Description of BCG and Tuberculosis Disease in a Cohort of 79 Patients with Chronic Granulomatous Disease.

PURPOSE: Chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by pathogenic variants of genes encoding the enzyme complex NADPH oxidase. In countries where tuberculosis (TB) is endemic and the Bacillus Calmette-Guérin (BCG) vaccine is routinely administered, mycobacteria are major disease-causing pathogens in CGD. However, information on the clinical evolution and treatment of mycobacterial diseases in patients with CGD is limited. The present study describes the adverse reactions to BCG and TB in Mexican patients with CGD. METHODS: Patients with CGD who were evaluated at the Immunodeficiency Laboratory of the National Institute of Pediatrics between 2013 and 2024 were included. Medical records were reviewed to determine the clinical course and treatment of adverse reactions to BCG and TB disease. RESULTS: A total of 79 patients with CGD were included in this study. Adverse reactions to BCG were reported in 55 (72%) of 76 patients who received the vaccine. Tuberculosis was diagnosed in 19 (24%) patients. Relapse was documented in three (10%) of 31 patients with BGC-osis and six (32%) of 19 patients with TB, despite antituberculosis treatment. There was no difference in the frequency of BCG and TB disease between patients with pathogenic variants of the X-linked CYBB gene versus recessive variants. CONCLUSIONS: This report highlights the importance of considering TB in endemic areas and BCG complications in children with CGD to enable appropriate diagnostic and therapeutic approaches to improve prognosis and reduce the risk of relapse.

Past, present, and future of sustainable intensive care: narrative review and a large hospital system experience.

Healthcare systems are large contributors to global emissions, and intensive care units (ICUs) are a complex and resource-intensive component of these systems. Recent global movements in sustainability initiatives, led mostly by Europe and Oceania, have tried to mitigate ICUs' notable environmental impact with varying success. However, there exists a significant gap in the U.S. knowledge and published literature related to sustainability in the ICU. After a narrative review of the literature and related industry standards, we share our experience with a Green ICU initiative at a large hospital system in Texas. Our process has led to a 3-step pathway to inform similar initiatives for sustainable (green) critical care. This pathway involves (1) establishing a baseline by quantifying the status quo carbon footprint of the affected ICU as well as the cumulative footprint of all the ICUs in the healthcare system; (2) forming alliances and partnerships to target each major source of these pollutants and implement specific intervention programs that reduce the ICU-related greenhouse gas emissions and solid waste; and (3) finally to implement a systemwide Green ICU which requires the creation of multiple parallel pathways that marshal the resources at the grass-roots level to engage the ICU staff and institutionalize a mindset that recognizes and respects the impact of ICU functions on our environment. It is expected that such a systems-based multi-stakeholder approach would pave the way for improved sustainability in critical care.

Urinary excretion of calcium, phosphate, magnesium, and uric acid in healthy infants and young children. Influence of feeding practices in early infancy.

BACKGROUND: Reference values for urinary calcium (Ca) and other solutes/creatinine (Cr) ratios in infants and young children are scarce. Its variation with type of lactation administered, breastfed (BF) or formula (F), is incompletely known. METHODS: A total of 511 spot urine samples from 136 children, aged 6 days to < 5 years, was collected. Urine was collected no fasting in infants < 18 months and first morning fasting in children aged 2.5-4 years. Urinary osmolality, Cr, urea, Ca, phosphate (P), magnesium (Mg), and uric acid (UA) were determined. Values are expressed as solute-to-Cr ratio. RESULTS: Urinary values were grouped according to the child's age: 6-17 days (G1), 1-5 months (G2), 6-12 months (G3), 13-18 months (G4), and 2.5-4 years (G5). G1 was excluded; Ca/Cr and UA/Cr (95th percentile) decreased with age (G2 vs. G5) from 1.64 to 0.39 and 2.33 to 0.83 mg/mg, respectively. The P/Cr median rises significantly with age from 0.31 (G2) to 1.66 mg/mg (G5). Mg/Cr was similar in all groups (median 0.20, 95th percentile 0.37 mg/mg). Ca/Cr (95th percentile) of BF infants was 1.80 mg/mg (< 3 months) and 1.63 mg/mg (3-5 months), much higher than F infants (0.93 and 0.90 mg/mg, respectively). P/Cr and P/Ca were lower in BF infants. CONCLUSIONS: Values for urinary Ca/Cr, P/Cr, Mg/Cr, and UA/Cr in infants and children < 5 years were updated. BF infants < 6 months showed higher Ca/Cr and lower P/Cr than F infants. New cutoff values to diagnose hypercalciuria in infants < 6 months, according to the type of lactation, are proposed.

Possible Role of Cannabis in the Management of Neuroinflammation in Patients with Post-COVID Condition.

The post-COVID condition (PCC) is a pathology stemming from COVID-19, and studying its pathophysiology, diagnosis, and treatment is crucial. Neuroinflammation causes the most common manifestations of this disease including headaches, fatigue, insomnia, depression, anxiety, among others. Currently, there are no specific management proposals; however, given that the inflammatory component involves cytokines and free radicals, these conditions must be treated to reduce the current symptoms and provide neuroprotection to reduce the risk of a long-term neurodegenerative disease. It has been shown that cannabis has compounds with immunomodulatory and antioxidant functions in other pathologies. Therefore, exploring this approach could provide a viable therapeutic option for PCC, which is the purpose of this review. This review involved an exhaustive search in specialized databases including PubMed, PubChem, ProQuest, EBSCO, Scopus, Science Direct, Web of Science, and Clinical Trials. Phytocannabinoids, including cannabidiol (CBD), cannabigerol (CBG), and Delta-9-tetrahydrocannabinol (THC), exhibit significant antioxidative and anti-inflammatory properties and have been shown to be an effective treatment for neuroinflammatory conditions. These compounds could be promising adjuvants for PCC alone or in combination with other antioxidants or therapies. PCC presents significant challenges to neurological health, and neuroinflammation and oxidative stress play central roles in its pathogenesis. Antioxidant therapy and cannabinoid-based approaches represent promising areas of research and treatment for mitigating adverse effects, but further studies are needed.

Changes in the Dentate Gyrus Gene Expression Profile Induced by Levetiracetam Treatment in Rats with Mesial Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE) is one of the most common forms of focal epilepsy. Levetiracetam (LEV) is an antiepileptic drug whose mechanism of action at the genetic level has not been fully described. Therefore, the aim of the present work was to evaluate the relevant gene expression changes in the dentate gyrus (DG) of LEV-treated rats with pilocarpine-induced TLE. Whole-transcriptome microarrays were used to obtain the differential genetic profiles of control (CTRL), epileptic (EPI), and EPI rats treated for one week with LEV (EPI + LEV). Quantitative RT-qPCR was used to evaluate the RNA levels of the genes of interest. According to the results of the EPI vs. CTRL analysis, 685 genes were differentially expressed, 355 of which were underexpressed and 330 of which were overexpressed. According to the analysis of the EPI + LEV vs. EPI groups, 675 genes were differentially expressed, 477 of which were downregulated and 198 of which were upregulated. A total of 94 genes whose expression was altered by epilepsy and modified by LEV were identified. The RT-qPCR confirmed that LEV treatment reversed the increased expression of Hgf mRNA and decreased the expression of the Efcab1, Adam8, Slc24a1, and Serpinb1a genes in the DG. These results indicate that LEV could be involved in nonclassical mechanisms involved in Ca2+ homeostasis and the regulation of the mTOR pathway through Efcab1, Hgf, SLC24a1, Adam8, and Serpinb1a, contributing to reduced hyperexcitability in TLE patients.

Aptamers: A Cutting-Edge Approach for Gram-Negative Bacterial Pathogen Identification.

Early and accurate diagnoses of pathogenic microorganisms is essential to correctly identify diseases, treating infections, and tracking disease outbreaks associated with microbial infections, to develop precautionary measures that allow a fast and effective response in epidemics and pandemics, thus improving public health. Aptamers are a class of synthetic nucleic acid molecules with the potential to be used for medical purposes, since they can be directed towards any target molecule. Currently, the use of aptamers has increased because they are a useful tool in the detection of specific targets. We present a brief review of the use of aptamers to detect and identify bacteria or even some toxins with clinical importance. This work describes the advances in the technology of aptamers, with the purpose of providing knowledge to develop new aptamers for diagnoses and treatment of different diseases caused by infectious microorganisms.

Unusual Trisomy X Phenotype Associated with a Concurrent Heterozygous 16p11.2 Deletion: Importance of an Integral Approach for Proper Diagnosis.

Trisomy X is the most frequent sex chromosome anomaly in women, but it is often underdiagnosed postnatally because most patients do not show any clinical manifestation. It is estimated that only 10% of patients with trisomy X are diagnosed by clinical findings. Thus, it has been proposed that the clinical spectrum is not yet fully delimited, and additional uncommon or atypical clinical manifestations could be related to this entity. The present report describes a female carrying trisomy X but presenting atypical manifestations, including severe intellectual disability, short stature, thymus hypoplasia, and congenital hypothyroidism (CH). These clinical findings were initially attributed to trisomy X. However, chromosome microarray analysis (CMA) subsequently revealed that the patient also bears a heterozygous 304-kb deletion at 16p11.2. This pathogenic copy-number variant (CNV) encompasses 13 genes, including TUFM. Some authors recommend that when a phenotype differs from that described for an identified microdeletion, the presence of pathogenic variants in the non-deleted allele should be considered to assess for an autosomal recessive disorder; thus, we used a panel of 697 genes to rule out a pathogenic variant in the non-deleted TUFM allele. We discuss the possible phenotypic modifications that might be related to an additional CNV in individuals with sex chromosome aneuploidy (SCA), as seen in our patient. The presence of karyotype-demonstrated trisomy X and CMA-identified 16p11.2 deletion highlights the importance of always correlating a patient's clinical phenotype with the results of genetic studies. When the phenotype includes unusual manifestations and/or exhibits discrepancies with that described in the literature, as exemplified by our patient, a more extensive analysis should be undertaken to enable a correct diagnosis that will support proper management, genetic counseling, and medical follow-up.

Antiangiogenic Effect of Dopamine and Dopaminergic Agonists as an Adjuvant Therapeutic Option in the Treatment of Cancer, Endometriosis, and Osteoarthritis.

Dopamine (DA) and dopamine agonists (DA-Ag) have shown antiangiogenic potential through the vascular endothelial growth factor (VEGF) pathway. They inhibit VEGF and VEGF receptor 2 (VEGFR 2) functions through the dopamine receptor D2 (D2R), preventing important angiogenesis-related processes such as proliferation, migration, and vascular permeability. However, few studies have demonstrated the antiangiogenic mechanism and efficacy of DA and DA-Ag in diseases such as cancer, endometriosis, and osteoarthritis (OA). Therefore, the objective of this review was to describe the mechanisms of the antiangiogenic action of the DA-D2R/VEGF-VEGFR 2 system and to compile related findings from experimental studies and clinical trials on cancer, endometriosis, and OA. Advanced searches were performed in PubMed, Web of Science, SciFinder, ProQuest, EBSCO, Scopus, Science Direct, Google Scholar, PubChem, NCBI Bookshelf, DrugBank, livertox, and Clinical Trials. Articles explaining the antiangiogenic effect of DA and DA-Ag in research articles, meta-analyses, books, reviews, databases, and clinical trials were considered. DA and DA-Ag have an antiangiogenic effect that could reinforce the treatment of diseases that do not yet have a fully curative treatment, such as cancer, endometriosis, and OA. In addition, DA and DA-Ag could present advantages over other angiogenic inhibitors, such as monoclonal antibodies.

Wetland hydropattern and vegetation greenness predict avian populations in Palo Verde, Costa Rica.

Many wetlands around the world that occur at the base of watersheds are under threat from land-use change, hydrological alteration, nutrient pollution, and invasive species. A relevant measure of whether the ecological character of these ecosystems has changed is the species diversity of wetland-dependent waterbirds, especially those of conservation value. Here, we evaluate the potential mechanisms controlling variability over time and space in avian species diversity of the wetlands in the Palo Verde National Park, a Ramsar Site of international importance in Costa Rica. To do so, we assessed the relative importance of several key wetland condition metrics (i.e., surface water depth, wetland extent, and vegetation greenness), and temporal fluctuations in these metrics, in predicting the abundance of five waterbirds of high conservation value as well as overall waterbird diversity over a 9-yr period. Generalized additive models revealed that mean NDVI, an indicator of vegetation greenness, combined with a metric used to evaluate temporal fluctuations in the wetland extent best predicted four of the five waterbird species of high conservation value as well as overall waterbird species richness and diversity. Black-bellied Whistling-ducks, which account for over one-half of all waterbird individuals, and all waterbird species together were better predicted by including surface water depth along with wetland extent and its fluctuations. Our calibrated species distribution model confidently quantified monthly averages of the predicted total waterbird abundances in seven of the 10 sub-wetlands making up the Ramsar Site and confirmed that the biophysical diversity of this entire wetland system is important to supporting waterbird populations both as a seasonal refuge and more permanently. This work further suggests that optimizing the timing and location of ongoing efforts to reduce invasive vegetation cover may be key to avian conservation by increasing waterbird habitat.

Genetic, Immunological, and Clinical Features of the First Mexican Cohort of Patients with Chronic Granulomatous Disease.

PURPOSE: Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by an inability of phagocytes to produce reactive oxygen species, impairing their killing of various bacteria and fungi. We summarize here the 93 cases of CGD diagnosed in Mexico from 2011 to 2019. METHODS: Thirteen Mexican hospitals participated in this study. We describe the genetic, immunological, and clinical features of the 93 CGD patients from 78 unrelated kindreds. RESULTS: Eighty-two of the patients (88%) were male. All patients developed bacterial infections and 30% suffered from some kind of fungal infection. Fifty-four BCG-vaccinated patients (58%) presented infectious complications of BCG vaccine. Tuberculosis occurred in 29%. Granulomas were found in 56% of the patients. Autoimmune and inflammatory diseases were present in 15% of patients. A biological diagnosis of CGD was made in 89/93 patients, on the basis of NBT assay (n = 6), DHR (n = 27), and NBT plus DHR (n = 56). The deficiency was complete in all patients. The median age of biological diagnosis was 17 months (range, 0-186 months). A genetic diagnosis was made in 83/93 patients (when material was available), corresponding to CYBB (n = 64), NCF1 (n = 7), NCF2 (n = 7), and CYBA (n = 5) mutations. CONCLUSIONS: The clinical manifestations in these Mexican CGD patients were similar to those in patients elsewhere. This cohort is the largest in Latin America. Mycobacterial infections are an important cause of morbidity in Mexico, as in other countries in which tuberculosis is endemic and infants are vaccinated with BCG. X-linked CGD accounted for most of the cases in Mexico, as in other Latin American countries. However, a significant number of CYBA and NCF2 mutations were identified, expanding the spectrum of known causal mutations.

Development and validation of a predictive model for incident type 2 diabetes in middle-aged Mexican adults: the metabolic syndrome cohort.

BACKGROUND: Type 2 diabetes mellitus (T2D) is a leading cause of morbidity and mortality in Mexico. Here, we aimed to report incidence rates (IR) of type 2 diabetes in middle-aged apparently-healthy Mexican adults, identify risk factors associated to ID and develop a predictive model for ID in a high-risk population. METHODS: Prospective 3-year observational cohort, comprised of apparently-healthy adults from urban settings of central Mexico in whom demographic, anthropometric and biochemical data was collected. We evaluated risk factors for ID using Cox proportional hazard regression and developed predictive models for ID. RESULTS: We included 7636 participants of whom 6144 completed follow-up. We observed 331 ID cases (IR: 21.9 per 1000 person-years, 95%CI 21.37-22.47). Risk factors for ID included family history of diabetes, age, abdominal obesity, waist-height ratio, impaired fasting glucose (IFG), HOMA2-IR and metabolic syndrome. Early-onset ID was also high (IR 14.77 per 1000 person-years, 95%CI 14.21-15.35), and risk factors included HOMA-IR and IFG. Our ID predictive model included age, hypertriglyceridemia, IFG, hypertension and abdominal obesity as predictors (Dxy = 0.487, c-statistic = 0.741) and had higher predictive accuracy compared to FINDRISC and Cambridge risk scores. CONCLUSIONS: ID in apparently healthy middle-aged Mexican adults is currently at an alarming rate. The constructed models can be implemented to predict diabetes risk and represent the largest prospective effort for the study metabolic diseases in Latin-American population.

Community-acquired febrile urinary tract infection caused by extended-spectrum beta-lactamase-producing bacteria in hospitalised infants. / Infección urinaria febril adquirida en la comunidad por bacterias productoras de betalactamasas de espectro extendido en niños hospitalizados.

INTRODUCTION: Extended-spectrum beta-lactamase (ESBL) producing bacteria are infrequent pathogens of urinary tract infections in children. The objective of our study was to investigate the presence, clinically associated characteristics and risk factors for acquisition of urinary tract infection/acute pyelonephritis (UTI/APN) in hospitalised children <2years old caused by community-acquired ESBL. METHODS: A case-control study in a second level community hospital in Spain, in which 537 episodes of UTI/APN were investigated in a retrospective study between November 2005 and August 2014. Cases were patients with ESBL strains. For each case, four ESBL-negative controls were selected. A questionnaire with the variables of interest was completed for every patient, and the groups were compared. RESULTS: ESBL-positive strains were found in 19 (3,5%) cultures. Of these 16 (84%) were Escherichia coli. Vesicoureteral reflux (VUR) of any grade was more frequent in the ESBL group (60 vs. 29%), although without statistical significance. Relapses were more frequent in the ESBL group (42% vs. 18%) (P=.029; OR=3.2; 95%CI: 1.09-9.5). The prevalence of UTI/APN due to ESBL-positive strains increased slightly from 2.7% in the period 2005-2009 to 4.4% in the period 2010-2014. CONCLUSIONS: ESBL UTI/APN were associated with more frequent relapses. VUR of any grade was twice more frequent in the ESBL group. Piperacillin/tazobactam, fosfomycin and meropenem showed an excellent activity. Aminoglycosides may be a therapeutic option, and in our patients gentamicin was the antibiotic most used.

Ships' Ballast Water Treatment by Chlorination Can Generate Toxic Trihalomethanes.

The International Maritime Organization (IMO) will enforce a new abundance-based performance standard for ballast water in September, 2017. Strong oxidants, like chlorine, have been proposed as a method for achieving this standard. However chlorine treatment of ballast water can produce hazardous trihalomethanes. We assessed maximum trihalomethane production from one chlorine dose for three types of ballast water (fresh, brackish and marine) and three levels of total organic carbon (TOC) concentration (natural, filtered, enhanced). While the current standard test considers a 5 day voyage, there is a high possibility of shorter trips and sudden change of plans that will release treated waters in the environment. Water source and TOC significantly affected trihalomethane production, with the highest amounts generated in brackish waters and enhanced TOC concentration. The concentration of brominated trihalomethanes increased from background levels and was highest in brackish water, followed by marine and fresh water.

[Trichomycosis (trichobacteriosis) capitis in an infant: Microbiological, dermoscopic and ultrastructural features]. / Tricomicosis (tricobacteriosis) en un infante: Aspectos microbiológicos, dermatoscópicos y ultraestructurales.

Trichomycosis is a superficial infection caused by Corynebacterium flavescens, which regularly affects axillary, and to a a lesser extent, pubic, scrotal and intergluteal, and exceptionally, head hairs or trichomycosis capitis (TC). This condition is characterised by the formation of bacterial nodules. Clinically, it can be confused with white piedra or pediculosis. The diagnosis is made by microscopic and dermoscopic observation and confirmed by culture. OBJECTIVE: To present a case of TC in an infant and illustrate the microscopic, dermoscopic, and ultrastructural characteristics. CLINICAL CASE: A 6 month-old boy, otherwise healthy, with multiple yellowish concretions on the hairs of the head. TC was confirmed by yellow fluorescence with Wood’s light; white-yellowish beads, like “rosaries of crystalline stones’’ were observed on dermoscopy, direct examination showed bacterial masses, and Corynebacterium flavescens was identified by culture. A superficial infection, without perforation of the hairs, was confirmed by electron microscopy. Treatment with fusidic acid for 3 weeks achieved a clinical and microbiological cure. CONCLUSION: TC is a rare condition that affects children, and tends to be mistaken for other diseases of the hair, such as pediculosis and mycotic infections.

Impaired intestinal immunity and microbial diversity in common carp exposed to cadmium.

Waterborne cadmium (Cd) accumulates in the fish intestine and causes irreversible toxicity by disrupting intestinal immunity and microbial diversity. To explore the toxicity of environmentally available high Cd concentration on intestinal immunity and microbial diversity of fish, we selected the widely used bioindicator model species, Common carp (Cyprinus carpio). Literature review and Cd pollution data supported sequential doses of 0.2, 0.4, 0.8, 1.6, 3.2, and 6.4 mg/L Cd for 30 days. Based on intestinal tissue Cd accumulation, previous studies, and environmentally available Cd data, 0.4 and 1.6 mg/L Cd were selected for further studies. Intestinal Cd bioaccumulation increased significantly to ~100 times in fish exposed to 1.6 mg/L Cd. We observed villous atrophy, increased goblet cells with mucus production, muscularis erosion, and thickened lamina propria due to intense inflammatory cell infiltration in the intestine at this Cd concentration. Cd-induced immunosuppression occurred with increased lysozyme, alkaline phosphate (AKP), and acid phosphate (ACP). High levels of catalase (CAT), total antioxidant capacity (T-AOC), malondialdehyde (MDA), and hydrogen peroxide (H2O2) suggested induced oxidative stress and poor metabolism by α-amylase and lipase suppression for Cd toxicity. Proteobacteria (41.2 %), Firmicutes (21.8 %), and Bacteroidetes (17.5 %) were the dominant bacterial phyla in the common carp intestine. Additionally, potential pathogenic Cyanobacteria increased in Cd-treated fish. The decrease of beneficiary bacteria like Aeromonas, and Cetobacterium indicated Cd toxicity. Overall, these findings indicate harmful consequences of high Cd concentration in the intestinal homeostasis and health status of fish.

Ing4-deficiency promotes a quiescent yet transcriptionally poised state in hematopoietic stem cells.

Defining the mechanisms that regulate stem cell maintenance, proliferation, and differentiation is critical for identifying therapies for improving stem cell function under stress. Here, we have identified the tumor suppressor, inhibitor of growth 4 (Ing4), as a critical regulator of hematopoietic stem cell (HSC) homeostasis. Cancer cell line models with Ing4 deficiency have shown that Ing4 functions as a tumor suppressor, in part, due to Ing4-mediated regulation of several major signaling pathways, including c-Myc. In HSCs, we show Ing4 deficiency promotes gene expression signatures associated with activation, yet HSCs are arrested in G0, expressing several markers of quiescence. Functionally, Ing4-deficient HSCs demonstrate robust regenerative capacity following transplantation. Our findings suggest Ing4 deficiency promotes a poised state in HSCs, where they appear transcriptionally primed for activation but remain in a resting state. Our model provides key tools for further identification and characterization of pathways that control quiescence and self-renewal in HSCs.

Efficacy and Safety of Habitual Consumption of a Food Supplement Containing Miraculin in Malnourished Cancer Patients: The CLINMIR Pilot Study.

Taste disorders (TDs) are common among systemically treated cancer patients and negatively impact their nutritional status and quality of life. The novel food approved by the European Commission (EFSA), dried miracle berries (DMB), contains the natural taste-modifying protein miraculin. DMB, also available as a supplement, has emerged as a possible alternative treatment for TDs. The present study aimed to evaluate the efficacy and safety of habitual DMB consumption in malnourished cancer patients undergoing active treatment. An exploratory clinical trial was carried out in which 31 cancer patients were randomized into three arms [standard dose of DMB (150 mg DMB/tablet), high dose of DMB (300 mg DMB/tablet) or placebo (300 mg freeze-dried strawberry)] for three months. Patients consumed a DMB tablet or placebo daily before each main meal (breakfast, lunch, and dinner). Throughout the five main visits, electrochemical taste perception, nutritional status, dietary intake, quality of life and the fatty acid profile of erythrocytes were evaluated. Patients consuming a standard dose of DMB exhibited improved taste acuity over time (% change right/left side: -52.8 ± 38.5/-58.7 ± 69.2%) and salty taste perception (2.29 ± 1.25 vs. high dose: 2.17 ± 1.84 vs. placebo: 1.57 ± 1.51 points, p < 0.05). They also had higher energy intake (p = 0.075) and covered better energy expenditure (107 ± 19%). The quality of life evaluated by symptom scales improved in patients receiving the standard dose of DMB (constipation, p = 0.048). The levels of arachidonic (13.1 ± 1.8; 14.0 ± 2.8, 12.0 ± 2.0%; p = 0.004) and docosahexaenoic (4.4 ± 1.7; 4.1 ± 1.0; 3.9 ± 1.6%; p = 0.014) acids in erythrocytes increased over time after DMB intake. The standard dose of DMB increased fat-free mass vs. placebo (47.4 ± 9.3 vs. 44.1 ± 4.7 kg, p = 0.007). Importantly, habitual patients with DMB did not experience any adverse events, and metabolic parameters remained stable and within normal ranges. In conclusion, habitual consumption of a standard 150 mg dose of DMB improves electrochemical food perception, nutritional status (energy intake, fat quantity and quality, fat-free mass), and quality of life in malnourished cancer patients receiving antineoplastic treatment. Additionally, DMB consumption appears to be safe, with no changes in major biochemical parameters associated with health status. Clinical trial registered (NCT05486260).

An intense 60-day weight-loss course leads to an 18 kg body weight reduction and metabolic reprogramming of soldiers with obesity.

Soldiers of the Mexican Army with obesity were subjected to an intense 60-day weight-loss course consisting of a controlled diet, daily physical training, and psychological sessions. The nutritional treatment followed the European Society of Cardiology (ESC) recommendations, incorporating elements of the traditional milpa diet in the nutritional intervention. The total energy intake was reduced by 200 kcal every 20 days, starting with 1,800 kcal and ending with 1,400 kcal daily. On average, the participants reduced their body weight by 18 kg. We employed an innovative approach to monitor the progress of the twelve soldiers who completed the entire program. We compared the untargeted metabolomics profiles of their urine samples, taken before and after the course. The data obtained through liquid chromatography and high-resolution mass spectrometry (LC-MS) provided insightful results. Classification models perfectly separated the profiles pre and post-course, indicating a significant reprogramming of the participants' metabolism. The changes were observed in the C1-, vitamin, amino acid, and energy metabolism pathways, primarily affecting the liver, biliary system, and mitochondria. This study not only demonstrates the potential of rapid weight loss and metabolic pathway modification but also introduces a non-invasive method for monitoring the metabolic state of individuals through urine mass spectrometry data.

Thinking outside the black box: are the brain endothelial cells the new main target in Alzheimer's disease?

The blood-brain barrier is the interface through which the brain interacts with the milieu and consists mainly of a sophisticated network of brain endothelial cells that forms blood vessels and selectively moves molecules inside and outside the brain through multiple mechanisms of transport. Although brain endothelial cell function is crucial for brain homeostasis, their role in neurodegenerative diseases has historically not been considered with the same importance as other brain cells such as microglia, astroglia, neurons, or even molecules such as amyloid beta, Tau, or alpha-synuclein. Alzheimer's disease is the most common neurodegenerative disease, and brain endothelial cell dysfunction has been reported by several groups. However, its impairment has barely been considered as a potential therapeutic target. Here we review the most recent advances in the relationship between Alzheimer's disease and brain endothelial cells commitment and analyze the possible mechanisms through which their alterations contribute to this neurodegenerative disease, highlighting their inflammatory phenotype and the possibility of an impaired secretory pattern of brain endothelial cells that could contribute to the progression of this ailment. Finally, we discuss why shall brain endothelial cells be appreciated as a therapeutic target instead of solely an obstacle for delivering treatments to the injured brain in Alzheimer's disease.