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Purpose: Recent changes in the profile of liver transplant (LT) recipients include an increasing number of patients with metabolic-associated steatotic liver disease (MASLD), which is associated with obesity and cardiovascular risk. We aimed to investigate the trend in the presence of obesity among LT recipients and its association with cardiovascular risk., Materials and Methods: Single-centre retrospective study, which included LT recipients between 2015 and 2020. Obesity and patient's demographic were assessed before LT and 12 months thereafter. Cardiovascular risk factors including ASCVD score were recorded and compared between patients with and without obesity., Results: During the study period, 358 LT were performed. The mean BMI before LT significantly increased over time during the study period (p trend  = 0.04). Pre-LT, patients with obesity were older and had a higher prevalence of MASLD, diabetes, hypertension and dyslipidaemia. Twelve months after LT, most patients gained weight, although mean BMI did not significantly increase over time (p trend  = 0.072). LT recipients with obesity 12 months after LT more frequently presented with diabetes and hypertension and had higher ASCVD score than LT recipients with BMI < 30 kg/m 2 . One-year mortality was similar between patients with or without obesity before LT (p = 0.816)., Conclusion: In the past few years, there has been a significant increase in the prevalence of obesity in LT recipients. LT recipients with obesity present a higher cardiovascular risk as assessed by the presence of cardiovascular risk factors and the ASCVD score. Our results may be useful when designing strategies to directly target obesity and weight management in this population., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Urinary tract infection is a worldwide health problem. According to the Clinical Laboratory Improvement Amendments and the European Urinalysis Guideline, urine samples should be tested within 2 h of collection. Thus, using chemical preservatives that guarantee the pre-analytical conditions is a practical tool. However, the effects of temperature and storage time as uropathogenic bacteria stressors are unclear. Methods: Gram-negative and -positive ATTC strains, E. coli , P. mirabilis , E. faecalis , and S. aureus , were used in this study. Strains in liquid media were stored at 4, 25, and 37 °C for 0, 2, 12, 24, and 48 h in tubes with and without preservatives. Then, reactive oxygen species (ROS) levels, viable but non-culturable bacteria (VBNC), and bacteria growth were analyzed. Results: A high ROS level was associated with the presence of VBNC and dead bacteria with low CFU counts, but a low ROS level increased the CFU number, depending on temperature and storage time in tubes without preservatives (boric acid, sodium borate, and formate). The BD Vacutainer™ Urine Culture & Sensitivity Preservative PLUS Plastic Tubes (C&S-PP) prevent this ROS increase, maintaining the CFU number for longer. Conclusions: C&S-PP tubes minimize the stressor effects (temperature and time storage) on uropathogenic bacteria when stored, improving the pre-analytical conditions of cultures realized by the clinical laboratory.

Purpose: Hydroxychloroquine is currently recommended for the treatment of systemic lupus erythematosus (SLE), but it can cause irreversible retinal toxicity. This study aimed to identify factors associated with early hydroxychloroquine-induced retinal toxicity in patients with SLE from a single centre for 20 years., Methods: SLE patients diagnosed between 1998 and 2017 and followed up for at least 1 year were included. Demographic, clinical, laboratory and therapeutic data were collected from the electronic medical records and retrospectively analysed. Early hydroxychloroquine-induced retinal toxicity was defined as the development of macular toxicity within the first 5 years of hydroxychloroquine treatment., Results: A total of 345 patients followed for a median of 15 years were analysed; 337 (97.7%) patients received hydroxychloroquine, 38 (11.3%) of them presented with retinal toxicity, and 10 (3%) developed early retinal toxicity. These patients had a mean treatment duration of 3.3 years with a mean cumulative dose of 241 g. Patients were diagnosed by visual field (VF) and fundoscopy, and two were also assessed using spectral domain optical coherence tomography (SD-OCT). The median (IQR) age of patients with early toxicity was 56 (51-66) years, and 80% were female. Factors independently associated with early hydroxychloroquine-induced retinal toxicity were lupus anticoagulant positivity (OR 4.2; 95% CI 1.2-15.5) and hypercholesterolaemia (OR 5.6; 95% CI 1.5-21.5)., Conclusion: Our results suggest that lupus anticoagulant positivity and hypercholesterolaemia among SLE patients may be risk factors for early hydroxychloroquine-induced retinal toxicity, regardless of the dose or duration of treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Education influences brain health and dementia. However, its impact across regions, specifically Latin America (LA) and the United States (US), is unknown., Methods: A total of 1412 participants comprising controls, patients with Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD) from LA and the US were included. We studied the association of education with brain volume and functional connectivity while controlling for imaging quality and variability, age, sex, total intracranial volume (TIV), and recording type., Results: Education influenced brain measures, explaining 24%-98% of the geographical differences. The educational disparities between LA and the US were associated with gray matter volume and connectivity variations, especially in LA and AD patients. Education emerged as a critical factor in classifying aging and dementia across regions., Discussion: The results underscore the impact of education on brain structure and function in LA, highlighting the importance of incorporating educational factors into diagnosing, care, and prevention, and emphasizing the need for global diversity in research., Highlights: Lower education was linked to reduced brain volume and connectivity in healthy controls (HCs), Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD). Latin American cohorts have lower educational levels compared to the those in the United States. Educational disparities majorly drive brain health differences between regions. Educational differences were significant in both conditions, but more in AD than FTLD. Education stands as a critical factor in classifying aging and dementia across regions., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background/objectives: Reduced serum magnesium (Mg) levels have been associated with obesity, insulin resistance (IR), type 2 diabetes, and metabolic syndrome in adults. However, in the children population, the evidence is still limited. In this cross-sectional study, we aimed to analyze the association of serum Mg levels with the frequency of overweight and obesity and cardiometabolic traits in 189 schoolchildren (91 girls and 98 boys) between 6 and 12 years old from Mexico City., Subjects/methods: Anthropometrical data were collected and biochemical parameters were measured by enzymatic colorimetric assay. Serum Mg level was analyzed by inductively coupled plasma mass spectrometry (ICP-MS). The triglyceride-glucose (TyG) index was used as a surrogate marker to evaluate IR., Results: Serum Mg level was negatively associated with overweight (Odds ratio [OR] = 0.377, 95% confidence interval [CI] 0.231-0.614, p < 0.001) and obesity (OR = 0.345, 95% CI 0.202-0.589, p < 0.001). Serum Mg level resulted negatively associated with body mass index (BMI, β = -1.16 ± 0.26, p < 0.001), BMI z-score (β = -0.48 ± 0.10, p < 0.001) and TyG index (β = -0.04 ± 0.04, p = 0.041). Through a mediation analysis was estimated that BMI z-score accounts for 60.5% of the negative association of serum Mg level with IR (Sobel test: z = 2.761; p = 0.005)., Conclusion: Our results evidence that BMI z-score mediate part of the negative association of serum Mg level and IR in Mexican schoolchildren., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: The relationship between dietary zinc (Zn) intake, metabolic diseases, and telomere length has been little explored in the children population. This observational cross-sectional study assesses the association between obesity (OB), cardiometabolic traits, telomere length, and dietary Zn intake in children with normal weight (NW) and OB from Mexico City., Methods: Anthropometric data, blood pressure, biochemical measurements, the homeostatic model assessment of insulin resistance (HOMA-IR) and leucocyte telomere length (determined by quantitative-PCR) were analyzed in 171 children with NW and 172 with OB. Furthermore, dietary Zn intake was evaluated in 117 children NW and 120 with OB., Results: Telomere shortening was associated with fasting plasma insulin (FPI) and HOMA-IR in NW (beta coefficient [β] FPI  = -0.022 ± 0.008, p = 0.009; β HOMA-IR  = -0.096 ± 0.040, p = 0.020) and OB (β FPI  = -0.007 ± 0.002, p = 0.003; β HOMA-IR  = -0.034 ± 0.012, p = 0.005) children. Dietary Zn intake resulted negatively associated with FPI (β = -2.418 ± 0.764, p = 0.002) and HOMA-IR (β = -0.399 ± 0.014, p = 0.009) in children with OB. Then, in children with OB, the association between FPI, HOMA-IR, and telomere shortening was evaluated separately in groups of low, medium, and high dietary Zn intake (according to tertiles). The association between FPI, HOMA-IR, and telomere shortening was not significant in the high Zn intake group (P FPI  = 0.633; P HOMA-IR  = 0.567)., Conclusion: Our results suggest that a high Zn intake may ameliorate the telomere shortening related to high FPI and HOMA-IR., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Dioecious plant species, i.e., those in which male and female functions are housed in different individuals, are particularly vulnerable to global environmental changes. For long-lived plant species, such as trees, long-term studies are imperative to understand how growth patterns and their sensitivity to climate variability differentially affect the sexes., Methods: Here, we explore long-term intersexual differences in wood traits, namely radial growth rates, water use efficiency quantified as stable carbon isotope abundance of wood cellulose, and their climate sensitivity in Ilex aquifolium trees growing in a natural population in NW Spain., Key Results: We found that sex differences in secondary growth rates were variable over time, with males outperforming females in both radial growth rates and water use efficiency in recent decades. Summer water stress significantly reduced the growth of female trees in the following growing season, while the growth of male trees was primarily favoured by cloudy and rainy conditions the previous fall and winter combined with low cloud cover and warm conditions in summer. Sex-dependent lagged correlations between radial growth and water availability were found, with a strong association between tree growth and cumulative water availability in females at 30 months and in males at 10 months., Conclusions: Overall, our results point to greater vulnerability of female tress to increasing drought, which could lead to sex-ratio biases threatening population viability in the future., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Annals of Botany Company.)

Cancer remains a leading cause of death, with increasing incidence. Conventional treatments offer limited efficacy and cause significant side effects, hence novel drugs with improved pharmacological properties and safety are required. Silvestrol (SLV) is a flavagline derived from some plants of the Aglaia genus that has shown potent anticancer effects, warranting further study. Despite its efficacy in inhibiting the growth of several types of cancer cells, SLV is characterized by an unfavorable pharmacokinetics that hamper its use as a drug. A consistent research over the recent years has led to develop novel SLV derivatives with comparable pharmacodynamics and an ameliorated pharmacokinetic profile, demonstrating potential applications in the clinical management of cancer. This comprehensive review aims to highlight the most recent data available on SLV and its synthetic derivatives, addressing their pharmacological profile and therapeutic potential in cancer treatment. A systematic literature review of both in vitro and in vivo studies focusing on anticancer effects, pharmacodynamics, and pharmacokinetics of these compounds is presented. Overall, literature data highlight that rationale chemical modifications of SLV are critical for the development of novel drugs with high efficacy on a broad variety of cancers and improved bioavailability in vivo. Nevertheless, SLV analogues need to be further studied to better understand their mechanisms of action, which can be partially different to SLV. Furthermore, clinical research is still required to assess their efficacy in humans and their safety., 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 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: To validate the comprehensive ICF core set for post-acute musculoskeletal conditions from the perspective of patients in a primary care physiotherapy setting., Materials and Methods: A qualitative study was conducted with patients suffering from musculoskeletal problems. A phenomenological approach based on focus groups was used to identify the most relevant aspects related to physical therapy care in their condition. The data were analyzed using a meaning condensation procedure, identifying relevant themes and concepts. The identified concepts were linked to the ICF and compared to the ICF core set for post-acute musculoskeletal conditions., Results: Forty-three patients were included in eight focus groups. A total of 1281 relevant concepts were extracted and related to 156 ICF second-level entities. Entities in the ICF core set for post-acute musculoskeletal conditions were 95.7% confirmed. Eighty-nine additional second-level ICF entities were identified., Conclusions: Entities in the ICF core set for post-acute musculoskeletal conditions are relevant to patients seen in primary care physical therapy units. However, there are areas of functioning related to community health care not covered by this ICF-based tool.IMPLICATIONS OF REHABILITATIONAn ICF-based framework is feasible for the assessment of musculoskeletal conditions.Post-acute musculoskeletal ICF core set was confirmed in patient focus groups.Additional ICF categories emerged for a primary care physical therapy setting.Community features of functioning could be addressed by a tailored ICF core set.

This study aimed to modify chitosan (CS) by gamma irradiation and use it as a surface coating of nanoparticles (NPs) fabricated of poly lactic-co-glycolic acid (PLGA) to create mostly biocompatible nanosystems that can transport drugs to neurons. Gamma irradiation produced irradiated CS (CSγ) with a very low molecular weight (15.2-19.2 kDa). Coating NPs-PLGA with CSγ caused significant changes in their Z potential, making it slightly positive (from -21.7 ± 2.8 mV to +7.1 ± 2.3 mV) and in their particle size (184.4 0.4 ± 7.9 nm to 211.9 ± 14.04 nm). However, these changes were more pronounced in NPs coated with non-irradiated CS (Z potential = +54.0 ± 1.43 mV, size = 348.1 ± 16.44 nm). NPs coated with CSγ presented lower cytotoxicity and similar internalization levels in SH-SY5Y neuronal cells than NPs coated with non-irradiated CS, suggesting higher biocompatibility. Highly biocompatible NPs are desirable as nanocarriers to deliver drugs to the brain, as they help maintain the structure and function of the blood-brain barrier. Therefore, the NPs developed in this study could be evaluated as drug-delivery systems for treating brain diseases., 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 Ltd.)

Objective: Report the prevalence and severity of the most common allergic diseases in children living in Monterrey, México., Methods: Cross-sectional multi-center survey on the most common allergic diseases, completed by parents of 6-7-year-old children and by 13-14- year-old adolescents in the Monterrey metropolitan area, between January 2018 and December 2019., Results: A total of 3,044 questionnaires were eligible for the analysis. Among children between 6-7 years old, 30.2% (n = 143/473) presented wheezing at any time in their life; with a higher prevalence in the male population. In the adolescent group, 26.4% reported having experienced wheezing at some point in their life, with a slight predominance in the female group (54.9%)., Conclusions: Knowing the prevalence of allergic diseases in our population gives us tools to generate strategies that allow us to provide the best quality healthcare to our patients., Competing Interests: The authors declare no conflicts of interest.

(1) Objective: To examine the effects of blood flow restriction (BFR) training on muscle strength, cross-sectional area and knee-related function in patients selected for anterior cruciate ligament reconstruction (ACLR). (2) Methods: A literature search was conducted in PubMed, PEDro, Cochrane Library, Web of Science, SCOPUS, and ProQuest databases until 20 May 2024. Controlled clinical trials comparing the effects of BFR training with unrestricted training in patients before or after ACLR were selected. The GRADE approach was used to assess the degree of certainty for each meta-analysis. (3) Results: Ten studies were included (n = 287 participants). Standardized mean differences in favor of BFR training applied postoperatively were observed in knee extensor (SMD = 0.79; 95% CI = 0.06 to 1.52; I 2 : 68%) and flexor isokinetic strength (SMD = 0.53; 95% CI = 0.04 to 1.01; I 2 : 0%), and quadriceps cross-sectional area (SMD = 0.76; 95% CI = 0.27 to 1.26; I 2 : 0%). No changes were found in knee extensor isometric strength and knee-related function. The degree of certainty according to the GRADE was very low. (4) Conclusions: Very low degree of certainty suggests that BFR training provides additional benefits to unrestricted training on isokinetic strength and quadriceps cross-sectional area in patients undergoing ACLR.

Tourist volcanic caves are in high demand for ecotourism and geotourism lovers, as well as by sun and beach tourists as a complementary activity during their holidays. There are six tourist volcanic caves in the Canary Islands, all of them managed by the local administration of the island. The managers of these caves must ensure the safety of visitors and workers, who are exposed to natural hazards, such as radon, inherent to the environment in which the activity takes place. The methodology for analyzing natural radon radiation is based on the latest studies published by experts in this field and on previous experiences in tourist caves. This article proposes a protocol for the correct management of radon in tourist caves in the Canary Islands, adapted to current regulations, to mitigate effects on the health of visitors and workers., Competing Interests: The authors declare no conflicts of interest relevant to this study., (© 2024 The Author(s). GeoHealth published by Wiley Periodicals LLC on behalf of American Geophysical Union.)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-beta plaques and neurofibrillary tangles, leading to neuronal loss. Curcumin, a polyphenolic compound derived from Curcuma longa, has shown potential neuroprotective effects due to its anti-inflammatory and antioxidant properties. This review aims to synthesize current preclinical data on the anti-neuroinflammatory mechanisms of curcumin in the context of AD, addressing its pharmacokinetics, bioavailability, and potential as a therapeutic adjunct. An exhaustive literature search was conducted, focusing on recent studies within the last 10 years related to curcumin's impact on neuroinflammation and its neuroprotective role in AD. The review methodology included sourcing articles from specialized databases using specific medical subject headings terms to ensure precision and relevance. Curcumin demonstrates significant neuroprotective properties by modulating neuroinflammatory pathways, scavenging reactive oxygen species, and inhibiting the production of pro-inflammatory cytokines. Despite its potential, challenges remain regarding its limited bioavailability and the scarcity of comprehensive human clinical trials. Curcumin emerges as a promising therapeutic adjunct in AD due to its multimodal neuroprotective benefits. However, further research is required to overcome challenges related to bioavailability and to establish effective dosing regimens in human subjects. Developing novel delivery systems and formulations may enhance curcumin's therapeutic potential in AD treatment., (© 2024 John Wiley & Sons Ltd.)

High voltage electrostatic field processing (HVEF) is a food preservation procedure frequently used to produce healthy minimally processed fruits and vegetables (F&V) as it reduces the growth of microorganisms and activates or inhibits various enzymes, thus retarding their natural ripening while preserving and even enhancing native nutritional quality and sensory characteristics. HVEF is one of the various nonthermal processing technology (NTPT) regarded as abiotic stress that can activate the antioxidant system of F&V and can also inhibith spoilage enzymes as, polyphenol oxidase (PPO), lipoxygenase (LOX), pectin methylesterase (PME), polygalacturonase (PG), cellulase (Cel), β-xylosidase, xyloglucan and endotransglycosylase/hydrolase, bringing positive effect on hardness, firmness, colour attributes, electric conductivity, antioxidant compounds, microstructure and decreasing electrolyte leakage (EL), malondialdehyde (MDA) contents and browning degree. This technique can also increase the contents of fructose, glucose, and sucrose and decrease the production of CO 2 and H 2 O 2 . Additionally, it has been reported that HVEF could be used with other treatments, such as modified atmosphere packaging (MAP) and acidic electrolyzed water (AEW) treatment, to enhance its effects. Future works should deepen on elucidating the activation of the antioxidant systems by applying HVEF of critical enzymes related to the synthesis pathways of phenolic compounds (PC) and carotenoids (Car). Holistic approaches to the effects of HVEF on metabolism based on systems biology also need to be studied by considering the overall biochemical, physical, and process engineering related aspects of this technique., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Sexually hyperactive bucks are more efficient than sexually hypoactive bucks in stimulating testosterone secretion and sexual behaviour in other bucks in seasonal sexual rest by the phenomenon that we called the "buck-to-buck effect". Here, we determined whether physical separation and reduction of the duration of contact with the sexually hyperactive bucks would modify those parameters in sexually hypoactive bucks exposed to the "buck-to-buck effect". Bucks were subjected to natural day length throughout the study; this was the sexually hypoactive group. Other bucks were subjected to artificial long days (16 h of light per day) from 15 November to 15 January followed by exposure to natural day length to stimulate their sexual activity during the rest season; this was the sexually hyperactive group. In Experiment 1, we determined testosterone concentrations and sexual behaviour of six sexually hypoactive bucks separated 1.5 m from six sexually hyperactive bucks for 60 days by a metal open work fence, while a control group of six sexually hypoactive bucks was in permanent contact with six sexually hyperactive bucks. In Experiment 2, the duration of contact with sexually hyperactive males was reduced from 31 days (contact group, six bucks) to 10 days (withdraw group, seven bucks). In experiments 1 and 2, there was an effect of time (P < 0.01) and an interaction between time and groups (P < 0.05). In Experiment 1, testosterone plasma concentrations were greater in bucks in contact with sexually hyperactive bucks than in those separated from bucks at 20 and 30 days after the introduction of sexually hyperactive bucks (P < 0.01). The bucks from the contact group also displayed more nudging than bucks from the separated group from 0 to 30 days (P < 0.001). In Experiment 2, testosterone concentrations were greater in the contact group than in those from the withdraw group from 19 to 31 days after the introduction of sexually hyperactive bucks (P < 0.05). Bucks from the withdraw group displayed more nudging than the contact group 7 days after the introduction of the sexually hyperactive bucks (P < 0.05). Afterwards, bucks from the contact group displayed more nudging than the withdraw group 14, 21 and 28 days after the introduction of the sexually hyperactive bucks. We concluded that physical separation and reduction of the duration of contact with the sexually hyperactive bucks decrease testosterone concentrations and sexual behaviour of bucks in sexual rest exposed to the "buck-to-buck effect"., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

SNAPSHOT USA is a multicontributor, long-term camera trap survey designed to survey mammals across the United States. Participants are recruited through community networks and directly through a website application (https://www.snapshot-usa.org/). The growing Snapshot dataset is useful, for example, for tracking wildlife population responses to land use, land cover, and climate changes across spatial and temporal scales. Here we present the SNAPSHOT USA 2021 dataset, the third national camera trap survey across the US. Data were collected across 109 camera trap arrays and included 1711 camera sites. The total effort equaled 71,519 camera trap nights and resulted in 172,507 sequences of animal observations. Sampling effort varied among camera trap arrays, with a minimum of 126 camera trap nights, a maximum of 3355 nights, a median 546 nights, and a mean 656 ± 431 nights. This third dataset comprises 51 camera trap arrays that were surveyed during 2019, 2020, and 2021, along with 71 camera trap arrays that were surveyed in 2020 and 2021. All raw data and accompanying metadata are stored on Wildlife Insights (https://www.wildlifeinsights.org/), and are publicly available upon acceptance of the data papers. SNAPSHOT USA aims to sample multiple ecoregions in the United States with adequate representation of each ecoregion according to its relative size. Currently, the relative density of camera trap arrays varies by an order of magnitude for the various ecoregions (0.22-5.9 arrays per 100,000 km 2 ), emphasizing the need to increase sampling effort by further recruiting and retaining contributors. There are no copyright restrictions on these data. We request that authors cite this paper when using these data, or a subset of these data, for publication. Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the US Government., (© 2024 The Ecological Society of America.)

Recently, the role of trace elements in the pathophysiology of obesity, insulin resistance (IR), and metabolic diseases has been explored. In this cross-sectional study, we aimed to assess the association of overweight, obesity, and cardiometabolic traits with serum copper (Cu) levels in 346 Mexican adults. Serum Cu level was measured by inductively coupled plasma mass spectrometry (ICP-MS). Anthropometrical data were collected, and biochemical parameters were measured. The triglyceride-glucose (TyG) index was used as a surrogate marker to evaluate IR. Overweight and obesity status was positively associated with the serum Cu level (β = 19.434 ± 7.309, p = 0.008). Serum Cu level was observed to have a positive association with serum triglycerides level (β = 0.160 ± 0.045, p < 0.001) and TyG (β = 0.001 ± 0.001, p < 0.001). Additionally, high serum Cu level was positively associated with overweight and obesity status (odds ratio [OR] = 1.9, 95% confidence interval [95% CI] 1.1-3.4, p = 0.014), hypertriglyceridemia (OR = 3.0, 95% CI 1.7-5.3, p < 0.001), and IR (OR = 2.6, 95% CI 1.4-4.6, p = 0.001). In conclusion, our results suggest that overweight, obesity, hypertriglyceridemia, and IR are positively associated with serum Cu levels in Mexican adults.

Aberrant cholesterol metabolism causes neurological disease and neurodegeneration, and mitochondria have been linked to perturbed cholesterol homeostasis via the study of pathological mutations in the ATAD3 gene cluster. However, whether the cholesterol changes were compensatory or contributory to the disorder was unclear, and the effects on cell membranes and the wider cell were also unknown. Using patient-derived cells, we show that cholesterol perturbation is a conserved feature of pathological ATAD3 variants that is accompanied by an expanded lysosome population containing membrane whorls characteristic of lysosomal storage diseases. Lysosomes are also more numerous in Drosophila neural progenitor cells expressing mutant Atad3, which exhibit abundant membrane-bound cholesterol aggregates, many of which co-localize with lysosomes. By subjecting the Drosophila Atad3 mutant to nutrient restriction and cholesterol supplementation, we show that the mutant displays heightened cholesterol dependence. Collectively, these findings suggest that elevated cholesterol enhances tolerance to pathological ATAD3 variants; however, this comes at the cost of inducing cholesterol aggregation in membranes, which lysosomal clearance only partly mitigates., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Purpose: To evaluate the short-term effects of adding a dry needling therapy to a standard care protocol based on education, exercise and electrotherapy, compared to a sham procedure and to a standard care protocol in isolation in patients with chronic neck pain., Material and Methods: A randomized placebo-controlled trial was performed. The participants in the dry needling group received a standard care protocol based on patient education, therapeutic exercise and electrotherapy, as well as two sessions of dry needling in the upper trapezius, levator scapulae, and/or sternocleidomastoid muscles. The participants in the sham dry needling group received the same standard care protocol and two sessions of sham dry needling. The participants in the control group received the same standard care protocol. The outcomes measured were pain intensity, pressure pain threshold, neck disability, range of movement, activation of deep cervical flexor muscles, kinesiophobia, pain catastrophizing, anxiety, and depression., Results: No significant group by time interactions were found for any of the outcome variables except for lower cervical spine range of movement (F = 3.79; p = 0.030)., Conclusion: The addition of two sessions of dry needling in the superficial neck muscles to a standard protocol did not yield superior results compared to either the standard care alone or the standard care plus sham dry needling in patients with chronic neck pain in any outcome except for cervical range of movement., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The quality of welds is critical to the safety of structures in construction, so early detection of irregularities is crucial. Advances in machine vision inspection technologies, such as deep learning models, have improved the detection of weld defects. This paper presents a new CNN model based on ResNet50 to classify four types of weld defects in radiographic images: crack, pore, non-penetration, and no defect. Stratified cross-validation, data augmentation, and regularization were used to improve generalization and avoid over-fitting. The model was tested on three datasets, RIAWELC, GDXray, and a private dataset of low image quality, obtaining an accuracy of 98.75 %, 90.255 %, and 75.83 %, respectively. The model proposed in this paper achieves high accuracies on different datasets and constitutes a valuable tool to improve the efficiency and effectiveness of quality control processes in the welding industry. Moreover, experimental tests show that the proposed approach performs well on even low-resolution images., Competing Interests: 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., (© 2024 The Authors. Published by Elsevier Ltd.)

Agavins are reserve carbohydrates found in agave plants; they present texture-modifying properties and prebiotic capacity by increasing the viability of the intestinal microbiota. Through its hydrolysis, agave syrup (AS) can be obtained and can be used as a sweetener in food matrices. The objective of this work was to evaluate the effect of the variation in the content of agavins and AS on the physical, structural, and viability properties of Saccharomyces boulardii encapsulates incorporated into gelatin gummies. An RSM was used to obtain an optimized formulation of gelatin gummies. The properties of the gel in the gummy were characterized by a texture profile analysis and Aw. The humidity and sugar content were determined. A sucrose gummy was used as a control for the variable ranges. Alginate microcapsules containing S. boulardii were added to the optimized gummy formulation to obtain a synbiotic gummy. The viability of S. boulardii and changes in the structure of the alginate gel of the microcapsules in the synbiotic gummy were evaluated for 24 days by image digital analysis (IDA). The agavins and agave syrup significantly affected the texture properties (<1 N) and the Aw (>0.85). The IDA showed a change in the gel network and an increase in viability by confocal microscopy from day 18. The number of pores in the gel increased, but their size decreased with an increase in the number of S. boulardii cells. Agavins and cells alter the structure of capsules in gummies without affecting their viability.

Background & Aims: Alcoholic foamy degeneration (AFD) is a condition with similar clinical presentation to alcohol-associated hepatitis (AH), but with a specific histologic pattern. Information regarding the prevalence and prognosis of AFD is scarce and there are no tools for a noninvasive diagnosis., Methods: A cohort of patients admitted to the Hospital Clinic of Barcelona for clinical suspicion of AH who underwent liver biopsy was included. Patients were classified as AFD, AH, or other findings, according to histology. Clinical features, histology, and genetic expression of liver biopsy specimens were analyzed. The accuracy of National Institute on Alcohol Abuse and Alcoholism criteria and laboratory parameters for differential diagnosis were investigated., Results: Of 230 patients with a suspicion of AH, 18 (8%) met histologic criteria for AFD, 184 (80%) had definite AH, and 28 (12%) had other findings. In patients with AFD, massive steatosis was more frequent and the fibrosis stage was lower. AFD was characterized by down-regulation of liver fibrosis and inflammation genes and up-regulation of lipid metabolism and mitochondrial function genes. Patients with AFD had markedly better long-term survival (100% vs 57% in AFD vs AH; P = .002) despite not receiving corticosteroid treatment, even in a model for end-stage liver disease-matched sensitivity analysis. Serum triglyceride levels had an area under the receiver operating characteristic of 0.886 (95% CI, 0.807-0.964) for the diagnosis of AFD, whereas the National Institute on Alcohol Abuse and Alcoholism criteria performed poorly. A 1-step algorithm using triglyceride levels of 225 mg/dL (sensitivity, 0.77; specificity, 0.90; and Youden index, 0.67) is proposed for differential diagnosis., Conclusions: AFD in the setting of suspicion of AH is not uncommon. A differential diagnosis is important because prognosis and treatment differ largely. Triglyceride levels successfully identify most patients with AFD and may be helpful in decision making., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Icaritin is a natural prenylated flavonoid derived from the Chinese herb Epimedium. The compound has shown antitumor effects in various cancers, especially hepatocellular carcinoma (HCC). Icaritin exerts its anticancer activity by modulating multiple signaling pathways, such as IL-6/JAK/STAT3, ER-α36, and NF-κB, affecting the tumor microenvironment and immune system. Several clinical trials have evaluated the safety and efficacy of icaritin in advanced HCC patients with poor prognoses, who are unsuitable for conventional therapies. The results have demonstrated that icaritin can improve survival, delay progression, and produce clinical benefits in these patients, with a favorable safety profile and minimal adverse events. Moreover, icaritin can enhance the antitumor immune response by regulating the function and phenotype of various immune cells, such as CD8+ T cells, MDSCs, neutrophils, and macrophages. These findings suggest that icaritin is a promising candidate for immunotherapy in HCC and other cancers. However, further studies are needed to elucidate the molecular mechanisms and optimal dosing regimens of icaritin and its potential synergistic effects with other agents. Therefore, this comprehensive review of the scientific literature aims to summarize advances in the knowledge of icaritin in preclinical and clinical studies as well as the pharmacokinetic, metabolism, toxicity, and mechanisms action to recognize the main challenge, gaps, and opportunities to develop a medication that cancer patients can use. Thus, our main objective was to clarify the current state of icaritin for use as an anticancer drug., (© 2024 Wiley Periodicals LLC.)

This study investigated the application of adsorption with activated carbons (ACs) and photodegradation to reduce the concentration of triclosan (TCS) in aqueous solutions. Concerning adsorption, ACs (Darco, Norit, and F400) were characterised and batch experiments were performed to elucidate the effect of pH on equilibrium. The results showed that at pH = 7, the maximum adsorption capacity of TCS onto the ACs was 18.5 mg g -1 for Darco, 16.0 mg g -1 for Norit, and 15.5 mg g -1 for F400. The diffusional kinetic model allowed an adequate interpretation of the experimental data. The effective diffusivity varied and increased with the amount of TCS adsorbed, from 1.06 to 1.68 × 10 -8  cm 2  s -1 . In the case of photodegradation, it was possible to ensure that the triclosan molecule was sensitive to UV light of 254 nm because the removal was over 80 % using UV light. The removal of TCS increased in the presence of sulfate radicals. It was possible to identify 2,4-dichlorophenol as one of the photolytic degradation products of triclosan, which does not represent an environmental hazard at low concentrations of triclosan in water. These results confirm that the use of AC Darco, Norit, and F400 and that photodegradation processes with UV light and persulfate radicals are effective in removing TCS from water, reaching concentration levels that do not constitute a risk to human health or environmental hazard. Both methods effectively eliminate pollutants with relatively easy techniques to implement., 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 Elsevier Inc. All rights reserved.)

Bioactive compounds from medicinal plants have applications in the development of functional foods. However, since they are unstable, encapsulation is used as a conservation alternative. This work aimed to assess the bioactive properties (antioxidant and hypoglycemic) of different extracts, including the infusion, as well as their spray-dried microencapsulates from Tecoma stans leaves. A factorial design was proposed to determine the best extraction conditions, based on ABTS and DPPH inhibition. Maltodextrin (MD), arabic gum (AG), and a 1:1 blend (MD:AG) were used as encapsulating agents. Moreover, characterization through physicochemical properties, gas chromatography/mass spectrometry (GC-MS) and scanning electron microscopy (SEM) of the best two powders based on the bioactive properties were analyzed. The results showed that the combination of stirring, water, and 5 min provided the highest inhibition to ABTS and DPPH (35.64 ± 1.25 mg Trolox/g d.s. and 2.77 ± 0.01 g Trolox/g d.s., respectively). Spray drying decreased the antioxidant activity of the extract while preserving it in the infusion. The encapsulated infusion with MD:AG had the highest hypoglycemic activity as it presented the lowest glycemic index (GI = 47). According to the results, the microencapsulates could potentially be added in foods to enhance nutritional quality and prevent/treat ailments.

Objective: To compare multimodal structural and functional diagnostic methods in patients with systemic lupus erythematosus (SLE) treated with hydroxychloroquine, to identify the best complementary approach for detecting subclinical retinal toxicity., Methods: A cross-sectional, unicentric study was conducted on patients with SLE treated with hydroxychloroquine. Each patient underwent a comprehensive ophthalmic evaluation, comprising structural tests (spectral-domain optical coherence tomography (SD-OCT), en face OCT, en face OCT angiography (OCTA), fundus autofluorescence (FAF)) and functional tests (automated perimetry for visual field (VF) testing, multifocal electroretinography (mfERG)). A diagnosis of macular toxicity required the presence of abnormalities in at least one structural and functional test. The Kappa Concordance Index was used to assess the concordance among the different tests in detecting potential macular toxicity-associated alterations., Results: Sixty-six patients with SLE (132 eyes) were consecutively enrolled. Four (6.1%) patients developed subclinical hydroxychloroquine-induced retinal toxicity without visual acuity impairment. The proportion of abnormal results was 24% for both en face OCT and en face OCTA. Regarding functional analysis, VF was less specific than mfERG in detecting subclinical retinal toxicity (VF specificity 47.5%). En face OCT and en face OCTA structural findings showed better concordance, with a kappa index >0.8, and both identified the same cases of toxicity as FAF., Conclusion: Although structural OCT and VF are frequently used to screen for hydroxychloroquine-induced retinal toxicity, our findings suggest that a combination of mfERG, en face OCT and en face OCTA could improve the diagnostic accuracy for subclinical retinal damage. This study emphasises the importance of a multimodal imaging strategy to promptly detect signs of hydroxychloroquine-induced retinal toxicity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Currently, the modeling of complex chemical-physical processes is drastically influencing industrial development. Therefore, the analysis and study of the combustion process of the boilers using machine learning (ML) techniques are vital to increase the efficiency with which this equipment operates and reduce the pollution load they contribute to the environment. This work aims to predict the emissions of CO, CO 2 , NOx, and the temperature of the exhaust gases of industrial boilers from real data. Different ML algorithms for regression analysis are discussed. The following are input variables: ambient temperature, working pressure, steam production, and the type of fuel used in around 20 industrial boilers. Each boiler's emission data was collected using a TESTO 350 Combustion Gas Analyzer. The modeling, with a machine learning approach using the Gradient Boosting Regression algorithm, showed better performance in the predictions made on the test data, outperforming all other models studied. It was achieved with predicted values showing a mean absolute error of 0.51 and a coefficient of determination of 99.80%. Different regression models (DNN, MLR, RFR, GBR) were compared to select the most optimal. Compared to models based on Linear Regression, the DNN model has better prediction performance. The proposed model provides a new method to predict CO 2 , CO, NOx emissions, and exhaust gas outlet temperature., Competing Interests: 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., (© 2024 The Authors. Published by Elsevier Ltd.)

Due to the distinctive characteristics of probiotics, it is essential to pinpoint strains originating from diverse sources that prove efficacious in addressing a range of pathologies linked to dysfunction of the intestinal barrier. Nine strains of lactic acid bacteria were isolated from two different sources of tepache kefir grains (KAS2, KAS3, KAS4, KAS7, KAL4, KBS2, KBS3, KBL1 and KBL3), and were categorized to the genus Lacticaseibacillus, Liquorilactobacillus, and Lentilactobacillus by 16S rRNA gene. Kinetic behaviors of these strains were evaluated in MRS medium, and their probiotic potential was performed: resistance to low pH, tolerance to pepsin, pancreatin, bile salts, antibiotic resistance, hemolytic activity, and adhesion ability. KAS7 strain presented a higher growth rate (0.50 h-1) compared with KAS2 strain, who presented a lower growth rate (0.29 h-1). KBS2 strain was the only strain that survived the in vitro stomach simulation conditions (29.3%). Strain KBL1 demonstrated significantly higher viability (90.6%) in the in vitro intestine simulation conditions. Strain KAS2 demonstrated strong hydrophilic character with chloroform (85.6%) and xylol (57.6%) and a higher percentage of mucin adhesion (87.1%). However, strains KBS2 (84.8%) and KBL3 (89.5%) showed the highest autoaggregation values. In terms of adhesion to the intestinal epithelium in rats, strains KAS2, KAS3 and KAS4 showed values above 80%. The growth of the strains KAS2, KAS3, KAS4, KBS2, and KBL3 was inhibited by cefuroxime, cefotaxime, tetracycline, ampicillin, erythromycin, and cephalothin. Strains KBS2 (41.9% and 33.5%) and KBL3 (42.5% and 32.8%) had the highest co-aggregation values with S. aureus and E. coli. The results obtained in this study indicate that lactic acid bacteria isolated from tepache can be considered as candidates for potentially probiotic bacteria, laying the foundations to evaluate their probiotic functionality in vivo and thus to be used in the formulation of functional foods., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Oviedo-León et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Aims: The role of medications for alcohol use disorder (MAUD) in patients with cirrhosis is not well established. Evidence on the efficacy and safety of these drugs in these patients is scarce., Approach and Results: We performed a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol guidelines on the efficacy of MAUD in patients with cirrhosis. A search was conducted in PubMed, Embase, and Scopus, including all studies until May 2022. The population was defined as patients with AUD and cirrhosis. The primary outcome was alcohol abstinence. Safety was a secondary outcome. We performed a random-effect analysis and expressed the results as relative risk of alcohol consumption. Heterogeneity was measured by I2 . Out of 4095 unique references, 8 studies on 4 different AUD treatments [baclofen (n = 6), metadoxine (n = 1), acamprosate (n = 1), and fecal microbiota transplant (n = 1)] in a total of 794 patients were included. Four were cohort studies, and 4 were RCTs. Only RCTs were included in the meta-analysis. MAUD was associated with a reduced rate of alcohol consumption [relative risk = 0.68 (CI: 0.48-0.97), P = 0.03], increasing alcohol abstinence by 32% compared to placebo or standard treatment, despite high heterogeneity ( I2 = 67%). Regarding safety, out of 165 serious adverse events in patients treated with MAUD, only 5 (3%) were possibly or probably related to study medications., Conclusion: MAUD in patients with cirrhosis is effective in promoting alcohol abstinence and has a good safety profile. Larger studies on the effects of MAUD are needed, especially in patients with advanced liver disease., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background and Purpose: fibromyalgia is a chronic condition causing widespread pain, fatigue, limited physical function, and reduced quality of life. Aquatic training is recommended as a first-line non-pharmacological treatment. This study aims to evaluate the effectiveness of aquatic training based on aerobic and strengthening exercises in improving symptoms in women with fibromyalgia., Material and Methods: a systematic review with meta-analysis was conducted by searching the PubMed, Scopus, Cochrane Library and Web of Science databases. Randomized clinical trials that compared aquatic therapy with either a control group or a land-based exercise group were included. Study quality was assessed using the PEDro scale, the risk of bias was evaluated using the Cochrane Risk of Bias Tool, and the certainty of the evidence was assessed the GRADE guidelines., Results: six randomized clinical trials comprising 9 publications showed that aquatic therapy had statistically significant benefits compared to no intervention, including pain, fatigue, fibromyalgia impact, depression, physical function, and mental health in the short term. In the medium term, improvements were observed in fibromyalgia impact, physical function, and mental health. However, aquatic therapy was not found to be superior to land-based exercise., Conclusion: low to very low certainty of evidence suggested that aquatic training may reduce pain, fibromyalgia impact, fatigue and depression and improve physical function and mental health in patients with fibromyalgia. Further studies should investigate the medium and long-term effects of aquatic training using larger sample sizes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

There is currently innumerable evidence showing that the lunar cycle affects various reproductive aspects in farm animals. However, there is very little information on the effect of the lunar cycle on productive traits in these species. A retrospective study was conducted (2015-2018) to evaluate the influence of the lunar cycle on some reproductive and productive traits in a guinea pig ( Cavia porcellus ) production system in the southern Andean region of Ecuador. A total of 7352 productive and reproductive records of guinea pig females housed in 3 m 2 cages with a breeding male were analyzed. The following variables were considered: offspring sex ratio, litter size per cage, number of weaned guinea pigs, mortality, individual and litter weaning weight of guinea pigs, and calving frequency. The lunar cycle was split into eight periods of ~3.7-d length each. Data were analyzed by logistic regression and general linear model, and means were compared by the least mean squares method of the SAS. The offspring sex ratio was not correlated to the lunar cycle. The lunar cycle at mating and calving influenced the litter size per cage, number of weaned, and mortality of guinea pigs. The individual and litter-weaning weights were influenced by the lunar cycle at calving. The frequency of calving was greater around the new and full moon than in the remaining periods of the lunar cycle. In conclusion, the lunar cycle influenced several productive and reproductive traits in guinea pigs, such as litter size, mortality, number of pups weaned, and individual and litter weaning weights. This valuable information may have practical applications in management of guinea pig production systems.

Aims: Perform the synthesis of novel fluoro phenyl triazoles via click chemistry with or without microwave irradiation and their evaluation as anti-proliferative agents in SiHa cells., Background: Triazoles are heterocyclic compounds containing a five-member ring with two carbon and three nitrogen atoms. They are of great importance since many of them have shown to have biological activity as antifungal, antiviral, antibacterial, anti-HIV, anti-tuberculosis, vasodilator, and anticancer agents., Objectives: Synthesize novel fluoro phenyl triazoles via click chemistry and evaluate their antiproliferative activity., Methods: First, several fluorophenyl azides were prepared. Reacting these aryl azides with phenylacetylene in the presence of Cu(I) catalyst, the corresponding fluoro phenyl triazoles were obtained by two methodologies, stirring at room temperature and under microwave irradiation at 40ºC. In addition, their antiproliferative activity was evaluated in cervical cancer SiHa cells., Results: Fluoro phenyl triazoles were obtained within minutes by means of microwave irradiation. The compound 3f, containing two fluorine atoms next to the carbon connected to the triazole ring, was the most potent among the fluoro phenyl triazoles tested in this study. Interestingly, the addition of a fluorine atom to the phenyl triazole structure in a specific site increases its antiproliferative effect as compared to parent phenyl triazole 3a without a fluorine atom., Conclusion: Several fluoro phenyl triazoles were obtained by reacting fluoro phenyl azides with phenylacetylene in the presence of copper sulphate, sodium ascorbate and phenanthroline. Preparation of these triazoles with MW irradiation represents a better methodology since they are obtained within minutes and higher yields of cleaner compounds are obtained. In terms of biological studies, the proximity between fluorine atom and triazole ring increases its biological activity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Seasonality of reproductive activity in rams and bucks is the major constraint in temperate and subtropical zones. Rapid alternation between 1 month of short days and 1 month of long days (LD) over three years in lightproof buildings eliminates this seasonality. We examined if this would also work in open barns, using only supplementary light. Over two years, one group of bucks (n = 7) was subjected to alternate 1 month of LD and 1 month of permanent light (LD-LL) and another group (n = 7) to alternate 1 month of LD and 1 month of natural light (LD-NL). A simultaneous control group, used for both experiments (CG1, n = 6; CG2, n = 6), remained under natural photoperiod. BW, testis weight (TW), plasma testosterone (T) and cortisol (C) were evaluated in all bucks. CG1 and CG2 bucks showed identical dramatic seasonal variations in BW (stable or decreasing in summer), TW (from 85 ± 12 g in February to 127 ± 7 g in July) and T (from 2.7 ± 1.2 ng/mL in January-April to 24.3 ± 3.2 ng/mL in June-October). By contrast, BW of LD-LL and LD-NL bucks increased regularly during the experiment. From 5 and 9 months after the experiment onset, LD-LL and LD-NL bucks, respectively, maintained constant TW of 115 ± 5 g until the experiment end. After the first 3 months <5 ng/mL, T of LD-LL bucks remained constant (5-10 ng/mL) until the experiment end. By contrast, T of LD-NL bucks showed four periods of low (<5 ng/mL) and two periods of high concentrations (18.1 ± 2.6 and 11.9 ± 3.4 ng/mL). Plasma C remained low (5-8 ng/mL) and did not change with group or light treatment. These results show for the first time in any seasonal photoperiodic species that it is possible to maintain the sexual activity of males all year round in open buildings using alternating periods of LD and LL. By contrast, return to NL instead of LL every other month does not prevent seasonality in T concentration. These results raise interesting questions about the photoperiodic control of neuroendocrine regulation of seasonal sexual activity and suggest that these treatments can be used to manage males in open barns in farms and in artificial insemination centres. (Spanish and French versions of the full text are available as Supplementary Materials S1 and S2)., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Alcohol is the leading cause of preventable liver morbidity and mortality worldwide, as it is also the most frequent cause of advanced liver disease. Alcohol-associated liver disease (ALD) covers different phenotypes ranging from steatosis to the development of inflammation (steatohepatitis), fibrosis and ultimately, in a proportion of patients, the development of liver cirrhosis and its associated complications. ALD has a complex pathogenesis that includes the interplay of both genetic and environmental factors, yet the precise mechanisms are largely unknown. Alcohol-associated hepatitis (AH) is a severe clinical presentation of ALD, which is characterized by abrupt jaundice and clinical decompensations of liver disease. AH occurs in a percentage of patients with underlying ALD and active alcohol consumption. Currently, there are no approved targeted therapies able to interfere in the pathogenesis of ALD and halt the progression of the disease, therefore alcohol abstinence is the most effective measure to improve prognosis in this patient population. In this regard, alcohol cessation remains the first-line treatment in all stages of alcohol disease. In patients with advanced ALD nonresponding to medical therapy, liver transplantation is the only approach that improves prognosis, and it should be considered in patients with decompensated cirrhosis. In the last years, AH has emerged as a new indication of early liver transplantation in non-responders to medical therapy, with promising results in highly selected patients. In this review, we provide an update on the epidemiology, risk factors, natural history, diagnosis, pathogenesis, and current treatments for ALD, taking into account the importance of assessing and managing alcohol consumption as the etiological factor and the main driver of prognosis in patients with ALD., (Copyright © 2023. Published by Elsevier España, S.L.U.)

(1) Background: Strength training (ST) and aerobic training (AT) are the most recommended interventions in patients with knee OA. These recommendations are supported by high-quality evidence, but it is still unknow whether one type of exercise is superior to the other. Thus, the aim was to investigate whether one type of exercise (ST or AT) is superior to the other for improving pain and physical function in patients with knee osteoarthritis. (2) Methods: A systematic review and meta-analysis was carried out following the PRISMA statement. The search strategy was conducted in PubMed, PEDro, Scopus, Web of Science and Cochrane Library databases. Randomized controlled trials comparing ST and AT on pain intensity and physical function in patients with knee osteoarthritis were included. Methodological quality and risk of bias were assessed with a PEDro scale and risk-of-bias tool, respectively. The certainty of evidence was evaluated using GRADE guidelines. (3) Results: Four studies (6 publications) were included. The qualitative and quantitative synthesis showed that ST produces no more improvement in pain intensity (SMD after intervention: 0.02; 95%CI: -0.15, 0.19; I 2 : 0%; three studies; 426 patients) and physical function (SMD after intervention: 0.07; 95%CI: -0.10, 0.24; I 2 : 0%; three studies; 426 patients) compared to AT in patients with knee osteoarthritis. The certainty of evidence was rated as very low. (4) Conclusions: Both type of exercises showed clinical benefits in people with knee osteoarthritis, but no differences between ST and AT were found.

Tree ring records are among the most valuable resources to create high-resolution climate reconstructions. Most climate reconstructions are based on old trees growing in inaccessible mountainous areas with low human activity. Therefore, reconstruction of climate conditions in lowlands is usually based on data from distant mountains. Albeit old trees can be common in humanized areas, they are not used for climate reconstructions. Pollarding was a common traditional management in Europe that enabled trees to maintain great vitality for periods exceeding the longevity of unmanaged trees. We evaluate the potential of pollarded deciduous oaks to record past climate signal. We sampled four pollarded woodlands in Central Spain under continental Mediterranean climate. We hypothesized that pollarded trees have a strong response to water availability during current period without pollarding management, but also in the period under traditional management if pruning was asynchronous among trees. Moreover, we hypothesized that if climate is a regional driver of oak secondary growth, chronologies from different woodlands will be correlated. Pollard oaks age exceeded 500 years with a strong response to Standardized Precipitation-Evapotranspiration Index (SPEI) from 9 to 11 months. Climate signal was exceptionally high in three of the sites (r 2  = 0.443-0.655) during low management period (1962-2022). The largest fraction of this climate signal (≈70 %) could be retrieved during the traditional management period (1902-1961) in the three sites where pollarding was asynchronous. Chronologies were significantly correlated since the 19th century for all the studied period, highlighting a shared climate forcing. We identified critical points to optimize pollard tree sampling schema. Our results show the enormous potential of pollarded woodlands to reconstruct hydroclimate conditions in the Mediterranean with a fine spatial grain. Studying pollarded trees is an urgent task, since the temporal window to retrieve the valuable information in pollarded trees is closing as these giants collapse and their wood rots., 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 © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: An imbalance between adipokines and micronutrient concentrations, such as those of copper (Cu), has been linked to dysregulation of energy homeostasis leading to weight gain and the development of other comorbidities; however, information on this issue remains limited. Our aim was to investigate the correlation between Cu status and serum adipokine levels and their relationship in normal-weight, overweight, and obese adult women., Methods: Sixty patients were evaluated and classified according to their body mass index (BMI) and biochemical parameters; adipokines and Cu were measured at fasting., Results: Leptin (Lep) and resistin (Res) levels were elevated, whereas adiponectin (Adpn) and ghrelin (Ghr) values were decreased in overweight and obese women (p = 0.001). The mean Adpn/Lep ratio was <0.5 in overweight and obese subjects, while the Lep/Ghr ratio increased significantly in relation to weight gain, suggesting an inverse link between the ratios of these hormones in the regulation of obesity. The analysis revealed a positive association between BMI and Cu levels in obese women. Moreover, a negative association between Cu and Res in normal-weight subjects was found., Conclusions: Circulating fasting Res levels are negatively associated with serum Cu concentration in normal-weight adult women. We also observed a close relationship between Adpn/Lep and Lep/Ghr ratios with obesity. However, more observational studies are required to confirm these results in future research., (© 2023. The Author(s), under exclusive licence to Hellenic Endocrine Society.)

Evidence supporting a starting dose of 2 g/day of mycophenolate mofetil (MMF) in combination with tacrolimus (TAC) for renal transplantation (RT) is still limited, but maintaining a dose of <2 g could result in worse clinical outcomes in terms of acute rejection (AR). This study aimed to determine the association between AR and infectious and noninfectious complications after RT with a dose of 1.5 g vs 2 g of MMF. A prospective cohort study was performed with a 12-month follow-up of recipients of RT from living donors with low (1.5 g/day) or standard (2 g/day) doses of MMF. The association between adverse effects and complications and doses of MMF was examined using Cox proportional hazard models, and survival free of AR, infectious diseases, and noninfectious complications was evaluated using the Kaplan-Meier test. At the end of the follow-up, the incidence of infectious diseases was 52% versus 50% (P = .71) and AR was 5% versus 5% (P = .86), respectively. The survival rate free of gastrointestinal (GI) complications requiring medical attention was higher in the low-dose group than in the standard-dose dose (88% vs 45%, respectively; P < .001). The use of 1.5 g/day of MMF confers a reduction in GI complications without an increase in infectious diseases or the risk of AR., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To assess content validity of the comprehensive International Classification of Functioning, Disability and Health (ICF) Core Set for post-acute musculoskeletal conditions in primary care physiotherapy services., Design: Multicentre cross-sectional study., Subjects: Patients with musculoskeletal disorders referred to primary care physiotherapy services., Methods: Structured interviews were conducted using categories from the ICF Core Set, and their relevance was assessed using a visual analogue scale. An ICF category had to represent a problem for at least 5% of the sample in order to be validated., Results: The study sample comprised 274 patients. All categories in the ICF Core Set were confirmed. Body functions related to pain and movement were the most commonly impaired, with ICF categories "b280 Sensation of pain" and "b710 Mobility of joint functions" having the highest prevalence (87.2% and 84.7%, respectively). Activity limitations and participation restrictions were concentrated in chapters "d4 Mobility" (63.5% for "d430 Lifting and carrying objects") and "d2 General tasks and demands" (59.5% for "d240 Handling stress and other psychological demands"). The most relevant environmental factors were "e225 Climate" (55.8%) and "e580 Health services, systems and policies" (39.4%)., Conclusion: The ICF Core Set for post-acute musculoskeletal conditions shows appropriate content validity for primary care physiotherapy services.

Background: Prolotherapy may be a good option in the complementary treatment of knee osteoarthritis (OA) patients, specifically for the increase of functionality., Objective: To determine the effectiveness of prolotherapy in OA grade II - III in the functionality and muscular work of knee flexors and extensors., Material and Methods: a double-blind randomized controlled clinical trial was conducted. It included patients diagnosed with OA grades II-III. The experimental group was infiltrated in both knees with 6 ml of 25% glucose solution and 0.05% lidocaine; control group with 0.45% saline solution and 0.05% lidocaine. All patients received a comprehensive rehabilitation program. The isokinetic work of the knee flexor and extensor muscles, pain and functionality were measured, prior to infiltration and at 3-month follow-up. To compare the difference in means, the Student's T test was applied, considering P<0.05 as significant. The project was approved by the local ethics and research committee., Results: 37 patients were recruited, 17 in the prolotherapy group. There were no intergroup differences in functionality, isokinetic knee flexor/extensor work, and pain at baseline, or during follow-up up to 12 weeks., Conclusions: In the present study we identify that both prolotherapy and saline infiltration increased functionality, strength, and decreased pain; however, no statistically significant difference was found between the two group., (Licencia CC 4.0 (BY-NC-ND) © 2023 Revista Médica del Instituto Mexicano del Seguro Social.)

In Saccharomyces cerevisiae, the transcriptional repressor Nrg1 (Negative Regulator of Glucose-repressed genes) and the β-Zip transcription factor Rtg3 (ReTroGrade regulation) mediate glucose repression and signalling from the mitochondria to the nucleus, respectively. Here, we show a novel function of these two proteins, in which alanine promotes the formation of a chimeric Nrg1/Rtg3 regulator that represses the ALT2 gene (encoding an alanine transaminase paralog of unknown function). An NRG1/NRG2 paralogous pair, resulting from a post-wide genome small-scale duplication event, is present in the Saccharomyces genus. Neo-functionalization of only one paralog resulted in the ability of Nrg1 to interact with Rtg3. Both nrg1 Δ and rtg3 Δ single mutant strains were unable to use ethanol and showed a typical petite (small) phenotype on glucose. Neither of the wild-type genes complemented the petite phenotype, suggesting irreversible mitochondrial DNA damage in these mutants. Neither nrg1 Δ nor rtg3 Δ mutant strains expressed genes encoded by any of the five polycistronic units transcribed from mitochondrial DNA in S. cerevisiae . This, and the direct measurement of the mitochondrial DNA gene complement, confirmed that irreversible damage of the mitochondrial DNA occurred in both mutant strains, which is consistent with the essential role of the chimeric Nrg1/Rtg3 regulator in mitochondrial DNA maintenance., Competing Interests: The authors declare that they have NO affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript., (© 2023 The Authors.)

Background & Aims: Although histology is considered the gold standard for diagnosis of alcohol-associated hepatitis (AH), it is not required for entry into therapeutic studies if patients meet National Institute on Alcohol Abuse and Alcoholism (NIAAA) consensus criteria for probable AH. Our aim was to assess the diagnostic accuracy of NIAAA criteria against liver biopsy and to explore new criteria to enhance diagnostic accuracy for AH., Methods: A total of 268 consecutive patients with alcohol-related liver disease with liver biopsy were prospectively included: 210 and 58 in the derivation and validation cohorts, respectively. NIAAA criteria and histological diagnosis of alcoholic steatohepatitis (ASH) were independently reviewed by clinical investigators and pathologists from Hospital Clínic and Mayo Clinic. Using biopsy-proven ASH as gold standard we determined diagnostic capability of NIAAA criteria and proposed the new improved criteria., Results: In the derivation cohort, diagnostic accuracy of NIAAA for AH was modest (72%) due to low sensitivity (63%). Subjects who did not meet NIAAA with ASH at liver biopsy had lower 1-year survival compared with subjects without ASH (70% vs 90%; P < .001). NIAAAm-CRP criteria, created by adding C-reactive protein and modifying the variables of the original NIAAA, had higher sensitivity (70%), accuracy (78%), and specificity (83%). Accuracy was also higher in a sensitivity analysis in severe AH (74% vs 65%). In the validation cohort, NIAAAm-CRP and NIAAA criteria had a sensitivity of 56% vs 52% and an accuracy of 76% vs 69%, respectively., Conclusion: NIAAA criteria are suboptimal for the diagnosis of AH. The proposed NIAAAm-CRP criteria may improve accuracy for noninvasive diagnosis of AH in patients with alcohol-related liver disease., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Second-generation biorefineries (2GBR) represent an innovative application of bioresources technologies to produce bioenergy and valuable products. This paper aims to introduce and analyze the joint production of bioethanol and ethyl lactate in a 2GBR. Techno-economic and profitability perspectives are considered in the analysis which is conducted via simulation considering corn stover as raw material. A key aspect in the analysis is a joint production parameter named α, whose values can dictate either the sole production of bioethanol (α = 0), joint production (0 < α < 1), or the unique production of ethyl lactate (α = 1). In other words, the proposed joint production scheme provides versatility in production. Simulations show that the lowest Total Capital Investment, Unit Production Cost, and Operating Cost values were associated with low values of α. Furthermore, when α ≥ 0.4, the 2GBR under study can achieve internal rates of return above 30%, which implies that the project offers a potentially high profitability., 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 © 2023 Elsevier Ltd. All rights reserved.)

Objective: Urinary tract infections (UTI) are a frequent reason for attendance at emergency department (ED). The present study evaluates the impact of a multidisciplinary program for the optimization of antibiotic therapy in patients with UTI caused by multi-drug resistant bacteria treated from the hospital ED., Methods: Descriptive study of the implementation of a program in which emergency, microbiology and pharmacy departments participated. Antibiotic treatment of the patients who consulted the ED with positive urine cultures caused by multidrug-resistant bacteria was reviewed upon discharge. In those patients with inappropriate treatment, doctors and/or pharmacists of the next level of healthcare or patients in the case of home discharge were contacted. The impact of the program was evaluated based on new visits to the ED at 30 days after discharge, compared with the results obtained from the usual practice three months prior the intervention., Results: During the first year, 2,474 urine cultures of patients with UTI were reviewed, 533 (21.7%) were caused by multidrug-resistant bacteria. Empirical treatment was inappropriate in 287 (53.4%), making treatment modifications in 243 of them. 73 (19.3%) patients returned to the ED 30 days after discharge, being lower than the results obtained in the three months prior intervention (27.9%; p=0.031), without significant differences in new visits associated with UTI., Conclusions: The implementation of a multidisciplinary program focused on multidrug resistant UTI at discharge form ED correct antibiotic therapy in a large number of patients, being a potentially tool to reduce the number of new ED visits., (©The Author 2023. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)