Variables Associated With In-Hospital Lethality in COVID-19: A Prospective Cohort Study From Colombia.

INTRODUCTION: The emergence of COVID-19 represents the most significant health crisis in recent history. Incidence and mortality rates depend on several factors. Many studies have focused on investigating which characteristics could be strongly related to higher mortality and lethality. OBJECTIVE: This study aims to analyze the variables associated with in-hospital mortality among patients admitted in a reference northeastern region of a Colombian institution. METHODS: An ambidirectional cohort, single-center study was carried out in a reference hospital in northeastern Colombia. All patients admitted to the Fundación Oftalmológica de Santander (FOSCAL) between March 2020 and September 2021, with COVID-19 real-time polymerase chain reaction (PCR) positive test, were included. RESULTS: A total of 3,028 patients were included, of whom 2,034 (67.8%) survived and 994 (32.8%) died during their hospital stay; 48.8% (1,479) of the patients were female. The most common comorbidities were hypertension (1,236 patients, 40.8%), obesity (body mass index (BMI) ≥ 30; 656 patients, 21.6%), and diabetes (618 patients, 20.4%). The average age of the surviving patients was 52.2 years, while for the deceased patients, it was 70.3 years. The variables that showed significant association with in-hospital mortality were as follows: male sex ≥ 45 years, dyspnea, oxygen saturation (SatO2) < 85%, hypertension, chronic kidney disease (CKD), and a Charlson Comorbidity Index (CCI) score of >1. CONCLUSIONS: Male sex, age ≥ 45 years, dyspnea, SatO2 < 85%, hypertension, CKD, and a CCI score of >1 were associated with a higher risk of in-hospital mortality in COVID-19-infected patients.

Deciphering the enigmatic PilY1 of Acidithiobacillus thiooxidans: An in silico analysis.

Thirty years since the first report on the PilY1 protein in bacteria, only the C-terminal domain has been crystallized; there is no study in which the N-terminal domain, let alone the complete protein, has been crystallized. In our laboratory, we are interested in characterizing the Type IV Pili (T4P) of Acidithiobacillus thiooxidans. We performed an in silico characterization of PilY1 and other pilins of the T4P of this acidophilic bacterium. In silico characterization is crucial for understanding how proteins adapt and function under extreme conditions. By analyzing the primary and secondary structures of proteins through computational methods, researchers can gain valuable insights into protein stability, key structural features, and unique amino acid compositions that contribute to resilience in harsh environments. Here, it is presented a description of the particularities of At. thiooxidans PilY1 through predictor software and homology data. Our results suggest that PilY1 from At. thiooxidans may have the same role as has been described for other PilY1 associated with T4P in neutrophilic bacteria; also, its C-terminal interacts (interface interaction) with the minor pilins PilX, PilW and PilV. The N-terminal region comprises domains such as the vWA and the MIDAS, involved in signaling, ligand-binding, and protein-protein interaction. In fact, the vWA domain has intrinsically disordered regions that enable it to maintain its structure over a wide pH range, not only at extreme acidity to which At. thiooxidans is adapted. The results obtained helped us design the correct methodology for its heterologous expression. This allowed us partially experimentally characterize it by obtaining the N-terminal domain recombinantly and evaluating its acid stability through fluorescence spectroscopy. The data suggest that it remains stable across pH changes. This work thus provides guidance for the characterization of extracellular proteins from extremophilic organisms.

Hepatitis E Virus Genotype 3 among Hemodialysis Patients in Mexico: First Identification of Chronic Infection.

The global distribution of hepatitis E virus (HEV) is attributed to its capacity to spread through several routes of transmission; hemodialysis has gained increased amounts of attention in recent years. Although Mexico is considered a hyperendemic region for hepatitis E, no HEV surveillance is performed in the country. The frequency of HEV in hemodialysis (HD) patients has not been determined. Herein, we conducted a cross-sectional single-center analytical study including 67 serum samples from HD patients. Anti-HEV IgG and IgM antibodies and the viral genome were determined; partial regions within the HEV genome were sequenced for further phylogenetic analysis. Globally, 14.9% of the tested patients exhibited reactivity for IgG antibodies against HEV, and none showed reactivity to IgM. A total of 5.9% of the samples showed HEV genome amplification, and sequencing confirmed the identity of genotype 3; subsequent analysis of positive cases revealed two acute cases and chronic hepatitis E infection in one patient. Notably, the chronic patient was negative for anti-HEV IgG antibodies. Our findings highlight the importance of viral genome testing in HD patients and the need to establish guidelines for HEV detection in Mexico.

Cendakimab in Patients With Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial.

Importance: Cendakimab selectively targets interleukin (IL)-13, a type 2 cytokine implicated in atopic dermatitis (AD) pathogenesis, by inhibiting binding to its receptors (IL13R-α1 and IL13R-α2). Proof-of-concept work in AD supports using cendakimab for type 2 inflammatory diseases. Objective: To evaluate the efficacy and safety of cendakimab compared with placebo in patients with moderate to severe AD. Design, Setting, and Participants: This phase 2, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging clinical trial was conducted from May 2021 to November 2022. Adult patients with moderate to severe AD and inadequate response to topical medications were enrolled at 69 sites in 5 countries (US [n = 26], Japan [n = 17], Canada [n = 9], Poland [n = 9], and Czech Republic [n = 8]). Data were analyzed between April 25, 2023, and October 16, 2023. Interventions: Patients were randomized (1:1:1:1) to receive subcutaneous cendakimab, 360 mg, every 2 weeks; 720 mg, every 2 weeks; 720 mg, once weekly; or placebo. Main Outcome and Measure: Mean percentage change in Eczema Area and Severity Index scores from baseline to week 16. Hierarchical testing with multiplicity adjustment was performed for 720 mg, once weekly vs placebo, then 720 mg, every 2 weeks vs placebo, and then 360 mg, every 2 weeks vs placebo. Results: Overall, 221 patients were randomized, and 220 received study drug (95 women [43%]; mean [SD] age, 37.7 [13.9] years; 720 mg, once weekly [54 (24%)]; 720 mg, every 2 weeks [55 (25%)]; 360 mg, every 2 weeks [55 (25%)]; placebo [56 (26%)]). The primary efficacy end point was met for cendakimab, 720 mg, once weekly vs placebo (-84.4 vs -62.7; P = .003) but missed statistical significance for 720 mg, every 2 weeks (-76.0 vs -62.7; P = .06). The treatment effect for 360 mg, every 2 weeks (-16.3; nominal P = .03 vs placebo) was comparable with 720 mg, once weekly (-21.8); however, significance was not claimed because the hierarchical testing sequence was interrupted. Of patients with treatment-emergent adverse events leading to discontinuation, 4 (7.4%) received 720 mg, once weekly; 2 (3.6%) 720 mg, every 2 weeks; 1 (1.8%) 360 mg, every 2 weeks; and 2 (3.6%) placebo. Conclusions and Relevance: The results of this randomized clinical trial indicated that cendakimab was effective, generally safe, and well-tolerated in patients with moderate to severe AD. The primary end point was met with a significant reduction in Eczema Area and Severity Index scores with 720 mg, once weekly at week 16. Cendakimab demonstrated progressive AD improvement at all doses during 16 weeks of treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT04800315.

Dietary supplementation of mineral nanoparticles for channel catfish (Ictalurus punctatus).

This study evaluated the supplementation of iron and copper nanoparticles in channel catfish diets and their influences on growth and health. A comparative feeding trial was carried out for 9 weeks to evaluate combinations of iron and copper nanoparticles: only iron nanoparticles (IronNP), only copper nanoparticles (CopperNP), CopperNP + IronNP, and a control diet supplemented with inorganic iron and copper (FeSO4 and CuSO4). After a 9-week feeding trial, growth performance, hematological parameters, whole-body proximate composition, and intestinal microbiota were evaluated, and fish were subjected to a bacterial challenge against Edwardsiella ictaluri to evaluate the contribution of the experimental treatments to fish health status. No statistical differences were detected for catfish fed the various diets in terms of production performance or survival after bacterial challenge. The hematocrit and RBC counts from fish fed the diet containing copper nanoparticles were significantly lower than the control group. A higher relative abundance of gram-positive bacteria was found in the digesta of catfish fed diets containing copper nanoparticles. Furthermore, in the context of hematology, iron nanoparticles did not impact the blood parameters of channel catfish; however, reduced hematocrits were observed in fish fed the copper nanoparticle diet, which lacked supplemental dietary iron, thus reinforcing the importance of dietary iron to catfish hematopoiesis. Nonetheless, additional studies are needed to investigate the effects of dietary copper nanoparticle supplementation in catfish diets to better illuminate its effects on the intestinal microbiota.

Development of a value-based healthcare burns core set for adult burn care.

BACKGROUND: Value-based healthcare (VBHC) is increasingly implemented in healthcare worldwide. Transparent measurement of the outcomes most important and relevant to patients is essential in VBHC, which is supported by a core set of most important quality indicators and outcomes. Therefore, the aim of this study was to develop a VBHC-burns core set for adult burn patients. METHODS: A three-round modified national Delphi study, including 44 outcomes and 24 quality indicators, was conducted to reach consensus among Dutch patients, burn care professionals and researchers. Items were rated on a nine-point Likert scale and selected if ≥ 70% in each group considered an item 'important'. Subsequently, instruments quantifying selected outcomes were identified based on a literature review and were chosen in a consensus meeting using recommendations from the Dutch consensus-based standard set and the Dutch Centre of Expertise on Health Disparities. Time assessment points were chosen to reflect the burn care and patient recovery process. Finally, the initial core set was evaluated in practice, leading to the adapted VBHC-burns core set. RESULTS: Twenty-seven patients, 63 burn care professionals and 23 researchers participated. Ten outcomes and four quality indicators were selected in the Delphi study, including the outcomes pain, wound healing, physical activity, self-care, independence, return to work, depression, itching, scar flexibility and return to school. Quality indicators included shared decision-making (SDM), the number of patients receiving aftercare, determination of burn depth, and assessment of active range of motion. After evaluation of its use in clinical practice, the core set included all items except SDM, which are assessed by 9 patient-reported outcome instruments or measured in clinical care. Assessment time points included are at discharge, 2 weeks, 3 months, 12 months after discharge and annually afterwards. CONCLUSION: A VBHC-burns core set was developed, consisting of outcomes and quality indicators that are important to burn patients and burn care professionals. The VBHC-burns core set is now systemically monitored and analysed in Dutch burn care to improve care and patient relevant outcomes. As improving burn care and patient relevant outcomes is important worldwide, the developed VBHC-burns core set could be inspiring for other countries.

Exploring surface properties and premelting in crystals.

Crystal surfaces play a pivotal role in governing various significant processes, such as adsorption, nucleation, wetting, friction, and wear. A fundamental property that influences these processes is the surface free energy, γ. We have directly calculated γ(T) for low-index faces of Lennard-Jones (LJ), germanium, and silicon crystals along their sublimation lines using the computational cleavage technique. Our calculations agree well with experimental values for Si(111) and Ge(111), highlighting the accuracy of the method and models used. For LJ crystals, we identified a premelting onset at Tpm = 0.75Tm, marked by a sharp increase in atom mobility within the second outermost surface layer. Notably, Tpm closely aligned with the endpoint of the LJ melting line at negative pressures, Tend = 0.76Tm. We hypothesize that the emergence and coexistence of a liquid film atop the LJ crystal at Tpm < T < Tm correspond to the metastable melting line under negative pressures experienced by stretched crystal surfaces. Furthermore, our study of thin LJ crystal slabs reveals that premelting-induced failure leads to recrystallization below the homogeneous freezing limit, offering a promising avenue to explore crystal nucleation and growth at extremely deep supercoolings. Finally, no evidence of premelting was detected in the model crystals of Ge and Si, which is consistent with the experimental observations. Overall, our findings offer valuable insights into crystal surface phenomena at the atomic scale.

Large, ulcerated infantile hemangioma of the chest wall complicated by life-threatening hemorrhage: Case report and literature review.

While ulceration is one of the most common infantile hemangioma (IH) complications, severe bleeding is a rare consequence, with a paucity of patients reported. We report a 5-month-old girl with a very large, mixed, partial segmental IH of the upper chest wall who, despite medical intervention, developed severe ulceration and multiple episodes of life-threatening bleeding that ultimately led to hemorrhagic shock. Experience in our patient and a review of six previous reports shows that severe bleeding is a risk when ulceration extends directly into an arterial feeding vessel that is often visible clinically. Other potential predictors for severe bleeding include large to very large IH size with extension of the tumor into underlying structures, segmental or partial segmental patterning, mixed and bulky morphology, and white discoloration as a sign of impending or worsening ulceration.

Incorporating climate-readiness into fisheries management strategies.

Tropical oceans are among the first places to exhibit climate change signals, affecting the habitat distribution and abundance of marine fish. These changes to stocks, and subsequent impacts on fisheries production, may have considerable implications for coastal communities dependent on fisheries for food security and livelihoods. Understanding the impacts of climate change on tropical marine fisheries is therefore an important step towards developing sustainable, climate-ready fisheries management measures. We apply an established method of spatial meta-analysis to assess species distribution modelling datasets for key species targeted by the Philippines capture fisheries. We analysed datasets under two global emissions scenarios (RCP4.5 and RCP8.5) and varying degrees of fishing pressure to quantify potential climate vulnerability of the target community. We found widespread responses to climate change in pelagic species in particular, with abundances projected to decline across much of the case study area, highlighting the challenges of maintaining food security in the face of a rapidly changing climate. We argue that sustainable fisheries management in the Philippines in the face of climate change can only be achieved through management strategies that allow for the mitigation of, and adaptation to, pressures already locked into the climate system for the near term. Our analysis may support this, providing fisheries managers with the means to identify potential climate change hotspots, bright spots and refugia, thereby supporting the development of climate-ready management plans.

Understanding a Core Pilin of the Type IVa Pili of Acidithiobacillus thiooxidans, PilV.

Pilins are protein subunits of pili. The pilins of type IV pili (T4P) in pathogenic bacteria are well characterized, but anything is known about the T4P proteins in acidophilic chemolithoautotrophic microorganisms such as the genus Acidithiobacillus. The interest in T4P of A. thiooxidans is because of their possible role in cell recruitment and bacterial aggregation on the surface of minerals during biooxidation of sulfide minerals. In this study we present a successful ad hoc methodology for the heterologous expression and purification of extracellular proteins such as the minor pilin PilV of the T4P of A. thiooxidans, a pilin exposed to extreme conditions of acidity and high oxidation-reduction potentials, and that interact with metal sulfides in an environment rich in dissolved minerals. Once obtained, the model structure of A. thiooxidans PilV revealed the core basic architecture of T4P pilins. Because of the acidophilic condition, we carried out in silico characterization of the protonation status of acidic and basic residues of PilV in order to calculate the ionization state at specific pH values and evaluated their pH stability. Further biophysical characterization was done using UV-visible and fluorescence spectroscopy and the results showed that PilV remains soluble and stable even after exposure to significant changes of pH. PilV has a unique amino acid composition that exhibits acid stability, with significant biotechnology implications such as biooxidation of sulfide minerals. The biophysics profiles of PilV open new paradigms about resilient proteins and stimulate the study of other pilins from extremophiles.

Kinetics of physical aging of a silicate glass following temperature up- and down-jumps.

In this article, we investigate the structural relaxation of lithium silicate glass during isothermal physical aging by monitoring the temporal evolution of its refractive index and enthalpy following relatively large (10-40 °C) up- and down-jumps in temperature. The Kohlrausch-Williams-Watts function aptly describes the up- and down-jump data when analyzed separately. For temperature down-jumps, the glass exhibits a typical stretched exponential kinetic behavior with the non-exponentiality parameter ß < 1, whereas up-jumps show a compressed exponential behavior (ß > 1). We analyzed these datasets using the non-exponential and non-linear Tool-Narayanaswamy-Moynihan (TNM) model, aiming to provide a comprehensive description of the primary or α-relaxation of the glass. This model described both up- and down-jump datasets using a single value of ß ≤ 1. However, the standard TNM model exhibited a progressively reduced capacity to describe the data for larger temperature jumps, which is likely a manifestation of the temperature dependence of the non-exponentiality or non-linearity of the relaxation process. We hypothesize that the compressed exponential relaxation kinetics observed for temperature up-jumps stems from a nucleation-growth-percolation-based evolution on the dynamically mobile regions within the structure, leading to a self-acceleration of the dynamics. On the other hand, temperature down-jumps result in self-retardation, as the slow-relaxing denser regions percolate in the structure to give rise to a stretched exponential behavior.

Pegbelfermin in Patients With Nonalcoholic Steatohepatitis and Stage 3 Fibrosis (FALCON 1): A Randomized Phase 2b Study.

BACKGROUND & AIMS: Pegbelfermin is a polyethlene glycol-conjugated analog of human fibroblast growth factor 21, a nonmitogenic hormone that regulates energy metabolism. This phase 2b study evaluated 48-week pegbelfermin treatment in patients with nonalcoholic steatohepatitis (NASH) and stage 3 (bridging) fibrosis. METHODS: The FALCON 1 study (NCT03486899) was a multicenter, randomized (1:1:1:1), double-blind, placebo-controlled study. Patients with biopsy-confirmed NASH and stage 3 fibrosis (N = 197) received weekly subcutaneous pegbelfermin (10, 20, or 40 mg) or placebo injections for 48 weeks. The week 24 primary endpoint was a ≥1-point decrease in fibrosis score without NASH worsening or NASH improvement without fibrosis worsening; pegbelfermin dose response was assessed using a Cochran-Armitage trend test across proportions (1-sided α = 0.05). Secondary/exploratory endpoints included histological and noninvasive measures of steatosis, fibrosis, and liver injury/inflammation. RESULTS: At week 24, the primary endpoint was met by 14% (placebo) vs 24%-31% (pegbelfermin arms); statistical significance was not reached due to lack of pegbelfermin dose response (P = .134). At weeks 24 and 48, more patients who received pegbelfermin had ≥30% relative reductions in hepatic fat fraction (magnetic resonance imaging-proton density fat fraction) vs placebo, although no differences reached statistical significance. In the pegbelfermin arms, improvements in liver fibrosis (magnetic resonance elastography and N-terminal type III collagen propeptide) and liver injury/inflammation (alanine aminotransferase, aspartate aminotransferase) were observed vs placebo. Adverse events occurred at similar frequencies across arms. No treatment-related serious adverse events were observed. CONCLUSIONS: The FALCON 1 study did not meet its primary endpoint; a ≥1-point decrease in fibrosis score without NASH worsening or NASH improvement without fibrosis worsening assessed via biopsy. Pegbelfermin was generally well tolerated during 48 weeks of treatment.

Pegbelfermin in Patients With Nonalcoholic Steatohepatitis and Compensated Cirrhosis (FALCON 2): A Randomized Phase 2b Study.

BACKGROUND & AIMS: Pegbelfermin is a polyethylene glycol-conjugated analog of human fibroblast growth factor 21, a nonmitogenic hormone that regulates energy metabolism. This phase 2b study evaluated 48-week pegbelfermin treatment in patients with nonalcoholic steatohepatitis (NASH) with compensated cirrhosis. METHODS: FALCON 2 (NCT03486912) was a randomized (1:1:1:1), double-blind, placebo-controlled study. Eligible adults had biopsy-confirmed NASH and stage 4 fibrosis. Pegbelfermin (10, 20, or 40 mg) or placebo was injected subcutaneously once weekly. The primary endpoint was 1 or more stages of improvement in the NASH Clinical Research Network fibrosis score without NASH worsening at week 48; pegbelfermin dose response was assessed using a Cochran-Armitage trend test across proportions (1-sided α = .05). Additional endpoints included histologic and noninvasive measures of steatosis, fibrosis, and liver injury/inflammation. RESULTS: Overall, 155 patients were randomized, and 154 patients received treatment. At week 48, 24% to 28% of the pegbelfermin arms had primary endpoint responses vs 31% of the placebo arm (P = .361). Nonalcoholic fatty liver disease activity score improvements were more frequent with pegbelfermin vs placebo and were driven primarily by reduced lobular inflammation. Numerically higher proportions of the pegbelfermin arms had liver stiffness (magnetic resonance elastography) and steatosis (magnetic resonance imaging-proton density fat fraction) improvements vs placebo; these differences were not statistically significant. Mean N-terminal type III collagen propeptide, alanine aminotransferase, and aspartate aminotransferase values were numerically lower in the 20- and/or 40-mg pegbelfermin arms compared with placebo. Serious adverse events were more frequent with pegbelfermin vs placebo, although none were treatment related. One patient (40-mg pegbelfermin) discontinued treatment because of a treatment-emergent adverse event (worsening ascites). CONCLUSIONS: FALCON 2 did not meet its primary endpoint of 1 or more stages of improvement in the NASH Clinical Research Network fibrosis without NASH worsening assessed via biopsy. Pegbelfermin generally was well tolerated in this advanced NASH population.

Disorder and amino acid composition in proteins: their potential role in the adaptation of extracellular pilins to the acidic media, where Acidithiobacillus thiooxidans grows.

There are few biophysical studies or structural characterizations of the type IV pilin system of extremophile bacteria, such as the acidophilic Acidithiobacillus thiooxidans. We set out to analyze their pili-comprising proteins, pilins, because these extracellular proteins are in constant interaction with protons of the acidic medium in which At. thiooxidans grows. We used the web server Operon Mapper to analyze and identify the cluster codified by the minor pilin of At. thiooxidans. In addition, we carried an in-silico characterization of such pilins using the VL-XT algorithm of PONDR® server. Our results showed that structural disorder prevails more in pilins of At. thiooxidans than in non-acidophilic bacteria. Further computational characterization showed that the pilins of At. thiooxidans are significantly enriched in hydroxy (serine and threonine) and amide (glutamine and asparagine) residues, and significantly reduced in charged residues (aspartic acid, glutamic acid, arginine and lysine). Similar results were obtained when comparing pilins from other Acidithiobacillus and other acidophilic bacteria from another genus versus neutrophilic bacteria, suggesting that these properties are intrinsic to pilins from acidic environments, most likely by maintaining solubility and stability in harsh conditions. These results give guidelines for the application of extracellular proteins of acidophiles in protein engineering.

Pharmacokinetics, safety, and tolerability of BMS-986263, a lipid nanoparticle containing HSP47 siRNA, in participants with hepatic impairment.

BMS-986263 is a retinoid-conjugated lipid nanoparticle delivering small interfering RNA designed to inhibit synthesis of HSP47 protein, a collagen-specific chaperone protein involved in fibrosis development. This is a phase I, open-label, two-part study evaluating pharmacokinetics and safety of BMS-986263 in participants with hepatic impairment (HI). Part 1 (n = 24) of this study enrolled two cohorts with mild and moderate HI and a separate cohort of age- and body mass index (BMI)-matched participants with normal hepatic function. Part 2 enrolled eight participants with severe HI and eight age- and BMI-matched participants with normal hepatic function. All participants received a single intravenous 90 mg BMS-986263 infusion. Compared with normal-matched participants, geometric mean area under the plasma concentration-time curve time zero to the time of the last quantifiable concentration (AUC(0-T) ) and AUC from zero to infinity (AUC(INF) ) of HSP47 siRNA were similar in participants with mild HI and 34% and 163% greater in those with moderate and severe HI, respectively, whereas the maximum plasma concentration was ~25% lower in mild and moderate HI groups but 58% higher in the severe HI group than in the normal group. Adverse events were reported by two of eight, four of eight, and three of eight participants with mild, moderate, or severe HI, respectively; none were reported in the normal-matched group. Overall, single-dose BMS-986263 was generally safe and well-tolerated and dose adjustment is not considered necessary for participants with mild or moderate HI. Although available data do not indicate that dose adjustment should be performed in patients with severe HI; the optimal posology of BMS-986263 in patients with severe HI may be determined later in its clinical development when additional data to establish exposure-safety/efficacy relationship becomes available.

Neuropsychiatric Effects in Patients With Invasive Prolactinomas Treated With Cabergoline.

Background and objective Invasive prolactinoma accounts for 1-5% of all prolactinomas. Its mass and compromise of the diencephalon and frontal and temporal lobes may result in a range of neuropsychiatric symptoms that are often missed during initial evaluations. Cabergoline is a dopaminergic agonist used as the first-line treatment for these patients; however, its effect on neuropsychiatric symptoms in this particular setting remains unexplored. In this study, our primary objective was to describe the epidemiology of neuropsychiatric comorbidities in Mexican patients with invasive prolactinomas. The secondary aim of the study was to describe how these comorbidities are modified by treatment with cabergoline, through follow-up with standardized clinical scales. Methods This was a retrospective analytic study. Data were pulled from clinical records and evaluations of patients at baseline and at six-month follow-ups.  Results A total of 10 patients were included in the study. None of them had any prior psychiatric diagnosis. At the initial evaluation, 70% were diagnosed with depression or anxiety. During follow-up, two patients developed neuropsychiatric symptoms; there was a significant reduction in tumor size but no difference was found in clinimetric scores for neuropsychiatric comorbidities. Conclusions Patients with giant prolactinomas may present with several neuropsychiatric symptoms throughout the course of their disease. Although there are several mechanisms involved, it is important to keep in mind that cabergoline may interfere with the dopaminergic pathways involved. This study was underpowered to determine the association but can serve as a pilot for further research on this topic.

Is it Mandatory to do a 24 hour ABPM in all Patients with Moderate to Severe Obstructive Sleep Apnoea?

Background Obstructive sleep apnoea (OSA) has been described as a risk factor for arterial hypertension (HT). One of the proposed mechanisms linking these conditions is non dipping (ND) pattern in nocturnal blood pressure, however evidence is variable and based on specific populations with underlying conditions. Data for OSA and ND in subjects residing at high altitude are currently unavailable. Objective Identify the prevalence and association of moderate to severe OSA with HT and ND pattern in hypertensive and non-hypertensive otherwise healthy middle-aged individuals in residing at high altitude (Bogotá:2640 mt) Methods Adult individuals with diagnosis of moderate to severe OSA underwent 24 hour- ambulatory blood pressure monitoring (ABPM) between 2015 and 2017. Univariable and multivariable logistic regression analysis were performed to identify predictors of HT and ND pattern. Results Ninety-three (93) individuals (male 62.4% and median age 55) were included in the final analysis. Overall, 30.1% showed a ND pattern in ABPM and 14.9% had diurnal and nocturnal hypertension. Severe OSA (higher apnea-hiponea index [AHI]) was associated with HT (p = 0.006), but not with ND patterns (p = 0.54) in multivariable regression. Smoking status and lowest oxygen saturation during respiratory events where independently associated with ND pattern (p = 0.04), whereas age (p = 0.001) was associated with HT. Conclusions In our sample, one in three individuals with moderate to severe OSA have non dipping patterns suggesting lack of straight association between OSA and ND. Older individuals who have higher AHI are more likely to have HT, and those who smoke have a higher risk of ND. These findings add aditional information to the multiple mechanisms involved in the relationship between OSA and ND pattern, and questions the routine use of 24-hour ABPM, particullary in our region, with limited resources and healthcare acces. However, further work with more robust methodology is needed to draw conclusions.

IL-18 discriminates highly frequent hepatitis E virus positive from negative blood donors in Mexico.

INTRODUCTION AND OBJECTIVES: Hepatitis E virus (HEV) is not routinely screened in blood banks in low- and middle-income countries, and no specific biomarkers of exposure to this virus have yet been identified. We aimed to identify HEV seropositivity and detect virus RNA among blood donors from Mexico to further correlate risk factors related to infection and levels of interleukin-18 (IL-18) and interferon-gamma (IFN-γ) as potential biomarkers. MATERIALS AND METHODS: This cross-sectional, single-center study included 691 serum samples of blood donors obtained in 2019. Anti-HEV IgG and IgM antibodies were detected in sera and the viral genome was screened in pooled samples. A statistical comparison of risk factors for infection, demographic and clinical features was performed; IL-18 and IFN- Î³ values were tested in sera. RESULTS: Of all the individuals, 9.4% were positive for anti-HEV antibodies and viral RNA detection was confirmed in one of the pools positive for anti-HEV. From the analysis of risk factors, age and having pets were statistically significant for anti-HEV antibody detection. Seropositive samples showed significantly higher IL-18 concentrations relative to samples from seronegative donors. Interestingly, IL-18 values were similar when HEV seropositive samples were compared to samples from clinically acute previously confirmed HEV patients. CONCLUSIONS: Our findings highlight the need to follow up on HEV in blood banks in Mexico and underscore that IL-18 could represent a biomarker of HEV exposure.

Impact of environmental interventions based on social programs on physical activity levels: A systematic review.

Background: The design of social programs at the environmental level such as in schools, parks, bicycle paths, or workspaces generates changes in the behavior of individuals and modifies lifestyles by increasing physical activity (PA) levels. Objective: To determine the effectiveness of environmental interventions based on social programs by changing the population's level of PA. Methodology: Natural experiment studies that involved environmental intervention programs at a social level were included. The primary outcome was PA levels with consideration of both objective and subjective measurements. An electronic search was carried out in Medline/Pubmed, SCIENCE DIRECT, WEB OF SCIENCE, and CINAHL databases up to January 2022 with two reviewers screening titles and abstracts and selecting studies for full-text reading. Two reviewers also acquired relevant data and evaluated study quality using the ROBINS I tool. A qualitative analysis was performed. Results: Three thousand eight hundred and sixty-five articles were found in the 4 consulted databases. After eliminating duplication (200), two reviewers screened 3,665 titles and abstracts and excluded 3,566 that did not meet the inclusion criteria, leaving 99 articles to be read in full text. The 99 full texts were reviewed of which 24 papers met the eligibility criteria. All were natural experiments published between 2011 and 2020 and all evaluated environmental social programs revealing that social programs at the environmental level promoted PA in various populations at the community level worldwide. Conclusion: The 24 reviewed studies suggest innovative proposals for social programs that seek to increase PA and promote healthy lifestyles related to public activity policies developed in the countries in which they were generated. Environmental social programs can positively impact PA levels among children and adults. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=229718, identifier: CRD42021229718.

Impact of structural-level environmental interventions on physical activity: a systematic review.

OBJECTIVE: To determine the effectiveness of structural-level environmental interventions on the changes in PA levels in the populations examined. METHODS: Natural experiments that involve environmental intervention with structural modification were included. The primary outcome PA levels with consideration of both objective and subjective measurements. An electronic search was carried out in Medline/Pubmed, SCIENCE DIRECT, WEB OF SCIENCE, and CINAHL up to January 2022. Two reviewers screened titles and abstracts, selected studies, extracted relevant data, and examined study quality. A qualitative synthesis was performed. RESULTS: Twenty-six articles were included. The structural-level environmental interventions included 4 fundamental areas: schools, work environments, streets or cities, and neighborhoods or parks. Of the 26 studies, 21 examined outdoor environments like parks, cities, pedestrian walkways, or steps, while 5 examined indoor or closed environments like schools and workplaces revealing that structural-level environmental interventions improve PA levels with the greatest effect in parks and active transportation. A risk of bias is inherent in natural experiments which is a limitation of this study. In schools and work areas, there is evidence of both decrease in sedentary time and an increase in PA related to environmental modifications. CONCLUSION: Structural-level environmental modifications in parks and active transportation demonstrated greater effects in promoting PA. Environmental modifications can impact physical activity in the population. Given that the economic and cultural setting is a key variable when considering the effectiveness of structural interventions, and since only 1 of the 26 reviewed articles included such data, more studies examining economic factors are needed especially in low- and middle-income countries like in South America. TRIAL REGISTRATION: PROSPERO CRD42021229718.