Association between chronic kidney disease stages and changes in ambulatory blood pressure monitoring parameters / Associação entre estágios da doença renal crônica e alterações dos parâmetros da monitorização ambulatorial da pressão arterial

Abstract Introduction: Blood pressure (BP) assessment affects the management of arterial hypertension (AH) in chronic kidney disease (CKD). CKD patients have specific patterns of BP behavior during ambulatory blood pressure monitoring (ABPM). Objectives: The aim of the current study was to evaluate the associations between progressive stages of CKD and changes in ABPM. Methodology: This is a cross-sectional study with 851 patients treated in outpatient clinics of a university hospital who underwent ABPM examination from January 2004 to February 2012 in order to assess the presence and control of AH. The outcomes considered were the ABPM parameters. The variable of interest was CKD staging. Confounding factors included age, sex, body mass index, smoking, cause of CKD, and use of antihypertensive drugs. Results: Systolic BP (SBP) was associated with CKD stages 3b and 5, irrespective of confounding variables. Pulse pressure was only associated with stage 5. The SBP coefficient of variation was progressively associated with stages 3a, 4 and 5, while the diastolic blood pressure (DBP) coefficient of variation showed no association. SBP reduction was associated with stages 2, 4 and 5, and the decline in DBP with stages 4 and 5. Other ABPM parameters showed no association with CKD stages after adjustments. Conclusion: Advanced stages of CKD were associated with lower nocturnal dipping and greater variability in blood pressure.

Resumo Introdução: A avaliação da pressão arterial (PA) tem impacto no manejo da hipertensão arterial (HA) na doença renal crônica (DRC). O portador de DRC apresenta padrão específico de comportamento da PA ao longo da monitorização ambulatorial da pressão arterial (MAPA). Objetivos: O objetivo do corrente estudo é avaliar as associações entre os estágios progressivos da DRC e alterações da MAPA. Metodologia: Trata-se de um estudo transversal com 851 pacientes atendidos nos ambulatórios de um hospital universitário que foram submetidos ao exame de MAPA no período de janeiro de 2004 a fevereiro de 2012 para avaliar a presença e o controle da HA. Os desfechos considerados foram os parâmetros de MAPA. A variável de interesse foi o estadiamento da DRC. Foram considerados como fatores de confusão idade, sexo, índice de massa corporal, tabagismo, causa da DRC e uso de anti-hipertensivos. Resultados: A PA sistólica (PAS) se associou aos estágios 3b e 5 da DRC, independentemente das variáveis de confusão. Pressão de pulso se associou apenas ao estágio 5. O coeficiente de variação da PAS se associou progressivamente aos estágios 3a, 4 e 5, enquanto o coeficiente de variação da pressão arterial diastólica (PAD) não demonstrou associação. O descenso da PAS obteve associação com estágios 2, 4 e 5, e o descenso da PAD, com os 4 e 5. Demais parâmetros da MAPA não obtiveram associação com os estágios da DRC após os ajustes. Conclusão: Estágios mais avançados da DRC associaram-se a menor descenso noturno e a maior variabilidade da pressão arterial.

A Comparison of 06:00 AM Versus 09:00 AM Serum Cortisol as a Basal Morning Cortisol in Guwahati, Assam: A Pilot Study.

Introduction: Cortisol secretion is regulated by circadian rhythm, which is influenced by zeitgebers like light. In India, the entire country operates under a single time zone, Indian Standard Time, which may not align with the local sunrise timing across different regions. Aims: This study aimed to compare the basal serum cortisol levels between 06:00 AM and 09:00 AM in Guwahati, Assam, where sunrise occurs earlier compared with the western part of the country. A cross-sectional pilot study was conducted from December 2022 to June 2023 in a tertiary care hospital in Guwahati. Methods: Serum cortisol samples were collected at 06:00 AM and 09:00 AM from 25 healthy adult participants once in winter and again in summer. Descriptive statistics and paired Student's t-tests were used. Results: The mean serum cortisol levels at 06:00 AM in winter, summer and overall were 13.2, 13.4 and 13.3 µg/dL, respectively. At 09:00 AM, the mean serum cortisol levels in winter, summer and overall were 8.2, 7.7 and 8.0 µg/dL, respectively. Significant differences were observed between the 06:00 AM and 09:00 AM cortisol levels in both winter and summer (P <0.001). Conclusion: This study highlights the importance of considering the influence of earlier sunrise on circadian rhythm, cortisol secretion and sampling protocols. Recognising the impact of earlier sunrise on cortisol secretion and adapting sampling protocols accordingly to align with the local sunrise can provide a more accurate assessment of basal cortisol levels and help avoid potential misinterpretation and diagnostic challenges associated with low values.

The optimal measurement period of actigraphy for circadian rhythm in relation to adiposity: A retrospective case-control study.

BACKGROUND: This study focused on the relationship between adiposity and Rest-Activity Rhythms (RAR), utilizing both parametric cosine-based models and non-parametric algorithms. The emphasis was on the impact of varying measurement periods (7-28 days) on this relationship. METHODS: We retrieved actigraphy data from two datasets, encompassing a diverse cohort recruited from an obesity outpatient clinic and a workplace health promotion program. Participants were required to wear a research-grade wrist actigraphy device continuously for a minimum of four weeks. The final dataset included 115 individuals (mean age 40.7 ± 9.5 years, 51 % female). We employed both parametric and non-parametric methods to quantify RAR using six standard variables. Additionally, the study evaluated the correlations between three key adiposity indices - Body Mass Index (BMI), Visceral Adipose Tissue (VAT) area, and Body Fat Percentage (BF%) - and circadian rhythm indicators, controlling for factors like physical activity, age, and gender. RESULTS: The obesity group displayed a significantly lower relative amplitude (RA) as per non-parametric algorithm findings, with a decreased amplitude noted in the parametric algorithm analysis, in comparison to the overweight and control groups. The relationship between circadian rhythm indicators and adiposity metrics over 7- to 28-day periods was examined. A notable negative correlation was observed between RA and both BMI and VAT, while correlation coefficients between adiposity indicators and non-parametric circadian parameters increased with extended durations of actigraphy data. Specifically, RA over a 28-day period was significantly correlated with BF%, a trend not seen in the 7-day measurement (p = 0.094) in multivariate linear regression. The strength of the correlation between BF% and 28-day RA was more pronounced than that in the 7-day period (p = 0.044). However, replacing RA with amplitude as per parametric cosinor fitting yielded no significant correlations for any of the measurement periods. CONCLUSION: The study concludes that a 28-day measurement period more effectively captures the link between disrupted circadian rhythms and adiposity. Non-parametric algorithms, in particular, were more effective in characterizing disrupted circadian rhythms, especially when extending the measurement period beyond the standard 7 days.

Nobiletin promotes lipolysis of white adipose tissue in a circadian clock-dependent manner.

Nobiletin has been reported to protect against obesity-related metabolic disorders by enhancing the circadian rhythm; however its effects on lipid metabolism in adipose tissue are unclear. In this study, mice were fed with high-fat diet (HFD) for four weeks firstly and gavaged with 50 or 200 mg/kg bodyweight/day nobiletin at Zeitgeber time (ZT) 4 for another four weeks while still receiving HFD. At the end of the 8-week experimental period, the mice were sacrificed at ZT4 or ZT8 on the same day. Mature 3T3-L1 adipocytes were treated with nobiletin in the presence or absence of siBmal1, siRora, siRorc, SR8278 or SR9009. Nobiletin reduced the weight of white adipose tissue (WAT) and the size of adipocytes in WAT. At ZT4, nobiletin decreased the TG, TC and LDL-c levels and increased serum FFA level and glucose tolerance. Nobiletin triggered the lipolysis of mesenteric and epididymal WAT at both ZT4 and ZT16. Nobiletin increased the level of RORγ at ZT16, that of BMAL1 and PPARγ at ZT4, and that of ATGL at both ZT4 and ZT16. Nobiletin increased lipolysis and ATGL levels in 3T3-L1 adipocytes in Bmal1- or Rora/c- dependent manner. Dual luciferase assay indicated that nobiletin enhanced the transcriptional activation of RORα/γ on Atgl promoter and decreased the repression of RORα/γ on PPARγ-binding PPRE. Promoter deletion analysis indicated that nobiletin inhibited the suppression of PPARγ-mediated Atgl transcription by RORα/γ. Taken together, nobiletin elevated lipolysis in WAT by increasing ATGL levels through activating the transcriptional activity of RORα/γ and decreasing the repression of RORα/γ on PPARγ-binding PPRE.

Atrial fibrillation rhythm management: a matter of timing.

Rhythm control in patients with atrial fibrillation (AF) has evolved dramatically in the last decades. Several studies have informed us of the benefits of an early rhythm control strategy and primary rhythm control by catheter ablation (CA). Similarly, several studies have investigated the effects of CA in patients with longer AF duration and more comorbidities, especially heart failure. In the current review, we summarize the current evidence on rhythm control at different time points during the disease course of AF [Table 1 and Central illustration].

Circadian Temperature in Moderate to Severe Acute Stroke Patients.

Background: Stroke patients often present circadian disruption due to multiple causes e.g., primary disease, comorbidities, medication, immobilization, reduced daylight entrainment and sleep disturbances. Objective: To investigate the circadian rhythm of temperature in forehead skin in patients with moderate to severe stroke admitted for rehabilitation. Methods: A physiologic study in form of a secondary analysis of a former randomized study. In total 27 patients with moderate to severe stroke were included between May 1st 2014, and June 1st 2015. Circadian temperature was collected approx. seven days after admission at the acute stroke unit by a skin surface temperature probe as part of a Polysomnography (PSG) measurement. Results: Temperature variations show no circadian rhythm (Type 3 tests of fixed effects by SAS, p = 0.1610). The median temperature variance did fluctuate, but not significantly, and the small changes in circadian temperature variance did not follow the normal temperature variance. Conclusion: Patients with moderate to severe stroke show an abrogated circadian rhythm of temperature. There is an unmet need to understand the mechanisms for this, significance for stroke outcome and treatment.

Implementation of an atrial fibrillation better care (ABC) pathway management strategy: Findings from the Iranian registry of atrial fibrillation.

Introduction: The Atrial Fibrillation Better Care (ABC) pathway is such an integrated care approach, recommended in guidelines. The aim of this service evaluation study was to evaluate the impact of implementing the ABC pathway in Iranian population. Methods: In this prospective longitudinal cohort study, consecutive patients with a diagnosis of AF were initially evaluated. Patients at baseline were evaluated in hence of adherence to ABC pathway strategy. After study enrolment, first and second follow-up service evaluations were conducted at 6 and 12 months, respectively. Results: The use of vitamin K antagonists (VKA) decreased from 25.1 % at enrolment to 13.8 % at follow-up; instead, non-VKA oral anticoagulants (NOAC) utilization increased from 40.0 % to 86.1 %, while antiplatelet treatment decreased from 34.9 % to 0 %. Use of antihypertensive drugs, ARBs, diuretics, and statins increased after implementation of the ABC pathway. Implementation of the ABC pathway approach led to a decrease in the occurrence of stroke/TIA (from 6.3 % to 2.2 %, p = 0.002), systemic thromboembolism (from 1.4 % to 0.0 %, p = 0.04), nose bleeds (from 0.8 % to 0.6 %, p = 0.04), skin bruising (from 1.2 % to 0.0 %, p = 0.002), and heart failure (from 7.7 % to 4.7 %, p = 0.04). The proportion of patients in EHRA Class I-II increased from 93.3 % at enrolment to 98.1 % at follow-up. Conclusion: In this first study from a Middle East population, compliance with ABC pathway strategy in the management of AF was associated with optimization of management and general improvements in patient outcomes during follow-up.

Thirty-Day High-Grade Aortic Valve Block Post-Transcatheter Aortic Valve Replacement in Patients Discharged on Heart Rhythm Monitor.

Background: Conduction disease is an important and common complication post-transcatheter aortic valve replacement (TAVR). Previously, we developed a conduction disease risk stratification and management protocol post-TAVR. This study aims to evaluate high-grade aortic valve block (HAVB) incidence and risk factors in a large cohort undergoing ambulatory cardiac monitoring post-TAVR according to conduction risk grouping. Methods: This single-center, retrospective study evaluated all patients discharged on ambulatory cardiac monitoring between 2016 and 2021 and stratified them into 3 groups based on electrocardiogram predictors of HAVB risk (group 1 [low], group 2 [intermediate], and group 3 [high]). HAVB was defined as ≥2 consecutive nonconducted P waves in sinus rhythm or bradycardia <50 beats/minute with a fixed rate for atrial fibrillation/flutter. Descriptive statistics were used to show the incidence and timeline, while logistic regression was utilized to evaluate predictors of HAVB. Results: Five hundred twenty-eight patients were included (median age 80 years [74-85]; 43.8% female). Forty-one patients (7.8%) developed HAVB during ambulatory monitoring (68% were asymptomatic). Over a median follow-up of 2 years (1.3-2.7), the overall mortality rate was 15.0% (30-day mortality rate of 0.57%, n = 3). Risk factors for HAVB were male sex (odds ratio [OR] = 2.46, p = 0.02, 95% CI = 1.21-5.43), baseline right bundle branch block (OR = 2.80, p = 0.01, 95% CI = 1.17-6.19), and post-TAVR QRS >150 â€‹ms (OR = 2.16, p = 0.03, 95% CI = 1.01-4.40). The negative predictive value for patients in groups 1 and 2 for 30-day HAVB was 95.0 and 93.8%, respectively. Conclusions: The risk of 30-day HAVB post-TAVR on ambulatory monitoring post-TAVR varies according to post-TAVR electrocardiogram findings, and a 3-group algorithm effectively identifies groups with a low negative predictive value for HAVB.

Assessment of parameters reflecting the reactivity of the autonomic nervous system of Polish firefighters on the basis of a test in a smoke chamber.

Objective: Measurement and analysis of heart rate variability in a population of professional firefighters based on heart rate (RR) recording. Assessment based on a smoke chamber test in correlation with age, length of service, body mass index. Materials and methods: The smoke chamber test for the officers of the State Fire Service (SFS) is aimed at improving the skills and techniques of working in special clothing and in a respiratory protection set (RPS) under high psychophysical burden. The study was divided into 3 stages: 1. measurement of parameters at rest - sitting position for 5 min, 2. measurement of parameters during the firefighter's activity, effort related to the training path and the test in the smoke chamber, indefinite time (different for each firefighter), 3. measurement of parameters at rest after exercise - sitting position for 5 min. Each firefighter included in the study had fitted onto his chest a Polar H10 band with a sensor (size XXL) that measures parameters HR, HRV (sensor connected via Bluetooth to an application on the phone of a person controlling the test). Results: The study involved 96 firefighters aged 19-45 (Mean 27.9; SD 7.4), with 1-19 years of service (Mean 5.2; SD 4.6). The study included 75 firefighters who completed the entire activity and their results were recorded completely in a way that allowed for analysis and interpretation. Results of 17 firefighters were selected (parameters describing HRV changes was carried out, which are important from the authors' experience: RMSSD, HF ms2, DFA α1). Conclusion: The presence of excessive body weight did not affect HR parameters, which may be related to the limited possibilities of using the BMI index among people with high muscle mass. Longer work experience has a health-promoting effect on heart rate values through increased adaptation of the circulatory system to increased effort and stress. HRV parameter and ANS activity have a wide range of clinical applications, in addition to monitoring health status in the course of diseases, ANS activity can be analyzed in correlation with occupational risk factors.

Circadian rhythm of brain-derived neurotrophic factor in serum and plasma.

The neurotrophic growth factor brain-derived neurotrophic factor (BDNF) plays a crucial role in various neurodegenerative and psychiatric diseases, such as Alzheimer's disease, schizophrenia and depression. BDNF has been proposed as a potential biomarker for diagnosis, prognosis and monitoring therapy. Understanding the factors influencing BDNF levels and whether they follow a circadian rhythm is essential for interpreting fluctuations in BDNF measurements. We aimed to investigate the circadian rhythm of BDNF by collecting multiple peripheral venous blood samples from young, healthy male participants at 12 different time points over 24 h. In addition, vital parameters, cortisol and insulin like growth factor 1 (IGF1) were measured to explore potential regulatory mechanisms, interfering variables and their correlations with BDNF concentration. The findings revealed that plasma BDNF did not exhibit any significant fluctuations over 24 h, suggesting the absence of a circadian rhythm. However, serum BDNF levels decreased during sleep. Furthermore, serum BDNF showed a positive correlation with heart rate but a negative correlation with IGF1. No significant correlation was observed between cortisol and BDNF or IGF1. Although plasma BDNF suggests steady-state conditions, the decline of serum BDNF during the nocturnal period could be attributed to physical inactivity and associated with reduced haemodynamic blood flow (heart rate reduction during sleep). The type of sample collection (peripheral venous cannula vs. blood sampling using a butterfly system) does not significantly affect the measured BDNF levels. The sample collection during the day did not significantly affect BDNF analysis, emphasizing the importance of considering activity levels rather than timing when designing standardized protocols for BDNF assessments.

Investigative agents for atrial fibrillation: agonists and stimulants, progress and expectations.

INTRODUCTION: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. Its prevalence has increased due to worldwide populations that are aging in combination with the growing incidence of risk factors associated. Recent advances in our understanding of AF pathophysiology and the identification of nodal players involved in AF-promoting atrial remodeling highlights potential opportunities for new therapeutic approaches. AREAS COVERED: This detailed review summarizes recent developments in the field antiarrhythmic drugs in the field AF. EXPERT OPINION: The current situation is far than optimal. Despite clear unmet needs in drug development in the field of AF treatment, the current development of new drugs is absent. The need for a molecule with absence of cardiac and non-cardiac toxicity in the short and long term is a limitation in the field. Improvement in the understanding of AF genetics, pathophysiology, molecular alterations, big data and artificial intelligence with the objective to provide a personalized AF treatment will be the cornerstone of AF treatment in the coming years.

Amplitude rise time sensitivity in children with and without dyslexia: differential task effects and longitudinal relations to phonology and literacy.

The speech amplitude envelope carries important acoustic information required for speech intelligibility and contains sensory cues (amplitude rise times, ARTs) that play a key role in both sensory rhythm perception and neural speech encoding. Individual differences in children's sensitivity to ARTs have been related to the development of children's phonological processing skills across languages by the Temporal Sampling theory. Impaired processing of ARTs also characterises children with dyslexia. However, different ART tasks have been employed in different studies, in different languages, and at different ages. Here, we compare the sensitivity of three frequently used ART tasks (based on synthetic syllables, sine tones, and speech-shaped noise) in a longitudinal study of English-speaking children with and without dyslexia. Children's ability to discriminate rising frequency, duration, and intensity was also tested. ART discrimination in all 3 tasks was significantly inter-related, but different relations to phonology and literacy were found for different ART tasks at different ages. In particular, the often-used sine tone and speech-shaped noise ART tasks showed greater sensitivity in older children, while the synthetic syllable task (/ba/ rise) showed greater sensitivity in younger children. Sensitivity to rising frequency was also related to phonology and literacy across ages. The data are interpreted with respect to the Temporal Sampling theory of developmental dyslexia.

Cxcr4a regulates heart progenitor development and cardiac rhythm in zebrafish.

Cxcr4a is involved in multiple organ development including coronary vasculature formation and heart left-right (LR) patterning, whether it is involved in heart progenitor determination and cardiac rhythm regulation is not addressed. Here we showed that in cxcr4a mutants, from 2 days post fertilization (dpf) to 4dpf the embryos transiently displayed pericardial edema and increased cardiac rhythm. While from 5dpf, the heart phenotype disappeared. Detailed analysis demonstrated that, at 36hpf and 48hpf, even though there was no distinct difference in the heart size between cxcr4a mutants and controls, the expression of myl7 was decreased. Further data showed that, the heart progenitors were decreased at 18SS(Somite Stage). Mechanically, RNA-seq, RT-qPCR and in situ experiments showed that the retinoic acid (RA) signaling was upregulated, and the up-regulation of RA signaling may mediate the role of cxcr4a in regulating heart progenitor development. In addition, we also identified that low dose of RA treatment accelerated the cardiac rhythm, being similar to that in cxcr4a mutants. Decreasing RA signaling partially restored the rapid cardiac rhythm in cxcr4a mutants, implying the possibility that RA signaling partially mediates the role of cxcr4a in regulating cardiac rhythm. In conclusion, our study identified cxcr4a simultaneously regulates heart progenitor determination and cardiac rhythm.

Association between PER and CRY gene polymorphisms and the response to caffeine citrate treatment in infants with apnea of prematurity.

Background: Circadian rhythms impact metabolism and the therapeutic effects of drugs. The purpose of this study was to determine the association between PER and CRY polymorphisms and caffeine citrate treatment response in infants with apnea of prematurity. Methods: A total of 221 preterm infants of gestational age <34 weeks were included in this study (160 in the response group and 61 in the non-response group). The propensity score matching method was used to perform a 1:1 matching for all premature infants, and the general characteristics and clinical outcomes of the two groups were compared. The association between polymorphisms of the circadian transcription repressors PER and CRY and caffeine citrate treatment response in infants with apnea of prematurity was analyzed with co-dominant, dominant, recessive, and over-dominant models, as well as analysis of alleles. Generalized multifactor dimensionality reduction (GMDR) analysis was used to analyze the interaction between the PER and CRY genes. Results: After propensity score matching, 45 preterm infants were included in each of the response and non-response groups, and there were no statistically significant differences in general characteristics between the two groups (P > 0.05). Infants in the non-response groups had a higher incidence of moderate and severe bronchopulmonary dysplasia (BPD) (P = 0.043), retinopathy of prematurity (ROP) (P = 0.035), and invasive ventilation (P = 0.027), and their duration of oxygen use (P = 0.041) was longer. When corrected for false discovery rate, the PER3 rs228669 recessive model (P FDR = 0.045) and the over-dominant model (P FDR = 0.045) were both associated with caffeine citrate treatment response. Preterm infants with the rs228669 CC genotype had a significantly lower rate of caffeine citrate non-response in the recessive model (OR = 0.28, 95% CI = 0.12-0.66), which was significantly higher in preterm infants with the CT genotype in the over-dominant model (OR = 4.18, 95% CI = 1.64-10.66). GMDR analysis revealed an interaction between the PER and CRY genes (P < 0.05). Conclusions: Circadian rhythms may play a role in the response of premature infants to caffeine citrate, and polymorphisms of the PER and CRY genes may influence the effectiveness of caffeine citrate treatment for apnea of prematurity.

Effect of time of day on outcomes in elective surgery: a systematic review.

BACKGROUND: The timing of elective surgery could affect clinical outcome because of diurnal rhythms of patient physiology as well as surgical team performance. Waiting times for elective surgery are increasing in many countries, leading to increasing interest in undertaking elective surgery in the evening or at night. We aimed to systematically review the literature on the effect of the timing of elective (but not urgent or emergency) surgery on mortality, morbidity and other clinical outcomes. METHODS: We searched databases for relevant studies combining the terms 'circadian rhythm' and 'anaesthesia/surgery'. Additional relevant articles were found by hand-searching the references. All studies were screened for bias. Included studies examined daytime vs. evening/night-time surgery, morning vs. afternoon surgery, multiple timeslots or used time as a continuous variable. RESULTS: Nineteen retrospective cohort studies, one prospective cohort study and one randomised controlled trial were included (n = 798,914). Evening/night-time elective surgery was associated with a higher risk of mortality when compared with daytime procedures in three studies (n = 611,230), with odds ratios (95%CI) for mortality ranging from 1.35 (1.16-1.56) to 3.98 (1.54-10.30), while no differences were found in three other studies (n = 142,355). No differences were found for morning vs. afternoon surgery (four studies, n = 3277). However, most studies had a low quality of evidence due to their retrospective nature and because not all studies corrected for patient characteristics. Moreover, the studies were heterogeneous in terms of the reported time slots and clinical outcomes. CONCLUSIONS: We found that evening/night-time elective surgery is associated with a higher risk of mortality compared with daytime surgery. However, the quality of evidence was graded as low, and thus, future prospective research should publish individual patient data and standardise outcome measures to allow firm conclusions and facilitate interventions.

Incidence and nationwide estimates of cryptogenic ischemic stroke or TIA eligible for prolonged cardiac rhythm monitoring.

INTRODUCTION: Current guidelines indicate prolonged cardiac rhythm monitoring for atrial fibrillation screening in patients with cryptogenic ischemic stroke (IS) or transient ischemic attack (TIA). This study aimed to assess the incidence of cryptogenic IS/TIA eligible for such investigation, and to estimate the number of patients potentially concerned in whole France annually. METHODS: All cryptogenic acute IS/TIA cases ⩾35 years old were retrieved from the population-based Dijon Stroke Registry, France (2013-2020). Patients eligible for prolonged cardiac rhythm monitoring were defined after excluding those who died in-hospital or within the first 30 days, or with preexisting major impairment. Annual incidence rates of eligible cryptogenic IS/TIA were calculated by age groups and sex. The total number of eligible patients in France was estimated by standardization to age- and sex-specific incidence. RESULTS: Among 2811 IS/TIA patients recorded in the Dijon Stroke Registry, 1239 had cryptogenic IS/TIA of whom 1045 were eligible for prolonged cardiac rhythm monitoring (517 IS and 528 TIA, mean age 73.6 ± 14.6 years old, 55.4% women). Crude incidence rates of eligible cryptogenic IS/TIA were 169/100,000 per year (95% CI: 159-179) in overall sexes, 83/100,000 per year (95% CI: 76-91) for IS, and 85/100,000 per year (95% CI: 78-93) for TIA. The total number of patients with cryptogenic IS/TIA eligible for prolonged cardiac rhythm monitoring in France was estimated to be 66,125 (95% CI: 65,622-66,630) for the calendar year 2022, including 32,764 (95% CI: 32,410-33,120) with IS and 33,361 (95% CI: 33,004-33,721) with TIA. CONCLUSIONS: This study demonstrated a high incidence of cryptogenic IS/TIA eligible for prolonged cardiac rhythm monitoring. Estimates at a national level pointed out the large number of patients who may require access to such atrial fibrillation screening, with attention to be paid on regarding organization of care networks and related costs.

A Bibliometric Study from 1992 to 2023 on the Relationship between Biological Clock and Diabetes.

AIMS: A bibliometric study was conducted to gain deeper insights into the current state of research on diabetes and the biological clock (BC). METHODS: The study involved a comprehensive search for literature related to diabetes and BC published between 1992 and 2023 in the Web of Science database. RESULTS: Ninety-five articles were published in 65 journals, with six of these journals not included in the Journal Citation Reports as of 2022. Among the remaining 59 journals, 10 had an impact factor (IF) greater than 10, and 21 had an IF greater than 5. Twenty-nine journals belonged to Quartile 1, while 16 journals were part of Quartile 2. The articles were contributed by researchers from 22 countries, with the Netherlands and the USA being the most prolific contributors. However, the total number of citations for articles from the USA was significantly higher than that of the Netherlands. The co-occurrence analysis of title and abstract keywords primarily focused on investigating the mechanisms of BC. Regarding author keywords and keyword-plus, the co-occurrence analysis centered around diabetes and BC. International collaboration was prominent among developed countries, with the Netherlands, the USA, and France being major participants. Institution- wise cooperation primarily occurred between two research institutions in the Netherlands. In total, the 95 articles received 5,157 citations, averaging 54.28 citations per article. CONCLUSION: To foster advancements in this area, more attention and international cooperation are necessary. Emphasizing collaborative efforts can drive the development of novel approaches to manage diabetes and regulate blood glucose levels effectively.

Alzheimer's disease and sleep disorders: A bidirectional relationship.

Alzheimer's disease (AD) is the most prevalent dementia, pathologically featuring abnormal accumulation of amyloid-ß (Aß) and hyperphosphorylated tau, while sleep, divided into rapid eye movement sleep (REM) and nonrapid eye movement sleep (NREM), plays a key role in consolidating social and spatial memory. Emerging evidence has revealed that sleep disorders such as circadian disturbances and disruption of neuronal rhythm activity are considered as both candidate risks and consequence of AD, suggesting a bidirectional relationship between sleep and AD. This review will firstly grasp basic knowledge of AD pathogenesis, then highlight macrostructural and microstructural alteration of sleep along with AD progression, explain the interaction between accumulation of Aß and hyperphosphorylated tau, which are two critical neuropathological processes of AD, as well as neuroinflammation and sleep, and finally introduce several methods of sleep enhancement as strategies to reduce AD-associated neuropathology. Although theories about the bidirectional relationship and relevant therapeutic methods in mice have been well developed in recent years, the knowledge in human is still limited. More studies on how to effectively ameliorate AD pathology in patients by sleep enhancement and what specific roles of sleep play in AD are needed.

Influence of circadian rhythm on effects induced by mechanical strain in periodontal ligament cells.

PURPOSE: The aim of this study was to investigate the influence of mechanical strain on clock gene function in periodontal ligament (PDL) cells. Furthermore, we wanted to analyze whether effects induced by mechanical stress vary in relation to the circadian rhythm. METHODS: Human PDL fibroblasts were synchronized in their circadian rhythm with dexamethasone and stretched over 24 h. Unstretched cells served as controls. Gene expression of the core clock genes were analyzed at 4 h intervals by quantitative real-time polymerase chain reaction (qRT-PCR). Time points 0 h (group SI1) and 12 h (group SI2) after synchronization served as starting points of a 4 h force application period. Collagen-1α (COL-1α/Col-1α), interleukin-1ß (IL1-ß), and runt-related transcription factor 2 (RUNX2/Runx2) were assessed by qRT-PCR and enzyme-linked immunosorbent assay (ELISA) after 2 and 4 h. Statistical analysis comprised one-way analysis of variance (ANOVA) and post hoc tests. RESULTS: After synchronization, the typical pattern for clock genes was visible in control cells over the 24 h period. This pattern was significantly altered by mechanical strain. Under tensile stress, ARNTL gene expression was reduced, while Per1 and 2 gene expression were upregulated. In addition, mechanical stress had a differential effect on the expression of Col-1α and IL1­ß depending on its initiation within the circadian rhythm (group SI1 vs group SI2). For RUNX2, no significant differences in the two groups were observed. CONCLUSION: Our results suggest that mechanical stress affects the molecular peripheral oscillator of PDL cells. Vice versa, the circadian rhythm also seems to partially influence the effects that mechanical stress exerts on PDL cells.