Biomarkers of endothelial glycocalyx damage are associated with microvascular dysfunction in resuscitated septic shock patients.

BACKGROUND: Microvascular dysfunction plays a central role in organ dysfunction during septic shock. Endothelial glycocalyx (eGC) damage could contribute to impaired microcirculation. The aim was to assess whether several eGC-damaged biomarkers are associated with microvascular dysfunction in resuscitated septic shock patients. METHODS: This cross-sectional study included resuscitated septic shock patients (N = 31), and a group of healthy individuals (N = 20). The eGC damage biomarkers measured were syndecan-1 (SDC-1), soluble CD44 (CD44s), hyaluronic acid (HYAL) in blood sample; sulfated glycosaminoglycans (GAGs) in urine sample; and thrombomodulin (TBML) in blood sample as biomarker of endothelial cell damage. Microcirculation was assessed through sublingual videocapillaroscopy using the GlycoCheck™, which estimated the perfused vascular density (PVD); the perfused boundary region (PBR), an inverse parameter of the eGC thickness; and the microvascular health score (MVHS). We defined a low MVHS (<50th percentile in septic patients) as a surrogate for more impaired microvascular function. RESULTS: The SDC-1, CD44s, TBML and GAGs levels were correlated with impaired microvascular parameters (PVD of vessels with diameter < 10 µm, MVHS and flow-adjusted PBR); p < 0.05 for all comparisons, except for GAGs and flow-adjusted PBR. The SDC-1 [78 ng/mL (interquartile range (IQR) 45-336) vs. 48 ng/mL (IQR 9-85); p = 0.052], CD44s [796ρg/mL (IQR 512-1995) vs. 526ρg/mL (IQR 287-750); p = 0.036], TBML [734ρg/mL (IQR 237-2396) vs. 95ρg/mL (IQR 63-475); p = 0.012] and GAGs levels [0.42 ρg/mg (IQR 0.04-1.40) vs. 0.07 ρg/mg (IQR 0.02-0.20); p = 0.024]; were higher in septic patients with more impaired sublingual microvascular function (low MVHS vs. high MVHS). CONCLUSION: SDC-1, CD44s, TBML and GAGs levels were associated with impaired microvascular function in resuscitated septic shock patients.

Novel MECP2 gene therapy is effective in a multicenter study using two mouse models of Rett syndrome and is safe in non-human primates.

The AAV9 gene therapy vector presented in this study is safe in mice and non-human primates and highly efficacious without causing overexpression toxicity, a major challenge for clinical translation of Rett syndrome gene therapy vectors to date. Our team designed a new truncated methyl-CpG-binding protein 2 (MECP2) promoter allowing widespread expression of MECP2 in mice and non-human primates after a single injection into the cerebrospinal fluid without causing overexpression symptoms up to 18 months after injection. Additionally, this new vector is highly efficacious at lower doses compared with previous constructs as demonstrated in extensive efficacy studies performed by two independent laboratories in two different Rett syndrome mouse models carrying either a knockout or one of the most frequent human mutations of Mecp2. Overall, data from this multicenter study highlight the efficacy and safety of this gene therapy construct, making it a promising candidate for first-in-human studies to treat Rett syndrome.

Preclinical evaluation of FLT190, a liver-directed AAV gene therapy for Fabry disease.

Fabry disease is an X-linked lysosomal storage disorder caused by loss of alpha-galactosidase A (α-Gal A) activity and is characterized by progressive accumulation of glycosphingolipids in multiple cells and tissues. FLT190, an investigational gene therapy, is currently being evaluated in a Phase 1/2 clinical trial in patients with Fabry disease (NCT04040049). FLT190 consists of a potent, synthetic capsid (AAVS3) containing an expression cassette with a codon-optimized human GLA cDNA under the control of a liver-specific promoter FRE1 (AAV2/S3-FRE1-GLAco). For mouse studies FLT190 genome was pseudotyped with AAV8 for efficient transduction. Preclinical studies in a murine model of Fabry disease (Gla-deficient mice), and non-human primates (NHPs) showed dose-dependent increases in plasma α-Gal A with steady-state observed 2 weeks following a single intravenous dose. In Fabry mice, AAV8-FLT190 treatment resulted in clearance of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) in plasma, urine, kidney, and heart; electron microscopy analyses confirmed reductions in storage inclusion bodies in kidney and heart. In NHPs, α-Gal A expression was consistent with the levels of hGLA mRNA in liver, and no FLT190-related toxicities or adverse events were observed. Taken together, these studies demonstrate preclinical proof-of-concept of liver-directed gene therapy with FLT190 for the treatment of Fabry disease.

Confirmatory Factor Analysis, Internal Consistency, Gender Differential Item Functioning and Discriminant Validity of the Fear of COVID-5 Scale Amidst Emerging Adult University Students in Mexico.

The study aimed to perform confirmatory factor analysis, internal consistency, gender differential item functioning, and discriminant validity of the Fear of COVID-5 Scale in emerging adult students of a university in Mexico. Confirmatory factor analysis, internal consistency (Cronbach's alpha and McDonald's omega), and gender differential item functioning were estimated (Kendall tau b correlation). The Fear of COVID-5 Scale showed a one-dimension structure (RMSEA = 0.07, CFI = 0.98, TLI = 0.96, and SRMR = 0.02), with high internal consistency (Cronbach's alpha of 0.78 and McDonald's omega of 0.81), non-gender differential item functioning (Kendall tau b between 0.07 and 0.10), and significant discriminant validity (Higher scores for fear of COVID-19 were observed in high clinical anxiety levels). In conclusion, the Fear of COVID-5 Scale presents a clear one-dimension structure similar to a previous study.

High-Dose Convalescent Plasma for Treatment of Severe COVID-19.

To assess whether high-dose coronavirus disease (COVID-19) convalescent plasma (CCP) transfusion may benefit patients with severe COVID-19, we conducted a multicenter randomized trial in Brazil. Patients with severe COVID-19 who were within 10 days of initial symptom onset were eligible. Patients in the CCP group received 3 daily doses of CCP (600 mL/d) in addition to standard treatment; control patients received standard treatment only. Primary outcomes were death rates at days 30 and 60 of study randomization. Secondary outcomes were ventilator-free days and hospital-free days. We enrolled 107 patients: 36 CCP and 71 control. At day 30, death rates were 22% for CCP and 25% for the control group; at day 60, rates were 31% for CCP and 35% for control. Needs for invasive mechanical ventilation and durations of hospital stay were similar between groups. We conclude that high-dose CCP transfused within 10 days of symptom onset provided no benefit for patients with severe COVID-19.

Regional myocardial sympathetic denervation precedes the development of left ventricular systolic dysfunction in chronic Chagas' cardiomyopathy.

BACKGROUND: Regional myocardial sympathetic denervation is a conspicuous and early disorder in patients with chronic Chagas' cardiomyopathy (CCC), potentially associated to the progression of myocardial dysfunction OBJECTIVE: To evaluate in a longitudinal study the association between the presence and the progression of regional myocardial sympathetic denervation with the deterioration of global and segmental left ventricular dysfunction in CCC. METHODS: 18 patients with CCC were submitted at initial evaluation and after 5.5 years to rest myocardial scintigraphy with 123Iodo-metaiodobenzylguanidine and 99mTc-sestamibi and to two-dimensional echocardiography to assess myocardial sympathetic denervation, extent of fibrosis, and the left ventricular ejection fraction (LVEF) and wall motion abnormalities. RESULTS: In the follow-up evaluation, compared to the initial one, we observed a significant decrease in LVEF (56 ± 11 to 49% ± 12; P = .01) and increased summed defects scores in the myocardial innervation scintigraphy (15 ± 10 to 20 ± 9; P < .01). The presence of regional myocardial sympathetic denervation in ventricular regions of viable non-fibrotic myocardium presented an odds ratio of 4.25 for the development of new wall motion abnormalities (P = .001). CONCLUSION: Regional and global myocardial sympathetic denervation is a progressive derangement in CCC. In addition, the regional denervation is topographically associated with areas of future development of regional systolic dysfunction in patients with CCC.

Histo-blood group A is a risk factor for severe COVID-19.

OBJECTIVES: Evaluate the impact of ABO histo-blood group type on COVID-19 severity. BACKGROUND: ABO histo-blood type has been associated with different outcomes in infectious diseases. It has also shown a higher proportion of type A patients with SARS-CoV-2. In this observational study, extracted from an ongoing clinical trial on the efficacy of convalescent plasma transfused in COVID-19 patients, we describe the impact of ABO blood type on the risk of developing severe COVID-19. MATERIALS AND METHODS: Seventy-two consecutive patients (37 type A, 23 type O, 11 type B, 1 type AB) with severe (respiratory failure) COVID-19 were included. Control group was composed of 160 individuals randomly selected from the same populational basis. RESULTS: Blood group A was overrepresented (51.39%) in the patient group in relation to the control group (30%), whereas blood group O was less represented (31.94%) in patient than in control group (48%). Odds ratio (A vs. O) was 2.581 (1.381-4.817), CI 95%; p = 0.004. Also, blood group A patients appeared to have more severe disease, given by the scores of the Sequential Organ Failure Assessment and Simplified Acute Physiologic Score 3 (p = 0.036 and p = 0.058, respectively). CONCLUSION: Histo-blood type A is associated with a higher risk of developing severe COVID-19 in relation to blood type O.

Adaptation and psychometric evaluation of the Fear of COVID-19 Scale in the general Colombian population.

The study aimed to adapt and explore the psychometric performance of the Fear of COVID-19 Scale (FCV-19S) in the general Colombian population. The original FCV-19S is a 7-item scale that underwent an adaptation (Item 1 and 5 were deleted). From an online sample of 1,687 adults (59% female), exploratory and confirmatory factor analyses were performed for versions of the scale with 6 and 5 items. Cronbach's alpha and McDonald's omega were calculated. The confirmatory factor analysis showed that the 5-item scale (Fear of COVID-5) presented better indicators. In conclusion, the Fear of COVID-5 has acceptable performance in the Colombian population.

Mixed-Methods Evaluation of the Initial Implementation of Advanced Home Visits in Chile.

Home visiting programs are evidence-based interventions that have a myriad outcomes for mothers and newborns. Chile offers these services as part of the Chile Crece Contigo, a nationwide program. However, implementing home visiting programs in community settings is difficult. In this study, we report clinic, provider, and participant engagement with the implementation of advanced home visits (ViDAs) in Chilean primary care clinics. ViDAs include a high number of visits, external supervision, and the use of technology. In this study, qualitative and quantitative data were collected to assess the initial implementation of the home visiting strategy. Qualitative data consisted of individual interviews and focus groups with directors of city health departments, clinic managers, and providers conducting home visits. Quantitative data included clinic, provider, and participant recruitment. City health departments were approached to authorize the participation of primary care clinics in the ViDAs program. Then, clinic directors were invited to approve the implementation of the home visiting program at their health centers. In total, 16 clinics, 42 practitioners, and 185 participants were recruited. A large amount of resources was needed to recruit clinics, providers, and participants. The intervention had low acceptability, low adoption, and a high implementation cost. Initial program implementation experienced several challenges. Identified facilitators and barriers both highlighted the need for community engagement at all levels for the successful implementation of an innovation in Chilean primary care clinics. In addition, this article provides recommendations for practitioners and researchers regarding the conduct of research in community-based settings.

Mitogenomic phylogeny of Callithrix with special focus on human transferred taxa.

BACKGROUND: Callithrix marmosets are a relatively young primate radiation, whose phylogeny is not yet fully resolved. These primates are naturally para- and allopatric, but three species with highly invasive potential have been introduced into the southeastern Brazilian Atlantic Forest by the pet trade. There, these species hybridize with each other and endangered, native congeners. We aimed here to reconstruct a robust Callithrix phylogeny and divergence time estimates, and identify the biogeographic origins of autochthonous and allochthonous Callithrix mitogenome lineages. We sequenced 49 mitogenomes from four species (C. aurita, C. geoffroyi, C. jacchus, C. penicillata) and anthropogenic hybrids (C. aurita x Callithrix sp., C. penicillata x C. jacchus, Callithrix sp. x Callithrix sp., C. penicillata x C. geoffroyi) via Sanger and whole genome sequencing. We combined these data with previously published Callithrix mitogenomes to analyze five Callithrix species in total. RESULTS: We report the complete sequence and organization of the C. aurita mitogenome. Phylogenetic analyses showed that C. aurita was the first to diverge within Callithrix 3.54 million years ago (Ma), while C. jacchus and C. penicillata lineages diverged most recently 0.5 Ma as sister clades. MtDNA clades of C. aurita, C. geoffroyi, and C. penicillata show intraspecific geographic structure, but C. penicillata clades appear polyphyletic. Hybrids, which were identified by phenotype, possessed mainly C. penicillata or C. jacchus mtDNA haplotypes. The biogeographic origins of mtDNA haplotypes from hybrid and allochthonous Callithrix were broadly distributed across natural Callithrix ranges. Our phylogenetic results also evidence introgression of C. jacchus mtDNA into C. aurita. CONCLUSION: Our robust Callithrix mitogenome phylogeny shows C. aurita lineages as basal and C. jacchus lineages among the most recent within Callithrix. We provide the first evidence that parental mtDNA lineages of anthropogenic hybrid and allochthonous marmosets are broadly distributed inside and outside of the Atlantic Forest. We also show evidence of cryptic hybridization between allochthonous Callithrix and autochthonous C. aurita. Our results encouragingly show that further development of genomic resources will allow to more clearly elucidate Callithrix evolutionary relationships and understand the dynamics of Callithrix anthropogenic introductions into the Brazilian Atlantic Forest.

Characterization of multidrug-resistant and virulent Klebsiella pneumoniae strains belonging to the high-risk clonal group 258 (CG258) isolated from inpatients in northeastern Brazil.

Multidrug-resistant (MDR) and hypervirulent Klebsiella pneumoniae (hvKp) clones have become a major threat to global public health. The clonal group 258 (CG258) is considered a high-risk CG and the K. pneumoniae strains belonging to it are often multi-resistant and to spread mainly in the hospital environment. This study aimed to characterize the antimicrobial resistance profile, virulence factors, and the clonal relationships among 13 K. pneumoniae strains belonging to CG258 from patients admitted to a tertiary hospital in Teresina, in the state of Piauí, northeastern Brazil. Ten strains were classified as MDR and three as extensively drug-resistant (XDR). Three different ß-lactamase-encoding genes (blaKPC, blaOXA-1-like, and blaCTX-M-Gp1) and six virulence genes (fimH, ycfM, mrkD, entB, ybtS, and kfu) were detected. Moreover, two hypermucoviscous K. pneumoniae strains and one capsular K-type 2 were found. Multilocus sequence typing analysis revealed ten different sequence types (STs) (ST14, ST17, ST20, ST29, ST45, ST101, ST268, ST1800, ST3995, and ST3996) belonging to CG258, being two (ST3995 and ST3996) described for the first time in this study.

Sox11 is an Activity-Regulated Gene with Dentate-Gyrus-Specific Expression Upon General Neural Activation.

Neuronal activity initiates transcriptional programs that shape long-term changes in plasticity. Although neuron subtypes differ in their plasticity response, most activity-dependent transcription factors (TFs) are broadly expressed across neuron subtypes and brain regions. Thus, how region- and neuronal subtype-specific plasticity are established on the transcriptional level remains poorly understood. We report that in young adult (i.e., 6-8 weeks old) mice, the developmental TF SOX11 is induced in neurons within 6 h either by electroconvulsive stimulation or by exploration of a novel environment. Strikingly, SOX11 induction was restricted to the dentate gyrus (DG) of the hippocampus. In the novel environment paradigm, SOX11 was observed in a subset of c-FOS expressing neurons (ca. 15%); whereas around 75% of SOX11+ DG granule neurons were c-FOS+, indicating that SOX11 was induced in an activity-dependent fashion in a subset of neurons. Environmental enrichment or virus-mediated overexpression of SOX11 enhanced the excitability of DG granule cells and downregulated the expression of different potassium channel subunits, whereas conditional Sox11/4 knock-out mice presented the opposite phenotype. We propose that Sox11 is regulated in an activity-dependent fashion, which is specific to the DG, and speculate that activity-dependent Sox11 expression may participate in the modulation of DG neuron plasticity.

Atypical COVID-19 presentation with Budd-Chiari syndrome leading to an outbreak in the emergency department.

We described a case report of a 50 years-old-woman admitted to the emergency department with abdominal pain associated with febrile hepatosplenomegaly with the final diagnosis of suprahepatic vein thrombosis secondary to COVID-19. Initially, this patient stayed out of a private room because of this atypical presentation and caused a COVID-19 outbreak in the emergency department.

New Pyridone-Based Derivatives as Cannabinoid Receptor Type 2 Agonists.

The activation of the human cannabinoid receptor type II (CB2R) is known to mediate analgesic and anti-inflammatory processes without the central adverse effects related to cannabinoid receptor type I (CB1R). In this work we describe the synthesis and evaluation of a novel series of N-aryl-2-pyridone-3-carboxamide derivatives tested as human cannabinoid receptor type II (CB2R) agonists. Different cycloalkanes linked to the N-aryl pyridone by an amide group displayed CB2R agonist activity as determined by intracellular [cAMP] levels. The most promising compound 8d exhibited a non-toxic profile and similar potency (EC50 = 112 nM) to endogenous agonists Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) providing new information for the development of small molecules activating CB2R. Molecular docking studies showed a binding pose consistent with two structurally different agonists WIN-55212-2 and AM12033 and suggested structural requirements on the pyridone substituents that can satisfy the orthosteric pocket and induce an agonist response. Our results provide additional evidence to support the 2-pyridone ring as a suitable scaffold for the design of CB2R agonists and represent a starting point for further optimization and development of novel compounds for the treatment of pain and inflammation.

Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy.

BACKGROUND: Spinal muscular atrophy type 1 (SMA1) is a progressive, monogenic motor neuron disease with an onset during infancy that results in failure to achieve motor milestones and in death or the need for mechanical ventilation by 2 years of age. We studied functional replacement of the mutated gene encoding survival motor neuron 1 (SMN1) in this disease. METHODS: Fifteen patients with SMA1 received a single dose of intravenous adeno-associated virus serotype 9 carrying SMN complementary DNA encoding the missing SMN protein. Three of the patients received a low dose (6.7×1013 vg per kilogram of body weight), and 12 received a high dose (2.0×1014 vg per kilogram). The primary outcome was safety. The secondary outcome was the time until death or the need for permanent ventilatory assistance. In exploratory analyses, we compared scores on the CHOP INTEND (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders) scale of motor function (ranging from 0 to 64, with higher scores indicating better function) in the two cohorts and motor milestones in the high-dose cohort with scores in studies of the natural history of the disease (historical cohorts). RESULTS: As of the data cutoff on August 7, 2017, all 15 patients were alive and event-free at 20 months of age, as compared with a rate of survival of 8% in a historical cohort. In the high-dose cohort, a rapid increase from baseline in the score on the CHOP INTEND scale followed gene delivery, with an increase of 9.8 points at 1 month and 15.4 points at 3 months, as compared with a decline in this score in a historical cohort. Of the 12 patients who had received the high dose, 11 sat unassisted, 9 rolled over, 11 fed orally and could speak, and 2 walked independently. Elevated serum aminotransferase levels occurred in 4 patients and were attenuated by prednisolone. CONCLUSIONS: In patients with SMA1, a single intravenous infusion of adeno-associated viral vector containing DNA coding for SMN resulted in longer survival, superior achievement of motor milestones, and better motor function than in historical cohorts. Further studies are necessary to confirm the safety and efficacy of this gene therapy. (Funded by AveXis and others; ClinicalTrials.gov number, NCT02122952 .).

Secondary forest fragments offer important carbon and biodiversity cobenefits.

Tropical forests store large amounts of carbon and high biodiversity, but are being degraded at alarming rates. The emerging global Forest and Landscape Restoration (FLR) agenda seeks to limit global climate change by removing carbon dioxide from the atmosphere through the growth of trees. In doing so, it may also protect biodiversity as a free cobenefit, which is vital given the massive shortfall in funding for biodiversity conservation. We investigated whether natural forest regeneration on abandoned pastureland offers such cobenefits, focusing for the first time on the recovery of taxonomic diversity (TD), phylogenetic diversity (PD) and functional diversity (FD) of trees, including the recovery of threatened and endemic species richness, within isolated secondary forest (SF) fragments. We focused on the globally threatened Brazilian Atlantic Forest, where commitments have been made to restore 1 million hectares under FLR. Three decades after land abandonment, regenerating forests had recovered ~20% (72 Mg/ha) of the above-ground carbon stocks of a primary forest (PF), with cattle pasture containing just 3% of stocks relative to PFs. Over this period, SF recovered ~76% of TD, 84% of PD and 96% of FD found within PFs. In addition, SFs had on average recovered 65% of threatened and ~30% of endemic species richness of primary Atlantic forest. Finally, we find positive relationships between carbon stock and tree diversity recovery. Our results emphasize that SF fragments offer cobenefits under FLR and other carbon-based payments for ecosystem service schemes (e.g. carbon enhancements under REDD+). They also indicate that even isolated patches of SF could help to mitigate climate change and the biodiversity extinction crisis by recovering species of high conservation concern and improving landscape connectivity.

Volatility Study of Amino Acids by Knudsen Effusion with QCM Mass Loss Detection.

This work presents a new Knudsen effusion apparatus employing continuous monitoring of sample deposition using a quartz-crystal microbalance sensor with internal calibration by gravimetric determination of the sample mass loss. The apparatus was tested with anthracene and 1,3,5-triphenylbenzene and subsequently used for the study of sublimation behavior of several proteinogenic amino acids. Their low volatility and thermal instability strongly limit possibilities of studying their sublimation behavior and available literature data. The results presented in this work are unique in their temperature range and low uncertainty required for benchmarking theoretical studies of sublimation behavior of molecular crystals. The possibility of dimerization in the gas phase that would invalidate the effusion experiments is addressed and disproved by theoretical calculations. The enthalpy of sublimation of each amino acid is analyzed based on the contributions in two hypothetical sublimation paths involving the proton transfer in the solid and in the gas phase.

Urban wild meat consumption and trade in central Amazonia.

The switch from hunting wild meat for home consumption to supplying more lucrative city markets in Amazonia can adversely affect some game species. Despite this, information on the amounts of wild meat eaten in Amazonian cities is still limited. We estimated wild meat consumption rates in 5 cities in the State of Amazonas in Brazil through 1046 door-to-door household interviews conducted from 2004 to 2012. With these data, we modeled the relationship between wild meat use and a selection of socioeconomic indices. We then scaled up our model to determine the amounts of wild meat likely to be consumed annually in the 62 urban centers in central Amazonia. A total of 80.3% of all interviewees reported consuming wild meat during an average of 29.3 (CI 11.6) days per year. Most wild meat was reported as bought in local markets (80.1%) or hunted by a family member (14.9%). Twenty-one taxa were cited as consumed, mostly mammals (71.6%), followed by reptiles (23.2%) and then birds (5.2%). The declared frequency of wild meat consumption was positively correlated with the proportion of rural population as well as with the per capita gross domestic product of the municipality (administrative divisions) where the cities were seated. We estimated that as much as 10,691 t of wild meat might be consumed annually in the 62 urban centers within central Amazonia, the equivalent of 6.49 kg per person per year. In monetary terms, this amounts to US$21.72 per person per year or US$35.1 million overall, the latter figure is comparable to fish and timber production in the region. Given this magnitude of wild meat trade in central Amazonia, it is fundamental to integrate this activity into the formal economy and actively develop policies that allow the trade of more resilient taxa and restrict trade in species sensitive to hunting.

Mercado y Consumo Urbano de Carne Silvestre en la Amazonia Central Resumen El cambio de la caza de animales silvestres para consumo del hogar a caza para surtir mercados urbanos más lucrativos en la Amazonia puede afectar negativamente a algunas especies de caza. A pesar de esto, la información sobre la cantidad de carne silvestre que se consume en las ciudades de la Amazonia todavía es limitada. Estimamos las tasas de consumo de carne silvestre en cinco ciudades del Estado de Amazonas, Brasil, por medio de 1046 entrevistas presenciales a hogares realizadas entre 2004 y 2012. Con estos datos modelamos la relación entre el uso de la carne silvestre y una selección de índices socioeconómicos. Después aumentamos nuestro modelo para determinar la cantidad de carne silvestre que tal vez se consume anualmente en los 62 centros urbanos de la Amazonia central. Un total de 80.3% de todos los entrevistados reportaron el consumo de carne silvestre durante un promedio de 29.3 (CI 11.6) días por año. La mayoría de la carne silvestre fue reportada como comprada en mercados locales (80.1%) o cazada por algún integrante de la familia (14.9%). Se citaron 21 taxones como parte del consumo, principalmente mamíferos (71.6%), seguidos por reptiles (23.2%) y aves (5.2%). La frecuencia declarada de consumo de carne silvestre estuvo correlacionada positivamente con la proporción de población rural, así como con el producto doméstico bruto per cápita de la municipalidad (divisiones administrativas) en donde se encuentran las ciudades. Estimamos que un máximo de 10,691 toneladas de carne silvestre podrían ser consumidas anualmente en los 62 centros urbanos de la Amazonia central, el equivalente a 6.49 kg/persona/año. En términos monetarios, esto equivale a US$21.72/persona/año o US$35.1 millones en general. Esta última cifra es comparable con la producción de madera y de peces en la región. Dada esta magnitud del mercado de carne silvestre en la Amazonia central, es fundamental la integración de esta actividad en la economía formal y el desarrollo activo de políticas que permitan el mercado de taxones más resilientes y que restrinjan el mercado para las especies sensibles a la caza.

In vivo demonstration of microvascular thrombosis in severe COVID-19.

Several autopsy studies showed microthrombi in pulmonary circulation of severe COVID-19 patients. The major limitation of these investigations is that the autopsy provided static information. Some of these alterations could be secondary to the disseminated intravascular coagulation (DIC) observed as the final standard route to the multisystem organ failure exhibited in critically ill patients. We report preliminary results of an in vivo evaluation of sublingual microcirculation in thirteen patients with severe COVID-19 requiring mechanical ventilation. We observed multiple filling defects moving within the microvessels indicative of thrombi in most of the cases 11/13 (85%). This is the first imaging documentation of microvascular thrombosis in living severe COVID-19 patients since the beginning of the hospitalization. The clinical relevance of microvascular thrombosis in this disease requires further research.

Metformin use is associated with a lower risk of osteoporosis in adult women independent of type 2 diabetes mellitus and obesity. REDLINC IX study.

Metformin may decrease cell senescence, including bone; hence we aimed at evaluating the association between metformin use and osteoporosis. This was a cross-sectional study carried out in 1259 Latin American adult women aged 40 or more who were not on anti-osteoporotic drugs, were on metformin and had a bone densitometry performed. Of the whole sample, 40.3% reported being on metformin (at least 1 year), 30.2% had type 2 diabetes mellitus and 22.6% had osteoporosis. Median (interquartile range) body mass index (BMI) for the whole cohort was 27.7 (4.6) kg/m2 and 30.2% had type 2 diabetes mellitus. Current use of hormone therapy, calcium, and vitamin D corresponded respectively to 10.7%, 47.7%, and 43.1% of all surveyed women. A logistic regression model was used to analyze the association of osteoporosis with various covariates incorporated into the model such as age (OR: 1.07, 95% CI: 1.05-1.09), BMI (OR: 0.92, 95% CI: 0.89-0.96) and metformin use (OR: 0.44, 95% CI: 0.32-0.59). Metformin use, regardless of the presence of type 2 diabetes or obesity, was associated with a lower risk of osteoporosis in adult women. We propose that one explanation for this observation could be the effect of the drug over cellular senescence.