Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22.275
Filtrar
1.
Nat Commun ; 11(1): 4410, 2020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32879310

RESUMO

The hypothalamic suprachiasmatic (SCN) clock contains several neurochemically defined cell groups that contribute to the genesis of circadian rhythms. Using cell-specific and genetically targeted approaches we have confirmed an indispensable role for vasoactive intestinal polypeptide-expressing SCN (SCNVIP) neurons, including their molecular clock, in generating the mammalian locomotor activity (LMA) circadian rhythm. Optogenetic-assisted circuit mapping revealed functional, di-synaptic connectivity between SCNVIP neurons and dorsomedial hypothalamic neurons, providing a circuit substrate by which SCNVIP neurons may regulate LMA rhythms. In vivo photometry revealed that while SCNVIP neurons are acutely responsive to light, their activity is otherwise behavioral state invariant. Single-nuclei RNA-sequencing revealed that SCNVIP neurons comprise two transcriptionally distinct subtypes, including putative pacemaker and non-pacemaker populations. Altogether, our work establishes necessity of SCNVIP neurons for the LMA circadian rhythm, elucidates organization of circadian outflow from and modulatory input to SCNVIP cells, and demonstrates a subpopulation-level molecular heterogeneity that suggests distinct functions for specific SCNVIP subtypes.


Assuntos
Ritmo Circadiano/fisiologia , Neurônios/metabolismo , Núcleo Supraquiasmático , Animais , Mapeamento Encefálico , Relógios Circadianos/fisiologia , Locomoção/fisiologia , Camundongos , Optogenética/métodos , Núcleo Supraquiasmático/citologia , Núcleo Supraquiasmático/metabolismo
2.
Nat Commun ; 11(1): 4411, 2020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32879313

RESUMO

The glymphatic system is a network of perivascular spaces that promotes movement of cerebrospinal fluid (CSF) into the brain and clearance of metabolic waste. This fluid transport system is supported by the water channel aquaporin-4 (AQP4) localized to vascular endfeet of astrocytes. The glymphatic system is more effective during sleep, but whether sleep timing promotes glymphatic function remains unknown. We here show glymphatic influx and clearance exhibit endogenous, circadian rhythms peaking during the mid-rest phase of mice. Drainage of CSF from the cisterna magna to the lymph nodes exhibits daily variation opposite to glymphatic influx, suggesting distribution of CSF throughout the animal depends on time-of-day. The perivascular polarization of AQP4 is highest during the rest phase and loss of AQP4 eliminates the day-night difference in both glymphatic influx and drainage to the lymph nodes. We conclude that CSF distribution is under circadian control and that AQP4 supports this rhythm.


Assuntos
Aquaporina 4/metabolismo , Líquido Cefalorraquidiano/metabolismo , Ritmo Circadiano/fisiologia , Sistema Glinfático/metabolismo , Animais , Astrócitos/metabolismo , Encéfalo/metabolismo , Cisterna Magna/metabolismo , Linfonodos/metabolismo , Camundongos
3.
Cochrane Database Syst Rev ; 9: CD010054, 2020 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-32888198

RESUMO

BACKGROUND: Beta-blockers are commonly used in the treatment of hypertension. We do not know whether the blood pressure (BP) lowering efficacy of beta-blockers varies across the day. This review focuses on the subclass of beta-blockers with partial agonist activity (BBPAA). OBJECTIVES: To assess the degree of variation in hourly BP lowering efficacy of BBPAA over a 24-hour period in adults with essential hypertension. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for relevant studies up to June 2020: the Cochrane Hypertension Specialised Register; CENTRAL; 2020, Issue 5; MEDLINE Ovid; Embase Ovid; the World Health Organization International Clinical Trials Registry Platform; and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. SELECTION CRITERIA: We sought to include all randomised and non-randomised trials that assessed the hourly effect of BBPAA by ambulatory monitoring, with a minimum follow-up of three weeks. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the included trials and extracted the data. We assessed the certainty of the evidence using the GRADE approach. Outcomes included in the review were end-point hourly systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR), measured using a 24-hour ambulatory BP monitoring (ABPM) device. MAIN RESULTS: Fourteen non-randomised baseline controlled trials of BBPAA met our inclusion criteria, but only seven studies, involving 121 participants, reported hourly ambulatory BP data that could be included in the meta-analysis. Beta-blockers studied included acebutalol, pindolol and bopindolol. We judged most studies at high or unclear risk of bias for selection bias, attrition bias, and reporting bias. We judged the overall certainty of the evidence to be very low for all outcomes. We analysed and presented data by each hour post-dose. Very low-certainty evidence showed that hourly mean reduction in BP and HR visually showed an attenuation over time. Over the 24-hour period, the magnitude of SBP lowering at each hour ranged from -3.68 mmHg to -17.74 mmHg (7 studies, 121 participants), DBP lowering at each hour ranged from -2.27 mmHg to -9.34 mmHg (7 studies, 121 participants), and HR lowering at each hour ranged from -0.29 beats/min to -10.29 beats/min (4 studies, 71 participants). When comparing between three 8-hourly time intervals that correspond to day, evening, and night time hours, BBPAA was less effective at lowering BP and HR at night, than during the day and evening. However, because we judged that these outcomes were supported by very low-certainty evidence, further research is likely to have an important impact on the estimate of effect and may change the conclusion. AUTHORS' CONCLUSIONS: There is insufficient evidence to draw general conclusions about the degree of variation in hourly BP-lowering efficacy of BBPAA over a 24-hour period, in adults with essential hypertension. Very low-certainty evidence showed that BBPAA acebutalol, pindolol, and bopindolol lowered BP more during the day and evening than at night. However, the number of studies and participants included in this review was very small, further limiting the certainty of the evidence. We need further and larger trials, with accurate recording of time of drug intake, and with reporting of standard deviation of BP and HR at each hour.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Ritmo Circadiano/fisiologia , Hipertensão/tratamento farmacológico , Acebutolol/uso terapêutico , Agonistas Adrenérgicos beta/uso terapêutico , Adulto , Viés , Pressão Sanguínea/fisiologia , Ensaios Clínicos Controlados como Assunto , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pindolol/análogos & derivados , Pindolol/uso terapêutico , Fatores de Tempo
4.
Chronobiol Int ; 37(8): 1214-1222, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32856947

RESUMO

This study aimed to investigate the relationship between chronotype preference/sleep problems and symptom severity of children with Attention Deficit Hyperactivity Disorder (ADHD) during the COVID-19 outbreak and to assess the chronotype preference/sleep problems that may play a mediating role in the relationship between the reactions to trauma and severity of ADHD symptoms. The sample of this single-center cross-sectional study consisted of 76 children with ADHD and their parents. Trauma symptoms were evaluated with the Children's Impact of Event Scale (CRIES-8); sleep habits were assessed using the Children's Sleep Habits Questionnaire (CSHQ); and chronotype was assessed using the Children's Chronotype Questionnaire (CCQ). There were significant differences in CRIES-8 and CSHQ scores between the eveningness type group and the non-eveningness type group. The CRIES-8 scores of children with ADHD were related to the CCQ and CSHQ scores and severity of ADHD symptoms. In mediation analyses, sleep problems were found to be the full mediating factor in the relationship between CRIES-8 scores and severity of ADHD symptoms and the relationship between CCQ scores and the severity of ADHD symptoms. Our findings indicate that chronotype plays an important role on the negative effects of home confinement of ADHD children during the COVID-19 outbreak. The role of the full mediator of sleep problems in the path from cognition to the behavior of young ADHD and non-ADHD children confined to the home environment during the pandemic period requires further assessment.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Betacoronavirus , Ritmo Circadiano/fisiologia , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , Transtornos do Sono-Vigília/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Criança , Infecções por Coronavirus/fisiopatologia , Estudos Transversais , Feminino , Humanos , Masculino , Pandemias , Pneumonia Viral/fisiopatologia , Transtornos do Sono-Vigília/diagnóstico
5.
Chronobiol Int ; 37(8): 1207-1213, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32746638

RESUMO

This study aimed to investigate the relationship between chronotype preference/sleep problems and symptom severity of children with Autism spectrum disorder (ASD) during the confinement and social isolation of the COVID-19 outbreak. This study included 46 drug-naive children aged 4-17 y diagnosed with ASD. The Autism Behavior Checklist (AuBC), Children's Sleep Habits Questionnaire (CSHQ), and Children's chronotype questionnaire (CCQ) were filled out before and at the end of the COVID-19 mandated home confinement by the children's parents. Children with ASD during the home confinement reported higher chronotype scores, i.e., eveningness chronotype, sleep problems, and autism symptom scores compared to the normal non-hone confinement state. The chronotype score and sleep problems of children with ASD during the home confinement period varied according to the AuBC score. The sleep problems of the children with ASD during the home confinement period mediated the relationship between chronotype score and severity of autism symptoms. It is essential to validate the role of the mediator effect of sleep problems and chronotype in larger samples of children with ASD with restricted to home confinement during the pandemic period. If sleep problems can be controlled with parental education, pharmacotherapy, and psychotherapeutic interventions, the impact on children with ASD of home confinement can be reduced.


Assuntos
Transtorno do Espectro Autista/epidemiologia , Betacoronavirus , Ritmo Circadiano/fisiologia , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Sono/fisiologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/fisiopatologia , Feminino , Humanos , Masculino , Pandemias , Pneumonia Viral/fisiopatologia , Índice de Gravidade de Doença , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/fisiopatologia
6.
Chronobiol Int ; 37(8): 1181-1190, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32757673

RESUMO

The Chinese Government quarantined Wuhan on 23 January 2020 and thereafter the Hubei province, affecting a total of 59 million citizens, to cease the spread of the coronavirus disease in 2019 (COVID-19). The effects of this lockdown on the psychological and mental health of both the affected and unaffected Chinese are largely unknown currently. We utilized one of the largest crowdsourced databases (Sleep as Android) that consisted of 15,681 sleep records from 563 users in China to estimate the change in the sleep pattern of Chinese users during the span of 30 December 2019 to 8 March 2020 with reference to 64,378 sleep records of 1,628 users for the same calendar period of years 2011-2019. The sleep pattern in China changed drastically after 23 January 2020 when the law of quarantine and suspension of Wuhan became effective. The two major findings are: (1) Chinese people increased their sleep duration by an average of 20 min and delayed their sleep onset by an average of 30 min at weekdays, while they maintained a similar sleep duration at weekends, and (2) larger changes were found in several subgroups, including those in Wuhan (80 sleep records from 3 users), female subjects, and those aged ≤ 24 years. Overall, Chinese people slept later and longer than usual during the COVID-19 pandemic quarantine.


Assuntos
Betacoronavirus/metabolismo , Ritmo Circadiano/fisiologia , Infecções por Coronavirus/fisiopatologia , Crowdsourcing , Pneumonia Viral/fisiopatologia , Sono/fisiologia , Vigília , China/epidemiologia , Infecções por Coronavirus/virologia , Surtos de Doenças , Humanos , Saúde Mental , Pandemias , Pneumonia Viral/virologia , Quarentena/psicologia , Transtornos do Sono-Vigília/epidemiologia , Smartphone
7.
PLoS Med ; 17(8): e1003235, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32760068

RESUMO

BACKGROUND: Temporal patterns in the frequency and characteristics of self-harm episodes across the Australian asylum seeker population may have implications for self-harm prevention and public health policy. The aim of this study was to examine how the distribution of self-harm episodes and method(s) of self-harm used across the Australian asylum seeker population vary according to the 24-hour cycle, day, and month, and to establish a basis for further research. METHODS AND FINDINGS: We conducted an observational study of all 949 self-harm incidents reported across the Australian asylum seeker population (representing a monthly average of 28,992 adults) between 1 August 2014 and 31 July 2015, obtained by Freedom of Information (FOI) from the Department of Immigration. Time of self-harm, day, and month of occurrence were investigated across all five Australian asylum seeker populations (i.e., community-based arrangements, community detention, onshore immigration detention, offshore immigration detention [Nauru], and offshore immigration detention [Manus Island]). Significant variations in distributions over the 24-hour cycle were observed by processing arrangements. Compared with the average distribution across all other processing arrangements, self-harm more commonly occurred among community-based asylum seekers (36.3%) between 12:00 AM and 3:59 AM (p < 0.001), in asylum seekers on Manus Island (36.4%) between 4:00 PM and 7:59 PM (p = 0.02), and among asylum seekers in onshore detention (20.4%) between 8:00 PM and 11:59 PM (p < 0.001). Compared with the average distribution across all other methods, self-poisoning (by medication) (25%) was significantly more likely to occur between 12:00 AM and 3:59 AM (p = 0.009), and self-battery (42%) between 8:00 AM and 11:59 AM (p < 0.001). The highest and lowest monthly self-harm episode rates for the whole asylum seeker population were in August (2014) (5 episodes per 1,000 asylum seekers; 95% confidence interval [CI] 1-11) and in both January and February (2015) (2.1 episodes per 1,000 asylum seekers; 95% CI 0.6-7.2), respectively; however, the overlapping CIs indicate no statistically significant differences across the months. When examining monthly trends by processing arrangements, we observed that self-harm was significantly more likely to occur in August (2014) than other months of the year among asylum seekers in onshore detention (19%) (p < 0.001), in January (2015) on Manus Island (18%) (p = 0.002), and in October (2014) on Nauru (15%) (p < 0.001). The main study limitations were that we could not investigate certain characteristics associated with self-harm (e.g., gender, country of origin), as the Department of Immigration did not routinely collect such data. There was also the potential risk of making a type 1 error, given the exploratory nature of the comparisons we undertook; we minimised this by lowering our significance threshold from 0.05 to 0.01. CONCLUSIONS: Self-harm in the Australian asylum seeker population was found to vary according to time of day and month of the year, by processing arrangements. A series of procedure-related and detention-related factors were observed to be associated with the temporal variations in self-harm. These findings should form the basis for further investigation into temporal variations in self-harm among asylum seekers, which may in turn lead to effective self-harm prevention strategies.


Assuntos
Ritmo Circadiano , Vigilância da População , Refugiados/psicologia , Estações do Ano , Comportamento Autodestrutivo/epidemiologia , Comportamento Autodestrutivo/psicologia , Adulto , Austrália/epidemiologia , Ritmo Circadiano/fisiologia , Feminino , Humanos , Masculino , Vigilância da População/métodos , Comportamento Autodestrutivo/diagnóstico , Fatores de Tempo , Adulto Jovem
8.
Nat Commun ; 11(1): 3794, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32732906

RESUMO

Defective rhythmic metabolism is associated with high-fat high-caloric diet (HFD) feeding, ageing and obesity; however, the neural basis underlying HFD effects on diurnal metabolism remains elusive. Here we show that deletion of BMAL1, a core clock gene, in paraventricular hypothalamic (PVH) neurons reduces diurnal rhythmicity in metabolism, causes obesity and diminishes PVH neuron activation in response to fast-refeeding. Animal models mimicking deficiency in PVH neuron responsiveness, achieved through clamping PVH neuron activity at high or low levels, both show obesity and reduced diurnal rhythmicity in metabolism. Interestingly, the PVH exhibits BMAL1-controlled rhythmic expression of GABA-A receptor γ2 subunit, and dampening rhythmicity of GABAergic input to the PVH reduces diurnal rhythmicity in metabolism and causes obesity. Finally, BMAL1 deletion blunts PVH neuron responses to external stressors, an effect mimicked by HFD feeding. Thus, BMAL1-driven PVH neuron responsiveness in dynamic activity changes involving rhythmic GABAergic neurotransmission mediates diurnal rhythmicity in metabolism and is implicated in diet-induced obesity.


Assuntos
Fatores de Transcrição ARNTL/genética , Ritmo Circadiano/fisiologia , Obesidade/patologia , Núcleo Hipotalâmico Paraventricular/metabolismo , Receptores de GABA-A/metabolismo , Animais , Ritmo Circadiano/genética , Dieta Hiperlipídica , Metabolismo Energético/fisiologia , Comportamento Alimentar/fisiologia , Camundongos , Camundongos Knockout , Neurônios/fisiologia , Obesidade/genética , Núcleo Hipotalâmico Paraventricular/citologia
9.
Medicine (Baltimore) ; 99(30): e21227, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791697

RESUMO

Variability of blood pressure (BP) is known as a prognostic value for the subsequent target organ damage in hypertensive patients. Arterial stiffness is a risk factor for cardiovascular morbidity and mortality. The relationship between the arterial stiffness and the BP variability has been controversial. The objective of the present study was to investigate the relationship between arterial stiffness and home BP variability in patients with high normal BP and new onset hypertension (HTN).Four hundred sixty three patients (252 males, 49 ±â€Š12 year-old) with high normal BP or HTN were enrolled. Using radial applanation tonometry, pulse wave analysis (PWA) was performed for evaluation of systemic arterial stiffness. All patients underwent both home BP monitoring (HBPM) and PWA. Home BP variability was calculated as the standard deviation (SD) of 7 measurements of HBPM. Multiple linear regression analysis was performed to estimate and test the independent effects of home BP variability on the arterial stiffness.Mutivariate analysis showed that both systolic and diastolic morning BP variabilities were correlated with arterial stiffness expressed as augmentation pressure (AP, ß-coefficient = 1.622, P = .01 and ß-coefficient = 1.07, P = .035). The SDs of systolic and diastolic BP of evening were also associated with AP (ß-coefficient = 1.843, P = .001 and ß-coefficient = 1.088, P = .036). The SDs of morning and evening systolic BP were associated with augmentation index (AI, ß-coefficient = 1.583, P = .02 and ß-coefficient = 1.792, P = .001) and heart rate (75 bpm) adjusted AI (ß-coefficient = 1.592, P = .001 and ß-coefficient = 1.792, P = .001).In present study, the variability of systolic BP was closely related with arterial stiffness. The home BP variability might be important indicator of arterial stiffness.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Hipertensão/fisiopatologia , Rigidez Vascular/fisiologia , Adulto , Pressão Sanguínea/fisiologia , Ritmo Circadiano/fisiologia , Feminino , Humanos , Hipertensão/diagnóstico , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Reprodutibilidade dos Testes , Fatores de Risco
10.
PLoS One ; 15(8): e0236566, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785281

RESUMO

INTRODUCTION: Many sleep and circadian studies require participants to adhere to structured sleep-wake schedules designed to stabilize sleep outcomes and circadian phase prior to in-laboratory testing. The effectiveness of this approach has not been rigorously evaluated, however. We therefore investigated the differences between participants' unstructured and structured sleep over a three-week interval. METHODS: Twenty-three healthy young adults completed three weeks of sleep monitoring, including one week of unstructured sleep and two weeks of structured sleep with consistent bed and wake times. Circadian phase was assessed via salivary dim light melatonin onset (DLMO) during both the unstructured and structured sleep episodes. RESULTS: Compared to their unstructured sleep schedule, participants' bed- and wake times were significantly earlier in their structured sleep, by 34 ± 44 mins (M ± SD) and 44 ± 41 mins, respectively. During structured sleep, circadian phase was earlier in 65% of participants (40 ± 32 mins) and was later in 35% (41 ± 25 mins) compared to unstructured sleep but did not change at the group level. While structured sleep reduced night-to-night variability in sleep timing and sleep duration, and improved the alignment (phase angle) between sleep onset and circadian phase in the most poorly aligned individuals (DLMO < 1h or > 3h before sleep onset time; 25% of our sample), sleep duration and quality were unchanged. CONCLUSION: Our results show adherence to a structured sleep schedule results in more regular sleep timing, and improved alignment between sleep and circadian timing for those individuals who previously had poorer alignment. Our findings support the use of structured sleep schedules prior to in-laboratory sleep and circadian studies to stabilize sleep and circadian timing in healthy volunteers.


Assuntos
Ritmo Circadiano/fisiologia , Melatonina/metabolismo , Privação do Sono/fisiopatologia , Sono/fisiologia , Adulto , Ritmo Circadiano/genética , Feminino , Humanos , Individualidade , Luz , Masculino , Pessoa de Meia-Idade , Saliva/metabolismo , Sono/genética , Privação do Sono/metabolismo , Transtornos do Sono-Vigília/metabolismo , Transtornos do Sono-Vigília/fisiopatologia , Fatores de Tempo , Adulto Jovem
11.
PLoS One ; 15(8): e0237922, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32845924

RESUMO

BACKGROUND: Levels of cortisol, melatonin, ghrelin, and leptin are highly correlated with circadian rhythmicity. The levels of these hormones are affected by sleep, feeding, and general behaviors, and fluctuate with light and dark cycles. During the fasting month of Ramadan, a shift to nighttime eating is expected to affect circadian rhythm hormones and, subsequently, the levels of melatonin, cortisol, ghrelin, and leptin. The present study aimed to examine the effect of diurnal intermittent fasting (DIF) during Ramadan on daytime levels of ghrelin, leptin, melatonin, and cortisol hormones in a group of overweight and obese subjects, and to determine how anthropometric, dietary, and lifestyle changes during the month of Ramadan correlate with these hormonal changes. METHODS: Fifty-seven overweight and obese male (40) and female (17) subjects were enrolled in this study. Anthropometric measurements, dietary intake, sleep duration, and hormonal levels of serum ghrelin, leptin, melatonin, and salivary cortisol were assessed one week before the start of Ramadan fasting and after 28 days of fasting at fixed times of the day (11:00 am-1:00 pm). RESULTS: At the end of Ramadan, serum levels of ghrelin, melatonin, and leptin significantly (P<0.001) decreased, while salivary cortisol did not change compared to the levels assessed in the pre-fasting state. CONCLUSIONS: DIF during Ramadan significantly altered serum levels of ghrelin, melatonin, and serum leptin. Further, male sex and anthropometric variables were the most impacting factors on the tested four hormones. Further studies are needed to assess DIF's impact on the circadian rhythmicity of overweight and obese fasting people.


Assuntos
Ritmo Circadiano/fisiologia , Jejum/sangue , Grelina/sangue , Hidrocortisona/sangue , Melatonina/sangue , Obesidade/sangue , Obesidade/fisiopatologia , Adulto , Dieta , Ingestão de Energia , Feminino , Hemodinâmica , Humanos , Leptina/sangue , Lipídeos/sangue , Masculino , Estudos Prospectivos , Sono/fisiologia
12.
PLoS One ; 15(8): e0236991, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785234

RESUMO

Disruption of circadian rhythms and variations in the FTO gene may interfere with energy homeostasis and play a role in the development of obesity. The current study assessed the association of common polymorphisms in the CLOCK and FTO genes with standardized body mass index scores (BMI z-scores) and their potential modification of the impact of a culinary nutrition and physical activity intervention in school-age children. Anthropometric measurements were collected in 121 children at the baseline and one-year follow-up of a controlled trial of a school-based culinary nutrition and physical activity intervention. Genotypes of the CLOCK polymorphism (rs1801260) and the FTO polymorphism (rs9939609) were obtained from buccal swabs. Linear mixed-effects regression was applied to evaluate the genetic association and adjust for clusters within families and schools. In our participants, obesity affected 6.6% (8/121) of the children at the baseline and 6.4% (7/109) of the children at the follow-up. The associations between the age- and sex-adjusted BMI z-scores and the two polymorphisms did not reach statistically significance. Yet, sex potentially modified the association between rs1801260 and BMI z-scores. In girls, the G allele carriers had a higher BMI z-scores at the baseline and the follow-up. These polymorphisms did not modify the effect of our culinary nutrition and physical activity intervention on BMI z-scores. Sex is a potential modifier for the association between the CLOCK polymorphism, rs1801260, and BMI z-scores in school-age children. Further investigation is warranted to delineate the sex-dependent role of the CLOCK polymorphisms in the development of childhood obesity.


Assuntos
Índice de Massa Corporal , Proteínas CLOCK/genética , Obesidade Pediátrica/genética , Polimorfismo de Nucleotídeo Único , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/fisiologia , Proteínas CLOCK/fisiologia , Criança , Ritmo Circadiano/genética , Ritmo Circadiano/fisiologia , Dieta Redutora , Exercício Físico , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Obesidade Pediátrica/dietoterapia , Obesidade Pediátrica/fisiopatologia , Caracteres Sexuais , Programas de Redução de Peso
13.
Proc Biol Sci ; 287(1932): 20200347, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32781954

RESUMO

Circadian clocks coordinate organisms' activities with daily cycles in their environment. Parasites are subject to daily rhythms in the within-host environment, resulting from clock-control of host activities, including immune responses. Parasites also exhibit rhythms in their activities: the timing of within-host replication by malaria parasites is coordinated to host feeding rhythms. Precisely which host feeding-related rhythm(s) parasites align with and how this is achieved are unknown. Understanding rhythmic replication in malaria parasites matters because it underpins disease symptoms and fuels transmission investment. We test if rhythmicity in parasite replication is coordinated with the host's feeding-related rhythms and/or rhythms driven by the host's canonical circadian clock. We find that parasite rhythms coordinate with the time of day that hosts feed in both wild-type and clock-mutant hosts, whereas parasite rhythms become dampened in clock-mutant hosts that eat continuously. Our results hold whether infections are initiated with synchronous or with desynchronized parasites. We conclude that malaria parasite replication is coordinated to rhythmic host processes that are independent of the core-clock proteins PERIOD 1 and 2; most likely, a periodic nutrient made available when the host digests food. Thus, novel interventions could disrupt parasite rhythms to reduce their fitness, without interference by host clock-controlled homeostasis.


Assuntos
Relógios Circadianos , Interações Hospedeiro-Parasita/fisiologia , Plasmodium chabaudi/fisiologia , Animais , Ritmo Circadiano/fisiologia , Homeostase , Malária , Parasitos , Proteínas Circadianas Period
14.
Life Sci ; 258: 118214, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32768585

RESUMO

Large numbers of rodents are often used in the study of disease progression and in the evaluation of its potential treatments. To avoid subjective observation and to minimize home cage interference, we developed a computerized home cage monitoring system (HCMS100) based on a standard cage rack adapted with a single laser beam and a detector mounted on each cage, enabling to monitor mice movements based on laser beam interruptions. This retrofit system provided continuous and uninterrupted monitoring of spontaneous movement of a group of mice in a home cage. Validity was evaluated using disease state induced by LPS modelling bacterial infection and by influenza virus. RESULTS: Spontaneous activity of different number of mice (2-8) per cage showed the expected circadian rhythm with increased activity during the night, and its extent dependent on the number of mice in the cage. Females and males show similar circadian rhythm. Intranasal LPS administration and pulmonary infection with live influenza virus resulted in major reduction of mice activity along disease progression. Increase in activity over time was a good indicator of the recovery process from both LPS exposure and the flu infection. CONCLUSIONS: HCMS100 was shown to be a reliable, inexpensive, easy to use system that requires no changes in the common housing of various experimental animals (mice, hamsters, rats etc.). With minimal intervention, HCMS100 provides a continuous record of group activity with clear pattern of circadian rhythm, allowing long term recording of home cage activity even in restricted access environments.


Assuntos
Progressão da Doença , Abrigo para Animais , Lipopolissacarídeos/toxicidade , Infecções por Orthomyxoviridae/fisiopatologia , Orthomyxoviridae , Recuperação de Função Fisiológica/fisiologia , Animais , Ritmo Circadiano/fisiologia , Feminino , Abrigo para Animais/tendências , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Infecções por Orthomyxoviridae/psicologia , Recuperação de Função Fisiológica/efeitos dos fármacos
15.
Br J Anaesth ; 125(4): 548-559, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32807382

RESUMO

BACKGROUND: Circadian differences in the induction, maintenance, or emergence from volatile anaesthesia have not been well studied. METHODS: The minimal alveolar concentration (MAC) for preventing movement in response to a painful stimulus, MAC for loss of righting reflex (MACLORR), and MAC for recovery of righting reflex (MACRORR) in C57BL/6J male mice with isoflurane or sevoflurane exposure were measured during either the light or dark phase. Time to onset of loss of righting reflex (TimeLORR) and recovery of righting reflex (TimeRORR) upon exposure to 1 MAC of isoflurane or sevoflurane were determined. EEG was also monitored in the light and dark phase under isoflurane or sevoflurane exposure. The noradrenergic toxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) was used to deplete noradrenergic neurones in the locus coeruleus to explore the impact of norepinephrine on these measurements. RESULTS: MACLORR, TimeLORR, and MAC did not show light- or dark-phase-dependent variations for either isoflurane or sevoflurane exposure. However, MACRORR was higher and TimeRORR was shorter in the dark phase than in the light phase for both isoflurane and sevoflurane exposure. The EEG delta wave power was higher but theta wave power was lower in the light phase than that in the dark phase during the rest state and emergence of anaesthesia. These light- and dark-phase-dependent changes in emergence were abolished in DSP-4-treated mice. CONCLUSION: Our data show that circadian differences exist during emergence but not during induction or maintenance of sevoflurane or isoflurane anaesthesia. The locus coeruleus noradrenergic system may contribute to these differences.


Assuntos
Anestésicos Inalatórios/farmacologia , Ritmo Circadiano/fisiologia , Locus Cerúleo/fisiologia , Norepinefrina/fisiologia , Anestésicos Inalatórios/farmacocinética , Animais , Benzilaminas/farmacologia , Temperatura Corporal/efeitos dos fármacos , Eletroencefalografia/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reflexo de Endireitamento/efeitos dos fármacos
16.
Chronobiol Int ; 37(8): 1191-1200, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32660352

RESUMO

COVID-19 has brought the world into uncharted waters. Many countries are under lockdown, the economy has ground to a halt, and almost everyone is afraid of dire consequences. The unprecedented changes that came on so quickly due to the pandemic and stay-at-home confinement to accomplish social distancing and mitigate risk for infection pose many challenges. These include compromised health, well-being, and sleep as a consequence of disruption of the daily life routine, anxiety, worry, isolation, greater family and work stress, and excessive screen time. Our study of 203 corporate sector professionals performing '9-5' work from home during this phase of the pandemic and of 325 undergraduate and postgraduate university students substantiates, relative to the before lockdown condition, more extensive feelings of sleepiness, with significantly (p < .05) increased daytime nap duration, and depressive symptomatology (p < .001) that is a matter of concern. Moreover, the chronic stress of living through a pandemic led to a host of physical symptoms, like headaches, insomnia, digestive problems, hormonal imbalances, and fatigue.


Assuntos
Ansiedade/fisiopatologia , Betacoronavirus , Ritmo Circadiano/fisiologia , Infecções por Coronavirus/fisiopatologia , Depressão/etiologia , Dor Nociceptiva/fisiopatologia , Dor/etiologia , Pneumonia Viral/fisiopatologia , Transtornos do Sono-Vigília/etiologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Feminino , Humanos , Índia , Masculino , Pandemias , Pneumonia Viral/virologia , Sono/fisiologia , Estudantes
17.
Chronobiol Int ; 37(7): 1115-1117, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32633583

RESUMO

With countless "natural" experiments triggered by the COVID-19-associated physical distancing, one key question comes from chronobiology: "When confined to homes, how does the reduced exposure to natural daylight arising from the interruption of usual outdoor activities plus lost temporal organization ordinarily provided from workplaces and schools affect the circadian timing system (the internal 24 h clock) and, consequently, health of children and adults of all ages?" Herein, we discuss some ethical and scientific facets of exploring such natural experiments by offering a hypothetical case study of circadian biology.


Assuntos
Betacoronavirus/patogenicidade , Ritmo Circadiano/fisiologia , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , Adulto , Criança , Humanos , Luz , Pandemias , Sono/fisiologia
18.
Nature ; 583(7816): 421-424, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32641825

RESUMO

The suprachiasmatic nucleus (SCN) serves as the body's master circadian clock that adaptively coordinates changes in physiology and behaviour in anticipation of changing requirements throughout the 24-h day-night cycle1-4. For example, the SCN opposes overnight adipsia by driving water intake before sleep5,6, and by driving the secretion of anti-diuretic hormone7,8 and lowering body temperature9,10 to reduce water loss during sleep11. These responses can also be driven by central osmo-sodium sensors to oppose an unscheduled rise in osmolality during the active phase12-16. However, it is unknown whether osmo-sodium sensors require clock-output networks to drive homeostatic responses. Here we show that a systemic salt injection (hypertonic saline) given at Zeitgeber time 19-a time at which SCNVP (vasopressin) neurons are inactive-excited SCNVP neurons and decreased non-shivering thermogenesis (NST) and body temperature. The effects of hypertonic saline on NST and body temperature were prevented by chemogenetic inhibition of SCNVP neurons and mimicked by optogenetic stimulation of SCNVP neurons in vivo. Combined anatomical and electrophysiological experiments revealed that osmo-sodium-sensing organum vasculosum lamina terminalis (OVLT) neurons expressing glutamic acid decarboxylase (OVLTGAD) relay this information to SCNVP neurons via an excitatory effect of γ-aminobutyric acid (GABA). Optogenetic activation of OVLTGAD neuron axon terminals excited SCNVP neurons in vitro and mimicked the effects of hypertonic saline on NST and body temperature in vivo. Furthermore, chemogenetic inhibition of OVLTGAD neurons blunted the effects of systemic hypertonic saline on NST and body temperature. Finally, we show that hypertonic saline significantly phase-advanced the circadian locomotor activity onset of mice. This effect was mimicked by optogenetic activation of the OVLTGAD→ SCNVP pathway and was prevented by chemogenetic inhibition of OVLTGAD neurons. Collectively, our findings provide demonstration that clock time can be regulated by non-photic physiologically relevant cues, and that such cues can drive unscheduled homeostatic responses via clock-output networks.


Assuntos
Relógios Circadianos/fisiologia , Vias Neurais , Neurônios/metabolismo , Sódio/metabolismo , Núcleo Supraquiasmático/fisiologia , Ácido gama-Aminobutírico/metabolismo , Animais , Temperatura Corporal/efeitos dos fármacos , Temperatura Corporal/fisiologia , Relógios Circadianos/efeitos dos fármacos , Ritmo Circadiano/efeitos dos fármacos , Ritmo Circadiano/fisiologia , Ingestão de Líquidos/efeitos dos fármacos , Glutamato Descarboxilase/metabolismo , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Camundongos , Vias Neurais/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Optogenética , Organum Vasculosum/citologia , Organum Vasculosum/efeitos dos fármacos , Organum Vasculosum/enzimologia , Organum Vasculosum/fisiologia , Concentração Osmolar , Solução Salina Hipertônica/administração & dosagem , Solução Salina Hipertônica/metabolismo , Solução Salina Hipertônica/farmacologia , Sódio/administração & dosagem , Sódio/farmacologia , Núcleo Supraquiasmático/citologia , Núcleo Supraquiasmático/efeitos dos fármacos , Vasopressinas/metabolismo
19.
Am J Physiol Cell Physiol ; 319(3): C533-C540, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32726159

RESUMO

Humans have internal circadian clocks that ensure that important physiological functions occur at specific times of the day. These molecular clocks are regulated at the genomic level and exist in most cells of the body. Multiple circadian resetting cues have been identified, including light, temperature, and food. Recently, oxygen has been identified as a resetting cue, and emerging science indicates that this occurs through interactions at the cellular level between the circadian transcription-translation feedback loop and the hypoxia-inducible pathway (hypoxia-inducible factor; subject of the 2019 Nobel Prize in Physiology or Medicine). This review will cover recently identified relationships between HIF and proteins of the circadian clock. Interactions between the circadian clock and hypoxia could have wide-reaching implications for human diseases, and understanding the molecular mechanisms regulating these overlapping pathways may open up new strategies for drug discovery.


Assuntos
Relógios Circadianos/genética , Ritmo Circadiano/fisiologia , Fator 1 Induzível por Hipóxia/metabolismo , Fatores de Tempo , Animais , Descoberta de Drogas , Humanos , Hipóxia/metabolismo
20.
Chronobiol Int ; 37(7): 1106-1109, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32498625

RESUMO

SARS-CoV-2/COVID-19 leads to numerous unplanned or natural experiments with health and disease. Physical (social) distancing - a counter-measure with no alternative, but with no precedence in scope and scale either - is a key intervention and trigger of natural experiments. From a practical perspective, concerned disciplines should increase awareness of, provide recommendations to meet, and develop research for, health challenges arising from physical distancing at home. From the field of chronobiology, prolonged home stays may place undue strain on the body's circadian timing system but straightforward and often underestimated advice for coping can be provided (herein we provide such advice). Of course, advice or recommendations from other concerned disciplines that identify challenges associated with current COVID-19 mitigation strategies are also needed. From a research perspective, different disciplines should rise to the occasion and explore unsuspected natural experiment angles toward novel insights to promote health and prevent disease.


Assuntos
Adaptação Psicológica/fisiologia , Betacoronavirus/patogenicidade , Ritmo Circadiano/fisiologia , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , Comportamento/fisiologia , Humanos , Pandemias , Risco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA