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1.
Artículo en Inglés | MEDLINE | ID: mdl-39243256

RESUMEN

BACKGROUND: Patients with rare, pathogenic cardiomyopathy (CM) and arrhythmia variants can present with atrial fibrillation (AF). The efficacy of AF ablation in these patients is unknown. OBJECTIVE: This study tested the hypotheses that: 1) patients with a pathogenic variant in any CM or arrhythmia gene have increased recurrence following AF ablation; and 2) patients with a pathogenic variant associated with a specific gene group (arrhythmogenic left ventricular CM [ALVC], arrhythmogenic right ventricular CM, dilated CM, hypertrophic CM, or a channelopathy) have increased recurrence. METHODS: We performed a prospective, observational, cohort study of patients who underwent AF catheter ablation and whole exome sequencing. The primary outcome measure was ≥30 seconds of any atrial tachyarrhythmia that occurred after a 90-day blanking period. RESULTS: Among 1,366 participants, 109 (8.0%) had a pathogenic or likely pathogenic (P/LP) variant in a CM or arrhythmia gene. In multivariable analysis, the presence of a P/LP variant in any gene was not significantly associated with recurrence (HR 1.15; 95% CI 0.84-1.60; P = 0.53). P/LP variants in the ALVC gene group, predominantly LMNA, were associated with increased recurrence (n = 10; HR 3.75; 95% CI 1.84-7.63; P < 0.001), compared with those in the arrhythmogenic right ventricular CM, dilated CM, hypertrophic CM, and channelopathy gene groups. Participants with P/LP TTN variants (n = 46) had no difference in recurrence compared with genotype-negative-controls (HR 0.93; 95% CI 0.54-1.59; P = 0.78). CONCLUSIONS: Our results support the use of AF ablation for most patients with rare pathogenic CM or arrhythmia variants, including TTN. However, patients with ALVC variants, such as LMNA, may be at a significantly higher risk for arrhythmia recurrence.

2.
J Physiol ; 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39165238

RESUMEN

The exercise pressor reflex (EPR) is exaggerated in type 2 diabetes mellitus (T2DM), but the underlying central nervous system aberrations have not been fully delineated. Stimulation of muscle afferents within working skeletal muscle activates the EPR, by sending information to neurons in the brainstem, where it is integrated and results in reflexively increased mean arterial pressure (MAP) and sympathetic nerve activity. Brain insulin is known to regulate neural activity within the brainstem. We hypothesize that brain insulin injection in T2DM rats attenuates the augmented EPR, and that T2DM is associated with decreased brain insulin. Using male Sprague-Dawley rats, T2DM and control rats were generated via an induction protocol with two low doses of streptozotocin (35 and 25 mg/kg, i.p.) in combination with a 14-23-week high-fat diet or saline injections and a low-fat diet, respectively. After decerebration, MAP and renal sympathetic nerve activity (RSNA) were evaluated during EPR stimulation, evoked by electrically induced muscle contraction via ventral root stimulation, before and after (1 and 2 h post) intracerebroventricular (i.c.v.) insulin microinjections (500 mU, 50 nl). i.c.v. insulin decreased peak MAP (ΔMAP Pre (36 ± 14 mmHg) vs. 1 h (21 ± 14 mmHg) vs. 2 h (11 ± 6 mmHg), P < 0.05) and RSNA (ΔRSNA Pre (107.5 ± 40%), vs. 1 h (75.4 ± 46%) vs. 2 h (51 ± 35%), P < 0.05) responses in T2DM, but not controls. In T2DM rats, cerebrospinal fluid insulin was decreased (0.41 ± 0.19 vs. 0.11 ± 0.05 ng/ml, control (n = 14) vs. T2DM (n = 4), P < 0.01). The results demonstrated that insulin injections into the brain normalized the augmented EPR in brain hypoinsulinaemic T2DM rats, indicating that the EPR can be regulated by brain insulin. KEY POINTS: The reflexive increase in blood pressure and sympathetic nerve activity mediated by the autonomic nervous system during muscle contractions is also known as the exercise pressor reflex. The exercise pressor reflex is dangerously augmented in type 2 diabetes, in both rats and humans. In type 2 diabetic rats both cerebrospinal fluid insulin and phosphoinositide 3-kinase signalling within cardiovascular brainstem neurons decrease in parallel. Brain insulin injections decrease the magnitude of the reflexive pressor and sympathetic responses to hindlimb muscle contraction in type 2 diabetic rats. Partial correction of low insulin within the central nervous system in type 2 diabetes may treat aberrant exercise pressor reflex function.

3.
Skinmed ; 22(2): 147-148, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39090002

RESUMEN

A 68-year-old Latino man presented at our clinic with asymptomatic, indurated red nodules and macules of 2-month duration on the left arm, forearm, and palm (Figure 1). Performed punch biopsy presented characteristic -features of Kaposi sarcoma (KS). Immunohistochemistry was positive for human herpesvirus 8 (HHV8), a highly correlated viral marker, confirming the diagnosis of KS (Figure 2). He was referred to oncology for further management, where he was found to be fully immunocompetent with a negative assessment of human immunodefi-ciency virus (HIV). Computed tomography (CT) performed of his chest and abdomen revealed no involvement of internal organs.


Asunto(s)
Inmunocompetencia , Sarcoma de Kaposi , Humanos , Masculino , Anciano , Sarcoma de Kaposi/diagnóstico , Sarcoma de Kaposi/patología , Herpesvirus Humano 8/aislamiento & purificación , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología
4.
Phys Rev Lett ; 133(7): 071801, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39213562

RESUMEN

Millicharged particles appear in several extensions of the standard model, but have not yet been detected. These hypothetical particles could be produced by an intense proton beam striking a fixed target. We use data collected in 2020 by the SENSEI experiment in the MINOS cavern at the Fermi National Accelerator Laboratory to search for ultrarelativistic millicharged particles produced in collisions of protons in the NuMI beam with a fixed graphite target. The absence of any ionization events with 3 to 6 electrons in the SENSEI data allow us to place world-leading constraints on millicharged particles for masses between 30 to 380 MeV. This work also demonstrates the potential of utilizing low-threshold detectors to investigate new particles in beam-dump experiments, and motivates a future experiment designed specifically for this purpose.

5.
AIDS Care ; : 1-8, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38991109

RESUMEN

Antiretroviral therapy (ART) has been adopted as a form of HIV treatment and prevention. This study assesses rapid ART initiation using clinical outcomes such as viral load (VL) and CD4+ T lymphocytes count. Over the course of one year, the progress of newly diagnosed people living with HIV who started ART early in a hospital in Panama City was followed. The evaluation of early initiation of ART in achieving viral suppression (VL <200 copies/ml) was analyzed using descriptive statistics. Additionally, the cost difference between early (first 7 days) and late initiation of ART was evaluated from the perspective of the service provider. In total, 209 people were followed up during the study; 85% were male, 70% started ART on same day from hospital arrival, 80% had suppressed viral load at 6 months, and the median count of CD4 increased from 285 (IQR: 166-429) to 509 (IQR: 373-696) over 12 months. Starting ART early led to a 42% increase for the provider in terms of staffing costs; however, the clients had the opportunity to decrease absenteeism in daily activities. The results reveal that early initiation of ART generates clinical and economic benefits for the person in treatment.

6.
Clin Neurol Neurosurg ; 242: 108353, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38830290

RESUMEN

OBJECTIVES: This study aims to describe resting state networks (RSN) in patients with disorders of consciousness (DOC)s after acute severe traumatic brain injury (TBI). METHODS: Adult patients with TBI with a GCS score <8 who remained in a coma, minimally conscious state (MCS), or unresponsive wakefulness syndrome (UWS), between 2017 and 2020 were included. Blood-oxygen-level dependent imaging was performed to compare their RSN with 10 healthy volunteers. RESULTS: Of a total of 293 patients evaluated, only 13 patients were included according to inclusion criteria: 7 in coma (54%), 2 in MCS (15%), and 4 (31%) had an UWS. RSN analysis showed that the default mode network (DMN) was present and symmetric in 6 patients (46%), absent in 1 (8%), and asymmetric in 6 (46%). The executive control network (ECN) was present in all patients but was asymmetric in 3 (23%). The right ECN was absent in 2 patients (15%) and the left ECN in 1 (7%). The medial visual network was present in 11 (85%) patients. Finally, the cerebellar network was symmetric in 8 patients (62%), asymmetric in 1 (8%), and absent in 4 (30%). CONCLUSIONS: A substantial impairment in activation of RSN is demonstrated in patients with DOC after severe TBI in comparison with healthy subjects. Three patterns of activation were found: normal/complete activation, 2) asymmetric activation or partially absent, and 3) absent activation.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Trastornos de la Conciencia , Humanos , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/fisiopatología , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Masculino , Femenino , Adulto , Persona de Mediana Edad , Trastornos de la Conciencia/fisiopatología , Trastornos de la Conciencia/etiología , Trastornos de la Conciencia/diagnóstico por imagen , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Imagen por Resonancia Magnética , Anciano , Adulto Joven , Descanso/fisiología , Estado Vegetativo Persistente/fisiopatología , Estado Vegetativo Persistente/diagnóstico por imagen , Estado Vegetativo Persistente/etiología
7.
J Opt Soc Am A Opt Image Sci Vis ; 41(6): 1104-1113, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38856424

RESUMEN

Here, we present a technique that predicts the radiation's distribution in any optical system. It is based on decomposing the emitting source power by assigning a fraction of the total power to each emitted ray. All kinds of power losses in the rays' optical paths are considered. Fractioned radiation patterns are created in the last optical system surface, each associated with a single ray. We refer to fractioned patterns as those that conform to a whole radiating pattern. Thus, the irradiance of the completely illuminated surface is calculated by adding the optical system's fractioned radiation maps. This method is non-zero étendue. The result presented here allows for predicting the radiation patterns accurately with a handful of equations and can help design any image and non-image-forming optical systems.

8.
J Opt Soc Am A Opt Image Sci Vis ; 41(6): 1114-1121, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38856425

RESUMEN

In Part I, the authors proposed a theoretical background for predicting the radiation distribution in any optical system based on decomposing the emitting source power. Here, we describe the validity of this decomposition through a practical example that uses a radiating source and a single surface optical system. This source is calibrated in a metrology testbed that guarantees its traceability to the candela (cd), the International System (SI) base unit for luminous intensity I v. A second example, this time numerical, shows the method's performance in a multisurface optical system.

9.
Circ Arrhythm Electrophysiol ; 17(6): e012635, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38804141

RESUMEN

BACKGROUND: Irrigated radiofrequency ablation with half-normal saline can potentially increase lesion size but may increase the risk of steam pops with the risk of emboli or perforation. We hypothesized that pops would be preceded by intracardiac echocardiography (ICE) findings as well as a large impedance fall. METHODS: In 100 consecutive patients undergoing endocardial ventricular arrhythmia radiofrequency ablation with half-normal saline, we attempted to observe the ablation site with ICE. Radiofrequency ablation power was titrated to a 15 to 20 Ohm impedance fall and could be adjusted for tissue whitening and increasing bubble formation on ICE. Steam pops were defined as audible or a sudden explosion of microbubbles on ICE. RESULTS: Of 2190 ablation applications in 100 patients (82% cardiomyopathy, 50% sustained ventricular tachycardia), pops occurred during 43 (2.0%) applications. Sites with pops had greater impedance decreases of 18 [14, 21]% versus 13 [10, 17]% (P<0.001). ICE visualized 1308 (59.7%) radiofrequency sites, and fewer pops occurred when ICE visualized the radiofrequency ablation site (1.4%) compared with without ICE visualization (2.8%; P=0.016). Of the 18 ICE-visible pops, 7 (39%) were silent but recognized as an explosion of bubbles on ICE. With ICE, 89% of pops were preceded by either tissue whitening or a sudden increase in bubbles. In a multivariable model, tissue whitening and a sudden increase in bubbles were associated with steam pops (odds ratio, 7.186; P=0.004, and odds ratio, 29.93; P<0.001, respectively), independent of impedance fall and power. There were no pericardial effusions or embolic events with steam pops. CONCLUSIONS: Steam pops occurred in 2% of half-normal saline radiofrequency applications titrated to an impedance fall and are likely under-recognized without ICE. On ICE, steam pops are usually preceded by tissue whitening or a sudden increase in bubble formation, which can potentially be used to adjust radiofrequency application to help reduce pops.


Asunto(s)
Ablación por Catéter , Ecocardiografía , Solución Salina , Vapor , Taquicardia Ventricular , Irrigación Terapéutica , Humanos , Masculino , Femenino , Solución Salina/administración & dosificación , Persona de Mediana Edad , Ablación por Catéter/efectos adversos , Taquicardia Ventricular/cirugía , Taquicardia Ventricular/fisiopatología , Taquicardia Ventricular/diagnóstico por imagen , Anciano , Embolia Aérea/prevención & control , Embolia Aérea/etiología , Embolia Aérea/diagnóstico por imagen , Resultado del Tratamiento , Factores de Riesgo , Valor Predictivo de las Pruebas , Impedancia Eléctrica
10.
Animals (Basel) ; 14(9)2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38731307

RESUMEN

This study evaluated the impact of supplementing ZH in combination with D3 on the growth performance, energy efficiency, carcass traits, and meat quality of feedlot lambs. Thirty-two Dorper × Katahdin cross lambs (37.3 ± 5.72 kg) were utilized in a 29 d experiment in a completely randomized block design with a 2 × 2 factorial structure consisting of two levels of ZH for 26 d (0 and 0.20 mg/kg PV-1) and two levels of D3 for 7 d (0 and 1.5 × 106 IU/d-1). ZH improved (p ≤ 0.05) the average daily gain (ADG) and feed efficiency by 9.9% and 17.8%, respectively, as well as hot carcass weight (HCW) and dressing carcass by 4.3% and 2.6%, respectively. (p ≤ 0.03). However, ZH increased (p < 0.01) muscle pH and Warner-Bratzler shear force (WBSF) (2.5 and 23.0%, respectively). D3 supplementation negatively affected (p ≤ 0.02) dry matter intake (DMI) (last 7 d) and ADG by 15.7% and 18.1%. On the other hand, D3 improved the pH of the longissimus thoracis muscle by 1.7% (p = 0.03) without affecting WBSF. When D3 was supplemented in combination with ZH, it was observed that meat quality was improved by reducing muscle pH compared to lambs treated only with ZH. However, D3 did not improve the meat tenderness negatively affected by ZH supplementation.

11.
Animals (Basel) ; 14(5)2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38473144

RESUMEN

No studies have evaluated the peripartum follicular dynamics resulting in foal heat under tropical environments. We aimed to assess retrospectively the peripartum follicular dynamics in Colombian Paso Fino mares that were inseminated at the foal heat, becoming pregnant or not. Records including follicular dynamics of pregnant mares prepartum and from foaling until foal heat ovulation were assessed in Colombian Paso Fino mares (CPF, n = 24) bred under permanent grazing in a tropical herd in Colombia. The number of ovarian follicles >10 mm before foaling and the largest follicle (F1) growth rate (mm/day) from foaling until the F1 reached the largest diameter (pre-ovulatory size) at the foal heat were assessed. Mares were inseminated at foal heat with 20 mL of semen (at least 500 million live spermatozoa) with >75% motility and 80% viability from a stallion of proven fertility. Ovulation was confirmed the day after follicles had reached the largest diameter. Quantitative data from follicular growth, the day at ovulation, from mares that became pregnant (PM) or not (NPM) at 16 days post-insemination were compared by one-way ANOVA, repeated measures ANOVA (follicle growth rate data) or Chi-square test (edema and cytology scores data). Epidemiological data, gestation length, and the number of follicles on third prepartum days did not significantly differ between PM and NPM (p > 0.05). Seventy-one percent of mares (17/24) got pregnant. Ovulatory follicles grew faster in the NPM group (n = 7), which ovulated between the seventh and ninth postpartum days, compared to PM (n = 17), which ovulated between the 11th and 13th postpartum days. Pre-ovulatory follicle diameter in PM (48.57 ± 0.8 mm) was significantly larger than in NPM (42.99 ± 1.0 mm) (p < 0.05). In addition, the PM edema score (2.93 ± 0.32 mm) on ovulation day was significantly lower (p < 0.05) than NPM (4.47 ± 0.05 mm). First postpartum ovulation occurred at 12.6 ± 0.3 and 8.5 ± 0.4 days (p < 0.05) in PM and NPM, respectively. Colombian Paso Fino mares bred under permanent grazing under tropical rainforest conditions with no foaling or postpartum complications showed a 71% gestation rate when inseminated at foal heat when ovulation occurs between the second and third postpartum week.

12.
Mar Environ Res ; 196: 106440, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38479297

RESUMEN

The heat waves on the South Pacific coast could lead to thermal stress in native fish. The red cusk-eel (Genypterus chilensis) is relevant for Chilean artisanal fisheries and aquaculture diversification. This study examined the effect of high-temperature stress in the gills of G. chilensis in control (14 °C) and high-temperature stress (19 °C) conditions. High-temperature stress induces a significant increase in gills cortisol levels. Additionally, oxidative damage was observed in gills (protein carbonylation and lipoperoxidation). RNA-seq data was used to build the first transcriptome assembly of gills in this species (23,656 annotated transcripts). A total of 1138 down-regulated and 1531 up-regulated transcripts were observed in response to high-temperature stress in gills. The enrichment analysis showed immune response and replication enriched processes (on down-regulated transcripts), and processes related to the folding of proteins, endoplasmic reticulum, and transporter activity (on up-regulated transcripts). The present study showed how gills could be affected by high-temperature stress.


Asunto(s)
Gadiformes , Branquias , Animales , Peces , Transcriptoma , Estrés Oxidativo , Anguilas/genética , Inmunidad
13.
J Am Heart Assoc ; 13(6): e031029, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38471835

RESUMEN

BACKGROUND: Recurrence after atrial fibrillation (AF) ablation remains common. We evaluated the association between recurrence and levels of biomarkers of cardiac remodeling, and their ability to improve recurrence prediction when added to a clinical prediction model. METHODS AND RESULTS: Blood samples collected before de novo catheter ablation were analyzed. Levels of bone morphogenetic protein-10, angiopoietin-2, fibroblast growth factor-23, insulin-like growth factor-binding protein-7, myosin-binding protein C3, growth differentiation factor-15, interleukin-6, N-terminal pro-brain natriuretic peptide, and high-sensitivity troponin T were measured. Recurrence was defined as ≥30 seconds of an atrial arrhythmia 3 to 12 months postablation. Multivariable logistic regression was performed using biomarker levels along with clinical covariates: APPLE score (Age >65 years, Persistent AF, imPaired eGFR [<60 ml/min/1.73m2], LA diameter ≥43 mm, EF <50%; which includes age, left atrial diameter, left ventricular ejection fraction, persistent atrial fibrillation, and estimated glomerular filtration rate), preablation rhythm, sex, height, body mass index, presence of an implanted continuous monitor, year of ablation, and additional linear ablation. A total of 1873 participants were included. A multivariable logistic regression showed an association between recurrence and levels of angiopoietin-2 (odds ratio, 1.08 [95% CI, 1.02-1.15], P=0.007) and interleukin-6 (odds ratio, 1.02 [95% CI, 1.003-1.03]; P=0.02). The area under the receiver operating characteristic curve of a model that only contained clinical predictors was 0.711. The addition of any of the 9 studied biomarkers to the predictive model did not result in a statistically significant improvement in the area under the receiver operating characteristic curve. CONCLUSIONS: Higher angiopoietin-2 and interleukin-6 levels were associated with recurrence after atrial fibrillation ablation in multivariable modeling. However, the addition of biomarkers to a clinical prediction model did not significantly improve recurrence prediction.


Asunto(s)
Fibrilación Atrial , Remodelación Atrial , Ablación por Catéter , Humanos , Anciano , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Angiopoyetina 2 , Interleucina-6 , Modelos Estadísticos , Volumen Sistólico , Remodelación Ventricular , Factores de Riesgo , Pronóstico , Recurrencia , Función Ventricular Izquierda , Biomarcadores , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , Resultado del Tratamiento
14.
Surg Neurol Int ; 15: 16, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38344081

RESUMEN

Background: A ventriculoatrial shunt (VAS) proves to be an excellent alternative in the treatment of hydrocephalus. Its usage is a viable option when ventriculoperitoneal shunt (VPS) is contraindicated in any age of patients. Case Description: This report highlights a successful case involving a 6-month-old patient who underwent VAS catheter positioning. The child presented with hydrocephalus and biliary atresia, making him a candidate for a liver transplant. Notably, a VPS was considered a relative contraindication in this scenario. Conclusion: The VAS emerges as a viable option for patients in whom a VPS might be contraindicated. This case demonstrates the successful application of a VAS in a pediatric patient.

15.
Europace ; 26(2)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38367008

RESUMEN

AIMS: Failure of radiofrequency (RF) ablation of ventricular arrhythmias is often due to inadequate lesion size. Irrigated RF ablation with half-normal saline (HNS) has the potential to increase lesion size and reduce sodium delivery to the patient if the same volume of RF irrigant were used for normal saline (NS) and HNS but could increase risks related to steam pops and lesion size. This study aims to assess periprocedural complications and acute ablation outcome of ventricular arrhythmias ablation with HNS. METHODS AND RESULTS: Prospective assessment of outcomes was performed in 1024 endocardial and/or epicardial RF ablation procedures in 935 consecutive patients (median age 64 years, 71.2% men, 73.4% cardiomyopathy, 47.2% sustained ventricular tachycardia). Half-normal saline was selected at the discretion of the treating physician. Radiofrequency ablation power was generally titrated to a ≤15â€…Ω impedance fall with intracardiac echocardiography monitoring. Half-normal saline was used in 900 (87.9%) and NS in 124 (12.1%) procedures. Any adverse event within 30 days occurred in 13.0% of patients treated with HNS RF ablation including 4 (0.4%) strokes/transient ischaemic attacks and 34 (3.8%) pericardial effusions requiring treatment (mostly related to epicardial access). Two steam pops with perforation required surgical repair (0.2%). Patients who received NS irrigation had less severe disease and arrhythmias. In multivariable models, adverse events and acute success of the procedure were not related to the type of irrigation. CONCLUSION: Half-normal saline irrigation RF ablation with power guided by impedance fall and intracardiac echocardiography has an acceptable rate of complications and acute ablation success while administering half of the saline load expected for NS irrigation.


Asunto(s)
Ablación por Catéter , Ablación por Radiofrecuencia , Taquicardia Ventricular , Masculino , Humanos , Persona de Mediana Edad , Femenino , Solución Salina/efectos adversos , Vapor , Estudios Prospectivos , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/cirugía , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , Taquicardia Ventricular/cirugía , Irrigación Terapéutica/efectos adversos
16.
Horm Behav ; 160: 105479, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38278060

RESUMEN

In vertebrates, male testosterone levels vary across the year being generally higher during the mating season relative to the offspring rearing season. However, male testosterone levels may also be associated with male anogenital distance (AGD) length (a proxy of prenatal androgen exposition), and influenced by the social group environment. In social species, it has been proposed that high levels of testosterone could be incompatible with the development of an amicable social environment. Thus, in these species, it is predicted that males have relatively low levels of testosterone. Our goal was to examine the potential association between male serum testosterone levels, season, male AGD length, and the social environment in the rodent Octodon degus under natural conditions. We quantified male serum testosterone levels during the mating and offspring rearing seasons, and we determined the number of females and males in each social group, as well as the composition of groups, in terms of the AGD length of the female and male group mates, from 2009 to 2019. Our results revealed that male testosterone levels covary with season, being highest during the offspring rearing season. Additionally, male testosterone levels vary with male AGD length, and female and male social group environments. More importantly, male degus exhibit low levels of testosterone that are indistinguishable from female levels during offspring rearing season. Similar to other highly social mammals, where males and females live together year-round, male amicable behavior could be the best male mating strategy, thus leading to a reduction in circulating testosterone levels.


Asunto(s)
Octodon , Roedores , Embarazo , Animales , Masculino , Femenino , Octodon/genética , Testosterona , Medio Social , Fenotipo
17.
Horm Behav ; 160: 105486, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38295731

RESUMEN

Testosterone is known as a "male" hormone; however, females also synthetize testosterone, which influences female sexual and aggressive behavior. In female vertebrates, as in males, testosterone levels can vary seasonally. However, female testosterone levels may also be related with female anogenital distance (AGD) length phenotype (a proxy of prenatal androgen exposure), and the social group environment. We used data from a long-term rodent study (2009-2019) in a natural population of degus (Octodon degus) to examine the potential associations between female serum testosterone levels, season, female AGD phenotype, and social group composition. We quantified female serum testosterone levels during the mating and offspring rearing seasons, and we determined the number of females and males in social groups, as well the composition of groups, in terms of the AGD of the female and male group mates. Our results indicate that female testosterone levels vary with season, being highest during the offspring rearing season. Additionally, female testosterone levels were associated with the number of male group-members and the AGD of male group-members but were not associated with female social environment and focal female AGD phenotype. Together, our results suggest that female testosterone levels are sensitive to intersexual interactions. Our results also reveal that female and male testosterone levels do not differ between the sexes, a finding previously reported only in rock hyraxes. We discuss how the complex social system of degus could be driving this physiological similarity between the sexes.


Asunto(s)
Roedores , Testosterona , Embarazo , Animales , Masculino , Femenino , Reproducción , Medio Social , Fenotipo
18.
Cancer Discov ; 14(1): 90-103, 2024 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-37861452

RESUMEN

The tumor-associated antigen STEAP1 is a potential therapeutic target that is expressed in most prostate tumors and at increased levels in metastatic castration-resistant prostate cancer (mCRPC). We developed a STEAP1-targeted XmAb 2+1 T-cell engager (TCE) molecule, AMG 509 (also designated xaluritamig), that is designed to redirect T cells to kill prostate cancer cells that express STEAP1. AMG 509 mediates potent T cell-dependent cytotoxicity of prostate cancer cell lines in vitro and promotes tumor regression in xenograft and syngeneic mouse models of prostate cancer in vivo. The avidity-driven activity of AMG 509 enables selectivity for tumor cells with high STEAP1 expression compared with normal cells. AMG 509 is the first STEAP1 TCE to advance to clinical testing, and we report a case study of a patient with mCRPC who achieved an objective response on AMG 509 treatment. SIGNIFICANCE: Immunotherapy in prostate cancer has met with limited success due to the immunosuppressive microenvironment and lack of tumor-specific targets. AMG 509 provides a targeted immunotherapy approach to engage a patient's T cells to kill STEAP1-expressing tumor cells and represents a new treatment option for mCRPC and potentially more broadly for prostate cancer. See related commentary by Hage Chehade et al., p. 20. See related article by Kelly et al., p. 76. This article is featured in Selected Articles from This Issue, p. 5.


Asunto(s)
Anticuerpos Biespecíficos , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Ratones , Animales , Humanos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Linfocitos T , Inmunoterapia , Anticuerpos Biespecíficos/uso terapéutico , Microambiente Tumoral , Antígenos de Neoplasias , Oxidorreductasas/uso terapéutico
19.
JACC Clin Electrophysiol ; 10(2): 193-202, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38069975

RESUMEN

BACKGROUND: Risks of radiofrequency catheter ablation for ventricular arrhythmias include emboli and bleeding complications but data on antithrombotic regimens are limited and guidelines do not specify a systematic approach. OBJECTIVES: This study sought to assess embolic and bleeding complications in relation to pre-periprocedure and post-periprocedure antithrombotic regimens. METHODS: Prospective assessment for complications was performed for 663 endocardial radiofrequency catheter ablation procedures in 616 consecutive patients (median age 64 years [Q1-Q3: 54-73 years], 70.3% men, 71.6% with cardiomyopathy, 44.5% with sustained ventricular tachycardia). RESULTS: There were 2 strokes (0.3%; 95% CI: 0.0%-0.8%), 1 transient ischemic attack (0.15%), and 2 pulmonary emboli (0.3%). There were 39 bleeding complications (5.9%) including 11 pericardial effusions (1.7%), and 28 related to vascular access (4.2%). Consistent with the prevalence of coronary artery disease (47.5%), atrial fibrillation (30.0%), and prior stroke (10.6%), preprocedure, 464 patients (70.0%) were taking antithrombotic agents including 220 (33.2%) taking aspirin alone (ASA), and 163 (24.6%) taking warfarin or a direct acting oral anticoagulant (DOAC). Preprocedure non-ASA antiplatelet use (OR: 2.846; P = 0.011) and DOAC use (OR: 2.585; P = 0.032) were associated with risk of bleeding complications. Following ablation, 49.8% of patients were treated with ASA 325 mg/d and 30.3% received DOACs or warfarin. New DOAC or warfarin administration was initiated in only 6.6% of patients. Overall, 39.7% of patients continued the same preprocedure antithrombotic regimen. CONCLUSIONS: Stroke is a rare complication of radiofrequency catheter ablation for ventricular arrhythmia using ASA 325 mg/d as a minimal postprocedure regimen with more potent regimens for selected patients.


Asunto(s)
Fibrilación Atrial , Accidente Cerebrovascular , Masculino , Humanos , Persona de Mediana Edad , Femenino , Warfarina/efectos adversos , Anticoagulantes/efectos adversos , Hemorragia/etiología , Hemorragia/inducido químicamente , Fibrinolíticos , Estudios Prospectivos , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/epidemiología , Fibrilación Atrial/cirugía , Aspirina/efectos adversos
20.
Animals (Basel) ; 13(17)2023 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-37684962

RESUMEN

This study aims to assess the acquisition of surgical skills for laparoscopic ovariectomy (LOE) in dogs by veterinary surgeons with no experience in minimally invasive surgery using the CALMA Veterinary Lap-trainer simulator (CVLTS) in an experimental and analytical setting. Veterinary surgeons with no experience in minimally invasive surgery (MIS) (experimental, n = 5), and MIS experts (experts, n = 3) were evaluated. Experimental and expert group participants watched an instructional video (initial time) before practicing the LOE on uterine tissues and ovaries freshly reconstituted after elective ovariohysterectomy (initial time evaluation). Then, the experimental group practiced five training sessions on the composite simulator with permanent feedback and then performed the LOE again (final time evaluation). Surgical performances in initial and final evaluations were video recorded and further evaluated by three external MIS experts using Global objective assessment of laparoscopic skills (GOALS) and LOE-specific rating scales (SRSs) in a double-blinded schedule. In addition, a hands movement assessment system (HMAS) attached to the back of the hands was used to quantitatively measure completion time, angularity, and movement smoothness. Data were analyzed with one-factor ANOVA and Tukey's contrast test. No statistically significant differences were found between the novice group's performance after training and the expert group's performance according to the GOALS (p < 0.01) and SRS (p < 0.05) scores. Moreover, the novices had significantly improved time, number of movements, and angularity in the final time compared with the initial time (p < 0.05), with no significant differences compared to the expert group (p > 0.05). LOE training using a composed simulator resulted in significantly improved laparoscopic skills and time, number, and angularity of movements data, providing evidence of the usefulness and reliability of CVLTS in training LOE.

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