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1.
Int J Emerg Med ; 17(1): 61, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38698343

RESUMEN

BACKGROUND: Emergency department (ED) crowding is a common healthcare issue with multiple causes. One important knowledge area is understanding where patients arrived from and what care they received prior to ED admission. This information could be used to inform strategies to provide care for low acuity patients outside of the hospital and reduce unnecessary ED admissions. The aim of this scoping review was to provide a comprehensive overview of global published research examining the acute care trajectory of all ED patients. METHODS: The scoping review was performed according to the JBI Manual for Evidence Synthesis and the PRISMA-SCR checklist. A comprehensive literature search was performed to identify studies describing where patients arrived from and/or whose pathway of care was before an ED visit. The search was conducted in MEDLINE, Embase, and the Cochrane Library from inception through December 5th, 2022. Two reviewers independently screened the records. RESULTS: Out of the 6,465 records screened, 14 studies from Australia, Canada, Haiti, Norway, Sweden, Switzerland, Belgium, Indonesia, and the UK met the inclusion criteria. Four studies reported on where patients physically arrived from, ten reported how patients were transported, six reported who referred them, and six reported whether medical care or advice was sought prior to visiting an ED. CONCLUSION: This scoping review revealed a lack of studies describing patients' pathways to the ED. However, studies from some countries indicate that a relatively large proportion of patients first seek care or guidance from a primary care physician (PCP) before visiting an ED. However, further research and published data are needed. To improve the situation, we recommend the development and implementation of a template for the uniform reporting of factors outside the ED, including where the patient journey began, which healthcare facilities they visited, who referred them to the ED, and how they arrived.

3.
Arch Sex Behav ; 53(4): 1499-1518, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38429569

RESUMEN

Unhealthy alcohol use and sexually transmitted infections (STIs) are significant public health concerns for US college students. Because alcohol use and condomless sex often co-occur in this population, alcohol-associated condomless sex has been identified as a behavioral intervention target. Existing theoretical frameworks have not garnered sufficient empirical support to serve as the foundation for interventions. The primary goal of the current study was to use a mixed-methods approach to develop a model of college student alcohol-associated condomless sex that combines elements from well-established health behavior theories. In Aim 1, multilevel modeling was used to predict condomless vaginal sex in a sample of heterosexual college student drinkers (N = 53). Aim 2 consisted of in-depth interviews (n = 18) to gather perceptions about the role of alcohol in sexual activity and identify supplemental constructs omitted from theories in Aim 1. The multilevel model explained a significant proportion of variance in condomless vaginal sex at the between- and within-person level. Themes derived from the in-depth interviews identified complementary elements of condom use decision-making. Findings from both aims were synthesized to construct a combined model of alcohol-associated condomless sex. This model can be further refined and ultimately serve as the foundation of an alcohol-STI prevention-intervention.


Asunto(s)
Infecciones por VIH , Enfermedades de Transmisión Sexual , Femenino , Humanos , Sexo Inseguro/prevención & control , Conducta Sexual , Enfermedades de Transmisión Sexual/prevención & control , Enfermedades de Transmisión Sexual/epidemiología , Sexo Seguro , Estudiantes , Condones , Infecciones por VIH/epidemiología
4.
Am Surg ; : 31348241241707, 2024 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-38520278

RESUMEN

BACKGROUND: This study analyzed the overall incidence of delirium, comorbid conditions, injury patterns, and pharmacological risk factors for the development of delirium in an alert, geriatric trauma population. METHODS: IRB-approved, prospective, consecutive cohort series at two Southeastern Level 1 trauma centers from June 11 to August 15, 2023. Delirium was assessed using the Confusion Assessment Method (CAM) score. Comorbidities and medications were detailed from electronic medical records. Inclusion criteria: age ≥55, GCS ≥14, and ICU admission for trauma. Patients on a ventilator were excluded. Data was analyzed using SPSS version 28 (Armonk, NY: IBM Corp). RESULTS: In total, 196 patients met inclusion criteria. Incidences of delirium for Hospital 1 (n = 103) and Hospital 2 (n = 93) were 15.5% and 12.9%, respectively, with an overall incidence of 14.3% and with no statistical differences between hospitals (P = .599). CAD, CKD, dementia, stroke history, and depression were statistically significant risk factors for developing delirium during ICU admission. Inpatient SSRI/SNRIs, epinephrine/norepinephrine, and lorazepam were significant risk factors. Injury patterns, operative intervention, and use of lidocaine infusions and gabapentin were not statistically significant in delirium development. Using binary linear regression (BLR) analysis, independent risk factors for delirium were dementia, any stage CKD, home SSRI/SRNI prescription, any spine injury and cerebrovascular disease, or injury. DISCUSSION: Comorbidities of CAD, CHF, CKD, and depression, and these medications: home lorazepam and ICU epinephrine/norepinephrine statistically are more common in patients developing delirium. Dementia, CKD, home SSRI/SRNI and stroke/cerebrovascular disease/injury, and spine injuries are independent predictors by BLR.

5.
Am Surg ; : 31348241241639, 2024 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-38520292

RESUMEN

Unplanned admission to an intensive care unit (ICU) is a trauma quality improvement indicator associated with increased morbidity, mortality, and hospital resource usage. We identified demographics, injuries, and other clinical factors between early ICU admission, <72 hrs after admission (EAd), and delayed admission, >72 hrs (DelAd) from a medical/surgical floor. 146 trauma patients admitted to ICU at a level 1 trauma center from January 2020 to March 2023 met inclusion criteria and were divided into EAd and DelAd. No statistical differences in injury mechanism or severity were observed. Delayed admission demonstrated higher mortality (P = .001), more frequent decline in GCS (P = .045), and initiation of anticoagulation (P = .002). Abnormal EKG, orthopedic surgery during admission, and home anticoagulant and antidepressant use were statistically significant in identifying patients requiring early ICU admission.

6.
Am Surg ; : 31348241241619, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38509028

RESUMEN

Surgical palliative care (PC) facilitates communication between surgeons and patients/family about prognosis, symptom control, and therapeutic goals. Surgical critical care (SCC) fellows are at the forefront of the intensive care team; thus, we aim to assess previous and ongoing experiences in delivering PC by surveying fellows at a large academic center. Seventeen surveys were completed in which 59% of fellows reported no previous PC education. Six fellows (35%) reported participating in goals of care/end-of-life (GOC/EOL) discussions "a few times a year" during residency, while 41% responded the same for transitioning patients to comfort-focused care (CFC). When asked if respondents felt comfortable facilitating GOC/EOL discussions prior to fellowship, 7 (41%) answered "disagree" or "strongly disagree." Most fellows reported that more training in navigating GOC/EOL discussions (88%) and transitioning patients to CFC (76%) is needed. This assessment demonstrates variability in fellows' prior PC exposure and a strong desire for more structured training.

7.
J Pediatr ; 270: 114019, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38514003

RESUMEN

Pediatric fellowship programs have conducted virtual interviews since the start of the COVID-19 pandemic in 2020. In this national survey of fellowship program directors and fellows interviewed in-person and virtually, fellowship program directors and fellows formed accurate impressions, regardless of format, but our data did not clearly support one interview format over another.

8.
Artículo en Inglés | MEDLINE | ID: mdl-38409998

RESUMEN

Compared to the large body of maternal mental health research for other pediatric disorders, we know far less about the experience of mothers of children with 22q11DS. This study investigates the coping methods, protective factors, and mental health of this population. These findings might lead to better support for 22q11DS maternal mental health. An international sample of 71 mothers (M = 40.5 years) of children with 22q11DS (M = 9.2 years) was recruited and completed an online survey assessing maternal mental health (symptoms of depression, anxiety, traumatic stress, general stress, and alcohol consumption), coping methods, and mental health protective factors (social support, dyadic adjustment, parenting competence). Maternal ratings of child mental health symptoms were also obtained. Mothers' self-report revealed a high percentage who screened positive for elevated levels of general stress (69%), hazardous alcohol consumption (30.9%), traumatic stress (33.8%), anxiety (26.8%), and depression (26.8%). After controlling for demographic variables and child mental health symptoms, maternal self-reported maladaptive coping methods were positively associated with maternal symptoms of depression, anxiety, stress, and traumatic stress. Reducing maladaptive coping methods may be a promising intervention for improving mental health in mothers of children with 22q11DS.

9.
J Am Coll Surg ; 238(4): 762-767, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38193566

RESUMEN

BACKGROUND: Better means of identifying patients with increased cardiac complication (CC) risk is needed. Coronary artery calcification (CAC) is reported on routine chest CT scans. We assessed the correlation of CAC and CCs in the geriatric trauma population. STUDY DESIGN: A prospective, observational study of patients 55 years and older who had chest CT scan from May to September 2022 at a level 1 trauma center. Radiologists scored CAC as none, mild, moderate, or severe. None-to-mild CAC (NM-CAC) and moderate-to-severe CAC (MS-CAC) were grouped and in-hospital CCs assessed (arrhythmia, ST elevation myocardial infarction [STEMI], non-STEMI, congestive heart failure, pulmonary edema, cardiac arrest, cardiogenic shock, and cardiac mortality). Univariate and bivariate analyses were performed. RESULTS: Five hundred sixty-nine patients had a chest CT, of them 12 were excluded due to missing CAC severity. Of 557 patients, 442 (79.3%) had none-to-mild CAC and 115 (20.7%) has MS-CAC; the MS-CAC group was older (73.3 vs 67.4 years) with fewer male patients (48.7% vs 54.5%), had higher cardiac-related comorbidities, and had higher abbreviated injury scale chest injury scores. The MS-CAC group had an increased rate of CC (odds ratio [OR] 1.81, p = 0.016). Cardiac complications statistically more common in MS-CAC were congestive heart failure (OR 3.41, p = 0.003); cardiogenic shock (OR 3.3, p = 0.006); non-STEMI I or II (OR 2.8, p = 0.017); STEMI (OR 5.9, p = 0.029); and cardiac-caused mortality (OR 5.27, p = 0.036). No statistical significance between pulmonary edema (p = 0.6), new-onset arrhythmia (p = 0.74), or cardiac arrest (p = 0.193). CONCLUSIONS: CAC as reported on chest CT scans demonstrates a significant correlation with CC and should warrant additional cardiac monitoring.


Asunto(s)
Enfermedad de la Arteria Coronaria , Paro Cardíaco , Insuficiencia Cardíaca , Edema Pulmonar , Infarto del Miocardio con Elevación del ST , Calcificación Vascular , Anciano , Humanos , Masculino , Arritmias Cardíacas/complicaciones , Angiografía Coronaria/efectos adversos , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Estudios Prospectivos , Edema Pulmonar/complicaciones , Factores de Riesgo , Choque Cardiogénico/complicaciones , Infarto del Miocardio con Elevación del ST/complicaciones , Calcificación Vascular/complicaciones , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/epidemiología , Persona de Mediana Edad , Femenino
10.
J Lipid Res ; 65(3): 100503, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38246235

RESUMEN

Circulating levels of the soluble ligand-binding ectodomain of the LDL receptor (sLDLR) that is proteolytically cleaved from the cell surface have been shown to correlate with plasma triglycerides, but the lipid and lipoprotein effects of longitudinal changes in sLDLR have not been examined. We sought to assess associations between changes in sLDLR and detailed lipoprotein measurements between baseline and 6 months in participants in the DIETFITS (Diet Intervention Examining The Factors Interacting with Treatment Success) weight loss trial who were randomly assigned to the low-fat (n = 225) or low-carbohydrate (n = 236) diet arms. sLDLR was assayed using a proteomic procedure, lipids and apoprotein (apo) B and apoAI were measured by standard assays, and lipoprotein particle subfractions were quantified by ion mobility methodology. Changes in sLDLR were significantly positively associated with changes in plasma cholesterol, triglycerides, apoB, large-sized and medium-sized VLDL, and small and very small LDL, and inversely with changes in large LDL and HDL. The lipoprotein subfraction associations with sLDLR were independent of age, sex, diet, and BMI, but all except for large LDL were reduced to insignificance when adjusted for triglyceride change. Principal component analysis identified three independent clusters of changes in lipoprotein subfractions that accounted for 78% of their total variance. Change in sLDLR was most strongly correlated with change in the principal component that was loaded positively with large VLDL and small and very small LDL and negatively with large LDL and HDL. In conclusion, sLDLR is a component of a cluster of lipids and lipoproteins that are characteristic of atherogenic dyslipidemia.


Asunto(s)
Lipoproteínas , Proteómica , Humanos , Triglicéridos , Receptores de LDL , Dieta , Pérdida de Peso , Lipoproteínas LDL , Lipoproteínas VLDL
12.
Am J Psychiatry ; 181(2): 153-165, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37434487

RESUMEN

OBJECTIVE: The authors investigated cortico-striatal reactivity to drug cues (as compared with neutral and food cues), drug cue reappraisal, food cue savoring, and their correlations with heroin craving in individuals with heroin use disorder compared with healthy control subjects. METHODS: Cross-sectional changes in functional MRI blood-oxygen-level-dependent signal during a novel cue reactivity task were assessed in 32 individuals with heroin use disorder (mean age, 40.3 years; seven women) and 21 age- and sex-matched healthy control subjects (mean age, 40.6 years; eight women). RESULTS: Drug cue reactivity (vs. neutral cues) was significantly higher in the nucleus accumbens in the heroin use disorder group compared with the control group and nominally significantly higher in the orbitofrontal cortex (OFC); ventromedial prefrontal cortex (vmPFC) activity positively correlated with drug craving. Drug cue reactivity (vs. salient food cues) was also higher in the inferior frontal gyrus (IFG) in the heroin use disorder group compared with the control group. Drug reappraisal and food savoring (vs. passive viewing) showed increased IFG and supplementary motor area activity in all participants; in the heroin use disorder group, higher IFG/dorsolateral PFC (dlPFC) activity during drug reappraisal and rostral anterior cingulate cortex (ACC) activity during food savoring were associated with lower drug cue-induced craving and longer treatment, respectively. A direct comparison of regulation of reactivity to both salient cues revealed widespread group differences such that drug reappraisal activity was higher in the heroin use disorder group and food savoring activity was higher in the control group in both cortical (e.g., OFC, IFG, ACC, vmPFC, and insula) and subcortical (e.g., dorsal striatum and hippocampus) regions. Higher drug reappraisal versus food savoring in the dlPFC was associated with higher self-reported methadone dosage in the heroin use disorder group. CONCLUSIONS: The results demonstrate cortico-striatal upregulation during drug cue exposure and impaired reactivity during processing of alternative non-drug rewards in the heroin use disorder group. Normalizing cortico-striatal function by reducing drug cue reactivity and enhancing natural reward valuation may inform therapeutic mechanisms for reducing drug craving and seeking in heroin addiction.


Asunto(s)
Encéfalo , Dependencia de Heroína , Humanos , Femenino , Adulto , Ansia , Heroína , Señales (Psicología) , Estudios Transversales , Imagen por Resonancia Magnética/métodos
13.
Matern Child Nutr ; 20(2): e13612, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38143422

RESUMEN

Children under-5 years of age are particularly vulnerable to severe acute malnutrition (SAM), and the risk factors associated with relapse to SAM are poorly understood. Possible causes are asymptomatic or symptomatic infection with enteric pathogens, with contaminated food as a critical transmission route. This cross-sectional study comprised a household survey with samples of child food (n = 382) and structured observations of food preparation (n = 197) among children aged 6-59 months that were discharged from treatment in community management of acute malnutrition (CMAM) programmes in South Sudan. We quantified Escherichia coli and total coliforms (TCs), measured in colony forming units per g of food (CFU/g), as indicators of microbial contamination of child food. A modified hazard analysis critical control point (HACCP) approach was utilised to determine critical control points (CCPs) followed by multivariate logistic regression analysis to understand the risk factors associated with contamination. Over 40% (n = 164) of samples were contaminated with E. coli (43% >0 E. coli CFU/g, 95% CI 38%-48%), and 90% (n = 343) had >10 TCs (CFU/g) (>10 TC CFU/g, 95% CI 87%-93%). Risk factors associated (p < 0.05) with child food contamination included if the child fed themselves (9.05 RR, 95% CI [3.18, 31.16]) and exposure to animals (2.63 RR, 95% CI [1.33, 5.34]). This study highlights the risk factors and potential control strategies that can support interventions that reduce food contamination exposure in young children and help further protect those that are highly vulnerable to recurrent exposure to enteric pathogens.


Asunto(s)
Contaminación de Alimentos , Desnutrición , Preescolar , Humanos , Lactante , Estudios Transversales , Escherichia coli , Análisis de Peligros y Puntos de Control Críticos , Alta del Paciente , Factores de Riesgo , Desnutrición Aguda Severa/terapia , Sudán del Sur/epidemiología
14.
Nutrients ; 15(23)2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-38068713

RESUMEN

A non-randomized prospective cohort study was conducted in 2022 to compare recovery rate and length of stay (LoS) for acutely malnourished children treated under South Sudan's standard Community Management of Acute Malnutrition (CMAM) protocol and a COVID-modified protocol. Children aged 6-59 months received acute malnutrition (AM) treatment under the standard or modified protocol (mid-upper-arm circumference-only entry/exit criteria and simplified dosing). Primary (recovery rate and LoS) were compared for outpatient therapeutic (OTP) and therapeutic supplementary feeding programs (TSFP) using descriptive statistics and mixed-effects models. Children admitted to OTP under both protocols were similar in age and sex; children admitted to TSFP were significantly older under the modified protocol than the standard protocol. Shorter LoS and higher recovery rates were observed under the modified protocol for both OTP (recovery: 93.3% vs. 87.2%; LoS: 38.3 vs. 42.8 days) and TSFP (recovery: 79.8% vs. 72.7%; LoS: 54.0 vs. 61.9 days). After adjusting for site and child characteristics, neither differences in adjusted odds of recovery [OTP: 2.63; TSFP 1.80] nor LoS [OTP -10.0; TSFP -7.8] remained significant. Modified protocols for AM performed well. Adjusted models indicate similar treatment outcomes to the standard protocol. Adopting simplified protocols could be beneficial post-pandemic; however, recovery and relapse will need to be monitored.


Asunto(s)
COVID-19 , Desnutrición , Desnutrición Aguda Severa , Niño , Humanos , Lactante , Sudán del Sur , Estudios Prospectivos , Desnutrición Aguda Severa/terapia , COVID-19/terapia , Desnutrición/terapia , Protocolos Clínicos
15.
J Int AIDS Soc ; 26(12): e26187, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38054564

RESUMEN

INTRODUCTION: Unhealthy alcohol use significantly contributes to viral non-suppression among persons with HIV (PWH). It is unknown whether brief behavioural interventions to reduce alcohol use can improve viral suppression among PWH with unhealthy alcohol use in sub-Saharan Africa (SSA). METHODS: As part of the SEARCH study (NCT04810650), we conducted an individually randomized trial in Kenya and Uganda of a brief, skills-based alcohol intervention among PWH with self-reported unhealthy alcohol use (Alcohol Use Disorders Identification Test-Consumption [AUDIT-C], prior 3 months, ≥3/female; ≥4/male) and at risk of viral non-suppression, defined as either recent HIV viral non-suppression (≥400 copies/ml), missed visits, out of care or new diagnosis. The intervention included baseline and 3-month in-person counselling sessions with interim booster phone calls every 3 weeks. The primary outcome was HIV viral suppression (<400 copies/ml) at 24 weeks, and the secondary outcome was unhealthy alcohol use, defined by AUDIT-C or phosphatidylethanol (PEth), an alcohol biomarker, ≥50 ng/ml at 24 weeks. RESULTS: Between April and September 2021, 401 persons (198 intervention, 203 control) were enrolled from HIV clinics in Uganda (58%) and Kenya (27%) and alcohol-serving venues in Kenya (15%). At baseline, 60% were virally suppressed. Viral suppression did not differ between arms at 24 weeks: suppression was 83% in intervention and 82% in control arms (RR: 1.01, 95% CI: 0.93-1.1). Among PWH with baseline viral non-suppression, 24-week suppression was 73% in intervention and 64% in control arms (RR 1.15, 95% CI: 0.93-1.43). Unhealthy alcohol use declined from 98% at baseline to 73% in intervention and 84% in control arms at 24 weeks (RR: 0.86, 95% CI: 0.79-0.94). Effects on unhealthy alcohol use were stronger among women (RR 0.70, 95% CI: 0.56-0.88) than men (RR 0.93, 95% CI: 0.85-1.01) and among participants with a baseline PEth⩽200 ng/ml (RR 0.68, 95% CI: 0.53-0.87) versus >200 ng/ml (RR 0.97, 95% CI: 0.92-1.02). CONCLUSIONS: In a randomized trial of 401 PWH with unhealthy alcohol use and risk for viral non-suppression, a brief alcohol intervention reduced unhealthy alcohol use but did not affect viral suppression at 24 weeks. Brief alcohol interventions have the potential to improve the health of PWH in SSA by reducing alcohol use, a significant driver of HIV-associated co-morbidities.


Asunto(s)
Alcoholismo , Infecciones por VIH , Humanos , Masculino , Femenino , Infecciones por VIH/diagnóstico , Alcoholismo/complicaciones , Alcoholismo/terapia , Uganda/epidemiología , Kenia/epidemiología , Consejo , Etanol
16.
J Lipid Res ; 64(12): 100471, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37944753

RESUMEN

Despite great progress in understanding lipoprotein physiology, there is still much to be learned about the genetic drivers of lipoprotein abundance, composition, and function. We used ion mobility spectrometry to survey 16 plasma lipoprotein subfractions in 500 Diversity Outbred mice maintained on a Western-style diet. We identified 21 quantitative trait loci (QTL) affecting lipoprotein abundance. To refine the QTL and link them to disease risk in humans, we asked if the human homologs of genes located at each QTL were associated with lipid traits in human genome-wide association studies. Integration of mouse QTL with human genome-wide association studies yielded candidate gene drivers for 18 of the 21 QTL. This approach enabled us to nominate the gene encoding the neutral ceramidase, Asah2, as a novel candidate driver at a QTL on chromosome 19 for large HDL particles (HDL-2b). To experimentally validate Asah2, we surveyed lipoproteins in Asah2-/- mice. Compared to wild-type mice, female Asah2-/- mice showed an increase in several lipoproteins, including HDL. Our results provide insights into the genetic regulation of circulating lipoproteins, as well as mechanisms by which lipoprotein subfractions may affect cardiovascular disease risk in humans.


Asunto(s)
Ratones de Colaboración Cruzada , Estudio de Asociación del Genoma Completo , Femenino , Humanos , Ratones , Animales , Lipoproteínas/genética , Sitios de Carácter Cuantitativo/genética , Fenotipo , Lipoproteínas VLDL
17.
J Lipid Res ; 64(12): 100468, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37913995

RESUMEN

Common noncoding variants at the human 1p13.3 locus associated with SORT1 expression are among those most strongly associated with low-density lipoprotein cholesterol (LDL-C) in human genome-wide association studies. However, validation studies in mice and cell lines have produced variable results regarding the directionality of the effect of SORT1 on LDL-C. This, together with the fact that the 1p13.3 variants are associated with expression of several genes, has raised the question of whether SORT1 is the causal gene at this locus. Using whole exome sequencing in members of an Amish population, we identified coding variants in SORT1 that are associated with increased (rs141749679, K302E) and decreased (rs149456022, Q225H) LDL-C. Further, analysis of plasma lipoprotein particle subclasses by ion mobility in a subset of rs141749679 (K302E) carriers revealed higher levels of large LDL particles compared to noncarriers. In contrast to the effect of these variants in the Amish, the sortilin K302E mutation introduced into a C57BL/6J mouse via CRISPR/Cas9 resulted in decreased non-high-density lipoprotein cholesterol, and the sortilin Q225H mutation did not alter cholesterol levels in mice. This is indicative of different effects of these mutations on cholesterol metabolism in the two species. To our knowledge, this is the first evidence that naturally occurring coding variants in SORT1 are associated with LDL-C, thus supporting SORT1 as the gene responsible for the association of the 1p13.3 locus with LDL-C.


Asunto(s)
Amish , Estudio de Asociación del Genoma Completo , Humanos , Ratones , Animales , LDL-Colesterol/genética , Ratones Endogámicos C57BL , Colesterol , Proteínas Adaptadoras del Transporte Vesicular/genética , Proteínas Adaptadoras del Transporte Vesicular/metabolismo
18.
medRxiv ; 2023 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-37961156

RESUMEN

Movies captivate groups of individuals (the audience), especially if they contain themes of common motivational interest to the group. In drug addiction, a key mechanism is maladaptive motivational salience attribution whereby drug cues outcompete other reinforcers within the same environment or context. We predicted that while watching a drug-themed movie, where cues for drugs and other reinforcers share a continuous narrative context, fMRI responses in individuals with heroin use disorder (iHUD) will preferentially synchronize during drug scenes. Results revealed such drug-biased synchronization in the orbitofrontal cortex (OFC), ventromedial and ventrolateral prefrontal cortex, and insula. After 15 weeks of inpatient treatment, there was a significant reduction in this drug-biased shared response in the OFC, which correlated with a concomitant reduction in dynamically-measured craving, suggesting synchronized OFC responses to a drug-themed movie as a neural marker of craving and recovery in iHUD.

19.
Glob Chang Biol ; 29(24): 6900-6911, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37804212

RESUMEN

The global decline of terrestrial species is largely due to the degradation, loss and fragmentation of their habitats. The conversion of natural ecosystems for cropland, rangeland, forest products and human infrastructure are the primary causes of habitat deterioration. Due to the paucity of data on the past distribution of species and the scarcity of fine-scale habitat conversion maps, however, accurate assessment of the recent effects of habitat degradation, loss and fragmentation on the range of mammals has been near impossible. We aim to assess the proportions of available habitat within the lost and retained parts of mammals' distribution ranges, and to identify the drivers of habitat availability. We produced distribution maps for 475 terrestrial mammals for the range they occupied 50 years ago and compared them to current range maps. We then calculated the differences in the percentage of 'area of habitat' (habitat available to a species within its range) between the lost and retained range areas. Finally, we ran generalized linear mixed models to identify which variables were more influential in determining habitat availability in the lost and retained parts of the distribution ranges. We found that 59% of species had a lower proportion of available habitat in the lost range compared to the retained range, thus hypothesizing that habitat loss could have contributed to range declines. The most important factors negatively affecting habitat availability were the conversion of land to rangeland and high density of livestock. Significant intrinsic traits were those related to reproductive timing and output, habitat breadth and medium body size. Our findings emphasize the importance of implementing conservation strategies to mitigate the impacts caused by human activities on the habitats of mammals, and offer evidence indicating which species have the potential to reoccupy portions of their former range if other threats cease to occur.


Asunto(s)
Ecosistema , Ganado , Animales , Humanos , Conservación de los Recursos Naturales , Mamíferos , Bosques
20.
Radiat Res ; 200(5): 456-461, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37758035

RESUMEN

Diffuse intrinsic pontine gliomas (DIPG) are an aggressive type of pediatric brain tumor with a very high mortality rate. Surgery has a limited role given the tumor's location. Palliative radiation therapy alleviates symptoms and prolongs survival, but median survival remains less than 1 year. There is no clear role for chemotherapy in DIPGs as trials adding chemotherapy to palliative radiation therapy have failed to improve survival compared to radiation alone. Thus, there is a critical need to identify tissue-specific radiosensitizers to improve clinical outcomes for patients with DIPGs. Pharmacologic (high dose) ascorbate (P-AscH-) is a promising anticancer therapy that sensitizes human tumors, including adult high-grade gliomas, to radiation by acting selectively as a generator of hydrogen peroxide (H2O2) in cancer cells. In this study we demonstrate that in contrast to adult glioma models, P-AscH- does not radiosensitize DIPG. DIPG cells were sensitive to bolus of H2O2 but have faster H2O2 removal rates than GBM models which are radiosensitized by P-AscH-. These data support the hypothesis that P-AscH- does not enhance DIPG radiosensitivity, likely due to a robust capacity to detoxify and remove hydroperoxides.


Asunto(s)
Antineoplásicos , Neoplasias del Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Glioma , Niño , Adulto , Humanos , Glioma Pontino Intrínseco Difuso/tratamiento farmacológico , Glioma Pontino Intrínseco Difuso/patología , Neoplasias del Tronco Encefálico/radioterapia , Neoplasias del Tronco Encefálico/patología , Peróxidos/uso terapéutico , Peróxido de Hidrógeno/farmacología , Peróxido de Hidrógeno/uso terapéutico , Glioma/radioterapia , Glioma/patología , Antineoplásicos/uso terapéutico
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