Endogenous LXR signaling controls pulmonary surfactant homeostasis and prevents lung inflammation.

Lung type 2 pneumocytes (T2Ps) and alveolar macrophages (AMs) play crucial roles in the synthesis, recycling and catabolism of surfactant material, a lipid/protein fluid essential for respiratory function. The liver X receptors (LXR), LXRα and LXRß, are transcription factors important for lipid metabolism and inflammation. While LXR activation exerts anti-inflammatory actions in lung injury caused by lipopolysaccharide (LPS) and other inflammatory stimuli, the full extent of the endogenous LXR transcriptional activity in pulmonary homeostasis is incompletely understood. Here, using mice lacking LXRα and LXRß as experimental models, we describe how the loss of LXRs causes pulmonary lipidosis, pulmonary congestion, fibrosis and chronic inflammation due to defective de novo synthesis and recycling of surfactant material by T2Ps and defective phagocytosis and degradation of excess surfactant by AMs. LXR-deficient T2Ps display aberrant lamellar bodies and decreased expression of genes encoding for surfactant proteins and enzymes involved in cholesterol, fatty acids, and phospholipid metabolism. Moreover, LXR-deficient lungs accumulate foamy AMs with aberrant expression of cholesterol and phospholipid metabolism genes. Using a house dust mite aeroallergen-induced mouse model of asthma, we show that LXR-deficient mice exhibit a more pronounced airway reactivity to a methacholine challenge and greater pulmonary infiltration, indicating an altered physiology of LXR-deficient lungs. Moreover, pretreatment with LXR agonists ameliorated the airway reactivity in WT mice sensitized to house dust mite extracts, confirming that LXR plays an important role in lung physiology and suggesting that agonist pharmacology could be used to treat inflammatory lung diseases.

Enhanced Stature in the Elderly: The Immediate Impact of Acute Postural Exercises.

This study investigates the immediate effects of acute postural exercises on the stature of seniors, focusing on changes in both upright and supine stature measurements. A within-subject design with repeated measures was applied, involving seniors participating in continuous exercises aimed at enhancing core musculature strength and promoting muscle relaxation. Stature measurements were recorded pre- and post-exercise in both upright and supine positions, alongside assessments of body mass index (BMI) category classifications. The results revealed a post-exercise increase in stature ranging from 0.9 to 6.0 cm and from 0.2 to 7.2 cm in upright and supine positions, respectively, with an average increase of approximately 3.5 cm in both upright and supine positions. Statistically significant and clinically relevant changes were observed (p < 0.05), including a modification of BMI by approximately two units, reclassifying 55% of participants from overweight or obese to normal weight or overweight. Furthermore, the similarity between post-exercise upright stature and pre-exercise supine stature suggested that the supine position might provide a more accurate measure of stature in seniors. Conclusively, acute postural exercises have an immediate positive impact on the stature of seniors, suggesting their potential utility in clinical settings for accurate stature measurement. However, BMI results should be interpreted with caution because they are only related to the acute change in stature and therefore may lead to the misinterpretation of the study findings, so future studies focused on evaluating the chronic effect of postural exercises integration on the health outcomes of older adults are needed to demonstrate their potential utility in clinical settings to improve postural health and general well-being.

Body composition and risk for sarcopenia in transgender women.

OBJECTIVES: Body composition and strength of cisgender (cis) individuals are well established. However, those for transgender women (trans women) undergoing gender-affirming hormone therapy remain unclear. This study aimed to detect possible body composition and strength variations related to sarcopenia. METHODS: This was a cross-sectional comparative study of 37 trans women, 34 cis men, and 34 cis women. Body composition was measured in all individuals by bioelectrical impedance analysis; prehensile strength by dynamometry was studied in trans women. RESULTS: In this study, trans women had higher body mass index values than cis individuals (P < 0.01). Fat mass was 41% higher for trans women than cis men. Muscle mass (MM) was lower in trans women than cis men (-10%), and higher than cis women (24%). Bone mass was lower in trans women than cis men and higher in cis women (P < 0.01). Trans women's prehensile strengths were 25.26 kg for the right hand and 24.8 kg for the left. Appendicular skeletal muscle mass was 23.63 kg, and appendicular skeletal muscle mass index was 8.14 kg. CONCLUSION: Trans women undergoing gender-affirming hormone therapy show a tendency to adapt body compartments to those of cis women with increased fat mass and reduced muscle mass. Prehensile strength in trans women was close to the cutoff points for sarcopenia risk. Nutrition, physical activity, strength, and body composition are important to avoid the possible risk for sarcopenia. More studies along these lines are necessary, especially in older adults.

A new physiological medium uncovers biochemical and cellular alterations in Lesch-Nyhan disease fibroblasts.

BACKGROUND: Lesch-Nyhan disease (LND) is a severe neurological disorder caused by the genetic deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGprt), an enzyme involved in the salvage synthesis of purines. To compensate this deficiency, there is an acceleration of the de novo purine biosynthetic pathway. Most studies have failed to find any consistent abnormalities of purine nucleotides in cultured cells obtained from the patients. Recently, it has been shown that 5-aminoimidazole-4-carboxamide riboside 5'-monophosphate (ZMP), an intermediate of the de novo pathway, accumulates in LND fibroblasts maintained with RPMI containing physiological levels (25 nM) of folic acid (FA), which strongly differs from FA levels of regular cell culture media (2200 nM). However, RPMI and other standard media contain non-physiological levels of many nutrients, having a great impact in cell metabolism that does not precisely recapitulate the in vivo behavior of cells. METHODS: We prepared a new culture medium containing physiological levels of all nutrients, including vitamins (Plasmax-PV), to study the potential alterations of LND fibroblasts that may have been masked by the usage of non-physiological media. We quantified ZMP accumulation under different culture conditions and evaluated the activity of two known ZMP-target proteins (AMPK and ADSL), the mRNA expression of the folate carrier SLC19A1, possible mitochondrial alterations and functional consequences in LND fibroblasts. RESULTS: LND fibroblasts maintained with Plasmax-PV show metabolic adaptations such a higher glycolytic capacity, increased expression of the folate carrier SCL19A1, and functional alterations such a decreased mitochondrial potential and reduced cell migration compared to controls. These alterations can be reverted with high levels of folic acid, suggesting that folic acid supplements might be a potential treatment for LND. CONCLUSIONS: A complete physiological cell culture medium reveals new alterations in Lesch-Nyhan disease. This work emphasizes the importance of using physiological cell culture conditions when studying a metabolic disorder.

Molecular diagnosis of cystic fibrosis by RNA obtained from nasal epithelial cells.

BACKGROUND: The diagnosis of cystic fibrosis (CF) is established when characteristic clinical signs are coupled with biallelic CFTR pathogenic variants. No previously reported non-canonical splice site variants have to be considered as variants of uncertain significance unless their effect on splicing has been validated. METHODS: Two variants identified by next-generation sequencing were evaluated. We assayed their effects on splicing employing RNA analysis and real-time expression quantification from RNA obtained from the nasal epithelial cells of a patient with clinically suspected CF and of two patients with milder phenotypes (CFTR-related disorders). RESULTS: The variant c.164+2dup causes skipping of exon 2 (p.(Ser18_Glu54del)) and exon 2 plus 3 (p.(Ser18Argfs*16)) in CFTR mRNA. Exon 2 expression in the patient heterozygous for c.164+2dup was decreased to 7 % of the exon 2 expression in the controls. The synonymous variant c.1584G>A causes a partial skipping of exon 11. The exon 11 expression in the two patients heterozygous for this variant was 22 % and 42 % of that of the controls, respectively. CONCLUSION: We conclude that variant c.164+2dup affects mRNA processing and can be considered a CF-causing variant. The results of the functional assay also showed that the p.(Glu528=) variant, usually categorized as a neutral variant based on epidemiological data, partially affects mRNA processing in our patients. This finding would allow us to reclassify the variant as a CFTR-related variant with incomplete penetrance. RNA obtained from nasal epithelial cells is an easy and accurate tool for CFTR functional studies in patients with unclassified splice variants.

Lesiones cutáneas relacionadas con la dependencia en el paciente crítico pronado. Estudio de incidencia / Dependency-related skin lesions in the prone critical patient. Incidence study

Objetivo: Determinar la incidencia de las lesiones cutáneas relacionadas con la dependencia (LCRD) en los pacientes en decúbito prono (DP) e identificar los factores predisponentes. Método: Estudio descriptivo-longitudinal en 2 unidades de cuidados intensivos (UCI) polivalentes. Se incluyeron pacientes con ventilación mecánica invasiva y DP, sin lesiones al ingreso. Se registraron 3 tipos de LCRD: (lesiones por presión [LPP], lesiones cutáneas asociadas a la humedad [LESCAH] y lesiones por fricción [LF]), variables demográficas, diagnóstico, estancia, episodios en DP, cambios posturales, APACHE II (Acute Physiology and Chronic Health Disease Classification System), prealbúmina al ingreso, índice de masa corporal (IMC), diabetes, hipertensión arterial, tabaquismo, enfermedad vascular periférica (EVP), fármacos vasoactivos, escala de Braden y mortalidad. Análisis bivariante: prueba de χ2, t-Student o U de Mann-Whitney. Multivariante: regresión logística. Resultados: Se incluyeron 49 pacientes. Se realizaron 170 DP. Aparecieron 41 LCRD en 22 pacientes con una incidencia acumulada del 44,9% (IC 95%: 31,6-58,7). El 63,4% LPP (73,1% faciales; 76,9% categoría II), el 12,2% LESCAH (60% inguinales; 60% categoría II) y el 24,4% LF (50% torácicas; 70% categoría III). La mediana de edad del grupo con lesiones (GCL) fue de 66,5 (61,8-71,3) frente al 64 (43-71) años del grupo sin lesiones (GSL); p=0,04. El 80% del GCL tenía EVP frente al 20% del GSL; p=0,03. La mediana de horas totales en DP del GCL fue de 96,9 (56,1-149,4) frente a 38,2 (18,8-57) del GSL; p<0,001. El análisis multivariante seleccionó horas totales DP (OR: 1,03; IC 95%: 1,01-1,05) y la EVP (OR: 8,9; IC 95%: 1,3-58,9) como factores predisponentes para desarrollar LCRD. Conclusiones: Existe una elevada incidencia de LCRD en DP, mayoritariamente lesiones por presión, aunque de baja severidad. Las horas acumuladas en DP y la enfermedad vascular periférica favorecen su desarrollo.(AU)

Objective: To determine the incidence of dependence-related skin lesions (DRSL) in patients in prone position (PP) and to identify the predisposing factors. Method: Follow-up study in two polyvalent intensive care units. Patients undergoing invasive mechanical ventilation and PP with no skin lesions on admission were included. We recorded the 3 types of DRSL:(pressure ulcers (PU), moisture-associated skin damage (MASD) and friction injuries (FI)), demographic variables, diagnosis, length of stay, PP episodes, postural changes, APACHE II (Acute Physiology and Chronic Health Disease Classification System), prealbumin level on admission, body mass index (BMI), diabetes, hypertension, smoking, peripheral vascular disease (PVD), vasoactive drugs, Braden scale and mortality. Bivariate analysis: Chi-square test, t-test or Mann-Whitney U test. Multivariate analysis: logistic regression. Results: Forty nine patients were included and 170 PP were performed. Forty-one DRSL appeared in 22 patients with a cumulative incidence of 44.9% (95% CI: 31.6-58.7). PU accounted for 63.4% (73.1% facial; 76.9% stage II), 12.2% were MASD (60% inguinal; 60% stage II) and 24.4% were FI (50% thoracic; 70% stage III). The median age of the lesion group (LG) was 66.5 (61.8-71.3) vs 64 (43-71) years old in the non-lesion group (NLG), P=.04. Eighty percent of the LG had PVD vs 20% of the NLG, p=0.03. The median total hours on PP of the LG was 96.9 (56.1-149.4) vs 38.2 (18.8-57) of the NIG, P<.001. Multivariate analysis selected total PP hours (OR: 1.03; 95% CI: 1.01-1.05) and PVD (OR: 8.9; 95% CI: 1.3-58.9) as predisposing factors for developing DRSL. Conclusions: There is a high incidence of skin lesions related to prone decubitus dependence, mostly pressure lesions, although of low severity. The accumulated hours in probe position and peripheral vascular disease favor their development.(AU)

Dependency-related skin lesions in the prone critical patient. Incidence study.

OBJECTIVE: To determine the incidence of dependence-related skin lesions (DRSL) in patients in prone position (PP) and to identify the predisposing factors. METHOD: Follow-up study in two polyvalent intensive care units. Patients undergoing invasive mechanical ventilation and PP with no skin lesions on admission were included. We recorded the 3 types of DRSL: (pressure ulcers [PU], moisture-associated skin damage [MASD] and friction injuries [FI]), demographic variables, diagnosis, length of stay, PP episodes, postural changes, APACHE II (Acute Physiology and Chronic Health Disease Classification System), prealbumin level on admission, body mass index (BMI), diabetes, hypertension, smoking, peripheral vascular disease (PVD), vasoactive drugs, Braden scale and mortality. Bivariate analysis: chi-square test, t-test or Mann-Whitney U test. Multivariate analysis: logistic regression. RESULTS: Forty nine patients were included and 170PP were performed.Forty-one DRSL appeared in 22 patients with a cumulative incidence of 44.9% (95%CI: 31.6-58.7). PU accounted for 63.4% (73.1% facial; 76.9% stage II), 12.2% were MASD (60% inguinal; 60% stage II) and 24.4% were FI (50% thoracic; 70% stage III). The median age of the lesion group (LG) was 66.5 [61.8-71.3] vs. 64 [43-71] years old in the non-lesion group (NLG), p=0.04. Eighty percent of the LG had PVD vs. 20% of the NLG, p=0.03. The median total hours on PP of the LG was 96.9 [56.1-149.4] vs. 38.2 [18.8-57] of the NIG, p<0.001. Multivariate analysis selected total PP hours (OR=1.03; 95%CI:1.01-1.05) and PVD (OR=8.9; 95%CI:1.3-58.9) as predisposing factors for developing DRSL. CONCLUSIONS: There is a high incidence of skin lesions related to prone decubitus dependence, mostly pressure lesions, although of low severity.The accumulated hours in probe position and peripheral vascular disease favor their development.

Clinical and genetic characteristics of a patient with phosphoribosyl pyrophosphate synthetase 1 deficiency and a systematic literature review.

Phosphoribosylpyrophosphate synthetase 1 (PRS-I) is an enzyme involved in nucleotide metabolism. Pathogenic variants in the PRPS1 are rare and PRS-I deficiency can manifest as three clinical syndromes: X-linked non-syndromic sensorineural deafness (DFN2), X-linked Charcot-Marie-Tooth neuropathy type 5 (CMTX5) and Arts syndrome. We present a Slovenian patient with PRS-I enzyme deficiency due to a novel pathogenic variant - c.424G > A (p.Val142Ile) in the PRPS1 gene, who presented with gross motor impairment, severe sensorineural deafness, balance issues, ataxia, and frequent respiratory infections. In addition, we report the findings of a systemic literature review of all described male cases of Arts syndrome and CMTX5 as well as intermediate phenotypes. As already proposed by other authors, our results confirm PRS-I deficiency should be viewed as a phenotypic continuum rather than three separate syndromes because there are multiple reports of patients with an intermediary clinical presentation.

Oral Focal Mucinosis of the Tongue: A Rare Localization for a Rare Entity.

ABSTRACT: Oral focal mucinosis (OFM) is a rare connective tissue disorder that is characterized by the excessive production of hyaluronic acid due to myxoid degeneration of submucosal connective tissue. The disorder typically presents as an asymptomatic nodule or mass in the gingiva or hard palate, and OFM of the tongue is even more unusual. In this report, we present a case of OFM on the tongue in a 72-year-old female patient who presented with a symptomatic lump that had been growing for 6 months on the dorsum of her tongue. The patient reported discomfort and pain while speaking and swallowing, and the lump was visually apparent on examination. OFM is a benign condition that does not have any specific clinical or radiographical features that distinguish it from other more common oral lesions, such as lipoma or fibroma. Therefore, histopathological examination is essential for a definitive diagnosis. The management of OFM typically involves surgical excision of the lesion. In this case, complete surgical removal of the lesion under general anesthesia was performed, and the patient was followed up for 10 months postoperatively. During the follow-up period, there was no evidence of recurrence, and the patient reported significant improvement in her symptoms. In conclusion, OFM is a rare connective tissue disorder that can occur in the oral cavity. Although OFM of the tongue is even rarer, it should be considered in the differential diagnosis of oral lesions. Histopathological examination is essential for definitive diagnosis, and surgical excision is typically the preferred treatment modality.

Outcomes of Valvular Endocarditis in Patients With and Without Pericardial Effusion: A National Inpatient Sample Study.

Over the last decade, hospitalizations for infective endocarditis (IE) have been steadily increasing, leading to a significant healthcare burden. Pericardial effusion (PCE) has been identified as a serious complication of IE, yet no significant association with mortality has been established. Our study aims to further analyze and understand the significance of PCE in patients with IE. We performed a retrospective analysis using the national inpatient sample database to identify all the hospital admissions with IE using ICD 10 codes and stratified them into 2 groups based on the presence of PCE. The outcomes of interest were inhospital mortality, inhospital complications, need for cardiac surgery, and length of stay. From 2015 Q4-2019, a total of 76,260 hospitalizations were included (weighted: 381,300), of which 2.7% included a PCE diagnosis. Hospitalizations with a PCE diagnosis included patients that were younger (51 vs 61, P < 0.001), as well as slightly more males (58.0% vs 55.2%, P = 0.011), and black patients (16.9% vs 12.9%, P < 0.001). PCE was associated with higher in-hospital death (12.7% vs 9.0%, P < 0.001), longer lengths of stay (12 days vs 7 days, P < 0.001), higher rates of cardiac surgery (22.4% vs 7.3%, P < 0.001). The rates of heart failure, heart block, renal failure, cardiogenic shock, and embolic stroke were higher on PCE group. We found that presence of PCE is associated with higher inhospital mortality, longer length of stay, and greater utilization of cardiac surgery, as well as presence of heart failure, heart block, cardiogenic shock, and embolic stroke.

Cation leak through the ATP1A3 pump causes spasticity and intellectual disability.

ATP1A3 encodes the α3 subunit of the sodium-potassium ATPase, one of two isoforms responsible for powering electrochemical gradients in neurons. Heterozygous pathogenic ATP1A3 variants produce several distinct neurological syndromes, yet the molecular basis for phenotypic variability is unclear. We report a novel recurrent variant, ATP1A3(NM_152296.5):c.2324C>T; p.(Pro775Leu), in nine individuals associated with the primary clinical features of progressive or non-progressive spasticity and developmental delay/intellectual disability. No patients fulfil diagnostic criteria for ATP1A3-associated syndromes, including alternating hemiplegia of childhood, rapid-onset dystonia-parkinsonism or cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss (CAPOS), and none were suspected of having an ATP1A3-related disorder. Uniquely among known ATP1A3 variants, P775L causes leakage of sodium ions and protons into the cell, associated with impaired sodium binding/occlusion kinetics favouring states with fewer bound ions. These phenotypic and electrophysiologic studies demonstrate that ATP1A3:c.2324C>T; p.(Pro775Leu) results in mild ATP1A3-related phenotypes resembling complex hereditary spastic paraplegia or idiopathic spastic cerebral palsy. Cation leak provides a molecular explanation for this genotype-phenotype correlation, adding another mechanism to further explain phenotypic variability and highlighting the importance of biophysical properties beyond ion transport rate in ion transport diseases.

Age differences in the use of positive and negative cues to filter distracting information from working memory.

Previous research has demonstrated that as people age, visual working memory (VWM) declines. One potential explanation for this decline is that older adults are less able to ignore irrelevant information, which contributes to VWM filtering deficits. Most research examining age differences in filtering ability has used positive cues (indicating which items to pay attention to), but negative cues (indicating which items to ignore) may be even harder for older adults to implement as some work suggests that negatively cued items are first paid attention to before they are suppressed. The current study aimed to test whether older adults can use negative cues to filter irrelevant information from VWM. Across two experiments, young and older adults were presented with two (Experiment 1) or four (Experiment 2) display items, preceded by a neutral, negative, or positive cue. After a delay, participants reported the target's orientation in a continuous-response task. Results show that both groups benefitted from being provided with a cue (positive or negative) compared to no cue (i.e., neutral condition), but the benefit was smaller for negative cues. Thus, although negative cues aid in filtering of VWM, they are less effective than positive cues, possibly due to residual attention being directed towards distractor items.

[Physical activity programs that include self-efficacy in school children with obesity: a systematic review]. / Programas de actividad física que incluyen la autoeficacia en escolares con obesidad: revisión sistemática.

Introduction: Introduction: this research aims to carry out a systematic review of physical activity programs that improve self-efficacy in children and adolescents with obesity, to realize their characteristics and thus design a more comprehensive and effective program for this population. Objective: to analyze the characteristics of physical activity programs that improve self-efficacy in children and adolescents with obesity, through a systematic review. Methodology: systematic review of observational-descriptive design; the search was realized in databases of the health area: PubMed, ERIC, Cochrane, Redalyc, and Google academic. Free access articles in English and Spanish from the last 10 years were selected. The temporality was from March 2012 to May 2022. The descriptors used were; "physical activity program", "training program", "self-efficacy", "children", "adolescents", and "obesity". Results: six studies were included (n = 10). Different types of interventions that improved self-efficacy in the participant were identified, such as recreational activities, traditional games, sports, and structured activities for health care. The methodology implemented and the timing and duration were key variables to show positive changes in childhood overweight and obesity (6 a 19 years). Conclusions: it is crucial to identify the principal health care characteristics included in programs focused on increasing self-efficacy in childhood. These features lay the foundation for designing comprehensive programs.

Introducción: Introducción: se pretende realizar una revisión sistemática de los programas de actividad física que incluyan y mejoren la autoeficacia en niños y adolescentes con obesidad con la finalidad de analizar sus características y diseñar un programa integral y efectivo en esta población. Objetivo: analizar las características de los programas de actividad física que mejoran la autoeficacia en niños y adolescentes con obesidad a través de una revisión sistemática. Metodología: revisión sistemática de diseño observacional-descriptiva; se realizó la búsqueda en bases de datos del área de la Salud: PubMed, ERIC, Cochrane, Redalyc y Google académico. Se seleccionaron artículos originales de libre acceso en inglés y español de los últimos 10 años. La temporalidad fue de marzo 2012 a mayo de 2022. Los descriptores utilizados fueron: "physical activity program", "training program", "auto efficacy", "children", "teenagers" y "obesity". Resultados: seis estudios fueron incluidos (n = 10). Se identificaron diferentes tipos de intervenciones tales como actividades recreativas, de juegos tradicionales, deportivos y actividades estructuradas para el cuidado de la salud, mismas que mejoraron la autoeficacia en el participante. La metodología implementada y la temporalidad y duración fueron variables clave para evidenciar cambios positivos en el sobrepeso y obesidad infantil (6 a 19 años). Conclusiones: es importante identificar las características de los programas orientados a la mejora de la autoeficacia en la etapa de la infancia y adolescencia. Sus características principales pueden utilizarse para diseñar programas integrales.

Association Among Different Aerobic Threshold Markers and FATmax in Men With Obesity.

Purpose: This work studies the interrelation of the first ventilatory threshold (VT1), the heart rate inflection point (HRIP), and the exercise intensity at which blood lactate started to accumulate (LIAB) or increased 1 mmol∙L-1 above baseline (LT+1.0); and examinee their association with the exercise intensity eliciting maximal fat oxidation (FATmax). Methods: Eighteen young men with obesity performed an incremental-load exercise test on a treadmill after overnight fasting. Gas exchange, heart rate, and blood lactate concentration were recorded. Linear regression analysis was used to determine the association among FATmax and AeT markers. A standard error of estimate (SEE) ≤9 beats∙min-1 and the concordance correlation coefficient (CCC) were used to examine the accuracy of different AeT for predicting FATmax heart rate. Results: The FATmax occurred at 36±7%VO2peak before the HRIP (41±6%VO2peak), LIAB (42±10%VO2peak), LT+1.0 (61±9%VO2peak) and VT1 (40±7%VO2peak). Furthermore, the HRIP (R2= 0.71; SEE= 6 beats∙min-1; CCC=0.77), VT1 (R2= 0.76; SEE= 5 beats∙min-1; CCC=0.84) and LIAB (R2= 0.77; SEE= 5 beats∙min-1; CCC=0.85) were strongly associated to FATmax and showed an acceptable estimation error for predicting FATmax heart rate. Otherwise, LT+1.0 showed a moderate correlation with FATmax, a low accuracy for predicting FATmax HR (R2= 0.57; SEE= 7 beats∙min-1; CCC=0.66) and a poor agreement with the rest of AeT markers (Bias: +20%VO2peak). Conclusion: The HRIP, LIAB and VT1 did not perfectly captured the FATmax, however, these could be exchanged for predicting the FATmax heart rate in men with obesity. Moreover, the LT+1.0 should not be used for AeT or FATmax assessment in men with obesity.

Association of Gout Polygenic Risk Score With Age at Disease Onset and Tophaceous Disease in European and Polynesian Men With Gout.

OBJECTIVE: To determine whether a gout polygenic risk score (PRS) is associated with age at gout onset and tophaceous disease in European, East Polynesian, and West Polynesian men and women with gout. METHODS: A 19-variant gout PRS was produced in 7 European gout cohorts (N = 4,016), 2 East Polynesian gout cohorts (N = 682), and 1 West Polynesian gout cohort (N = 490). Sex-stratified regression models were used to estimate the relationship between the PRS and age at gout onset and tophaceous disease. RESULTS: The PRS was associated with earlier age at gout onset in men (ß = -3.61 in years per unit PRS [95% confidence interval (95% CI) -4.32, -2.90] in European men; ß = -6.35 [95% CI -8.91, -3.80] in East Polynesian men; ß = -3.51 [95% CI -5.46, -1.57] in West Polynesian men) but not in women (ß = 0.07 [95% CI -2.32, 2.45] in European women; ß = 0.20 [95% CI -7.21, 7.62] in East Polynesian women; ß -3.33 [95% CI -9.28, 2.62] in West Polynesian women). The PRS showed a positive association with tophaceous disease in men (odds ratio [OR] for the association 1.15 [95% CI 1.00, 1.31] in European men; OR 2.60 [95% CI 1.66, 4.06] in East Polynesian men; OR 1.53 [95% CI 1.07, 2.19] in West Polynesian men) but not in women (OR for the association 0.68 [95% CI 0.42, 1.10] in European women; OR 1.45 [95% CI 0.39, 5.36] in East Polynesian women). The PRS association with age at gout onset was robust to the removal of ABCG2 variants from the PRS in European and East Polynesian men (ß = -2.42 [95% CI -3.37, -1.46] and ß = -6.80 [95% CI -10.06, -3.55], respectively) but not in West Polynesian men (ß = -1.79 [95% CI -4.74, 1.16]). CONCLUSION: Genetic risk variants for gout also harbor risk for earlier age at gout onset and tophaceous disease in European and Polynesian men. Our findings suggest that earlier gout onset involves the accumulation of gout risk alleles in men but perhaps not in women, and that this genetic risk is shared across multiple ancestral groups.

Real-world use of ustekinumab therapeutic drug monitoring in moderate to severe psoriasis.

Introduction: There is growing evidence that therapeutic drug monitoring of biologic therapy is beneficial in psoriatic patients. With respect to ustekinumab, the available evidence has not shown any relationship yet. The objective of this study is to identify correlations among ustekinumab trough concentrations, anti-ustekinumab antibodies and clinical response in moderate-to-severe plaque psoriasis patients, in a real-world setting. Methods: Observational prospective follow-up study in psoriatic patients treated with ustekinumab. Patients were classified in optimal (PASI ≤ 3) and suboptimal responders (PASI > 3). Mann-Whitney U test and Spearman's rank correlation coefficient were used. Receiver-operator characteristic curve analysis was performed to identify ustekinumab concentration cut-off to achieve optimal response. A p-value < 0.05 was considered statistically significant. Results: A total of 59 patients were included. Forty-eight patients (81.4%) corresponded to optimal responders and 11 (18.6%) to suboptimal responders. There was significant difference to ustekinumab concentrations: 0.7 µg/mL (range <0.1-1.8) vs. 0.4 µg/mL (range <0.1-0.8) respectively (p = 0.007). Positive correlation between ustekinumab concentration and psoriasis area and severity index (PASI) value was detected (p = 0.009). A cut-off value of 0.6 µg/mL ustekinumab concentration was found to achieve clinical response. Anti-ustekinumab antibodies were detected in 2 (3.4%) samples, both suboptimal responders. Conclusion: A positive correlation exits between ustekinumab concentration and clinical response (optimal response PASI values ≤ 3) in blood draws performed before drug administration. The measurement of anti-ustekinumab antibodies could be considered in treatment failure.

Sex difference in clinical and procedural outcomes in patients undergoing coronary atherectomy: a systematic review and meta-analysis.

BACKGROUND: Rotational and orbital coronary atherectomy (CA) are commonly utilized to treat complex calcified coronary lesions. We conducted a meta-analysis to evaluate sex differences in procedural complications and clinical outcomes after CA. METHODS: PubMed, Google Scholar, and Cochrane databases were searched for all studies comparing sex differences in procedural and clinical outcomes following CA. The outcomes of interest were procedural complications (coronary dissection, stroke, major bleeding, coronary perforation, cardiac tamponade, and slow or no flow in target vessel) and the clinical outcomes (including early mortality, mid-term all-cause mortality, stroke, myocardial infarction, and target vessel revascularization). Pooled risk ratios (RRs) with their corresponding 95% confidence intervals (CIs) were calculated using the Mantel-Haenszel random-effects model. RESULTS: Six observational studies with 3517 patients (2420 men and 1035 women) were included in this meta-analysis. While there was no significant difference in the early mortality (RR, 1.14; 95% CI, 0.37-3.53; P = 0.83) between men and women, at a mean follow-up of 2.9 years, all-cause mortality was significantly higher in women (RR, 1.29; 95% CI, 1.11-1.49; P = 0.0009). Women had an increased risk of procedure-related stroke (RR, 3.98; 95% CI, 1.06-14.90; P = 0.04), coronary dissection (RR, 2.10; 95% CI, 1.23-3.58; P = 0.006), and bleeding (RR, 2.26; 95% CI, 1.30-3.93; P = 0.004), whereas the rates of coronary perforation, cardiac tamponade, and the risk of slow or no flow in the revascularized artery were similar in both. CONCLUSION: In our analysis, women undergoing CA are at increased risk of mid-term mortality and procedure-related complications including stroke, coronary dissection, and major bleeding.

The Detection of Early Reading Performance and Its Relationship with Biopsychosocial Risk Factors in the Study of Learning Difficulties.

The study of the multiple processes involved in learning how to read can contribute towards the early detection of good and bad readers. However, it is necessary to take into consideration different biopsychosocial risk factors (pre- and perigestational, neonatal, medical, developmental and family-related) that may have a significant impact on neurodevelopment, producing atypical cognitive development that could lead to the presence of reading difficulties. The objective of this study was to identify the main psycholinguistic abilities involved in the early reading performance and analyse their relationship to biopsychosocial risk factors. A total of 110 subjects between the ages of 4 and 7 years old and enrolled in state-run schools in Spain participated in the study. Significant correlations were found between different psycholinguistic abilities and certain biopsychosocial risk factors (having had hyperbilirubinemia, having obtained a score lower than 9 on the Apgar test, having had language problems or a sibling with dyslexia). This relationship should be taken into account in the study of learning difficulties as a potential indicator to predict later reading development and even the presence of developmental dyslexia.

Anthropometric Equations to Determine Maximum Height in Adults ≥ 60 Years: A Systematic Review.

Although it is common to measure bone lengths for study, methodological errors in data measurement and processing often invalidate their clinical and scientific usefulness. This manuscript reviews the validity of several published equations used to determine the maximum height in older adults, since height is an anthropometric parameter widely employed in health sciences. A systematic review of original articles published in the English, Spanish, or Portuguese languages was performed in PubMed, ScienceDirect, EBSCO, Springer Link, and two institutional publisher integrators (UACJ and CONRICYT). The search terms were included in the metasearch engines in a combined way and text form using the Boolean connectors AND and OR {(Determination OR Estimation OR Equation) AND Height AND (Elderly OR "Older adults")}. Eleven manuscripts were selected from 1935 records identified through database searching after applying the following criteria: (1) original articles that designed and validated equations for the determination of height by anthropometric methods in adults 60 years of age and older and (2) manuscripts that presented robust evidence of validation of the proposed regression models. The validity of the reported linear regression models was assessed throughout a manuscript review process called multi-objective optimization that considered the collection of the models, the prediction errors, and the adjustment values (i.e., R2, standard error of estimation, and pure error). A total of 64 equations were designed and validated in 45,449 participants (57.1% women) from four continents: America (85.3%, with 46 equations), Asia (8.1%, with 10), Europe (4.6%, with 7), and Africa (2.0%, with 1); the Hispanic American ethnic group was the most numerous in participants and equations (69.0%, with 28). Due to various omissions and methodological errors, this study did not find any valid and reliable equations to assess the maximum height in older adults by anthropometric methods. It is proposed to adjust allometric mathematical models that can be interpreted in the light of ontogenetic processes.

Physical Disturbance Reduces Cyanobacterial Relative Abundance and Substrate Metabolism Potential of Biological Soil Crusts on a Gold Mine Tailing of Central China.

As the critical ecological engineers, biological soil crusts (biocrusts) are considered to play essential roles in improving substrate conditions during ecological rehabilitation processes. Physical disturbance, however, often leads to the degradation of biocrusts, and it remains unclear how the physical disturbance affects biocrust microorganisms and their related metabolism. In this study, the photosynthetic biomass (indicated by chlorophyll a), nutrients, enzyme activities, and bacterial communities of biocrusts were investigated in a gold mine tailing of Central China to evaluate the impact of physical disturbance on biocrusts during the rehabilitation process of gold mine tailings. The results show that physical disturbance significantly reduced the photosynthetic biomass, nutrient contents (organic carbon, ammonium nitrogen, nitrate nitrogen, and total phosphorus), and enzyme activities (ß-glucosidase, sucrase, nitrogenase, neutral phosphatase, and urease) of biocrusts in the mine tailings. Furthermore, 16S rDNA sequencing showed that physical disturbance strongly changed the composition, structure, and interactions of the bacterial community, leading to a shift from a cyanobacteria dominated community to a heterotrophic bacteria (proteobacteria, actinobacteria, and acidobacteria) dominated community and a more complex bacterial network (higher complexity, nodes, and edges). Altogether, our results show that the biocrusts dominated by cyanobacteria could also develop in the tailings of humid region, and the dominants (e.g., Microcoleus) were the same as those from dryland biocrusts; nevertheless, physical disturbance significantly reduced cyanobacterial relative abundance in biocrusts. Based on our findings, we propose the future work on cyanobacterial inoculation (e.g., Microcoleus), which is expected to promote substrate metabolism and accumulation, ultimately accelerating the development of biocrusts and the subsequent ecological restoration of tailings.