Acute Aromatase Inhibition Impairs Neural and Behavioral Auditory Scene Analysis in Zebra Finches.

Auditory perception can be significantly disrupted by noise. To discriminate sounds from noise, auditory scene analysis (ASA) extracts the functionally relevant sounds from acoustic input. The zebra finch communicates in noisy environments. Neurons in their secondary auditory pallial cortex (caudomedial nidopallium, NCM) can encode song from background chorus, or scenes, and this capacity may aid behavioral ASA. Furthermore, song processing is modulated by the rapid synthesis of neuroestrogens when hearing conspecific song. To examine whether neuroestrogens support neural and behavioral ASA in both sexes, we retrodialyzed fadrozole (aromatase inhibitor, FAD) and recorded in vivo awake extracellular NCM responses to songs and scenes. We found that FAD affected neural encoding of songs by decreasing responsiveness and timing reliability in inhibitory (narrow-spiking), but not in excitatory (broad-spiking) neurons. Congruently, FAD decreased neural encoding of songs in scenes for both cell types, particularly in females. Behaviorally, we trained birds using operant conditioning and tested their ability to detect songs in scenes after administering FAD orally or injected bilaterally into NCM. Oral FAD increased response bias and decreased correct rejections in females, but not in males. FAD in NCM did not affect performance. Thus, FAD in the NCM impaired neuronal ASA but that did not lead to behavioral disruption suggesting the existence of resilience or compensatory responses. Moreover, impaired performance after systemic FAD suggests involvement of other aromatase-rich networks outside the auditory pathway in ASA. This work highlights how transient estrogen synthesis disruption can modulate higher-order processing in an animal model of vocal communication.

Social reinforcement guides operant behaviour and auditory learning in a songbird.

Motivation to seek social interactions is inherent to all social species. For instance, even with risk of disease transmission in a recent pandemic, humans sought out frequent in-person social interactions. In other social animals, socialization can be prioritized even over water or food consumption. Zebra finches, Taeniopygia guttata, are highly gregarious songbirds widely used in behavioural and physiological research. Songbirds, like humans, are vocal learners during development, which rely on intense auditory learning. Aside from supporting song learning, auditory learning further supports individual identification, mate choice and outcome associations in songbirds. To study auditory learning in a laboratory setting, studies often employ operant paradigms with food restriction and reinforcement and require complete social isolation, which can result in stress and other unintended physiological consequences for social species. Thus, in this work, we designed an operant behavioural method leveraging the sociality of zebra finches for goal-directed behaviours. Our approach relies on visual social reinforcement, without depriving the animals of food or social contact. Using this task, we found that visual social reinforcement was a strong motivational drive for operant behaviour. Motivation was sensitive to familiarity towards the stimulus animal and higher when engaging with a familiar versus a novel individual. We further show that this tool can be used to assess auditory discrimination learning using either songs or synthetic pure tones as stimuli. As birds gained experience in the task, they developed a strategy to maximize reward acquisition in spite of receiving more punishment, i.e. liberal response bias. Our operant paradigm provides an alternative to tasks using food reinforcement and could be applied to a variety of highly social species, such as rodents and nonhuman primates.

The long-lasting shadow of litter size in rodents: litter size is an underreported variable that strongly determines adult physiology.

BACKGROUND/PURPOSE: Litter size is a biological variable that strongly influences adult physiology in rodents. Despite evidence from previous decades and recent studies highlighting its major impact on metabolism, information about litter size is currently underreported in the scientific literature. Here, we urge that this important biological variable should be explicitly stated in research articles. RESULTS/CONCLUSION: Below, we briefly describe the scientific evidence supporting the impact of litter size on adult physiology and outline a series of recommendations and guidelines to be implemented by investigators, funding agencies, editors in scientific journals, and animal suppliers to fill this important gap.

Mortalidad en pacientes críticos con síndrome de distrés respiratorio agudo por Covid-19 en la unidad de cuidados intensivos de un hospital público del norte de Perú / Mortality in critical patients with acute respiratory distress syndrome by Covid-19 in the intensive care unit of a public hospital in northern Peru

La enfermedad COVID-19 tiene como complicación el de Síndrome Agudo Respiratorio Severo (SDRA), que es considerada la principal causa de mortalidad dentro de las unidades de cuidados intensivos, a pesar de brindar soporte ventilatorio precoz y óptimo. Sin embargo, es necesario identificar los factores que se asocian a mortalidad en estos pacientes. Objetivo: Determinar cuáles son los factores asociados a mortalidad en pacientes críticos con Síndrome de distrés respiratorio agudo severo por COVID-19 en unidad de cuidados intensivos. Material y métodos: Estudio transversal analítico. Se usó una base de datos obtenida de 176 historias clínicas de los pacientes con distrés respiratorio agudo severo por COVID-19 en un hospital público de Trujillo desde marzo 2020 a junio 2021. Se dividieron un grupo de pacientes que sobreviven y otro grupo de los que fallecen, subdividiéndose según presentaron o no factores de mortalidad asociados. Se realizó un análisis bivariado y con los factores que resultaron estadísticamente significativos se realizó un análisis multivariado para determinar variables asociadas a mortalidad. Resultados: Se halló una mortalidad de 57% del total de pacientes, al realizar el análisis multivariado se encontró asociación estadística significativa en la presencia de comorbilidades medidas con el Índice de Charlson (RPa=1,348; IC 95%: 1,01-1,79; p=0,040) y dentro de los parámetros ventilatorios a la presión pico (RPa=1,261 IC; 95%: 1,13-1,40; p<=0,000). Es necesario identificar aquellas variables de riesgo de mortalidad para estratificar a pacientes y optimizar la terapéutica(AU)

The COVID-19 disease is complicated by severe acute respiratory syndrome (ARDS), which is considered the main cause of mortality within intensive care units, despite providing early and optimal ventilatory support. However, it is necessary to identify the factors associated with mortality in these patients. Objective: To determine the factors associated with mortality in critically ill patients with severe acute respiratory distress syndrome due to COVID-19 in the intensive care unit. Material and methods: Analytical cross-sectional study. A database obtained from 176 medical records of patients with severe acute respiratory distress due to COVID-19 was used in a public hospital in Trujillo from March 2020 to June 2021. A group of patients who survived and another group of those who died were divided, being subdivided according to whether or not they present associated mortality factors. A bivariate analysis was performed and with the factors that were statistically significant, a multivariate analysis was performed to determine variables associated with mortality. Results: A mortality of 57% of the total number of patients was found, when performing the multivariate analysis, a significant statistical association was found in the presence of comorbidities measured with the Charlson Index (RPa = 1.348; 95% CI: 1.01-1.79; p = 0.040) and within the ventilatory parameters at peak pressure (RPa = 1.261 CI; 95%: 1.13-1.40; p <= 0.000). It is necessary to identify those mortality risk variables to stratify patients and optimize therapy(AU)

Time-Restricted Feeding during Puberty Ameliorates Adiposity and Prevents Hepatic Steatosis in a Mouse Model of Childhood Obesity.

BACKGROUND: Time restricted feeding (TRF) refers to dietary interventions in which food access is limited during a specific timeframe of the day. TRFs have proven useful in improving metabolic health in adult subjects with obesity. Their beneficial effects are mediated, in part, through modulating the circadian rhythm. Nevertheless, the translation of these dietary interventions onto obese/overweight children and adolescents remains uncharacterized. The objective of this study is to explore the feasibility of temporal dietary interventions for improving metabolic health in the context of childhood obesity. METHODS: We have previously developed a mouse model of early adiposity (i.e., childhood obesity) through litter size reduction. Mice raised in small litters (SL) became obese as early as by two weeks of age, and as adults, they developed several obesity-related co-morbidities, including insulin resistance, glucose intolerance and hepatic steatosis. Here, we explored whether two independent short-term chrono-nutritional interventions might improve metabolic health in 1-month-old pre-pubertal SL mice. Both TRFs comprised 8 h feeding/14 h fasting. In the first one (TRF1) Control and SL mice had access to the diet for 8 h during the dark phase. In the second intervention (TRF2) food was available during the light:dark transitions. RESULTS: TRF1 did not alter food intake nor ameliorate adiposity in SL-TRF1. In contrast, SL-TRF2 mice showed unintentional reduction of caloric intake, which was accompanied by reduced total body weight and adiposity. Strikingly, hepatic triglyceride content was completely normalized in SL-TRF1 and SL-TRF2 mice, when compared to the ad lib-fed SL mice. These effects were partially mediated by (i) clock-dependent signals, which might modulate the expression of Pparg or Cpt1a, and (ii) clock-independent signals, such as fasting itself, which could influence Fasn expression. CONCLUSIONS: Time-restricted feeding is an effective and feasible nutritional intervention to improve metabolic health, namely hepatic steatosis, in a model of childhood obesity. These data open new avenues for future safe and efficient chrono-nutritional interventions aimed to improve metabolic health in children with overweight/obesity.

Neonatal overfeeding during lactation rapidly and permanently misaligns the hepatic circadian rhythm and programmes adult NAFLD.

Childhood obesity is a strong risk factor for adult obesity, type 2 diabetes, and cardiovascular disease. The mechanisms that link early adiposity with late-onset chronic diseases are poorly characterised. We developed a mouse model of early adiposity through litter size reduction. Mice reared in small litters (SLs) developed obesity, insulin resistance, and hepatic steatosis during adulthood. The liver played a major role in the development of the disease. OBJECTIVE: To gain insight into the molecular mechanisms that link early development and childhood obesity with adult hepatic steatosis and insulin resistance. METHODS: We analysed the hepatic transcriptome (Affymetrix) of control and SL mice to uncover potential pathways involved in the long-term programming of disease in our model. RESULTS: The circadian rhythm was the most significantly deregulated Gene Ontology term in the liver of adult SL mice. Several core clock genes, such as period 1-3 and cryptochrome 1-2, were altered in two-week-old SL mice and remained altered throughout their life course until they reached 4-6 months of age. Defective circadian rhythm was restricted to the periphery since the expression of clock genes in the hypothalamus, the central pacemaker, was normal. The period-cryptochrome genes were primarily entrained by dietary signals. Hence, restricting food availability during the light cycle only uncoupled the central rhythm from the peripheral and completely normalised hepatic triglyceride content in adult SL mice. This effect was accompanied by better re-alignment of the hepatic period genes, suggesting that they might have played a causal role in mediating hepatic steatosis in the adult SL mice. Functional downregulation of Per2 in hepatocytes in vitro confirmed that the period genes regulated lipid-related genes in part through peroxisome proliferator-activated receptor alpha (Ppara). CONCLUSIONS: The hepatic circadian rhythm matures during early development, from birth to postnatal day 30. Hence, nutritional challenges during early life may misalign the hepatic circadian rhythm and secondarily lead to metabolic derangements. Specific time-restricted feeding interventions improve metabolic health in the context of childhood obesity by partially re-aligning the peripheral circadian rhythm.

Nutritional Approaches for the Management of Nonalcoholic Fatty Liver Disease: An Evidence-Based Review.

Nonalcoholic fatty liver disease (NAFLD) is on the rise worldwide representing a public health issue. Its coexistence with obesity and other metabolic alterations is highly frequent. Therefore, current therapy interventions for NAFLD are mainly focused on progressive weight loss through modulation of overall calorie intake with or without specific macronutrient adjustments. Furthermore, other relevant nutritional interventions are built on food selection and time-restricted eating. Since every strategy might bring different results, choosing the optimal diet therapy for a patient is a complicated task, because NAFLD is a multifactorial complex disease. Importantly, some factors need to be considered, such as nutrition-based evidence in terms of hepatic morphophysiological improvements as well as adherence of the patient to the meal plan and adaptability in their cultural context. Thus, the purpose of this review is to explore and compare the subtleties and nuances of the most relevant clinical practice guidelines and the nutritional approaches for the management of NAFLD with a special attention to tangible outcomes and long-term adherence.

Size Does Matter: Litter Size Strongly Determines Adult Metabolism in Rodents.

In this essay, we highlight how litter size in rodents is a strong determinant of neonatal growth and long-term metabolic health. Based on these effects, we strongly advise that scientific articles that utilize rodent models for obesity and metabolic research should include information on the litter sizes in the study to increase the data transparency of such reports.

Synchronous Closure of A Large Medial Perforator-Based Superficial Circumflex Iliac Artery Perforator Free Flap Donor Site Using an Ipsilateral Lateral Perforator-Based Superficial Circumflex Iliac Artery Perforator Propeller Flap.

A superior advantage of the superficial circumflex iliac artery perforator flap is that any donor site residue can easily be hidden by clothing. Usually designed as narrow or moderate-sized flaps based on medial perforators of the superficial branch, this readily allows primary donor site closure. However, for larger flaps, tension-free closure requires that the thigh remain flexed or even a skin graft used. Another alternative would be to use an adequate lateral perforator of the deep branch, if available, as the vascular hub of a propeller flap that extended into the adjacent flank, that could then be rotated into the medial groin to facilitate simultaneous direct closure of both flap donor sites.

Perception of clinical educational environment by student of physiotherapy based on the Educational Environment Measurement Questionnaire of the Postgraduate Hospital in Chile.

PURPOSE: It aimed at describing the perception of the clinical educational environment by physiotherapy students based on the Educational Environment Measurement Questionnaire of the Postgraduate Hospital in Chile. METHODS: The clinical education environment was evaluated according to the PHEEM by 192 students originally enrolled in the fifth year of the physiotherapy career at three different headquarters of the academic institution: Santiago, Viña del Mar and Concepcion Campus (Metropolitan, Valparaiso and Bio Bio region, respectively), from March to October 2018. The Cronbach's alpha was applied to measure the reliability of the instrument and the Student t and ANOVA tests were used to compare the differences of PHEEM scores by headquarters, environmental areas, and experience of internship. RESULTS: A total overall average score of 125.88 was obtained, which meant an excellent educational environment. The overall score was 127.6±22.7 for Headquarters1, 125.6±21.6 for Headquarters2 and 122.5±26.9 for Headquarters3. According to the type of establishment, the scores were of 127.1±22.1 for private and 123.5±26.3 for public institutes. According to the type of area, the score was cataloged as an excellent educational environment in all cases, except in the respiratory care area (lowest score: 117.5±29.1). Finally, the score was 126.9±20.5 for the first internship, 121.7±29.3 for the second and 129.4±19.6 for the third. CONCLUSION: There is relative homogeneity of the clinical educational environment for different headquarters, types of establishment or type of area; but there are significant differences in the number of the internship. The promotion of a good clinical educational environment can have an important impact on the development and performance of the future professional, being the detection of negative aspects an opportunity to improve the hidden curriculum.

Delphinidin Ameliorates Hepatic Triglyceride Accumulation in Human HepG2 Cells, but Not in Diet-Induced Obese Mice.

Anthocyanin consumption is linked to benefits in obesity-related metabolic alterations and non-alcoholic fatty liver disease (NAFLD), though the functional role of delphinidin (Dp) is yet to be established. Therefore, this study examined the effects of Dp on metabolic alterations associated with NAFLD, and molecular mechanisms in HepG2 cells and diet-induced obese mice. Cells incubated with palmitate to induce lipid accumulation, concomitantly treated with Dp, reduced triglyceride accumulation by ~53%, and downregulated gene expression of CPT1A, SREBF1, and FASN without modifying AMP-activated protein kinase (AMPK) levels. C57BL/6Nhsd mice were fed a standard diet (control) or a high-fat/high-carbohydrate diet (HFHC) for 16 weeks. Mice in the HFHC group were subdivided and treated with Dp (HFHC-Dp, 15 mg/kg body weight/day) or a vehicle for four weeks. Dp did not affect body weight, energy intake, hyperglycemia, insulin resistance, or histological abnormalities elicited by the HFHC diet. Furthermore, the messenger RNA (mRNA) expressions of Acaca, and Fasn in hepatic or epididymal adipose tissue, and the hepatic sirtuin 1 (SIRT1)/liver kinase B1 (LKB1)/AMPK and proliferator-activated receptor alpha (PPARα) signaling axis did not significantly change due to the HFHC diet or Dp. In summary, Dp effectively reduced triglyceride accumulation in vitro through the modulation of lipid metabolic gene expression. However, a dose of Dp administrated in mice simulating the total daily anthocyanin intake in humans had no effect on either metabolic alterations or histological abnormalities associated with HFHC diets.

Black Jacobin hummingbirds vocalize above the known hearing range of birds.

Hummingbirds are a fascinating group of birds, but some aspects of their biology are poorly understood, such as their highly diverse vocal behaviors. We show here that the predominant vocalization of black jacobins (Florisuga fusca), a hummingbird prevalent in the mountains of the Brazilian Atlantic Forest, consists of a triplet of syllables with high fundamental frequency (mean F0 ∼11.8 kHz), rapid frequency oscillations and strong ultrasonic harmonics and no detectable elements below ∼10 kHz. These are the most common vocalizations of these birds, and their frequency range is above the known hearing range of any bird species recorded to date, including hearing specialists such as owls. These observations suggest that black jacobins either have an atypically high frequency hearing range, or alternatively their primary vocalization has a yet unknown function unrelated to vocal communication. Black jacobin vocalizations challenge current notions about vocal communication in birds.

Diet switch and omega-3 hydroxy-fatty acids display differential hepatoprotective effects in an obesity/nonalcoholic fatty liver disease model in mice.

AIM: To study the effect of 18-hydroxy-eicosapentaenoic acid (18-HEPE) and 17-hydroxy-docosahexaenoic acid (17-HDHA) in a murine model of obesity/nonalcoholic fatty liver disease. METHODS: C57BL/6 mice were fed with standard chow diet (CD) or high-fat, fructose-enriched diet (HFD) for 16 wk. Then, three groups were treated for 14 d with either, diet switch (HFD for CD), 18-HEPE, or 17-HDHA. Weight and fasting glucose were recorded on a weekly basis. Insulin tolerance test was performed at the end of treatment. Histological analysis (HE and Masson's trichrome stain) and determination of serum insulin, glucagon, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide, adiponectin and resistin were carried out as well as liver proteins by western blot. RESULTS: Mice treated with hydroxy-fatty acids 18-HEPE and 17-HDHA displayed no weight loss or improved insulin sensitivity. However, these mice groups showed a significant amelioration on serum GLP-1, adiponectin and resistin levels. Also, a significant reduction on inflammatory infiltrate was observed at both portal and lobular zones. Furthermore, up-regulation of PPARα/γ protein levels was observed in liver tissue and it was associated with decreased levels of NF-κB also determined by western blot analysis. On the other hand, diet switch regimen resulted in a marked improvement in most parameters including: weight loss, increased insulin sensitivity, decreased steatosis, restored levels of insulin, glucagon, leptin, adiponectin and resistin. However, no significant changes were observed regarding inflammatory infiltrate in this last group. CONCLUSION: 18-HEPE and 17-HDHA differentially exert hepatoprotective effects through up-regulation of nuclear receptors PPARα/γ and amelioration of serum adipokines profile.

Pediatric Patient With Altered Mental Status and Hypoxemia: Case Report.

Childhood cases of myxedema coma are extremely rare. We report a case of a 5-year-old girl transferred to a tertiary care pediatric emergency department with hypoxemia and altered mental status and diagnosed with severe hypothyroidism and myxedema coma in the setting of acute influenza infection. Although it is rare, myxedema coma must remain in the differential diagnosis for altered mental status and organ dysfunction in the pediatric population.

Mujer Sana, Familia Fuerte: The Effects of a Culturally-Relevant, Community-Based, Promotores Program to Increase Cervical Cancer Screening among Latinas.

OBJECTIVE: Although cervical cancer can be prevented through screening and follow-up, Latinas' rate of Pap tests remains low due to knowledge gaps and cultural and attitudinal factors. METHODS: This study used a single-group pre-/post-test design to evaluate the effectiveness of Mujer Sana, Familia Fuerte (Healthy Woman, Strong Family), an intervention intended to improve Latinas' cervical cancer prevention knowledge, attitudes, self-efficacy to obtain a Pap test, and intention to get tested. The intervention is delivered through a single session by promotores de salud, who use a culturally competent, linguistically appropriate toolkit. A total of 5,211 Latinas participated in the study. RESULTS: The evaluation indicated that participants had increases in knowledge, positive attitudes, self-efficacy, and intention to test. CONCLUSION: Latinas have a low rate of cervical cancer screening but a high rate of cervical cancer, and Mujer Sana, Familia Fuerte shows promise as a public health practice for use with this population.

Ultrasonic vocalizations in golden hamsters (Mesocricetus auratus) reveal modest sex differences and nonlinear signals of sexual motivation.

Vocal signaling is one of many behaviors that animals perform during social interactions. Vocalizations produced by both sexes before mating can communicate sex, identity and condition of the caller. Adult golden hamsters produce ultrasonic vocalizations (USV) after intersexual contact. To determine whether these vocalizations are sexually dimorphic, we analyzed the vocal repertoire for sex differences in: 1) calling rates, 2) composition (structural complexity, call types and nonlinear phenomena) and 3) acoustic structure. In addition, we examined it for individual variation in the calls. The vocal repertoire was mainly composed of 1-note simple calls and at least half of them presented some degree of deterministic chaos. The prevalence of this nonlinear phenomenon was confirmed by low values of harmonic-to-noise ratio for most calls. We found modest sexual differences between repertoires. Males were more likely than females to produce tonal and less chaotic calls, as well as call types with frequency jumps. Multivariate analysis of the acoustic features of 1-note simple calls revealed significant sex differences in the second axis represented mostly by entropy and bandwidth parameters. Male calls showed lower entropy and inter-quartile bandwidth than female calls. Because the variation of acoustic structure within individuals was higher than among individuals, USV could not be reliably assigned to the correct individual. Interestingly, however, this high variability, augmented by the prevalence of chaos and frequency jumps, could be the result of increased vocal effort. Hamsters motivated to produce high calling rates also produced longer calls of broader bandwidth. Thus, the sex differences found could be the result of different sex preferences but also of a sex difference in calling motivation or condition. We suggest that variable and complex USV may have been selected to increase responsiveness of a potential mate by communicating sexual arousal and preventing habituation to the caller.

[Methylenetetrahydrofolate reductase polymorphisms as risk factors for myelomeningocele]. / Estudio de asociación de base familiar entre polimorfismos de MTHFR y mielomeningocele en Chile.

BACKGROUND: Mandatory fortification with folic acid (FA) was implemented in Chile in 2000. Thereafter, the rate of spina bifida decreased by 52 to 55%. Genetic abnormalities in folate metabolism may be involved in the etiology of spina bifida. AIM: To evaluate the association between myelomeningocele (MM) and c.A1298C and c.C677T polymorphisms within the coding gene for 5,10-methylenetetrahydrofolate reductase (MTHFR) in the Chilean population. MATERIAL AND METHODS: These polymorphisms were genotyped in 105 patients showing isolated MM, born after the onset of FA fortification, and in their parents. The transmission disequilibrium test (TDT) was performed to evaluate alterations in the transmission of both alleles and haplotypes MTHFR polymorphism. We also evaluated the presence of parent-origin-effect (POE) of alleles using the Clayton's extension of the TDT. RESULTS: TDT analysis showed no significant distortions in the transmission of alleles or haplotypes. Moreover, although the POE showed increased risk for maternally derived allele, this risk was not statistically significant. CONCLUSIONS: The studied variants in the MTHFR gene (c.C677T and c.A1298C) do not constitute risk factors for MM in this sample of Chilean patients and their parents.