present in idiopathic uveitis (p=0.05), while synechiae was more frequent in uveitis associated with JIA (p=0.02). Conclusion: Idiopathic uveitis and uveitis associated JIA frequently follow a chronic course and an increased risk of visual loss in childhood. The uveitis associated with JIA showed better response to systemic corticotherapy and total response to biologic disease modifying antirheumatic drugs more frequently.

Kings and queens of eusocial termites can live for decades, while queens sustain a nearly maximal fertility. To investigate the molecular mechanisms underlying their long lifespan, we carried out transcriptomics, lipidomics and metabolomics in Macrotermes natalensis on sterile short-lived workers, long-lived kings and five stages spanning twenty years of adult queen maturation. Reproductives share gene expression differences from workers in agreement with a reduction of several aging-related processes, involving upregulation of DNA damage repair and mitochondrial functions. Anti-oxidant gene expression is downregulated, while peroxidability of membranes in queens decreases. Against expectations, we observed an upregulated gene expression in fat bodies of reproductives of several components of the IIS pathway, including an insulin-like peptide, Ilp9. This pattern does not lead to deleterious fat storage in physogastric queens, while simple sugars dominate in their hemolymph and large amounts of resources are allocated towards oogenesis. Our findings support the notion that all processes causing aging need to be addressed simultaneously in order to prevent it.

Online fundraisers often showcase information about the number of donations received and the proximity to the campaign goal. This practice follows research on descriptive norms and goal-directed motivation, which predicts higher contributions as the number of donors increases and as the campaign goal is approached. However, across three studies, we demonstrate that when the campaign is close to completion, individuals give more when they see that there are few (vs. many) donors to the campaign. We observe this result across real campaigns on a fundraising website and obtain causal evidence for this effect in two laboratory experiments. We find that this effect is driven in part by an increase in the perceived progress that ones donation makes towards reaching the campaign goal. This work identifies a counterintuitive consequence of norm-based marketing appeals and has important implications for fundraisers.

The SARS-CoV-2 helicase, non-structural protein 13 (Nsp13), plays an essential role in viral replication, translocating in the 5′ → 3′ direction as it unwinds double-stranded RNA/DNA. We investigated the impact of structurally distinct DNA lesions on DNA unwinding catalyzed by Nsp13. The selected lesions include two benzo[a]pyrene (B[a]P)-derived dG adducts, the UV-induced cyclobutane pyrimidine dimer (CPD), and the pyrimidine (6–4) pyrimidone (6–4PP) photolesion. The experimentally observed unwinding rate constants (kobs) and processivities (P) were examined. Relative to undamaged DNA, the kobs values were diminished by factors of up to ~15 for B[a]P adducts but only by factors of ~2–5 for photolesions. A minor-groove-oriented B[a]P adduct showed the smallest impact on P, which decreased by ~11% compared to unmodified DNA, while an intercalated one reduced P by ~67%. However, the photolesions showed a greater impact on the processivities; notably, the CPD, with the highest kobs value, exhibited the lowest P, which was reduced by ~90%. Our findings thus show that DNA unwinding efficiencies are lesion-dependent and most strongly inhibited by the CPD, leading to the conclusion that processivity is a better measure of DNA lesions’ inhibitory effects than unwinding rate constants.

The mucosal immunity is crucial for restricting SARS-CoV-2 at its entry site. Intramuscularly applied vaccines against SARS-CoV-2 stimulate high levels of neutralizing Abs in serum, but the impact of these intramuscular vaccinations on features of mucosal immunity is less clear. Here, we analyzed kinetic and functional properties of anti-SARS-CoV-2 Abs in the saliva after vaccination with BNT162b2. We analyzed a total of 24 healthy donors longitudinally for up to 16 months. We found that specific IgG appeared in the saliva after the second vaccination, declined thereafter and reappeared after the third vaccination. Adjusting serum and saliva for the same IgG concentration revealed a strong correlation between the reactivity in these two compartments. Reactivity to VoCs correlated strongly as seen by ELISAs against RBD variants and by live-virus neutralizing assays against replication-competent viruses. For further functional analysis, we purified IgG and IgA from serum and saliva. In vaccinated donors we found neutralizing activity towards authentic virus in the IgG, but not in the IgA fraction of the saliva. In contrast, IgA with neutralizing activity appeared in the saliva only after breakthrough infection. In serum, we found neutralizing activity in both the IgA and IgG fractions. Together, we show that intramuscular mRNA vaccination transiently induces a mucosal immunity that is mediated by IgG and thus differs from the mucosal immunity after infection. Waning of specific mucosal IgG might be linked to susceptibility for breakthrough infection.

ObjectiveThe risk of developing micro- and macrovascular complications is higher for individuals with type 1 diabetes (T1D). Numerous studies have indicated variations in gut microbial composition between healthy individuals and those with T1D. These changes in the gut ecosystem may lead to inflammation, modifications in intestinal permeability, and alterations in metabolites. Such effects can collectively impact the metabolic regulation system, thereby influencing blood glucose control. This review aims to explore the relationship between the gut microbiome, inflammation, and blood glucose parameters in patients with T1D.MethodsGoogle Scholar, PubMed, and Web of Science were systematically searched from 2003 to 2023 using the following keywords: “gut microbiota,” “gut microbiome,” “bacteria,” “T1D,” “type 1 diabetes,” “autoimmune diabetes,” “glycemic control,” “glucose control,” “HbA1c,” “inflammation,” “inflammatory,” and “cytokine.” The examination has shown 18,680 articles with relevant keywords. After the exclusion of irrelevant articles, seven observational papers showed a distinct gut microbial signature in T1D patients.ResultsThis review shows that, in T1D patients, HbA1c level was negatively correlated with abundance of Prevotella, Faecalibacterium, and Ruminococcaceae and positively correlated with abundance of Dorea formicigenerans, Bacteroidetes, Lactobacillales, and Bacteriodes. Instead, Bifidobacteria was negatively correlated with fasting blood glucose. In addition, there was a positive correlation between Clostridiaceae and time in range. Furthermore, a positive correlation between inflammatory parameters and gut dysbiosis was revealed in T1D patients.ConclusionWe draw the conclusion that the gut microbiome profiles of T1D patients and healthy controls differ. Patients with T1D may experience leaky gut, bacterial translocation, inflammation, and poor glucose management due to microbiome dysbiosis. Direct manipulation of the gut microbiome in humans and its effects on gut permeability and glycemic control, however, have not been thoroughly investigated. Future research should therefore thoroughly examine other potential pathophysiological mechanisms in larger studies.

IntroductionTo explore whether the reported lower pathogenicity in infected individuals of variant of concern (VoC) Omicron and its current subvariants compared to VoC Delta may be related to fundamental differences in the initial virus-tissue interaction, we assessed their ability to penetrate, replicate and cause damage in a human 3D respiratory model.MethodsFor this, we used TEER measurements, real-time PCR, LDH, cytokine and complex confocal imaging analyses.Results and discussionWe observed that Delta readily penetrated deep into the respiratory epithelium and this was associated with major tissue destruction, high LDH activity, high viral loads and pronounced innate immune activation as observed by intrinsic C3 activation and IL-6 release at infection sites. In contrast, Omicron subvariants BA.5, BQ.1.1 and BF7 remained superficially in the mucosal layer resulting merely in outward-directed destruction of cells, maintenance of epithelial integrity, minimal LDH activity and low basolateral release of virus at infection sites, as well as significantly smaller areas of complement activation and lower IL-6 secretion. Interestingly, also within Omicron subvariants differences were observed with newer Omicron subvariants BQ.1.1 and BF.7 illustrating significantly reduced viral loads, IL-6 release and LDH activity compared to BA.5. Our data indicate that earliest interaction events after SARS-CoV-2 transmission may have a role in shaping disease severity.

ABSTRACT Currently, SARS-CoV-2 Omicron BA.5 subvariants BF.7 and BQ.1.1 are rapidly emerging worldwide. To evaluate the SARS-CoV-2-neutralizing capacity of sera and saliva from triple vaccinated individuals, either boosted with an adapted bivalent COVID-19 vaccine or recovered from BA.4/BA.5 infection, we analyzed the sensitivity of replication-competent SARS-CoV-2 Omicron subvariants BA.4/5, BQ.1.1 and BF.7 to neutralization. Analysis of SARS-CoV-2-specific IgGs and IgAs showed increased serum IgG titers in the vaccinated group, while the serum and salivary IgA levels were comparable. Similar and efficient serum neutralization against the ancestral strain of SARS-CoV-2 and Omicron BA.4/BA.5 was detected in both cohorts, but critically reduced for BQ.1.1 and BF.7. In contrast, salivary neutralization against BA.4/BA.5 was increased in the convalescent compared to the vaccinated group, while salivary neutralizing capacity against BQ.1.1 and BF.7 was comparable in these groups. Further, personalized protective effects studied in a human 3D respiratory model revealed the importance of salivary protection against different Omicron subvariants. IMPORTANCE In BA.4/BA.5-convalescent versus vaccinated groups, salivary neutralization capacity increased against SARS-CoV-2 Omicron BA.4/BA.5. In contrast, it neutralized novel Omicron subvariants BQ.1.1 and BF.7 similarly. Salivary protection against various Omicron subvariants was even more evident when tested in a personalized approach using highly differentiated respiratory human 3D models.

ABSTRACT Population-based HIV Impact Assessments (PHIAs) are national household (HH) surveys that provide HIV diagnosis and CD4 testing with an immediate return of results. Accurate CD4 results improve HIV-positive participants’ clinical care and inform the effectiveness of HIV programs. Here, we present CD4 results from the PHIA surveys that were conducted in 11 countries in sub-Saharan Africa between 2015 and 2018. All of the HIV-positive participants and 2 to 5% of the HIV-negative participants were offered Pima CD4 (Abbott, IL, USA) point-of-care (POC) tests. The quality of the CD4 test was ensured by conducting instrument verification, comprehensive training, quality control, a review of testing errors and an analysis of unweighted CD4 data by HIV status, age, gender, and antiretroviral (ARV) treatment status. Overall, CD4 testing was completed for 23,085 (99.5%) of the 23,209 HIV-positive and 7,329 (2.7%) of the 270,741 negative participants in 11 surveys. The instrument error rate was 11.3% (range, 4.4% to 15.7%). The median CD4 values among HIV-positive and HIV-negative participants (aged 15+) were 468 cells/mm3 (interquartile range [IQR], 307 to 654) and 811 cells/mm3 (IQR, 647 to 1,013), respectively. Among the HIV-positive participants (aged 15+), those with detectable ARVs had higher CD4 values (508 cells/mm3) than those with undetectable ARVs (385.5 cells/mm3). Among the HIV-positive participants (aged 15+), 11.4% (2,528/22,253) had a CD4 value of less than 200 cells/mm3, and approximately half of them (1,225/2,528 = 48.5%) had detectable ARVs, whereas 51.5% (1,303/2,528) had no detectable ARVs (P < 0.0001). We successfully implemented high quality POC CD4 testing using Pima instruments. Our data come from nationally representative surveys in 11 countries and provide unique insights regarding the CD4 distribution among HIV-positive individuals as well as the baseline CD4 values among HIV-negative individuals. IMPORTANCE The manuscript describes CD4 levels among HIV-positive individuals and baseline CD4 levels among HIV-negative individuals from 11 sub-Saharan countries, thereby highlighting the importance of CD4 markers in the context of the HIV epidemic. Despite increased ARV access in each country, advanced HIV disease (CD4

Glycogen storage disease Type III (GSD III) is an autosomal recessive disease due to the deficiency of the debranching enzyme, which has two main consequences: a reduced availability of glucose due to the incomplete degradation of glycogen, and the accumulation of abnormal glycogen in liver and cardiac/skeletal muscle. The role of dietary lipid manipulations in the nutritional management of GSD III is still debated. A literature overview shows that low-carbohydrate (CHO) / high-fat diets may be beneficial in reducing muscle damage. We present a 24-year GSD IIIa patient with severe myopathy and cardiomyopathy in whom a gradual shift from a high-CHO diet (61% total energy intake), low-fat (18%), high-protein (21%) to a low-CHO (32 %) high-fat (45%) / high-protein (23%) diet was performed. CHO was mainly represented by high-fiber, low glycemic index food, and fat consisted prevalently of mono and polyunsaturated fatty acids. After a 2-year follow-up, all biomarkers of muscle and heart damage markedly decreased (by 50–75%), glucose levels remained within the normal range and lipid profile was unchanged. At echocardiography, there was an improvement in geometry and left ventricular function. A low -CHO, high-fat, high-protein diet seems to be safe, sustainable and effective in reducing muscle damage without worsening cardiometabolic profile in GSDIIIa. This dietary approach could be started as early as possible in GSD III displaying skeletal/cardiac muscle disease in order to prevent/minimize organ damage.

Séité, Harrison, et al. investigate the mechanisms underlying long lifespan in queens and kings of the highly social termite Macrotermes natalensis. Using transcriptomics, lipidomics and metabolomics, this study shows that several aging-related processes are reduced in the fat bodies of these reproductives and that an upregulated insulin-like peptide, Ilp9, does not lead to deleterious fat storage in old queens, while simple sugars dominate in their hemolymph.

Hemorrhagic shock is a leading cause of morbidity and mortality worldwide. Significant blood loss may lead to decreased blood pressure and inadequate tissue perfusion with resultant organ failure and death, even after replacement of lost blood volume. One reason for this high acuity is that the fundamental mechanisms of shock are poorly understood. Proteomic and metabolomic approaches have been used to investigate the molecular events occurring in hemorrhagic shock but, to our knowledge, a systematic analysis of the transcriptomic profile is missing. Therefore, a pilot analysis using paired-end RNA sequencing was used to identify changes that occur in the blood transcriptome of rats subjected to hemorrhagic shock after blood reinfusion. Hemorrhagic shock was induced using a Wigger's shock model. The transcriptome of whole blood from shocked animals shows modulation of genes related to inflammation and immune response (Tlr13, Il1b, Ccl6, Lgals3), antioxidant functions (Mt2A, Mt1), tissue injury and repair pathways (Gpnmb, Trim72) and lipid mediators (Alox5ap, Ltb4r, Ptger2) compared with control animals. These findings are congruent with results obtained in hemorrhagic shock analysis by other authors using metabolomics and proteomics. The analysis of blood transcriptome may be a valuable tool to understand the biological changes occurring in hemorrhagic shock and a promising approach for the identification of novel biomarkers and therapeutic targets. Impact statement This study provides the first pilot analysis of the changes occurring in transcriptome expression of whole blood in hemorrhagic shock (HS) rats. We showed that the analysis of blood transcriptome is a useful approach to investigate pathways and functional alterations in this disease condition. This pilot study encourages the possible application of transcriptome analysis in the clinical setting, for the molecular profiling of whole blood in HS patients.

Prosocial lies, or lies intended to benefit others, are ubiquitous behaviors that have important social and economic consequences. Though emotions play a central role in many forms of prosocial behavior, no work has investigated how emotions influence behavior when one has the opportunity to tell a prosocial lie-a situation that presents a conflict between two prosocial ethics: lying to prevent harm to another, and honesty, which might also provide benefits to the target of the lie. Here, we examine whether the emotion of compassion influences prosocial lying, and find that compassion causally increases and positively predicts prosocial lying. In Studies 1 and 2, participants evaluated a poorly written essay and provided feedback to the essay writer. Experimentally induced compassion felt toward the essay writer (Study 1) and individual differences in trait compassion (Study 2) were positively associated with inflated feedback to the essay writer. In both of these studies, the relationship between compassion and prosocial lying was partially mediated by an enhanced importance placed on preventing emotional harm. In Study 3, we found moderation such that experimentally induced compassion increased lies that resulted in financial gains for a charity, but not lies that produced financial gains for the self. This research illuminates the emotional underpinnings of the common yet morally complex behavior of prosocial lying, and builds on work highlighting the potentially harmful effects of compassion-an emotion typically seen as socially beneficial. (PsycINFO Database Record

Summary: Bacterial DnaK belongs to the Hsp70 chaperone family, which plays a critical role in maintaining proteostasis by catalyzing protein folding, and is a proposed antibacterial target in the pathogen Mycobacterium tuberculosis. Here, we describe an experimental toolbox for evaluating inhibitors against the mycobacterial DnaK chaperone network: a coupled-enzymatic assay to monitor ATPase activity, a proteolytic cleavage assay to study DnaK conformational changes upon ligand addition, as well as a protein renaturation assay to assess chaperone function.For complete details on the use and execution of this protocol, please refer to Hosfelt et al. (2021).

Sleep disorders are bidirectionally linked with eating behaviors and glucose metabolism, which could be clinically relevant in type 1 diabetes (T1D). We investigated the relationship between dietary habits and sleep quality in individuals with T1D on insulin pumps and continuous glucose monitoring (CGM). In a cross-sectional study, dietary habits (7-day food diary, EPIC questionnaire) and sleep quality (Pittsburgh Sleep Quality Index questionnaire) were assessed in 59 men and 58 women with T1D, aged 19–79 years, using CGM and insulin pump. Differences in dietary habits and blood glucose after dinner (6 h) between participants differing in sleep quality, sleep duration, and sleep onset latency were evaluated. Bad Sleepers (n = 81) were twice as prevalent as Good Sleepers (n = 36) and had a significantly higher intake of fat than Good Sleepers (dinner: 30.7 ± 10.7 vs. 24.0 ± 10.5 g, p = 0.004). Short sleepers had a significantly higher usual intake (g/1000 kcal) of coffee and tea (90.4 ± 71.7 vs. 62.0 ± 35.6), alcoholic (47.8 ± 51.1 vs. 28.9 ± 31.5) and carbonated beverages (21.8 ± 38.1 vs. 9.3 ± 17.2) (p < 0.05 for all) than Long Sleepers. Long Sleep Onset Latency was associated with a significantly higher fat intake at dinner (41.8 ± 7.4 vs. 38.1 ± 9.1 % total energy, p = 0.029) than Short Sleep Onset Latency. No significant differences in post-dinner blood glucose levels were detected between participants with good or bad sleep quality. Sleep disruption is common in T1D and is associated with unhealthy dietary choices, especially at dinner, independently of post-dinner blood glucose control. • Sleep disruption is common in patients with type 1 diabetes. • Bad sleep quality is associated with high intake of saturated fat and alcoholic, carbonated, and caffeinated drinks, especially at dinner. • This association is independent of overall and post-dinner blood glucose control. [ABSTRACT FROM AUTHOR]

To evaluate the maternal and fetal hemodynamic effects of treatment with a nitric oxide donor and oral fluid in pregnancies complicated by fetal growth restriction. 30 normotensive participants with early fetal growth restriction were enrolled. 15 participants were treated until delivery with transdermal glyceryl trinitrate and oral fluid intake (Treated group), and 15 comprised the untreated group. All women underwent non-invasive assessment of fetal and maternal hemodynamics and repeat evaluation 2 weeks later. In the treated group, maternal hemodynamics improved significantly after two weeks of therapy compared to untreated participants. Fetal hemodynamics in the treated group showed an increase in umbilical vein diameter by 18.87 % (p < 0.01), in umbilical vein blood flow by 48.16 % (p < 0.01) and in umbilical vein blood flow corrected for estimated fetal weight by 30.03 % (p < 0.01). In the untreated group, the characteristics of the umbilical vein were unchanged compared to baseline. At the same time, the cerebro-placental ratio increased in the treated group, while it was reduced in the untreated group, compared to baseline values. The treated group showed a higher birthweight centile (p = 0.03) and a lower preeclampsia rate (p = 0.04) compared to the untreated group. The combined therapeutic approach with nitric oxide donor and oral fluid intake in fetal growth restriction improves maternal hemodynamics, which becomes more hyperdynamic (volume-dominant). At the same time, in the fetal circuit, umbilical vein flow increased and fetal brain sparing improved. Although a modest sample size, there was less preeclampsia and a higher birthweight suggesting beneficial maternal and fetal characteristics of treatment. • Early fetal growth restriction is characterized by altered maternal hemodynamics. • NO donor improves maternal hemodynamics reducing vascular resistance. • NO donor increases fetal umbilical vein blood flow and fetal oxygenation. • NO donor might reduce the incidence of preeclampsia and improve the birthweight. [ABSTRACT FROM AUTHOR]

Abstract Background Patients with type 1 diabetes (T1D) have higher mortality risk compared to the general population; this is largely due to increased rates of cardiovascular disease (CVD). As accurate CVD risk stratification is essential for an appropriate preventive strategy, we aimed to evaluate the concordance between 2019 European Society of Cardiology (ESC) CVD risk classification and the 10-year CVD risk prediction according to the Steno Type 1 Risk Engine (ST1RE) in adults with T1D. Methods A cohort of 575 adults with T1D (272F/303M, mean age 36 ± 12 years) were studied. Patients were stratified in different CVD risk categories according to ESC criteria and the 10-year CVD risk prediction was estimated with ST1RE within each category. Results Men had higher BMI, WC, SBP than women, while no difference was found in HbA1c levels between genders. According to the ESC classification, 92.5% of patients aged 20 years) alone identified few patients (

BackgroundThe Nigeria AIDS Indicator and Impact Survey (NAIIS), a cross-sectional household survey, was conducted in 2018 with primary objectives to estimate HIV prevalence, HIV-1 incidence, and status of UNAIDS 90-90-90 cascade. We conducted retrospective analysis of the performance of HIV rapid tests and the national HIV testing algorithm used in Nigeria.MethodsThe national algorithm included Determine HIV-1/2 as test 1 (T1), Unigold HIV-1/2 as test 2 (T2), and StatPak HIV-1/2 as the tie-breaker test (T3). Individuals reactive with T1 and either T2 or T3 were considered HIV-positive. HIV-positive specimens from the algorithm were further confirmed for the survey using supplemental test Geenius HIV-1/2. If Geenius did not confirm HIV-positive status, HIV-1 Western blot was performed. We calculated the concordance between tests and positive predictive value (PPV) of the algorithm on unweighted data.ResultsOf 204,930 participants (ages ≥18 months) 5,103 (2.5%) were reactive on T1. Serial testing of T1 reactive specimens with T2 or if needed by tiebreaker T3 identified 2958 (1.44%) persons as HIV-positive. Supplemental testing confirmed 2,800 (95%) as HIV-positive (HIV-1 = 2,767 [98.8%]; HIV-2 = 5 [0.2%]; dual infections = 22 [0.8%]). Concordance between T1 and T2 was 56.6% while PPV of the national algorithm was 94.5%.ConclusionsOur results show high discordant rates and poor PPV of the national algorithm with a false-positive rate of about 5.5% in the NAIIS survey. Considering our findings have major implications for HIV diagnosis in routine HIV testing services, additional evaluation of testing algorithm is warranted in Nigeria.

Online fundraisers often showcase information about the number of donations received and the proximity to the campaign goal. This practice follows research on descriptive norms and goal-directed motivation, which predicts higher contributions as the number of donors increases and as the campaign goal is approached. However, across three studies, we demonstrate that when the campaign is close to completion, individuals give more when they see that there are few (vs. many) donors to the campaign. We observe this result across real campaigns on a fundraising website and obtain causal evidence for this effect in two laboratory experiments. We find that this effect is driven in part by an increase in the perceived progress that one's donation makes towards reaching the campaign goal. This work identifies a counterintuitive consequence of norm-based marketing appeals and has important implications for fundraisers.

Introduction Ulcerative STIs, including syphilis, increase the risk for HIV acquisition and transmission due to the presence of ulcers/chancres that serve as a point-of-entry and exit for HIV. In Zimbabwe, diagnosis of syphilis often occurs in pregnant women who seek ANC services where syphilis testing is offered, and among men and women who seek health care for STIs. Zimbabwe’s national syphilis estimates are based on these diagnosed cases, with little information available about the prevalence of untreated syphilis among the general population. This analysis uses data from ZIMPHIA (2015–2016) to describe factors associated with active syphilis among men and women ages 15 years and older. Methods ZIMPHIA collected blood specimens for HIV and syphilis testing from 22,501 consenting individuals (ages 15 years and older). Household HIV testing used the national HIV rapid-testing algorithm with HIV-positive results confirmed at satellite laboratories using Geenius HIV-1/2 rapid test (Bio-rad, Hercules, California, USA). Point-of-care non-Treponemal and Treponemal syphilis testing was performed using Chembio’s Dual-Path Platform Syphilis Screen & Confirm Assay. Factors associated with active syphilis were explored using multiple variable, weighted logistic regression and were stratified by gender. Results The likelihood of active syphilis in HIV-positive females was 3.7 times greater in HIV-positive females than HIV-negative females (aOR: 3.7, 95% CI 2.3–5.9). Among males odds of having active syphilis was 5 times higher among those that engaged in transactional sex than those who did not have sex or transactional sex (aOR: 5.3, 95% CI 1.9–14.7), and 6 times higher if HIV positive versus negative (aOR: 5.9, 95% CI 3.0–12.0). Urban residence, province, education (highest attended), marital status, number of sex partners, consistency of condom use, pregnancy status (females), and circumcision status (males) were not significant in the adjusted model for either females or males. Conculsion HIV status was found to be the only factor associated with active syphilis in both females and males. Given the persistent link between HIV and active syphilis, it is prudent to link individuals’ diagnoses and treatments, as recommended by the WHO. Enhanced integration of STI and HIV services in health delivery points such as ANC, reproductive services, or male circumcision clinics, combined with consistent, targeted outreach to high-risk populations and their partners, may assist the MOHCC to eliminate active syphilis in Zimbabwe.

ObjectiveObsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD.MethodThe authors conducted a GWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders.ResultsAlthough no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders. Polygenic score analyses identified a significant polygenic component for OCD (p=2×10(-4)), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, Tourette's syndrome had a smaller, nonsignificant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and co-occurring Tourette's syndrome/chronic tics were included in the analysis (p=0.01).ConclusionsPrevious work has shown that Tourette's syndrome and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of these two disorders. Furthermore, OCD with co-occurring Tourette's syndrome/chronic tics may have different underlying genetic susceptibility compared with OCD alone.

Rosario Peluso,1 Francesco Caso,1 Marco Tasso,1 Vincenzo Sabbatino,1 Roberta Lupoli,2 Matteo Nicola Dario Di Minno,3 Francesco Ursini,4 Luisa Costa,1 Raffaele Scarpa1, On behalf of CaRRDs study group1Department of Clinical Medicine and Surgery, Rheumatology Research Unit, Federico II University, Naples, Italy; 2Department of Clinical Medicine and Surgery, Division of Internal Medicine, Federico II University, Naples, Italy; 3Department of Advanced Biomedical Sciences, Division of Cardiology, Federico II University, Naples, Italy; 4Internal Medicine Unit, Department of Medical Sciences, University of Ferrara, Ferrara, ItalyBackground: Psoriatic arthritis (PsA) is a chronic immune-mediated disease. It is associated with an increase in cardiovascular risk factors (obesity, hypertension, diabetes, and dyslipidemia), giving a higher risk of major adverse cardiovascular events. Patients with PsA have an increased incidence of subclinical atherosclerosis and endothelial dysfunction. The aim of this study is to perform a review of the biomarkers of subclinical atherosclerosis in patients with PsA.Methods: A search was performed in the electronic databases (PubMed, Web of Science, Scopus, and Embase) up until July 2017. Studies were considered if they included data on biomarkers of subclinical atherosclerosis in PsA, and each article was then reviewed for quality and clinical relevance. After completing the literature search, all screened literature was summarized and discussed in our study group (CaRRDs study group).Results: The initial search produced 532 abstracts, which were limited to 258 potentially relevant articles by preliminary review of the titles and by excluding review articles and case reports (n=274). A further 102 articles were deemed ineligible after examining the abstracts. Full texts of the remaining 156 articles were retrieved. Most articles were excluded because they were not relevant to the biomarkers of subclinical atherosclerosis in psoriasis and/or PsA. In the end, 54 articles were deemed eligible for this review.Conclusion: Patients with PsA showed more severe atherosclerotic disease compared with patients with only psoriasis. This may have been due to the higher systemic inflammatory burden from the combination of both diseases. In patients with PsA some molecules may be considered as markers of atherosclerotic disease, and their detection may be a prognostic marker, in addition to imaging procedures, for the development of atherosclerotic disease, and could be suitable for the management of patients with PsA.Keywords: psoriatic disease, insulin resistance, lipid profile, serum uric acid, complement C3, primary and secondary hemostasis

In order for a coaching program to truly take off in a school, the leaders need to be aware of their starting point and what they need to create or change to make the coaching impactful. This article, written by a consultant who trains coaches, includes a checklist that school leaders can use to determine their school's readiness for coaching and give action steps to take.

Post-bariatric hypoglycemia (PBH) is a potentially serious complication that may occur after bariatric surgery. Recurrent hypoglycemia may exert detrimental effects on vascular function. The aim of the present study was to evaluate endothelial function and oxygen reactive compounds in patients who experience PBH compared with controls. We performed a cross-sectional study on subjects with PBH (HYPO) and those without (NO-HYPO), detected by seven-day continuous glucose monitoring (CGM) performed at least twelve months after bariatric surgery. We enrolled 28 post-bariatric subjects (17.9% males, mean age 40.6 ± 10.7 years), with 18 in the HYPO group and 10 in the NO-HYPO group. In the two groups, we measured brachial artery flow-mediated dilation (FMD), oxidized low-density lipoproteins (oxLDL) and reactive oxygen metabolites (D-ROMs). The HYPO group had significantly lower FMD values than the NO-HYPO group (3.8% ± 3.0 vs. 10.5% ± 2.0, p < 0.001). A significant correlation was found between FMD and the time spent in hypoglycemia (rho = −0.648, p < 0.001), the number of hypoglycemic events (rho = −0.664, p < 0.001) and the mean glucose nadir (rho = 0.532, p = 0.004). The HYPO group showed significantly higher levels of D-ROMs (416.2 ± 88.7 UCARR vs. 305.5 ± 56.3 UCARR, p < 0.001) and oxLDLs (770.5 ± 49.7 µEq/L vs. 725.1 ± 51.6 µEq/L, p = 0.035) compared to the NO-HYPO group. In the multiple linear regression analysis, hypoglycemia independently predicted FMD values (β = −0.781, p < 0.001), D-ROMs (β = 0.548, p = 0.023) and oxLDL levels (β = 0.409, p = 0.031). PBH is associated with impaired endothelial function accompanied by increased oxidative stress.

Objectiveto explore the association between genetic markers and Oligoclonal Bands (OCB) in the Cerebro Spinal Fluid (CSF) of Italian Multiple Sclerosis patients.MethodsWe genotyped 1115 Italian patients for HLA-DRB1*15 and HLA-A*02. In a subset of 925 patients we tested association with 52 non-HLA SNPs associated with MS susceptibility and we calculated a weighted Genetic Risk Score. Finally, we performed a Genome Wide Association Study (GWAS) with OCB status on a subset of 562 patients. The best associated SNPs of the Italian GWAS were replicated in silico in Scandinavian and Belgian populations, and meta-analyzed.ResultsHLA-DRB1*15 is associated with OCB+: p = 0.03, Odds Ratio (OR) = 1.6, 95% Confidence Limits (CL) = 1.1-2.4. None of the 52 non-HLA MS susceptibility loci was associated with OCB, except one SNP (rs2546890) near IL12B gene (OR: 1.45; 1.09-1.92). The weighted Genetic Risk Score mean was significantly (p = 0.0008) higher in OCB+ (7.668) than in OCB- (7.412) patients. After meta-analysis on the three datasets (Italian, Scandinavian and Belgian) for the best associated signals resulted from the Italian GWAS, the strongest signal was a SNP (rs9320598) on chromosome 6q (p = 9.4×10(-7)) outside the HLA region (65 Mb).Discussiongenetic factors predispose to the development of OCB.

Annalisa Panico,1 Giovanni Messina,2,3 Gelsy Arianna Lupoli,1 Roberta Lupoli,1 Marianna Cacciapuoti,1 Fiorenzo Moscatelli,2 Teresa Esposito,3 Ines Villano,3 Anna Valenzano,2 Vincenzo Monda,3 Antonietta Messina,3 Francesco Precenzano,4 Giuseppe Cibelli,2 Marcellino Monda,3 Giovanni Lupoli1 1Department of Clinical Medicine and Surgery, University of Napoli Federico II, Naples, Italy; 2Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy; 3Department of Experimental Medicine, Second University of Naples, Naples, Italy; 4Department of Mental and Physical Health, and Preventive Medicine, Child and Adolescent Neuropsychiatry Unit, Second University of Naples, Naples, Italy Objective: Polycystic ovary syndrome (PCOS) is characterized by phenotypic heterogeneity and has a wide variety of consequences. Approximately half of women with PCOS are overweight or obese, and their obesity may be a contributing factor to PCOS pathogenesis through different mechanisms. The aim of this study was to evaluate if PCOS alone affects the patients’ quality of life and to what extent obesity contributes to worsen this disease. Design: To evaluate the impact of PCOS on health-related quality-of-life (HRQoL), 100 Mediterranean women with PCOS (group A), 50 with a body mass index (BMI) >25 kg/m2 (group A1) and 50 with BMI 25 (A1) showed a significant and more marked reduction in scores, suggesting a lower quality of life, compared with controls (B) and with normal-weight PCOS patients (A2). Conclusion: PCOS is a complex disease that alone determines a deterioration of HRQoL. The innovative use of these psychometric questionnaires in this study, in particular the PCOS questionnaire, has highlighted that obesity has a negative effect on HRQoL. It follows that a weight decrease is associated to phenotypic spectrum improvement and relative decrement in psychological distress. Keywords: polycystic ovary syndrome, obesity, normal-weight, health-related quality-of-life, psychological disturbances

Introduction: A relevant role is now emerging for nutraceuticals and specific functional foods in the treatment of dyslipidemia. The aim of this study was to evaluate the efficacy of a nutraceutical multi-target approach in subjects with moderate cardiovascular risk and to compare it with red yeast rice (RYR) treatment alone. Materials and Methods: Sixty patients with a first diagnosis of moderate dyslipidemia were included in a 6-week open-label, randomized, parallel-group controlled clinical trial and were treated with a nutraceutical supplement of Red Yeast Rice (RYR) extract containing 10 mg of monacolin k or its combination with 48 mg of an improved form of highly bioavailable resveratrol. The dosage of RYR was selected on the basis of its expected efficacy in reducing low-density lipoprotein- cholesterol also approved by the EFSA panel. All differences were assessed by Student’s t test with P values .05 are considered as statistically significant. Statistical analysis was performed by using Excel. Results: Treatment with RYR (10 mg monacolin K) led to a reduction of total cholesterol (20%) and low-density lipoprotein- cholesterol (21%). The combination with resveratrol however, compared to RYR alone significantly reduced triglyceride (-18 %) levels, systolic blood pressure (-2 %) and HOMA index (-17 %). Discussion: These results indicate that the nutraceutical supplementation of RYR associated with resveratrol not only shows lipid-lowering activity but compared to RYR treatment alone significantly also ameliorates other metabolic parameters. Thus, may represent a valid and safe approach, especially in people with moderate cardiovascular risk, in which a pharmacologic intervention may not be appropriate.

Many reports in different populations have demonstrated linkage of the 10q24–q26 region to schizophrenia, thus encouraging further analysis of this locus for detection of specific schizophrenia genes. Our group previously reported linkage of the 10q24–q26 region to schizophrenia in a unique, homogeneous sample of Arab-Israeli families with multiple schizophrenia-affected individuals, under a dominant model of inheritance. To further explore this candidate region and identify specific susceptibility variants within it, we performed re-analysis of the 10q24-26 genotype data, taken from our previous genome-wide association study (GWAS) (Alkelai et al, 2011). We analyzed 2089 SNPs in an extended sample of 57 Arab Israeli families (189 genotyped individuals), under the dominant model of inheritance, which best fits this locus according to previously performed MOD score analysis. We found significant association with schizophrenia of the TCF7L2 gene intronic SNP, rs12573128, (p = 7.01×10−6) and of the nearby intergenic SNP, rs1033772, (p = 6.59×10−6) which is positioned between TCF7L2 and HABP2. TCF7L2 is one of the best confirmed susceptibility genes for type 2 diabetes (T2D) among different ethnic groups, has a role in pancreatic beta cell function and may contribute to the comorbidity of schizophrenia and T2D. These preliminary results independently support previous findings regarding a possible role of TCF7L2 in susceptibility to schizophrenia, and strengthen the importance of integrating linkage analysis models of inheritance while performing association analyses in regions of interest. Further validation studies in additional populations are required.

Mitochondrial deficiencies with unknown causes have been observed in schizophrenia (SZ) and bipolar disorder (BD) in imaging and postmortem studies. Polymorphisms and somatic mutations in mitochondrial DNA (mtDNA) were investigated as potential causes with next generation sequencing of mtDNA (mtDNA-Seq) and genotyping arrays in subjects with SZ, BD, major depressive disorder (MDD), and controls. The common deletion of 4,977 bp in mtDNA was compared between SZ and controls in 11 different vulnerable brain regions and in blood samples, and in dorsolateral prefrontal cortex (DLPFC) of BD, SZ, and controls. In a separate analysis, association of mitochondria SNPs (mtSNPs) with SZ and BD in European ancestry individuals (n = 6,040) was tested using Genetic Association Information Network (GAIN) and Wellcome Trust Case Control Consortium 2 (WTCCC2) datasets. The common deletion levels were highly variable across brain regions, with a 40-fold increase in some regions (nucleus accumbens, caudate nucleus and amygdala), increased with age, and showed little change in blood samples from the same subjects. The common deletion levels were increased in the DLPFC for BD compared to controls, but not in SZ. Full mtDNA genome resequencing of 23 subjects, showed seven novel homoplasmic mutations, five were novel synonymous coding mutations. By logistic regression analysis there were no significant mtSNPs associated with BD or SZ after genome wide correction. However, nominal association of mtSNPs (p

Background Bempedoic acid (BA) is a novel lipid‐lowering drug. We performed a systematic review and meta‐analysis on efficacy and safety of BA compared with standard treatment in patients with hypercholesterolemia. Methods and Results Studies were systematically searched in the PubMed, Web of Science, Scopus, and EMBASE databases. Efficacy outcome was represented by percentage changes (mean difference [MD] with pertinent 95% CIs) in total cholesterol, low‐density lipoprotein cholesterol, triglycerides, high‐density lipoprotein cholesterol, apolipoprotein B, non–high‐density lipoprotein cholesterol, and hs‐CRP (high‐sensitivity C‐reactive protein) in BA patients and controls. Seven studies were included (2767 BA‐treated patients and 1469 controls), showing a more significant reduction in low‐density lipoprotein cholesterol (MD, −17.5%; 95% CI, −22.9% to −12.0%), total cholesterol (MD, −10.9%; 95% CI, −13.3% to −8.5%), non–high‐density lipoprotein cholesterol (MD, −12.3%; 95% CI, −15.3% to −9.20%), apolipoprotein B (MD, −10.6%; 95% CI, −13.2% to −8.02%), and hs‐CRP (MD, −13.2%; 95% CI, −16.7% to −9.79%) in BA‐treated patients compared with controls. Results were confirmed when separately analyzing studies on patients with high cardiovascular risk, studies on statin‐intolerant patients, and studies on patients with hypercholesterolemia on maximally tolerated lipid‐lowering therapy. BA‐treated subjects reported a higher rate of treatment discontinuation caused by adverse effects, of gout flare, and of increase in uric acid compared with controls. On the other hand, BA‐treated patients showed a lower incidence of new‐onset diabetes mellitus than controls. Conclusions BA is associated with a significant reduction in low‐density lipoprotein cholesterol, total cholesterol, non–high‐density lipoprotein cholesterol, apolipoprotein B, and hs‐CRP compared with standard treatment. Documented efficacy is accompanied by an acceptable safety profile.

As β-lactams are reconsidered for the treatment of tuberculosis (TB), their targets are assumed to be peptidoglycan transpeptidases, as verified by adduct formation and kinetic inhibition of Mycobacterium tuberculosis (Mtb) transpeptidases by carbapenems active against replicating Mtb. Here, we investigated the targets of recently described cephalosporins that are selectively active against non-replicating (NR) Mtb. NR-active cephalosporins failed to inhibit recombinant Mtb transpeptidases. Accordingly, we used alkyne analogs of NR-active cephalosporins to pull down potential targets through unbiased activity-based protein profiling and identified over 30 protein binders. None was a transpeptidase. Several of the target candidates are plausibly related to Mtb’s survival in an NR state. However, biochemical tests and studies of loss of function mutants did not identify a unique target that accounts for the bactericidal activity of these beta-lactams against NR Mtb. Instead, NR-active cephalosporins appear to kill Mtb by collective action on multiple targets. These results highlight the ability of these β-lactams to target diverse classes of proteins.

ObjectivesThe main objectives of the study are to estimate HIV prevalence, active syphilis prevalence, and correlates of co-infection with HIV in Zambia, among recently sexually active individuals aged 15 to 59 years old.MethodsWe used data from the 2016 Zambia Population-based HIV Impact Assessment (ZAMPHIA), a national household survey that included biomarker testing for HIV and syphilis. Chembio DPP® Syphilis Screen and Confirm Assay was used to distinguish between active and older syphilis infections. This is the first time Chembio DPP® has been used in a national survey. Log-binominal modelling was utilized to understand the risk of acquiring HIV/active syphilis co-infection using select socio-demographic and sexual behavior variables. Multivariable analysis compared those with co-infection and those with no infection. All reported results account for the complex survey design and are weighted.ResultsA total of 19,114 individuals aged 15-59 years responded to the individual interview and had a valid syphilis and/or HIV test. The prevalence for those sexually active in the 12 months preceding ZAMPHIA 2016 was 3.5% and 13% for active syphilis and HIV, respectively. The prevalence of HIV/active syphilis co-infection was 1.5%. Factors associated with higher prevalence of co-infection versus no infection among females included, but were not limited to, those living in urban areas (adjusted prevalence ratio (aPR) = 3.0, 95% CI = 1.8, 4.8), those had sexual intercourse before age 15 years (aPR = 1.8, 95% CI = 1.1, 2.9), and those who had two or more sexual partners in the 12 months preceding the survey (aPR = 2.7, 95% CI = 1.6, 4.7).ConclusionThese findings show high prevalence for both mono-infection with HIV and syphilis, as well as co-infection with HIV/active syphilis in Zambia. There is a need for better screening and partner services, particularly among those engaging in high-risk sexual behaviors (e.g., engaging in transactional sex).

Introduction Tinnitus, which is considered the third worst symptom for humans, is a common complaint among people living with hearing loss and may negatively affect the quality of life of those who have it. Objective To analyze the perception of the handicap in patients with tinnitus and hearing loss as well as the possible associations between the variables hearing loss, loudness, onset, frequency and annoyance by tinnitus, and the correlation between the visual analogue scale (VAS) and the Tinnitus Handicap Inventory (THI). Methods A total of 30 patients with complaints of tinnitus and the presence of sensorineural hearing impairment were selected for this cross-sectional, observational, and descriptive study. The loudness of the tinnitus was measured by a VAS and classified as mild, moderate, or severe. The THI was classified as slight, mild, moderate, severe, and catastrophic. Data were submitted to statistical analysis using the Fisher exact test and Spearman correlation coefficient. Results Eleven male (36.7%) and 19 female (63.3%) subjects with a mean age of 56.5 years old were evaluated. There was no significant association between loudness, annoyance, time and frequency of tinnitus, nor between hearing loss and tinnitus. There was a significant association between the variables hearing loss and loudness, and a weak correlation between VAS and THI. Conclusion Tinnitus has a practical impact in the lives of patients with hearing loss in terms of catastrophic, functional, and emotional aspects, regardless of loudness, frequency, or time of onset. Hearing loss was a factor that had an impact on the loudness of tinnitus. There was no statistically significant correlation between VAS and THI.