In utero exposure to HIV and/or antiretroviral therapy: a systematic review of preclinical and clinical evidence of cognitive outcomes

Introducion With the increasing number of children exposed to HIV or antiretroviral therapy in utero, there are concerns that this population may have worse neurodevelopmental outcomes compared to those who are unexposed. The objective of this study was to systematically review the clinical and preclinical literature on the effects of in utero exposure to HIV and/or antiretroviral therapy (ART) on neurodevelopment. Methods We systematically searched OVID Medline, PsycINFO and Embase, as well as the Cochrane Collaborative Database, Google Scholar and bibliographies of pertinent articles. Titles, abstracts, and full texts were assessed independently by two reviewers. Data from included studies were extracted. Results are summarized qualitatively. Results The search yielded 3027 unique titles. Of the 255 critically reviewed full-text articles, 25 met inclusion criteria for the systematic review. Five articles studied human subjects and looked at brain structure and function. The remaining 20 articles were preclinical studies that mostly focused on behavioural assessments in animal models. The few clinical studies had mixed results. Some clinical studies found no difference in white matter while others noted higher fractional anisotropy and lower mean diffusivity in the brains of HIV-exposed uninfected children compared to HIV-unexposed uninfected children, correlating with abnormal neurobehavioral scores. Preclinical studies focused primarily on neurobehavioral changes resulting from monotherapy with either zidovudine or lamivudine. Various developmental and behavioural changes were noted in preclinical studies with ART exposure, including decreased grooming, decreased attention, memory deficits and fewer behaviours associated with appropriate social interaction. Conclusions While the existing literature suggests that there may be some neurobehavioral differences associated with HIV and ART exposure, limited data are available to substantially support these claims. More research is needed comparing neurobiological factors between HIV-exposed uninfected and HIV-unexposed uninfected children and using exposures consistent with current clinical care

COVID-19 Vaccine Hesitancy in Italy: Predictors of Acceptance, Fence Sitting and Refusal of the COVID-19 Vaccination

Background: The hesitancy in taking the COVID-19 vaccine is a global challenge. The need to identify predictors of COVID-19 vaccine reluctance is critical. Our objectives were to evaluate sociodemographic, psychological, and behavioral factors, as well as attitudes and beliefs that influence COVID-19 vaccination hesitancy in the general population of Italy. Methods: A total of 2,015 people were assessed in two waves (March, April and May, 2021). Participants were divided into three groups: (1) individuals who accepted the vaccination (“accepters”); (2) individuals who refused the vaccination (“rejecters”); and (3) individuals who were uncertain about their attitudes toward the vaccination (“fence sitters”). Group comparisons were performed using ANOVA, the Kruskal-Wallis test and chi-square tests. The strength of the association between the groups and the participants' characteristics was analyzed using a series of multinomial logistic regression models with bootstrap internal validation (one for each factor). Results: The “fence sitters” group, when compared to the others, included individuals of younger age, lower educational level, and worsening economic situation in the previous 3 months. After controlling for sociodemographic factors, the following features emerged as the main risk factors for being “fence sitters” (compared with vaccine “accepters”): reporting lower levels of protective behaviors, trust in institutions and informational sources, frequency of use of informational sources, agreement with restrictions and higher conspirative mentality. Higher levels of COVID-19 perceived risk, trust in institutions and informational sources, frequency of use of informational sources, agreement with restrictions and protective behaviors were associated with a higher likelihood of becoming “fence sitters” rather than vaccine “rejecters.” Conclusions: The “fence sitters” profile revealed by this study is intriguing and should be the focus of public programmes aimed at improving adherence to the COVID-19 vaccination campaign

Parma consensus statement on metabolic disruptors

A multidisciplinary group of experts gathered in Parma Italy for a workshop hosted by the University of Parma, May 16–18, 2014 to address concerns about the potential relationship between environmental metabolic disrupting chemicals, obesity and related metabolic disorders. The objectives of the workshop were to: 1. Review findings related to the role of environmental chemicals, referred to as “metabolic disruptors”, in obesity and metabolic syndrome with special attention to recent discoveries from animal model and epidemiology studies; 2. Identify conclusions that could be drawn with confidence from existing animal and human data; 3. Develop predictions based on current data; and 4. Identify critical knowledge gaps and areas of uncertainty. The consensus statements are intended to aid in expanding understanding of the role of metabolic disruptors in the obesity and metabolic disease epidemics, to move the field forward by assessing the current state of the science and to identify research needs on the role of environmental chemical exposures in these diseases. We propose broadening the definition of obesogens to that of metabolic disruptors, to encompass chemicals that play a role in altered susceptibility to obesity, diabetes and related metabolic disorders including metabolic syndrome

Morphological, Functional and Texture Analysis Magnetic Resonance Imaging Features in the Assessment of Radiotherapy-Induced Xerostomia in Oropharyngeal Cancer

The aim of this single-center, observational, retrospective study was to investigate magnetic resonance imaging (MRI) biomarkers for the assessment of radiotherapy (RT)-induced xerostomia. Twenty-seven patients who underwent radiation therapy for oropharyngeal cancer were divided into three groups according to the severity of their xerostomia—mild, moderate, and severe—clinically confirmed with the Common Terminology Criteria for Adverse Events (CTCAE). No severe xerostomia was found. Conventional and functional MRI (perfusion- and diffusion- weighted imaging) performed both pre- and post-RT were studied for signal intensity, mean apparent diffusion coefficient (ADC) values, k-trans, and area under the perfusion curves. Contrast-enhanced T1 images and ADC maps were imported into 3D slicer software, and salivary gland volumes were segmented. A total of 107 texture features were derived. T-Student and Wilcoxon signed-rank tests were performed on functional MRI parameters and texture analysis features to identify the differences between pre- and post-RT populations. A p-value < 0.01 was defined as acceptable. Receiver operating characteristic (ROC) curves were plotted for significant parameters to discriminate the severity of xerostomia in the pre-RT population. Conventional and functional MRI did not yield statistically significant results; on the contrary, five texture features showed significant variation between pre- and post-RT on the ADC maps, of which only informational measure of correlation 1 (IMC 1) was able to discriminate the severity of RT-induced xerostomia in the pre-RT population (area under the curve (AUC) > 0.7). Values lower than the cut-off of −1.473 × 10−11 were associated with moderate xerostomia, enabling the differentiation of mild xerostomia from moderate xerostomia with a 73% sensitivity, 75% specificity, and 75% diagnostic accuracy. Therefore, the texture feature IMC 1 on the ADC maps allowed the distinction between different degrees of severity of RT-induced xerostomia in the pre-RT population. Accordingly, texture analysis on ADC maps should be considered a useful tool to evaluate salivary gland radiosensitivity and help identify patients at risk of developing more serious xerostomia before radiation therapy is administered

Thyroid hormone metabolism and environmental chemical exposure

<p>Abstract</p> <p>Background</p> <p>Polychlorinated dioxins and –furans (PCDD/Fs) and polychlorinated-biphenyls (PCBs) are environmental toxicants that have been proven to influence thyroid metabolism both in animal studies and in human beings. In recent years polybrominated diphenyl ethers (PBDEs) also have been found to have a negative influence on thyroid hormone metabolism. The lower brominated flame retardants are now banned in the EU, however higher brominated decabromo-diphenyl ether (DBDE) and the brominated flame retardant hexabromocyclododecane (HBCD) are not yet banned. They too can negatively influence thyroid hormone metabolism. An additional brominated flame retardant that is still in use is tetrabromobisphenol-A (TBBPA), which has also been shown to influence thyroid hormone metabolism.</p> <p>Influences of brominated flame retardants, PCDD/F’s and dioxin like-PCBs (dl-PCB’s) on thyroid hormone metabolism in adolescence in the Netherlands will be presented in this study and determined if there are reasons for concern to human health for these toxins. In the period 1987-1991, a cohort of mother-baby pairs was formed in order to detect abnormalities in relation to dioxin levels in the perinatal period. The study demonstrated that PCDD/Fs were found around the time of birth, suggesting a modulation of the setpoint of thyroid hormone metabolism with a higher 3,3’, 5,5’tetrathyroxine (T4) levels and an increased thyroid stimulating hormone (TSH). While the same serum thyroid hormone tests (- TSH and T4) were again normal by 2 years of age and were still normal at 8-12 years, adolescence is a period with extra stress on thyroid hormone metabolism. Therefore we measured serum levels of TSH, T4, 3,3’,5- triiodothyronine (T3), free T4 (FT4), antibodies and thyroxine-binding globulin (TBG) in our adolescent cohort.</p> <p>Methods</p> <p>Vena puncture was performed to obtain samples for the measurement of thyroid hormone metabolism related parameters and the current serum dioxin (PCDD/Fs), PCB and PBDE levels.</p> <p>Results</p> <p>The current levels of T3 were positively correlated to BDE-99. A positive trend with FT4 and BDE-99 was also seen, while a positive correlation with T3 and dl-PCB was also seen. No correlation with TBG was seen for any of the contaminants. Neither the prenatal nor the current PCDD/F levels showed a relationship with the thyroid parameters in this relatively small group.</p> <p>Conclusion</p> <p>Once again the thyroid hormone metabolism (an increase in T3) seems to have been influenced by current background levels of common environmental contaminants: dl-PCBs and BDE-99. T3 is a product of target organs and abnormalities might indicate effects on hormone transporters and could cause pathology. While the influence on T3 levels may have been compensated, because the adolescents functioned normal at the time of the study period, it is questionable if this compensation is enough for all organs depending on thyroid hormones.</p

Gestational diabesity and foetoplacental vascular dysfunction

Gestational diabetes mellitus (GDM) shows a deficiency in the metabolism of D-glucose and other nutrients, thereby negatively affecting the foetoplacental vascular endothelium. Maternal hyperglycaemia and hyperinsulinemia play an important role in the aetiology of GDM. A combination of these and other factors predisposes women to developing GDM with pre-pregnancy normal weight, viz. classic GDM. However, women with GDM and prepregnancy obesity (gestational diabesity, GDty) or overweight (GDMow) show a different metabolic status than women with classic GDM. GDty and GDMow are associated with altered l-arginine/nitric oxide and insulin/adenosine axis signalling in the human foetoplacental microvascular and macrovascular endothelium. These alterations differ from those observed in classic GDM. Here, we have reviewed the consequences of GDty and GDMow in the modulation of foetoplacental endothelial cell function, highlighting studies describing the modulation of intracellular pH homeostasis and the potential implications of NO generation and adenosine signalling in GDty-associated foetal vascular insulin resistance. Moreover, with an increase in the rate of obesity in women of childbearing age worldwide, the prevalence of GDty is expected to increase in the next decades. Therefore, we emphasize that women with GDty and GDMow should be characterized with a different metabolic state from that of women with classic GDM to develop a more specific therapeutic approach for protecting the mother and foetus

Phthalate exposure and neurodevelopmental outcomes in early school age children from Poland

Some phthalates are known endocrine disrupting chemicals (EDC). They are widely present in the environment thus their impact on children's health is of particular scientific interest. The aim of the study was to evaluate the association between phthalate exposure and neurodevelopmental outcomes, in particular behavioral, cognitive and psychomotor development, in 250 early school age children from the Polish Mother and Child Cohort (REPRO_PL). Urine samples were collected at the time of children's neurodevelopmental assessment and were analysed for 21 metabolites of 11 parent phthalates. Behavioral and emotional problems were assessed by the Strengths and Difficulties Questionnaire (SDQ) filled in by the mothers. To assess children's cognitive and psychomotor development, Polish adaptation of the Intelligence and Development Scales (IDS) was administered. The examination was performed by trained psychologists. Dimethyl phthalate (DMP) and di-n-butyl phthalate (DnBP) were the two phthalates showing the highest statistically significant associations, with higher total difficulties scores (β = 1.5, 95% CI 0.17; 2.7; β = 1.5, 95% CI 0.25; 2.8, respectively) as well as emotional symptoms and hyperactivity/inattention problems for DnBP (β = 0.46, 95% CI -0.024; 0.94; β = 0.72, 95% CI 0.065; 1.4, respectively), and peer relationships problems for DMP (β = 0.37, 95% CI -0.013; 0.76). In addition, DnBP and DMP have been found to be negatively associated with fluid IQ (β = -0.14, 95% CI -0.29; 0.0041) and crystallized IQ (β = -0.16, 95% CI -0.29; -0.025), respectively. In the case of mathematical skills, three phthalates, namely DMP (β = -0.17, 95% CI -0.31; -0.033), DEP (β = -0.16, 95% CI -0.29; -0.018) and DnBP (β = -0.14, 95% CI -0.28; 0.0012), have also shown statistically significant associations. This study indicates that exposure to some phthalates seems to be associated with adverse effects on behavioral and cognitive development of early school age children. Further action including legislation, educational and interventional activities to protect this vulnerable population is still needed.This work has received financial support from the European Union's Seventh Framework Programme under grant agreement No. 603946 (Health and Environment-wide Associations based on Large population Surveys, HEALS); the National Science Centre, Poland, under grant No. DEC-2014/15/B/NZ7/00998 and the Medical Faculty of the Ludwig-Maximilians-Universität München, Germany, under grant No. WIFOMED-80926024. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe