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PURPOSE. This article evaluates the comparability of the telephone and in-person Structured Clinical Interview for DSM-IV (SCID) interviews in assessing patients with social anxiety disorder (SAD) as an independent anxiety diagnosis. DESIGN AND METHODS. One hundred subjects were randomly selected and interviewed with the SCID, once by telephone and once in person (1-3 months later). FINDINGS. The prevalence of SAD assessed with the telephone interviews was 56%, whereas the in-person prevalence was 52%, with no statistically significant difference. The test-retest kappa for the 200 interviews was .84, indication of excellent agreement. PRACTICE IMPLICATIONS. These findings, along with the existing evidence of their validity, should encourage the use of SCID by telephone for SAD diagnostic interviews. [ABSTRACT FROM AUTHOR]

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Lippia origanoides Kunth (LO, Verbenaceae), commonly known in Brazil as salva-de-marajó, is an aromatic plant native to the Americas. Quilombola women from Oriximiná (Pará State, Brazil) use decoctions and decoction vapors of LO aerial parts orally or in sitz baths to alleviate symptoms of dysmenorrhea. This study aimed to evaluate LO decoctions and essential oils through a chemo-qualitative approach. Aerial parts of LO were collected from two individuals, and other two commercial samples were acquired from a public market. Aqueous extract of each sample was obtained by decoction and spray drying. The spray-dried decoctions were chemically characterized using UPLC-APCI(-)-IT-MS 2 and cluster heatmap analysis to discern compositional patterns. Essential oils were obtained through hydrodistillation and analyzed using GC-MS and GC-FID. In total, 12 compounds were tentatively identified from LO decoctions. Their product ion spectra were characteristic of flavonoid aglycones (5) and glycosides (4), and phenylpropanoids, including two stilbene glycosides and one hydroxycinnamic acid glycoside. Variations were noted in the chemical fingerprints of the decoctions, but the flavonoid glycosides orientin, isoorientin, and vitexin emerged as potential markers for the species. The essential oils of the samples contained high amounts of oxygenated monoterpenoids, with a predominance of the p-menthanes carvacrol (up to 61.9 %) and/or thymol (up to 17.0 %), and p-cymene (up to 24.9 %). This study was the first to explore the chemical composition of decoctions derived from LO, highlighting the species as an untapped source of phenolic glycosides, an aspect that has received limited discussion thus far., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

We calculate the second-order moments, the Robertson-Schrödinger uncertainty product, and the Mandel factor for various superpositions of coherent phase states with opposite arguments, comparing the results with similar superpositions of the usual (Klauder-Glauber-Sudarshan) coherent states. We discover that the coordinate variance in the analog of even coherent states can show the most strong squeezing effect, close to the maximal possible squeezing for the given mean photon number. On the other hand, the Robertson-Schrödinger (RS) uncertainty product in superpositions of coherent phase states increases much slower (as function of the mean photon number) than in superpositions of the usual coherent states. A nontrivial behavior of the Mandel factor for small mean photon numbers is discovered in superpositions with unequal weights of two components. An exceptional nature of the even and odd superpositions is demonstrated.

The humanization of camelid-derived variable domain heavy chain antibodies (VHHs) poses challenges including immunogenicity, stability, and potential reduction of affinity. Critical to this process are complementarity-determining regions (CDRs), Vernier and Hallmark residues, shaping the three-dimensional fold and influencing VHH structure and function. Additionally, the presence of non-canonical disulfide bonds further contributes to conformational stability and antigen binding. In this study, we systematically humanized two camelid-derived VHHs targeting the natural cytotoxicity receptor NKp30. Key structural positions in Vernier and Hallmark regions were exchanged with residues from the most similar human germline sequences. The resulting variants were characterized for binding affinities, yield, and purity. Structural binding modes were elucidated through crystal structure determination and AlphaFold2 predictions, providing insights into differences in binding affinity. Comparative structural and molecular dynamics characterizations of selected variants were performed to rationalize their functional properties and elucidate the role of specific sequence motifs in antigen binding. Furthermore, systematic analyses of next-generation sequencing (NGS) and Protein Data Bank (PDB) data was conducted, shedding light on the functional significance of Hallmark motifs and non-canonical disulfide bonds in VHHs in general. Overall, this study provides valuable insights into the structural determinants governing the functional properties of VHHs, offering a roadmap for their rational design, humanization, and optimization for therapeutic applications., (© 2024 The Author(s). Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)

We report a novel cause of partial lipodystrophy associated with early B cell factor 2 ( EBF2 ) nonsense variant ( EBF2 8:26033143 C>A, c.493G>T, p.E165X) in a patient with an atypical form of partial lipodystrophy. The patient presented with progressive adipose tissue loss and metabolic deterioration at pre-pubertal age. In vitro and in vivo disease modeling demonstrates that the EBF2 variant impairs adipogenesis, causing excess accumulation of undifferentiated CD34 + cells, extracellular matrix proteins, and inflammatory myeloid cells in subcutaneous adipose tissues. Thus, this EBF2 p.E165X variant disrupts adipose tissue structure and function, leading to the development of partial lipodystrophy syndrome.

Background: There is a lack of information on the clinical and molecular presentation of familial partial lipodystrophy (FPLD), a rare genetic disorder characterized by partial subcutaneous fat loss., Objective: This study aimed to provide a comprehensive assessment of the clinical, metabolic, and genetic features of FPLD in the Brazilian population., Methods: In a multicenter cross-sectional investigation we evaluated patients with FPLD across five Brazilian reference centers for lipodystrophies. Diagnosis of FPLD was made by clinical evaluation and genetic confirmation. Data on genetic, clinical, and metabolic characteristics were captured. Statistical analysis involved the utilization of the Kruskal-Wallis test to identify differences., Results: The study included 106 patients with genetic confirmation of FPLD. The mean age was 44 ± 15 years, and they were predominantly female (78.3%). LMNA pathogenic variants were identified in 85.8% of patients, PPARG in 10.4%, PLIN1 in 2.8%, and MFN2 in 0.9%. Diabetes mellitus (DM) was highly prevalent (57.5%), affecting 54 females (50.9%). Median triglycerides levels were 199 mg/dL (54-2724 mg/dL), severe hypertriglyceridemia (≥ 500 mg/dL) was found in 34.9% and pancreatitis in 8.5%. Metabolic-associated fatty liver disease (MAFLD) was observed in 56.6%, and cardiovascular disease in 10.4%. The overall mortality rate was 3.8%, due to cardiovascular events., Conclusion: This study presents an extensive cohort of Brazilian patients with FPLD, predominantly DM with several multisystem complications. A comprehensive characterization of lipodystrophy syndromes is crucial for effective patient management and care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AS declared a shared affiliation with the authors NG, FP at the time of the review., (Copyright © 2024 Guidorizzi, Valerio, Viola, Veras, Fernandes, Lima, Flor, Araújo, Gonçalves Muniz, Moreira, De Paula, Zajdenverg, Dantas, Godoy-Matos, Montenegro Júnior and Foss-Freitas.)

The last decade observed rapid progress in soft electronics. Yet, the ultimate desired goal for many research fields is to fabricate fully integrated soft-matter electronics with sensors, interconnects, and batteries, at the ease of pushing a print button. In this work, an important step is taken toward this by demonstrating an ultra-stretchable thin-film Silver-Gallium (Ag-Ga) battery with an unprecedented combination of areal capacity and mechanical strain tolerance. The Biphasic Gallium-Carbon anode electrode demonstrates a record-breaking areal capacity of 78.7 mAh cm -2 , and an exceptional stretchability of 170%, showing clear progress over state-of-the-art. The exceptional theoretical capacity of gallium, along with its natural liquid phase self-healing, and its dendrite-free operation permits excellent electromechanical cycling. All composites of the battery including liquid-metal-based current collectors, and electrodes are sinter-free and digitally printable at room temperature, enabling the use of a wide range of substrates, including heat-sensitive polymer films. Consequently, it is demonstrated for the first time multi-layer, and multi-material digital printing of complex battery-on-the-board stretchable devices that integrate printed sensor, multiple cells of printed battery, highly conductive interconnects, and silicone chips, and demonstrate a tailor-made patch for body-worn electrophysiological monitoring., (© 2024 The Authors. Small published by Wiley‐VCH GmbH.)

Objective  The Body Image Disturbance Questionnaire for Scoliosis (BIDQ-S) for scoliosis derives from the Body Image Disturbance Questionnaire (BIDQ) with specific adaptation for scoliosis patients. Despite its significance and applicability, this instrument has never been translated into Brazilian Portuguese. The current study aimed to translate, transculturally adapt, and validate the BIDQ-S into Brazilian Portuguese. Methods  BIDQ-S was translated and culturally adapted into Brazilian Portuguese using the American Association of Orthopedic Surgeons (AAOS) criteria. The questionnaire validation relied on internal consistency and comparison with the Cobb angle, Pediatric Quality of Life Inventory (PedsQL), and Scoliosis Research Society (SRS-22). The Brazilian version (BR-)BIDQ-S validation occurred in a sample of 35 adolescents with scoliosis waiting for specialized treatment. Results  Internal consistency of the BR-BIDQ-S was 0.899 according to the Cronbach's index (i.e., virtually perfect). Although BR-BIDQ-S did not correlate with the Cobb angle, it presented correlations with the Physical, Emotional, and Social domains from the PedsQL and the Function/Activity domain from the SRS-22. Conclusion  BR-BIDQ-S was reliable in evaluating the body image of adolescents with scoliosis, presenting an internal consistency of 0,899 (virtually perfect). Moreover, similar to the original instrument, it correlated with PedsQL and SRS-22., Competing Interests: Conflitos de Interesse Os autores declaram não haver conflitos de interesse., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ( https://creativecommons.org/licenses/by/4.0/ ).)

Objective: Glucagon-like peptide 1 receptor agonists (GLP-1RA) are widely used for the management of diabetes mellitus (DM), but their efficacy in familial partial lipodystrophy (FPLD) is unknown. In this retrospective study, we evaluated the effect of GLP-1RA in patients with FPLD., Research Design and Methods: We analyzed data, reported with SDs, from 14 patients with FPLD (aged 58 ± 12 years; 76.47% female) and 14 patients with type 2 DM (aged 58 ± 13 years; 71% female) before and 6 months after starting GLP-1RA., Results: We observed reduction in weight (95 ± 23 to 91 ± 22 kg; P = 0.002), BMI (33 ± 6 to 31 ± 6 kg/m2; P = 0.001), HbA1c (8.2% ± 1.4% to 7.7% ± 1.4%; P = 0.02), and fasting glucose (186 ± 64 to 166 ± 53 mg/dL; P = 0.04) in patients with FPLD. The change in triglycerides after treatment was greater in the FPLD group compared with the DM group (P = 0.02). We noted acute pancreatitis in two case subjects with FPLD with longer therapy., Conclusions: Our study demonstrates the relative safety and effectiveness of GLP-1RA in patients with FPLD., (© 2024 by the American Diabetes Association.)

Context: Lipodystrophy syndromes are a heterogeneous group of rare genetic or acquired disorders characterized by generalized or partial loss of adipose tissue. LMNA-related lipodystrophy syndromes are classified based on the severity and distribution of adipose tissue loss., Objective: We aimed to annotate all clinical and metabolic features of patients with lipodystrophy syndromes carrying pathogenic LMNA variants and assess potential genotype-phenotype relationships., Methods: We retrospectively reviewed and analyzed all our cases (n = 115) and all published cases (n = 379) curated from 94 studies in the literature., Results: The study included 494 patients. The most common variants in our study, R482Q and R482W, were associated with similar metabolic characteristics and complications though those with the R482W variant were younger (aged 33 [24] years vs 44 [25] years; P < .001), had an earlier diabetes diagnosis (aged 27 [18] vs 40 [17] years; P < .001) and had lower body mass index levels (24 [5] vs 25 [4]; P = .037). Dyslipidemia was the earliest biochemical evidence described in 83% of all patients at a median age of 26 (10) years, while diabetes was reported in 61% of cases. Among 39 patients with an episode of acute pancreatitis, the median age at acute pancreatitis diagnosis was 20 (17) years. Patients who were reported to have diabetes had 3.2 times, while those with hypertriglyceridemia had 12.0 times, the odds of having pancreatitis compared to those who did not., Conclusion: This study reports the largest number of patients with LMNA-related lipodystrophy syndromes to date. Our report helps to quantify the prevalence of the known and rare complications associated with different phenotypes and serves as a comprehensive catalog of all known cases., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The receptor tyrosine kinase MET is activated by hepatocyte growth factor binding, followed by phosphorylation of the intracellular kinase domain (KD) mainly within the activation loop (A-loop) on Y1234 and Y1235. Dysregulation of MET can lead to both tumor growth and metastatic progression of cancer cells. Tepotinib is a highly selective, potent type Ib MET inhibitor and approved for treatment of non-small cell lung cancer harboring METex14 skipping alterations. Tepotinib binds to the ATP site of unphosphorylated MET with critical π-stacking contacts to Y1230 of the A-loop, resulting in a high residence time. In our study, we combined protein crystallography, biophysical methods (surface plasmon resonance, differential scanning fluorimetry), and mass spectrometry to clarify the impacts of A-loop conformation on tepotinib binding using different recombinant MET KD protein variants. We solved the first crystal structures of MET mutants Y1235D, Y1234E/1235E, and F1200I in complex with tepotinib. Our biophysical and structural data indicated a linkage between reduced residence times for tepotinib and modulation of A-loop conformation either by mutation (Y1235D), by affecting the overall Y1234/Y1235 phosphorylation status (L1195V and F1200I) or by disturbing critical π-stacking interactions with tepotinib (Y1230C). We corroborated these data with target engagement studies by fluorescence cross-correlation spectroscopy using KD constructs in cell lysates or full-length receptors from solubilized cellular membranes as WT or activated mutants (Y1235D and Y1234E/1235E). Collectively, our results provide further insight into the MET A-loop structural determinants that affect the binding of the selective inhibitor tepotinib., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of the article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Modern drug discovery relies on combinatorial screening campaigns to find drug molecules targeting specific disease-associated proteins. The success of such campaigns often relies on functional and structural information of the selected therapeutic target, only achievable once its purification is mastered. With the aim of bypassing the protein purification process to gain insights on the druggability, ligand binding, and/or characterization of protein-protein interactions, herein, we describe the Extract2Chip method. This approach builds on the immobilization of site-specific biotinylated proteins of interest, directly from cellular extracts, on avidin-coated sensor chips to allow for the characterization of molecular interactions via surface plasmon resonance (SPR). The developed method was initially validated using Cyclophilin D (CypD) and subsequently applied to other drug discovery projects in which the targets of interest were difficult to express, purify, and crystallize. Extract2Chip was successfully applied to the characterization of Yes-associated protein (YAP): Transcriptional enhancer factor TEF (TEAD1) protein-protein interaction inhibitors, in the validation of a ternary complex assembly composed of Dyskerin pseudouridine synthase 1 (DKC1) and RuvBL1/RuvBL2, and in the establishment of a fast-screening platform to select the most suitable NUAK family SNF1-like kinase 2 (NUAK2) surrogate for binding and structural studies. The described method paves the way for a potential revival of the many drug discovery campaigns that have failed to deliver due to the lack of suitable and sufficient protein supply.

Menthofuran is a monoterpene present in various essential oils derived from species from Mentha genus, and in Brazil, those species are widely used in treating gastrointestinal and respiratory disorders. Considering the wide pharmacological potential of monoterpenes, including their antioxidant activity, this study aimed to evaluate menthofuran-gastroprotective activity, as well as the involvement of antioxidant mechanisms in this effect. The acute toxicity was evaluated according to the fixed dose method. The antiulcerogenic activity was investigated by using experimental models of gastric ulcers induced by ethanol, indomethacin, and ischemia/reperfusion in rats. The antisecretory gastric activity, the catalase activity, and the gastric wall mucus were determined in pylorus ligated rats. Gastric wall nonprotein sulfhydryl (NPSH) group content, myeloperoxidase (MPO) activity, and malondialdehyde (MDA) content were evaluated in ethanol-induced the gastric ulcer model. Menthofuran (2 g/kg) presented low acute toxicity and showed gastroprotective activity against ethanol-, indomethacin-, and ischemia/reperfusion-induced ulcers. Moreover, menthofuran presented antisecretory activity, reduced the total acidity, and increased pH of gastric secretion. On the other hand, a decrease in mucus content of gastric wall without alteration of gastric juice volume and catalase activity was observed. Interestingly, menthofuran increased NPSH levels and reduced MDA levels and MPO activity. Gastroprotective effects of menthofuran appear to be mediated, at least in part, by the NOS pathway, endogenous prostaglandins, reduced gastric juice acidity, increased concentration of the NPSH groups, and reduced lipidic peroxidation. These findings support the menthofuran as an effective gastroprotective agent, as well as the marked participation of antioxidant mechanisms in this response., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2023 Naira Moura Alves et al.)

Obstructive Sleep Apnea (OSA) corresponds to episodes of complete or partial upper airway obstruction during sleep. The gold standard for diagnosing OSA is polysomnography; however, metabolomics is an innovative and highly sensitive method that seeks to identify and quantify small molecules in biological systems. Identify the metabolites most frequently associated with obstructive sleep apnea in adults. The search for articles was conducted between October 2020 and August 2021, in electronic databases, such as MEDLINE/PubMed, Scielo, Embase, and Cochrane, through the combination of descriptors: obstructive sleep apnea, metabolomic, adult. This systematic review included all cross-sectional studies published, including human patients aged 18 years or older, of both genders who underwent type I or II polysomnography and metabolomics study. The search strategy selected 3697 surveys, and 4 of them were selected to be a part of this systematic review. Based on the analyzed surveys, it was found that all of them were able to diagnose OSA, reaching a sensitivity of 75-97%, and specificity that ranged from 72 to 100%; besides differentiating patients with OSA (severe, moderate, and mild) from simple snorers with a mean sensitivity of 77.2% and specificity of 66.25%. These findings suggest that, in addition to being used as a screening and diagnostic strategy for OSA, metabolomics has the potential to be used for severity stratification and to monitor the disease's progression., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Japanese Society of Sleep Research 2023, corrected publication 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objectives: to construct statements of nursing diagnoses for the clinical practice of rehabilitation of people with spinal cord injury using the International Classification for Nursing Practice (ICNP®) and Orem's theory of self-care., Methods: methodological study developed in four steps: identification of relevant terms to clinical nursing practice in the rehabilitation of people with spinal cord injury; mapping of selected terms with ICNP® terms; construction of nursing diagnoses statements; mapping of statements constructed with pre-coordinated concepts of the ICNP®., Results: 241 statements of nursing diagnoses were constructed and categorized according to the self-care requisites of the theory. The most prevalent statements were those related to universal requisites, followed by developmental requisites and health deviation requisites., Conclusions: the constructed nursing diagnoses reflect the complexity of phenomena evidenced in the clinical practice of rehabilitation, allowing a systematic and comprehensive care to the person with spinal cord injury.

Objectives: The present study aimed to identify associations between extremes in body weight status (underweight and excess body weight) before a COVID-19 diagnosis and clinical outcomes in patients infected with SARS coronavirus type 2., Methods: A multicenter cohort study was conducted in eight different states in northeastern Brazil. Demographic, clinical (previous diagnosis of comorbidities), and anthropometric (self-reported weight and height) data about individuals who tested positive for COVID-19 were collected. Outcomes included hospitalization, mechanical ventilation, and death. Multivariable logistic regression models, adjusted based on age, sex and previous comorbidities, were used to assess the effects of extremes in body weight status on clinical outcomes., Results: A total of 1308 individuals were assessed (33.6% were elderly individuals). The univariable analyses showed that only hospitalization was more often observed among underweight (3.2% versus 1.2%) and overweight (68.1% versus 63.3%) individuals. In turn, cardiovascular diseases were more often observed in all clinical outcomes (hospitalization: 19.7% versus 4.8%; mechanical ventilation: 19.9% versus 13.5%; death: 21.8% versus 14.1%). Based on the multivariable analysis, body weight status was not associated with risk of hospitalization (underweight: odds ratio [OR]: 1.10; 95% confidence interval [CI] 95%, 0.50-2.41 and excess body weight: OR: 0.81; 95 CI, 0.57-1.14), mechanical ventilation (underweight: OR: 0.92; 95% CI, 0.52-1.62 and excess weight: OR: 0.90; 95% CI, 0.67-1.19), and death (underweight: OR: 0.61; 95% CI, 0.31-1.20 and excess body weight: OR 0.88; 95% CI, 0.63-1.23)., Conclusions: Being underweight and excess body weight were not independently associated with clinical outcomes in patients with COVID-19 in the herein analyzed cohort. This finding indicates that the association between these variables may be confounded by both age and comorbidities., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To present a reflection on the importance of logical thinking for clinical nursing care., Method: Reflection paper., Reflection: The exercise of an effective clinical care brings with it the need for logical thinking and adequate reasoning for safe and effective nursing practices. Therefore, training based on philosophical principles that encourage the increase of logical and critical thinking is considered unquestionable, ensuring professionals the systematization of assistance with the application of the nursing process based on scientific understanding and strong arguments supported by the path of truthfulness, morality, ethics and critical self-reflection in order to value clinical practices., Final Considerations: The importance of logical thinking for nursing care is ratified here, supporting nursing care systematization and the nursing process stages. Thus, nurses can use clinical reasoning skills to deliver a humane, ethical, and effective professional performance.

Dietary restriction (DR) reduces adiposity and improves metabolism in patients with one or more symptoms of metabolic syndrome. Nonetheless, it remains elusive whether the benefits of DR in humans are mediated by calorie or nutrient restriction. This study was conducted to determine whether isocaloric dietary protein restriction is sufficient to confer the beneficial effects of dietary restriction in patients with metabolic syndrome. We performed a prospective, randomized controlled dietary intervention under constant nutritional and medical supervision. Twenty-one individuals diagnosed with metabolic syndrome were randomly assigned for caloric restriction (CR; n = 11, diet of 5941 ± 686 KJ per day) or isocaloric dietary protein restriction (PR; n = 10, diet of 8409 ± 2360 KJ per day) and followed for 27 days. Like CR, PR promoted weight loss due to a reduction in adiposity, which was associated with reductions in blood glucose, lipid levels, and blood pressure. More strikingly, both CR and PR improved insulin sensitivity by 62.3% and 93.2%, respectively, after treatment. Fecal microbiome diversity was not affected by the interventions. Adipose tissue bulk RNA-Seq data revealed minor changes elicited by the interventions. After PR, terms related to leukocyte proliferation were enriched among the upregulated genes. Protein restriction is sufficient to confer almost the same clinical outcomes as calorie restriction without the need for a reduction in calorie intake. The isocaloric characteristic of the PR intervention makes this approach a more attractive and less drastic dietary strategy in clinical settings and has more significant potential to be used as adjuvant therapy for people with metabolic syndrome.

This study aimed to investigate the effects of acute capsaicin analog (Capsiate - CAP) supplementation on maximal voluntary isometric contraction (MVIC) performance in healthy young men. Thirteen subjects (25.2±3.2 yrs) participated in the present study. In two different days separated by one week, the subjects ingested capsiate (12 mg) or placebo (starch: 12 mg) 45 minutes before a MVIC test. The MVIC test consisted of five 10-second knee extension maximal isometric contractions with 45 seconds of recovery between efforts. The peak force, mean force, minimum force, fatigue index, and area under the curve of each contraction were calculated. Main condition effect was found, with higher values of peak force (+4.83%, F=6.867, p=0.02), fatigue index (+8.96%, F=5.228, p=0.041), and area under the curve (+4.19%, F=4.774, p=0.04) for CAP compared to placebo, however, no interaction effect was found for any variable (F=0.090 to 1.356, p≥0.276). In summary, healthy young men produced higher maximal isometric force and delayed fatigue in the CAP condition compared to placebo condition (condition effect) but without significant difference between each effort., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme. All rights reserved.)

Background: Chronic benzodiazepine use is a challenge in primary care practice. Protocols to support safe discontinuation are still needed, especially in countries with high utilization rates., Objectives: To evaluate the feasibility, effectiveness, and safety of a benzodiazepine discontinuation protocol in primary care setting., Methods: Nonrandomized, single-arm interventional study, at primary care units. Family physicians (FPs) recruited patients (18-85 years-old) with benzodiazepine dependence and chronic daily use ≥3 months. Patients with daily dosages ≥30 mg diazepam-equivalent, taking zolpidem, with a history of other substance abuse or major psychiatric disease were excluded. After the switch to diazepam, the dosage was gradually tapered according to a standardized protocol. Primary endpoint was the percentage of patients who stopped benzodiazepine at the intervention last visit. Dosage reduction, withdrawal symptoms, patients' and FPs' satisfaction with the protocol were evaluated., Results: From 66 enrolled patients (74% female; 66.7% aged >64 years; median time of benzodiazepine use was 120 months), 2 withdrew due to medical reasons and 3 presented protocol deviations. Overall, 59.4% of participants successfully stopped benzodiazepine (60.7% when excluding protocol deviations). Men had higher probability of success (relative risk = 0.51, P = 0.001). A total of 31 patients reported at least 1 withdrawal symptom, most frequently insomnia and anxiety. Most of participating FP considered the clinical protocol useful and feasible in daily practice. Among patients completing the protocol, 77% were satisfied. For the patients who reduced dosage, 85% kept without benzodiazepines after 12 months., Conclusion: The discontinuation protocol with standardized dosage reduction was feasible at primary care and showed long-term effectiveness., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Several single nucleotide polymorphisms (SNPs) could indirectly, as well directly, influence metabolic parameters related to health effects in response to selenium (Se) supplementation. This study aimed to investigate whether the selenoprotein SNPs were associated with the response of Se status biomarkers to the Brazil nut consumption in patients using statins and if the variation in Se homoeostasis could affect antioxidant protection, lipid profile, muscle homoeostasis and selenoproteins mRNA. The study was performed in the Ribeirão Preto Medical School University Hospital. Thirty-two patients using statins received one unit of Brazil nut daily for 3 months. Body composition, blood Se concentrations, erythrocyte glutathione peroxidase (GPX) activity, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triacylglycerol (TAG), creatine kinase (CK) activity and gene expression of GPX1 and selenoprotein P (SELENOP) were evaluated before and after Brazil nut consumption. The volunteers were genotyped for SNP in GPX1 (rs1050450) and SELENOP (rs3877899 and rs7579). SNPs in selenoproteins were not associated with plasma and erythrocyte Se, but SNPs in SELENOP influenced the response of erythrocyte GPX activity and CK activity, TAG and LDL after Brazil nut consumption. Also, Brazil nut consumption increased GPX1 mRNA expression only in subjects with rs1050450 CC genotype. SELENOP mRNA expression was significantly lower in subjects with rs7579 GG genotype before and after the intervention. Thus, SNP in SELENOP could be associated with interindividual differences in Se homeostasis after Brazil nut consumption, emphasising the involvement of genetic variability in response to Se consumption towards health maintenance and disease prevention.

Objective: Insulin sensitivity evaluation by hyperinsulinemic-euglycemic clamp in nonclassical congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxilase deficiency., Design and Setting: Cross-sectional study at university hospital outpatient clinics., Patients and Methods: NC-CAH patients (25 females, 6 males; 24 ± 10 years) subdivided into C/NC (compound heterozygous for 1 classical and 1 nonclassical allele) and NC/NC (2 nonclassical alleles) genotypes were compared to controls., Results: At diagnosis, C/NC patients presented higher basal and adrenocorticotropin-stimulated 17-hydroxyprogesterone and androstenedione levels than NC/NC genotype. Patients and controls presented similar weight, body mass index, abdominal circumference, and total fat body mass. NC-CAH patients showed higher waist-to-hip ratio, lower adiponectin and lower high-density lipoprotein cholesterol levels with no changes in fasting plasma glucose, glycated hemoglobin, homeostatic model assessment for insulin resistance, leptin, interleukin 6, tumor necrosis factor alpha, C-reactive protein, and carotid-intima-media thickness. All patients had used glucocorticoid (mean time of 73 months). Among the 22 patients with successful clamp, 13 were still receiving glucocorticoid-3 patients using cortisone acetate, 9 dexamethasone, and 1 prednisone (hydrocortisone equivalent dose of 5.5mg/m²/day), while 9 patients were off glucocorticoid but had previously used (hydrocortisone equivalent dose of 5.9mg/m2/day). The NC-CAH patients presented lower Mffm than controls (31 ± 20 vs 55 ± 23µmol/min-1/kg-1, P = 0.002). The Mffm values were inversely correlated with the duration of glucocorticoid treatment (r = -0.44, P = 0.04). There was association of insulin resistance and glucocorticoid type but not with androgen levels., Conclusion: Using the gold standard method, the hyperinsulinemic-euglycemic clamp, insulin resistance was present in NC-CAH patients and related to prolonged use and long-acting glucocorticoid treatment. Glucocorticoid replacement and cardiometabolic risks should be monitored regularly in NC-CAH., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Type 1 diabetes (T1D) arises from autoimmune-mediated destruction of insulin-producing β -cells leading to impaired insulin secretion and hyperglycemia. T1D is accompanied by DNA damage, oxidative stress, and inflammation, although there is still scarce information about the oxidative stress response and DNA repair in T1D pathogenesis. We used the microarray method to assess mRNA expression profiles in peripheral blood mononuclear cells (PBMCs) of 19 T1D patients compared to 11 controls and identify mRNA targets of microRNAs that were previously reported for T1D patients. We found 277 differentially expressed genes (220 upregulated and 57 downregulated) in T1D patients compared to controls. Analysis by gene sets (GSA and GSEA) showed an upregulation of processes linked to ROS generation, oxidative stress, inflammation, cell death, ER stress, and DNA repair in T1D patients. Besides, genes related to oxidative stress responses and DNA repair ( PTGS2 , ATF3 , FOSB , DUSP1 , and TNFAIP3 ) were found to be targets of four microRNAs (hsa-miR-101, hsa-miR148a, hsa-miR-27b, and hsa-miR-424). The expression levels of these mRNAs and microRNAs were confirmed by qRT-PCR. Therefore, the present study on differential expression profiles indicates relevant biological functions related to oxidative stress response, DNA repair, inflammation, and apoptosis in PBMCs of T1D patients relative to controls. We also report new insights regarding microRNA-mRNA interactions, which may play important roles in the T1D pathogenesis., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Paula Takahashi et al.)

Objective: An experimental infection based on a tissue cage model was reproduced to evaluate the interference subinhibitory concentration (SIC) of metronidazole in Bacteroides fragilis OMV production patterns and immunological and histological characteristics of the host facing the experimental challenge., Methods: A tissue cage model was reproduced for B. fragilis experimental challenge in three Wistar rats groups: negative control group (NC) without bacterial inoculation; positive control group (PC) infected with parental strain; and experimental group (EG) infected with the parental strain and treated with metronidazole SIC. Tissue cage sections and histological preparations were evaluated under optical and transmission electron microscope. Observations included OMV identification and count and cellular envelope evaluation. Transcriptional analyses were performed to evaluate cytokines expression levels., Results: Total counts of leukocytes and neutrophils were higher for EG, and slight increase in PC group. It was observed an exacerbated inflammatory infiltrate after 8 days on infection. The expression of TNF-α was increased during the experiments, along with IL-1α and IL-6. MCP-1 levels were suppressed in almost every evaluated time-point. The IL-10 was exacerbated in EG group. A massive production and release of OMV and cell wall thickening were observed especially the EG group., Conclusions: Despite literature data suggest positive association between OMV and antimicrobial stress for Gram negatives, no correlations are made for B. fragilis and drug-response during experimental model of infection. Results corroborate observations in which OMV may be involved in bacterial pathogenicity once the phenomenon was observed along histological evidence of exacerbated inflammation and cytokines modulation., Competing Interests: Declaration of competing interest We have no conflicts of interest to declare., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Studies have shown that narcolepsy patients may present with low serum acylcarnitine levels, demonstrating a dysfunctional beta fatty acid oxidation pathway in these patients., Objective: Evaluate the therapeutic efficacy of L-carnitine as a treatment for narcolepsy patients., Methods: This study runned in form of systematic review. The terms used for the search: ("narcolepsy"[MeSH Terms] OR "narcolepsy"[All Fields]) AND ("carnitine"[MeSH Terms] OR "carnitine"[All Fields] OR "l carnitine"[All Fields]). Were included all surveys published until January 2021, with the diagnosis of narcolepsy, that performed drug treatment with I-carnitine. The clinical endpoints of interest were: excessive daytime sleepiness, dissociative REM sleep manifestations: cataplexy, sleep paralysis, hypnagogic hallucinations, and early REM sleep (REM sleep naps, SOREMP)., Results: L-carnitine was found to be well-tolerated and without side effects in all surveys, at dosages ranging from 500 to 510 mg/day. Newborns did not present complications during delivery., Conclusion: This study corroborates the efficacy and good tolerability of L-carnitine therapy as a treatment for patients with narcolepsy, including during pregnancy.

Abstract: de Freitas, MC, Cholewa, JM, Panissa, VLG, Toloi, GG, Netto, HC, Zanini de Freitas, C, Freire, RV, Lira, FS, and Rossi, FE. Acute capsaicin supplementation improved resistance exercise performance performed after a high-intensity intermittent running in resistance-trained men. J Strength Cond Res 36(1): 130-134, 2022-We sought to investigate the acute effects of capsaicin supplementation on the rate of perceived exertion (RPE) and heart rate during high-intensity intermittent exercise (HIIE) and resistance exercise performance executed after HIIE in resistance-trained men. Eleven resistance-trained men completed 2 randomized, double-blind trials: capsaicin condition or a placebo condition. The concurrent exercise session was composed of a 5-km intermittent run (1:1 effort and passive recovery ratio) and subsequent resistance exercise (4 × 70% of 1RM until muscle failure in the half-squat exercise). Heart rate was recorded during HIIE and after the protocol RPE (0-10 scale) was accessed. The resistance exercise performance was analyzed by the maximum number of repetitions performed for each set and the total volume (repetitions × weight lifted). During HIIE, the RPE (capsaicin = 7 ± 1 vs. placebo = 8 ± 1 points, t = -3.674, p = 0.005) and mean heart rate (capsaicin = 153 ± 13 vs. placebo = 158 ± 12 bpm, t = -2.292, p = 0.048) were significantly lower in the capsaicin compared with placebo condition. For subsequent resistance exercise, there was a significant decrease in volume across time (F = 19.889, p < 0.001, η2= 0.69) with maximal number of repetitions performed in capsaicin than placebo condition (2,077.6 ± 465.2 kg vs. 1,838.9 ± 624.1 kg, p = 0.028, d = 0.43), but the condition vs. set was not significant (F = 0.582, p = 0.632, η2= 0.06). Acute capsaicin supplementation induced a lower mean heart rate and RPE during HIIE and improved subsequent resistance exercise performance in resistance-trained men., (Copyright © 2019 National Strength and Conditioning Association.)

Background: Familial partial lipodystrophy (FPLD) is a rare disease characterized by selective loss of peripheral subcutaneous fat, associated with dyslipidemia and diabetes mellitus. Reductions in circulating levels of ANGPTL3 are associated with lower triglyceride and other atherogenic lipids, making it an attractive target for treatment of FPLD patients. This proof-of-concept study was conducted to assess the efficacy and safety of targeting ANGPTL3 with vupanorsen in patients with FPLD., Methods: This was an open-label study. Four patients with FPLD (two with pathogenic variants in LMNA gene, and two with no causative genetic variant), diabetes (HbA1c ≥ 7.0 % and ≤ 12 %), hypertriglyceridemia (≥ 500 mg/dL), and hepatic steatosis (hepatic fat fraction, HFF ≥ 6.4 %) were included. Patients received vupanorsen subcutaneously at a dose of 20 mg weekly for 26 weeks. The primary endpoint was the percent change from baseline in fasting triglycerides at Week 27. Other endpoints analyzed at the same time point included changes in ANGPTL3, fasting lipids and lipoproteins, insulin secretion/sensitivity, postprandial lipids, and glycemic changes in response to a mixed meal test, HFF measured by MRI, and body composition measured by dual-energy absorptiometry (DEXA)., Results: Baseline mean ± SD fasting triglyceride level was 9.24 ± 4.9 mmol/L (817.8 ± 431.9 mg/dL). Treatment resulted in reduction in fasting levels of triglycerides by 59.9 %, ANGPTL3 by 54.7 %, and in several other lipoproteins/lipids, including very low-density lipoprotein cholesterol by 53.5 %, non-high-density lipoprotein cholesterol by 20.9 %, and free fatty acids (FFA) by 41.7 %. The area under the curve for postprandial triglycerides, FFA, and glucose was reduced by 60 %, 32 %, and 14 %, respectively. Treatment with vupanorsen also resulted in 55 % reduction in adipose tissue insulin resistance index, while other insulin sensitivity indices and HbA1c levels were not changed. Additional investigations into HFF and DEXA parameters suggested dynamic changes in fat partitioning during treatment. Adverse events observed were related to common serious complications associated with diabetes and FPLD. Vupanorsen was well tolerated, and there was no effect on platelet count., Conclusions: Although limited, these results suggest that targeting ANGPTL3 with vupanorsen could address several metabolic abnormalities in patients with FPLD., (© 2021. The Author(s).)

Abstract: Conrado de Freitas, M, Ricci-Vitor, AL, de Oliveira, JVNS, Quizzini, GH, Vanderlei, LCM, Silva, BSA, Zanchi, NE, Cholewa, JM, Lira, FS, and Rossi, FE. Appetite is suppressed after full-body resistance exercise compared with split-body resistance exercise: the potential influence of lactate and autonomic modulation. J Strength Cond Res 35(9): 2532-2540, 2021-The purposes of this study were to investigate the effects of full- vs. split-body resistance training on appetite and leptin response and to verify the potential involvement of lactate and autonomic modulation during this response in trained men. Twelve recreationally resistance-trained men (age = 26.1 ± 5.5 years) performed 3 randomized trials in 3 conditions: upper body (UB), lower body (LB), and full body (FB). The subjective rating of hunger was obtained through a visual analog scale. Leptin and lactate concentration were evaluated at rest, immediately after exercise, and during recovery. Heart rate variability in the time and frequency domains was recorded at baseline and during recovery (until 60 minutes after exercise) to assess autonomic modulation. The FB condition induced lower subjective hunger ratings than the UB at Post-1 hour (p < 0.05) and a significant difference in the area under the curve between conditions (p = 0.028) with lower hunger sensation for FB in relation to UB (p = 0.041). The FB presented greater lactate concentration and induced slower heart rate variability recovery in relation to UB and LB conditions (p < 0.05), and heart rate variability remained lower until 60 minutes after exercise compared with rest only in the FB condition. There was a significant negative correlation between subjective hunger ratings and lactate concentration only for the FB condition (r = -0.72, p = 0.028). Full-body resistance exercise induced lower subjective hunger ratings after exercise in relation to UB resistance exercise. The FB also induced higher lactate production and slower recovery of autonomic modulation compared with the UB and LB conditions. Future research is necessary to investigate a mechanistic relationship between lactate concentrations and hunger suppression after resistance exercise., (Copyright © 2019 National Strength and Conditioning Association.)

Mechanisms by which autosomal recessive mutations in Lmna cause familial partial lipodystrophy type 2 (FPLD2) are poorly understood. To investigate the function of lamin A/C in adipose tissue, we created mice with an adipocyte-specific loss of Lmna ( Lmna ADKO ). Although Lmna ADKO mice develop and maintain adipose tissues in early postnatal life, they show a striking and progressive loss of white and brown adipose tissues as they approach sexual maturity. Lmna ADKO mice exhibit surprisingly mild metabolic dysfunction on a chow diet, but on a high-fat diet they share many characteristics of FPLD2 including hyperglycemia, hepatic steatosis, hyperinsulinemia, and almost undetectable circulating adiponectin and leptin. Whereas Lmna ADKO mice have reduced regulated and constitutive bone marrow adipose tissue with a concomitant increase in cortical bone, FPLD2 patients have reduced bone mass and bone mineral density compared with controls. In cell culture models of Lmna deficiency, mesenchymal precursors undergo adipogenesis without impairment, whereas fully differentiated adipocytes have increased lipolytic responses to adrenergic stimuli. Lmna ADKO mice faithfully reproduce many characteristics of FPLD2 and thus provide a unique animal model to investigate mechanisms underlying Lmna -dependent loss of adipose tissues., (© 2021 by the American Diabetes Association.)

Objective: To construct nursing diagnosis statements of the International Classification for Nursing Practice (ICNP®) for the spinal cord rehabilitation specialty based on the Callista Roy Adaptation Model., Method: Descriptive study developed in sequential steps of identification and cross-mapping of terms relevant to care with the health priority, construction and cross-mapping of nursing diagnosis statements based on the ICNP®, and categorization of diagnoses according to adaptive modes., Results: Ninety-two statements of nursing diagnoses were developed, of which 66 were classified in the Physiological Mode, 12 in Functional Role Mode, 10 in Self-Concept Mode and four in Interdependence Mode., Conclusion: The nursing diagnoses developed portray focuses of attention for nursing care to people with spinal cord injury in rehabilitation and contribute to the direction of nursing care actions in a systematic, individualized and resolutive way.

Context: Data quantifying the impact of metreleptin therapy on survival in non-human immunodeficiency virus (HIV)-related generalized lipodystrophy (GL) and partial lipodystrophy (PL) are unavailable., Objective: This study aimed to estimate the treatment effect of metreleptin on survival in patients with GL and PL., Design/setting/patients: Demographic and clinical characteristics were used to match metreleptin-treated and metreleptin-naïve patients with GL and PL. Differences in mortality risk were estimated between matched cohorts of metreleptin-treated and metreleptin-naïve patient cohorts using Cox proportional hazard models. Sensitivity analyses assessed the impact of study assumptions and the robustness of results., Outcome Measures: This study assessed time-to-mortality and risk of mortality., Results: The analysis evaluated 103 metreleptin-naïve patients with characteristics matched to 103 metreleptin-treated patients at treatment initiation. Even after matching, some metabolic and organ abnormalities were more prevalent in the metreleptin-treated cohort due to bias toward treating more severely affected patients. A Cox proportional hazards model associated metreleptin therapy with an estimated 65% decrease in mortality risk (hazard ratio [HR] 0.348, 95% confidence interval (CI): 0.134-0.900; P = 0.029) even though the actual number of events were relatively small. Results were robust across a broad range of alternate methodological assumptions. Kaplan-Meier estimates of time-to-mortality for the metreleptin-treated and the matched metreleptin-naïve cohorts were comparable., Conclusions: Metreleptin therapy was associated with a reduction in mortality risk in patients with lipodystrophy syndromes despite greater disease severity in treated patients, supporting the view that metreleptin can have a positive disease-modifying impact. Confirmatory studies in additional real-world and clinical datasets are warranted., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)