Estimated glomerular filtration rate in clinical practice: Consensus positioning of the Brazilian Society of Nephrology (SBN) and Brazilian Society of Clinical Pathology and Laboratory Medicine (SBPC/ML) / Estimativa da taxa de filtração glomerular na prática clínica: posicionamento consensual da Sociedade Brasileira de Nefrologia (SBN) e Sociedade Brasileira de Patologia Clínica e Medicina Laboratorial (SBPC/ML)

ABSTRACT Chronic kidney disease (CKD) represents one of today's main public health problems. Serum creatinine measurement and estimation of the glomerular filtration rate (GFR) are the main tools for evaluating renal function. There are several equations to estimate GFR, and CKD-EPI equation (Chronic Kidney Disease - Epidemiology) is the most recommended one. There are still some controversies regarding serum creatinine measurement and GFR estimation, since several factors can interfere in this process. An important recent change was the removal of the correction for race from the equations for estimating GFR, which overestimated kidney function, and consequently delayed the implementation of treatments such as dialysis and kidney transplantation. In this consensus document from the Brazilian Societies of Nephrology and Clinical Pathology and Laboratory Medicine, the main concepts related to the assessment of renal function are reviewed, as well as possible existing controversies and recommendations for estimating GFR in clinical practice.

RESUMO A doença renal crônica (DRC) representa um dos principais problemas de saúde pública da atualidade. A dosagem da creatinina sérica e a estimativa da taxa de filtração glomerular (TFG) são as principais ferramentas para avaliação da função renal. Para a estimativa da TFG, existem diversas equações, sendo a mais recomendada a CKD-EPI (Chronic Kidney Disease - Epidemiology). Existem ainda algumas controvérsias com relação à dosagem da creatinina sérica e da estimativa da TFG, uma vez que vários fatores podem interferir nesse processo. Uma importante mudança recente foi a retirada da correção por raça das equações para estimativa da TFG, que superestimavam a função renal, e consequentemente retardavam a implementação de tratamentos como diálise e transplante renal. Neste documento de consenso da Sociedade Brasileira de Nefrologia e Sociedade Brasileira de Patologia Clínica e Medicina Laboratorial são revisados os principais conceitos relacionados à avaliação da função renal, possíveis controvérsias existentes e recomendações para a estimativa da TFG na prática clínica.

Understanding Public Perceptions of Nipple and Scar Characteristics After Chest Wall Masculinization Surgery.

BACKGROUND: Surgical chest masculinization procedures, especially gender-affirming top surgery (GATS), are becoming increasingly prevalent in the USA. While a variety of surgical techniques have been established as both safe and effective, there is limited research examining ideal aesthetic nipple appearance and incision scar pattern. This study employs patient images to understand the public's perception on top surgery outcomes when adjusting for BMI ranges and Fitzpatrick skin types. METHODS: Images from RealSelf modified via Adobe Photoshop depicted various scar types and nipple-areolar complex (NAC) sizes/positions. A Qualtrics survey was distributed utilizing Amazon Mechanical Turk. Statistical analysis was performed through JMP Pro 17 for ordinal and categorical values, with a p value less than or equal to 0.05 statistically significant. RESULTS: A moderately sized and laterally placed NAC was preferred. A transverse scar that resembles the pectoral border between the level of the inframammary fold and pectoral insertion was deemed most masculine and aesthetic. Majority of results demonstrated that this is unaffected by Fitzpatrick skin types. Increased BMI images impacted public preferences, as a nipple placed farther from the transverse incision (p = 0.04) and a transverse scar position closer to the IMF was preferred in higher BMI patients. CONCLUSIONS: An understanding of the most popular NAC and scar choices, as well as how these factors may differ when considering a Fitzpatrick skin type or BMI categorization was attained. This validates the importance of patient-centered approach when employing surgical techniques in GATS. Future studies intend to obtain reports from actual patients considering GATS. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable.

Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 Genotypes and Beta-Blocker Therapy.

Beta-blockers are widely used medications for a variety of indications, including heart failure, myocardial infarction, cardiac arrhythmias, and hypertension. Genetic variability in pharmacokinetic (e.g., CYP2D6) and pharmacodynamic (e.g., ADRB1, ADRB2, ADRA2C, GRK4, GRK5) genes have been studied in relation to beta-blocker exposure and response. We searched and summarized the strength of the evidence linking beta-blocker exposure and response with the six genes listed above. The level of evidence was high for associations between CYP2D6 genetic variation and both metoprolol exposure and heart rate response. Evidence indicates that CYP2D6 poor metabolizers experience clinically significant greater exposure and lower heart rate in response to metoprolol compared with those who are not poor metabolizers. Therefore, we provide therapeutic recommendations regarding genetically predicted CYP2D6 metabolizer status and metoprolol therapy. However, there was insufficient evidence to make therapeutic recommendations for CYP2D6 and other beta-blockers or for any beta-blocker and the other five genes evaluated (updates at www.cpicpgx.org).

Movement of juvenile migratory birds from settlement to adulthood across the non-breeding range.

Among migratory vertebrates, high levels of fidelity to non-breeding sites during adulthood are common. If occupied sites vary in quality, strong site fidelity can have profound consequences for individual fitness and population demography. Given the prevalence of adult site fidelity, the regions of the non-breeding range to which juveniles first migrate, and the scale of any subsequent movements, are likely to be pivotal in shaping distributions and demographic processes across population ranges. However, inherent difficulties in tracking migratory individuals through early life mean that opportunities to quantify juvenile settlement and movements across non-breeding ranges, and the mechanisms involved, are extremely rare. Through long-term, range-wide resightings of hundreds of colour-marked individuals from their first migration to adulthood and the application of state-space models, we quantify levels of juvenile and adult regional-scale movements and distances at different life stages across the whole non-breeding distribution range in a migratory shorebird, the Black-tailed Godwit (Limosa limosa islandica). We show that the probability of individuals changing non-breeding regions (seven historical wintering regions spanning the Western Europe range) at all ages is very low (mean movement probability = 10.9% from first to subsequent winter, and 8.3% from first adult winter to later winters). Movement between regions was also low between autumn and winter of the same year for both juveniles (mean movement probability = 17.0%) and adults (10.4%). The great majority of non-breeding movements from the first autumn to adulthood were within regions and less than 100 km. The scarcity of regional-scale non-breeding movements from the first autumn to adulthood means that the factors influencing where juveniles settle will be key determinants of non-breeding distributions and of the rate and direction of changes in distributions.

Case study: Evaluating deep-water start techniques and training demands in seated slalom waterskiing for an athlete with paraplegia.

Purpose: Recreational and competitive slalom waterskiing is increasingly popular among individuals with spinal cord injuries (SCI), particularly for those with paraplegia using sit-skis. A key component of slalom skiing is the deep-water start (DWS), yet little is known about the physiological and physical demands of this activity when the athlete is seated. This study aims to fill this gap by focusing on the training requirements for a seated slalom athlete. Materials and methods: Focusing on a young male athlete with paraplegia, this case study evaluates the effectiveness and efficiency of traditional (TDWS) and alternative (ADWS) DWS techniques during seated slalom waterskiing sessions. It assesses internal training load (TL) through heart rate (HR) zones and session rating of perceived exertion (sRPE), alongside pre- and post-session handgrip strength measurements to gauge peripheral muscle fatigue. Results and conclusions: Performing the ADWS, achieving a full success rate, proved more effective but slightly more time-consuming than TDWS, which had limited success. HR during DWS maneuvers ranged from 63.2 to 81.3% of maximal HR, with most sessions occurring below the ventilatory threshold, thus perceived as hard effort. A moderate yet non-significant correlation was found between HR and sRPE-based TL. A significant reduction in handgrip strength post-session underscores the activity's demands. These insights illuminate the technical, physiological, and physical challenges in mastering DWS for seated slalom athletes with SCI, providing valuable guidance for the development of tailored training programs and techniques in this sport.

Executive Summary of the Spanish Guidelines for the Diagnosis and Management of Imported Febrile Illnesses from the Spanish Society of Tropical Medicine and International Health (SEMTSI), the Imported Pathology Group of the Spanish Society of Infectious Diseases and Clinical Microbiology (GEPI-SEIMC), the Spanish Society of Family and Community Medicine (SEMFYC), the Spanish Society of Primary Care Physicians (SEMERGEN) and the Spanish Society of Emergency Medicine (SEMES).

The Spanish Society of Tropical Medicine and International Health (SEMTSI), the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Emergency Medicine (SEMES), the Spanish Society of Primary Care Physicians (SEMERGEN) and the Spanish Society of Family and Community Medicine (SEMFYC) have prepared a consensus statement on the diagnosis and management of patients with imported febrile illnesses. Twenty authors with different backgrounds and representing different healthcare perspectives (ambulatory primary care, travel and tropical medicine specialists, emergency medicine, hospital care, microbiology and parasitology and public health), identified 39 relevant questions, which were organised in 7 thematic blocks. After a systematic review of the literature and a thoughtful discussion, the authors prepared 125 recommendations, as well as several tables and figures to be used as a consulting tool. The present executive summary shows a selection of some of the most relevant questions and recommendations included in the guidelines.

[Improving the nutritional care of oncology patients - Validation of a multidisciplinary protocol in the Spanish clinical setting]. / Mejorando la atención nutricional del paciente oncológico: validación de un protocolo multidisciplinar en el entorno clínico español.

INTRODUCTION: malnutrition is a very frequent problem in oncology patients and can have serious repercussions. Adequate nutritional management is cost-effective in terms of health and survival in this population, but it requires multidisciplinary coordination, specific training, and continuous follow-up. OBJECTIVE: to validate the applicability and efficacy of a multidisciplinary nutritional support protocol in oncology patients. METHODS: a multidisciplinary nutritional protocol was developed for oncology patients, with guidelines for screening and assessment of malnutrition, treatment, re-evaluation, and management of side effects, as well as guidance on supplementation and eating patterns. The protocol would be implemented in various clinical centers, collecting data through a structured questionnaire, registering variables before and after implementation. RESULTS: the protocol and its impact were implemented and evaluated in 39 centers. An improvement in nutritional care was observed, evidenced by an earlier initiation of nutritional assessment and an increase in the number of patients receiving adequate care following the protocol implementation. Problems related to inadequate malnutrition coding in the centers, limited resources, and the need for greater interdepartmental collaboration were identified. CONCLUSIONS: the conduct of this study provides insights into how the implementation of a multidisciplinary nutritional support protocol can improve the nutritional care received by patients and informs about the main obstacles to adequate implementation.

Use of calibration to improve the precision of estimates obtained from All of Us data.

OBJECTIVES: To highlight the use of calibration weighting to improve the precision of estimates obtained from All of Us data and increase the return of value to communities from the All of Us Research Program. MATERIALS AND METHODS: We used All of Us (2017-2022) data and raking to obtain prevalence estimates in two examples: discrimination in medical settings (N = 41 875) and food insecurity (N = 82 266). Weights were constructed using known population proportions (age, sex, race/ethnicity, region of residence, annual household income, and home ownership) from the 2020 National Health Interview Survey. RESULTS: About 37% of adults experienced discrimination in a medical setting. About 20% of adults who had not seen a doctor reported being food insecure compared with 14% of adults who regularly saw a doctor. CONCLUSIONS: Calibration using raking is cost-effective and may lead to more precise estimates when analyzing All of Us data.

[4]Rhombene: Solution-Phase Synthesis and Application for Distributed Feedback Lasers With Emission Beyond 830 nm.

Graphene-like molecules with multiple zigzag edges are emerging as promising gain materials for organic lasers. Their emission wavelengths can vary widely, ranging from visible to near-infrared (NIR), as molecular size increases. Specifically, rhombus-shaped molecular graphenes with two pairs of parallel zigzag edges, known as [n]rhombenes, are excellent candidates for NIR lasers due to their small energy gaps. However, synthesizing large-size rhombenes with emission beyond 800 nm in solution remains a significant challenge. In this study, we present a straightforward synthesis of an aryl-substituted [4]rhombene derivative, [4]RB-Ar, using a method that combines intramolecular radical-radical coupling with Bi(OTf)3-mediated cyclization of vinyl ethers. The structure of [4]RB-Ar was confirmed through X-ray crystallographic analysis. Bond length analysis and theoretical calculations indicate that aromatic sextets are predominantly localized along the molecule's long axis. Significantly, [4]RB-Ar demonstrates narrow amplified spontaneous emission at around 834 nm when dispersed in polystyrene thin films. Moreover, solution-processed distributed feedback lasers employing [4]RB-Ar as the active gain material display tunable narrow emissions in the range of 830 to 844 nm.

Caregiver-reported emotional-behavioral symptoms in Spanish youth during the COVID-19 pandemic: a longitudinal study.

BACKGROUND: COVID-19 pandemic stressors affected youth's mental health. This longitudinal study aims to explore these effects while considering predictive factors such as age and sex. METHODS: An initial sample of 1502 caregivers answered a longitudinal survey evaluating their youths' (4-17 years of age) emotional/behavioral symptoms using the Pediatric Symptom Checklist (PSC) screening tool. First assessment in May-July 2020 included the prior year's retrospective (TR) and since-lockdown-start (T0) PSC, followed by monthly evaluations until February 2021. RESULTS: A positive screening PSC (PSC+) was reported in 13.09% of cases at TR and 35.01% at T0, but the likelihood of PSC+ quickly decreased over time. At T0, a more pronounced impact was found on children (39.7%) compared to adolescents (25.4%); male children exhibited higher risk for a PSC+ at T0 and longitudinally than females. Adolescents presented a weaker effect of time-improvement. PSC+ at TR, experienced stressors, and caregiver's stress/depressive symptoms positively predicted PSC+ at T0 and longitudinally; adolescents' unproductive coping style predicted PSC+ at T0. CONCLUSION: The study shows a caregiver-reported increase in emotional/behavioral symptoms in youths during the COVID-19 pandemic, affecting predominantly younger children in the early stages and showing gradual improvement over time, albeit possibly slower in adolescents. IMPACT: The results show the anticipated surge in emotional and behavioral symptoms during the COVID-19 lockdown in youth reported by caregivers, followed by subsequent amelioration. Of greater significance, the study reveals a heightened impact on young children initially, yet it suggests a slower improvement trajectory in adolescents. The study also identifies risk factors linked to emotional and behavioral symptoms within each age group. Alongside the longitudinal approach, the authors underscore the remarkable inclusion of a significant representation of young children, an unusual feature in such surveys.

Unveiling a New 2D Semiconductor: Biphenylene-Based InN.

The two-dimensional (2D) materials class earned a boost in 2021 with biphenylene synthesis, which is structurally formed by the fusion of four-, six-, and eight-membered carbon rings, usually named 4-6-8-biphenylene network (BPN). This research proposes a detailed study of electronic, structural, dynamic, and mechanical properties to demonstrate the potential of the novel biphenylene-like indium nitride (BPN-InN) via density functional theory and molecular dynamics simulations. The BPN-InN has a direct band gap energy transition of 2.02 eV, making it promising for optoelectronic applications. This structure exhibits maximum and minimum Young modulus of 22.716 and 22.063 N/m, Poisson ratio of 0.018 and -0.008, and Shear modulus of 11.448 and 10.860 N/m, respectively. To understand the BPN-InN behavior when subjected to mechanical deformations, biaxial and uniaxial strains in armchair and zigzag directions from -8 to 8% were applied, achieving a band gap energy modulation of 1.36 eV over tensile deformations. Our findings are expected to motivate both theorists and experimentalists to study and obtain these new 2D inorganic materials that exhibit promising semiconductor properties.

Thermal, viscoelastic, and electrical properties of thermoplastic polyurethane films reinforced with multi-walled carbon nanotubes.

Thermoplastic polyurethane (TPU) doped with multi-walled carbon nanotubes (MWCNTs) at 1, 3, 5, and 7 wt% has been studied. The effect of MWCNTs on thermal, viscoelastic, and electric properties in the TPU matrix was characterized by differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and by impedance spectroscopy. The results show that the thermal, electrical, and viscoelastic properties, such as the glass transition temperature, shifted towards high temperatures. The melting temperature decreased, and the conductivity and the storage modulus increased by 61.5 % and 58.3 %. The previously observed behavior on the films is due to the increase in the mass percentage of carbon nanotubes (CNTs) in the TPU matrix. Also, it can be said that the CNTs were homogeneously dispersed in the TPU matrix, preventing the movement of the polymer chains, and generating channels or connections that increase the conductivity and improve the thermal properties of the material.

Treatment Outcomes Among Patients With a Positive Candida Culture Close to Randomization Receiving Rezafungin or Caspofungin in the ReSTORE Study.

BACKGROUND: Rezafungin, a novel, once-weekly echinocandin for the treatment of candidemia and/or invasive candidiasis (IC) was non-inferior to caspofungin for Day 30 all-cause mortality (ACM) and Day 14 global cure in the Phase 3 ReSTORE trial (NCT03667690). We conducted pre-planned subgroup analyses for patients with a positive culture close to randomization in ReSTORE. METHODS: ReSTORE was a multicenter, double-blind, double-dummy, randomized trial in patients aged ≥18 years with candidemia and/or IC treated with once-weekly intravenous rezafungin (400 mg/200 mg) or once-daily intravenous caspofungin (70 mg/50 mg). This analysis comprised patients with a positive blood culture drawn between 12 hours before and 72 hours after randomization, or a positive culture from another normally sterile site sampled between 48 hours before and 72 hours after randomization. Efficacy endpoints included Day 30 ACM, Day 14 global cure rate, and Day 5 and 14 mycological response. Adverse events were evaluated. RESULTS: This analysis included 38 patients randomized to rezafungin and 46 to caspofungin. In the rezafungin and caspofungin groups, respectively: Day 30 ACM was 26.3% and 21.7% (between-group difference [95% confidence interval] 4.6% [-13.7, 23.5]); Day 14 global response was 55.3% and 50.0% (between-group difference 5.3% [-16.1, 26.0]); and Day 5 mycological eradication was 71.1% and 50.0% (between-group difference 21.1% [-0.2, 40.2]). Safety was comparable between treatments. CONCLUSIONS: These findings support the efficacy and safety of rezafungin compared with caspofungin for the treatment of candidemia and/or IC in patients with a positive culture close to randomization, with potential early treatment benefits for rezafungin.

A systematic review on the contribution of DNA methylation to hearing loss.

BACKGROUND: DNA methylation may have a regulatory role in monogenic sensorineural hearing loss and complex, polygenic phenotypic forms of hearing loss, including age-related hearing impairment or Meniere disease. The purpose of this systematic review is to critically assess the evidence supporting a functional role of DNA methylation in phenotypes associated with hearing loss. RESULTS: The search strategy yielded a total of 661 articles. After quality assessment, 25 records were selected (12 human DNA methylation studies, 5 experimental animal studies and 8 studies reporting mutations in the DNMT1 gene). Although some methylation studies reported significant differences in CpG methylation in diverse gene promoters associated with complex hearing loss phenotypes (ARHI, otosclerosis, MD), only one study included a replication cohort that supported a regulatory role for CpG methylation in the genes TCF25 and POLE in ARHI. Conversely, several studies have independently confirmed pathogenic mutations within exon 21 of the DNMT1 gene, which encodes the DNA (cytosine-5)-methyltransferase 1 enzyme. This methylation enzyme is strongly associated with a rare disease defined by autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN). Of note, rare variants in DNMT1 and DNMT3A genes have also been reported in noise-induced hearing loss. CONCLUSIONS: Evidence supporting a functional role for DNA methylation in hearing loss is limited to few genes in complex disorders such as ARHI. Mutations in the DNMT1 gene are associated with ADCA-DN, suggesting the CpG methylation in hearing loss genes deserves further attention in hearing research.

Amphiphilic Single-Chain Polymer Nanoparticles as Imaging and Far-Red Photokilling Agents for Photodynamic Therapy in Zebrafish Embryo Xenografts.

This work introduces rationally designed, improved amphiphilic single-chain polymer nanoparticles (SCNPs) for imaging and photodynamic therapy (PDT) in zebrafish embryo xenografts. SCNPs are ultrasmall polymeric nanoparticles with sizes similar to proteins, making them ideal for biomedical applications. Amphiphilic SCNPs result from the self-assembly in water of isolated synthetic polymeric chains through intrachain hydrophobic interactions, mimicking natural biomacromolecules and, specially, proteins (in size and when loaded with drugs, metal ions or fluorophores also in function). These ultrasmall, soft nanoparticles have various applications, including catalysis, sensing, and nanomedicine. Initial in vitro experiments with nonfunctionalized, amphiphilic SCNPs loaded with a photosensitizing Zn phthalocyanine with four nonperipheral isobutylthio substituents, ZnPc, showed promise for PDT. Herein, the preparation of improved, amphiphilic SCNPs containing ZnPc as highly efficient photosensitizer encapsulated within the nanoparticle and surrounded by anthracene units is disclosed. The amount of anthracene groups and ZnPc molecules within each single-chain nanoparticle controls the imaging and PDT properties of these nanocarriers. Critically, this work opens the way to improved PDT applications based on amphiphilic SCNPs as a first step toward ideal, long-term artificial photo-oxidases (APO).

Sirolimus to treat chronic and steroid-resistant allograft rejection-related fibrosis in pediatric liver transplantation.

This study aimed to report our experience with the use of sirolimus in pediatric liver transplant patients with chronic rejection or steroid-resistant rejection with hepatic fibrosis, focusing on their histological evolution. All pediatric liver transplant recipients who received off-label treatment with sirolimus for chronic ductopenic rejection or cortico-resistant rejection between July 2003 and July 2022 were included in the study. All nine patients included in the study showed improvement in liver enzymes and cholestasis parameters as soon as 1-month after postsirolimus introduction. A decrease in fibrosis stage was observed in 7/9 (77.7%) patients at 36 months. All but one patient experienced an improvement in the Rejection Activity Index and ductopenia at 12 months. A single patient had to discontinue sirolimus treatment owing to nephrotic proteinuria. In conclusion, sirolimus may be a safe and effective treatment for chronic and steroid-resistant rejection and may improve allograft rejection-related fibrosis and ductal damage.

Endurance Training Improves Leg Proton Release and Decreases Potassium Release During High-Intensity Exercise in Normoxia and Hypobaric Hypoxia.

AIM: To assess the impact of endurance training on skeletal muscle release of H+ and K+. METHODS: Nine participants performed one-legged knee extension endurance training at moderate and high intensities (70%-85% of Wpeak), three to four sessions·week-1 for 6 weeks. Post-training, the trained and untrained (control) leg performed two-legged knee extension at low, moderate, and high intensities (40%, 62%, and 83% of Wpeak) in normoxia and hypoxia (~4000 m). The legs were exercised simultaneously to ensure identical arterial inflow concentrations of ions and metabolites, and identical power output was controlled by visual feedback. Leg blood flow was measured (ultrasound Doppler), and acid-base variables, lactate- and K+ concentrations were assessed in arterial and femoral venous blood to study K+ and H+ release. Ion transporter abundances were assessed in muscle biopsies. RESULTS: Lactate-dependent H+ release was similar in hypoxia to normoxia (p = 0.168) and was lower in the trained than the control leg at low-moderate intensities (p = 0.060-0.006) but similar during high-intensity exercise. Lactate-independent and total H+ releases were higher in hypoxia (p < 0.05) and increased more with power output in the trained leg (leg-by-power output interactions: p = 0.02). K+ release was similar at low intensity but lower in the trained leg during high-intensity exercise in normoxia (p = 0.024) and hypoxia (p = 0.007). The trained leg had higher abundances of Na+/H+ exchanger 1 (p = 0.047) and Na+/K+ pump subunit α (p = 0.036). CONCLUSION: Moderate- to high-intensity endurance training increases lactate-independent H+ release and reduces K+ release during high-intensity exercise, coinciding with increased Na+/H+ exchanger 1 and Na+/K+ pump subunit α muscle abundances.

Weighting the United States All of Us Research Program data to known population estimates using raking.

Background: The All of Us Research Program aims to collect longitudinal health-related data from a million individuals in the United States. An inherent challenge of a non-probability sampling strategy through voluntary participation in All of Us is that findings may not be nationally representative for addressing health and health care at the population level. We generated survey weights for the All of Us data that can be used to address the challenge. Research design: We developed raked weights using demographic, health, and socioeconomic variables available in both the 2020 National Health Interview Survey (NHIS) and All of Us. We then compared the unweighted and weighted prevalence of a set of health-related variables (health behaviors, health conditions, and health insurance coverage) estimated from All of Us data with the weighted prevalence estimates obtained from NHIS data. Subjects: The sample included 100,391 All of Us participants 18 years of age and older with complete data collected between May 2017 and January 2022 across the United States. Results: Final variables in the raking procedure included age, sex, race/ethnicity, region of residence, annual household income, and home ownership. The mean percentage difference between known proportions obtained from the NHIS and All of Us was reduced by 18.89% for health-related variables after applying the raked weights. Conclusions: Raking improved the comparability of prevalence estimates obtained from All of Us to known national prevalence estimates. Refining the process of variable selection for raking may further improve the comparability between All of Us and nationally representative data.

Genetic ablation of the isoform γ of PI3K decreases antidepressant efficacy of ketamine in male mice.

About one-third of major depressive disorder (MDD) patients demonstrate unresponsiveness to classic antidepressants, and even the clinical efficacy of fast-acting drugs such as ketamine varies significantly among patients with treatment-resistant depression. Nevertheless, the lack of suitable animal models that mimic a possible ketamine-resistant phenotype challenges the understanding of resistance to drug treatment. In this study, we showed that PI3Kγ knock-out (KO) mice do not respond to classical doses of ketamine and classical antidepressants. PI3Kγ KO mice were unresponsive to both the rapid and sustained antidepressant-like effects of a single dose of ketamine in the forced swimming test. Additionally, they were unresponsive to the antidepressant-like effects induced by the tricyclic antidepressant imipramine and the selective serotonin reuptake inhibitor fluoxetine. However, acute pharmacological inhibition of PI3Kγ did not block the antidepressant-like effect of ketamine, showing that a chronic deficiency of the PI3Kγ-mediated pathway is necessary for the effects of classic doses of ketamine and antidepressants. Therefore, we propose that PI3Kγ participates in the antidepressant activity and is likely implicated in the neurobiology and phenotype observed in patients with MDD who demonstrate treatment resistance.

Lactase persistence in the Jordanian population: Potential effects of the Arabian Peninsula and Sahara's aridification.

The single nucleotide polymorphism (SNP) -13910 C > T has proved a good predictor of the incidence of lactase persistence in Europe and South Asia. Yet, this is not the case in the Near East, although this region is a passageway between the two continents. Lactase persistence is associated with cattle breeding, which originated in the Fertile Crescent of the Near East and spread later during the Middle Neolithic throughout Europe. Here we analyzed five SNPs (-13915 T > G (rs41380347), -13910 C > T (rs4988235), -13907 C > G (rs41525747), -14009 T > G (rs869051967), and -14010 G > C (rs145946881)) in three Jordanian human groups, namely the Bedouins, Jordan valley farmers, and Jordanian urban people. The SNPs -14009 T > G and -14010 G > C were not detected in the sample, -13907 C > G was virtually non-existent, -13910 C > T showed low frequencies, and -13915 T > G exhibited salient frequencies. The estimated incidence of lactase persistence was lower in the urban population (16 %), intermediate in the Jordan Valley's farmer population (30 %), and higher among the Bedouins (62 %). In explaining our findings, we postulated climatic change brought about by the aridification episode of the Arabian Peninsula and the Sahara 4200 years ago. This climatic milestone caused the collapse of the Akkadian Empire and the Old Kingdom in Egypt. Also, it could have led to a drastic decline of cattle in the region, being replaced by the domestication of camels. Loss of traditional crops and increasing dependence on camel milk might have triggered local selective pressures, mainly associated with -13915 T > G and differentiated from the ones in Europe, associated with -13910 C > T.