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1.
Nature ; 570(7761): 326-331, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31189958

RESUMO

Mutation or disruption of the SH3 and ankyrin repeat domains 3 (SHANK3) gene represents a highly penetrant, monogenic risk factor for autism spectrum disorder, and is a cause of Phelan-McDermid syndrome. Recent advances in gene editing have enabled the creation of genetically engineered non-human-primate models, which might better approximate the behavioural and neural phenotypes of autism spectrum disorder than do rodent models, and may lead to more effective treatments. Here we report CRISPR-Cas9-mediated generation of germline-transmissible mutations of SHANK3 in cynomolgus macaques (Macaca fascicularis) and their F1 offspring. Genotyping of somatic cells as well as brain biopsies confirmed mutations in the SHANK3 gene and reduced levels of SHANK3 protein in these macaques. Analysis of data from functional magnetic resonance imaging revealed altered local and global connectivity patterns that were indicative of circuit abnormalities. The founder mutants exhibited sleep disturbances, motor deficits and increased repetitive behaviours, as well as social and learning impairments. Together, these results parallel some aspects of the dysfunctions in the SHANK3 gene and circuits, as well as the behavioural phenotypes, that characterize autism spectrum disorder and Phelan-McDermid syndrome.


Assuntos
Comportamento Animal , Encéfalo/fisiopatologia , Macaca fascicularis/genética , Macaca fascicularis/psicologia , Mutação , Proteínas do Tecido Nervoso/genética , Vias Neurais/fisiopatologia , Animais , Encéfalo/patologia , Movimentos Oculares/genética , Feminino , Mutação em Linhagem Germinativa/genética , Hereditariedade/genética , Relações Interpessoais , Imageamento por Ressonância Magnética , Masculino , Tono Muscular/genética , Vias Neurais/patologia , Sono/genética , Vocalização Animal
2.
J Acoust Soc Am ; 145(2): 654, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30823820

RESUMO

This paper introduces an end-to-end feedforward convolutional neural network that is able to reliably classify the source and type of animal calls in a noisy environment using two streams of audio data after being trained on a dataset of modest size and imperfect labels. The data consists of audio recordings from captive marmoset monkeys housed in pairs, with several other cages nearby. The network in this paper can classify both the call type and which animal made it with a single pass through a single network using raw spectrogram images as input. The network vastly increases data analysis capacity for researchers interested in studying marmoset vocalizations, and allows data collection in the home cage, in group housed animals.


Assuntos
Redes Neurais de Computação , Processamento de Sinais Assistido por Computador , Vocalização Animal/classificação , Animais , Callithrix , Espectrografia do Som
4.
Sex Med Rev ; 12(1): 3-13, 2023 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-37183167

RESUMO

INTRODUCTION: Preventative surgical procedures for patients who are breast cancer (BRCA) positive-namely, bilateral salpingo-oophorectomy and mastectomy-have been linked to changes in sexual function, including surgically induced menopause. A patient's decision to undergo preventive surgery as opposed to high-risk screening is heavily reliant on advice received from one's health care provider. Quality of life should be considered when shared decision making is conducted with patients. OBJECTIVES: To assemble and analyze findings related to patient-reported sexual function after these surgical procedures, to see if and how either procedure affects sexual function from patient baseline, and to determine whether the effects can be mitigated with menopausal hormone therapy. METHODS: A literature review based on the PubMed, Embase, and MEDLINE databases was conducted from inception through January 25, 2022. To be included, studies had to meet an a priori list of Medical Subject Headings: "BRCA" AND "sexual dysfunction" OR "dyspareunia." GRADE criteria were used to determine the quality of studies relating to menopause hormone therapy. RESULTS: The search yielded 14 results, and 11 reported sufficient data for systematic review. Sexual function was measured via validated and investigator-generated surveys. All studies, no matter the survey metric, found significant reduction in sexual function with bilateral salpingo-oophorectomy; no studies revealed sexual function changes associated with mastectomy postsurgery. Few studies indicated that menopause hormone therapy resulted in significant improvement in sexual function, and all studies reported that postoperative sexual function could not reach baseline levels with therapy. No studies were high quality by GRADE metrics. CONCLUSION: Prophylactic mastectomies and bilateral salpingo-oophorectomies among patients who are BRCA positive cause SF changes postprocedure. Menopausal hormone therapy offers little help in mediating symptoms. Significantly more research is needed to explore potential changes in sexual function, as it is an important aspect of quality of life for patients with BRCA positivity.


Assuntos
Neoplasias da Mama , Mastectomia Profilática , Feminino , Humanos , Salpingo-Ooforectomia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/prevenção & controle , Mastectomia , Qualidade de Vida , Genes BRCA2 , Terapia de Reposição Hormonal , Menopausa
5.
Aging Med (Milton) ; 6(4): 320-327, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38239717

RESUMO

Objective: To assess prevalence of elevated blood pressure readings, rates of established hypertension diagnosis, and blood pressure control medication prescription rates in a cohort of older people experiencing unsheltered homelessness presenting to a Street Medicine clinic in Miami-Dade County, Florida. In addition, we will compare outcomes found in the study cohort to that of the general population. Methods: Demographic information, clinical history, blood pressure control medication prescription, and blood pressure measurements were taken by a Street Medicine team of medical providers. The team routinely provides medical evaluations and care for people experiencing unsheltered homelessness who reside in rough sleeper tent encampments located on the street. Clinical information and vitals were recorded in REDCap. De-identified data from patients 65 years and above were downloaded and compared to a general population data set-the Centers for Disease Control National Health and Nutrition Examination Survey (CDC NHANES) 2017-2020 Pre-pandemic cohort. Data analysis was performed using R Studio version 4.3.2. Results: Blood pressure was reported in 120 distinct interactions with older people experiencing homelessness. Compared to the age-matched NHANES data, older people experiencing unsheltered homelessness were at significantly increased relative risk for elevated blood pressure within the range of Stage 1 Hypertension (RR: 3.914, 95% CI: 2.560-5.892, P < 0.001), and within range of Stage 2 Hypertension (RR: 5.550, 95% CI: 4.272-7.210, P < 0.001). According to NHANES, 49.6% of adults over 60 with diagnosed hypertension receive treatment. Of study participants, 69% of those with elevated blood pressure had previously received a diagnosis of hypertension and 15.9% on medication to control blood pressure. Conclusion: Our cohort of older people experiencing unsheltered homelessness had higher rates of elevated blood pressure and reduced rates of hypertension diagnosis and treatment as compared to the general population. Older people experiencing unsheltered homelessness are a growing population, and future research should seek to evaluate and understand older adult care vulnerabilities, including chronic disease management, to improve health outcomes for those who are aging, hypertensive, and unhoused.

6.
PLoS One ; 15(4): e0227392, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298305

RESUMO

Vocal communication in animals often involves taking turns vocalizing. In humans, turn-taking is a fundamental rule in conversation. Among non-human primates, the common marmoset is known to engage in antiphonal calling using phee calls and trill calls. Calls of the trill type are the most common, yet difficult to study, because they are not very loud and uttered in conditions when animals are in close proximity to one another. Here we recorded trill calls in captive pair-housed marmosets using wearable microphones, while the animals were together with their partner or separated, but within trill call range. Trills were exchanged mainly with the partner and not with other animals in the room. Animals placed outside the home cage increased their trill call rate and uttered more trills in response to their partner compared to strangers. The fundamental frequency, F0, of trills increased when animals were placed outside the cage. Our results indicate that trill calls can be monitored using wearable audio equipment and that minor changes in social context affect trill call interactions and spectral properties of trill calls.


Assuntos
Callithrix/psicologia , Comportamento Social , Vocalização Animal/fisiologia , Animais , Técnicas de Observação do Comportamento/instrumentação , Feminino , Masculino , Meio Social , Dispositivos Eletrônicos Vestíveis
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