Genetic and early life factors influence on time-to-multiple sclerosis diagnosis: A UK Biobank study.

BACKGROUND: Previous investigations into multiple sclerosis (MS) risk factors predominantly relied on retrospective studies, which do not consider different follow-up times and assume a constant risk effect throughout lifetime. OBJECTIVE: We aimed to evaluate the impact of genetic and early life factors on MS diagnosis by employing a time-to-event analysis in a prospective cohort. METHODS: We used the UK Biobank data, considering the observation period from birth up to 31 December 2022. We considered genetic risk, using a multiple sclerosis polygenic risk score (MS-PRS), and various early life factors. Tobacco smoking and infectious mononucleosis diagnosis were also considered as time-varying variables along the follow-up. Using a Cox proportional hazards model, we examined the associations between these factors and MS diagnosis instantaneous risk. RESULTS: We analyzed 345,027 participants, of which 1669 had an MS diagnosis. Our analysis revealed age-dependent effects for sex (females vs males) and higher MS-PRS, with greater hazard ratios observed in young adults. CONCLUSION: The age-dependent effects suggest that retrospective studies could have underestimated sex and genetic variants' risk roles during younger ages. Therefore, we emphasize the importance of a time-to-event approach using longitudinal data to better characterize age-dependent risk effects.

Disentangling Multiple Sclerosis heterogeneity in the French territory among genetic and environmental factors via Bayesian heritability analysis.

BACKGROUND: This study aimed to investigate the factors contributing to the variability of Multiple Sclerosis (MS) among individuals born and residing in France. Geographical variation in MS prevalence was observed in France, but the role of genetic and environmental factors in explaining this heterogeneity has not been yet elucidated. METHODS: We employed a heritability analysis on a cohort of 403 trios with an MS-affected proband in the French population. This sample was retrieved from REFGENSEP register of MS cases collected in 23 French hospital centers from 1992 to 2017. Our objective was to quantify the proportion of MS liability variability explained by genetic variability, sex, shared environment effects, region of birth and year of birth. We further considered gene x environment (GxE) interaction effects between genetic variability and region of birth. We have implemented a Bayesian liability threshold model to obtain posterior distributions for the parameters of interest adjusting for ascertainment bias. RESULTS: Our analysis revealed that GxE interaction effects between genetic variability and region of birth represent the primary significant explanatory factor for MS liability variability in French individuals (29 % [95 %CI: 5 %; 53 %]), suggesting that additive genetic effects are modified by environmental factors associated to the region of birth. The individual contributions of genetic variability and region of birth explained, respectively, ≈15 % and ≈16 % of MS variability, highlighting a significantly higher MS liability in individuals born in the Northern regions compared to the Southern region. Overall, the joint contribution of genetic variability, region of birth, and their interaction was then estimated to explain 65 % [95 %CI: 35 %; 92 %] of MS liability variability. The remaining proportion of MS variability is attributed to environmental exposures associated with the year of birth, shared within the same household, and specific to individuals. CONCLUSION: Overall, our analysis highlighted the interaction between genetic variability and environmental exposures linked to the region of birth as the main factor explaining MS variability within individuals born and residing in France. Among the environmental exposures prevalent in the Northern regions, and potentially interacting with genetic variability, lower vitamin D levels due to reduced sun exposure, higher obesity prevalence and higher pollution levels represent the main risk factors in influencing MS risk. These findings emphasize the importance of accounting for environmental factors linked to geographical location in the investigation of MS risk factors, as well as to further explore the influence of GxE interactions in modifying genetic risk.

Contribution of Nutritional, Lifestyle, and Metabolic Risk Factors to Parkinson's Disease.

BACKGROUND: Modifiable risk factors for Parkinson's disease (PD) are poorly known. OBJECTIVES: The aim is to evaluate independent associations of different nutritional components, physical activity, and sedentary behavior and metabolic factors with the risk of PD. METHODS: In this population-based prospective cohort study using the data of the United Kingdom Biobank (from 2006-2010), 502,017 men and women who were free from PD (International Classification of Diseases 10th edition; "G20") at baseline were included. We implemented a Cox proportion hazard's model to evaluate the associations of different levels of physical activity, sitting time, sleep habits, diet quality, alcohol and coffee consumption, smoking, and body mass index with PD risk, adjusting for several confounding variables. RESULTS: During a median follow-up of 12.8 years, lifestyle factors including vigorous physical activity (hazard ration [HR] = 0.84; 95% confidence interval [CI], 0.75-0.94), low-to-moderate sitting time (HR = 0.89; 95% CI, 0.81-0.97), and high sleep quality (HR = 0.89; 95% CI, 0.80-0.99) were associated with a reduced risk of PD. Small amounts of coffee (HR = 0.88; 95% CI, 0.82-0.95), red meat (HR = 0.86; 95% CI, 0.76-0.97), and current smoking (HR = 0.65; 95% CI, 0.56-0.75) were also associated with a lower risk of PD, whereas alcohol intake (HR = 1.29; 95% CI, 1.06-1.56) with higher PD risk. Secondary analysis, including metabolic risk factors, confirmed these findings and highlighted the potential protective effect of plasma vitamin D and uric acid, but of low-density lipoprotein-cholesterol, triglycerides, and C-reactive protein as well. CONCLUSIONS: Vigorous physical activity, reduced sitting time, good sleep quality together with small coffee intake and vitamin D supplementation are potentially neuroprotective lifestyle interventions for the prevention of PD. © 2024 International Parkinson and Movement Disorder Society.

Multiple Sclerosis Heritability Estimation on Sardinian Ascertained Extended Families Using Bayesian Liability Threshold Model.

Heritability studies represent an important tool to investigate the main sources of variability for complex diseases, whose etiology involves both genetics and environmental factors. In this paper, we aimed to estimate multiple sclerosis (MS) narrow-sense heritability (h2), on a liability scale, using extended families ascertained from affected probands sampled in the Sardinian province of Nuoro, Italy. We also investigated the sources of MS liability variability among shared environment effects, sex, and categorized year of birth (<1946, ≥1946). The latter can be considered a proxy for different early environmental exposures. To this aim, we implemented a Bayesian liability threshold model to obtain posterior distributions for the parameters of interest adjusting for ascertainment bias. Our analysis highlighted categorized year of birth as the main explanatory factor, explaining ~70% of MS liability variability (median value = 0.69, 95% CI: 0.64, 0.73), while h2 resulted near to 0% (median value = 0.03, 95% CI: 0.00, 0.09). By performing a year of birth-stratified analysis, we found a high h2 only in individuals born on/after 1946 (median value = 0.82, 95% CI: 0.68, 0.93), meaning that the genetic variability acquired a high explanatory role only when focusing on this subpopulation. Overall, the results obtained highlighted early environmental exposures, in the Sardinian population, as a meaningful factor involved in MS to be further investigated.

A systematic review of Mendelian randomization studies on multiple sclerosis.

Mendelian randomization (MR) is a powerful approach for assessing the causal effect of putative risk factors on an outcome, using genetic variants as instrumental variables. The methodology and application developed in the framework of MR have been dramatically improved, taking advantage of the many public genome-wide association study (GWAS) data. The availability of summary-level data allowed to perform numerous MR studies especially for complex diseases, pinpointing modifiable exposures causally related to increased or decreased disease risk. Multiple sclerosis (MS) is a complex multifactorial disease whose aetiology involves both genetic and non-genetic risk factors and their interplay. Previous observational studies have revealed associations between candidate modifiable exposures and MS risk; although being prone to confounding, and reverse causation, these studies were unable to draw causal conclusions. MR analysis addresses the limitations of observational studies and allows to establish reliable and accurate causal conclusions. Here, we systematically reviewed the studies evaluating the causal effect, through MR, of genetic and non-genetic exposures on MS risk. Among 107 papers found, only 42 were eligible for final evaluation and qualitative synthesis. We found that, above all, low vitamin D levels and high adult body mass index (BMI) appear to be uncontested risk factors for increased MS risk.

The Association between Dysnatraemia during Hospitalisation and Post-COVID-19 Mental Fatigue.

COVID-19 may induce short- and long-term cognitive failures after recovery, but the underlying risk factors are still controversial. Here, we investigated whether (i) the odds of experiencing persistent cognitive failures differ based on the patients' disease course severity and sex at birth; and (ii) the patients' electrolytic profile in the acute stage represents a risk factor for persistent cognitive failures. We analysed data from 204 patients suffering from COVID-19 and hospitalised during the first pandemic wave. According to the 7-point WHO-OS scale, their disease course was classified as severe or mild. We investigated the presence of persistent cognitive failures collected after hospital discharge, while electrolyte profiles were collected during hospitalisation. The results showed that females who suffered from a mild course compared to a severe course of COVID-19 had a higher risk of presenting with persistent mental fatigue after recovery. Furthermore, in females who suffered from a mild course of COVID-19, persistent mental fatigue was related to electrolyte imbalance, in terms of both hypo- and hypernatremia, during hospitalisation in the acute phase. These findings have important implications for the clinical management of hospitalised COVID-19 patients. Attention should be paid to potential electrolyte imbalances, mainly in females suffering from mild COVID-19.

Improving stress management, anxiety, and mental well-being in medical students through an online Mindfulness-Based Intervention: a randomized study.

Pressures and responsibilities of medical school put a strain on medical student's personal wellbeing, leading among all to high rates of anxiety, emotional discomfort and stress. In this work we evaluated the effectiveness of a comprehensive Mindfulness-Based Intervention (MBI) in reducing this load. The intervention comprised 10 twice-a-week Integral Meditation classes, dietary advice, and brief yoga sessions. We performed a randomized trial on two cohort of medical students from Italian universities: 239 in cohort 1 (106 treated and 133 controls), and 123 in cohort 2 (68 treated and 55 control) for a total sample of 362 students. Nine questionnaires for evaluating the effectiveness of our intervention on stress (PSS), state anxiety (STAIX-1), well-being (WEMWBS), mind-wandering (MW-S), overall distress (PANAS), emotion regulation (DERS), resilience (RS-14), and attentional control (ACS-C and ACS-D) were collected both pre and post intervention. Linear mixed effect models were run on the whole sample showing that, after multiple testing correction, our intervention was effective in reducing perceived stress (ß = - 2.57 [- 4.02; - 1.12], p = 0.004), improving mental well-being (ß = 2.82 [1.02; 4.63], p = 0.008) and emotional regulation (ß = - 8.24 [- 12.98; - 3.51], p = 0.004), resilience (ß = 3.79 [1.32; 6.26], p = 0.008), reducing the tendency to wander with the mind (ß = - 0.70 [- 0.99; - 0.39], p = 0.0001), ameliorating the ability to maintain attention (AC-S (ß = - 0.23 [- 0.44; - 0.02], p = 0.04) and AC-D (ß = - 0.19 [- 0.36; - 0.01], p = 0.04)), and the overall distress (ß = 1.84 [0.45; 3.23], p = 0.02).

"I feel your fear": superior fear recognition in organised crime members.

Individuals who deviate from social norms by committing crimes may have reduced facial emotion recognition abilities. Nevertheless, a specific category of offenders - i.e. organised crime (OC) members - is characterised by hierarchically organised social networks and a tendency to manipulate others to reach their illicit goals. Since recognising emotions is crucial to building social networks, OC members may be more skilled in recognising the facial emotion expressions of others to use this information for their criminal purposes. Evidence of a difference between OC and non-organised crime (NOC) offenders in terms of facial emotion recognition is still lacking. To fill this gap in the literature, we tested 50 OC, 50 NOC offenders, and 50 non-offender controls for their ability to identify six basic emotions (happiness, sadness, fear, anger, disgust, and surprise). All participants underwent a cognitive and psychological evaluation to avoid alternative explanations. Results show that OC members were more able to detect the expression of fear in others as compared to NOC. We interpreted this finding in light of the social context and the behavioural criminal attitude of OC members.

Beneficial Effects of an Online Mindfulness-Based Intervention on Sleep Quality in Italian Poor Sleepers during the COVID-19 Pandemic: A Randomized Trial.

Sleep of inadequate quantity and quality is increasing in the present 24 h society, with a negative impact on physical and mental health. Mindfulness-based interventions (MBIs) generate a state of calm behavior that can reduce hyperactivity and improve sleep. We hypothesized that our specific MBI, administered online, may improve sleep quality and foster emotion regulation and mindfulness. The Pittsburgh Sleep Quality Index (PSQI), Sleep Condition Indicator (SCI), Arousal Predisposition Scale (APS), Ford Insomnia Response to Stress Test (FIRST), Sleep Hygiene Index (SHI) and Insomnia Severity Index (ISI) were used to measure sleep quality and stability. Emotion regulation and mindfulness were measured via the Emotion Regulation Questionnaire (ERQ) and Five Facet Mindfulness Questionnaire (FFMQ). Our MBI included 12 biweekly integral meditation (IM) classes, recorded IM training for individual practice, and dietary advice to promote sleep regulation. Fifty-six voluntary poor sleepers with a PSQI score of >5 were randomly allocated to treated (n = 28) and control (n = 28) groups. Linear mixed models were used to estimate the effectiveness of the intervention. Statistically significant results were observed in the FFMQ sub-domain non-reactivity to inner experience (ß = 0.29 [0.06; -0.52], p = 0.01), PSQI (ß = -1.93 [-3.43; -0.43], p = 0.01), SCI (ß = 3.39 [0.66; 6.13], p = 0.02) and ISI (ß = -3.50 [-5.86; -1.14], p = 0.004). These results confirm our hypothesis regarding the beneficial effects of our intervention on sleep quality.

A 60-Day Green Tea Extract Supplementation Counteracts the Dysfunction of Adipose Tissue in Overweight Post-Menopausal and Class I Obese Women.

Menopause is characterized by weight gain and increased visceral fat, which acts as an endocrine organ secreting proinflammatory adipocytokines, with consequent increased risk of metabolic disorders. The aim of this double-blind, placebo-controlled randomized trial was to evaluate the effects of a 60-day dietary supplementation using Camellia sinensis leaf extract on adipose tissue dysfunction in overweight or class I obese post-menopausal, sedentary women. Primary endpoints were the respiratory quotient (RQ), the percentage of carbohydrates (%CHO), the percentage of fat oxidation (%FAT), and the resting energy expenditure (REE) measured by indirect calorimetry. Secondary endpoints included body composition, by dual x-ray absorptiometry (DXA), glucose profile, lipid profile, inflammatory state, liver and kidney function, hormonal status regarding satiety, and status of catecholamines. Twenty-eight women were randomized into two groups: 14 (BMI 31.1 ± 3.5) were supplemented and 14 (BMI 31.9 ± 2.2) received placebo. In regards to the between-group differences over time (ß), a statistically significant difference between the supplemented and placebo group was observed for: RQ (ß = -0.04, p = 0.009), % fat oxidation (ß = 11.04, p = 0.0006), insulin (ß = -1.74, p = 0.009), HOMA (ß = -0.31, p = 0.02), waist circumference (ß = -1.07, p = 0.007), REE (ß = 83.21, p = 0.009), and CRP (ß = -0.14, p = 0.02). These results demonstrate that a 60-day green tea extract supplementation counteracts the dysfunction of adipose tissue in overweight post-menopausal and class I obese women.

A Pipeline for Phasing and Genotype Imputation on Mixed Human Data (Parents-Offspring Trios and Unrelated Subjects) by Reviewing Current Methods and Software.

Genotype imputation has become an essential prerequisite when performing association analysis. It is a computational technique that allows us to infer genetic markers that have not been directly genotyped, thereby increasing statistical power in subsequent association studies, which consequently has a crucial impact on the identification of causal variants. Many features need to be considered when choosing the proper algorithm for imputation, including the target sample on which it is performed, i.e., related individuals, unrelated individuals, or both. Problems could arise when dealing with a target sample made up of mixed data, composed of both related and unrelated individuals, especially since the scientific literature on this topic is not sufficiently clear. To shed light on this issue, we examined existing algorithms and software for performing phasing and imputation on mixed human data from SNP arrays, specifically when related subjects belong to trios. By discussing the advantages and limitations of the current algorithms, we identified LD-based methods as being the most suitable for reconstruction of haplotypes in this specific context, and we proposed a feasible pipeline that can be used for imputing genotypes in both phased and unphased human data.

Heritability Estimation of Multiple Sclerosis Related Plasma Protein Levels in Sardinian Families with Immunochip Genotyping Data.

This work aimed at estimating narrow-sense heritability, defined as the proportion of the phenotypic variance explained by the sum of additive genetic effects, via Haseman-Elston regression for a subset of 56 plasma protein levels related to Multiple Sclerosis (MS). These were measured in 212 related individuals (with 69 MS cases and 143 healthy controls) obtained from 20 Sardinian families with MS history. Using pedigree information, we found seven statistically significant heritable plasma protein levels (after multiple testing correction), i.e., Gc (h2 = 0.77; 95%CI: 0.36, 1.00), Plat (h2 = 0.70; 95%CI: 0.27, 0.95), Anxa1 (h2 = 0.68; 95%CI: 0.27, 1.00), Sod1 (h2 = 0.58; 95%CI: 0.18, 0.96), Irf8 (h2 = 0.56; 95%CI: 0.19, 0.99), Ptger4 (h2 = 0.45; 95%CI: 0.10, 0.96), and Fadd (h2 = 0.41; 95%CI: 0.06, 0.84). A subsequent analysis was performed on these statistically significant heritable plasma protein levels employing Immunochip genotyping data obtained in 155 healthy controls (92 related and 63 unrelated); we found a meaningful proportion of heritable plasma protein levels' variability explained by a small set of SNPs. Overall, the results obtained, for these seven MS-related proteins, emphasized a high additive genetic variance component explaining plasma levels' variability.

Hunting for protective drugs at the break of a pandemic: Causal inference from hospital data.

At the break of a pandemic, the protective efficacy of therapeutic interventions needs rapid evaluation. An experimental approach to the problem will not always be appropriate. An alternative route are observational studies, whether based on regional health service data or hospital records. In this paper, we discuss the use of methods of causal inference for the analysis of such data, with special reference to causal questions that may arise in a pandemic. We apply the methods by using the aid of a directed acyclic graph (DAG) representation of the problem, to encode our causal assumptions and to logically connect the scientific questions. We illustrate the usefulness of DAGs in the context of a controversy over the effects of renin aldosterone system inhibitors (RASIs) in hypertensive individuals at risk of (or affected by) severe acute respiratory syndrome coronavirus 2 disease. We consider questions concerning the existence and the directions of those effects, their underlying mechanisms, and the possible dependence of the effects on context variables. This paper describes the cognitive steps that led to a DAG representation of the problem, based on background knowledge and evidence from past studies, and the use of the DAG to analyze our hospital data and assess the interpretive limits of the results. Our study contributed to subverting early opinions about RASIs, by suggesting that these drugs may indeed protect the older hypertensive Covid-19 patients from the consequences of the disease. Mechanistic interaction methods revealed that the benefit may be greater (in a sense to be made clear) in the older stratum of the population.

Online Short-Term Mindfulness-Based Intervention During COVID-19 Quarantine in Italy: Effects on Wellbeing, Stress, and Anxiety.

To limit the first spread of COVID-19 in March 2020, the Italian government imposed strict lockdown measures to the population. Despite necessary to reduce the virus transmission and the burden to the hospitals, social isolation has caused detrimental effects on psychological wellbeing and mental health. Moreover, during this period, it was also difficult to deliver psychological treatments and psychiatric assistance. A short (a weekly session for 9 weeks) mindfulness-based meditation program, named Integral Meditation (IM), was administered entirely online to healthy adults from Italy. This is a two-groups pre-post-quasi-experimental study in which the two groups, treated and control, were not randomized. Through matching procedures aimed at overcoming the absence of randomization, we analyzed a sample of 84 subjects (42 for each group). By applying linear mixed effect models, we tested the hypothesis of a beneficial effect of IM on wellbeing, perceived stress, and state anxiety, as measured by three self-reported questionnaires (WEMWBS, PSS, and STAI-X1, respectively), assuming that this effect could be different according to the level of baseline trait anxiety, as measured by STAI-X2. The results showed a statistically significant effect of STAI-X1 (ß = -8.24 [95%CI -15.39; -1.09], p = 0.02) and WEMWBS (ß = 4.61 [95%CI 0.94; 8.29], p = 0.01) in the higher trait anxiety subgroup only. No statistically significant effect of IM was observed for PSS. These results suggest that our IM, delivered online, may increase mental wellbeing and decrease anxiety specifically in subjects with higher trait anxiety.

Positive Effects of a Lecithin-Based Delivery Form of Boswellia serrata Extract in Acute Diarrhea of Adult Subjects.

Acute diarrhea is a frequent problem worldwide, mostly due to gastrointestinal infections or food poisoning. Boswellia serrata could be active in the treatment of acute diarrhea due to its anti-inflammatory, antispasmodic, and antimicrobial activity. In this randomized, double-blind, placebo-controlled clinical study, 49 adults with acute diarrhea were randomly allocated to receive 250 mg of a lecithin-based delivery form of Boswellia serrata (CASP) or placebo for 5 days. The time it took to become healthy with stoppage of diarrhea (primary end point) was significantly shorter in the intervention group (3.08 vs. 4.44 days: p-value < 0.0001). The probability of subjects treated with CASP to recover sooner was equal to 80.2%. A significantly lower number of stools was observed in the CASP group over time (ß = −0.17, p-value < 0.0001). A significant difference was observed between the two groups for abdominal pain, nausea, and GAE (global assessment of efficacy). In conclusion, the lecithin-based delivery form of Boswellia serrata extract could be a useful addition to the treatment of acute diarrhea in adults. CASP is safe and reduces the time it takes to become healthy, the frequency of stools, the abdominal pain and nausea of subjects with acute diarrhea. Further studies are needed to confirm these promising results.

Beneficial Effects on Abdominal Bloating with an Innovative Food-Grade Formulation of Curcuma longa and Boswellia serrata Extracts in Subjects with Irritable Bowel Syndrome and Small Bowel Dysbiosis.

Bloating is a symptom frequently reported by subjects with irritable bowel syndrome (IBS) and small bowel dysbiosis, and Low FODMAP's diet (LFD) has been used to treat them. Extracts of Curcumalonga and Boswelliaserrata share anti-inflammatory and antimicrobial effects that could be useful in the management of these clinical conditions. The aim of this study was to evaluate the efficacy of curcumin and boswellia extracts (as Curcumin Boswellia Phytosome, CBP) and LFD on the relief of abdominal bloating in IBS subjects with small bowel dysbiosis, in comparison to LFD alone, in a 30-day supplementation, randomized trial. IBS participants were randomized to either the intervention (500 mg bid of CBP and LFD) or control arm (LFD). Small bowel dysbiosis has been defined by an increase of urinary indican with normal urinary skatole. A total of 67 subjects were recruited. The intervention group (33 subjects) showed a significant decrease (p < 0.0001) of bloating, abdominal pain, and indican values at the end of the study, when compared to the control group (34 subjects). Moreover, the subjects of the intervention group showed a significantly better (p < 0.0001) global assessment of efficacy (GAE) as compared to controls. In conclusion, in subjects with IBS and small bowel dysbiosis, abdominal bloating can be successfully reduced with a supplementation with CBP and LFD.

Plasma Protein Levels Analysis in Multiple Sclerosis Sardinian Families Identified C9 and CYP24A1 as Candidate Biomarkers.

Here we investigate protein levels in 69 multiple sclerosis (MS) cases and 143 healthy controls (HC) from twenty Sardinian families to search for promising biomarkers in plasma. Using antibody suspension bead array technology, the plasma levels of 56 MS-related proteins were obtained. Differences between MS cases and HC were estimated using Linear Mixed Models or Linear Quantile Mixed Models. The proportion of proteins level variability, explained by a set of 119 MS-risk SNPs as to the literature, was also quantified. Higher plasma C9 and CYP24A1 levels were found in MS cases compared to HC (p < 0.05 after Holm multiple testing correction), with protein level differences estimated as, respectively, 0.53 (95% CI: 0.25, 0.81) and 0.42 (95% CI: 0.19, 0.65) times plasma level standard deviation measured in HC. Furthermore, C9 resulted in both statistically significantly higher relapsing-remitting MS (RRMS) and secondary-progressive MS (SPMS) compared to HC, with SPMS showing the highest differences. Instead, CYP24A1 was statistically significantly higher only in RRMS as compared to HC. Respectively, 26% (95% CI: 10%, 44%) and 16% (95% CI: 9%, 39%) of CYP24A1 and C9 plasma level variability was explained by known MS-risk SNPs. Our results highlight C9 and CYP24A1 as potential biomarkers in plasma for MS and allow us to gain insight into molecular disease mechanisms.

Antecedent use of renin-angiotensin system inhibitors is associated with reduced mortality in elderly hypertensive Covid-19 patients.

OBJECTIVES: The effect of renin-angiotensin system inhibitors (RASIs) on mortality in patients with coronavirus disease (Covid-19) is debated. From a cohort of 1352 consecutive patients admitted with Covid-19 to Papa Giovanni XXIII Hospital in Bergamo, Italy, between February and April 2020, we selected and studied hypertensive patients to assess whether antecedent (prior to hospitalization) use of RASIs might affect mortality from Covid-19 according to age. METHODS AND RESULTS: Arterial hypertension was present in 688 patients. Overall mortality (in-hospital or shortly after discharge) was 35% (N = 240). After adjusting for 26 medical history variables via propensity score matching, antecedent use of RASIs (N = 459, 67%) was associated with a lower mortality in older hypertensive patients (age above the median of 68 years in the whole series), whereas no evidence of a significant effect was found in the younger group of the same population (P interaction = 0.001). In an analysis of the subgroup of 432 hypertensive patients older than 68 years, we considered two RASI drug subclasses, angiotensin-converting enzyme inhibitors (ACEIs, N = 156) and angiotensin receptor blockers (ARBs, N = 140), and assessed their respective effects by taking no-antecedent-use of RASIs as reference. This analysis showed that both antecedent use of ACEIs and antecedent use of ARBs were associated with a lower Covid-19 mortality (odds ratioACEI = 0.57, 95% confidence interval 0.36--0.91, P = 0.018) (odds ratioARB = 0.49, 95% confidence interval 0.29--0.82, P = 0.006). CONCLUSION: In the population of over-68 hypertensive Covid-19 patients, antecedent use of ACEIs or ARBs was associated with a lower all-cause mortality, whether in-hospital or shortly after discharge, compared with no-antecedent-use of RASIs.

Homozygosity Haplotype and Whole-Exome Sequencing Analysis to Identify Potentially Functional Rare Variants Involved in Multiple Sclerosis among Sardinian Families.

Multiple Sclerosis (MS) is a complex multifactorial autoimmune disease, whose sex- and age-adjusted prevalence in Sardinia (Italy) is among the highest worldwide. To date, 233 loci were associated with MS and almost 20% of risk heritability is attributable to common genetic variants, but many low-frequency and rare variants remain to be discovered. Here, we aimed to contribute to the understanding of the genetic basis of MS by investigating potentially functional rare variants. To this end, we analyzed thirteen multiplex Sardinian families with Immunochip genotyping data. For five families, Whole Exome Sequencing (WES) data were also available. Firstly, we performed a non-parametric Homozygosity Haplotype analysis for identifying the Region from Common Ancestor (RCA). Then, on these potential disease-linked RCA, we searched for the presence of rare variants shared by the affected individuals by analyzing WES data. We found: (i) a variant (43181034 T > G) in the splicing region on exon 27 of CUL9; (ii) a variant (50245517 A > C) in the splicing region on exon 16 of ATP9A; (iii) a non-synonymous variant (43223539 A > C), on exon 9 of TTBK1; (iv) a non-synonymous variant (42976917 A > C) on exon 9 of PPP2R5D; and v) a variant (109859349-109859354) in 3'UTR of MYO16.

Mindfulness meditation training in an occupational setting: Effects of a 12-weeks mindfulness-based intervention on wellbeing.

BACKGROUND: Mindfulness-based interventions (MBIs) are known for their beneficial effects on positive and negative psychological factors. When applied in an occupational context, MBIs might help workers to cope with stress, increase their professional outcomes and wellbeing. OBJECTIVE: In this two-groups pre-post experimental design we tested the effect of our MBI, called Integral Meditation (IM), among the employers of an Italian service company by measuring positive and negative aspects of psychological wellbeing related to mindfulness and workplace functioning through eight self-report questionnaires (CORE-OM, FFMQ, WEMWBS, MAIA, PSS, PANAS, STAI-X1, SCS). METHOD: Forty-two voluntary non-clinical employers of the company, randomly assigned to the experimental or the control group, were analyzed. The experimental group underwent our IM program, which consists of 12 weekly meditation classes given after the afternoon shift, while the control group did not receive any intervention. Data was analyzed via linear mixed models. RESULTS: Statistically significant results were obtained for FFMQ observing subscale (ß= 0.49, p = 0.014), WEMWBS (ß= 5.31, p = 0.02), PSS (ß= -3.31, p = 0.03), the whole scale of SCS (ß= 0.47, p = 0.01) and self-judgment (ß= 0.68, p = 0.003) and isolation (ß= -0.66, p = 0.01) SCS subscales. Statistically significant results were also found in four out of eight subscales of MAIA: emotional awareness (ß= 1.26, p < 0.001), self-regulation (ß= 1.28, p < 0.001), body listening (ß= 1.08, p < 0.001) and trusting (ß= 1.1, p < 0.001). CONCLUSION: Our intervention has demonstrated to bring beneficial effects in a mindfulness subdomain, in perceived stress, self-compassion, interoception and psychological wellbeing. Based on our results, we conclude that our intervention was effective in increasing the positive aspects of wellbeing and in reducing stress.