Effect of timed dosing of usual antihypertensives according to patient chronotype on cardiovascular outcomes: the Chronotype sub-study cohort of the Treatment in Morning versus Evening (TIME) study.

Background: Timing drug administration to endogenous circadian rhythms may enhance treatment efficacy. In the Chronotype sub-study of the Treatment in Morning versus Evening (TIME) clinical trial we examined whether timing of usual antihypertensive medications according to patient chronotype (a behavioural marker of personal circadian rhythm) may influence clinical cardiovascular outcomes. Methods: This was a cohort sub-study of TIME, a prospective, randomised, open-label, blinded-endpoint, UK clinical trial of morning versus evening dosing of usual antihypertensive medications and cardiovascular outcomes. On August 3rd, 2020, all active TIME participants were invited to complete a validated chronotype questionnaire. Chronotype was quantitatively assessed as the mid sleep time on free days corrected for sleep debt on workdays (MSFsc). We analysed associations between chronotype and antihypertensive dosing time and explored their combined effect on cardiovascular outcomes (a composite endpoint of hospitalisation for non-fatal myocardial infarction (MI) or non-fatal stroke, and single components) using proportional hazard time-to-event models adjusted for baseline covariates. These were used to specifically test for interactions between dosing time and chronotype. Findings: Between August 3, 2020, and March 31, 2021, 5358 TIME participants completed the online questionnaire. 2778 were previously randomised to morning dosing and 2580 to evening dosing of their usual antihypertensives. Chronotype was symmetrically distributed around a median MSFsc of 3:07 am. The composite endpoint increased for later MSFsc (later chronotype) dosed in the morning but not in those dosed in the evening (hazard ratios 1.46 [95% CI 1.14-1.86] and 0.96 [95% CI 0.70-1.30] per hour of MSFsc, respectively; interaction p = 0.036). Later chronotype was associated with increased risk of hospitalisation for non-fatal MI in the morning dosing group, and reduced risk in the evening dosing group (hazard ratios 1.62 [95% CI 1.18-2.22] and 0.66 [95% CI 0.44-1.00] per hour of MSFsc, respectively; interaction p < 0.001). No interaction between chronotype and antihypertensive dosing time was observed for stroke events. Interpretation: Alignment of dosing time of usual antihypertensives with personal chronotype could lower the incidence of non-fatal MI compared to a 'misaligned' dosing time regimen. Future studies are warranted to establish whether synchronizing administration time of antihypertensive therapy with individual chronotype reduces risk of MI. Funding: The TIME study was funded by the British Heart Foundation (CS/14/1/30659) with support from the British and Irish Hypertension Society.

Cardiac rehabilitation and acute aortic dissection: understanding and addressing the evidence GAP a systematic review.

Despite guideline recommendations, strategies for implementing cardiac rehabilitation (CR) in patients with acute aortic dissection (AAD) are not well established with little evidence to risk stratify prudent and effective guidelines for the many required variables. We conducted a systematic review of studies (2004-2023) reporting CR following type A (TA) and type B (TB) AAD. Our review is limited to open surgical repair for TA and medical treatment for TB. A total of 5 studies were included (4 TA-AAD and 1 TB-AAD) in the qualitative analysis. In general, observational data included 311 patients who had an overall favorable effect of CR in AAD consisting of a modestly improved exercise capacity and work load during cycle cardiopulmonary exercise test (TB-AAD), and improved quality of life (QoL). No adverse events were reported during symptom limited pre-CR treadmill or cycle exercise VO2 max or CR. Given the overall potential in this high risk population without adequate evidence for important variables such as safe time from post-op to CR, intensity of training, duration and frequency of sessions and followup it is time for a moderate sized well designed safe trial for patients' post-op surgery for TA-AAD and medically treated TB-AAD who are treated with standardized evidence based medical therapy and physical therapy from discharge randomized to CR versus usual care. PROSPERO registry ID: CRD42023392896.

Investigating Chronotype and Sleep Quality in Psoriatic Patients: Results from an Observational, Web-Based Survey.

BACKGROUND: Psoriasis is an inflammatory disease for which the implications and repercussions go far beyond the skin. Psoriasis patients suffer not only due to its skin manifestations and related symptoms but also because of comorbidities and a huge emotional impact. OBJECTIVE: The objective of this study was to investigate chronotype and sleep quality in a group of Italian psoriatic patients. MATERIALS AND METHODS: An observational, cross-sectional, web-based study was set up by the Dermatology and Clinical Medicine Sections of the Department of Medical Sciences, University of Ferrara, Italy. The web questionnaire was sent to an email list of an Italian association of psoriatic patients with the aim of recording their main demographic, social, historical, and clinical data. The survey included two questionnaires: the Morningness-Eveningness Questionnaire (MEQ) and the Pittsburg Sleep Quality Index (PSQI). RESULTS: Two hundred and forty-three psoriatic patients (mean age 52.9 ± 12.8 yrs., 32.5% males and 67.5% females) filled out the questionnaire. A good 63.8% of them were affected with psoriasis for more than 10 years, 25.9% reported having a diffuse psoriasis, and 66.7% were on treatment at the time they completed the questionnaire. With reference to chronotype, the mean MEQ score was 55.2 ± 10.7; furthermore, 44% of the patients were "morning-oriented types", M-types, or "larks", 44.5% were "intermediate-types" or I-types, and 11.5% were "evening-oriented types", E-types, or "owls". No correlations were found between chronotype and psoriasis extension. Based on the PSQI results, 72.8% of the study population was judged to have a low sleep quality. Sleep disturbance was significantly related to female sex, living alone, and the presence of comorbidities. CONCLUSIONS: Sleep disturbance is very common in psoriatic patients, especially in those with comorbidities, in females, and in patients who live alone. The chronotype in psoriatic patients does not appear different when compared to the general population, nor does it seem to have any link with psoriasis severity.

Foot Temperature by Infrared Thermography in Patients with Peripheral Artery Disease before and after Structured Home-Based Exercise: A Gender-Based Observational Study.

Decreased arterial perfusion is a typical condition of patients with peripheral artery disease (PAD), with the microvascular picture particularly present among women. This observational study aimed to detect foot perfusion changes by infrared thermography (IRT) after a home-based exercise program in both sexes. A total of 76 PAD patients with claudication (72 ± 4 years; 52 males) were enrolled in a structured in-home exercise program composed of two daily 8 min interval walking sessions (1:1 walk:rest ratio) with progressively increasing speed. Outcome measures collected at baseline (T0) and at each hospital visit after 5 weeks, 12 weeks and 20 weeks included foot temperature measured by IRT (anterior tibial, posterior tibial, dorsalis pedis and arcuate artery regions), ankle brachial index and the 6 min walking test. After 20 weeks, foot temperature in both limbs showed a significant increasing trend, with a mean variation of 1.3 °C for the more impaired limb and 0.9 °C for the contralateral limb (t = 8.88, p < 0.001 and t = 5.36; p < 0.001, respectively), with significant changes occurring after 5 weeks of training. The sex-oriented analysis did not highlight any significant difference, with an improvement of mean foot temperature of 1.5 ± 0.6 °C in females versus 1.2 ± 0.5 °C in males (p = 0.42). Ankle brachial index and performance also significantly improved over time (p < 0.001) without gender differences. In patients with PAD, a structured low-intensity exercise program significantly improved foot temperature and exercise capacity without any sex-related difference.

Sex- and Gender-Specific Drug Abuse Dynamics: The Need for Tailored Therapeutic Approaches.

Sex and gender have been gaining ever greater attention due to their associated risks, dynamics, patterns and protective factors underlying substance abuse and addiction. Such differentiations and the clarification of complexities thereof take on even greater relevance in light of drug abuse scope worldwide. According to the 2022 World Drug Report released by the United Nations Office on Drugs and Crime (UNODC), in 2020 an estimated 284 million people worldwide aged 15-64 had used a drug within the last 12 months. The authors have set out to shed a light on determinants and contributing factors of drug abuse based on sex and gender and outline policy and medicolegal remarks aimed at delineating sex- and gender-based approaches towards drug abuse therapeutic interventions that are both therapeutically and ethically/legally viable and grounded in an evidence-based set of standards. Neurobiological data suggest that estrogen may facilitate drug taking by interacting with reward- and stress-related systems. In animal research, the administration of estrogen increases drug taking and facilitates the acquisition, escalation, and reinstatement of cocaine-seeking behavior. From a medicolegal perspective, it is of utmost importance to take into account the whole picture constituting each patient profile, which certainly includes gender factors and contributors, when outlining a therapeutic approach. Failure to do so could lead to negligence-based malpractice allegations, in light of the scientific findings representing best practices with which clinicians need to comply when caring for SUD patients.

Visits to Sexually Transmitted Infection Clinics in Italy from January 2016 to November 2021: A Multicenter, Retrospective Study.

There is no evidence of seasonal variation in visits to clinics dedicated to sexually transmitted infections (STIs) in Italy, nor of changes after the advent of the COVID-19 pandemic. An observational, retrospective, multicentric study was conducted to record and analyze all the visits to the STI clinics of the Dermatology Units of the University Hospitals of Ferrara and Bologna and of the Infectious Disease Unit of Ferrara, Italy, between January 2016 and November 2021. Overall, 11.733 visits were registered over a 70-month study period (63.7% males, mean age 34.5 ± 12.8 yrs). The mean number of monthly visits significantly decreased from the advent of the pandemic (136) compared to before (177). In the pre-pandemic period, visits to STI clinics increased in the autumn/winter months when compared to spring/summer, while the trend was the opposite in the pandemic period. Thus, during the pandemic, both an overall significant reduction in visits to STI clinics and a reversal in their seasonality were observed. These trends affected males and females equally. The marked decrease, mostly found in the pandemic winter months, can be linked to the "lockdown"/self-isolation ordinances and social distancing measures during the colder months, coinciding with the spread of the COVID-19 infection, which limited the opportunities for meeting and socializing.

CHRONOFALLS: A multicentre nurse-led intervention in the chronoprevention of in-hospital falls in adults.

BACKGROUND: Falls are among the most common and serious adverse events for hospitalised patients. In-hospital falls pose a major medical and economic challenge for public health worldwide. Nevertheless, the issue is often addressed without regard to certain relevant variables such as the time of the fall. The aim of this study was to determine the effect of the implementation of a nurse-led intervention based on the temporal patterns of falls and their aetiology on the occurrence of falls. METHODS: A mixed-method research design was carried out in three phases: a) a longitudinal prospective study (audits, chronobiological analyses and implementation of a multicentre nurse-led intervention based on temporal patterns of falls); b) a retrospective study of fall records; and c) a qualitative study based on focus groups. The protocol was published in 2021. RESULTS: A difference was observed in the number of fall records before and after the chronopreventive intervention (retrospective: 64.4% vs. 35.6%; p < 0,001). According to the interrupted series analysis, considering the influence of the COVID-19 pandemic, a reduction in falls of 2.96% (95% CI 1.70%-4.17%) was observed. The concepts of falls, the COVID-19 pandemic and the causes of non-registration have emerged as categories for qualitative analysis. CONCLUSIONS: A multicentric nurse-led program based on tailored organisational, educational and behavioural chronopreventive measures seems to lead to a reduction in the number of in-hospital falls. The findings of the present study, highlighting the implementation of chronopreventive measures, can serve as a basis for future health policies. TRIAL REGISTRATION: The project was registered on the Clinical Trials Registry NCT04367298 (29/04/2020).

Lower All-Cause Mortality Risk in Females and Males with Peripheral Artery Disease following Pain-Free Home-Based Exercise: A 7-Year Observational Study.

We evaluated the sex-specific difference in response upon participation in an exercise program with respect to the risk of adverse clinical outcomes among patients with peripheral artery disease (PAD) and claudication. The records of 400 PAD patients were assessed between 2012 and 2015. Two hundred of them were addressed to a walking program prescribed at the hospital and executed at home at symptom-free walking speed (Ex), while the remaining 200 acted as a control group (Co). The number and date of deaths, all-cause hospitalizations, and amputations for a 7-year period were collected from the regional registry. At baseline, no differences were observed (MEXn = 138; FEXn = 62; MCOn = 149; FCOn = 51). The 7-year survival rate was significantly higher in FEX (90%) than in MEX (82% hazard ratio, HR: 0.542 95% CI 0.331-0.885), FCO (45%, HR: 0.164 95% CI 0.088-0.305), and MCO (44%; HR: 0.157 95% CI 0.096-0.256). A significantly lower rate of hospitalization (p < 0.001) and amputations (p = 0.016) was observed for the Ex group compared to the Co group, without differences by sex. In conclusion, in PAD patients, active participation in a home-based pain-free exercise program was associated with a lower rate of death and better long-term clinical outcomes, particularly among women.

The Issue of Gender Bias Represented in Authorship in the Fields of Exercise and Rehabilitation: A 5-Year Research in Indexed Journals.

Despite progress made in recent decades, gender bias is still present in scientific publication authorship. The underrepresentation of women and overrepresentation of men has already been reported in the medical fields but little is known in the fields of exercise sciences and rehabilitation. This study examines trends in authorship by gender in this field in the last 5 years. All randomized controlled trials published in indexed journals from April 2017 to March 2022 through the widely inclusive Medline dataset using the MeSH term "exercise therapy" were collected, and the gender of the first and last authors was identified through names, pronouns and photographs. Year of publication, country of affiliation of the first author, and ranking of the journal were also collected. A chi-squared test for trends and logistic regression models were performed to analyze the odds of a woman being a first or last author. The analysis was performed on a total of 5259 articles. Overall, 47% had a woman as the first author and 33% had a woman as the last author, with a similar trend over five years. The trend in women's authorship varied by geographical area, with the higher representation of women authors in Oceania (first: 53.1%; last: 38.8%), North-Central America (first: 45.3%; last: 37.2%), and Europe (first: 47.2%; last: 33.3%). The logistic regression models (p < 0.001) indicated that women have lower odds of being authors in prominent authorship positions in higher-ranked journals. In conclusion, over the last five years, in the field of exercise and rehabilitation research, women and men are almost equally represented as first authors, in contrast with other medical areas. However, gender bias, unfavoring women, still exists, especially in the last authorship position, regardless of geographical area and journal ranking.

Daylight Saving Time transitions and Cardiovascular Disease in Andalusia: Time Series Modeling and Analysis Using Visibility Graphs.

The present study aimed to determine whether transitions both to and from daylight saving time (DST) led to an increase in the incidence of hospital admissions for major acute cardiovascular events (MACE). To support the analysis, natural visibility graphs (NVGs) were used with data from Andalusian public hospitals between 2009 and 2019. We calculated the incidence rates of hospital admissions for MACE, and specifically acute myocardial infarction and ischemic stroke during the 2 weeks leading up to, and 2 weeks after, the DST transition. NVG were applied to identify dynamic patterns. The study included 157 221 patients diagnosed with MACE, 71 992 with AMI (42 975 ST-elevation myocardial infarction (STEMI) and 26 752 non-ST-elevation myocardial infarction (NSTEMI)), and 51 420 with ischemic stroke. Observed/expected ratios shown an increased risk of AMI (1.06; 95% CI (1.00-1.11); P = .044), NSTEMI (1.12; 95% CI (1.02-1.22); P = .013), and acute coronary syndrome (1.05; 95% CI (1.00-1.10); P = .04) around the autumn DST. The NVG showed slight variations in the daily pattern of pre-DST and post-DST hospitalization admissions for all pathologies, but indicated that the increase in the incidence of hospital admissions after the DST is not sufficient to change the normal pattern significantly.

Seasonal pattern in elderly hospitalized with acute kidney injury: a retrospective nationwide study in Italy.

PURPOSE: Acute kidney injury (AKI) frequently complicates hospitalization and is associated with in-hospital mortality (IHM). It has been reported a seasonal trend in different clinical conditions. The aim of this study was to evaluate the possible relationship between seasons of the year and IHM in elderly hospitalized patients with AKI. METHODS: We selected all admissions complicated by AKI between 2000 and 2015 recorded in the Italian National Hospital Database. ICD-9-CM code 584.xx identified subjects with age ≥ 65 years and age, sex, comorbidity burden, need of dialysis treatment and IHM were compared in hospitalizations recorded during the four seasons. Moreover, we plotted the AKI observed/expected ratio and percentage of mortality during the study period. RESULTS: We evaluated 759,720 AKI hospitalizations (mean age 80.5 ± 7.8 years, 52.2% males). Patients hospitalized with AKI during winter months had higher age, prevalence of dialysis-dependent AKI, and number of deceased patients. In whole population IHM was higher in winter and lower in summer, while the AKI observed/expected ratio demonstrated two peaks, one in summer and one in winter. Logistic regression analysis demonstrated that parameters such as age, autumn, winter, comorbidity burden were positively associated with IHM. CONCLUSION: We conclude that a seasonality exists in AKI, however, relationship between seasons and AKI could vary depending on the aspects considered. Both autumn and winter months are independent risk factors for IHM in patients with AKI regardless of age, sex and comorbidity burden. On the contrary, summer time reduces the risk of death during hospitalizations with AKI.

Ambulatory diastolic blood pressure: a marker of comorbidity in elderly fit hypertensive individuals?

BACKGROUND: Masked diastolic hypotension is a new blood pressure (BP) pattern detected by ambulatory blood pressure monitoring (ABPM) in elderly hypertensives. The aim of this study was to relate ABPM and comorbidity in a cohort of fit elderly subjects attending an outpatient hypertension clinic. METHODS: Comorbidity was assessed by Charlson comorbidity index (CCI) and CHA2DS2VASc score. All subjects evaluated with ABPM were aged ≥ 65 years. CCI and CHA2DS2VASc score were calculated. Diastolic hypotension was defined as mean ambulatory diastolic BP < 65 mmHg and logistic regression analysis was carried out in order to detect and independent relationship between comorbidity burden and night-time diastolic BP < 65 mmHg. RESULTS: We studied 174 hypertensive elderly patients aged 72.1 ± 5.2 years, men were 93 (53.4%). Mean CCI was 0.91 ± 1.14 and mean CHA2DS2VASc score of 2.68 ± 1.22. Subjects with night-time mean diastolic values < 65 mmHg were higher in females [54.7% vs. 45.3%, P = 0.048; odds ratio (OR) = 1.914, 95% CI: 1.047-3.500]. Logistic regression analysis showed that only CHA2DS2VASc score was independently associated with night-time mean diastolic values < 65 mmHg (OR = 1.518, 95% CI: 1.161-1.985; P = 0.002), but CCI was not. CONCLUSIONS: ABPM and comorbidity evaluation appear associated in elderly fit subjects with masked hypotension. Comorbid women appear to have higher risk for low ambulatory BP.

Individual Circadian Preference, Eating Disorders and Obesity in Children and Adolescents: A Dangerous Liaison? A Systematic Review and a Meta-Analysis.

BACKGROUND: Obesity and other eating disorders are an actual public health problem, especially in childhood and adolescents, and could be also related with chronotype. The aim of this systematic review was to determine the relationship between eating disorders, obesity and the different chronotypes in children and adolescents. METHODS: A systematic review of observational studies evaluating young populations dealing with and evaluating chronotype was conducted. Electronic searches were performed in six international databases. A qualitative thematic-categorical analysis was carried out and a random-effects model was used for the quantitative analysis (meta-analysis). RESULTS: Fifteen studies were included, but quantitative analysis was only carried out in three of them. Children and adolescents with an evening chronotype had higher body mass index, consumed more junk food or were more predisposed to suffer from food addiction and night eating syndrome. CONCLUSIONS: Children and adolescents with evening chronotype had higher tendency to incorrect eating behaviors and were suffering from overweight/obesity. Environment but also lifestyle factors should be considered in the association between chronotype and eating disorders and obesity.

Chronobiology of transient global amnesia.

INTRODUCTION: The etiology of transient global amnesia (TGA) is still a matter of debate. Based, among others, on the observation of a close temporal relation between certain events and subsequent TGA episodes, recent proposals discuss the relevance of stress-associated processes impacting on hippocampal functioning. Circadian, infra- and ultradian rhythmicity has been found to play a relevant role in the multifactorial pathomechanisms of various disorders but has not been thoroughly studied in TGA. METHODS: Data of patients with a final diagnosis of TGA were collected in Mannheim, Germany (06/1999-01/2018, n = 404), and in the Kansai district, Japan (04/2006-03/2018, n = 261). Chronological patterns of TGA occurrence were determined. RESULTS: Significant circadian rhythmicity of TGA occurrence with bimodal peaks (mid-morning, late afternoon) was found for the entire population (p = 0.002) and for either sub-cohort (Mannheim: p = 0.003, Kansai: p = 0.007). This finding was confirmed for either sex (women: p = 0.004, men: p = 0.004) and different age groups (< 65 years: p = 0.0009, ≥ 65 years: p = 0.003). There was no variation according to day of the week, month or season, but the proportion of patients with a weekday episode was significantly higher in the Mannheim cohort (p = 0.002). DISCUSSION: We identified a robust circadian rhythm in TGA occurrence which remarkably applied to either of the two study sites located on different continents and which was independent of sex and age. In light of abundant evidence of circadian rhythmicity of both, components of the human stress response system and memory, chronobiological analyses may provide an opportunity to further uncover the mechanisms underlying TGA.

Structured pain-free exercise progressively improves ankle-brachial index and walking ability in patients with claudication and compressible arteries: an observational study.

In patients with peripheral artery disease (PAD), supervised exercise at near-moderate pain improves walking ability but not ankle-brachial index (ABI) values. In a retrospective observational study, we determined vascular and functional effects of a 6-month structured pain-free exercise program in patients with claudication and compressible vessels. Four-hundred and fifty-nine consecutive patients were studied. Segmental limb pressures were measured and ABI calculated during circa-monthly hospital visits. The 6-min (6MWD) and the pain-free walking distance (PFWD) during the 6-min walking test were determined. Two daily 8-min sessions of slow-moderate in-home walking at increasing metronome-paced speed were prescribed. After excluding patients with unmeasurable ABI or incompletion of the program, 239 patients were studied. Safe and satisfactory (88%) execution of the prescribed training sessions was reported. During the visits, bilateral ABI improved (+ 0.07; p < 0.001) as well as the segmental pressures in the more impaired limb, with changes already significant after 5 weeks of slow walking. Both systolic and diastolic blood pressure decreased overtime (F = 46.52; p < 0.001; F = 5.52; p < 0.001, respectively). 6MWD and PFWD improved (41[0‒73]m p < 0.001 and 107[42‒190]m p < 0.001, respectively) with associated decrease of walking heart rate (F = 15.91; p < 0.001) and Physiological Cost Index (F = 235.93; p < 0.001). The variations of most parameters at different visits correlated to the training load calculated. In a regression model, the PFWD variations directly correlated with rate sessions completed, training load and ABI change and inversely with the baseline value (R2 = 0.27; p < 0.001). In the PAD population studied, moderate pain-free exercise improved ABI with associated progressive functional and cardiovascular changes occurring regardless of subjects characteristics.

Home-Based Exercise in Elderly Patients with Claudication and Chronic Kidney Disease Is Associated with Lower Progressive Renal Function Worsening: A 5-Year Retrospective Study.

This observational study aimed to monitor the 5-year trends of kidney function in patients with peripheral artery disease (PAD) and concomitant chronic kidney disease (CKD) enrolled or not enrolled into a rehabilitative exercise program. Sixty-six patients (aged 72 ± 10, males n = 52) at KDOQI stages III-IV and PAD at Rutherford's stage I-III were included in the study, with a group (Exercise, EX; n = 32) receiving a 6-month structured pain-free home-based walking program and a group (Control, CO; n = 34) receiving walking advice and optimal nephrological care. Outcomes included kidney function measured through serum creatinine (sCr) and clinical outcomes, including the rate of advance of CKD stages and admission to dialysis, revascularizations, and hospitalizations. At baseline, the two groups were comparable for age, nephropathy, medications, comorbidities, and PAD severity. Patients in the EX group safely completed the exercise program. SCr values were slightly increased in EX (baseline: 2.35 ± 0.32; 5-year: 2.71 ± 0.39 mg/dL) and progressively worsened in CO (baseline: 2.30 ± 0.31; 5-year 4.22 ± 0.42 mg/dL), with a significant between-group difference (p = 0.002). The control group also showed a higher number of dialysis admissions (5 vs. 0, p = 0.025) and advancing CKD stage as well a higher risks for lower limb revascularization (hazard ratio: 2.59; 95%CI: 1.11-6.02; p = 0.027) and for all-cause hospitalization (hazard ratio: 1.77; 95%CI: 1.05-2.97; p = 0.031). PAD-CKD patients enrolled in a low-moderate intensity home-exercise program showed more favorable long-term trends in kidney function and clinical outcomes than patients with usual care. These preliminary observations need to be confirmed in randomized trials.

Risky Behaviours of Spanish University Students: Association with Mediterranean Diet, Sexual Attitude and Chronotype.

The most common drugs that are consumed by young people are alcohol and tobacco, which are especially prevalent in universities. These risk behaviours can be determined by a series of intrinsic and extrinsic factors. The aim of this study was to evaluate the consumption of alcohol and tobacco by Spanish university students and the relationship between the Mediterranean diet, sexual attitudes and opinions, and chronotype. A multicentre observational study enrolled 457 students from two public universities in Spain. The study period was from December 2017 to January 2018. The majority of the participants consumed alcohol (90.2%), tobacco consumption was low (27.2%), with a high percentage of students (78.6%) having a low dependence on nicotine. The surveyed students demonstrated a high adherence to the Mediterranean diet, which was shown to be associated with less risky alcohol consumption. The Mediterranean diet is a part of healthy lifestyle, and avoiding heavy drinking results in the intention to maintain such a lifestyle. In addition, unhealthy eating habits (skipping breakfast, eating sweets and pastries daily, and fast-food consumption) had a tendency to induce risky alcohol consumption. Therefore, to promote healthy lifestyle habits, it is considered important to establish programs that promote healthy diets in university settings and to evaluate them periodically.

Chronobiology and Chronotherapy in Inflammatory Joint Diseases.

Circadian rhythm perturbations can impact the evolution of different conditions, including autoimmune diseases. This narrative review summarizes the current understanding of circadian biology in inflammatory joint diseases and discusses the potential application of chronotherapy. Proinflammatory cytokines are key players in the development and progression of rheumatoid arthritis (RA), regulating cell survival/apoptosis, differentiation, and proliferation. The production and secretion of inflammatory cytokines show a dependence on the human day-night cycle, resulting in changing cytokine plasma levels over 24 h. Moreover, beyond the circadian rhythm of cytokine secretion, disturbances in timekeeping mechanisms have been proposed in RA. Taking into consideration chronotherapy concepts, modified-release (MR) prednisone tablets have been introduced to counteract the negative effects of night-time peaks of proinflammatory cytokines. Low-dose MR prednisone seems to be able to improve the course of RA, reduce morning stiffness and morning serum levels of IL-6, and induce significant clinical benefits. Additionally, methotrexate (MTX) chronotherapy has been reported to be associated with a significant improvement in RA activity score. Similar effects have been described for polymyalgia rheumatica and gout, although the available literature is still limited. Growing knowledge of chronobiology applied to inflammatory joint diseases could stimulate the development of new drug strategies to treat patients in accordance with biological rhythms and minimize side effects.

Oral Microbiome Dysbiosis Is Associated With Symptoms Severity and Local Immune/Inflammatory Response in COVID-19 Patients: A Cross-Sectional Study.

The human oral microbiome (HOM) is the second largest microbial community after the gut and can impact the onset and progression of several localized and systemic diseases, including those of viral origin, especially for viruses entering the body via the oropharynx. However, this important aspect has not been clarified for the new pandemic human coronavirus SARS-CoV-2, causing COVID-19 disease, despite it being one of the many respiratory viruses having the oropharynx as the primary site of replication. In particular, no data are available about the non-bacterial components of the HOM (fungi, viruses), which instead has been shown to be crucial for other diseases. Consistent with this, this study aimed to define the HOM in COVID-19 patients, to evidence any association between its profile and the clinical disease. Seventy-five oral rinse samples were analyzed by Whole Genome Sequencing (WGS) to simultaneously identify oral bacteria, fungi, and viruses. To correlate the HOM profile with local virus replication, the SARS-CoV-2 amount in the oral cavity was quantified by digital droplet PCR. Moreover, local inflammation and secretory immune response were also assessed, respectively by measuring the local release of pro-inflammatory cytokines (L-6, IL-17, TNFα, and GM-CSF) and the production of secretory immunoglobulins A (sIgA). The results showed the presence of oral dysbiosis in COVID-19 patients compared to matched controls, with significantly decreased alpha-diversity value and lower species richness in COVID-19 subjects. Notably, oral dysbiosis correlated with symptom severity (p = 0.006), and increased local inflammation (p < 0.01). In parallel, a decreased mucosal sIgA response was observed in more severely symptomatic patients (p = 0.02), suggesting that local immune response is important in the early control of virus infection and that its correct development is influenced by the HOM profile. In conclusion, the data presented here suggest that the HOM profile may be important in defining the individual susceptibility to SARS-CoV-2 infection, facilitating inflammation and virus replication, or rather, inducing a protective IgA response. Although it is not possible to determine whether the alteration in the microbial community is the cause or effect of the SARS-CoV-2 replication, these parameters may be considered as markers for personalized therapy and vaccine development.