Norepinephrine activates ß1 -adrenergic receptors at the inner nuclear membrane in astrocytes.

Norepinephrine exerts powerful influences on the metabolic, neuroprotective and immunoregulatory functions of astrocytes. Until recently, all effects of norepinephrine were believed to be mediated by receptors localized exclusively to the plasma membrane. However, recent studies in cardiomyocytes have identified adrenergic receptors localized to intracellular membranes, including Golgi and inner nuclear membranes, and have shown that norepinephrine can access these receptors via transporter-mediated uptake. We recently identified a high-capacity norepinephrine transporter, organic cation transporter 3 (OCT3), densely localized to outer nuclear membranes in astrocytes, suggesting that adrenergic signaling may also occur at the inner nuclear membrane in these cells. Here, we used immunofluorescence and western blot to show that ß1 -adrenergic receptors are localized to astrocyte inner nuclear membranes; that key adrenergic signaling partners are present in astrocyte nuclei; and that OCT3 and other catecholamine transporters are localized to astrocyte plasma and nuclear membranes. To test the functionality of nuclear membrane ß1 -adrenergic receptors, we monitored real-time protein kinase A (PKA) activity in astrocyte nuclei using a fluorescent biosensor. Treatment of astrocytes with norepinephrine induced rapid increases in PKA activity in the nuclear compartment. Pretreatment of astrocytes with inhibitors of catecholamine uptake blocked rapid norepinephrine-induced increases in nuclear PKA activity. These studies, the first to document functional adrenergic receptors at the nuclear membrane in any central nervous system cell, reveal a novel mechanism by which norepinephrine may directly influence nuclear processes. This mechanism may contribute to previously described neuroprotective, metabolic and immunoregulatory actions of norepinephrine.

Travel from the United Kingdom to the United States by a Symptomatic Patient Infected with the SARS-CoV-2 B.1.1.7 Variant - Texas, January 2021.

In December 2020, the B.1.1.7 genetic variant of SARS-CoV-2, the virus that causes COVID-19, was first reported after emergence and rapid circulation in the United Kingdom (1). Evidence suggests that the B.1.1.7 variant is more efficiently transmitted than are other SARS-CoV-2 variants, and widespread circulation could thereby increase SARS-CoV-2 infection and hospitalization rates (1,2). The first reported SARS-CoV-2 B.1.1.7 variant case in the United States was confirmed by sequencing in Colorado on December 29, 2020.* This report describes a person who traveled from the United Kingdom to the United States after experiencing COVID-19-compatible symptoms† and was eventually confirmed to be infected with the B.1.1.7 variant.

Estrategia combinada en fertilización in vitro: mínima estimulación y transferencia de embrión único con diagnóstico genético. Experiencia de 3 años en dos centros de reproducción en México / A combined in-vitro fertilization strategy: minimal stimulation IVF, PGT-A and SET. Results from 3 years' experience at two IVF centers in Mexico

Resumen OBJETIVO: Evaluar los desenlaces de una estrategia combinada para fertilización in vitro: mínima estimulación ovárica, diagnóstico genético preimplantación para aneuploidias y transferencia de un solo embrión. MATERIALES Y MÉTODOS: Estudio de cohorte, retrospectivo, efectuado en dos centros de reproducción de México, en un periodo de tres años. Se incluyeron pacientes entre 25 y 45 años, en protocolo de fertilización in vitro, con mínima estimulación, diagnóstico genético preimplantación para aneuploidias (PGT-A) y transferencia de embrión único. El diagnóstico genético preimplantación se estableció mediante microarreglos y secuenciación de nueva generación (NGS). Para el análisis estadístico se integraron 5 grupos, según la edad de las pacientes: menores de 35 años; 35 a 37 años; 38 a 40 años; 41 a 42 años; y mayores de 42 años. Mediante estadística descriptiva se analizaron las variables numéricas y categóricas. RESULTADOS: Se analizaron 175 ciclos, en 125 pacientes (edad promedio: 39 años ± 5). Se obtuvieron, en promedio, 5 óvulos por ciclo. La tasa de fertilización fue de 86.5% y la de blastocisto por óvulo fertilizado de 50.7%. Se tomó biopsia para diagnóstico genético preimplantación para aneuploidias a 404 embriones. La tasa general de euploidia fue de 33%. Se efectuaron 69 transferencias de embrión único, con una tasa de embarazo por transferencia de 71%. La tasa de nacimiento por transferencia fue de 60.8% (42 nacimientos). CONCLUSIONES: La combinación de mínima estimulación, diagnóstico genético preimplantación para aneuploidias y transferencia de embrión único, es un procedimiento adecuado para alcanzar una tasa de nacimiento alta.

Abstract OBJECTIVE: To evaluate results of a combined approach in IVF, using minimal stimulation, preimplantation genetic testing for aneuploidy, and single blastocyst transfer. MATERIALS AND METHODS: Retrospective cohort study over a three years' period in two fertility centers in Mexico. A total of 125 patients were included, between 25 and 45 years old, with minimal stimulation IVF, preimplantation genetic testing for aneuploidy (PGT-A) and single euploid embryo transfer. PGT was performed using microarrays and next generation sequencing (NGS). RESULTS: A total of 175 cycles (mean age: 39 years old) were analyzed in 125 patients. On average, five eggs were collected per cycle; fertilization rate was 86.57%; blastocyst rate was 50.7% per fertilized egg. Only 33% of embryos were euploid. Pregnancy rate per transferred embryo was 71%. Live birth rate was 60.8% (42 births). CONCLUSIONS: A combination of minimal stimulation, PGT-A and single blastocyst embryo transfer can yield a high live birth rate.

Vitamina D y su relación con factores de riesgo metabólicos para enfermedad cardiovascular en mujeres adultas / Vitamin D and relationship with metabolic risk factors for cardiovascular disease in adult women

Introducción. La deficiencia de vitamina D es considerada como un problema de salud pública en otros países. Se ha reportado que esta deficiencia se relaciona con el riesgo a desarrollar enfermedades metabólicas Métodos. Estudio descriptivo, transversal, en 110 mujeres adultas de Lima Metropolitana. Se calculó el índice de masa corporal (IMC) para definir el estado nutricional. Se determinó niveles de insulina, glucosa, perfil lipídico y 25(OH)-D (vitamina D). Se calculó el Homeostatic Model of Assesment Index (HOMA-I). Para definir resistencia a la insulina (RI) se consideró un HOMA-I ≥ 2,7. Para la deficiencia de la 25 (OH)-D el punto de corte fue 30 ng/ mL. Para la ingesta de vitamina D se usó la frecuencia de consumo. La identificación de dislipidemias se hizo con lo recomendado por el Third Report of the National Cholesterol Education Program. Resultados. En las pacientes con déficit de vitamina D, los promedios de edad, IMC, insulina, glucosa, HOMA-I, colesterol total, colesterol HDL, colesterol LDL, y trigliceridos fueron superiores respecto a las pacientes con dosaje de vitamina D normal, encontrándose diferencia estadísticamente significativa para el IMC (p<0,03), niveles de insulina (p<0,01), HOMA-I (p<0,01), y trigliceridos (p<0,01). Además, se determinó déficit de vitamina D en pacientes con resistencia a la insulina con la presencia de obesidad y sobrepeso así como en las pacientes con hipertrigliceridemia (p<0,05); el riesgo de tener déficit de esta vitamina estuvo asociado a resistencia a la insulina (OR:3,28; IC:1,3-8,3) y con hipertrigliceridemia (OR:4,07; IC:1,8-9,3). Conclusiones. La deficiencia de vitamina D mostró asociación con dos variables que identifican el riesgo metabólico: la resistencia a la insulina y la hipertrigliceridemia, en la población estudiada, lo que podría explicar la posible relación de esta vitamina con enfermedades cardiovasculares.

Introduction. Vitamin D deficiency is considered a public health problem in other countries. Has been reported that this deficiency is related to the risk of developing metabolic diseases. Methods. Study descriptive, cross-sectional design in 110 adult women of Lima Metropolitana. The Body Mass Index (MBI) was calculated to define the nutritional status. Blood levels of insulin, glucose, lipid profile and 25 (OH) D (vitamin D) were determined. It was calculated Homeostatic Model of Assessment Index (HOMA-I). Was calculated and to define insulin resistance (IR) a HOMA-I ≥ 2,7. For the deficiency of 25 (OH)-D, the cut-off point was 30 ng/mL for the intake of vitamin D a frequency of consumption was used. The identification of dyslipidemias was made as recommended by the Third Report of the National Cholesterol Education Program Results. In patients with vitamin D deficiency, the average age, BMI, insulin, glucose, HOMA-I, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides were higher compared to patients with normal vitamin D dosage, finding difference statistically significant for BMI (p<0,03), insulin levels (p<0,01), HOMA-I (p<0,01), and triglycerides (p<0,01). In addition, vitamin D deficiency was determined in patients with insulin resistance with the presence of obesity and overweight as well as in patients with hypertriglyceridemia (p<0,05); the risk of having vitamin D deficiency was associated with insulin resistance (OR: 3,28, CI:1,3-8,3) and with hypertriglyceridemia (OR: 4,07, CI:1,8-9,3). Conclusions. The deficiency of vitamin D showed association with two variables that identify metabolic risk: insulin resistance and hypertriglyceridemia, in the study population, which could explain the possible relationship of this vitamin with cardiovascular diseases.

Gluteoplastia Técnica Intramuscular (XYZ) / Gluteoplasty using the Intramuscular (XYZ) Method

INTRODUÇÃO: No conceito de beleza corporal, a forma e o tamanho das nádegas são fundamentais, provocando uma crescente busca não só de mulheres, como também de homens, pela cirurgia de gluteoplastia. O objetivo deste trabalho é apresentar a experiência do autor em gluteoplastia com a técnica intramuscular (XYZ). MÉTODO: No período de 2010 a 2015 foram operados 29 pacientes com idades entre 22 e 64 anos (média 43 anos), sendo 26 mulheres (89,66%) e três homens (10,34%). Foram usados implantes redondos ou ovais, com volumes entre 240 e 420 ml (média de 330 ml), dependendo da melhor indicação para cada caso. RESULTADOS: Foram obtidos bons resultados sob o aspecto de aumento de volume e harmonia da região glútea, com alto índice de satisfação dos pacientes. CONCLUSÕES: Na casuística do estudo a técnica intramuscular (XYZ) se mostrou segura, tanto nas cirurgias primárias como nas cirurgias secundárias, para tratar casos de assimetria e/ou implantes visíveis. Com a pré- determinação dos pontos fixos XYZ, o procedimento torna-se seguro e reprodutível.

INTRODUCTION: The shape and size of the buttocks are essential to the notion of bodily beauty. This has resulted in a growing interest in gluteoplasty among both women and men. The aim of the present study was to present the author's experience with gluteoplasty using the intramuscular XYZ method. METHOD: Between 2010 and 2015, 29 patients aged 22 to 64 years (average, 43 years) underwent gluteoplasty; of these 26 were women (89.66%) and 3 were men (10.34%). Round or oval implants were used, with volumes of 240 to 420 ml (average, 330 ml), depending on the individual case. RESULTS: Good results were obtained in terms of volume increase and harmony of the gluteal region, with a high degree of patient satisfaction. CONCLUSIONS: The intramuscular XYZ method was safe, both for primary and secondary surgery, to treat cases of asymmetry and/or visible implants. Predetermining the XYZ reference points makes this procedure safe and reproducible.

Neural basis of reward anticipation and its genetic determinants.

Dysfunctional reward processing is implicated in various mental disorders, including attention deficit hyperactivity disorder (ADHD) and addictions. Such impairments might involve different components of the reward process, including brain activity during reward anticipation. We examined brain nodes engaged by reward anticipation in 1,544 adolescents and identified a network containing a core striatal node and cortical nodes facilitating outcome prediction and response preparation. Distinct nodes and functional connections were preferentially associated with either adolescent hyperactivity or alcohol consumption, thus conveying specificity of reward processing to clinically relevant behavior. We observed associations between the striatal node, hyperactivity, and the vacuolar protein sorting-associated protein 4A (VPS4A) gene in humans, and the causal role of Vps4 for hyperactivity was validated in Drosophila Our data provide a neurobehavioral model explaining the heterogeneity of reward-related behaviors and generate a hypothesis accounting for their enduring nature.

S6 Kinase Reflects and Regulates Ethanol-Induced Sedation.

Alcohol use disorders (AUDs) affect people at great individual and societal cost. Individuals at risk for AUDs are sensitive to alcohol's rewarding effects and/or resistant to its aversive and sedating effects. The molecular basis for these traits is poorly understood. Here, we show that p70 S6 kinase (S6k), acting downstream of the insulin receptor (InR) and the small GTPase Arf6, is a key mediator of ethanol-induced sedation in Drosophila. S6k signaling in the adult nervous system determines flies' sensitivity to sedation. Furthermore, S6k activity, measured via levels of phosphorylation (P-S6k), is a molecular marker for sedation and overall neuronal activity: P-S6k levels are decreased when neurons are silenced, as well as after acute ethanol sedation. Conversely, P-S6k levels rebound upon recovery from sedation and are increased when neuronal activity is enhanced. Reducing neural activity increases sensitivity to ethanol-induced sedation, whereas neuronal activation decreases ethanol sensitivity. These data suggest that ethanol has acute silencing effects on adult neuronal activity, which suppresses InR/Arf6/S6k signaling and results in behavioral sedation. In addition, we show that activity of InR/Arf6/S6k signaling determines flies' behavioral sensitivity to ethanol-induced sedation, highlighting this pathway in acute responses to ethanol. SIGNIFICANCE STATEMENT: Genetic factors play a major role in the development of addiction. Identifying these genes and understanding their molecular mechanisms is a necessary first step in the development of targeted therapeutic intervention. Here, we show that signaling from the insulin receptor in Drosophila neurons determines flies' sensitivity to ethanol-induced sedation. We show that this signaling cascade includes the small GTPase Arf6 and S6 kinase (S6k). In addition, activity of S6k is regulated by acute ethanol exposure and by neuronal activity. S6k activity is therefore both an acute target of ethanol exposure and a regulator of ethanol's effects on behavior.

Simulation study of melanoma detection in human skin tissues by laser-generated surface acoustic waves.

Air pollution has been correlated to an increasing number of cases of human skin diseases in recent years. However, the investigation of human skin tissues has received only limited attention, to the point that there are not yet satisfactory modern detection technologies to accurately, noninvasively, and rapidly diagnose human skin at epidermis and dermis levels. In order to detect and analyze severe skin diseases such as melanoma, a finite element method (FEM) simulation study of the application of the laser-generated surface acoustic wave (LSAW) technique is developed. A three-layer human skin model is built, where LSAW's are generated and propagated, and their effects in the skin medium with melanoma are analyzed. Frequency domain analysis is used as a main tool to investigate such issues as minimum detectable size of melanoma, filtering spectra from noise and from computational irregularities, as well as on how the FEM model meshing size and computational capabilities influence the accuracy of the results. Based on the aforementioned aspects, the analysis of the signals under the scrutiny of the phase velocity dispersion curve is verified to be a reliable, a sensitive, and a promising approach for detecting and characterizing melanoma in human skin.

Calf lipo-reshaping.

BACKGROUND: Augmentation and remodelling of the calf is becoming more and more frequent, representing a challenge for the surgeon who must consider this body zone as a functional and aesthetical whole. Historically, calf reshaping has been carried out with silicone implants, mainly in the subaponeurotic plane; nonetheless, as in other body sites it is possible to perform lipoinjection which is a reliable procedure with minimal scarring and a lasting outcome with rare, long-term complications. MATERIALS AND METHODS: Between the years 2009 and 2011, five patients (three women and two men) underwent bilateral calf liporemodelling. Follow-up was between 6 and 18 months. The larger perimeter of each calf was measured for follow-up. Magnetic resonance imaging was used to localise the injected fat at the end of the follow-up period in two of the patients. RESULTS: An average of 126.8±21.2 cc was lipoinjected into each calf. The average final augmentation in the larger perimeter of each leg was 2.8 cm. All patients obtained a good aesthetical outcome and were satisfied. No important complications were seen in this series. CONCLUSION: According to our experience and outcomes we can recommend the liporemodelling technique of the calf as a valid alternative for the reshaping of the distal third of the inferior extremity.

A four-quadrant PVDF transducer for surface acoustic wave detection.

In this paper, a polyvinylidene fluoride (PVDF) piezoelectric transducer was developed to detect laser-induced surface acoustic waves in a SiO(2)-thin film-Si-substrate structure. In order to solve the problems related to, firstly, the position of the probe, and secondly, the fact that signals at different points cannot be detected simultaneously during the detection process, a four-quadrant surface acoustic wave PVDF transducer was designed and constructed for the purpose of detecting surface acoustic waves excited by a pulse laser line source. The experimental results of the four-quadrant piezoelectric detection in comparison with the commercial nanoindentation technology were consistent, the relative error is 0.56%, and the system eliminates the piezoelectric surface wave detection direction deviation errors, improves the accuracy of the testing system by 1.30%, achieving the acquisition at the same time at different testing positions of the sample.

Development of a hybrid atomic force microscopic measurement system combined with white light scanning interferometry.

A hybrid atomic force microscopic (AFM) measurement system combined with white light scanning interferometry for micro/nanometer dimensional measurement is developed. The system is based on a high precision large-range positioning platform with nanometer accuracy on which a white light scanning interferometric module and an AFM head are built. A compact AFM head is developed using a self-sensing tuning fork probe. The head need no external optical sensors to detect the deflection of the cantilever, which saves room on the head, and it can be directly fixed under an optical microscopic interferometric system. To enhance the system's dynamic response, the frequency modulation (FM) mode is adopted for the AFM head. The measuring data can be traceable through three laser interferometers in the system. The lateral scanning range can reach 25 mm × 25 mm by using a large-range positioning platform. A hybrid method combining AFM and white light scanning interferometry is proposed to improve the AFM measurement efficiency. In this method, the sample is measured firstly by white light scanning interferometry to get an overall coarse morphology, and then, further measured with higher resolution by AFM. Several measuring experiments on standard samples demonstrate the system's good measurement performance and feasibility of the hybrid measurement method.

Prediction of maximal aerobic capacity in severely burned children.

INTRODUCTION: Maximal oxygen uptake (VO2 peak) is an indicator of cardiorespiratory fitness, but requires expensive equipment and a relatively high technical skill level. PURPOSE: The aim of this study is to provide a formula for estimating VO2 peak in burned children, using information obtained without expensive equipment. METHODS: Children, with ≥ 40% total surface area burned (TBSA), underwent a modified Bruce treadmill test to assess VO(2) peak at 6 months after injury. We recorded gender, age, %TBSA, %3rd degree burn, height, weight, treadmill time, maximal speed, maximal grade, and peak heart rate, and applied McHenry's select algorithm to extract important independent variables and Robust multiple regression to establish prediction equations. RESULTS: 42 children; 7-17 years old were tested. Robust multiple regression model provided the equation: VO2 =10.33-0.62 × age (years)+1.88 × treadmill time (min)+2.3 (gender; females = 0, males = 1). The correlation between measured and estimated VO2 peak was R = 0.80. We then validated the equation with a group of 33 burned children, which yielded a correlation between measured and estimated VO2 peak of R = 0.79. CONCLUSIONS: Using only a treadmill and easily gathered information, VO2 peak can be estimated in children with burns.

Evaluation of BCG vaccine and Mycobacterium bovis culture filtrate proteins against bovine tuberculosis.

The objective of this study was to evaluate the degree of protection against TB of three immunogens in calves experimentally challenged with a pathogenic Mycobacterium bovis strain by identification of lesions during necropsy. Twenty-four calves free of TB were distributed into four groups: group 1 was inoculated with M. bovis CFPE, group 2 with CFPE/IFN-gamma, group 3 with M. bovis BCG, and group 4 remained as control. After 6 months all animals were challenged with an M. bovis field strain, and 6 months later the animals were euthanized and the presence of lesions was evaluated. Several degrees of protection were observed in the vaccinated groups, particularly in the group vaccinated with BCG, as shown by the absence or decrease in severity of lesions. Vaccination could be useful in high-prevalence zones where it is economically unfeasible to slaughter animals.