Neurotensin expression, regulation, and function during the ovulatory period in the mouse ovary†.

The luteinizing hormone (LH) surge induces paracrine mediators within the ovarian follicle that promote ovulation. The present study explores neurotensin (NTS), a neuropeptide, as a potential ovulatory mediator in the mouse ovary. Ovaries and granulosa cells (GCs) were collected from immature 23-day-old pregnant mare serum gonadotropin primed mice before (0 h) and after administration of human chorionic gonadotropin (hCG; an LH analog) across the periovulatory period (4, 8, 12, and 24 h). In response to hCG, Nts expression rapidly increased 250-fold at 4 h, remained elevated until 8 h, and decreased until 24 h. Expression of Nts receptors for Ntsr1 remained unchanged across the periovulatory period, Ntsr2 was undetectable, whereas Sort1 expression (also called Ntsr3) gradually decreased in both the ovary and GCs after hCG administration. To better understand Nts regulation, inhibitors of the LH/CG signaling pathways were utilized. Our data revealed that hCG regulated Nts expression through the protein kinase A (PKA) and p38 mitogen-activated protein kinase (p38MAPK) signaling pathways. Additionally, epidermal-like-growth factor (EGF) receptor signaling also mediated Nts induction in GCs. To elucidate the role of NTS in the ovulatory process, we used a Nts silencing approach (si-Nts) followed by RNA-sequencing (RNA-seq). RNA-seq analysis of GCs collected after hCG with or without si-Nts identified and qPCR confirmed Ell2, Rsad2, Vps37a, and Smtnl2 as genes downstream of Nts. In summary, these findings demonstrate that hCG induces Nts and that Nts expression is mediated by PKA, p38MAPK, and EGF receptor signaling pathways. Additionally, NTS regulates several novel genes that could potentially impact the ovulatory process.

Parkinson Disease and Subthalamic Nucleus Deep Brain Stimulation: Cognitive Effects in GBA Mutation Carriers.

OBJECTIVE: This study was undertaken to compare the rate of change in cognition between glucocerebrosidase (GBA) mutation carriers and noncarriers with and without subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson disease. METHODS: Clinical and genetic data from 12 datasets were examined. Global cognition was assessed using the Mattis Dementia Rating Scale (MDRS). Subjects were examined for mutations in GBA and categorized as GBA carriers with or without DBS (GBA+DBS+, GBA+DBS-), and noncarriers with or without DBS (GBA-DBS+, GBA-DBS-). GBA mutation carriers were subcategorized according to mutation severity (risk variant, mild, severe). Linear mixed modeling was used to compare rate of change in MDRS scores over time among the groups according to GBA and DBS status and then according to GBA severity and DBS status. RESULTS: Data were available for 366 subjects (58 GBA+DBS+, 82 GBA+DBS-, 98 GBA-DBS+, and 128 GBA-DBS- subjects), who were longitudinally followed (range = 36-60 months after surgery). Using the MDRS, GBA+DBS+ subjects declined on average 2.02 points/yr more than GBA-DBS- subjects (95% confidence interval [CI] = -2.35 to -1.69), 1.71 points/yr more than GBA+DBS- subjects (95% CI = -2.14 to -1.28), and 1.49 points/yr more than GBA-DBS+ subjects (95% CI = -1.80 to -1.18). INTERPRETATION: Although not randomized, this composite analysis suggests that the combined effects of GBA mutations and STN-DBS negatively impact cognition. We advise that DBS candidates be screened for GBA mutations as part of the presurgical decision-making process. We advise that GBA mutation carriers be counseled regarding potential risks associated with STN-DBS so that alternative options may be considered. ANN NEUROL 2022;91:424-435.

The effect of obesity on the ED(95) of propofol for loss of consciousness in children and adolescents.

INTRODUCTION: Anesthesiologists face a dilemma in determining appropriate dosing of anesthetic drugs in obese children. In this study we determined the dose of propofol that caused loss of consciousness in 95% (ED(95)) of obese and nonobese children as determined by loss of eye lash reflex. METHODS: Forty obese (body mass index [BMI] > 95th percentile for age and gender) and 40 normal weight (BMI 25th to 84th percentile) healthy ASA 1 to 2 children ages 3 to 17 years presenting for surgical procedures were studied using a biased coin design. The primary endpoint was loss of lash reflex at 20 seconds after propofol administration. The first patient in each group received 1.0 mg/kg of IV propofol, and subsequent patients received predetermined propofol doses based on the lash reflex response in the previous patient. If the lash reflex was present, the next patient received a dose increment of 0.25 mg/kg. If the lash reflex was absent, the next patient was randomized to receive either the same dose (95% probability) or a dose decrement of 0.25 mg/kg (5% probability). The ED(95) and 95% confidence intervals (CI) were calculated using isotonic regression and bootstrapping methods respectively. RESULTS: The ED(95) of propofol for loss of lash reflex was significantly lower in obese pediatric patients (2.0 mg/kg, approximate 95% CI, 1.8 to 2.2 mg/kg) in comparison with nonobese patients (3.2 mg/kg, approximate 95% CI, 2.7 to 3.2 mg/kg), P ≤ 0.05. DISCUSSION: A simple approach to deciding what dose of propofol should be used for induction of anesthesia in children ages 3 to 17 years is to first establish the child's BMI on readily available gender-specific charts. Obese children (BMI >95th percentile for age and gender) require a lower weight-based dose of propofol for induction of anesthesia, than do normal-weight children.

Immediate Lymphatic Reconstruction during Axillary Node Dissection for Breast Cancer: A Systematic Review and Meta-analysis.

The objective of this study is to summarize the current body of evidence detailing the impact of immediate lymphatic reconstruction (ILR) on the incidence of breast cancer-related lymphedema (BCRL) following axillary node dissection (ALND). Methods: Medline and Embase databases were queried for publications, where ILR was performed at the time of ALND for breast cancer. Exclusion criteria included lymphaticovenous anastomosis for established BCRL, animal studies, non-breast cancer patient population studies, and descriptive studies detailing surgical technique. Meta-analysis was performed with a forest plot generated using a Mantel -Haenszel statistical method, with a random-effect analysis model. Effect measure was reported as risk ratios with associated 95% confidence intervals. The risk of bias within studies was assessed by the Cochrane Collaboration tool. Results: This systematic review yielded data from 11 studies and 417 breast cancer patients who underwent ILR surgery at the time of ALND. There were 24 of 417 (5.7%) patients who developed BCRL following ILR. Meta-analysis revealed that in the ILR group, 6 of 90 patients (6.7%) developed lymphedema, whereas in the control group, 17 of 50 patients (34%) developed lymphedema. Patients in the ILR group had a risk ratio of 0.22 (CI, 0.09 -0.52) of lymphedema with a number needed to treat of four. Conclusions: There is a clear signal indicating the benefit of ILR in preventing BCRL. Randomized control trials are underway to validate these findings. ILR may prove to be a beneficial intervention for improving the quality of life of breast cancer survivors.

Thyroid Hemiagenesis in a Thyroiditis Prone Mouse Strain.

BACKGROUND: Thyroid hemiagenesis, a rare congenital condition detected by ultrasound screening of the neck, is usually not manifested clinically in humans. This condition has been reported in mice with hypothyroidism associated with induced deficiency in paired box 8 and NK2 homeobox 1, sonic hedgehog, or T-box 1. Unexpectedly, we observed thyroid hemiagenesis in NOD.H2h4 mice, an unusual strain that spontaneously develops iodide enhanced thyroid autoimmunity but remains euthyroid. OBJECTIVES AND METHODS: First, to compare mice with thyroid hemiagenesis versus bilobed littermates for serum T4, autoantibodies to thyroglobulin (ELISA) and thyroid peroxidase (TPO; flow cytometry with eukaryotic cells expressing mouse TPO), gross anatomy, and thyroid histology; second, to estimate the percentage of mice with thyroid hemiagenesis in the NOD.H2h4 mice we have studied over 6 years. RESULTS: Thyroid hemiagenesis was observed in 3 of 1,025 NOD.H2h4 mice (2 females, 1 male; 0.3$). Two instances of hemiagenesis were in wild-type females and one in a transgenic male expressing the human TSHR A-subunit in the thyroid. Two mice had very large unilobed glands, as in some human cases with this condition. Thyroid lymphocytic infiltration, serum T4, and the levels of thyroid autoantibodies were similar in mice with thyroid hemiagenesis and bilobed littermates. CONCLUSIONS: Unlike hypothyroidism associated with hemiagenesis in transcription factor knockout mice, hemiagenesis in euthyroid NOD.H2h4 mice occurs spontaneously and is phenotypically similar to that occasionally observed in humans.

[Anaphylaxis secondary to prick-to-prick tests to foods and its risk factors]. / Anafilaxia secundaria a pruebas cutáneas prick-to-prick para alimentos y sus factores de riesgo.

The diagnosis of food allergy requires a proper anamnesis and diagnostic testing with skin prick tests with fresh foods and/or standardized allergen, or specific IgE tests. The risk of systemic reactions is of 15-23 per 100,000 skin tests performed by prick method, specifically anaphylaxis at 0.02%. This paper reports the case of four patients, who while performing prick to prick test with fresh food presented anaphylactic reaction. Implicated foods were fruits of the Rosaceae, Anacardiaceae and Caricaceae families. The severity of anaphylaxis was: two patients with grade 4, one patient grade 2 and one grade 3, all with appropriate response to drug treatment. The risk factors identified were: female sex, personal history of atopy, previous systemic reaction to Hymenoptera venom, prior anaphylaxis to prick tests to aeroallergens. We found that a history of positive skin test for Betulla v, can be a risk factor for anaphylaxis in patients with oral syndrome. During testing prick to prick with food anaphylaxis can occur, so it should be made with aerial red team on hand. The history of positivity Betulla v is an additional risk factor in these patients.

El diagnóstico de alergia alimentaria requiere una anamnesis adecuada y la realización de pruebas diagnósticas, las pruebas cutáneas con alimentos en fresco, con alergenos estandarizados, o con ambos; las pruebas de IgE específica para alimentos son útiles. El riesgo de reacciones sistémicas por pruebas cutáneas por punción es de 15 a 23 por cada 100,000 y el de anafilaxia es de 0.02%. Comunicamos el caso de cuatro pacientes que sufrieron anafilaxia durante la realización de prueba Prick-to-Prick con alimentos frescos. Los alimentos implicados fueron frutas de las familias Rosaceae, Anacardiaceae y Caricaceae. En dos pacientes la anafilaxia fue de grado 4, en una grado 2 y en otra grado 3, todas con adecuada respuesta al tratamiento farmacológico. Los factores de riesgo fueron: sexo femenino, antecedente personal de atopia, reacción sistémica previa a veneno de himenópteros y anafilaxia previa con pruebas por punción para aeroalergenos. Las cuatro pacientes tuvieron síndrome de alergia oral y 50% tenía antecedente de prueba por punción positiva a betuláceas. Durante la realización de pruebas Prick-to-Prick para alimentos los pacientes pueden presentar anafilaxia, por lo que deben realizarse en un área que cuente con equipo rojo. El antecedente de síndrome de alergia oral se observó en todos los casos y la mitad de las pacientes tuvieron positividad a betuláceas, estos antecedentes pueden ser factores de riesgo adicional de anafilaxia dura te la realización de pruebas Prick-to-Prick para alimentos.

Incidência de LER/DORT em trabalhadores de enfermagem / Incidence of occupational disorders in nursing workers

As LER/DORT estão relacionadas às mudanças em curso na organização do trabalho e às inovações tecnológicas resultantes da reestruturação produtiva. O trabalho de enfermagem, por suas características, acaba por provocar lesões físicas relacionadas ao trabalho, muitas vezes irreversíveis. Este estudo analisa a produção científica sobre a LER/DORT em trabalhadores de enfermagem. A amostra foi composta por 14 artigos que abordavam as LER/DORT na saúde do profissional de enfermagem indexados nas bases de dados Medline, Scielo e Lilacs, no período de 1996 a 2006, publicados em periódicos nacionais e internacionais. Conclui-se que maior atenção deve ser direcionada às posturas adotadas pelos trabalhadores na execução das atividades laborais, além de mobiliários adequados às execuções das tarefas, bem como se faz necessário disponibilizar instrumentos e equipamentos ergonomicamente idealizados, visando a redução da incidência das doenças relacionadas ao trabalho.

Incidence of occupational disorders in nursing workers. Occupational disorders are connected to changes in work organization and to technological innovations caused by a restructuring of the production process. The Nursing profession, by nature, can lead to work-related physical lesions, some of which can be irreversible. This study analyzes scientific literature on the subject of occupational disorders in nursing professionals. The sample was composed of 14 articles that discuss the effects of these disorders on the health of nursing professionals. It aims to detect the main problems associated with nursing according to the Medline, Scielo and Lilacs databases, from 1996 to 2006, published in national and international annals. Evidence has demonstrated that attention must be paid to the nurses? posture while they work, as well as to provide adequate furniture; additionally, it is necessary to ergonomically appropriate instruments and equipment, in order to reduce the incidence of occupational disorders.