Skin assessment in congenital untreated isolated GH deficiency.

PURPOSE: The separation between the inside and outside through the skin was fundamental for the evolution of prevertebrates, which grow through extrapituitary circuits, to vertebrates, which grow through the somatotrophic axis, namely pituitary growth hormone (GH). and circulating IGF1.Individuals with untreated isolated growth hormone (GH) deficiency (IGHD) due to a mutation in the GH-releasing hormone receptor (GHRH) gene, residing in Itabaianinha, Brazil, are vulnerable to skin cancer and have reduced sweating. However other aspects of their skin physiology are still unknown. Our objectives were to evaluate the number of skin cancers, skin aging, and functional aspects of the skin in this IGHD cohort. METHODS: Twenty-six IGHD individuals and 26 controls matched by age, sex, ethnicity, and occupation were submitted to a biochemical, dermatological and a functional skin assessment by the Multi Probe Adapter Cutometer® MPA 580. RESULTS: There was no difference in the number of skin cancers and in the degrees of photodamage between the groups. The melanin content in the forearm was similar between the groups but was lower in the buttocks (p = 0.005), as well as skin resistance (p < 0.0001) and elasticity (p = 0.003), lower in the IGHD. There was no difference in hydration and sebum content between the two groups. CONCLUSION: IGHD is apparently associated with a neutral profile in terms of skin cancer and photodamage, with similar melanin on the forearm and lower buttocks, lower skin resistance and elasticity, with hydration and sebum similar to controls.

Brain morphometry and estimation of aging brain in subjects with congenital untreated isolated GH deficiency.

PURPOSE: Individuals with isolated GH deficiency (IGHD) due to a mutation in the GHRH receptor gene have a normal life expectancy and above 50 years of age, similar total cognitive performance, with better attention and executive function than controls. Our objectives were to evaluate their brain morphometry and brain aging using MRI. METHODS: Thirteen IGHD and 14 controls matched by age, sex, and education, were enrolled. Quantitative volumetric data and cortical thickness were obtained by automatic segmentation using Freesurfer software. The volume of each brain region was normalized by the intracranial volume. The difference between the predicted brain age estimated by MRI using a trained neuronal network, and the chronological age, was obtained. p < 0.005 was considered significant and 0.005 < p < 0.05 as a suggestive evidence of difference. RESULTS: In IGHD, most absolute values of cortical thickness and regional brain volumes were similar to controls, but normalized volumes were greater in the white matter in the frontal pole and in the insula bilaterally, and in the gray matter, in the right insula and in left Caudate (p < 0.005 for all comparisons) We also noticed suggestive evidence of a larger volume in IGHD in left thalamus (p = 0.006), right thalamus (p = 0.025), right caudate (p = 0.046) and right putamen (p = 0.013). Predicted brain ages were similar between groups. CONCLUSION: IGHD is primarily associated with similar absolute brain measurements, and a set of larger normalized volumes, and does not appear to alter the process of brain aging.

Gender-Specific Effects on the Cardiorespiratory System and Neurotoxicity of Intermittent and Permanent Low-Level Lead Exposures.

Lead exposure is a significant health concern, ranking among the top 10 most harmful substances for humans. There are no safe levels of lead exposure, and it affects multiple body systems, especially the cardiovascular and neurological systems, leading to problems such as hypertension, heart disease, cognitive deficits, and developmental delays, particularly in children. Gender differences are a crucial factor, with women's reproductive systems being especially vulnerable, resulting in fertility issues, pregnancy complications, miscarriages, and premature births. The globalization of lead exposure presents new challenges in managing this issue. Therefore, understanding the gender-specific implications is essential for developing effective treatments and public health strategies to mitigate the impact of lead-related health problems. This study examined the effects of intermittent and permanent lead exposure on both male and female animals, assessing behaviours like anxiety, locomotor activity, and long-term memory, as well as molecular changes related to astrogliosis. Additionally, physiological and autonomic evaluations were performed, focusing on baro- and chemoreceptor reflexes. The study's findings revealed that permanent lead exposure has more severe health consequences, including hypertension, anxiety, and reactive astrogliosis, affecting both genders. However, males exhibit greater cognitive, behavioural, and respiratory changes, while females are more susceptible to chemoreflex hypersensitivity. In contrast, intermittent lead exposure leads to hypertension and reactive astrogliosis in both genders. Still, females are more vulnerable to cognitive impairment, increased respiratory frequency, and chemoreflex hypersensitivity, while males show more reactive astrocytes in the hippocampus. Overall, this research emphasizes the importance of not only investigating different types of lead exposure but also considering gender differences in toxicity when addressing this public health concern.

Cognitive performance during senescence in untreated congenital isolated GH deficiency.

Individuals with untreated isolated GH deficiency (IGHD) due to a mutation in the GHRH receptor gene from Itabaianinha Brazil have increased insulin sensitivity, normal life expectancy, and an extended health span, i.e. the period of life free from disabilities. We hypothesize that their prolonged health span is accompanied by a delayed cognitive decline in senescence. To test this hypothesis, we have administered the Literacy-Independent Cognitive Assessment (LICA) to 15 IGHD individuals aged over 50 years and 15 controls matched by age, sex, years of education, and percentage of illiteracy. All individuals were negative for HIV and syphilis serology, and there were no differences in serum levels of folate, vitamin B12 and TSH between the two groups, while free T4 was higher in the IGHD group. IGHD subjects had a higher total LICA score than controls, 215 (22.7) vs 204.2 (18.1), without reaching statistical significance. Scores of memory, visuoconstruction, language and calculation were similar between the two groups, with better attention (9.5 (1.4) vs 8.3 (1.1), P = 0.01) and executive function (38.3 (4.8) vs 35.1 (2.5), P = 0.03) scores in IGHD. MANCOVA revealed that group (but no age) had a significant effect on the LICA variables (partial eta squared of 0.455, power of 0.812, P = 0.02). This effect is verified on attention (partial eta squared 0.216, power of 0.749, P = 0.01) and executive function (partial eta squared 0.154, power of 0.570, P = 0.03. In conclusion, IGHD in senescence is associated with similar total cognitive performance but better attention and executive function than controls.

From Metagenomics to Ecogenomics: NGS-Based Approaches for Discovery of New Circular DNA Single-Stranded Viral Species.

Viruses comprise the most abundant genetic material in the biosphere; however, global viral genomic population (virome) has been largely underestimated. Recently, high-throughput sequencing (HTS) has provided a powerful tool for the detection of known viruses and the discovery of novel viral species from environmental and individual samples using metagenomics and ecogenomics approaches, respectively. Viruses with circular DNA single-stranded (ssDNA) genomes belonging to the begomovirus genera (family Geminiviridae) constitute the largest group of emerging plant viruses worldwide. The knowledge of begomoviruses viromes is mostly restricted to crop plant systems; nevertheless, it has been described that noncultivated plants specifically at the interface between wild and cultivated plants are important reservoirs leading to viral evolution and the emergence of new diseases. Here we present a protocol that allows the identification and isolation of known and novel begomoviruses species infecting cultivated and noncultivated plant species. The method consists of circular viral molecules enrichment by rolling circle amplification (RCA) from begomovirus-positive total plant DNA, followed by NGS-based metagenomic sequencing. Subsequently, metagenomic reads are processed for taxonomic classification using Viromescan software and a customized Geminiviridae family database, and begomovirus-related reads are used for contigs assembly and annotation using Spades software and Blastn algorithm, respectively. Then, the obtained begomovirus-related signatures are used as templates for specific primers design and implemented for PCR-based ecogenomic identification of individual samples harboring the corresponding viral species. Lastly, full-length begomovirus genomes are obtained by RCA-based amplification from total plant DNA of selected individual samples, cloning, and viral molecular identity corroborated by Sanger sequencing. Conclusively, the identification and isolation of a novel monopartite begomovirus species native to the New World (NW) named Gallium leaf deformation virus (GLDV) is shown.

Doxorubicin Dose-Dependent Impact on Physiological Balance-A Holistic Approach in a Rat Model.

Doxorubicin (DOX) is commonly used in several chemotherapies to treat various cancers, but it is known to cause cardiotoxicity and cardiac symptoms. Autonomic dysfunction is thought to contribute to the cardiotoxic effects of DOX, but the specific dose required to disrupt homeostatic processes is still unclear and is influenced by numerous factors. This study aimed to investigate how the DOX dosage affects autonomic function and physiological parameters, to elucidate the neurocardiac mechanisms underlying the observed cardiovascular side effects. Wistar rats were treated with DOX for four weeks and divided into three dosing groups: DOX8 (2 mg/kg/week), DOX16 (4 mg/kg/week), and DOX20 (5 mg/kg/week). A control group received NaCl 0.9% saline (1 mL/kg/week). In an acute experiment, we recorded blood pressure (BP), electrocardiogram, heart rate (HR), and respiratory rate (RF). Baroreflex gain and chemoreflex sensitivity were calculated, and cardiac tissue was analyzed with picrosirius histochemistry to measure collagen content. Our results showed that the LF/HF ratio, indicative of autonomic activity, was altered along with hypotension and bradycardia at a cumulative DOX dose threshold of 16 mg/kg. We observed a positive correlation between DOX dose and BP, HR, urinary norepinephrine, LF/HF ratio, and fibrotic heart area. Lower LF/HF ratios were associated with high DOX doses, reflecting drug-induced impairment of autonomic control of HR. This study provides valuable insights into the dose-dependent effects of DOX on physiological parameters and the development of cardiovascular dysfunction. These findings are critical, which is important for optimizing the management and therapeutic strategies for patients undergoing DOX-based chemotherapy.

A novel tomato spotted wilt virus isolate encoding a noncanonical NSm C118F substitution associated with Sw-5 tomato gene resistance breaking.

The nonstructural protein NSm of tomato spotted wilt virus (TSWV) has been identified as the avirulence determinant of the tomato single dominant Sw-5 resistance gene. Although Sw-5 effectiveness has been shown for most TSWV isolates, the emergence of resistance-breaking (RB) isolates has been observed. It is strongly associated with two point mutations (C118Y or T120N) in the NSm viral protein. TSWV-like symptoms were observed in tomato crop cultivars (+Sw-5) in the Baja California peninsula, Mexico, and molecular methods confirmed the presence of TSWV. Sequence analysis of the NSm 118-120 motif and three-dimensional protein modelling exhibited a noncanonical C118F substitution in seven isolates, suggesting that this substitution could emulate the C118Y-related RB phenotype. Furthermore, phylogenetic and molecular analysis of the full-length genome (TSWV-MX) revealed its reassortment-related evolution and confirmed that putative RB-related features are restricted to the NSm protein. Biological and mutational NSm 118 residue assays in tomato (+Sw-5) confirmed the RB nature of TSWV-MX isolate, and the F118 residue plays a critical role in the RB phenotype. The discovery of a novel TSWV-RB Mexican isolate with the presence of C118F substitution highlights a not previously described viral adaptation in the genus Orthotospovirus, and hence, the necessity of further crop monitoring to alert the establishment of novel RB isolates in cultivated tomatoes.

Differential Expression of miRNAs Involved in Response to Candidatus Liberibacter asiaticus Infection in Mexican Lime at Early and Late Stages of Huanglongbing Disease.

Huanglongbing (HLB) is one of the most destructive diseases threatening citriculture worldwide. This disease has been associated with α-proteobacteria species, namely Candidatus Liberibacter. Due to the unculturable nature of the causal agent, it has been difficult to mitigate the disease, and nowadays a cure is not available. MicroRNAs (miRNAs) are key regulators of gene expression, playing an essential role in abiotic and biotic stress in plants including antibacterial responses. However, knowledge derived from non-model systems including Candidatus Liberibacter asiaticus (CLas)-citrus pathosystem remains largely unknown. In this study, small RNA profiles from Mexican lime (Citrus aurantifolia) plants infected with CLas at asymptomatic and symptomatic stages were generated by sRNA-Seq, and miRNAs were obtained with ShortStack software. A total of 46 miRNAs, including 29 known miRNAs and 17 novel miRNAs, were identified in Mexican lime. Among them, six miRNAs were deregulated in the asymptomatic stage, highlighting the up regulation of two new miRNAs. Meanwhile, eight miRNAs were differentially expressed in the symptomatic stage of the disease. The target genes of miRNAs were related to protein modification, transcription factors, and enzyme-coding genes. Our results provide new insights into miRNA-mediated regulation in C. aurantifolia in response to CLas infection. This information will be useful to understand molecular mechanisms behind the defense and pathogenesis of HLB.

Intermittent Lead Exposure Induces Behavioral and Cardiovascular Alterations Associated with Neuroinflammation.

The nervous system is the primary target for lead exposure and the developing brain appears to be especially susceptible, namely the hippocampus. The mechanisms of lead neurotoxicity remain unclear, but microgliosis and astrogliosis are potential candidates, leading to an inflammatory cascade and interrupting the pathways involved in hippocampal functions. Moreover, these molecular changes can be impactful as they may contribute to the pathophysiology of behavioral deficits and cardiovascular complications observed in chronic lead exposure. Nevertheless, the health effects and the underlying influence mechanism of intermittent lead exposure in the nervous and cardiovascular systems are still vague. Thus, we used a rat model of intermittent lead exposure to determine the systemic effects of lead and on microglial and astroglial activation in the hippocampal dentate gyrus throughout time. In this study, the intermittent group was exposed to lead from the fetal period until 12 weeks of age, no exposure (tap water) until 20 weeks, and a second exposure from 20 to 28 weeks of age. A control group (without lead exposure) matched in age and sex was used. At 12, 20 and 28 weeks of age, both groups were submitted to a physiological and behavioral evaluation. Behavioral tests were performed for the assessment of anxiety-like behavior and locomotor activity (open-field test), and memory (novel object recognition test). In the physiological evaluation, in an acute experiment, blood pressure, electrocardiogram, and heart and respiratory rates were recorded, and autonomic reflexes were evaluated. The expression of GFAP, Iba-1, NeuN and Synaptophysin in the hippocampal dentate gyrus was assessed. Intermittent lead exposure induced microgliosis and astrogliosis in the hippocampus of rats and changes in behavioral and cardiovascular function. We identified increases in GFAP and Iba1 markers together with presynaptic dysfunction in the hippocampus, concomitant with behavioral changes. This type of exposure produced significant long-term memory dysfunction. Regarding physiological changes, hypertension, tachypnea, baroreceptor reflex impairment and increased chemoreceptor reflex sensitivity were observed. In conclusion, the present study demonstrated the potential of lead intermittent exposure inducing reactive astrogliosis and microgliosis, along with a presynaptic loss that was accompanied by alterations of homeostatic mechanisms. This suggests that chronic neuroinflammation promoted by intermittent lead exposure since fetal period may increase the susceptibility to adverse events in individuals with pre-existing cardiovascular disease and/or in the elderly.

Discriminative value of pulse wave velocity for arterial stiffness and cardiac injury in prediabetic patients / Valor discriminativo da velocidade da onda de pulso para rigidez arterial e lesão cardíaca em pacientes pré-diabéticos

Abstract Background Prediabetes (PD) is defined as impaired fasting glucose and/or impaired glucose tolerance (IGT) and may be associated with high risk of cardiovascular injury. It is recommended that PD patients be screened for signs of arterial stiffness and cardiovascular injury to reinforce therapeutic strategies. Objectives To identify pulse wave velocity values discriminative for arterial stiffness and cardiovascular injury in PD patients. Methods A cross-sectional study was conducted with PD (N=43) and normoglycemic (N=37) patients who underwent clinical evaluation, arterial stiffness assessment by carotid-femoral pulse wave velocity (cfPWV) using SphygmoCor, laboratory blood analysis, investigation of morphological and functional cardiac variables by transthoracic echocardiogram, and assessment of carotid intima-media-thickness (CIMT) by carotid ultrasonography. A statistical analysis was performed using SPSS software and values of p<0.05 were considered significant. Results A cfPWV cut-off value of 6.9 m/s was identified for IGT (Sensitivity [SE]: 74% and Specificity [SP]: 51%). Comparison of general data and risk factors between subsets with values above and below this cutoff value revealed higher rates of fasting glucose (p=0.02), obesity (p=0.03), dyslipidemia (p=0.004), early signs of left ventricle (p=0.017) and right ventricle (p=0.03) impaired diastolic function, and elevated CIMT in subjects with cfPWV ≥ 6.9m/s (p=0.04). Conclusions In PD patients, a cfPWV cutoff of 6.9 m/s was considered a discriminative value for arterial stiffness. These findings highlight the value of early investigation of cardiovascular injury and aggressive therapy strategies with good control of risk factors in PD.

Resumo Contexto O pré-diabetes (PD) é definido como glicemia de jejum alterada e/ou tolerância à glicose alterada (TGA) e pode estar associado a alto risco de lesão cardiovascular. Recomenda-se discriminar quais pacientes com PD podem apresentar sinais de rigidez arterial e lesão cardiovascular para reforçar as estratégias terapêuticas. Objetivos Identificar os valores discriminativos da velocidade de onda de pulso determinantes de rigidez arterial e lesão cardiovascular em pacientes com PD. Métodos Estudo transversal em pacientes com PD (N=43) e normoglicêmicos (N=37) submetidos a avaliação clínica, avaliação da rigidez arterial pela velocidade da onda de pulso carótido-femoral (cfPWV) utilizando SphygmoCor, análise laboratorial de sangue, investigação de alterações morfológicas e variáveis cardíacas funcionais por ecocardiograma transtorácico e avaliação da espessura íntima-média carotídea (EIMC) pela ultrassonografia da carótida. A análise estatística foi realizada no software SPSS, e valores de p<0,05 foram considerados significativos. Resultados Foi identificado um valor de corte cfPWV de 6,9 m/s para TGA (sensibilidade 74% e especificidade 51%). A comparação dos dados e fatores de risco entre valores acima e abaixo do valor de corte estabelecido revelou glicemia de jejum elevada (p=0,02), obesidade (p=0,03), dislipidemia (p=0,004), sinais precoces de função diastólica prejudicada do ventrículo esquerdo (p=0,017) e ventrículo direito (p=0,03) e maior EIMC em cfPWV ≥6,9m/s (p=0,04). Conclusões Em pacientes com PD, o cfPWV de 6,9 m/s foi considerado um valor discriminativo de rigidez arterial. Esses achados reforçam que a investigação precoce da lesão cardiovascular e uma estratégia com terapia agressiva são valiosas no controle dos fatores de risco na PD.

Discriminative value of pulse wave velocity for arterial stiffness and cardiac injury in prediabetic patients.

Background: Prediabetes (PD) is defined as impaired fasting glucose and/or impaired glucose tolerance (IGT) and may be associated with high risk of cardiovascular injury. It is recommended that PD patients be screened for signs of arterial stiffness and cardiovascular injury to reinforce therapeutic strategies. Objectives: To identify pulse wave velocity values discriminative for arterial stiffness and cardiovascular injury in PD patients. Methods: A cross-sectional study was conducted with PD (N=43) and normoglycemic (N=37) patients who underwent clinical evaluation, arterial stiffness assessment by carotid-femoral pulse wave velocity (cfPWV) using SphygmoCor, laboratory blood analysis, investigation of morphological and functional cardiac variables by transthoracic echocardiogram, and assessment of carotid intima-media-thickness (CIMT) by carotid ultrasonography. A statistical analysis was performed using SPSS software and values of p<0.05 were considered significant. Results: A cfPWV cut-off value of 6.9 m/s was identified for IGT (Sensitivity [SE]: 74% and Specificity [SP]: 51%). Comparison of general data and risk factors between subsets with values above and below this cutoff value revealed higher rates of fasting glucose (p=0.02), obesity (p=0.03), dyslipidemia (p=0.004), early signs of left ventricle (p=0.017) and right ventricle (p=0.03) impaired diastolic function, and elevated CIMT in subjects with cfPWV ≥ 6.9m/s (p=0.04). Conclusions: In PD patients, a cfPWV cutoff of 6.9 m/s was considered a discriminative value for arterial stiffness. These findings highlight the value of early investigation of cardiovascular injury and aggressive therapy strategies with good control of risk factors in PD.

Contexto: O pré-diabetes (PD) é definido como glicemia de jejum alterada e/ou tolerância à glicose alterada (TGA) e pode estar associado a alto risco de lesão cardiovascular. Recomenda-se discriminar quais pacientes com PD podem apresentar sinais de rigidez arterial e lesão cardiovascular para reforçar as estratégias terapêuticas. Objetivos: Identificar os valores discriminativos da velocidade de onda de pulso determinantes de rigidez arterial e lesão cardiovascular em pacientes com PD. Métodos: Estudo transversal em pacientes com PD (N=43) e normoglicêmicos (N=37) submetidos a avaliação clínica, avaliação da rigidez arterial pela velocidade da onda de pulso carótido-femoral (cfPWV) utilizando SphygmoCor, análise laboratorial de sangue, investigação de alterações morfológicas e variáveis cardíacas funcionais por ecocardiograma transtorácico e avaliação da espessura íntima-média carotídea (EIMC) pela ultrassonografia da carótida. A análise estatística foi realizada no software SPSS, e valores de p<0,05 foram considerados significativos. Resultados: Foi identificado um valor de corte cfPWV de 6,9 m/s para TGA (sensibilidade 74% e especificidade 51%). A comparação dos dados e fatores de risco entre valores acima e abaixo do valor de corte estabelecido revelou glicemia de jejum elevada (p=0,02), obesidade (p=0,03), dislipidemia (p=0,004), sinais precoces de função diastólica prejudicada do ventrículo esquerdo (p=0,017) e ventrículo direito (p=0,03) e maior EIMC em cfPWV ≥6,9m/s (p=0,04). Conclusões: Em pacientes com PD, o cfPWV de 6,9 m/s foi considerado um valor discriminativo de rigidez arterial. Esses achados reforçam que a investigação precoce da lesão cardiovascular e uma estratégia com terapia agressiva são valiosas no controle dos fatores de risco na PD.

From Molecular to Functional Effects of Different Environmental Lead Exposure Paradigms.

Lead is a heavy metal whose widespread use has resulted in environmental contamination and significant health problems, particularly if the exposure occurs during developmental stages. It is a cumulative toxicant that affects multiple systems of the body, including the cardiovascular and nervous systems. Chronic lead exposure has been defined as a cause of behavioral changes, inflammation, hypertension, and autonomic dysfunction. However, different environmental lead exposure paradigms can occur, and the different effects of these have not been described in a broad comparative study. In the present study, rats of both sexes were exposed to water containing lead acetate (0.2% w/v), from the fetal period until adulthood. Developmental Pb-exposed (DevPb) pups were exposed to lead until 12 weeks of age (n = 13); intermittent Pb exposure (IntPb) pups drank leaded water until 12 weeks of age, tap water until 20 weeks, and leaded water for a second time from 20 to 28 weeks of age (n = 14); and the permanent (PerPb) exposure group were exposed to lead until 28 weeks of age (n = 14). A control group (without exposure, Ctrl), matched in age and sex was used. After exposure protocols, at 28 weeks of age, behavioral tests were performed for assessment of anxiety (elevated plus maze test), locomotor activity (open-field test), and memory (novel object recognition test). Metabolic parameters were evaluated for 24 h, and the acute experiment was carried out. Blood pressure (BP), electrocardiogram, and heart (HR) and respiratory (RF) rates were recorded. Baroreflex gain, chemoreflex sensitivity, and sympathovagal balance were calculated. Immunohistochemistry protocol for NeuN, Syn, Iba-1, and GFAP staining was performed. All Pb-exposed groups showed hypertension, concomitant with a decrease in baroreflex gain and chemoreceptor hypersensitivity, without significant changes in HR and RF. Long-term memory impairment associated with reactive astrogliosis and microgliosis in the dentate gyrus of the hippocampus, indicating the presence of neuroinflammation, was also observed. However, these alterations seemed to reverse after lead abstinence for a certain period (DevPb) and were enhanced when a second exposure occurred (IntPb), along with a synaptic loss. These results suggest that the duration of Pb exposure is more relevant than the timing of exposure, since the PerPb group presented more pronounced effects and a significant increase in the LF and HF bands and anxiety levels. In summary, this is the first study with the characterization and comparison of physiological, autonomic, behavioral, and molecular changes caused by different low-level environmental lead exposures, from the fetal period to adulthood, where the duration of exposure was the main factor for stronger adverse effects. These kinds of studies are of immense importance, showing the importance of the surrounding environment in health from childhood until adulthood, leading to the creation of new policies for toxicant usage control.

Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss.

Given the increasing prevalence of diabetes and obesity worldwide, the deleterious effects of non-alcoholic fatty liver disease (NAFLD) are becoming a growing challenge for public health. NAFLD is the most common chronic liver disease in the Western world. NAFLD is closely associated with metabolic disorders, including central obesity, dyslipidaemia, hypertension, hyperglycaemia and persistent abnormalities of liver function tests.In general NAFLD is a common denominer for a broad spectrum of damage to the liver, which can be due to hepatocyte injury, inflammatory processes and fibrosis. This is normally seen on liver biopsy and can range from milder forms (steatosis) to the more severe forms (non-alcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis and liver failure). In these patients, advanced fibrosis is the major predictor of morbidity and liver-related mortality, and an accurate diagnosis of NASH and NAFLD is mandatory. Histologic evaluation with liver biopsy remains the gold standard to diagnose NAFLD. Diagnosis of NAFLD is defined as presence of hepatic steatosis, ballooning and lobular inflammation with or without fibrosis. Weight loss, dietary modification, and the treatment of underlying metabolic syndrome remain the mainstays of therapy once the diagnosis is established. Dietary recommendations and lifestyle interventions, weight loss, and the treatment of underlying metabolic syndrome remain the mainstays of therapy once the diagnosis is established with promising results but are difficult to maintain. Pioglitazone and vitamin E are recommended by guidelines in selected patients. This review gives an overview of NAFLD and its treatment options.

Comparison of two different biomaterials in the bone regeneration (15, 30 and 60 days) of critical defects in rats.

PURPOSE: To evaluate and compare two types of different scaffolds in critical bone defects in rats. METHODS: Seventy male Wistar rats (280 ± 20 grams) divided into three groups: control group (CG), untreated animals; biomaterial group 1 (BG1), animals that received the scaffold implanted hydroxyapatite (HA)/poly(lactic-co-glycolic) acid (PLGA); and biomaterial group 2 (BG2), animals that received the scaffolds HA/PLGA/Bleed. The critical bone defect was induced in the medial region of the skull calotte with the aid of an 8-mm-diameter trephine drill. The biomaterial was implanted in the form of 1.5 mm thick scaffolds, and samples were collected after 15, 30 and 60 days. Non-parametric Mann-Whitney test was used, with the significance level of 5% (p ≤ 0.05). RESULTS: Histology revealed morphological and structural differences of the neoformed tissue between the experimental groups. Collagen-1 (Col-1) findings are consistent with the histological ones, in which BG2 presented the highest amount of fibers in its tissue matrix in all evaluated periods. In contrast, the results of receptor activator of nuclear factor kappa-Β ligand (Rank-L) immunoexpression were higher in BG2 in the periods of 30 and 60 days, indicating an increase of the degradation of the biomaterial and the remodeling activity of the bone. CONCLUSIONS: The properties of the HA/PLGA/Bleed scaffold were superior when compared to the scaffold composed only by HA/PLGA.

Avaliação da função cardiovascular e qualidade de vida em pacientes com insuficiência cardíaca com e sem comportamento sedentário / Evaluation of cardiovascular function and quality of life in patients with heart failure with and without sedentary behavior

RESUMO: Fundamentos e objetivos: Apesar dos reconhecidos benefícios da prática de atividade física em pacientes com doença cardiovascular, acredita-se que pacientes com insuficiência cardíaca e fração de ejeção reduzida com comportamento não sedentário, mesmo que não pratiquem exercício físico regular, apresentem melhora da função cardiovascular e qualidade de vida em comparação a pacientes sedentários. Objetivo: comparar a capacidade funcional, função ventricular e quali-dade de vida de pacientes com insuficiência cardíaca sedentários e não sedentários. Métodos: Foram avaliados pacientes com Insuficiência Cardíaca e Fração de ejeção <50%, sendo compostos dois grupos, sedentários (n=45) e não sedentários (n=36), de acordo com o Questionário Internacional de Atividade Física. Os grupos foram submetidos à avaliação clínica e de qualidade de vida, teste de caminhada de Cooper, ecocardiograma e comparação pelo teste Qui-Quadrado para variáveis categóricas ou teste T de Student ou Mann-Whitney para variáveis contínuas. Nível de significância de 5%. Resultados: Os grupos foram homogêneos em relação às características basais e etiologia. Os pacientes do Grupo Não Sedentário apre-sentaram menos sintomas limitantes (p<0,01), menor necessidade de digitálicos (p=0,02), melhor fração de encurtamento ventricular (p=0,03) e menor aumento do volume indexado do átrio esquerdo (p=0,004). Não foram encontradas diferen-ças no teste de caminhada entre os grupos. Houve maior prejuízo do quesito capacidade funcional da qualidade de vida do grupo Sedentário. Conclusão: Considerando a limitação da amostra, pacientes com insuficiência cardíaca e comporta-mento não sedentário apresentam maior tolerabilidade ao exercício por apresentarem sintomas menos limitantes, melhor função ventricular e melhor qualidade de vida no quesito capacidade funcional quando comparados a pacientes sedentáriosRESUMOFundamentos e objetivos: Apesar dos reconhecidos benefícios da prática de atividade física em pacientes com doença cardiovascular, acredita-se que pacientes com insuficiência cardíaca e fração de ejeção reduzida com comportamento não sedentário, mesmo que não pratiquem exercício físico regular, apresentem melhora da função cardiovascular e qualidade de vida em comparação a pacientes sedentários. Objetivo: comparar a capacidade funcional, função ventricular e quali-dade de vida de pacientes com insuficiência cardíaca sedentários e não sedentários. Métodos: Foram avaliados pacientes com Insuficiência Cardíaca e Fração de ejeção <50%, sendo compostos dois grupos, sedentários (n=45) e não sedentários (n=36), de acordo com o Questionário Internacional de Atividade Física. Os grupos foram submetidos à avaliação clínica e de qualidade de vida, teste de caminhada de Cooper, ecocardiograma e comparação pelo teste Qui-Quadrado para variáveis categóricas ou teste T de Student ou Mann-Whitney para variáveis contínuas. Nível de significância de 5%. Resultados: Os grupos foram homogêneos em relação às características basais e etiologia. Os pacientes do Grupo Não Sedentário apre-sentaram menos sintomas limitantes (p<0,01), menor necessidade de digitálicos (p=0,02), melhor fração de encurtamento ventricular (p=0,03) e menor aumento do volume indexado do átrio esquerdo (p=0,004). Não foram encontradas diferen-ças no teste de caminhada entre os grupos. Houve maior prejuízo do quesito capacidade funcional da qualidade de vida do grupo Sedentário. Conclusão: Considerando a limitação da amostra, pacientes com insuficiência cardíaca e comporta-mento não sedentário apresentam maior tolerabilidade ao exercício por apresentarem sintomas menos limitantes, melhor função ventricular e melhor qualidade de vida no quesito capacidade funcional quando comparados a pacientes sedentários. (AU)

ABSTRACT: Purpose: Despite the recognized benefits of practicing physical activity in patients with cardiovascular disease, it is believed that patients with heart failure and reduced ejection fraction with non-sedentary behavior may present an improvement in cardiovascular function and quality of life compared to sedentary patients, even if they do not practice regular physical ex-ercise. The aim of the present study was to compare functional capacity, systolic and diastolic cardiac function and quality of life of sedentary and non-sedentary patients with heart failure and reduced ejection fraction. Methods: Patients with heart failure and ejection fraction below 50% were divided into two groups, Sedentary (n = 45) and Non-Sedentary (n = 36), using the IPAQ questionnaire. These two groups were evaluated with clinical evaluation, quality of life SF-36 questionnaire, Cooper walking test and transthoracic echocardiography. They were compared by Chi-Square test for categorical variables or Test T or Man-Whitney for continuous variables; the level of significance adopted in the statistical analysis was 5%. Results: The groups were homogeneous in relation to the baseline characteristics and etiology. The Non-Sedentary Group had fewer patients with severe symptoms (p <0.01), less necessity of digitalis (p = 0.02) and better left ventricle fractional shorten-ing (p = 0.03). There was no apparent difference in the walk-test data between groups. Additionally, there was a greater impairment in the functional capacity of the SF-36 Questionnaire in the Sedentary Group. Conclusion: Considering the sample limitation, patients with heart failure and non-sedentary behavior have greater tolerability to exercise because they have fewer limiting symptoms and better quality of life in the functional capacity domain than sedentary patients.

Sun-induced production of vitamin D3 throughout 1 year in tropical and subtropical regions: relationship with latitude, cloudiness, UV-B exposure and solar zenith angle.

This study evaluated the differences in vitamin D3 synthesis in two different latitudes throughout 1 year using an in vitro model, which simulates cutaneous vitamin D photoproduction. Borosilicate ampoules containing 7-dehydrocholesterol (7-DHC) were exposed to sunlight hourly throughout the daylight hours, 1 day per month for a year, in Fortaleza (latitude 03° 43' 01" S-LAT3° S) and Sao Paulo (latitude 23° 32' 53" S-LAT23° S). Later, vitamin D3 and photoisomers of 7-DHC (tachysterol and lumisterol) were measured by a high-performance liquid chromatography system (HPLC). Vitamin D synthesis weighted UV radiation (UVBVitD) and solar zenith angle (SZA) were calculated during the same periods for both latitudes. Vitamin D3 synthesis occurred throughout the year in both locations, as expected in latitudes lower than 35°. Median of photoconversion to vitamin D3 through the year was higher in LAT3°S [median (IQR): LAT 3°S 4.1% (6.0); LAT 23°S 2.9% (4.5); p value = 0.020]. Vitamin D3 production strongly correlated with UV-B (LAT3° S, r = 0.917; p < 0.0001 and at LAT23° S, r = 0.879; p < 0.0001) and SZA (LAT3° S, r = - 0.924; p < 0.0001 and in LAT23°S, r = - 0.808; p < 0.0001). Vitamin D3 production starts later in LAT23° S, especially in winter. Lowest percentages were observed in June in both cities, although, compared to LAT3° S, in LAT 23° S the conversion was over 50% lower in the winter period. Cloudiness impaired photoproduction of Vitamin D3 even in summer months in both latitudes. Our results provide data to help guide medical recommendations for sensible sun exposure to promote the cutaneous production of vitamin D3 at different latitudes, seasonality, time of day and cloudiness status in Brazil.

Emotional Resilience and Bariatric Surgical Teams: a Priority in the Pandemic.

The infection control measures implemented as a result of COVID-19 led to a postponement of bariatric surgical procedures across many countries worldwide. Many bariatric surgical teams were in essence left without a profession, with many redeployed to other areas of clinical care and were not able to provide the levels of patient support given before COVID-19. As the pandemic continues, some restrictions have been lifted, with staff adjusting to new ways of working, incorporating challenging working conditions and dealing with continuing levels of stress. This article explores the concept of emotional labour, defined as 'inducing or suppressing feelings in order to perform one's work', and its application to multidisciplinary teams working within bariatric surgery, to offer insight into the mental health issues that may be affecting healthcare professionals working in this discipline.

Comparison of two different biomaterials in the bone regeneration (15, 30 and 60 days) of critical defects in rats

ABSTRACT Purpose To evaluate and compare two types of different scaffolds in critical bone defects in rats. Methods Seventy male Wistar rats (280 ± 20 grams) divided into three groups: control group (CG), untreated animals; biomaterial group 1 (BG1), animals that received the scaffold implanted hydroxyapatite (HA)/poly(lactic-co-glycolic) acid (PLGA); and biomaterial group 2 (BG2), animals that received the scaffolds HA/PLGA/Bleed. The critical bone defect was induced in the medial region of the skull calotte with the aid of an 8-mm-diameter trephine drill. The biomaterial was implanted in the form of 1.5 mm thick scaffolds, and samples were collected after 15, 30 and 60 days. Non-parametric Mann-Whitney test was used, with the significance level of 5% (p ≤ 0.05). Results Histology revealed morphological and structural differences of the neoformed tissue between the experimental groups. Collagen-1 (Col-1) findings are consistent with the histological ones, in which BG2 presented the highest amount of fibers in its tissue matrix in all evaluated periods. In contrast, the results of receptor activator of nuclear factor kappa-Β ligand (Rank-L) immunoexpression were higher in BG2 in the periods of 30 and 60 days, indicating an increase of the degradation of the biomaterial and the remodeling activity of the bone. Conclusions The properties of the HA/PLGA/Bleed scaffold were superior when compared to the scaffold composed only by HA/PLGA.

Gene Expression Profile of Mexican Lime (Citrus aurantifolia) Trees in Response to Huanglongbing Disease caused by Candidatus Liberibacter asiaticus.

Nowadays, Huanglongbing (HLB) disease, associated with Candidatus Liberibacter asiaticus (CLas), seriously affects citriculture worldwide, and no cure is currently available. Transcriptomic analysis of host-pathogen interaction is the first step to understand the molecular landscape of a disease. Previous works have reported the transcriptome profiling in response to HLB in different susceptible citrus species; however, similar studies in tolerant citrus species, including Mexican lime, are limited. In this work, we have obtained an RNA-seq-based differential expression profile of Mexican lime plants challenged against CLas infection, at both asymptomatic and symptomatic stages. Typical HLB-responsive differentially expressed genes (DEGs) are involved in photosynthesis, secondary metabolism, and phytohormone homeostasis. Enrichment of DEGs associated with biotic response showed that genes related to cell wall, secondary metabolism, transcription factors, signaling, and redox reactions could play a role in the tolerance of Mexican lime against CLas infection. Interestingly, despite some concordance observed between transcriptional responses of different tolerant citrus species, a subset of DEGs appeared to be species-specific. Our data highlights the importance of studying the host response during HLB disease using as model tolerant citrus species, in order to design new and opportune diagnostic and management methods.

Therapeutic effects of IkB kinase inhibitor during systemic inflammation.

Animal models of inflammatory diseases support the idea that nuclear factor κB (NF-κB) activation plays a pathophysiological role and is widely implicated in multiple organ dysfunction (MOD). Indeed, the inhibition of the IκB kinase (IKK) complex, involved in the NF-κB pathway, can represent a promising approach to prevent MOD. The present work employed a rat model of systemic inflammation to investigate the preventive effects of Inhibitor of IKK complex (IKK16). In male Wistar rats, systemic inflammation was induced by a tail vein injection of lipopolysaccharides (LPS challenge; 12 mg/kg). Treatment with IKK16 (1 mg/kg body weight) was administered, by tail vein, 15 min post-LPS. Age- and sex-matched healthy rats and LPS rats without treatment were used as controls. At 24 h post-IKK16 treatment, serum enzyme levels indicative of liver, kidney, pancreas and muscle function were evaluated by biochemical analysis, and RT-PCR technique was used to analyze gene expression of pro-inflammatory cytokines. Hemodynamic parameters were also considered to assess the LPS-induced inflammation. IKK16 treatment yielded a strong therapeutic effect in preventing LPS-induced elevation of serological enzyme levels, attenuating hepatic, renal, pancreatic and muscular dysfunction after LPS challenge. Moreover, as expected, LPS promoted a significantly overexpression of TNF-α, IL-6 and IL-1ß in the heart, kidney, and liver; which was diminished by IKK16 treatment. The present study provides convincing evidence that selective inhibition of the IκB kinase complex through the action of IKK16, plays a protective role against LPS-induced multiple organ dysfunction by reducing the acute inflammatory response induced by endotoxin exposure.