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1.
J Interpers Violence ; : 8862605241275994, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39329408

RESUMEN

The current study presents preliminary efficacy findings of a pilot randomized controlled trial of Positive Change© (+Change© ). +Change© utilizes personalized normative feedback to target alcohol use, sexual assault (SA) victimization, SA perpetration, and bystander intervention tailored for heterosexual cisgender men, heterosexual cisgender women, and sexual and gender-minoritized (SGM) groups. Participants included 165 undergraduate students aged 18 to 25 years old from a large public university in the Southwestern U.S. who engaged in past month heavy episodic drinking. Participants (57 cisgender heterosexual men; 54 cisgender heterosexual women; and 54 SGM) were randomized to +Change© (n = 83) or an assessment-only control (n = 82) and completed surveys online at baseline and 3-month follow-up in a parallel design with a 1:1 ratio (NCT04089137). The current study presents the secondary outcomes of the pilot randomized controlled trial which include alcohol use, SA victimization, SA perpetration, and bystander intervention behavior. +Change© was associated with significantly less severe SA victimization and more bystander intervention behavior at 3-month follow-up relative to the control. There were no significant differences between conditions in alcohol use at 3-month follow-up, however, the magnitude of decreases in drinking in the +Change© condition in this pilot study were consistent with other personalized normative feedback interventions. The present study was unable to assess differences in SA perpetration due to low base rates. No adverse effects among those receiving the intervention were observed. Findings suggested that +Change© may be a feasible strategy to prevent SA, by reducing student SA victimization and increasing bystander intervention. A fully powered randomized clinical trial is needed to examine the effects of +Change©.

2.
Sensors (Basel) ; 24(17)2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39275502

RESUMEN

In many regions globally, including low-resource settings, there is a growing trend towards using mHealth technology, such as wearable sensors, to enhance health behaviors and outcomes. However, adoption of such devices in research conducted in low-resource settings lags behind use in high-resource areas. Moreover, there is a scarcity of research that specifically examines the user experience, readiness for and challenges of integrating wearable sensors into health research and community interventions in low-resource settings specifically. This study summarizes the reactions and experiences of young women (N = 57), ages 18 to 24 years, living in poverty in Kampala, Uganda, who wore Garmin vívoactive 3 smartwatches for five days for a research project. Data collected from the Garmins included participant location, sleep, and heart rate. Through six focus group discussions, we gathered insights about the participants' experiences and perceptions of the wearable devices. Overall, the wearable devices were met with great interest and enthusiasm by participants. The findings were organized across 10 domains to highlight reactions and experiences pertaining to device settings, challenges encountered with the device, reports of discomfort/comfort, satisfaction, changes in daily activities, changes to sleep, speculative device usage, community reactions, community dynamics and curiosity, and general device comfort. The study sheds light on the introduction of new technology in a low-resource setting and also on the complex interplay between technology and culture in Kampala's slums. We also learned some insights into how wearable devices and perceptions may influence behaviors and social dynamics. These practical insights are shared to benefit future research and applications by health practitioners and clinicians to advance and enhance the implementation and effectiveness of wearable devices in similar contexts and populations. These insights and user experiences, if incorporated, may enhance device acceptance and data quality for those conducting research in similar settings or seeking to address population-specific needs and health issues.


Asunto(s)
Telemedicina , Dispositivos Electrónicos Vestibles , Humanos , Femenino , Uganda , Adulto Joven , Telemedicina/instrumentación , Adolescente , Sueño/fisiología , Adulto , Grupos Focales
3.
Res Sq ; 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39149487

RESUMEN

Background: There is growing interest in use of transcutaneous spinal stimulation (TSS) for people with neurologic conditions both to augment volitional control (by facilitating motoneuron excitability), and to decrease spasticity (by activating inhibitory networks). Various electrode montages are used during TSS, with little understanding of how electrode position influences spinal circuit activation. We sought to identify the thoracolumbar electrode montage associated with the most robust activation of spinal circuits by comparing posterior root-muscle reflexes (PRM reflexes) elicited by 6 montages. Additionally, we assessed tolerability of the stimulation during PRM reflex testing. Methods: Fifteen adults with intact neurological systems participated in this randomized crossover study. PRM reflexes were evoked transcutaneously using electrode montages with dorsal-ventral (DV) or dorsal-midline (DM) current flow. DV montages included: [1] cathode over T11/T12, anodes over iliac crests (DV-I), [2] cathode over T11/T12, anodes over umbilicus (DV-U), [3] dual paraspinal cathodes at T11/12, anodes over iliac crests (DV-PI), and [4] dual paraspinal cathodes at T11/12, anodes over umbilicus (DV-PU). DM montages included: [5] cathode over T11/12, anode 5cm caudal (DM-C), and [6] cathode over T11/12, anode 5cm rostral (DM-R). PRM reflex recruitment curves were obtained in the soleus muscle of both lower extremities. Results: DV-U and DV-I montages elicited bilateral reflexes with lower reflex thresholds and larger recruitment curve area than other montages. There were no differences in response amplitude at 120% of RT(1.2xRT) or tolerability among montages. Conclusions: Differences in spinal circuit recruitment are reflected in the response amplitude of the PRM reflexes. DV-I and DV-U montages were associated with lower reflex thresholds, indicating that motor responses can be evoked with lower stimulation intensity. DV-I and DV-U montages therefore have the potential for lower and more tolerable interventional stimulation intensities. Our findings optimize electrode placement for interventional TSS and PRM reflex assessments.

4.
Euro Surveill ; 29(23)2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38847117

RESUMEN

BackgroundVancomycin-resistant enterococci (VRE) are increasing in Denmark and Europe. Linezolid and vancomycin-resistant enterococci (LVRE) are of concern, as treatment options are limited. Vancomycin-variable enterococci (VVE) harbour the vanA gene complex but are phenotypically vancomycin-susceptible.AimThe aim was to describe clonal shifts for VRE and VVE in Denmark between 2015 and 2022 and to investigate genotypic linezolid resistance among the VRE and VVE.MethodsFrom 2015 to 2022, 4,090 Danish clinical VRE and VVE isolates were whole genome sequenced. We extracted vancomycin resistance genes and sequence types (STs) from the sequencing data and performed core genome multilocus sequence typing (cgMLST) analysis for Enterococcus faecium. All isolates were tested for the presence of mutations or genes encoding linezolid resistance.ResultsIn total 99% of the VRE and VVE isolates were E. faecium. From 2015 through 2019, 91.1% of the VRE and VVE were vanA E. faecium. During 2020, to the number of vanB E. faecium increased to 254 of 509 VRE and VVE isolates. Between 2015 and 2022, seven E. faecium clusters dominated: ST80-CT14 vanA, ST117-CT24 vanA, ST203-CT859 vanA, ST1421-CT1134 vanA (VVE cluster), ST80-CT1064 vanA/vanB, ST117-CT36 vanB and ST80-CT2406 vanB. We detected 35 linezolid vancomycin-resistant E. faecium and eight linezolid-resistant VVEfm.ConclusionFrom 2015 to 2022, the numbers of VRE and VVE increased. The spread of the VVE cluster ST1421-CT1134 vanA E. faecium in Denmark is a concern, especially since VVE diagnostics are challenging. The finding of LVRE, although in small numbers, ia also a concern, as treatment options are limited.


Asunto(s)
Antibacterianos , Proteínas Bacterianas , Ligasas de Carbono-Oxígeno , Enterococcus faecium , Infecciones por Bacterias Grampositivas , Linezolid , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Resistencia a la Vancomicina , Enterococos Resistentes a la Vancomicina , Enterococos Resistentes a la Vancomicina/genética , Enterococos Resistentes a la Vancomicina/aislamiento & purificación , Enterococos Resistentes a la Vancomicina/efectos de los fármacos , Enterococcus faecium/genética , Enterococcus faecium/efectos de los fármacos , Enterococcus faecium/aislamiento & purificación , Humanos , Dinamarca/epidemiología , Infecciones por Bacterias Grampositivas/microbiología , Infecciones por Bacterias Grampositivas/epidemiología , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Ligasas de Carbono-Oxígeno/genética , Linezolid/farmacología , Resistencia a la Vancomicina/genética , Secuenciación Completa del Genoma , Vancomicina/farmacología , Vancomicina/uso terapéutico , Genotipo
5.
Artículo en Inglés | MEDLINE | ID: mdl-38397675

RESUMEN

Young women living in Kampala, Uganda, often face adversities related to Social Determinants of Mental Health (SDoMH) including poverty, food scarcity, environmental stressors such as high levels of community violence, and lack of adequate healthcare access. Two consecutive pilot studies were conducted to assess the feasibility and acceptability of survey questions, wearable fitness trackers, and daily diaries before launching a larger prospective cohort study. Preliminary associations between SDoMH factors with depressive symptoms, stress levels, and life satisfaction were examined among the total sample of 60 women across two pilot studies. A total of 32.2% of respondents (out of n = 59) reported being depressed most or all of the time in the past 30 days. Frequent depressive symptoms correlated with food insecurity (χ2 = 5.38, df = 1, p = 0.02). Higher stress levels were significantly associated with lower overall life satisfaction scores (t = 2.74, df = 6.20, p = 0.03). Additionally, frequent depressive symptoms were associated with lower satisfaction scores in the living conditions and lifestyle domain (t = 2.22, df = 36.18, p = 0.03). However, overall life satisfaction scores and other domains (social relationships and personal independence) were not statistically associated with frequent depressive symptoms. Identifying the most impactful SDoMH factors among young women in Kampala can inform targeted approaches to improve mental health outcomes.


Asunto(s)
Depresión , Satisfacción Personal , Humanos , Femenino , Depresión/epidemiología , Depresión/psicología , Estudios Prospectivos , Proyectos Piloto , Uganda/epidemiología
6.
Addict Behav ; 151: 107938, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38217943

RESUMEN

Suicide is a serious public health problem in the United States. Alcohol use has been substantially documented as a risk factors for suicide, yet it is unclear how alcohol is associated with suicidal ideation (SI) and behavior (SIB) at the event level. We examined the association between alcohol use and SI using a mixed methods approach that included daily assessments from 13 adults who engage in heavy episodic drinking with current SI and qualitative interviews among 12 of those adults. Participants were recruited on social media. Separate mixed effects logistic regression models indicated that individuals' alcohol use on a given day was associated with SI (OR = 1.37), and suicidal urges (OR = 1.41). Adjusting for repeated measures, the expected marginal mean for intensity of SI (EMM = 3.33) and urges (EMM = 2.94) were higher on days with reported drinking behavior than days without reported drinking (EMM = 2.68 and EMM = 2.62 respectively). Qualitative data indicated that the association between alcohol use and SIB is more complex than a single directionality. Instead, the association can be unidirectional, bidirectional, and/or dependent on factors including mental health and amount of alcohol consumed. Overall, these findings emphasize a need for integrated alcohol and SIB interventions while providing insight on possible daily, just-in-time adaptations.


Asunto(s)
Ideación Suicida , Suicidio , Adulto , Humanos , Estados Unidos/epidemiología , Intento de Suicidio/psicología , Factores de Riesgo , Modelos Logísticos , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/psicología
7.
Emerg Microbes Infect ; 13(1): 2309969, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38258968

RESUMEN

The emergence of bloodstream infections (BSI) caused by vancomycin-resistant Enterococci (VRE) has caused concern. Nonetheless, it remains unclear whether these types are associated with an excess risk of severe outcomes when compared with infections caused by vancomycin-susceptible Enterococci (VSE). This cohort study included hospitalized patients in Denmark with Enterococcus faecium-positive blood cultures collected between 2010 and 2019 identified in the Danish Microbiology Database. We estimated 30-day hazard ratio (HR) of death or discharge among VRE compared to VSE patients adjusted for age, sex, and comorbidity. The cohort included 6071 patients with E. faecium BSI (335 VRE, 5736 VSE) among whom VRE increased (2010-13, 2.6%; 2014-16, 6.3%; 2017-19; 9.4%). Mortality (HR 1.08, 95%CI 0.90-1.29; 126 VRE, 37.6%; 2223 VSE, 37.0%) or discharge (HR 0.89, 95%CI 0.75-1.06; 126 VRE, 37.6%; 2386 VSE, 41.6%) was not different between VRE and VSE except in 2014 (HR 1.87, 95% CI 1.18-2.96). There was no interaction between time from admission to BSI (1-2, 3-14, and >14 days) and HR of death (P = 0.14) or discharge (P = 0.45) after VRE compared to VSE, despite longer time for VRE patients (17 vs. 10 days for VSE, P < 0.0001). In conclusion, VRE BSI was not associated with excess morbidity and mortality. The excess mortality in 2014 only may be attributed to improved diagnostic- and patient-management practices after 2014, reducing time to appropriate antibiotic therapy. The high level of mortality after E. faecium BSI warrants further study.


Asunto(s)
Enterococcus faecium , Infecciones por Bacterias Grampositivas , Sepsis , Humanos , Vancomicina , Estudios de Cohortes , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/epidemiología , Enterococcus , Morbilidad , Dinamarca/epidemiología
8.
Artículo en Inglés | MEDLINE | ID: mdl-38028927

RESUMEN

Objective: To identify risk factors associated with methicillin-resistant Staphylococcus aureus (MRSA) colonization in neonatal patients during an MRSA outbreak to minimize future outbreaks. Design: Retrospective case-control study. Setting: Level-IV neonatal intensive care unit (NICU) at Copenhagen University Hospital, Rigshospitalet, Denmark. Patients: Neonates with either MRSA or methicillin-susceptible Staphylococcus aureus (MSSA). Methods: Methicillin-resistant Staphylococcus aureus-positive neonates were matched with those colonized or infected with MSSA in a 1:1 ratio. The control group was selected from clinical samples, whereas MRSA-positive neonates were identified from clinical samples or from screening. A total of 140 characteristics were investigated to identify risk factors associated with MRSA acquisition. The characteristics were categorized into three categories: patient, unit, and microbiological characteristics. Results: Out of 1,102 neonates screened for MRSA, between December 2019 and January 2022, 33 were MRSA positive. They were all colonized with an MRSA outbreak clone (spa type t127) and were included in this study. Four patients (12%) had severe infection. Admission due to respiratory diseases, need for intubation, need for peripheral venous catheters, admission to shared rooms with shared toilets and bath facilities in the aisles, and need for readmission were all correlated with later MRSA colonization (P < 0.05). Conclusion: We identified clinically relevant diseases, procedures, and facilities that predispose patients to potentially life-threatening MRSA infections. A specific MRSA reservoir remains unidentified; however, these findings have contributed to crucial changes in our NICU to reduce the number of MRSA infections and future outbreaks.

9.
J Sex Res ; : 1-12, 2023 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-37707442

RESUMEN

Access to sexual health education, such as education on sexual consent, is limited in the US. Artificial intelligence (AI), such as ChatGPT, provides a potential opportunity to increase access to sexual consent information and education. However, what ChatGPT knows about sexual consent and if this aligns with the current evidence-based literature on sexual consent is unclear. The goal of this research commentary was to explore what ChatGPT knows about sexual consent with a focus on: 1) the definition of consent, 2) how consent could be communicated, and 3) the impact that substances have on consent. We also examined the reliability of ChatGPT's responses by having three different researchers ask ChatGPT the same set of questions. Across our questions, ChatGPT provided similar and comprehensive responses that discussed key features of consent - that consent is freely given or reversible. ChatGPT provided examples of different verbal and nonverbal cues people can use to communicate and interpret consent and discussed the ways that substances can impact consent communication. Overall, ChatGPT could be a potential resource for educators and young people who seek information about sexual consent; however, we should proceed with caution. ChatGPT is not a replacement for an educator but rather a way to increase access to education.

11.
Artículo en Inglés | MEDLINE | ID: mdl-37490211

RESUMEN

Although studies have documented the relationships between physical health, health rumination/worry, and mental health, few investigations have assessed these linkages within African American communities. Using a community-based sample of residents in historically lower-income, African American communities (N = 306), this study assesses the mediating role of health rumination/worry in the physical limitation-depressive symptom relationship, and the moderating effect of gender on the relationship between health rumination/worry-depressive symptoms. Findings demonstrate that health rumination/worry explains half of the physical limitation-depressive symptom relationship, and the relationship between health rumination/worry and depressive symptoms is stronger for African American men than women. The findings underscore the importance of intersectional research for policy efforts aimed at reducing mental health morbidities within African American communities.

12.
Microb Genom ; 9(7)2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37410656

RESUMEN

Linezolid is used as first-line treatment of infections caused by vancomycin-resistant Enterococcus faecium. However, resistance to linezolid is increasingly detected. The aim of the present study was to elucidate the causes and mechanisms for the increase in linezolid-resistant E. faecium at Copenhagen University Hospital - Rigshospitalet. We therefore combined patient information on linezolid treatment with whole-genome sequencing data for vancomycin- or linezolid-resistant E. faecium isolates that had been systematically collected since 2014 (n=458). Whole-genome sequencing was performed for multilocus sequence typing (MLST), identification of linezolid resistance-conferring genes/mutations and determination of phylogenetically closely related strains. The collection of E. faecium isolates belonged to prevalent vancomycin-resistant MLST types. Among these, we identified clusters of closely related linezolid-resistant strains compatible with nosocomial transmission. We also identified linezolid-resistant enterococcus isolates not genetically closely related to other isolates compatible with de novo generation of linezolid resistance. Patients with the latter isolates were significantly more frequently exposed to linezolid treatment than patients with related linezolid-resistant enterococcus isolates. We also identified six patients who initially carried a vancomycin-resistant, linezolid-sensitive enterococcus, but from whom vancomycin-resistant, linezolid-resistant enterococci (LVRE) closely related to their initial isolate were recovered after linezolid treatment. Our data illustrate that linezolid resistance may develop in the individual patient subsequent to linezolid exposure and can be transmitted between patients in a hospital setting.


Asunto(s)
Enterococcus faecium , Enterococos Resistentes a la Vancomicina , Humanos , Linezolid/farmacología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Enterococcus faecium/genética , Vancomicina/farmacología , Vancomicina/uso terapéutico , Centros de Atención Terciaria , Tipificación de Secuencias Multilocus , Enterococos Resistentes a la Vancomicina/genética
14.
Viruses ; 15(4)2023 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-37112906

RESUMEN

Endogenous retroviruses (ERVs) account for 8% of our genome, and, although they are usually silent in healthy tissues, they become reactivated and expressed in pathological conditions such as cancer. Several studies support a functional role of ERVs in tumour development and progression, specifically through their envelope (Env) protein, which contains a region described as an immunosuppressive domain (ISD). We have previously shown that targeting of the murine ERV (MelARV) Env using virus-like vaccine (VLV) technology, consisting of an adenoviral vector encoding virus-like particles (VLPs), induces protection against small tumours in mice. Here, we investigate the potency and efficacy of a novel MelARV VLV with a mutated ISD (ISDmut) that can modify the properties of the adenoviral vaccine-encoded Env protein. We show that the modification of the vaccine's ISD significantly enhanced T-cell immunogenicity in both prime and prime-boost vaccination regimens. The modified VLV in combination with an α-PD1 checkpoint inhibitor (CPI) exhibited excellent curative efficacy against large established colorectal CT26 tumours in mice. Furthermore, only ISDmut-vaccinated mice that survived CT26 challenge were additionally protected against rechallenge with a triple-negative breast cancer cell line (4T1), showing that our modified VLV provides cross-protection against different tumour types expressing ERV-derived antigens. We envision that translating these findings and technology into human ERVs (HERVs) could provide new treatment opportunities for cancer patients with unmet medical needs.


Asunto(s)
Retrovirus Endógenos , Neoplasias , Vacunas Virales , Animales , Humanos , Ratones , Retrovirus Endógenos/genética , Vectores Genéticos/genética , Neoplasias/prevención & control , Neoplasias/genética , Linfocitos T , Vacunas Virales/genética , Receptor de Muerte Celular Programada 1/inmunología
15.
Euro Surveill ; 28(17)2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37103784

RESUMEN

A hypervirulent Klebsiella pneumoniae SL218 (ST23-KL57), phylogenetically distinct from the classical hypervirulent SL23 (ST23-KL1) lineage, was transmitted between hospitalised patients in Denmark in 2021. The isolate carried a hybrid resistance and virulence plasmid containing bla NDM-1 and a plasmid containing bla OXA-48 (pOXA-48); the latter plasmid was horizontally transferred within-patient to Serratia marcescens. The convergence of drug resistance and virulence factors in single plasmids and in different lineages of K. pneumoniae is concerning and requires surveillance.


Asunto(s)
Infecciones por Klebsiella , Klebsiella pneumoniae , Humanos , Klebsiella pneumoniae/genética , Serratia marcescens/genética , beta-Lactamasas/genética , Proteínas Bacterianas/genética , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/epidemiología , Plásmidos/genética , Dinamarca/epidemiología
16.
J Appl Physiol (1985) ; 134(4): 858-867, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36861674

RESUMEN

The purpose of this study was to evaluate in vivo endothelial function and nitric oxide (NO)-dependent vasodilation between women in either menstrual or placebo pill phases of their respective hormonal exposure [either naturally cycling (NC) or using oral contraceptive pills (OCPs)] and men. A planned subgroup analysis was then completed to assess endothelial function and NO-dependent vasodilation between NC women, women using OCP, and men. Endothelium-dependent and NO-dependent vasodilation were assessed in the cutaneous microvasculature using laser-Doppler flowmetry, a rapid local heating protocol (39°C, 0.1 °C/s), and pharmacological perfusion through intradermal microdialysis fibers. Data are represented as means ± standard deviation. Men displayed greater endothelium-dependent vasodilation (plateau, men: 71 ± 16 vs. women: 52 ± 20%CVCmax, P < 0.01), but lower NO-dependent vasodilation (men: 52 ± 11 vs. women: 63 ± 17%NO, P = 0.05) compared with all women. Subgroup analysis revealed NC women had lower endothelium-dependent vasodilation (plateau, NC women: 48 ± 21%CVCmax, P = 0.01) but similar NO-dependent vasodilation (NC women: 52 ± 14%NO, P > 0.99), compared with men. Endothelium-dependent vasodilation did not differ between women using OCP and men (P = 0.12) or NC women (P = 0.64), but NO-dependent vasodilation was significantly greater in women using OCP (74 ± 11%NO) than both NC women and men (P < 0.01 for both). This study highlights the importance of directly quantifying NO-dependent vasodilation in cutaneous microvascular studies. This study also provides important implications for experimental design and data interpretation.NEW & NOTEWORTHY This study supports differences in microvascular endothelial function and nitric oxide (NO)-dependent vasodilation between women in low hormone phases of two hormonal exposures and men. However, when separated into subgroups of hormonal exposure, women during placebo pills of oral contraceptive pill (OCP) use have greater NO-dependent vasodilation than naturally cycling women in their menstrual phase and men. These data improve knowledge of sex differences and the effect of OCP use on microvascular endothelial function.


Asunto(s)
Óxido Nítrico , Vasodilatación , Femenino , Humanos , Masculino , Anticonceptivos Orales , Endotelio , Óxido Nítrico/farmacología , Piel/irrigación sanguínea , Fenómenos Fisiológicos de la Piel
17.
Proc Natl Acad Sci U S A ; 120(14): e2220102120, 2023 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-36996103

RESUMEN

Molecular clocks in the periphery coordinate tissue-specific daily biorhythms by integrating input from the hypothalamic master clock and intracellular metabolic signals. One such key metabolic signal is the cellular concentration of NAD+, which oscillates along with its biosynthetic enzyme, nicotinamide phosphoribosyltransferase (NAMPT). NAD+ levels feed back into the clock to influence rhythmicity of biological functions, yet whether this metabolic fine-tuning occurs ubiquitously across cell types and is a core clock feature is unknown. Here, we show that NAMPT-dependent control over the molecular clock varies substantially between tissues. Brown adipose tissue (BAT) requires NAMPT to sustain the amplitude of the core clock, whereas rhythmicity in white adipose tissue (WAT) is only moderately dependent on NAD+ biosynthesis, and the skeletal muscle clock is completely refractory to loss of NAMPT. In BAT and WAT, NAMPT differentially orchestrates oscillation of clock-controlled gene networks and the diurnality of metabolite levels. NAMPT coordinates the rhythmicity of TCA cycle intermediates in BAT, but not in WAT, and loss of NAD+ abolishes these oscillations similarly to high-fat diet-induced circadian disruption. Moreover, adipose NAMPT depletion improved the ability of animals to defend body temperature during cold stress but in a time-of-day-independent manner. Thus, our findings reveal that peripheral molecular clocks and metabolic biorhythms are shaped in a highly tissue-specific manner by NAMPT-dependent NAD+ synthesis.


Asunto(s)
NAD , Nicotinamida Fosforribosiltransferasa , Animales , NAD/metabolismo , Nicotinamida Fosforribosiltransferasa/genética , Nicotinamida Fosforribosiltransferasa/metabolismo , Ritmo Circadiano/fisiología , Tejido Adiposo Pardo/metabolismo , Obesidad/metabolismo , Citocinas/metabolismo
18.
Exp Physiol ; 108(1): 5-11, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36448409

RESUMEN

NEW FINDINGS: What is the main observation in this case? The main observation of this case report is substantial improvement in cutaneous microvascular endothelial function after cessation of long-term use of a fourth-generation oral contraceptive pill. This improvement appears independent of relative changes in the contribution of nitric oxide. What insights does it reveal? Our findings suggest that cessation of long-term, fourth-generation oral contraceptive pill use improves endothelial function within 20 months of cessation. ABSTRACT: The purpose of this case report was to evaluate in vivo endothelial function and nitric oxide (NO)-dependent vasodilatation before and after the cessation of long-term (11-12 years) fourth-generation oral contraceptive pill (OCP) use in one young, healthy and premenopausal woman. This retrospective analysis includes data from six experimental visits: three visits during months 133-144 of fourth-generation OCP use and three visits 19-22 months after OCP cessation. Endothelium-dependent and NO-dependent vasodilatation were assessed in the cutaneous microvasculature using laser-Doppler flowmetry, a rapid local heating protocol (39°C, 0.1°C/s) and pharmacological perfusion through intradermal microdialysis fibres. The participant had consistent medical history and lifestyle behaviours throughout both hormonal exposures. Data are presented as the mean (SD). Endothelium-dependent vasodilatation was 42 (10)% of site-specific maximal cutaneous vascular conductance (CVCmax ) during OCP use and 63 (10)%CVCmax after OCP cessation (49% increase). Nitric oxide-dependent vasodilatation was 70 (5)% contribution of NO during OCP use and 60 (15)%NO after OCP cessation (15% reduction). Baseline blood flow was greater after OCP cessation, but maximal blood flow was reduced. Data from this case report support a substantial increase in cutaneous microvascular endothelial function assessed via local heating after cessation of long-term use of a fourth-generation OCP, which does not appear to be attributable to increased NO bioavailability. Overall, these data suggest an improvement in endothelial and microvascular function after the cessation of long-term use of a fourth-generation OCP.


Asunto(s)
Óxido Nítrico , Piel , Femenino , Humanos , Estudios Retrospectivos , Piel/irrigación sanguínea , Vasodilatación/fisiología , Endotelio , Anticonceptivos Orales/farmacología , Flujo Sanguíneo Regional/fisiología
19.
Sex Transm Dis ; 50(4): 196-202, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36538365

RESUMEN

BACKGROUND: The percentage of Neisseria gonorrhoeae (GC) isolates with resistance or elevated minimum inhibitory concentrations to antimicrobials has steadily increased. Current estimates are based on the Gonococcal Isolate Surveillance Project (GISP), a sentinel surveillance study of male GC in the United States. This analysis seeks to assess for adjustment before treating aggregated GISP estimates as nationally representative of all reported male urogenital infections. METHODS: We used multilevel regression with poststratification (MRP) to compute national estimates of the proportion of antimicrobial resistance (AMR) (defined as exceeding minimum inhibitory concentration thresholds) in male GC using data from 2008 to 2018 GISP and case reports. Sensitivity analyses investigated the impact of analysis assumptions and unmeasured variables. We additionally produced estimates of 2018 AMR GC cases among US men. RESULTS: National estimates were consistent with unweighted estimates. The estimated proportion of incident AMR GC infections in men with urogenital GC in 2018 was 51.5% (95% confidence interval [CI], 50.1%-52.9%), equating to an estimated 366,300 incident AMR GC infections in US men aged 15 to 39 years. Estimates of AMR for tested antimicrobials in male GC infections in 2018 ranged from 0.16% (95% CI, 0.08%-0.24%) for ceftriaxone to 29.9% (95% CI, 28.6%-31.1%) for ciprofloxacin. Sensitivity analyses revealed that unmeasured data on sex of sex partners could substantially impact weighted estimates. CONCLUSIONS: Antimicrobial resistance among reported incident male urogenital GC infections remains rare for ceftriaxone, the current standard of care. Aggregated GISP data are generally representative of men in the US who are reported with urogenital gonorrhea.


Asunto(s)
Antiinfecciosos , Gonorrea , Masculino , Humanos , Estados Unidos/epidemiología , Gonorrea/tratamiento farmacológico , Gonorrea/epidemiología , Neisseria gonorrhoeae , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Ceftriaxona/farmacología , Farmacorresistencia Bacteriana , Ciprofloxacina/farmacología , Antiinfecciosos/farmacología , Pruebas de Sensibilidad Microbiana
20.
APMIS ; 130(11): 657-660, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35851968

RESUMEN

Denmark has experienced an increase in the proportion of invasive vancomycin-resistant Enterococcus faecium (VRE) since 2002 (e.g. <4% in 2015, 7.1% in 2017 and 12% in 2018). At Rigshospitalet, we employ active screening at departments with high prevalence or in case of outbreaks. This includes the collection of rectal swabs specifically for VRE screening. Our purpose was to describe the carrier prevalence of vancomycin-resistant enterococci among acute patients admitted to the Neurointensive Care Unit, Department of Neuroanaesthesiology, Rigshospitalet, Copenhagen, Denmark (NICU). Between April 2018 and January 2019, we investigated 99 consecutive rectal swabs from patients admitted to NICU. The primary outcome was prevalence of VRE carriage. The median age was 64 years (range 23-87) and gender was equally distributed (Female = 47, Male = 46). 26 (28%) had previously been admitted within 179 days and 67 patients (72%) had no hospital admissions within 180 days prior to the admission to NICU. Of the 93 rectal swabs, 2 (2%, 95% CI 0.26-7.55%) were positive for vanA and none were positive for vanB. Routine screening of all patients at admission may be effective in hospital settings with high VRE prevalence, whereas the benefit of screening for VRE in hospitals with a low prevalence may be restricted to specific patient populations.


Asunto(s)
Enterococcus faecium , Infecciones por Bacterias Grampositivas , Enterococos Resistentes a la Vancomicina , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Femenino , Infecciones por Bacterias Grampositivas/diagnóstico , Infecciones por Bacterias Grampositivas/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Vancomicina , Resistencia a la Vancomicina , Adulto Joven
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