HIV pre-exposure prophylaxis during the SARS-CoV-2 pandemic: Results from a prospective observational study in Germany.

Aims: Since 2017, HIV pre-exposure prophylaxis (PrEP) care has been provided through an intersectoral collaboration at WIR (Walk-in-Ruhr, Center for Sexual Health and Medicine, Bochum, Germany). The aim of this study was to establish possible impact of COVID-restrictions on the sexual behavior of PrEP users in North Rhine-Westphalia. Methods: The current PrEP study collected data of individuals using PrEP, their sexual behavior and sexually transmitted infections (STIs) before (each quarter of year 2018) and during the COVID-19 pandemic (each quarter of year 2020). Results: During the first lockdown in Germany from mid-March until May 2020, PrEP-care appointments at WIR were postponed or canceled. Almost a third of PrEP users had discontinued their PrEP intake in the 2nd quarter of 2020 due to alteration of their sexual behavior. The number of sexual partners decreased from a median of 14 partners in the previous 6 months in 1st quarter of 2020, to 7 partners in 4th quarter of 2020. Despite such a significant reduction in partner number during the pandemic in comparison to the pre-pandemic period, a steady rate of STIs was observed among PrEP users in 2020. Conclusion: The SARS-CoV-2-pandemic has impacted PrEP-using MSM in North Rhine-Westphalia with respect to their PrEP intake regimen and sexual behavior in 2020. Our study revealed a steady rate of STI among PrEP users even during the pandemic, thus highlighting the importance of ensuring appropriate HIV/STI prevention services in times of crisis.

Initial investigation of associations between feeding practices, eating behaviours, and weight status in Vietnamese children using modified questionnaires.

AIMS: This cross-sectional study aims to extend the preliminary validation of the Feeding Practices and Structure Questionnaire (FPSQ) and Children's Eating Behaviour Questionnaire (CEBQ) in the Vietnamese context by examining associations between maternal feeding practices, child eating behaviours, and child weight status. METHODS: Modified versions of the FPSQ and CEBQ were used to measure maternal feeding practices and child eating behaviours, respectively, in a sample of Vietnamese mothers of children within the age range of two to five years (n = 100). Children's weight-for-height z-scores (WHZs) were calculated using weight and height measurements obtained by clinicians. Pearson's correlation coefficients were used to examine bivariate associations between maternal feeding practices, child eating behaviours, and child WHZs. Significant variables were then entered into a multivariable regression model. RESULTS: Child WHZs were associated with maternal persuasive feeding, and child slowness in eating, enjoyment of food/food responsiveness, and emotional undereating, but in multivariable regression analysis, only persuasive feeding (ß = -0.44, p = 0.027) and slowness in eating (ß = -0.39, p = 0.036) contributed significantly to the model. CONCLUSIONS: The findings provide some evidence of construct validity for the modified questionnaires. Potential implications of dietary-related behaviours on weight status in preschool-aged children in Viet Nam are evident. However, further validation and analysis in larger datasets must be undertaken in order to examine these associations with increased certainty.

Influence of dietary supplementation of short-chain fatty acid sodium propionate in people living with HIV (PLHIV).

BACKGROUND: Non-AIDS-associated chronic diseases in HIV+ patients have been on the rise since the advent of antiretroviral therapy. Especially cardiovascular diseases and disruption in the gastrointestinal tract have limited health-related quality of life (QoL). Several of those complications have been associated with chronic systemic inflammation. Short-chain fatty acids (SCFA), with propionate as one of the major compounds, have been described as an important link between gut microbiota and the immune system, defining the pro- and the anti-inflammatory milieu through direct and indirect regulation of T-cell homeostasis. The effects of dietary supplementation of sodium propionate (SP) in people living with HIV (PLHIV) have not yet been investigated prior to this study. OBJECTIVES: To investigate the impact of SP uptake among PLHIV and its relevance to improve QoL, the study aimed to investigate metabolic, immunological, microbiome and patient-reported QoL-related changes post-SP supplementation with follow-up. METHODS: A prospective, non-randomized, controlled, monocentric interventional study was conducted in WIR, Center for Sexual Health and Medicine, in Bochum, Germany. 32 HIV+ patients with unaltered ART-regimen in the last three months were included. Participants were given SP for a duration of 12 weeks in the form of daily oral supplementation and were additionally followed-up for another 12 weeks. RESULTS: The supplementation of SP was well tolerated. We found an improvement in lipid profiles and long-term blood glucose levels. A decrease in pro-inflammatory cytokines and a depletion of effector T cells was observed. Regulatory T cells and IL-10 decreased. Furthermore, changes in taxonomic composition of the microbiome during follow-up were observed and improvement of items of self-reported life-quality assessment. CONCLUSION: Taken together, the beneficial impact of SP in PLHIV reflects its potential in improving metabolic parameters and modulating pro-inflammatory immune responses. Thus, possibly reducing the risk of cardiovascular disorders and facilitating long-term improvement of the gut flora.

Preliminary exploration of the use of the Children's Eating Behaviour Questionnaire (CEBQ) and Feeding Practices and Structure Questionnaire (FPSQ) in Vietnamese mothers.

OBJECTIVE: This preliminary pilot study aims to explore the use of the Feeding Practices and Structure Questionnaire (FPSQ) and Children's Eating Behaviour Question (CEBQ) in a sample of Vietnamese mothers. SUBJECTS/METHODS: Cross-sectional data from the FPSQ and CEBQ were collected from a convenience sample of mothers (n = 102) who attended the Ho Chi Minh City Nutrition Centre in Viet Nam. Mothers had at least one child aged 2-5 years. The reliability of the questionnaire subscales was tested using Cronbach's alpha coefficients. Face validity was assessed using dialogue from a translation-back-translation procedure undertaken by an expert committee, and cognitive interviews conducted in a subsample of mothers (n = 6). Based on these findings, exploratory factor analyses (EFAs) were performed to assess the underlying structures of both questionnaires in this sample. RESULTS: Cronbach's alpha coefficients for the original questionnaires ranged from 0.23 to 0.92. Limitations in translation and comprehension of items surfaced, warranting modifications of the questionnaires, which were subsequently examined using EFA. EFA of the FPSQ and CEBQ revealed a six-factor structure with 23 items, and a six-factor structure with 27 items, respectively, which were interpretable solutions for this sample. Cronbach's alpha coefficients were >0.70 for all subscales in the revised questionnaires. CONCLUSIONS: Modified versions of the FPSQ and CEBQ are proposed for use in Viet Nam. However, prior to their use, further reliability and validity testing must be undertaken in larger samples, including assessment of test-retest reliability and construct validity, as well as confirmatory factor analysis to verify the proposed factor structures.

Sexual behaviour, STI knowledge and Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) prevalence in an asymptomatic cohort in Ruhr-area, Germany: PreYoungGo study.

BACKGROUND AND OBJECTIVES: STIs present a significant threat to individual and public health, disproportionately affecting youth. The study aimed to evaluate (a) the prevalence of asymptomatic Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections among youth using a rapid assay platform, (b) the participants' sexual behaviour and STI knowledge, (c) the utility of the rapid assay in reducing diagnosis-to-treatment time. METHODS: In this study, 272 subjects (14-31 years) were included between 12/2016 and 7/2018. A questionnaire was used to collect sociodemographic data, sexual behaviour and STI knowledge. Prevalence of CT and NG infections were tested from oral, vaginal and anal swabs for women and oral, anal swabs and urine for men, using the Cepheid Xpert® CT/NG assay. Time intervals between (i) test to the time the patient were informed of the result (turn around time - TAT) and (ii) test to therapy initiation was documented. RESULTS: Of the 272 subjects (48.9% female, 48.9% male, undisclosed 2.2%), 56.6 % reported university education. 46.6% were men who have sex with men (MSM), and 47.4% of women and 63.1% of men had anal intercourse. 59.9% had previously been tested for HIV, while only 39.7% had for CT, 20.6% for NG. Among these asymptomatic youth 7.7% were positive for CT and 5.5% for NG. The localization of CT were 3.7% genital, 5.5% anal and 2.2% oral, while the corresponding localization of NG were 0.4%, 2.9%, 4.4% respectively. 91.8% of the participants were informed of a positive result within 24 h with a median TAT of 03:09 h. 73.3% initiated therapy within 24 h, with a median time from testing to therapy initiation being 06:50 h. CONCLUSION: Asypmtomatic CT and NG infections are common and often not tested in persons at risk. The Cepheid Xpert® CT/NG assay is an effective strategy as it reduces STI diagnosis-to-treatment time to less than a day.

Age specific evaluation of sexual behavior, STI knowledge and infection among asymptomatic adolescents and young adults.

OBJECTIVES: Adolescents and young adults account for 50% of new infections with sexually transmitted infection (STI), while representing only 25% of the sexually active population. An evaluation of sexual behavior, STI knowledge and infection among youth of different age groups is relevant to formulate effective sexual health strategies. METHODS: In this monocentric, open, prospective cross-sectional study, 268 asymptomatic subjects (14-30 years) were partitioned into three cohorts I: 14-19 (n=42), II: 20-25 (n=147) and III: 25-30 (n=79) years. A comparative analysis of their sexual behavior and STI knowledge was performed using a 21-item questionnaire at the WIR-Center for Sexual Health and Medicine. Prevalence of chlamydia and gonococcal infections were tested, using the Cepheid Xpert® CT/NG assay. RESULTS: The three age-specific cohorts showed statistically significant differences in their relationship status, their sexual contacts and the number of life-time sexual partners. Independent of age, men who have sex with men had greater number of sexual partners across all age groups. Although >95% of participants were aware of HIV in all age groups, the corresponding awareness of non-HIV STI was consistently lower in cohort I. The awareness of trichomonas, mycoplasma and candida in particular was <50% across all agedemographies. Chlamydia screening remains poor despite current chlamydia infection among cohort I, II & III being 7.1%, 5.4%, & 11.4% respectively. CONCLUSION: Our study demonstrates a demographic divide in the knowledge on most frequent STI apart from HIV. Current education, screening and vaccination programs for STI among the younger demographic should be improved.

Young Children Display Diurnal Patterns of Salivary IgA and Alpha-Amylase Expression Which Are Independent of Food Intake and Demographic Factors.

BACKGROUND: Salivary alpha-amylase (sAA) and salivary immunoglobulin A (sIgA) have been proposed as biomarkers for research on the mucosal immune system and on stress. Expression of both sAA and sIgA has been described to follow opposing diurnal patterns. This knowledge is crucial for the interpretation of studies using these biomarkers. AIM: It was hypothesized that sAA and sIgA display diurnal patterns in children and that this is independent of food intake or demographic factors. METHODS: Whole saliva was collected from 78 healthy children (15-39 months old) in the morning and evening for two random nonconsecutive days. The samples have been analysed for sAA and sIgA. The total daily energy, fat, saturated fat, protein, carbohydrate and fibre, mineral, and vitamin consumption were analysed based on the two-day weighed food records collected by the parents. RESULTS: It was demonstrated that most young children followed the diurnal pattern when sAA increased and sIgA decreased from morning to evening. No correlation was observed between the intake of any of the nutrients and morning or evening values for both salivary proteins. The morning and evening values of sAA and sIgA did not correlate with age, sex, Asian ethnicity, and BMI of the children. CONCLUSION: Diurnal patterns of sAA and sIgA exist in healthy young children and are not affected by their nutrient intake, sex, Asian ethnicity, and BMI. Scientists including sIgA and sAA in their research must consider the diurnal pattern that these markers exhibit and design the study accordingly.

Carbon-nanotube-on-waveguide thermo-optic tuners.

We demonstrate on-waveguide thermo-optic tuners based on solution-processed metallic carbon nanotubes (CNTs) on silicon-on-insulator (SOI) and silicon nitride (SiN) microring resonators operating around 1550 nm. On SOI microring resonators using planarized wire waveguides, a thermo-optic power efficiency of 29 mW/FSR and a thermal transient of 1.3 µs are achieved. The heater is shown to be more power-efficient than conventional metal heaters and has lower thermal transient than both metal heaters and graphene-based heaters. On SiN microring resonators using rib waveguides, improvement in power efficiency with an increase in coverage of CNTs is demonstrated, indicating localized heating using the CNTs; this is favorable for low thermal cross-talk. An optimal power efficiency of 142 mW/FSR and a thermal transient of 5.8 µs are achieved.

Antibacterial drug development: challenges, recent developments, and future considerations.

A decline in antibacterial drug development coupled with emerging bacterial resistance has resulted in limited treatment options. One of the challenges facing antibacterial drug development is appropriate clinical trial designs. Noninferiority trials are appropriate to study new antibacterial drugs for the treatment of serious diseases; superiority trials can be challenging and cannot be the only acceptable trial design to study antibacterial drugs. Our efforts must continue to make new therapies available to meet patient needs.

Choice and doses of antibacterial agents for cement spacers in treatment of prosthetic joint infections: review of published studies.

BACKGROUND: Addition of antibacterial drugs to interim antibacterial cement spacers (ACSs) is considered to be standard of care for surgical revision in prosthetic joint infections (PJIs). We reviewed published studies evaluating the choice and doses of antibacterials in spacers. METHODS: We conducted a PubMed search of all clinical study reports evaluating the use of ACSS in a 2-stage hip or knee arthroplasty for treatment of PJI (1988 through August 2011). The trial design, antibacterials used, and end points studied were analyzed. RESULTS: No randomized trials were found comparing either ACSs with different concentrations of antibacterials or ACSs with or without antibacterials. Most of the studies were uncontrolled and used various time points to evaluate the outcome. Twenty publications that reported doses of antibacterials in spacers and had a follow-up of ≥ 24 months after the second stage were selected for review. Most ACSs included vancomycin and aminoglycosides. The doses of aminoglycosides and vancomycin ranged from 0.25 to 4.8 g and from 1 to 4 g, respectively, per 4 g of cement. No association between reported eradication of the infection and antibacterial load was found. CONCLUSIONS: Published data do not allow evaluation of whether antibacterials in temporary cement spacers provide additional benefits in the treatment of PJI, compared with systemic antibacterials, and are not sufficient to support recommendations on dosages. Complications of ACSs have not been consistently analyzed. Prospective randomized trials comparing spacers with and without antibacterials or spacers with different loads of antibacterials are needed to evaluate the safety and efficacy of ACSs.

Product quality of parenteral vancomycin products in the United States.

In response to concerns raised about the quality of parenteral vancomycin products, the U.S. Food and Drug Administration (FDA) is investigating the product quality of all FDA-approved parenteral vancomycin products available in the United States. Product quality was evaluated independently at two FDA Office of Testing and Research (FDA-OTR) sites. In the next phase of the investigation, being done in collaboration with the National Institute of Allergy and Infectious Diseases, the in vivo activity of these products will be evaluated in an appropriate animal model. This paper summarizes results of the FDA investigation completed thus far. One site used a validated ultrahigh-pressure liquid chromatography method (OTR-UPLC), and the second site used the high-performance liquid chromatography (HPLC) method for related substances provided in the British Pharmacopeia (BP) monograph for vancomycin intravenous infusion. Similar results were obtained by the two FDA-OTR laboratories using two different analytical methods. The products tested had 90 to 95% vancomycin B (active component of vancomycin) by the BP-HPLC method and 89 to 94% vancomycin by OTR-UPLC methods. Total impurities were 5 to 10% by BP-HPLC and 6 to 11% by OTR-UPLC methods. No single impurity was >2.0%, and the CDP-1 level was ≤ 2.0% across all products. Some variability in impurity profiles of the various products was observed. No adverse product quality issues were identified with the six U.S. vancomycin parenteral products. The quality parameters of all parenteral vancomycin products tested surpassed the United States Pharmacopeia acceptance criteria. Additional testing will characterize in vivo performance characteristics of these products.

The interaction between caveolin-1 and Rho-GTPases promotes metastasis by controlling the expression of alpha5-integrin and the activation of Src, Ras and Erk.

Proteins containing a caveolin-binding domain (CBD), such as the Rho-GTPases, can interact with caveolin-1 (Cav1) through its caveolin scaffold domain. Rho-GTPases are important regulators of p130(Cas), which is crucial for both normal cell migration and Src kinase-mediated metastasis of cancer cells. However, although Rho-GTPases (particularly RhoC) and Cav1 have been linked to cancer progression and metastasis, the underlying molecular mechanisms are largely unknown. To investigate the function of Cav1-Rho-GTPase interaction in metastasis, we disrupted Cav1-Rho-GTPase binding in melanoma and mammary epithelial tumor cells by overexpressing CBD, and examined the loss-of-function of RhoC in metastatic cancer cells. Cancer cells overexpressing CBD or lacking RhoC had reduced p130(Cas) phosphorylation and Rac1 activation, resulting in an inhibition of migration and invasion in vitro. The activity of Src and the activation of its downstream targets FAK, Pyk2, Ras and extracellular signal-regulated kinase (Erk)1/2 were also impaired. A reduction in α5-integrin expression, which is required for binding to fibronectin and thus cell migration and survival, was observed in CBD-expressing cells and cells lacking RhoC. As a result of these defects, CBD-expressing melanoma cells had a reduced ability to metastasize in recipient mice, and impaired extravasation and survival in secondary sites in chicken embryos. Our data indicate that interaction between Cav1 and Rho-GTPases (most likely RhoC but not RhoA) promotes metastasis by stimulating α5-integrin expression and regulating the Src-dependent activation of p130(Cas)/Rac1, FAK/Pyk2 and Ras/Erk1/2 signaling cascades.

Inverse association of p16 INK4a and p14 ARF methylation of the CDKN2a locus in different Gleason scores of prostate cancer.

BACKGROUND: Promoter hypermethylation is an important epigenetic mechanism in the regulation of several key modulators of prostate carcinoma progression. Recent studies suggest that the polycomb-group (PcG) protein BMI1 may have an impact on epigenetic regulation of several targets, including the CDKN2a locus. METHODS: In this study, we investigated the association of BMI1 expression, promoter methylation of CDKN2a (p16(INK4a) and p14(ARF)) and TMS1 with pathological variables (Gleason score, TNM stage, perineural invasion) in prostate cancer (PCa). RESULTS: Methylation of p16(INK4a) and p14(ARF) revealed an inverse association with Gleason score 7b and Gleason score 6. No significant association could be demonstrated for BMI1 -overexpression and promoter methylation of p16(INK4a), p14(ARF) and TMS1 as well as pT category. CONCLUSIONS: Our data suggest that the CDKN2a locus is a switch in PCa with methylation of p16(INK4a) being a marker for more aggressive tumours of Gleason score 7b, but no association with BMI overexpression was observed.

A comparison of two screening methods to determine the validity of 24-h food and drink records in children and adolescents.

BACKGROUND/OBJECTIVES: Dietary assessment in humans is hampered by the phenomena of under and overreporting of energy intake, when food records are used to evaluate habitual dietary intake. Different methods to evaluate mis-reporting have been proposed using cut-offs derived from estimates of reported energy intake and basal metabolic rate, or, from predictions of total energy expenditure. This study compares the effect of using two different cut-off approaches to screen food records for validity, completed by a large cohort of Australian children (n=2460), from Grades 1, 5 and 10 (aged 5-17 years). SUBJECTS/METHODS: Energy intake was calculated from 24-h food and drink records for each child. These data were screened using the Goldberg and McCrory cut-offs. The effect of using these two cut-offs on the collected dataset was explored by considering the mean and standard deviation of energy intake in each year level before and after the cut-offs were applied. RESULTS: The use of the Goldberg cut-off resulted in 9% of the total cohort being classified as underreporters, with 60% of these subjects being in Grade 10. The McCrory cut-offs revealed that overall, 22% of the total cohort underreported EI. 33.3% of Grade 1 children were classified as overreporters with this value falling to about 20% of Grade 10 children, while 10-15% of Grade 1 children underreported, with this figure rising to about 30% in Grade 10. CONCLUSIONS: Both the Goldberg and McCrory approaches have their advantages and disadvantages, and we suggest that consideration should be given to the reason for screening data before a particular approach is used, with recognition that these methods do differ in their aims and outcomes. The McCrory method consistently classified a greater number of children as underreporters.

Overview of recent studies of community-acquired pneumonia.

All recent studies of antibacterial drugs for the indication of community-acquired pneumonia submitted to the US Food and Drug Administration have been designed as noninferiority studies. We provide a summary of results of 7 recent clinical studies of oral antibacterial drugs for treatment of community-acquired pneumonia. In these 7 studies, the majority of patients enrolled had Pneumonia Patient Outcomes Research Team scores of I or II. The percentage of randomized subjects with pathogens identified at baseline ranged from 47% to 76%, and the percentage of subjects with Streptoccocus pneumoniae isolated at baseline ranged from approximately 6% to 20%. The primary end point in these studies was clinical cure, assessed 7-21 days after completion of therapy. Clinical cure rates were >80% in the intent-to-treat populations and >90% in the per-protocol populations. We also briefly summarize the results from several recently submitted clinical studies of intravenously administered antibacterial drugs for treatment of community-acquired pneumonia, in which we found similar results.

Historical and regulatory perspectives on the treatment effect of antibacterial drugs for community-acquired pneumonia.

A noninferiority margin based on the treatment effect of antibacterial drugs is required for noninferiority studies of community-acquired pneumonia. A quantitative estimate of treatment effect is generally determined from placebo-controlled trials, but, since the mid-to-late 1930s, no studies have compared outcomes for patients who received placebo (or no specific therapy) with those for patients who received an antibacterial drug for treatment of community-acquired pneumonia. In this article, early controlled studies, as well as observational data, are reviewed, and the beneficial effect of antibacterial drugs on mortality rates among patients with pneumococcal pneumonia is demonstrated. However, because these data were obtained in the early 20th century, several important factors have changed, including patient populations, the etiological agents of pneumonia, and medical standards of care. Thus, the applicability of these studies to the determination of a noninferiority margin for contemporary trials for community-acquired pneumonia remains in question.

Identification of functional genes during Fas-mediated apoptosis using a randomly fragmented cDNA library.

We describe a general strategy for the identification of functional genes that, when downregulated, result in a selectable phenotype. This strategy is based on expression selection of cDNA fragments that counteract their cognate genes. A cDNA library containing random fragments expressed in human HepG2, A375 and CLS-354 cells was used to identify functional genes whose inhibition conferred resistance to Fas-induced apoptosis. Thirty-five clones were isolated, 28 of which were derived from unknown genes, that tagged 19 individual genes and 7 of which referred to known genes that tagged the apoptosis-related protein (APR)-1, -2 and indoleamine-pyrrole 2,3,-dioxygenase (IDO). The ability of APR-1-, -2- and IDO-derived antisense RNAs to induce resistance to Fas in HepG2, A375 and CLS-354 cells suggested that APR-1, -2 and IDO genes are involved in the machinery of Fas-mediated apoptosis. Our gene discovery strategy provides a generally applicable procedure to identify functional genes that interfere with apoptosis, and may therefore be clinically relevant for tumor therapy.