Abstract Alzheimer's disease (AD), the most prevalent form of dementia, has been increasingly associated with disruptions in circadian rhythms and sleep–wake regulation. This narrative review synthesizes recent literature on how circadian dysfunction may contribute to AD pathogenesis, biomarker profiles, and treatment response. Mechanistic studies suggest important interactions between core clock genes and neurodegenerative cascades involving oxidative stress, neuroinflammation, glial reactivity, and proteostasis. Disruptions in circadian‐regulated molecular pathways, including brain and muscle ARNT‐like 1 (BMAL1)–sirtuin 1 (SIRT1), nuclear factor kappa B (NF‐κB)–NOD‐like receptor family pyrin domain containing 3 (NLRP3), and period circadian regulator 2 (PER2)–antioxidant signaling pathways, may compromise neuronal resilience and worsen AD‐related pathology. Emerging evidence also suggests distinct circadian patterns in AD‐relevant biomarkers, including melatonin, cortisol, orexin, core body temperature, blood–brain barrier permeability, and glial marker oscillations. These rhythmic patterns may have diagnostic and prognostic relevance and support the need for time‐aware biomarker interpretation. Chronotherapeutic strategies targeting circadian biology, including melatonin receptor agonists, light therapy, time‐restricted feeding, and circadian‐aligned drug delivery systems, may help improve targeted clinical endpoints in AD. This review also discusses chronoepigenetics as an emerging area in which clock‐regulated epigenetic modifications may influence neurodegenerative trajectories. Future directions include next‐generation chronotherapeutic targets, such as glial clocks, clock‐gated inflammatory mechanisms, and systemic comorbidities with circadian modulation, including diabetes and hypertension. Overall, the available evidence supports a close association between circadian disruption and both AD pathology and therapeutic response, while also highlighting important gaps in large‐scale clinical trials. This time‐oriented perspective may support the development of personalized, biomarker‐guided, and rhythm‐informed approaches to AD care. By bridging chronobiology and neurodegeneration, this review highlights how circadian precision medicine may refine future approaches to understanding and managing AD.

Objectives: Isolated non-albumin proteinuria (iNAP) has been linked to kidney function decline in diabetes, but its prognostic role in hypertensive patients with chronic kidney disease (CKD) and normal albuminuria remains uncertain. We evaluated whether baseline iNAP predicts longitudinal estimated glomerular filtration rate (eGFR) decline and kidney events in this setting. Methods: In a retrospective cohort of 166 hypertensive CKD outpatients with normal albuminuria, iNAP was defined as total 24-h proteinuria ≥150 mg/day with albuminuria <30 mg/day. Kidney function change was assessed as (i) eGFR trajectory over 6 years using linear mixed-effects models and (ii) a composite kidney endpoint (≥30% eGFR decline or incident end-stage kidney disease) using cumulative incidence and Fine-Gray competing-risk regression (death as competing event). Confounding control was guided by a directed acyclic graph (DAG), yielding a minimal adjustment set (age, sex, diabetes, on-treatment mean arterial pressure, baseline eGFR). Sensitivity analyses examined alternative model specifications and endpoint definitions. Results: Median follow-up was 5.4 years (interquartile range 4.5–6.0). iNAP was present in 41/166 participants; 32 reached the composite kidney endpoint and 25 died. Baseline eGFR was similar in iNAP versus normal proteinuria (57 ± 24 vs. 61 ± 24 mL/min/1.73 m2; p = 0.318). In mixed-effects models, eGFR declined by −0.61 mL/min/1.73 m2/year (95% confidence interval [CI]: −0.96 to −0.25) in normal proteinuria and by −1.53 mL/min/1.73 m2/year (95% CI: −2.15 to −0.91) in iNAP, with a between-group slope difference of −0.92 mL/min/1.73 m2/year (95% CI: −1.63 to −0.22; time × iNAP interaction p = 0.011). In competing-risk analyses, iNAP was associated with a higher risk of the composite kidney endpoint (Fine-Gray subdistribution hazard ratio 3.15, 95% CI: 1.58–6.31; p = 0.001), while cumulative incidence of death without prior kidney endpoint (the competing event) did not differ between groups (Gray’s test p = 0.920). Findings were consistent after DAG-minimal adjustment and across sensitivity analyses. Conclusions: In hypertensive CKD patients with normal albuminuria, baseline iNAP is associated with faster eGFR decline and a higher risk of kidney events, independent of key baseline risk factors in DAG-guided analyses.

INTRODUCTION:Circadian rhythm influences the clinical spectrum of stroke. Despite extensive research, studies examining the circadian influences on stroke occurrence, focusing on demographic factors and common risk factors, are limited. This study aims to examine the distribution and circadian patterns of ischemic stroke onset times and to analyze demographic factors and risk factors related to stroke timing. METHODS:Conducted at Shanghai East Hospital, an affiliated hospital of Tongji University, this study analyzed electronic medical records from 2021 and 2022, screening 1,320 patients. A total of 406 patients met the inclusion criteria: >18 years old, Chinese nationality, diagnosed with acute ischemic stroke, and without liver disease. Stroke occurrences were categorized into six time intervals for Cosinor analysis and chi-square tests. RESULTS:Among 406 patients (62.1% male, mean age 68.7 years), stroke occurrences showed a clear circadian pattern, peaking between 08:00 and 11:59 (36.2%) and occurring predominantly during daylight hours (75.9%). Cosinor analysis confirmed significant circadian rhythmicity. Hypertension (67.5%) and diabetes (33%) were not significantly associated with stroke onset timing. No significant differences in stroke timing were observed across gender or age groups. DISCUSSION:Patients with a history of previous stroke demonstrated a significant association with late afternoon onset (p = 0.038), a pattern infrequently reported in prior studies that may reflect altered vulnerability or treatment-related factors. CONCLUSION:This study demonstrates a pronounced circadian pattern in ischemic stroke, with a latemorning peak. The observed late-afternoon signal among patients with prior stroke warrants further investigation to clarify underlying mechanisms and implications for prevention strategies.

We read with interest the meta-analysis by Lee et al.[1] and the attached editorial by Reboldi et al.[2] addressing the unresolved issue of what the best timing is for antihypertensive medications to maximize their cardiovascular benefit. The controversy arises mainly as a consequence of clinical trials conducted in Spain [3,4]. They have been challenged with respect to the validity of the methods used and therefore the plausibility of their results [5], and they should be treated with caution. Likewise, studies from China included in the recent meta-analysis might have similar methodological inadequacies [1]. Nevertheless, the debate is far from settled. We agree with Lee et al. and Reboldi et al. that the decision about the optimal antihypertensive administration time (morning vs. evening) is complicated. However, we believe an answer could be found once the question is clearly defined and the study is appropriately designed. Clearly, more and better designed randomized clinical trials (RCTs) are needed. However, the confusion arises from several factors. First, there is ambivalence between the aim of answering clinically relevant questions pragmatically and that of establishing the underlying mechanisms of interventions via explanatory trials. For example, both TIME [6] and BedMed [7] were designed to answer a purely clinical question, not to elucidate mechanisms of action. Conversely, some small studies included in the latest meta-analysis [1] were focusing on the pharmacokinetics and pharmacodynamics of drug classes [8]. Second, there is ambivalence in focusing on blood pressure (BP) lowering effect (either daytime or nocturnal) vs. addressing the effectiveness of the treatment on fatal and nonfatal cardiovascular events. Hence, the choice of the clinical outcome can be a significant source of confusion. Elevated nocturnal BP is the strongest predictor of cardiovascular mortality and morbidity, however clinical guidelines do not take nighttime BP into account when setting BP targets, because it is not routinely measured and no properly designed RCTs have assessed the benefit of lowering night BP. Therefore, when debating the best dosing time of antihypertensive medications, a focus on fatal and nonfatal cardiovascular outcomes would be preferred, as indicated in the recent European Society of Cardiology (ESC) recommendations [9]. After all, both TIME and BedMed did not measure BP reliably. In sub-group analyses of self-reported home BP readings, TIME detected lower morning BP in the evening dosing group (1.8/0.4 mmHg) [6] and conversely lower evening BP in the morning dosing group (1.1/0.9 mmHg) [6]. BedMed on the other hand conducted 24 h ABPM in approximately 300 participants in the Alberta area [7]. They found lower nocturnal BP in the evening dosing group (BedMed 7 mmHg systolic [7]). Neither of these differences resulted in improved cardiovascular health outcomes. Third, the current studies failed to consider or satisfactorily deal with likely mediators of the relationship between dosing time and outcomes, amongst them, treatment adherence and chronotype. For example, one limitation of the TIME study – as well as other smaller studies - was the reliance on self-reported adherence to dosing time without any measure of adherence to prescribed antihypertensive medications [3]. Moreover, recent evidence has suggested chronotype (a behavioural marker of personal circadian rhythm) as a possible effect modifier. In the TIME chronotype sub-group, 5358 participants returned the ultra-short version of the Munich ChronoType Questionnaire (μMCTQ). We estimated chronotype as midpoint of sleep on free days (MSF) corrected for sleep debt on workdays (MSFsc). Sleep midpoint (hours:minutes) was treated as a continuous variable, with later midpoints of sleep indicating a 'later chronotype' (n = 1414; 26%) and earlier midpoints of sleep an 'earlier chronotype' (n = 1335; 24%); the remaining participants being intermediate (n = 2442; 45%) [10]. They were equally allocated to morning and evening dosing of their usual antihypertensive medications. After a median follow-up of 5.1 years, we observed a lower rate of hospitalization for nonfatal myocardial infarction when dosing time was synchronized with the participant's chronotype, specifically in later chronotypes receiving evening dosing and in earlier chronotypes receiving morning doses (interaction P < 0.001). Although the detailed analysis has not yet been published, the BedMed researchers have reported that 'there were some trends in the direction that the TIME group were suggesting' [11]. In line with the main TIME study results, we found no effect of dosing time on cardiovascular outcomes in the intermediate chronotypes. Additionally, we observed that later chronotypes showed a trend towards an increased risk of nonfatal stroke, independent of dosing time, in line with the evidence that a later chronotype is an independent predictor of cardiovascular events [12]. If confirmed in RCTs, these observations may suggest that simply establishing chronotype may identify individuals in whom a re-alignment of dosing time of antihypertensive medications with their circadian rhythm (personalized chronotherapy) might provide further cardiovascular clinical benefit. The recent debate at the ESC Congress in London has indicated that with the results of TIME and BedMed the controversy has been put to rest as far as the concept of 'chronotherapy' of hypertension is concerned [4]. However, no hypertension clinical trial to date has been designed with a good methodological understanding of both cardiovascular disease [3,4] and chronobiology [6,7]. Therefore, we would recommend a more careful approach to the interpretation of the results so far. More crucial factors may have been missed, that conceal a clearer answer. In the absence of clear evidence, let's not throw the baby out with the bathwater! ACKNOWLEDGEMENTS Conflicts of interest There are no conflicts of interest.

Introduction: An increased renal resistive index (RRI) and proteinuria can predict an estimated glomerular filtration rate (eGFR) decline in patients with chronic kidney disease (CKD) of various causes. This study hypothesized that the RRI and proteinuria interact to determine disease progression in patients with CKDs of unknown origin. Patients and Methods: One hundred and fifty six patients (age 76.0 ± 8.1 years, 63.5% males) were analyzed for anthropometric, kidney morphology, blood pressure, 24 h urinary protein excretion, and RRI. The CKD-EPI equation was used to calculate the eGFR at baseline and after a two-year follow-up. Patients with an elevated (≥0.80) or normal (<0.80) RRI and significant (≥150 mg/day) or physiological (<150 mg/day) proteinuria were evaluated for the likelihood of at least a 30% drop in the eGFR or the onset of end-stage kidney disease (endpoint). Results: Hypertension and diabetes were the predominant cardiovascular risk factors (90.4%). Fifty patients (32%) met the endpoint. Elevated RRIs (odds ratio, OR, 4.28; 95% confidence interval, CI, 1.82–10.6; p = 0.001) and significant proteinuria (OR 3.59, 95% CI 1.59–8.48, p = 0.003) were independent predictors of the endpoint in a multivariate logistic model. Patients with an elevated RRI and significant proteinuria were more likely to meet the endpoint (R1P1: 65.2%) compared to those with only proteinuria (R0P1: 39.5%, p = 0.043) or both normal factors (R0P0: 10.9%, p < 0.001) but not to those with only an elevated RRI (R1P0: 42.3%, p = 0.094). Continuous RRIs (partial correlation r = −0.245, p < 0.001) and 24 h urinary protein excretion (partial r = −0.226, p = 0.003) were inversely and independently correlated with eGFR% change. R1P1 showed a higher eGFR% reduction (−38.0% ± 20.4%) compared to R0P1 (−25.3% ± 19.0%, p = 0.043) and R0P0 (−8.8% ± 25.1%, p < 0.001) but not to R1P0 (−29.6% ± 21.0%, p = 0.192). Conclusions: An increased RRI and proteinuria were independent predictors of disease progression. When interaction was considered, the negative effect of an elevated RRI on CKD progression was evident in both proteinuric and non-proteinuric patients, whereas the negative effect of proteinuria on disease progression was only significant in patients with no elevated RRIs.

This retrospective study examines the effects of a 6-month home-based walking low-intensity interval training (LIIT) program on systolic blood pressure (SBP) in a cohort of patients with peripheral artery disease (PAD) and controlled (HT) or resistant hypertension (RH). From a cohort of 1011 PAD patients who completed the 6-month LIIT program, the data of those with hypertension without intercurrent therapy changes were analyzed. LIIT included eight bouts of in-home interval walking (walk:rest ratio of 1:1) at slow speed, progressively increased speed, and was maintained by a metronome. Office blood pressure was measured at baseline and after 5, 12, and 26 weeks by the same operator, with the patient lying in supine position. The ankle‒brachial index (ABI) and performance of the 6-min walking test (6MWD) were also assessed. Program updates were performed during visits, and adherence to exercise was verified and classified into tertiles according to the sessions executed. Among the 793 patients studied, 597 had HT, and 196 had RH. All patients safely completed the LIIT sessions (84 ± 11

Takotsubo syndrome (TTS) might exhibit particular chronobiological patterns in its onset, characterized by variations according to time of the day, day of the week, and month of the year.The aim of this study was to fully explore the temporal patterns (circadian, weekly and seasonal) in the onset of TTS. A systematic review and meta-analysis of literature were conducted for studies (2006-2024) reporting the temporal patterns (circadian, weekly and/or seasonal) in the onset of TTS. Among the 4257 studies retrieved, 20 (including 64,567 subjects) fulfilled all eligibility criteria. Data were aggregated used random effects model as pooled risk ratio and the attributable risk (AR).The proportion analysis (including 8 studies; n=853) showed a decreasing pattern of the pooled rates of TTS shifting from the morning to the night (pooled TTS rates: 34.0%; 32.1%; 21.7%; 12.7% in the morning, afternoon, evening and night, respectively). The same pattern was observed stratifying by type of preceding stressful factor or event, considering physical stressors (pooled rates in the morning and night: 37.6% and 9.8%, respectively), and also in case no event could be identified.The pooled rates of TTS onset peaked on Monday and Tuesday (17.3% and 18.4% respectively), then declined during the week, reaching the lowest rates on Friday and Saturday (10.6% and 10.8%, respectively), with no sex differences. TTS onset reached the highest values on summer, and the lowest in winter (27.9% versus 21.7% in summer and winter, respectively). The TTS morning peak based analyses (∼33% of all the registered events) account for a RR of 1.46 (95% CI: 1.38-1.54), the week-based for a RR of 1.26 (1.16-1.35), the season-based for a RR of 1.04 (1.04-1.05).TTS onset exhibits specific chronobiological patterns, characterized by a peak during the morning hours, and on Monday and Tuesday. Differing from other cardiovascular emergencies TTS was more frequent during summer. Further studies are needed to fully understand the underlying pathophysiological mechanisms in order to tailor relative management and preventive strategies.

Background: Peripheral artery disease (PAD) is recognized as a significant contributor to the public health burden in the cardiovascular field and has a significant rate of morbidity and mortality. In the intermediate stages, exercise therapy is recommended by the guidelines, although supervised programs are scarcely available. This single-center observational study aimed to evaluate the long-term outcomes of patients with PAD and claudication receiving optimal medical care and follow-up or revascularization procedures or structured home-based exercise. Methods: The records of 1590 PAD patients with claudication were assessed at the Vascular Surgery Unit between 2008 and 2017. Based on the findings of the recruitment visit, patients were assigned to one of the three following groups according to the available guidelines: Revascularization (Rev), structured exercise therapy (Ex), or control (Co). The exercise program was prescribed at the hospital and executed at home with two daily 10-minute interval walking sessions at a pain-free speed. The number and date of deaths, all-cause hospitalizations, and peripheral revascularizations for 5 years were collected from the Emilia-Romagna regional database. Results: At entry, 137 patients underwent revascularization; 1087 patients were included in the Ex group, and 366 were included in the Co group. At baseline, patients in the Rev group were significantly younger and had fewer comorbidities (p < 0.001). A propensity score matching analysis was performed, and three balanced subgroups of 119 patients were each created. The mortality rate was significantly (p < 0.001) greater in the Co (45%) group than in the Rev (11%) and Ex (11%) groups, as was the incidence of all-cause hospitalizations (Co: 95%; Rev 56%; Ex 60%; p < 0.001). There were no differences in peripheral revascularizations (Co: 19%; Rev: 17%; Ex 11%). Conclusions: In PAD patients with claudication, both revascularization procedures and structured home-based exercise sessions are associated with better long-term clinical outcomes than walking advice and follow-up only.

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 in fl uence 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 speci fi cally 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.

Background: Growing evidence on chronotherapy supports administering treatments according to endogenous biological rhythms. Objectives: To evaluate whether the administration time of dupilumab affects its effectiveness in patients with atopic dermatitis (AD), by virtue of the circadian oscillations of immune system activity. Methods: This retrospective study included all adult patients with AD treated with dupilumab from January 2020 to January 2024 at our unit. Data recorded at baseline (T0) and at the 16-week-treatment visit (T16) included itch severity, sleep disturbance, Eczema Area and Severity Index, Patient-Oriented Eczema Measure, Dermatology Life Quality Index, and immunoglobulin E levels. Therapeutic response was compared between two groups, based on injection time, that is, between 12:00 a.m. and 12:00 p.m. versus between 12:00 p.m. and 12:00 a.m. Results: Fifty-three patients were included, of whom 21 took dupilumab between 12:00 a.m. and 12:00 p.m. and 32 between 12:00 p.m. and 12:00 a.m. All clinical parameters improved from T0 to T16, without significant differences between groups. However, there was a greater improvement in these parameters in subjects taking dupilumab between 12:00 a.m. and 12:00 p.m., compared with the others. Conclusions: These preliminary results suggest a difference in therapeutic response to dupilumab based on the administration time, leading to potential optimization of its efficacy. Further studies on larger samples are needed.

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.

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).

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 (M-EX n = 138; F-EX n = 62; M-CO n = 149; F-CO n = 51). The 7-year survival rate was significantly higher in F-EX (90%) than in M-EX (82% hazard ratio, HR: 0.542 95% CI 0.331-0.885), F-CO (45%, HR: 0.164 95% CI 0.088-0.305), and M-CO (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.

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.

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.