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1.
Wilderness Environ Med ; 35(2): 198-218, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38651342

RESUMEN

The Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for the management of pain in austere environments. Recommendations are graded based on the quality of supporting evidence as defined by criteria put forth by the American College of Chest Physicians. This is an update of the 2014 version of the "WMS Practice Guidelines for the Treatment of Acute Pain in Remote Environments" published in Wilderness & Environmental Medicine 2014; 25:41-49.


Asunto(s)
Dolor Agudo , Manejo del Dolor , Sociedades Médicas , Medicina Silvestre , Medicina Silvestre/normas , Medicina Silvestre/métodos , Humanos , Dolor Agudo/terapia , Dolor Agudo/tratamiento farmacológico , Manejo del Dolor/métodos , Manejo del Dolor/normas , Configuración de Recursos Limitados
2.
J Morphol ; 285(4): e21692, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38573030

RESUMEN

Squamate placentas support physiological exchange between mothers and embryos. Uterine and embryonic epithelial cells provide sites for transporting mechanisms and extraembryonic membranes provide the scaffolding for embryonic epithelial cells and vascular systems. Diversity in placental structure involves variation in extraembryonic membrane development as well as epithelial cell specializations. Variation in placental ontogeny is known to occur and, although lineage specific patterns have been described, phylogenetic distribution of specific patterns is poorly understood. Xantusia vigilis is a viviparous lizard in a monophyletic clade, Xantusiidae, of predominantly viviparous species. Xantusiidae is one of two viviparous lineages within the clade Scincoidea that provides an important outgroup comparison for Scincidae, which includes the largest number of independent origins of viviparity among Squamata. Previous reports contain brief descriptions of placental structure of X vigilis but the developmental pattern is unknown including relevant details for comparison with skinks. We studied placental ontogeny in X. vigilis to address two hypotheses: (1) the pattern of development of placental architecture is similar to species of Scincidae and, (2) placental epithelial cell specializations are similar to species of Scincidae. The terminal placental stage of X. vigilis is similar to skinks in that it includes a chorioallantoic placenta and an omphaloplacenta. The chorioallantoic placenta is richly vascularized with thin, squamous epithelial cells separating the two vascular systems. This morphology differs from the elaborate epithelial cell specializations as occur in some skink species, but is similar to many species. Epithelial cells of the omphaloplacenta are enlarged, as they are in scincids, yet development of the omphaloplacenta includes a vascular pattern known to occur only in gerrhonotine lizards. Histochemical staining properties of the epithelium of the omphalopleure of the omphaloplacenta indicate the potential for protein transport, a function not previously reported for lizards.


Asunto(s)
Lagartos , Yucca , Embarazo , Femenino , Animales , Filogenia , Placenta , Útero
3.
JMIR Hum Factors ; 11: e41557, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38512325

RESUMEN

BACKGROUND: Medication incidents (MIs) causing harm to patients have far-reaching consequences for patients, pharmacists, public health, business practice, and governance policy. Medication Incident Reporting and Learning Systems (MIRLS) have been implemented to mitigate such incidents and promote continuous quality improvement in community pharmacies in Canada. They aim to collect and analyze MIs for the implementation of incident preventive strategies to increase safety in community pharmacy practice. However, this goal remains inhibited owing to the persistent barriers that pharmacies face when using these systems. OBJECTIVE: This study aims to investigate the harms caused by medication incidents and technological barriers to reporting and identify opportunities to incorporate persuasive design strategies in MIRLS to motivate reporting. METHODS: We conducted 2 scoping reviews to provide insights on the relationship between medication errors and patient harm and the information system-based barriers militating against reporting. Seven databases were searched in each scoping review, including PubMed, Public Health Database, ProQuest, Scopus, ACM Library, Global Health, and Google Scholar. Next, we analyzed one of the most widely used MIRLS in Canada using the Persuasive System Design (PSD) taxonomy-a framework for analyzing, designing, and evaluating persuasive systems. This framework applies behavioral theories from social psychology in the design of technology-based systems to motivate behavior change. Independent assessors familiar with MIRLS reported the degree of persuasion built into the system using the 4 categories of PSD strategies: primary task, dialogue, social, and credibility support. RESULTS: Overall, 17 articles were included in the first scoping review, and 1 article was included in the second scoping review. In the first review, significant or serious harm was the most frequent harm (11/17, 65%), followed by death or fatal harm (7/17, 41%). In the second review, the authors found that iterative design could improve the usability of an MIRLS; however, data security and validation of reports remained an issue to be addressed. Regarding the MIRLS that we assessed, participants considered most of the primary task, dialogue, and credibility support strategies in the PSD taxonomy as important and useful; however, they were not comfortable with some of the social strategies such as cooperation. We found that the assessed system supported a number of persuasive strategies from the PSD taxonomy; however, we identified additional strategies such as tunneling, simulation, suggestion, praise, reward, reminder, authority, and verifiability that could further enhance the perceived persuasiveness and value of the system. CONCLUSIONS: MIRLS, equipped with persuasive features, can become powerful motivational tools to promote safer medication practices in community pharmacies. They have the potential to highlight the value of MI reporting and increase the readiness of pharmacists to report incidents. The proposed persuasive design guidelines can help system developers and community pharmacy managers realize more effective MIRLS.


Asunto(s)
Aprendizaje , Comunicación Persuasiva , Humanos , Sugestión , Motivación , Canadá
4.
Sci Total Environ ; 918: 170544, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38309367

RESUMEN

Multiple lines of evidence at whole animal, cellular and molecular levels implicate polycyclic aromatic compounds (PACs) with three rings as drivers of crude oil toxicity to developing fish. Phenanthrene (P0) and its alkylated homologs (C1- through C4-phenanthrenes) comprise the most prominent subfraction of tricyclic PACs in crude oils. Among this family, P0 has been studied intensively, with more limited detail available for the C4-phenanthrene 1-methyl-7-isopropyl-phenanthrene (1-M,7-IP, or retene). While both compounds are cardiotoxic, P0 impacts embryonic cardiac function and development through direct blockade of K+ and Ca2+ currents that regulate cardiomyocyte contractions. In contrast, 1-M,7-IP dysregulates aryl hydrocarbon receptor (AHR) activation in developing ventricular cardiomyocytes. Although no other compounds have been assessed in detail across the larger family of alkylated phenanthrenes, increasing alkylation might be expected to shift phenanthrene family member activity from K+/Ca2+ ion current blockade to AHR activation. Using embryos of two distantly related fish species, zebrafish and Atlantic haddock, we tested 14 alkyl-phenanthrenes in both acute and latent developmental cardiotoxicity assays. All compounds were cardiotoxic, and effects were resolved into impacts on multiple, highly specific aspects of heart development or function. Craniofacial defects were clearly linked to developmental cardiotoxicity. Based on these findings, we suggest a novel framework to delineate the developmental toxicity of petrogenic PAC mixtures in fish, which incorporates multi-mechanistic pathways that produce interactive synergism at the organ level. In addition, relationships among measured embryo tissue concentrations, cytochrome P4501A mRNA induction, and cardiotoxic responses suggest a two-compartment toxicokinetic model that independently predicts high potency of PAC mixtures through classical metabolic synergism. These two modes of synergism, specific to the sub-fraction of phenanthrenes, are sufficient to explain the high embryotoxic potency of crude oils, independent of as-yet unmeasured compounds in these complex environmental mixtures.


Asunto(s)
Petróleo , Fenantrenos , Hidrocarburos Policíclicos Aromáticos , Animales , Pez Cebra , Cardiotoxicidad , Fenantrenos/toxicidad , Relación Estructura-Actividad , Petróleo/toxicidad , Hidrocarburos Policíclicos Aromáticos/toxicidad
5.
J Shoulder Elbow Surg ; 33(7): 1465-1472, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38182025

RESUMEN

BACKGROUND: Particle-induced osteolysis resulting from polyethylene wear remains a source of implant failure in anatomic total shoulder designs. Modern polyethylene components are irradiated in an oxygen-free environment to induce cross-linking, but reducing the resulting free radicals with melting or heat annealing can compromise the component's mechanical properties. Vitamin E has been introduced as an adjuvant to thermal treatments. Anatomic shoulder arthroplasty models with a ceramic head component have demonstrated that vitamin E-enhanced polyethylene show improved wear compared with highly cross-linked polyethylene (HXLPE). This study aimed to assess the biomechanical wear properties and particle size characteristics of a novel vitamin E-enhanced highly cross-linked polyethylene (VEXPE) glenoid compared to a conventional ultrahigh-molecular-weight polyethylene (UHMWPE) glenoid against a cobalt chromium molybdenum (CoCrMo) head component. METHODS: Biomechanical wear testing was performed to compare the VEXPE glenoid to UHMWPE glenoid with regard to pristine polyethylene wear and abrasive endurance against a polished CoCrMo alloy humeral head in an anatomic shoulder wear-simulation model. Cumulative mass loss (milligrams) was recorded, and wear rate calculated (milligrams per megacycle [Mc]). Under pristine wear conditions, particle analysis was performed, and functional biologic activity (FBA) was calculated to estimate particle debris osteolytic potential. In addition, 95% confidence intervals for all testing conditions were calculated. RESULTS: The average pristine wear rate was statistically significantly lower for the VEXPE glenoid compared with the HXLPE glenoid (0.81 ± 0.64 mg/Mc vs. 7.00 ± 0.45 mg/Mc) (P < .05). Under abrasive wear conditions, the VEXPE glenoid had a statistically significant lower average wear rate compared with the UHMWPE glenoid comparator device (18.93 ± 5.80 mg/Mc vs. 40.47 ± 2.63 mg/Mc) (P < .05). The VEXPE glenoid demonstrated a statistically significant improvement in FBA compared with the HXLPE glenoid (0.21 ± 0.21 vs. 1.54 ± 0.49 (P < .05). CONCLUSIONS: A new anatomic glenoid component with VEXPE demonstrated significantly improved pristine and abrasive wear properties with lower osteolytic particle debris potential compared with a conventional UHMWPE glenoid component. Vitamin E-enhanced polyethylene shows early promise in shoulder arthroplasty components. Long-term clinical and radiographic investigation needs to be performed to verify if these biomechanical wear properties translate to diminished long-term wear, osteolysis, and loosening.


Asunto(s)
Artroplastía de Reemplazo de Hombro , Ensayo de Materiales , Polietilenos , Diseño de Prótesis , Falla de Prótesis , Prótesis de Hombro , Vitamina E , Humanos , Artroplastía de Reemplazo de Hombro/métodos , Fenómenos Biomecánicos , Tamaño de la Partícula , Osteólisis/etiología , Osteólisis/prevención & control , Articulación del Hombro/cirugía
6.
Br J Haematol ; 204(3): 759-773, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38253961

RESUMEN

Iron deficiency (ID) and iron-deficiency anaemia (IDA) are global public health concerns, most commonly afflicting children, pregnant women and women of childbearing age. Pathological outcomes of ID include delayed cognitive development in children, adverse pregnancy outcomes and decreased work capacity in adults. IDA is usually treated by oral iron supplementation, typically using iron salts (e.g. FeSO4 ); however, dosing at several-fold above the RDA may be required due to less efficient absorption. Excess enteral iron causes adverse gastrointestinal side effects, thus reducing compliance, and negatively impacts the gut microbiome. Recent research has sought to identify new iron formulations with better absorption so that lower effective dosing can be utilized. This article outlines emerging research on oral iron supplementation and focuses on molecular mechanisms by which different supplemental forms of iron are transported across the intestinal epithelium and whether these transport pathways are subject to regulation by the iron-regulatory hormone hepcidin.


Asunto(s)
Anemia Ferropénica , Deficiencias de Hierro , Sobrecarga de Hierro , Adulto , Niño , Femenino , Humanos , Embarazo , Hierro/metabolismo , Anemia Ferropénica/terapia , Sobrecarga de Hierro/tratamiento farmacológico
7.
Orthop J Sports Med ; 12(1): 23259671231220371, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38188620

RESUMEN

Background: Deficiency in vitamin D has been shown to increase the risk of injury. Purpose: To synthesize current placebo-controlled randomized trials investigating the effect of vitamin D supplementation in elite athletes on (1) aerobic capacity; (2) anaerobic measures, such as strength, speed, and anaerobic power; (3) serum biomarkers of inflammation; and (4) bone health. Study Design: Systematic review; Level of evidence, 1. Methods: A literature search was conducted on November 30, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included were randomized, placebo-controlled studies of longer than 2 weeks on subjects with active participation in organized sport. Excluded were nonrandomized controlled trial study designs, vitamin D administration routes other than oral, studies that did not use vitamin D supplementation as the sole intervention, and studies with nonathletic or military populations. Results: Out of 2331 initial studies, 14 studies (482 athletes) were included. Of the 3 studies that assessed aerobic capacity, 2 demonstrated significantly greater improvements in maximal oxygen uptake and physical working capacity-170 (P < .05) in supplemented versus nonsupplemented athletes. Measurements of anaerobic power and strength were consistently increased in supplemented groups compared with nonsupplemented groups in 5 out of the 7 studies that assessed this. Of the 6 studies that assessed sprint speed, 4 found no significant difference between supplemented and nonsupplemented groups. Aside from 1 study that found significantly lower interleukin-6 levels in supplemented athletes, measures of other inflammatory cytokines were not affected consistently by supplementation. The 4 studies that assessed markers of bone health were conflicting regarding benefits of supplementation. One study found demonstrated improvements in bone mineral density in response to supplementation (P = .02) compared with control whereas another found no significant difference between supplemented and nonsupplemented groups. However, in 3 other studies, serum biomarkers of bone turnover such as bone-specific alkaline phosphatase, parathyroid hormone, and N-terminal telopeptide appeared to be higher in subjects with lower serum vitamin D levels (P < .05). Conclusion: Results of this systematic review indicated that the greatest benefit of vitamin D supplementation in elite athletes may be improving aerobic endurance, anaerobic power, and strength. More research is needed to determine the effect of vitamin D supplementation on bone health and injury risk in this population.

8.
Sci Rep ; 14(1): 2389, 2024 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-38287054

RESUMEN

The association between anemia and outcomes in glioblastoma patients is unclear. We analyzed data from 1346 histologically confirmed adult glioblastoma patients in the TriNetX Research Network. Median hemoglobin and hematocrit levels were quantified for 6 months following diagnosis and used to classify patients as anemic or non-anemic. Associations of anemia and iron supplementation of anemic patients with median overall survival (median-OS) were then studied. Among 1346 glioblastoma patients, 35.9% of male and 40.5% of female patients were classified as anemic using hemoglobin-based WHO guidelines. Among males, anemia was associated with reduced median-OS compared to matched non-anemic males using hemoglobin (HR 1.24; 95% CI 1.00-1.53) or hematocrit-based cutoffs (HR 1.28; 95% CI 1.03-1.59). Among females, anemia was not associated with median-OS using hemoglobin (HR 1.00; 95% CI 0.78-1.27) or hematocrit-based cutoffs (HR: 1.10; 95% CI 0.85-1.41). Iron supplementation of anemic females trended toward increased median-OS (HR 0.61; 95% CI 0.32-1.19) although failing to reach statistical significance whereas no significant association was found in anemic males (HR 0.85; 95% CI 0.41-1.75). Functional transferrin-binding assays confirmed sexually dimorphic binding in resected patient samples indicating underlying differences in iron biology. Anemia among glioblastoma patients exhibits a sex-specific association with survival.


Asunto(s)
Anemia , Glioblastoma , Adulto , Humanos , Masculino , Femenino , Hierro , Glioblastoma/complicaciones , Anemia/complicaciones , Hemoglobinas/metabolismo , Suplementos Dietéticos
9.
Environ Res ; 243: 117808, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38043901

RESUMEN

Pollen allergies pose a considerable global public health concern. Allergy risk can vary significantly within plant families, yet some key pollen allergens can only be identified to family level by current optical methods. Pollen information with greater taxonomic resolution is therefore required to best support allergy prevention and self-management. We used environmental DNA (eDNA) metabarcoding to deepen taxonomic insights into the seasonal composition of airborne pollen in cool temperate Australia, a region with high rates of allergic respiratory disease. In Hobart, Tasmania, we collected routine weekly air samples from December 2018 until October 2020 and sequenced the internal transcribed spacer 2 (ITS2) and chloroplastic tRNA-Leucine tRNA-Phenylalanine intergenic spacer (trnL-trnF) regions in order to address the following questions: a) What is the genus-level diversity of known and potential aeroallergens in Hobart, in particular, in the families Poaceae, Cupressaceae and Myrtaceae? b) How do the atmospheric concentrations of these taxa change over time, and c) Does trnL-trnF enhance resolution of biodiversity when used in addition to ITS2? Our results suggest that individuals in the region are exposed to temperate grasses including Poa and Bromus in the peak grass pollen season, however low levels of exposure to the subtropical grass Cynodon may occur in autumn and winter. Within Cupressaceae, both metabarcodes showed that exposure is predominantly to pollen from the introduced genera Cupressus and Juniperus. Only ITS2 detected the native genus, Callitris. Both metabarcodes detected Eucalyptus as the major Myrtaceae genus, with trnL-trnF exhibiting primer bias for this family. These findings help refine our understanding of allergy triggers in Tasmania and highlight the utility of multiple metabarcodes in aerobiome studies.


Asunto(s)
Polen , Rinitis Alérgica Estacional , Humanos , Estaciones del Año , Alérgenos/análisis , Poaceae , Australia , ARN de Transferencia
10.
Biol Trace Elem Res ; 202(3): 1031-1040, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37341874

RESUMEN

This study aimed to examine the impact of varying doses of whey protein (WP) and amylopectin/chromium complex (ACr) supplementation on muscle protein synthesis (MPS), amino acid and insulin levels, and the rapamycin (mTOR) signaling pathways in exercised rats. A total of 72 rats were randomly divided into nine groups: (1) Exercise (Ex), (2) Ex + WPI to (5) Ex + WPIV with various oral doses of whey protein (0.465, 1.55, 2.33, and 3.1 g/kg) and (6) Ex + WPI + ACr to (9) Ex + WPIV + ACr with various doses of whey protein combined with 0.155 g/kg ACr. On the day of single-dose administration, the products were given by oral gavage after exercise. To measure the protein fractional synthesis rate (FSR), a bolus dose of deuterium-labeled phenylalanine was given, and its effects were evaluated 1 h after supplementation. Rats that received 3.1 g/kg of whey protein (WP) combined with ACr exhibited the most significant increase in muscle protein synthesis (MPS) compared to the Ex group (115.7%, p < 0.0001). In comparison to rats that received the same dose of WP alone, those given the combination of WP and ACr at the same dosage showed a 14.3% increase in MPS (p < 0.0001). Furthermore, the WP (3.1 g/kg) + ACr group exhibited the highest elevation in serum insulin levels when compared to the Ex group (111.9%, p < 0.0001). Among the different groups, the WP (2.33 g/kg) + ACr group demonstrated the greatest increase in mTOR levels (224.2%, p < 0.0001). Additionally, the combination of WP (2.33 g/kg) and ACr resulted in a 169.8% increase in 4E-BP1 levels (p < 0.0001), while S6K1 levels rose by 141.2% in the WP (2.33 g/kg) + ACr group (p < 0.0001). Overall, supplementation with various doses of WP combined with ACr increased MPS and enhanced the mTOR signaling pathway compared to WP alone and the Ex group.


Asunto(s)
Amilopectina , Insulinas , Ratas , Animales , Proteína de Suero de Leche/farmacología , Proteína de Suero de Leche/metabolismo , Amilopectina/farmacología , Proteínas Musculares/metabolismo , Fosforilación , Músculo Esquelético/metabolismo , Cromo/farmacología , Cromo/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Insulinas/metabolismo , Insulinas/farmacología
11.
Environ Sci Technol ; 57(48): 19214-19222, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37963111

RESUMEN

Pacific herring (Clupea pallasii), a cornerstone of marine food webs, generally spawn on marine macroalgae in shallow nearshore areas that are disproportionately at risk from oil spills. Herring embryos are also highly susceptible to toxicity from chemicals leaching from oil stranded in intertidal and subtidal zones. The water-soluble components of crude oil trigger an adverse outcome pathway that involves disruption of the physiological functions of cardiomyocytes in the embryonic herring heart. In previous studies, impaired ionoregulation (calcium and potassium cycling) in response to specific polycyclic aromatic hydrocarbons (PAHs) corresponds to lethal embryolarval heart failure or subtle chamber malformations at the high and low ends of the PAH exposure range, respectively. Sublethal cardiotoxicity, which involves an abnormal outgrowth (ballooning) of the cardiac ventricular chamber soon after hatching, subsequently compromises juvenile heart structure and function, leading to pathological hypertrophy of the ventricle and reduced individual fitness, measured as cardiorespiratory performance. Previous studies have not established a threshold for these sublethal and delayed-in-time effects, even with total (∑)PAH exposures as low as 29 ng/g of wet weight (tissue dose). Here, we extend these earlier findings showing that (1) cyp1a gene expression provides an oil exposure metric that is more sensitive than typical quantitation of PAHs via GC-MS and (2) heart morphometrics in herring embryos provide a similarly sensitive measure of toxic response. Early life stage injury to herring (impaired heart development) thus occurs below the quantitation limits for PAHs in both water and embryonic tissues as a conventional basis for assessing oil-induced losses to coastal marine ecosystems.


Asunto(s)
Contaminación por Petróleo , Petróleo , Hidrocarburos Policíclicos Aromáticos , Contaminantes Químicos del Agua , Animales , Agua , Ecosistema , Hidrocarburos Policíclicos Aromáticos/toxicidad , Petróleo/toxicidad , Embrión no Mamífero/metabolismo , Embrión no Mamífero/patología , Peces/metabolismo , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/metabolismo
12.
Diabetes Spectr ; 36(4): 379-384, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38024219

RESUMEN

Background: Therapeutic inertia leading to delays in insulin initiation or intensification is a major contributor to lack of optimal diabetes care. This report reviews the literature summarizing data on therapeutic inertia and delays in insulin intensification in the management of type 2 diabetes. Methods: A literature search was conducted of the Allied & Complementary Medicine, BIOSIS Previews, Embase, EMCare, International Pharmaceutical Abstracts, MEDLINE, and ToxFile databases for clinical studies, observational research, and meta-analyses from 2012 to 2022 using search terms for type 2 diabetes and delay in initiating/intensifying insulin. Twenty-two studies met inclusion criteria. Results: Time until insulin initiation among patients on two to three antihyperglycemic agents was at least 5 years, and mean A1C ranged from 8.7 to 9.8%. Early insulin intensification was linked with reduced A1C by 1.4%, reduction of severe hypoglycemic events from 4 to <1 per 100 person-years, and diminution in risk of heart failure (HF) by 18%, myocardial infarction (MI) by 23%, and stroke by 28%. In contrast, delayed insulin intensification was associated with increased risk of HF (64%), MI (67%), and stroke (51%) and a higher incidence of diabetic retinopathy. In the views of both patients and providers, hypoglycemia was identified as a primary driver of therapeutic inertia; 75.5% of physicians reported that they would treat more aggressively if not for concerns about hypoglycemia. Conclusion: Long delays before insulin initiation and intensification in clinically eligible patients are largely driven by concerns over hypoglycemia. New diabetes technology that provides continuous glucose monitoring may reduce occurrences of hypoglycemia and help overcome therapeutic inertia associated with insulin initiation and intensification.

13.
J Addict Med ; 17(5): 612-614, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37788620

RESUMEN

OBJECTIVES: Medications for opioid use disorder (MOUDs) like buprenorphine are a first-line treatment for individuals who have opioid use disorder (OUD); however, these medications are not designed to impact the use of other classes of drugs. This descriptive study provides up-to-date information about nonopioid substance use among patients who recently initiated office-based buprenorphine treatment for OUD using data from 2 ongoing clinical trials. METHODS: The study sample was composed of 257 patients from 6 federally qualified health centers in the mid-Atlantic region who recently (i.e., within the past 28 days) initiated office-based buprenorphine treatment between July 2020 and May 2022. After the screening and informed consent processes, participants completed a urine drug screen and psychosocial interview as a part of the study baseline assessment. Descriptive analyses were performed on urine drug screen results to identify the prevalence and types of substances detected. RESULTS: More than half of participants provided urine specimens that were positive for nonopioid substances, with marijuana (37%, n = 95), cocaine (22%, n = 56), and benzodiazepines (11%, n = 28) detected with the highest frequencies. CONCLUSIONS: A significant number of participants used nonopioid substances after initiating buprenorphine treatment, suggesting that some patients receiving MOUDs could potentially benefit from adjunctive psychosocial treatment and supports to address their nonopioid substance use.


Asunto(s)
Buprenorfina , Cocaína , Trastornos Relacionados con Opioides , Humanos , Buprenorfina/uso terapéutico , Tratamiento de Sustitución de Opiáceos/métodos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/epidemiología , Analgésicos Opioides/uso terapéutico
14.
J Appl Physiol (1985) ; 135(5): 1070-1081, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37795531

RESUMEN

Menopause is associated with reduced nitric oxide bioavailability and vascular function. Although exercise is known to improve vascular function, this is blunted in estrogen-deficient females post-menopause (PM). Here, we examined the effects of acute exercise at differing intensities with and without inorganic nitrate (NO3-) supplementation on vascular function in females PM. Participants were tested in a double-blinded, block-randomized design, consuming ∼13 mmol NO3- in the form of beetroot juice (BRJ; n = 12) or placebo (PL; n = 12) for 2 days before experimental visits and 2 h before testing. Visits consisted of vascular health measures before (time point 0) and every 30 min after (time points 60, 90, 120, 150, and 180) calorically matched high-intensity exercise (HIE), moderate-intensity exercise (MIE), and a nonexercise control (CON). Blood was sampled at rest and 5-min postexercise for NO3-, NO2-, and ET-1. BRJ increased N-oxides and decreased ET-1 compared with PL, findings which were unchanged after experimental conditions (P < 0.05). BRJ improved peak Δflow-mediated dilation (FMD) compared with PL (P < 0.05), defined as the largest ΔFMD for each individual participant across all time points. FMD across time revealed an improvement (P = 0.05) in FMD between BRJ + HIE versus BRJ + CON, while BRJ + MIE had medium effects compared with BRJ + CON. In conclusion, NO3- supplementation combined with HIE improved FMD in postmenopausal females. NO3- supplementation combined with MIE may offer an alternative to those unwilling to perform HIE. Future studies should test whether long-term exercise training at high intensities with NO3- supplementation can enhance vascular health in females PM.NEW & NOTEWORTHY This study compared exercise-induced changes in flow-mediated dilation after acute moderate- and high-intensity exercise in females postmenopause supplementing either inorganic nitrate (beetroot juice) or placebo. BRJ improved peak ΔFMD postexercise, and BRJ + HIE increased FMD measured as FMD over time. Neither PL + MIE nor PL + HIE improved FMD. These findings suggest that inorganic nitrate supplementation combined with high-intensity exercise may benefit vascular health in females PM.


Asunto(s)
Beta vulgaris , Nitratos , Humanos , Femenino , Suplementos Dietéticos , Ejercicio Físico , Antioxidantes , Óxido Nítrico , Posmenopausia , Método Doble Ciego , Estudios Cruzados , Jugos de Frutas y Vegetales
15.
Biosci Rep ; 43(9)2023 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-37671923

RESUMEN

Iron deficiency anemia (IDA) is a leading global health concern affecting approximately 30% of the population. Treatment for IDA consists of replenishment of iron stores, either by oral or intravenous (IV) supplementation. There is a complex bidirectional interplay between the gut microbiota, the host's iron status, and dietary iron availability. Dietary iron deficiency and supplementation can influence the gut microbiome; however, the effect of IV iron on the gut microbiome is unknown. We studied how commonly used IV iron preparations, ferric carboxymaltose (FCM) and ferric derisomaltose (FDI), affected the gut microbiome in female iron-deficient anemic mice. At the phylum level, vehicle-treated mice showed an expansion in Verrucomicrobia, mostly because of the increased abundance of Akkermansia muciniphila, along with contraction in Firmicutes, resulting in a lower Firmicutes/Bacteroidetes ratio (indicator of dysbiosis). Treatment with either FCM or FDI restored the microbiome such that Firmicutes and Bacteroidetes were the dominant phyla. Interestingly, the phyla Proteobacteria and several members of Bacteroidetes (e.g., Alistipes) were expanded in mice treated with FCM compared with those treated with FDI. In contrast, several Clostridia class members were expanded in mice treated with FDI compared with FCM (e.g., Dorea spp., Eubacterium). Our data demonstrate that IV iron increases gut microbiome diversity independently of the iron preparation used; however, differences exist between FCM and FDI treatments. In conclusion, replenishing iron stores with IV iron preparations in clinical conditions, such as inflammatory bowel disease or chronic kidney disease, could affect gut microbiome composition and consequently contribute to an altered disease outcome.


Asunto(s)
Microbioma Gastrointestinal , Hierro , Femenino , Animales , Ratones , Disacáridos , Hierro de la Dieta , Bacteroidetes , Firmicutes
16.
J Biol Chem ; 299(10): 105243, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37690683

RESUMEN

Myosin-7a is an actin-based motor protein essential for vision and hearing. Mutations of myosin-7a cause type 1 Usher syndrome, the most common and severe form of deafblindness in humans. The molecular mechanisms that govern its mechanochemistry remain poorly understood, primarily because of the difficulty of purifying stable intact protein. Here, we recombinantly produce the complete human myosin-7a holoenzyme in insect cells and characterize its biochemical and motile properties. Unlike the Drosophila ortholog that primarily associates with calmodulin (CaM), we found that human myosin-7a utilizes a unique combination of light chains including regulatory light chain, CaM, and CaM-like protein 4. Our results further reveal that CaM-like protein 4 does not function as a Ca2+ sensor but plays a crucial role in maintaining the lever arm's structural-functional integrity. Using our recombinant protein system, we purified two myosin-7a splicing isoforms that have been shown to be differentially expressed along the cochlear tonotopic axis. We show that they possess distinct mechanoenzymatic properties despite differing by only 11 amino acids at their N termini. Using single-molecule in vitro motility assays, we demonstrate that human myosin-7a exists as an autoinhibited monomer and can move processively along actin when artificially dimerized or bound to cargo adaptor proteins. These results suggest that myosin-7a can serve multiple roles in sensory systems such as acting as a transporter or an anchor/force sensor. Furthermore, our research highlights that human myosin-7a has evolved unique regulatory elements that enable precise tuning of its mechanical properties suitable for mammalian auditory functions.


Asunto(s)
Actinas , Trastornos Sordoceguera , Miosina VIIa , Humanos , Actinas/metabolismo , Unión Proteica , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Miosina VIIa/genética , Miosina VIIa/metabolismo , Calmodulina/metabolismo , Proteínas de Unión al Calcio/metabolismo
17.
Neuro Oncol ; 25(12): 2136-2149, 2023 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-37539622

RESUMEN

Glioblastoma (GBM) is among the deadliest malignancies facing modern oncology. While our understanding of certain aspects of GBM biology has significantly increased over the last decade, other aspects, such as the role of bioactive metals in GBM progression, remain understudied. Iron is the most abundant transition metal found within the earth's crust and plays an intricate role in human physiology owing to its ability to participate in oxidation-reduction reactions. The importance of iron homeostasis in human physiology is apparent when examining the clinical consequences of iron deficiency or iron overload. Despite this, the role of iron in GBM progression has not been well described. Here, we review and synthesize the existing literature examining iron's role in GBM progression and patient outcomes, as well as provide a survey of iron's effects on the major cell types found within the GBM microenvironment at the molecular and cellular level. Iron represents an accessible target given the availability of already approved iron supplements and chelators. Improving our understanding of iron's role in GBM biology may pave the way for iron-modulating approaches to improve patient outcomes.


Asunto(s)
Glioblastoma , Hierro , Humanos , Hierro/metabolismo , Glioblastoma/metabolismo , Homeostasis/fisiología , Microambiente Tumoral
18.
JAMA Netw Open ; 6(8): e2327637, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37552479

RESUMEN

Importance: Very high-risk (VHR) prostate cancer is an aggressive substratum of high-risk prostate cancer, characterized by high prostate-specific antigen levels, high Gleason score, and/or advanced T category. Contemporary management paradigms involve advanced molecular imaging and multimodal treatment with intensified prostate-directed or systemic treatment-resources more readily available at high-volume centers. Objective: To examine radiation facility case volume and overall survival (OS) in men with VHR prostate cancer. Design, Setting, and Participants: A retrospective cohort study was performed from November 11, 2022, to March 4, 2023, analyzing data from US facilities reporting to the National Cancer Database. Patients included men diagnosed with nonmetastatic VHR prostate cancer by National Comprehensive Cancer Network criteria (clinical T3b-T4 category, primary Gleason pattern 5, >4 cores with grade group 4-5, and/or 2-3 high-risk features) and treated with curative-intent radiotherapy and androgen deprivation therapy between January 1, 2004, to December 31, 2016. Exposures: Treatment at high- vs low-average cumulative facility volume (ACFV), defined as the total number of prostate radiotherapy cases at an individual patient's treatment facility from 2004 until the year of their diagnosis. The nonlinear association between a continuous ACFV and OS was examined through a Martingale residual plot; an optimal ACFV cutoff was identified that maximized the separation between high vs low ACFV via a bias-adjusted log rank test. Main Outcomes and Measures: Overall survival was assessed between high vs low ACFV using Kaplan-Meier analysis with and without inverse probability score weighted adjustment and multivariable Cox proportional hazards. Results: A total of 25 219 men (median age, 71 [IQR, 64-76] years; 78.7% White) with VHR prostate cancer were identified, 6438 (25.5%) of whom were treated at high ACFV facilities. Median follow-up was 57.4 (95% CI, 56.7-58.1) months. Median OS for patients treated at high ACFV centers was 123.4 (95% CI, 116.6-127.4) months vs 109.0 (95% CI, 106.5-111.2) months at low ACFV centers (P < .001). On multivariable analysis, treatment at a high ACFV center was associated with lower risk of death (hazard ratio, 0.89; 95% CI, 0.84-0.95; P < .001). These results were also significant after inverse probability score weighted-based adjustment. Conclusions and Relevance: In this cohort study of patients with VHR prostate cancer who underwent definitive radiotherapy and androgen deprivation therapy, facility case volume was independently associated with longer OS. Further studies are needed to identify which factors unique to high-volume centers may be responsible for this benefit.


Asunto(s)
Neoplasias de la Próstata , Masculino , Humanos , Anciano , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/tratamiento farmacológico , Antagonistas de Andrógenos/uso terapéutico , Andrógenos/uso terapéutico , Estudios de Cohortes , Estudios Retrospectivos , Factores de Riesgo
19.
Environ Toxicol Chem ; 42(11): 2350-2357, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37431894

RESUMEN

Maternal transfer of selenium (Se) to developing fish eggs during vitellogenesis can cause larval deformity and mortality. Previous studies have shown wide variation among fish species in both the magnitude of maternal transfer (exposure) and the egg Se concentration causing effects (sensitivity). We studied maternal transfer and effects of Se on early life stage development, survival, and growth of redside shiner (Richardsonius balteatus), a small-bodied cyprinid that has been reported to have relatively high ovary:muscle Se concentration ratios. Gametes were collected from lentic areas in southeast British Columbia (Canada) with a range of dietary Se concentrations related to weathering of waste rock from coal mining. Eggs were fertilized and reared in the laboratory from hatch to the onset of exogenous feeding. Larvae were assessed for survival, length, weight, Se-characteristic deformities, and edema. Eggs from a total of 56 females were collected, with egg Se concentrations from 0.7 to 28 mg/kg dry weight. Maternal transfer varied among sites, with egg:muscle Se concentration ratios ranging from <1 to >4. We also found that sampling residual ovaries can overestimate Se concentrations in ripe eggs by up to a factor of 5.7. A correlation between larval weight and egg Se concentration was identified, although the relationship was weak (r2 < 0.1) and appeared to be a site effect. No other relationships were observed between larval endpoints and egg Se concentrations up to the highest concentration tested, indicating that the effects threshold for this species may be >28 mg/kg dry weight in eggs. These data indicate that redside shiner is less sensitive to maternally transferred Se than most other tested fish species. Environ Toxicol Chem 2023;42:2350-2357. © 2023 SETAC.


Asunto(s)
Cyprinidae , Selenio , Contaminantes Químicos del Agua , Animales , Femenino , Selenio/toxicidad , Selenio/análisis , Contaminantes Químicos del Agua/análisis , Larva , Colombia Británica
20.
Crohns Colitis 360 ; 5(3): otad026, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37265586

RESUMEN

Background and Aims: Vitamin D has a regulatory role in innate and adaptive immune processes. Previous studies have reported that low pretreatment vitamin D concentrations are associated with primary non-response (PNR) and non-remission to anti-TNF therapy. This study aimed to assess whether pretreatment 25-hydroxyvitamin D concentrations predicted PNR and non-remission to infliximab and adalimumab in patients with active luminal Crohn's disease. Methods: 25-Hydroxyvitamin D concentrations were measured in stored baseline samples from 659 infliximab- and 448 adalimumab-treated patients in the Personalised Anti-TNF Therapy in Crohn's disease (PANTS) study. Cut-offs for vitamin D were deficiency <25 nmol/L, insufficiency 25-50 nmol/L, and adequacy/sufficiency >50 nmol/L. Results: About 17.1% (189/1107; 95% CI, 15.0-19.4) and 47.7% (528/1107; 95% CI, 44.8-50.6) of patients had vitamin D deficiency and insufficiency, respectively. 22.2% (246/1107) of patients were receiving vitamin D supplementation. Multivariable analysis confirmed that sampling during non-summer months, South Asian ethnicity, lower serum albumin concentrations, and non-treatment with vitamin D supplementation were independently associated with lower vitamin D concentrations. Pretreatment vitamin D status did not predict response or remission to anti-TNF therapy at week 14 (infliximab Ppnr = .89, adalimumab Ppnr = .18) or non-remission at week 54 (infliximab P = .13, adalimumab P = .58). Vitamin D deficiency was, however, associated with a longer time to immunogenicity in patients treated with infliximab, but not adalimumab. Conclusions: Vitamin D deficiency is common in patients with active Crohn's disease. Unlike previous studies, pretreatment vitamin D concentration did not predict PNR to anti-TNF treatment at week 14 or nonremission at week 54.

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