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[This corrects the article DOI: 10.1371/journal.pone.0266026.].

Antimicrobials, such as antibiotics or antivirals are medications employed to prevent and treat infectious diseases in humans, animals, and plants. Antimicrobial Resistance occurs when bacteria, viruses, and parasites no longer respond to these medicines. This resistance renders antibiotics and other antimicrobial drugs ineffective, making infections challenging or impossible to treat. This escalation in drug resistance heightens the risk of disease spread, severe illness, disability, and mortality. With datasets now containing hundreds or even thousands of pathogen genomes, machine learning techniques are on the rise for predicting antibiotic resistance in pathogens, prediction based on gene content and genome composition. Aim of this work is to combine and incorporate machine learning methods on bacterial genomic data to predict antimicrobial resistance, we will focus on the case of Klebsiella pneumoniae in order to support clinicians in selecting appropriate therapy. [ABSTRACT FROM AUTHOR]

In this study, we have compared frequencies, phenotype, function and metabolic requirements of B cells isolated from the breast and abdominal subcutaneous adipose tissue (AT) of women with obesity who underwent weight reduction surgeries. Results show that B cells from the abdominal AT are more inflammatory than those from the breast, characterized by higher frequencies of inflammatory B cell subsets and higher expression of RNA for inflammatory markers associated with senescence. Secretion of autoimmune antibodies is also higher in the abdominal AT as compared to the breast, and is associated with higher frequencies of autoimmune B cells with the membrane phenotype CD21lowCD95+ B cells expressing the transcription factor T-bet. Moreover, glucose uptake is higher in B cells from the abdominal AT as compared to the breast, thereby suggesting a better capacity to perform glycolysis, needed to support intrinsic B cell inflammation and autoimmune antibody secretion.

Age and gender differences are prominent in the temperament literature, with the former particularly salient in infancy and the latter noted as early as the first year of life. This study represents a meta-analysis utilizing Infant Behavior Questionnaire-Revised (IBQ-R) data collected across multiple laboratories (N = 4438) to overcome limitations of smaller samples in elucidating links among temperament, age, and gender in early childhood. Algorithmic modeling techniques were leveraged to discern the extent to which the 14 IBQ-R subscale scores accurately classified participating children as boys (n = 2,298) and girls (n = 2,093), and into three age groups: youngest (< 24 weeks; n = 1,102), mid-range (24 to 48 weeks; n = 2,557), and oldest (> 48 weeks; n = 779). Additionally, simultaneous classification into age and gender categories was performed, providing an opportunity to consider the extent to which gender differences in temperament are informed by infant age. Results indicated that overall age group classification was more accurate than child gender models, suggesting that age-related changes are more salient than gender differences in early childhood with respect to temperament attributes. However, gender-based classification was superior in the oldest age group, suggesting temperament differences between boys and girls are accentuated with development. Fear emerged as the subscale contributing to accurate classifications most notably overall. This study leads infancy research and meta-analytic investigations more broadly in a new direction as a methodological demonstration, and also provides most optimal comparative data for the IBQ-R based on the largest and most representative dataset to date.

Barbiturates are proposed as a second/third line treatment for intracranial hypertension in traumatic brain injury (TBI) patients, but the literature remains uncertain regarding their benefit/risk balance. We aimed to evaluate the impact of barbiturates therapy in TBI patients with early intracranial hypertension on the intensive care unit (ICU) survival, the occurrence of ventilator-associated pneumonia (VAP), and the patient's functional status at three months. We used the French AtlanREA prospective cohort of trauma patients. Using a propensity score-based methodology (inverse probability of treatment weighting), we compared patients having received barbiturates within the first 24 hours of admission (barbiturates group) and those who did not (control group). We used cause-specific Cox models for ICU survival and risk of VAP, and logistic regression for the 3-month Glasgow Outcome Scale (GOS) evaluation. Among the 1396 patients with severe trauma, 383 had intracranial hypertension on admission and were analyzed. Among them, 96 (25.1%) received barbiturates. The early use of barbiturates was significantly associated with increased ICU mortality (HR = 1.85, 95%CI 1.03-3.33). However, barbiturates treatment was not significantly associated with VAP (HR = 1.02, 95%CI 0.75-1.41) or 3-month GOS (OR = 1.67, 95%CI 0.84-3.33). Regarding the absence of relevant clinical trials, our results suggest that each early prescription of barbiturates requires a careful assessment of the benefit/risk ratio.

SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus-2), cause of COVID-19 (Coronavirus Disease of 2019), represents a significant risk to people living with pre-existing conditions associated with exacerbated inflammatory responses and consequent dysfunctional immunity. In this paper, we have evaluated the influence of obesity, a condition associated with chronic systemic inflammation, on the secretion of SARS-CoV-2-specific IgG antibodies in the blood of COVID-19 patients. Our hypothesis is that obesity is associated with reduced amounts of specific IgG antibodies. Results have confirmed our hypothesis and have shown that SARS-CoV-2 IgG antibodies are negatively associated with Body Mass Index (BMI) in COVID-19 obese patients, as expected based on the known influence of obesity on humoral immunity. Antibodies in COVID-19 obese patients are also negatively associated with serum levels of pro-inflammatory and metabolic markers of inflammaging and pulmonary inflammation, such as SAA (serum amyloid A protein), CRP (C-reactive protein), and ferritin, but positively associated with NEFA (nonesterified fatty acids). These results altogether could help to identify an inflammatory signature with strong predictive value for immune dysfunction. Inflammatory markers identified may subsequently be targeted to improve humoral immunity in individuals with obesity and in individuals with other chronic inflammatory conditions.

In this study, we have compared frequencies, phenotype, function and metabolic requirements of B cells isolated from the breast and abdominal subcutaneous adipose tissue (AT) of women with obesity who underwent weight reduction surgeries. Results show that B cells from the abdominal AT are more inflammatory than those from the breast, characterized by higher frequencies of inflammatory B cell subsets and higher expression of RNA for inflammatory markers associated with senescence. Secretion of autoimmune antibodies is also higher in the abdominal AT as compared to the breast, and is associated with higher frequencies of autoimmune B cells with the membrane phenotype CD21lowCD95+ B cells expressing the transcription factor T-bet. Moreover, glucose uptake is higher in B cells from the abdominal AT as compared to the breast, thereby suggesting a better capacity to perform glycolysis, needed to support intrinsic B cell inflammation and autoimmune antibody secretion. [ABSTRACT FROM AUTHOR]

The visual exploration and analysis of biomolecular networks is of paramount importance for identifying hidden and complex interaction patterns among proteins. Although many tools have been proposed for this task, they are mainly focused on the query and visualization of a single protein with its neighborhood. The global exploration of the entire network and the interpretation of its underlying structure still remains difficult, mainly due to the excessively large size of the biomolecular networks. In this paper we propose a novel multi-resolution representation and exploration approach that exploits hierarchical community detection algorithms for the identification of communities occurring in biomolecular networks. The proposed graphical rendering combines two types of nodes (protein and communities) and three types of edges (protein-protein, community-community, protein-community), and displays communities at different resolutions, allowing the user to interactively zoom in and out from different levels of the hierarchy. Links among communities are shown in terms of relationships and functional correlations among the biomolecules they contain. This form of navigation can be also combined by the user with a vertex centric visualization for identifying the communities holding a target biomolecule. Since communities gather limited-size groups of correlated proteins, the visualization and exploration of complex and large networks becomes feasible on off-the-shelf computer machines. The proposed graphical exploration strategies have been implemented and integrated in UNIPred-Web, a web application that we recently introduced for combining the UNIPred algorithm, able to address both integration and protein function prediction in an imbalance-aware fashion, with an easy to use vertex-centric exploration of the integrated network. The tool has been deeply amended from different standpoints, including the prediction core algorithm. Several tests on networks of different size and connectivity have been conducted to show off the vast potential of our methodology; moreover, enrichment analyses have been performed to assess the biological meaningfulness of detected communities. Finally, a CoV-human network has been embedded in the system, and a corresponding case study presented, including the visualization and the prediction of human host proteins that potentially interact with SARS-CoV2 proteins.

The subset of pro-inflammatory B cells, called late memory, tissue-like or double negative (DN), accumulates in the blood of elderly individuals. Here we show that DN B cells do not proliferate and do not make antibodies to influenza antigens, but they secrete antibodies with autoimmune reactivity, in agreement with their membrane phenotype (CD95+CD21-CD11c+) and their spontaneous expression of the transcription factor T-bet. These cells also increase in the blood of individuals with obesity and autoimmune diseases, but causative mechanisms and signaling pathways involved are known only in part. In the present paper we compare frequencies and metabolic requirements of these cells in the blood of healthy individuals of different ages and in the blood and the subcutaneous adipose tissue (SAT) of individuals with obesity. Results show that DN B cells from young individuals have minimal metabolic requirements, DN B cells from elderly and obese individuals utilize higher amounts of glucose to perform autoimmune antibody production and enroll in aerobic glycolysis to support their function. DN B cells from the SAT have the highest metabolic requirements as they activate oxidative phosphorylation, aerobic glycolysis and fatty acid oxidation. DN B cells from the SAT also show the highest levels of ROS and the highest levels of phosphorylated AMPK (5'-AMP activated kinase) and Sestrin 1, both able to mitigate stress and cell death. This metabolic advantage drives DN B cell survival and function (secretion of autoimmune antibodies).

SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus-2), cause of COVID-19 (Coronavirus Disease of 2019), represents a significant risk to people living with pre-existing conditions associated with exacerbated inflammatory responses and consequent dysfunctional immunity. In this paper, we have evaluated the influence of obesity, a condition associated with chronic systemic inflammation, on the secretion of SARS-CoV-2-specific IgG antibodies in the blood of COVID-19 patients. Our hypothesis is that obesity is associated with reduced amounts of specific IgG antibodies. Results have confirmed our hypothesis and have shown that SARS-CoV-2 IgG antibodies are negatively associated with Body Mass Index (BMI) in COVID-19 obese patients, as expected based on the known influence of obesity on humoral immunity. Antibodies in COVID-19 obese patients are also negatively associated with serum levels of pro-inflammatory and metabolic markers of inflammaging and pulmonary inflammation, such as SAA (serum amyloid A protein), CRP (C-reactive protein), and ferritin, but positively associated with NEFA (nonesterified fatty acids). These results altogether could help to identify an inflammatory signature with strong predictive value for immune dysfunction. Inflammatory markers identified may subsequently be targeted to improve humoral immunity in individuals with obesity and in individuals with other chronic inflammatory conditions. [ABSTRACT FROM AUTHOR]

The adipose tissue (AT) contributes to systemic and B cell intrinsic inflammation, reduced B cell responses and secretion of autoimmune antibodies. In this study we show that adipocytes in the human obese subcutaneous AT (SAT) secrete several pro-inflammatory cytokines and chemokines, which contribute to the establishment and maintenance of local and systemic inflammation, and consequent suboptimal immune responses in obese individuals, as we have previously shown. We also show that pro-inflammatory chemokines recruit immune cells expressing the corresponding receptors to the SAT, where they also contribute to local and systemic inflammation, secreting additional pro-inflammatory mediators. Moreover, we show that the SAT generates autoimmune antibodies. During the development of obesity, reduced oxygen and consequent hypoxia and cell death lead to further release of pro-inflammatory cytokines, "self" protein antigens, cell-free DNA and lipids. All these stimulate class switch and the production of autoimmune IgG antibodies which have been described to be pathogenic. In addition to hypoxia, we have measured cell cytotoxicity and DNA damage mechanisms, which may also contribute to the release of "self" antigens in the SAT. All these processes are significantly elevated in the SAT as compared to the blood. We definitively found that fat-specific IgG antibodies are secreted by B cells in the SAT and that B cells express mRNA for the transcription factor T-bet and the membrane marker CD11c, both involved in the production of autoimmune IgG antibodies. Finally, the SAT also expresses RNA for cytokines known to promote Germinal Center formation, isotype class switch, and plasma cell differentiation. Our results show novel mechanisms for the generation of autoimmune antibody responses in the human SAT and allow the identification of new pathways to possibly manipulate in order to reduce systemic inflammation and autoantibody production in obese individuals.

Oral Human Papillomavirus (HPV) infection is rare in the general population but common in high-risk individuals. Recent data indicate that oral HPV is associated with the development of head and neck carcinomas. HPV16 infection, in particular, increases the risk of oropharyngeal cancer.We evaluated oral HPV prevalence and determinants of infection in cancer-free HIV-infected and uninfected men who have sex with men (MSM) recruited among attendees of an STI/HIV centre. Oral rinse and gargles were collected using a mouthwash and analyzed with the Linear Array HPV Genotyping Test. Socio-demographic and behavioral data were collected through face-to-face interviews.Overall, 170 MSM participated: 98 HIV-uninfected and 72 HIV-infected (91.7% under cART). Oral HPV was detected in 17.3% and 27.8% of the subjects, respectively (p = 0.13). Non-carcinogenic HPVs were significantly more common among HIV-infected MSM (18.1% vs. 5.1%, p = 0.01). Prevalence of the HPV types included in the quadrivalent HPV vaccine was similar (6.1% vs. 8.3% for the HIV-negative and positive MSM, respectively, p = 0.76). HPV16 was the most frequent type in HIV-negative (5.1%), and HIV-positive individuals, in the latter group together with HPV18, 72 and 84 (4.2% each). Older age at first sex (AOR: 4.02, 95% CI: 1.17-13.86 for those older than 18 years of age at first intercourse, p = 0.027) and a higher lifetime number of receptive oral sex partners (AOR: 9.14, 95% CI: 2.49-33.62 for those with >50 compared to ≤50 partners, p

A consistent association has been reported between low socioeconomic status (SES) and cardiovascular events (CE), whereas the association between SES and cerebrovascular events (CBVD) is less clear. The aim of this study was to investigate the association between SES (measured using education) and CE/CBVD in a cohort study, as well as to investigate lifestyle and clinical risk factors, to help to clarify the mechanisms by which SES influences CE/CBVD.We searched for diagnoses of CE and CBVD in the clinical records of 47,749 members of the EPICOR cohort (average follow-up time: 11 years). SES was determined by the relative index of inequality (RII).A total of 1,156 CE and 468 CBVD were found in the clinical records. An increased risk of CE was observed in the crude Cox model for the third tertile of RII compared to the first tertile (hazard ratio [HR] = 1.39; 95% confidence interval [CI] 1.21-1.61). The increased risk persisted after adjustment for lifestyle risk factors (HR = 1.19; 95%CI 1.02-1.38), clinical risk factors (HR = 1.35; 95%CI 1.17-1.56), and after full adjustment (HR = 1.17; 95%CI 1.01-1.37). Structural equation model showed that lifestyle rather than clinical risk factors are involved in the mechanisms by which education influences CE. No significant association was found between education and CBVD. A strong relationship was observed between education and diabetes at baseline.The most important burden of inequality in CE incidence in Italy is due to lifestyle risk factors.

INTRODUCTION:Successful HIV prevention and treatment requires evidence-based approaches that combine biomedical strategies with behavioral interventions that are socially and culturally appropriate for the population or community being prioritized. Although there has been a push for a combination approach, how best to integrate different strategies into existing behavioral HIV prevention interventions remains unclear. The need to develop effective combination approaches is of particular importance for men who have sex with men (MSM), who face a disproportionately high risk of HIV acquisition. MATERIALS AND METHODS:We collaborated with Latino male couples and providers to adapt Connect 'n Unite, an evidence-based intervention for Black male couples, for Latino male couples. We conducted a series of three focus groups, each with two cohorts of couples, and one focus group with providers. A purposive stratified sample of 20 couples (N = 40, divided into two cohorts) and 10 providers provided insights into how to adapt and integrate social, cultural, and biomedical approaches in a couples-based HIV/AIDS behavioral intervention. RESULTS:The majority (N = 37) of the couple participants had no prior knowledge of the following new biomedical strategies: non-occupational post-exposure prophylaxis (nPEP); pre-exposure prophylaxis (PrEP); and HIV self-testing kits. After they were introduced to these biomedical interventions, all participants expressed a need for information and empowerment through knowledge and awareness of these interventions. In particular, participants suggested that we provide PrEP and HIV self-testing kits by the middle or end of the intervention. Providers suggested a need to address behavioral, social and structural issues, such as language barriers; and the promotion of client-centered approaches to increase access to, adaptation of, and adherence to biomedical strategies. Corroborating what couple participants suggested, providers agreed that biomedical strategies should be offered after providing information about these tools. Regarding culturally sensitive and responsive approaches, participants identified stigma and discrimination associated with HIV and sexual identity as barriers to care, language barriers and documentation status as further barriers to care, the couple-based approach as ideal to health promotion, and the need to include family topics in the intervention. DISCUSSION:We successfully adapted an evidence-based behavioral HIV prevention intervention for Latino male couples. The adapted intervention, called Conectando Latinos en Pareja, integrates social, cultural, behavioral and biomedical strategies to address the HIV epidemic among Latino MSM. The study highlights the promise regarding the feasibility of implementing a combination approach to HIV prevention in this population.

OBJECTIVESThe purpose of Project Gel was to determine the safety and acceptability of rectal microbicides in young men who have sex with men (MSM) and transgender women (TGW) at risk of HIV infection.METHODSMSM and TGW aged 18-30 years were enrolled at three sites; Pittsburgh, PA; Boston, MA; and San Juan, PR. Stage 1A was a cross-sectional assessment of sexual health and behavior in MSM and TGW. A subset of participants from Stage 1A were then enrolled in Stage 1B, a 12-week evaluation of the safety and acceptability of a placebo rectal gel. This was followed by the final phase of the study (Stage 2) in which a subset of participants from Stage 1B were enrolled into a Phase 1 rectal safety and acceptability evaluation of tenofovir (TFV) 1% gel.RESULTS248 participants were enrolled into Stage 1A. Participants' average age was 23.3 years. The most common sexually transmitted infection (STIs) at baseline were Herpes simplex (HSV)-2 (16.1% by serology) and rectal Chlamydia trachomatis (CT) (10.1% by NAAT). 134 participants were enrolled into Stage 1B. During the 12 week period of follow-up 2 HIV, 5 rectal CT, and 5 rectal Neisseria gonorrhea infections were detected. The majority of adverse events (AEs) were infections (N = 56) or gastrointestinal (N = 46) and were mild (69.6%) or moderate (28.0%). Of the participants who completed Stage 1B, 24 were enrolled into Stage 2 and randomized (1:1) to receive TFV or placebo gel. All participants completed Stage 2. The majority of AEs were gastrointestinal (N = 10) and of mild (87.2%) or moderate (10.3%) severity.CONCLUSIONSIn this study we were able to enroll a sexually active population of young MSM and TGW who were willing to use rectal microbicides. TFV gel was safe and acceptable and should be further developed as an alternative HIV prevention intervention for this population.TRIAL REGISTRATIONClinicalTrials.gov NCT01283360.

Barbiturates are proposed as a second/third line treatment for intracranial hypertension in traumatic brain injury (TBI) patients, but the literature remains uncertain regarding their benefit/risk balance. We aimed to evaluate the impact of barbiturates therapy in TBI patients with early intracranial hypertension on the intensive care unit (ICU) survival, the occurrence of ventilator-associated pneumonia (VAP), and the patient's functional status at three months. We used the French AtlanREA prospective cohort of trauma patients. Using a propensity score-based methodology (inverse probability of treatment weighting), we compared patients having received barbiturates within the first 24 hours of admission (barbiturates group) and those who did not (control group). We used cause-specific Cox models for ICU survival and risk of VAP, and logistic regression for the 3-month Glasgow Outcome Scale (GOS) evaluation. Among the 1396 patients with severe trauma, 383 had intracranial hypertension on admission and were analyzed. Among them, 96 (25.1%) received barbiturates. The early use of barbiturates was significantly associated with increased ICU mortality (HR = 1.85, 95%CI 1.03–3.33). However, barbiturates treatment was not significantly associated with VAP (HR = 1.02, 95%CI 0.75–1.41) or 3-month GOS (OR = 1.67, 95%CI 0.84–3.33). Regarding the absence of relevant clinical trials, our results suggest that each early prescription of barbiturates requires a careful assessment of the benefit/risk ratio. [ABSTRACT FROM AUTHOR]

Colorectal cancer is the third most common cancer worldwide. Diet has been hypothesized as involved in colorectal cancer etiology, but few studies on the influence of total dietary antioxidant intake on colorectal cancer risk have been performed.We investigated the association between colorectal cancer risk and the total antioxidant capacity (TAC) of the diet, and also of intake of selected antioxidants, in 45,194 persons enrolled in 5 centers (Florence, Naples, Ragusa, Turin and Varese) of the European Prospective Investigation into Cancer and Nutrition (EPIC) Italy study. TAC was estimated by the Trolox equivalent antioxidant capacity (TEAC) assay. Hazard ratios (HRs) for developing colorectal cancer, and colon and rectal cancers separately, adjusted for confounders, were estimated for tertiles of TAC by Cox modeling, stratifying by center.Four hundred thirty-six colorectal cancers were diagnosed over a mean follow-up of 11.28 years. No significant association between dietary TAC and colorectal cancer incidence was found. However for the highest category of TAC compared to the lowest, risk of developing colon cancer was lower (HR: 0.63; 95% CI: 0.44-0.89, P trend: 0.008). By contrast, increasing TAC intake was associated with significantly increasing risks of rectal cancer (2nd tertile HR: 2.09; 95%CI: 1.19-3.66; 3rd tertile 2.48 95%CI: 1.32-4.66; P trend 0.007). Intakes of vitamin C, vitamin E, and ß-carotene were not significantly associated with colorectal cancer risk.Further prospective studies are needed to confirm the contrasting effects of high total antioxidant intake on risk of colon and rectal cancers.

The relationship between coffee consumption and coronary heart disease (CHD) has been investigated in several studies with discrepant results. We examined the association between Italian-style (espresso and mocha) coffee consumption and CHD risk.We investigated 12,800 men and 30,449 women without history of cardiovascular disease recruited to the EPICOR prospective cohort study. Coffee consumption was assessed at baseline. In a random sub-cohort of 1472 subjects, plasma triglycerides, and total, LDL and HDL cholesterol were determined to investigate the effect of coffee consumption on plasma lipids.After a mean follow up of 10.9 years, 804 cases of CHD (500 acute events, 56 fatal events and 248 revascularizations, all first events) were identified. Multivariable adjusted hazard ratios for CHD were: 1.18 (95% CI 0.87-1.60) for drinking 1-2 cups/day, 1.37 (95% CI 1.03-1.82) for >2-4 cups/day and 1.52 (95% CI 1.11-2.07) for over 4 cups/day (P trend

Metabolic syndrome (defined as at least three among abdominal obesity, high blood triglycerides, low high-density lipoprotein cholesterol, high blood glucose, and high blood pressure) is emerging as a risk factor for breast cancer; however few studies - most confined to postmenopausal women - have investigated associations between breast cancer risk and metabolic syndrome. The purpose of this study was to examine the association between metabolic syndrome and its components, and risk of breast cancer in postmenopausal and premenopausal women.We performed a case-cohort study on 22,494 women recruited in 1993-1998 to four Italian centres (Turin, Varese, Naples, Ragusa) of the European Prospective Investigation into Cancer and Nutrition (EPIC) and followed-up for up to 15 years. A random subcohort of 565 women was obtained and 593 breast cancer cases were diagnosed. Hazard ratios (HR) with 95% confidence intervals (CI), adjusted for potential confounders, were estimated by Prentice-weighted Cox proportional hazards models.Presence of metabolic syndrome was associated with significantly increased breast cancer risk in all women (HR 1.52, 95%CI 1.14-2.02). When the analyses were repeated separately for menopausal status, the association was limited to postmenopausal women (HR 1.80, 95%CI 1.22-2.65) and absent in premenopausal women (HR 0.71, 95%CI 0.43-1.16); P for interaction between metabolic syndrome and menopausal status was 0.001. Of metabolic syndrome components, only high blood glucose was significantly associated with increased breast cancer risk in all women (HR 1.47, 95%CI 1.13-1.91) and postmenopausal women (HR 1.89, 95%CI 1.29-2.77), but not premenopausal women (HR 0.80, 95%CI 0.52-1.22; P interaction=0.004).These findings support previous data indicating that metabolic syndrome is an important risk factor for breast cancer in postmenopausal women, but not in premenopausal women, and suggest that prevention of metabolic syndrome through lifestyle changes could confer protection against breast cancer.

Aging and HIV infection are independently associated with excessive immune activation and impaired immune responses to vaccines, but their relationships have not been examined.For selecting an aging population we enrolled 28 post-menopausal women including 12 healthy volunteers and 16 HIV-infected women on antiretroviral treatment with

CONTEXT: Levothyroxine monotherapy is the treatment of choice for hypothyroid patients because peripheral T4 to T3 conversion is believed to account for the overall tissue requirement for thyroid hormones. However, there are indirect evidences that this may not be the case in all patients. OBJECTIVE: To evaluate in a large series of athyreotic patients whether levothyroxine monotherapy can normalize serum thyroid hormones and thyroid-pituitary feedback. DESIGN: Retrospective study. SETTING: Academic hospital. PATIENTS: 1,811 athyreotic patients with normal TSH levels under levothyroxine monotherapy and 3,875 euthyroid controls. MEASUREMENTS: TSH, FT4 and FT3 concentrations by immunoassays. RESULTS: FT4 levels were significantly higher and FT3 levels were significantly lower (p

Background: Oral Human Papillomavirus (HPV) infection is rare in the general population but common in high-risk individuals. Recent data indicate that oral HPV is associated with the development of head and neck carcinomas. HPV16 infection, in particular, increases the risk of oropharyngeal cancer. Methods: We evaluated oral HPV prevalence and determinants of infection in cancer-free HIV-infected and uninfected men who have sex with men (MSM) recruited among attendees of an STI/HIV centre. Oral rinse and gargles were collected using a mouthwash and analyzed with the Linear Array HPV Genotyping Test. Socio-demographic and behavioral data were collected through face-to-face interviews. Results: Overall, 170 MSM participated: 98 HIV-uninfected and 72 HIV-infected (91.7% under cART). Oral HPV was detected in 17.3% and 27.8% of the subjects, respectively (p = 0.13). Non-carcinogenic HPVs were significantly more common among HIV-infected MSM (18.1% vs. 5.1%, p = 0.01). Prevalence of the HPV types included in the quadrivalent HPV vaccine was similar (6.1% vs. 8.3% for the HIV-negative and positive MSM, respectively, p = 0.76). HPV16 was the most frequent type in HIV-negative (5.1%), and HIV-positive individuals, in the latter group together with HPV18, 72 and 84 (4.2% each). Older age at first sex (AOR: 4.02, 95% CI: 1.17–13.86 for those older than 18 years of age at first intercourse, p = 0.027) and a higher lifetime number of receptive oral sex partners (AOR: 9.14, 95% CI: 2.49–33.62 for those with >50 compared to ≤50 partners, p<0.001) were determinants of oral HPV among HIV-infected MSM. Conclusion: Oral HPV infection among MSM attending an urban STI center is very frequent compared to the general population. Sexual behavior appears to be the major determinant of infection among the HIV-infected individuals. [ABSTRACT FROM AUTHOR]

Background: A consistent association has been reported between low socioeconomic status (SES) and cardiovascular events (CE), whereas the association between SES and cerebrovascular events (CBVD) is less clear. The aim of this study was to investigate the association between SES (measured using education) and CE/CBVD in a cohort study, as well as to investigate lifestyle and clinical risk factors, to help to clarify the mechanisms by which SES influences CE/CBVD. Material and Methods: We searched for diagnoses of CE and CBVD in the clinical records of 47,749 members of the EPICOR cohort (average follow-up time: 11 years). SES was determined by the relative index of inequality (RII). Results: A total of 1,156 CE and 468 CBVD were found in the clinical records. An increased risk of CE was observed in the crude Cox model for the third tertile of RII compared to the first tertile (hazard ratio [HR] = 1.39; 95% confidence interval [CI] 1.21–1.61). The increased risk persisted after adjustment for lifestyle risk factors (HR = 1.19; 95%CI 1.02–1.38), clinical risk factors (HR = 1.35; 95%CI 1.17–1.56), and after full adjustment (HR = 1.17; 95%CI 1.01–1.37). Structural equation model showed that lifestyle rather than clinical risk factors are involved in the mechanisms by which education influences CE. No significant association was found between education and CBVD. A strong relationship was observed between education and diabetes at baseline. Conclusion: The most important burden of inequality in CE incidence in Italy is due to lifestyle risk factors. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of Project Gel was to determine the safety and acceptability of rectal microbicides in young men who have sex with men (MSM) and transgender women (TGW) at risk of HIV infection. Methods: MSM and TGW aged 18–30 years were enrolled at three sites; Pittsburgh, PA; Boston, MA; and San Juan, PR. Stage 1A was a cross-sectional assessment of sexual health and behavior in MSM and TGW. A subset of participants from Stage 1A were then enrolled in Stage 1B, a 12-week evaluation of the safety and acceptability of a placebo rectal gel. This was followed by the final phase of the study (Stage 2) in which a subset of participants from Stage 1B were enrolled into a Phase 1 rectal safety and acceptability evaluation of tenofovir (TFV) 1% gel. Results: 248 participants were enrolled into Stage 1A. Participants’ average age was 23.3 years. The most common sexually transmitted infection (STIs) at baseline were Herpes simplex (HSV)-2 (16.1% by serology) and rectal Chlamydia trachomatis (CT) (10.1% by NAAT). 134 participants were enrolled into Stage 1B. During the 12 week period of follow-up 2 HIV, 5 rectal CT, and 5 rectal Neisseria gonorrhea infections were detected. The majority of adverse events (AEs) were infections (N = 56) or gastrointestinal (N = 46) and were mild (69.6%) or moderate (28.0%). Of the participants who completed Stage 1B, 24 were enrolled into Stage 2 and randomized (1:1) to receive TFV or placebo gel. All participants completed Stage 2. The majority of AEs were gastrointestinal (N = 10) and of mild (87.2%) or moderate (10.3%) severity. Conclusions: In this study we were able to enroll a sexually active population of young MSM and TGW who were willing to use rectal microbicides. TFV gel was safe and acceptable and should be further developed as an alternative HIV prevention intervention for this population. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Introduction: Successful HIV prevention and treatment requires evidence-based approaches that combine biomedical strategies with behavioral interventions that are socially and culturally appropriate for the population or community being prioritized. Although there has been a push for a combination approach, how best to integrate different strategies into existing behavioral HIV prevention interventions remains unclear. The need to develop effective combination approaches is of particular importance for men who have sex with men (MSM), who face a disproportionately high risk of HIV acquisition. Materials and Methods: We collaborated with Latino male couples and providers to adapt Connect ‘n Unite, an evidence-based intervention for Black male couples, for Latino male couples. We conducted a series of three focus groups, each with two cohorts of couples, and one focus group with providers. A purposive stratified sample of 20 couples (N = 40, divided into two cohorts) and 10 providers provided insights into how to adapt and integrate social, cultural, and biomedical approaches in a couples-based HIV/AIDS behavioral intervention. Results: The majority (N = 37) of the couple participants had no prior knowledge of the following new biomedical strategies: non-occupational post-exposure prophylaxis (nPEP); pre-exposure prophylaxis (PrEP); and HIV self-testing kits. After they were introduced to these biomedical interventions, all participants expressed a need for information and empowerment through knowledge and awareness of these interventions. In particular, participants suggested that we provide PrEP and HIV self-testing kits by the middle or end of the intervention. Providers suggested a need to address behavioral, social and structural issues, such as language barriers; and the promotion of client-centered approaches to increase access to, adaptation of, and adherence to biomedical strategies. Corroborating what couple participants suggested, providers agreed that biomedical strategies should be offered after providing information about these tools. Regarding culturally sensitive and responsive approaches, participants identified stigma and discrimination associated with HIV and sexual identity as barriers to care, language barriers and documentation status as further barriers to care, the couple-based approach as ideal to health promotion, and the need to include family topics in the intervention. Discussion: We successfully adapted an evidence-based behavioral HIV prevention intervention for Latino male couples. The adapted intervention, called Conectando Latinos en Pareja, integrates social, cultural, behavioral and biomedical strategies to address the HIV epidemic among Latino MSM. The study highlights the promise regarding the feasibility of implementing a combination approach to HIV prevention in this population. [ABSTRACT FROM AUTHOR]

Context: Levothyroxine monotherapy is the treatment of choice for hypothyroid patients because peripheral T4 to T3 conversion is believed to account for the overall tissue requirement for thyroid hormones. However, there are indirect evidences that this may not be the case in all patients. Objective: To evaluate in a large series of athyreotic patients whether levothyroxine monotherapy can normalize serum thyroid hormones and thyroid-pituitary feedback. Design: Retrospective study. Setting: Academic hospital. Patients: 1,811 athyreotic patients with normal TSH levels under levothyroxine monotherapy and 3,875 euthyroid controls. Measurements: TSH, FT4 and FT3 concentrations by immunoassays. Results: FT4 levels were significantly higher and FT3 levels were significantly lower (p,0.001 in both cases) in levothyroxinetreated athyreotic patients than in matched euthyroid controls. Among the levothyroxine-treated patients 15.2% had lower serum FT3 and 7.2% had higher serum FT4 compared to euthyroid controls. A wide range of FT3/FT4 ratios indicated a major heterogeneity in the peripheral T3 production capacity in different individuals. The correlation between thyroid hormones and serum TSH levels indicated an abnormal feedback mechanism in levothyroxine-treated patients. Conclusions: Athyreotic patients have a highly heterogeneous T3 production capacity from orally administered levothyroxine. More than 20% of these patients, despite normal TSH levels, do not maintain FT3 or FT4 values in the reference range, reflecting the inadequacy of peripheral deiodination to compensate for the absent T3 secretion. The longterm effects of chronic tissue exposure to abnormal T3/T4 ratio are unknown but a sensitive marker of target organ response to thyroid hormones (serum TSH) suggests that this condition causes an abnormal pituitary response. A more physiological treatment than levothyroxine monotherapy may be required in some hypothyroid patients. [ABSTRACT FROM AUTHOR]

The Covid-19 pandemic has sparked renewed attention to the risks of online misinformation, emphasizing its impact on individuals' quality of life through the spread of health-related myths and misconceptions. In this study, we analyze 6 years (2016–2021) of Italian vaccine debate across diverse social media platforms (Facebook, Instagram, Twitter, YouTube), encompassing all major news sources–both questionable and reliable. We first use the symbolic transfer entropy analysis of news production time-series to dynamically determine which category of sources, questionable or reliable, causally drives the agenda on vaccines. Then, leveraging deep learning models capable to accurately classify vaccine-related content based on the conveyed stance and discussed topic, respectively, we evaluate the focus on various topics by news sources promoting opposing views and compare the resulting user engagement. Our study uncovers misinformation not as a parasite of the news ecosystem that merely opposes the perspectives offered by mainstream media, but as an autonomous force capable of even overwhelming the production of vaccine-related content from the latter. While the pervasiveness of misinformation is evident in the significantly higher engagement of questionable sources compared to reliable ones (up to 11 times higher in median value), our findings underscore the need for consistent and thorough pro-vax coverage to counter this imbalance. This is especially important for sensitive topics, where the risk of misinformation spreading and potentially exacerbating negative attitudes toward vaccines is higher. While reliable sources have successfully promoted vaccine efficacy, reducing anti-vax impact, gaps in pro-vax coverage on vaccine safety led to the highest engagement with anti-vax content. [ABSTRACT FROM AUTHOR]

Introduction: Renal cell carcinoma (RCC) is one of the most prevalent cancers in kidney transplant recipients (KTR). The hereditary background of RCC in native kidneys has been determined, implicating its clinical importance. Materials and methods: This retrospective single-center pilot study aimed to identify a potential genetic predisposition to RCC of the transplanted kidney and outcome in KTR who underwent single kidney transplantation between January 2000 and December 2020 and manifested RCC of the transplanted kidney. Next-generation sequencing (NGS) based germline genetic analysis from peripheral blood-derived genomic DNA (gDNA) was performed in both the recipient and donor using a gene panel targeting 226 cancer predisposition genes. Results: The calculated incidence of RCC of the transplanted kidney among 4146 KTR was 0.43%. In fifteen KTR and donors, NGS was performed. The mean KTR age at transplantation and the diagnosis of RCC was 50.3 years (median 54; 5–67 years) and 66 years (median 66; 24–79 years), respectively. The mean donor age at transplantation and graft age at RCC diagnosis was 39.7 years (median 42; 7–68 years) and 50.2 years (median 46; 20–83 years), respectively. The mean follow-up after RCC diagnosis was 47 months (median 39.1; 0–112 months). Papillary RCC was the most prevalent (n = 8), followed by clear cell RCC (n = 6) and unspecified RCC (n = 1). Thirteen RCCs were low-stage (pT1a/b) diseases, one was pT3, and one was of unknown stage. Most RCC was higher graded. No germline pathogenic cancer-predisposition variant was found in either KTR or donors except for several variants of uncertain significance. Conclusion: RCC of the transplanted kidney is very rare. Germline cancer-predisposition testing has identified several variants of uncertain significance, but no germline genetic predisposition to graft RCC in KTR. Further research is needed to assess the clinical relevance of genetic testing for cancer risk in KTR. [ABSTRACT FROM AUTHOR]

Food wasted in primary and secondary education institutions creates nutritional losses, financial inefficiencies, and environmental degradation. While there is some evidence of how particular interventions within schools may influence the amount of waste created, there is little recent information about typical levels of food waste generated in U.S. primary and secondary schools and how waste correlates with school and meal characteristics. We analyze data reported by more than 100 schools from 24 states as part of the World Wildlife Fund's Food Waste Warriors project and identify how plate and beverage waste from school lunches are associated with school and meal service characteristics. We find schools that permit students to choose their own amount of milk report 76% less milk waste than those reliant upon individual milk cartons while schools that implement at least one non-curricular intervention (e.g., a table where students can share unopened food) report significantly less produce waste than other schools. We confirm several patterns observed or hypothesized in the literature, including more waste generated by younger students and during the earliest and shortest lunch periods. We document several novel associations including more plate waste at smaller schools, during winter months and in the Northeast region. We find several nuanced patterns of waste related to the prevalence of free and reduced meal service and whether all meal elements are offered versus served. While this study cannot support rigorous evaluation of intervention effectiveness, it provides insights into school and program characteristics that may pose challenges for schools interested in reducing student plate waste. [ABSTRACT FROM AUTHOR]

Aging profoundly affects the immune system leading to an increased propensity for inflammation. Age-related dysregulation of immune cells is implicated in the development and progression of numerous age-related diseases such as: cardiovascular diseases, neurodegenerative disorders, and metabolic syndromes. Monocytes and monocyte-derived macrophages, being important players in the inflammatory response, significantly influence the aging process and the associated increase in inflammatory disease risk. Ischemic stroke is among age-related diseases where inflammation, particularly monocyte-derived macrophages, plays an important deteriorating role but could also strongly promote post-stroke recovery. Also, biological sex influences the incidence, presentation, and outcomes of ischemic stroke, reflecting both biological differences between men and women. Here, we studied whether human peripheral blood monocyte subtype (classical, intermediate, and non-classical) expression of genes implicated in stroke-related inflammation and post-stroke tissue regeneration depends on age and sex. A flow cytometry analysis of blood samples from 44 healthy volunteers (male and female, aged 28 to 98) showed that in contrast to other immune cells, the proportion of NK-cells increased in females. The proportion of B-cells decreased in both sexes with age. Gene expression analysis by qPCR identified several genes differentially correlating with age and sex within different monocyte subtypes. Interestingly, ANXA1 and CD36 showed a consistent increase with aging in all monocytes, specifically in intermediate (CD36) and intermediate and non-classical (ANXA1) subtypes. Other genes (IL-1β, S100A8, TNFα, CD64, CD33, TGFβ1, TLR8, CD91) were differentially changed in monocyte subtypes with increasing age. Most age-dependent gene changes were differentially expressed in female monocytes. Our data shed light on the nuanced interplay of age and sex in shaping the expression of inflammation- and regeneration-related genes within distinct monocyte subtypes. Understanding these dynamics could pave the way for targeted interventions and personalized approaches in post-stroke care, particularly for the aging population and individuals of different sexes. [ABSTRACT FROM AUTHOR]

This review aimed to systematically compare and pool the prevalence of all the known evidence on caregiver hesitancy and to describe the factors influencing vaccine hesitancy among caregiver worldwide such as COVID-19, MMR, Influenza, HPV and others. We searched article from few electronic databases (PubMed, CENTRAL, ProQuest, and Web of Science) from inception to August 2023 using specific keywords for example caregiver, parents, prevalence, factor, hesitancy, and others. We included population-based studies that reported the prevalence of caregiver hesitancy. We used random-effects meta-analyses for pool prevalence estimates of caregiver hesitancy. A total of 765 studies met our inclusion criteria, containing data on 38,210,589 caregivers from seven regions across the globe. Overall or pool prevalence of vaccine hesitancy among caregiver is 25.0% (95% CI: 0.22–0.27, I2 = 99.91%, p = 0.001). Based on the evidence gathered, vaccine hesitancy was found to be religious sentiments, personal beliefs, perceived safety concerns, and a desire for more information from healthcare providers, along with factors related to availability, accessibility, affordability, and acceptability of vaccinations. Vaccine safety and efficiency have been identified as the main factor for caregiver vaccine hesitancy globally with a prevalence of 91.4%. Trial registration PROSPERO registration number: CRD42022331629. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022331629. [ABSTRACT FROM AUTHOR]

Pre-exposure prophylaxis (PrEP) is an effective HIV prevention strategy that consists in the use of antiretroviral drugs by seronegative people at risk of HIV. Negative perceptions, inadequate understanding, and access barriers have been associated with decreased medication adherence. Manaus is the largest city in the Brazilian Amazon, where the incidence of HIV/AIDS is high, and the rates of adherence to the antiretroviral treatment for HIV and PrEP are low. In this qualitative study among PrEP users, mostly MSM, we explored perceptions, knowledge, and access barriers. We conducted 21 in-depth interviews with an intentionally sampled group of participants who had used PrEP at least once in their lifetime, selected through the snowball technique, between April and July 2022. A thematic analysis was conducted with a predominantly inductive approach. We highlight three relevant themes: (i) access to information about PrEP and its influences on users, (ii) access, monitoring, and barriers encountered, and (iii) facilitators for PrEP adherence and sexual behaviors. One of the negative perceptions identified in the study involves a misunderstanding of the association between PrEP users and the HIV/AIDS status. Participants revealed that some non-PrEP users suspect that individuals claiming PrEP usage are concealing an HIV-positive status to engage in unprotected sex. Lack of information by health professionals regarding HIV prevention methods poses significant barriers to PrEP access and adherence. Participants emphasized social media's crucial role in PrEP awareness. The results suggest a need to increase digital outreach regarding PrEP, decentralize PrEP services, and provide comprehensive healthcare training to improve the effectiveness of the preventive measure. [ABSTRACT FROM AUTHOR]

Preptin, a 34-amino acid peptide derived from pro-IGF2, is believed to influence various physiological processes, including insulin secretion and the regulation of bone metabolism. Despite its recognized involvement, the precise physiological role of preptin remains enigmatic. To address this knowledge gap, we synthesized 16 analogs of preptin, spanning a spectrum from full-length forms to fragments, and conducted comprehensive comparative activity evaluations alongside native human, mouse and rat preptin. Our study aimed to elucidate the physiological role of preptin. Contrary to previous indications of broad biological activity, our thorough analyses across diverse cell types revealed no significant biological activity associated with preptin or its analogs. This suggests that the associations of preptin with various diseases or tissue-specific abundance fluctuations may be influenced by factors beyond preptin itself, such as higher levels of IGF2 or IGF2 proforms present in tissues. In conclusion, our findings challenge the conventional notion of preptin as an isolated biologically active molecule and underscore the complexity of its interactions within biological systems. Rather than acting independently, the observed effects of preptin may arise from experimental conditions, elevated preptin concentrations, or interactions with related molecules such as IGF2. [ABSTRACT FROM AUTHOR]