Circadian Rhythmic Characteristics in Men With Substance Use Disorder Under Treatment. Influence of Age of Onset of Substance Use and Duration of Abstinence

here is evidence of the reciprocal influence between the alteration of circadian rhythms and Substance Use Disorders (SUD), and part of the success of the SUD treatment lays in the patient's rhythmic recovery. We aim to elucidate the effect of the SUD treatment in circadian rhythmicity considering, for the first time, the age of onset of substance use (OSU) and duration of abstinence. We registered the sleep-wake schedules, the chronotype and the distal skin temperature of 114 SUD patients with at least 3 months of abstinence, considering whether they had begun consumption at age 16 or earlier (OSU ≤ 16, n = 56) or at 17 or later (OSU ≥ 17, n = 58), and duration of abstinence as short (SA: 3 to 5 months, n = 38), medium (MA: 6 to 9 months, n = 35) or long (LA: more than 9 months, n = 41). Moreover, we compared the patients' distal skin temperature pattern with a similar sample of healthy controls (HC, n = 103). SUD patients showed a morningness tendency and higher night values, amplitude and stability, a better adjustment to the cosine model and lower minimum temperature and circadianity index in the distal skin temperature rhythm, in contrast to the HC group. The OSU ≥ 17 and LA groups showed a more robust distal skin temperature pattern, as well as milder clinical characteristics when compared to the OSU ≤ 16 and SA groups, respectively. The circadian disturbances associated to substance consumption seem to improve with treatment, although the age of OSU and the duration of abstinence are modulating variables. Our results highlight the need to include chronobiological strategies that boost circadian rhythmicity both in SUD prevention and rehabilitation programs. The measurement of distal skin temperature rhythm, a simple and reliable procedure, could be considered an indicator of response to treatment in SUD patient

Impact of an intermittent and localized cooling intervention on skin temperature, sleep quality and energy expenditure in free-living, young, healthy adults

Where people live and work together it is not always possible to modify the ambient temperature; ways must therefore be found that allow individuals to feel thermally comfortable in such settings. The Embr Wave (R) is a wrist-worn device marketed as a 'personal thermostat' that can apply a local cooling stimulus to the skin. The aim of the present study was to determine the effect of an intermittent mild cold stimulus of 25 degrees C for 15-20 s every 5 min over 3.5 days under free-living conditions on 1) skin temperature, 2) perception of skin temperature, 3) sleep quality and 4) resting energy expenditure (REE) in young, healthy adults. Ten subjects wore the device for 3.5 consecutive days. This intervention reduced distal skin temperature after correcting for personal ambient temperature (P = 0.051). Thus, this intermittent mild cold regime can reduce distal skin temperature, and wearing it under free-living conditions for 3.5 days does not seem to impair the perception of skin temperature and sleep quality or modify REE.The study was funded by the Spanish Ministry of Economy and Competitiveness via the Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III (PI13/01393 and CB16/10/00239) and PTA 12264-I, Retos de la Sociedad (DEP2016-79512-R), and European Regional Development Funds (ERDF). Other funders included the Spanish Ministry of Education (FPU 16/05159, 15/04059 and 19/02326), the Fundacion Iberoamericana de Nutricion (FINUT), the Redes Tematicas De Investigacion Cooperativa RETIC (Red SAMID RD16/0022), the AstraZeneca Health Care Foundation, the University of Granada Plan Propio de Investigacion 2016 (Excellence actions: Unit of Excellence on Exercise, Nutrition and Health [UCEENS]), and by the Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades (ERDF, SOMM17/6107/UGR). AMT was supported by Seneca Foundation through grant 19899/GERM/15 and the Ministry of Science Innovation and Universities RTI2018-093528-B-I0, as well as DJP (MINECO; RYC-2014-16938). BMT was supported by an individual postdoctoral grant from the Fundacion Alfonso Martin Escudero. We thank Dr. Matt Smith of Embr Labs Inc. for configuring the Embr Wave (R) devices used in this experiment

The Mediating Role of Brown Fat and Skeletal Muscle Measured by 18F-Fluorodeoxyglucose in the Thermoregulatory System in Young Adults

The authors would like to thank all the participants who took part in this investigation. This study is part of a PhD thesis conducted in the Biomedicine Doctoral Studies of the University of Granada, Spain. We are grateful to Alberto Quesada-Aranda for helping with the development of the Temperatus software (free trial at http://profith.ugr.es/ temperatus?lang=en). We are grateful to Ms Carmen Sainz-Quinn for assistance with English-language editingObjective: This study aimed to examine whether brown adipose tissue (BAT) or skeletal muscle activity mediates the relationship between personal level of environmental temperature (Personal-ET) and wrist skin temperature (WT). Moreover, we examined whether BAT and skeletal muscle have a mediating role between Personal-ET and WT (as a proxy of peripheral vasoconstriction/vasodilation). Methods: The levels of BAT were quantified by cold-induced 18F-fluorodeoxyglucose–positron emission tomography/computed tomography scan and measured the Personal-ET and WT by using iButtons (Maxim Integrated, Dallas, Texas) in 75 participants (74.6% women). Results: The study found that BAT volume and metabolic activity played a positive and significant role (up to 25.4%) in the association between Personal-ET and WT. In addition, at the coldest temperatures, the participants with lower levels of WT (inducing higher peripheral vasoconstriction) had higher levels of BAT outcomes, whereas in warm temperatures, participants with higher levels of WT (inducing higher peripheral vasodilation) had lower levels of BAT outcomes. The study did not find any mediating role of skeletal muscle activity. Conclusions: BAT volume and metabolic activity play a role in the relationship between Personal-ET and WT. Moreover, the data suggest that there are two distinct phenotypes: individuals who respond better to the cold, both through nonshivering thermogenesis and peripheral vasoconstriction, and individuals who respond better to the heat.This study was supported by the Spanish Ministry of Economy and Competitiveness, Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI13/01393), Retos de la Sociedad (DEP2016‐79512‐R), and Fondos Estructurales de la Unión Europea (FEDER); by the Spanish Ministry of Education (FPU 13/04365); by the Fundación Iberoamericana de Nutrición; by the Redes Temáticas de Investigación Cooperativa RETIC (Red SAMID RD16/0022); by AstraZeneca HealthCare Foundation; by the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES); and by the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades and European Regional Development Fund (ERDF), ref. SOMM17/6107/UGR, Programa Contratos‐Puente. MAR is supported by a predoctoral research grant from University Jaume I (PREDOC/2015/13). AMN was supported by the Ministry of Economy and Competitiveness, the Instituto de Salud Carlos III through the Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CB16/10/00239), and grant 19899/GERM/15 (cofinanced by FEDER)

Relationship between the Daily Rhythm of Distal Skin Temperature and Brown Adipose Tissue 18F-FDG Uptake in Young Sedentary Adults

The present study examines whether the daily rhythm of distal skin temperature (DST) is associated with brown adipose tissue (BAT) metabolism as determined by 18F-fluorodeoxyglucose (18F-FDG) uptake in young adults. Using a wireless thermometer (iButton) worn on the nondominant wrist, DST was measured in 77 subjects (26% male; age 22 ± 2 years; body mass index 25.2 ± 4.8 kg/m2) for 7 consecutive days. The temperatures to which they were habitually exposed over the day were also recorded. The interday stability of DST was calculated from the collected data, along with the intraday variability and relative amplitude; the mean temperature of the 5 and 10 consecutive hours with the maximum and minimum DST values, respectively; and when these hours occurred. Following exposure to cold, BAT volume and mean and peak standardized 18F-FDG uptake (SUVmean and SUVpeak) were determined for each subject via static 18F-FDG positron emission tomography/computed tomography scanning. Relative amplitude and the time at which the 10 consecutive hours of minimum DST values occurred were positively associated with BAT volume, SUVmean, and SUVpeak (p ≤ 0.02), whereas the mean DST of that period was inversely associated with the latter BAT variables (p ≤ 0.01). The interday stability and intraday variability of the DST were also associated (directly and inversely, respectively) with BAT SUVpeak (p ≤ 0.02 for both). All of these associations disappeared, however, when the analyses were adjusted for the ambient temperature to which the subjects were habitually exposed. Thus, the relationship between the daily rhythm of DST and BAT activity estimated by 18F-FDG uptake is masked by environmental and likely behavioral factors. Of note is that those participants exposed to the lowest ambient temperature showed 3 to 5 times more BAT volume and activity compared with subjects who were exposed to a warmer ambient temperature

Major Histocompatibility Complex Class I Chain-Related (MICA) STR Polymorphisms in COVID-19 Patients

The SARS-CoV-2 disease presents different phenotypes of severity. Comorbidities, age, and being overweight are well established risk factors for severe disease. However, innate immunity plays a key role in the early control of viral infections and may condition the gravity of COVID-19. Natural Killer (NK) cells are part of innate immunity and are important in the control of virus infection by killing infected cells and participating in the development of adaptive immunity. Therefore, we studied the short tandem repeat (STR) transmembrane polymorphisms of the major histocompatibility complex class I chain-related A (MICA), an NKG2D ligand that induces activation of NK cells, among other cells. We compared the alleles and genotypes of MICA in COVID-19 patients versus healthy controls and analyzed their relation to disease severity. Our results indicate that the MICA*A9 allele is related to infection as well as to symptomatic disease but not to severe disease. The MICA*A9 allele may be a risk factor for SARS-CoV-2 infection and symptomatic disease.Instituto de Salud Carlos III - FEDER funds (European Union) PI 16/00752 B-CTS-410-UGR-20Junta de Andalucia CTS-143 C-0013-201

Comparative Analysis of Primary and Secondary Metabolites in the Peel of Eight Blood Orange Varieties

The global cultivation of blood oranges is experiencing an increase due to their remarkable nutritional properties. Blood orange by-products, especially the peel, have a high concentration of bioactive compounds with exceptional antioxidant potential, making them an ideal choice for incorporation into various food products. This study aimed to determine the morphological parameters and primary and secondary metabolite content of peel of eight blood orange varieties using 1H NMR and HPLC-ESI-DAD-MSn. “Tarocco Meli” had the highest weight (367.83 g), caliber (94.13 mm and 88.87 mm), peel thickness (6.73 mm), and peel weight (155.0 g). “Tarocco Rosso”, “Sanguinelli”, and “Tarocco Gallo” had the highest levels of total amino acids (25.57 g kg−1 DW), total organic acids (29.99 g kg−1 DW), and total sugars (68.56 g 100 g−1 DW), respectively. The peel of “Moro” had significantly higher concentrations of total anthocyanins, hydroxycinnamic acids, and flavones (650.67, 263.33, and 449.85 mg kg−1, respectively) compared to the other varieties. In conclusion, “Tarocco Meli” had the most interesting values for morphological parameters, “Tarocco Rosso”, “Sanguinelli”, and “Tarocco Gallo” for primary metabolites, and “Moro” for secondary metabolites. With the increasing interest in utilizing co-products, these findings could be useful in developing functional food products that meet consumer demands for healthier and more sustainable food choice

The ISLAndS project II: The Lifetime Star Formation Histories of Six Andromeda dSphs

The Initial Star formation and Lifetimes of Andromeda Satellites (ISLAndS) project uses Hubble Space Telescope imaging to study a representative sample of six Andromeda dSph satellite companion galaxies. The main goal of the program is to determine whether the star formation histories (SFHs) of the Andromeda dSph satellites demonstrate significant statistical differences from those of the Milky Way, which may be attributable to the different properties of their local environments. Our observations reach the oldest main sequence turn-offs, allowing a time resolution at the oldest ages of ~ 1 Gyr, which is comparable to the best achievable resolution in the MW satellites. We find that the six dSphs present a variety of SFHs that are not strictly correlated with luminosity or present distance from M31. Specifically, we find a significant range in quenching times (lookback times from 9 to 6 Gyr), but with all quenching times more than ~ 6 Gyr ago. In agreement with observations of Milky Way companions of similar mass, there is no evidence of complete quenching of star formation by the cosmic UV background responsible for reionization, but the possibility of a degree of quenching at reionization cannot be ruled out. We do not find significant differences between the SFHs of the three members of the vast, thin plane of satellites and the three off-plane dSphs. The primary difference between the SFHs of the ISLAndS dSphs and Milky Way dSph companions of similar luminosities and host distances is the absence of very late quenching (< 5 Gyr ago) dSphs in the ISLAndS sample. Thus, models that can reproduce satellite populations with and without late quenching satellites will be of extreme interest.Comment: 24 pages, 11 figures, 3 tables, submitted to the Ap

Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection

International audienceTwo of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic inflammation via the modulation of adipose tissue-related pathway

A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

Introduction: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.&lt;p&gt;&lt;/p&gt; Methods: Sixty-six non-HLA SNPs showing a P value &#60;10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays. Results: We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis.&lt;p&gt;&lt;/p&gt; Conclusion: Our results suggest a role of PPARG gene in the development of SSc