Cytotoxicity, chemical, and nutritional profile evaluation of biomass extracts of the Lemna aequinoctialis (duckweed) aquatic plant.

Lemna aequinoctialis (duckweed) is the smallest and fast-growing aquatic plant species producing protein-rich biomass with high protein nutritional value, phytoremediation capacity, and nutrient removal from wastewater. Duckweed may also be used as a new potential bioreactor for biological products, such as vaccines, antibodies, and pharmaceutical proteins. Based upon the potential importanc of L. aequinoctialis in phytoremediation and as a bioreactor the aim of this study was to (1) characterize the chemical and nutritional profiles of L. aequinoctialis biomass utilizing an integrated multi-trophic aquaculture system (IMTA) and a pond, and (2) investigate the cytotoxic potential of different concentrations of organic extracts and fractions using the MTT bioassay. EDXRF and ICP-MS analyses indicated the presence of trace elements in lower amounts in relation to the biomass of L. aequinoctialis in the lagoon, emphasizing the importance of plant inclusion management to reduce bioaccumulation of these elements. Analysis of mineral profiles, fatty acids, and amino acids indicated a satisfactory nutritional composition for the use of biomass as a bioproduct. Pigment analysis showed a high concentration of carotenoids, especially astaxanthin. After standardizing the controls, the MTT cell viability test was carried out utilizing rat hepatoma cell line (HTC), which are metabolizing cells that were treated with aqueous or ethanolic extracts and the dichloromethane, ethyl acetate, and methanol fractions at different concentrations. No apparent cytotoxic potential was observed following treatments, since there was no significant reduction in cell viability. Therefore, this study provides information regarding the biomass of L. aequinoctialis derived from the IMTA system, which might support further research into the application of this species as a bioproduct.

Cetacean responses to violation of expectation paradigm in a free-swim context.

The investigation of individual responses to unexpected stimuli or outcomes provides insights into basic cognitive processes, such as mental representations, emotional states of surprise, and detections of anomalies. Three experiments using a violation of expectation paradigm were conducted with 12 belugas and 17 bottlenose dolphins in managed care to test two classes of stimuli (humans and objects) in manipulated sequences of familiar and unfamiliar humans (Study 1, trainers and strangers), familiar and unfamiliar objects (Study 2, typical enrichment devices and new objects), and finally objects and humans (Study 3). Gaze durations were assessed for each condition in a given study during free-swim contexts. The results supported previous findings that visual stimuli, regardless of class, were stimulating and intriguing for both belugas and bottlenose dolphins. Belugas were more likely to gaze longer at human and object stimuli and tended to gaze longer at unexpected experiences than control or expected experiences. Bottlenose dolphins showed similar trends except when objects were involved. Individual variability was present for both species with some individuals showing stronger patterns of responses for expected experiences than others. After 2 years of intermittent experiments, belugas and bottlenose dolphins in managed care maintained their curiosity about visual stimuli, for which they received no primary reinforcement. Investigating responses to unexpected stimuli with animals in managed care may provide insight into how these animals respond to biologically relevant conditions, such as boat presence, predators, and unfamiliar conspecifics.

First characterization of vocalizations and passive acoustic monitoring of the vulnerable African manatee (Trichechus senegalensis).

Even among the understudied sirenians, African manatees (Trichechus senegalensis) are a poorly understood, elusive, and vulnerable species that is difficult to detect. We used passive acoustic monitoring in the first effort to acoustically detect African manatees and provide the first characterization of their vocalizations. Within two 3-day periods at Lake Ossa, Cameroon, at least 3367 individual African manatee vocalizations were detected such that most vocalizations were detected in the middle of the night and at dusk. Call characteristics such as fundamental frequency, duration, harmonics, subharmonics, and emphasized band were characterized for 289 high-quality tonal vocalizations with a minimum signal-to-noise ratio of 4.5 dB. African manatee vocalizations have a fundamental frequency of 4.65 ± 0.700 kHz (mean ± SD), duration of 0.181 ± 0.069 s, 97% contained harmonics, 21% contained subharmonics, and 27% had an emphasized band other than the fundamental frequency. Altogether, the structure of African manatee vocalizations is similar to other manatee species. We suggest utilizing passive acoustic monitoring to fill in the gaps in understanding the distribution and biology of African manatees.

Chronic high-fat diet affects food-motivated behavior and hedonic systems in the nucleus accumbens of male rats.

Environmental variations can influence eating and motivated behaviors, as well as the brain's feeding circuits to predisposing overweight and obesity. The identification of mechanisms through which a long-term consumption of caloric-dense palatable foods and its association with early life stress can cause neuroadaptations and possible modify motivational behaviors are relevant to elucidate the mechanisms associated with obesity. Here, we investigated the long-term effects of a chronic high-fat diet (HFD), and its interaction with early social isolation on hedonic feeding responses in adult rats. Rats were subjected, or not, to social isolation between postnatal days 21-28 and were fed a control diet or HFD, for 10 weeks post weaning. Hedonic feeding behavior was evaluated during adulthood and parameters related to the dopaminergic, cannabinoid, and opioid systems were measured in the nucleus accumbens. Animals with chronic HFD intake were less motivated to obtain sweet palatable foods. This reduced motivation did not appear to be associated with less pleasure upon tasting sweet food, as no alteration in reactivity to sweet taste was observed. Interestingly, the animals receiving HFD presented decreased immunocontents of the D1 and CB1 receptors, while the stressed group displayed a reduction in dopamine turnover. In summary, chronic HFD causes a significant motivational impairment for sweet palatable foods; these changes may be associated with a decreased dopaminergic and cannabinoid neurotransmission in the nucleus accumbens. In contrast, a brief social isolation during the prepubertal period was unable to alter the behavioral parameters studied but caused a decreased dopaminergic turnover in the nucleus accumbens of adult rats. These findings highlight the importance of long-term HFD exposure on the modulation of hedonic feeding behavior and related neurochemical systems.

Retrieval of morphine-associated context induces cFos in dentate gyrus neurons.

Addiction has been proposed to emerge from associations between the drug and the reward-associated contexts. This associative learning has a cellular correlate, as there are more cFos+ neurons in the hippocampal dentate gyrus (DG) after psychostimulant conditioned place preference (CPP) versus saline controls. However, it is unknown whether morphine CPP leads to a similar DG activation, or whether DG activation is due to locomotion, handling, pharmacological effects, or-as data from contextual fear learning suggests-exposure to the drug-associated context. To explore this, we employed an unbiased, counterbalanced, and shortened CPP design that led to place preference and more DG cFos+ cells. Next, mice underwent morphine CPP but were then sequestered into the morphine-paired (conditioned stimulus+ [CS+]) or saline-paired (CS-) context on test day. Morphine-paired mice sequestered to CS+ had ∼30% more DG cFos+ cells than saline-paired mice. Furthermore, Bregma analysis revealed morphine-paired mice had more cFos+ cells in CS+ compared to CS- controls. Notably, there was no significant difference in DG cFos+ cell number after handling alone or after receiving morphine in home cage. Thus, retrieval of morphine-associated context is accompanied by activation of hippocampal DG granule cell neurons.

Klebsiella pneumoniae DedA family proteins have redundant roles in divalent cation homeostasis and resistance to phagocytosis.

The DedA superfamily is a highly conserved family of membrane proteins. Deletion of Escherichia coli yqjA and yghB, encoding related DedA family proteins, results in sensitivity to elevated temperature, antibiotics, and alkaline pH. The human pathogen Klebsiella pneumoniae possesses genes encoding DedA family proteins with >90% amino acid identity to E. coli YqjA and YghB. We hypothesized that the deletion of K. pneumoniae yqjA and yghB will impact its physiology and may reduce its virulence. The K. pneumoniae ΔyqjA ΔyghB mutant (strain VT101) displayed a growth defect at 42°C and alkaline pH sensitivity, not unlike its E. coli counterpart. However, VT101 retained mostly wild-type resistance to antibiotics. We found VT101 was sensitive to the chelating agent EDTA, the anionic detergent SDS, and agents capable of alkalizing the bacterial cytoplasm such as bicarbonate or chloroquine. We could restore growth at alkaline pH and at elevated temperature by addition of 0.5-2 mM Ca2+ or Mg2+ to the culture media. VT101 displayed a slower uptake of calcium, which was dependent upon calcium channel activity. VT201, with similar deletions as VT101 but derived from a virulent K. pneumoniae strain, was highly susceptible to phagocytosis by alveolar macrophages and displayed a defect in the production of capsule. These findings suggest divalent cation homeostasis and virulence are interlinked by common functions of the DedA family.IMPORTANCEKlebsiella pneumoniae is a dangerous human pathogen. The DedA protein family is found in all bacteria and is a membrane transporter often required for virulence and antibiotic resistance. K. pneumoniae possesses homologs of E. coli YqjA and YghB, with 60% amino acid identity and redundant functions, which we have previously shown to be required for tolerance to biocides and alkaline pH. A K. pneumoniae strain lacking yqjA and yghB was found to be sensitive to alkaline pH, elevated temperature, and EDTA/SDS and displayed a defect in calcium uptake. Sensitivity to these conditions was reversed by addition of calcium or magnesium to the growth medium. Introduction of ΔyqjA and ΔyghB mutations into virulent K. pneumoniae resulted in the loss of capsule, increased phagocytosis by macrophages, and a partial loss of virulence. These results show that targeting the Klebsiella DedA family results in impaired divalent cation transport and, in turn, loss of virulence.

Standard rodent diets differentially impact alcohol consumption and preference and gut microbiome diversity.

Alcohol Use Disorder (AUD) is a complex and widespread disease with limited pharmacotherapies. Preclinical animal models of AUD use a variety of voluntary alcohol consumption procedures to recapitulate different phases of AUD including binge alcohol consumption and dependence. However, voluntary alcohol consumption in mice is widely variable rendering it difficult to reproduce results across labs. Accumulating evidence indicates that different brands of commercially available rodent chow can profoundly influence alcohol intake. In this study, we investigated the effects of three commercially available and widely used rodent diet formulations on alcohol consumption and preference in C57BL/6J mice using the 24h intermittent access procedure. The three brands of chow tested were LabDiet 5001 (LD 5001), LabDiet 5053 (LD 5053), and Teklad 2019S (TL2019S) from two companies (Research Diets and Envigo respectively). Mice fed LD5001 displayed the highest levels of alcohol consumption and preference followed by LD5053 and TL2019S. We also found that alcohol consumption and preference could be rapidly switched by changing the diet 48h prior to alcohol administration. Sucrose, saccharin, and quinine preference were not altered suggesting that the diets did not alter taste perception. We also found that mice fed LD5001 displayed increased quinine-resistant alcohol intake compared to mice fed TL2019S, suggesting that diets could influence the development of "compulsive" like alcohol consumption. We profiled the gut microbiome of water and alcohol drinking mice that were maintained on different diets and found significant differences in bacterial alpha and beta diversity, which could impact gut-brain axis signaling and alcohol consumption.

Standard rodent diets differentially impact alcohol consumption, preference, and gut microbiome diversity.

Alcohol use disorder (AUD) is a complex and widespread disease with limited pharmacotherapies. Preclinical animal models of AUD use a variety of voluntary alcohol consumption procedures to recapitulate different phases of AUD, including binge alcohol consumption and dependence. However, voluntary alcohol consumption in mice is widely variable, making it difficult to reproduce results across labs. Accumulating evidence indicates that different brands of commercially available rodent chow can profoundly influence alcohol intake. In this study, we investigated the effects of three commercially available and widely used rodent diet formulations on alcohol consumption and preference in C57BL/6 J mice using the 24 h intermittent access procedure. The three brands of chow tested were LabDiet 5,001 (LD5001), LabDiet 5,053 (LD5053), and Teklad 2019S (TL2019S) from two companies (Research Diets and Envigo, respectively). Mice fed LD5001 and LD5053 displayed higher levels of alcohol consumption and preference compared to mice fed TL2019S. We also found that alcohol consumption and preference could be rapidly switched by changing the diet 48 h prior to alcohol administration. Sucrose, saccharin, and quinine preferences were not altered, suggesting that the diets did not alter sweet and bitter taste perception. We also found that mice fed LD5001 displayed increased quinine-resistant alcohol intake compared to mice fed TL2019S, suggesting that diets could influence the development of compulsive behaviors such as alcohol consumption. We profiled the gut microbiome of water- and alcohol-drinking mice that were maintained on different diets and found significant differences in bacterial alpha- and beta-diversities, which could impact the gut-brain axis signaling and alcohol consumption.

Activated Carbon Electrodes for Supercapacitors from Purple Corncob (Zea maysL.).

Activated carbon-based supercapacitor electrodes synthesized from biomass or waste-derived biomass have recently attracted considerable attention because of their low cost, natural abundance, and power delivery performance. In this work, purple-corncob-based active carbons are prepared by KOH activation and subsequently evaluated as a composite electrode for supercapacitors using either an acidic or an alkali solution as the electrolyte. The synthesis of the material involves mixing the purple corncob powder with different concentrations of KOH (in the range of 5% to 30%) and a thermal treatment at 700 °C under an inert atmosphere. Physicochemical characterizations were performed using scanning electron microscopy, Raman spectroscopy, N2 physisorption analysis, Fourier-transform infrared spectroscopy, and X-ray photoelectron spectroscopy, while the electrochemical characteristics were determined using cyclic voltammetry, a galvanostatic charge/discharge curve, and electrochemical impedance techniques measured in a three- and two-electrode system. Composite electrodes activated with 10% KOH had a specific surface area of 728 m2 g-1, and high capacitances of 195 F g-1 at 0.5 A g-1 in 1 mol L-1 H2SO4 and 116 F g-1 at 0.5 A g-1 in 1 mol L-1 KOH were obtained. It also presented a 76% capacitance retention after 50 000 cycles. These properties depend significantly on the microporous area and micropore volume characteristics of the activated carbon. Overall, our results indicate that purple corncob has an interesting prospect as a carbon precursor material for supercapacitor electrodes.

Effect of Chronic Tibolone Administration on Memory and Choline Acetyltransferase and Tryptophan Hydroxylase Content in Aging Mice.

Gonadal steroids exert different effects on the central nervous system (CNS), such as preserving neuronal function and promoting neuronal survival. Estradiol, progesterone, and testosterone reduce neuronal loss in the CNS in animal models of neurodegeneration. However, hormone replacement therapy has been associated with higher rates of endometrial, prostate, and breast cancer. Tibolone (TIB), the metabolites of which show estrogenic and progestogenic effects, is an alternative to reduce this risk. However, the impact of TIB on memory and learning, as well as on choline acetyltransferase (ChAT) and tryptophan hydroxylase (TPH) levels in the hippocampus of aging males, is unknown. We administered TIB to aged C57BL/6J male mice at different doses (0.01 or 1.0 mg/kg per day for 12 weeks) and evaluated its effects on memory and learning and the content of ChAT and TPH. We assessed memory and learning with object recognition and elevated T-maze tasks. Additionally, we determined ChAT and TPH protein levels in the hippocampus by Western blotting. TIB administration increased the percentage of time spent on the novel object in the object recognition task. In addition, the latency of leaving the enclosed arm increased in both TIB groups, suggesting an improvement in fear-based learning. We also observed decreased ChAT content in the group treated with the 0.01 mg/kg TIB dose. In the case of TPH, no changes were observed with either TIB dose. These results show that long-term TIB administration improves memory without affecting locomotor activity and modulates cholinergic but not serotonergic systems in the hippocampus of aged male mice.

The mitochondrial Ca 2+ channel MCU is critical for tumor growth by supporting cell cycle progression and proliferation.

The mitochondrial uniporter (MCU) Ca 2+ ion channel represents the primary means for Ca 2+ uptake into mitochondria. Here we employed in vitro and in vivo models with MCU genetically eliminated to understand how MCU contributes to tumor formation and progression. Transformation of primary fibroblasts in vitro was associated with increased MCU expression, enhanced mitochondrial Ca 2+ uptake, suppression of inactivating-phosphorylation of pyruvate dehydrogenase, a modest increase of basal mitochondrial respiration and a significant increase of acute Ca 2+ -dependent stimulation of mitochondrial respiration. Inhibition of mitochondrial Ca 2+ uptake by genetic deletion of MCU markedly inhibited growth of HEK293T cells and of transformed fibroblasts in mouse xenograft models. Reduced tumor growth was primarily a result of substantially reduced proliferation and fewer mitotic cells in vivo , and slower cell proliferation in vitro associated with delayed progression through S-phase of the cell cycle. MCU deletion inhibited cancer stem cell-like spheroid formation and cell invasion in vitro , both predictors of metastatic potential. Surprisingly, mitochondrial matrix Ca 2+ concentration, membrane potential, global dehydrogenase activity, respiration and ROS production were unchanged by genetic deletion of MCU in transformed cells. In contrast, MCU deletion elevated glycolysis and glutaminolysis, strongly sensitized cell proliferation to glucose and glutamine limitation, and altered agonist-induced cytoplasmic Ca 2+ signals. Our results reveal a dependence of tumorigenesis on MCU, mediated by a reliance on mitochondrial Ca 2+ uptake for cell metabolism and Ca 2+ dynamics necessary for cell-cycle progression and cell proliferation.

The mitochondrial Ca2+ channel MCU is critical for tumor growth by supporting cell cycle progression and proliferation.

Introduction: The mitochondrial uniporter (MCU) Ca2+ ion channel represents the primary means for Ca2+ uptake by mitochondria. Mitochondrial matrix Ca2+ plays critical roles in mitochondrial bioenergetics by impinging upon respiration, energy production and flux of biochemical intermediates through the TCA cycle. Inhibition of MCU in oncogenic cell lines results in an energetic crisis and reduced cell proliferation unless media is supplemented with nucleosides, pyruvate or α-KG. Nevertheless, the roles of MCU-mediated Ca2+ influx in cancer cells remain unclear, in part because of a lack of genetic models. Methods: MCU was genetically deleted in transformed murine fibroblasts for study in vitro and in vivo. Tumor formation and growth were studied in murine xenograft models. Proliferation, cell invasion, spheroid formation and cell cycle progression were measured in vitro. The effects of MCU deletion on survival and cell-death were determined by probing for live/death markers. Mitochondrial bioenergetics were studied by measuring mitochondrial matrix Ca2+ concentration, membrane potential, global dehydrogenase activity, respiration, ROS production and inactivating-phosphorylation of pyruvate dehydrogenase. The effects of MCU rescue on metabolism were examined by tracing of glucose and glutamine utilization for fueling of mitochondrial respiration. Results: Transformation of primary fibroblasts in vitro was associated with increased MCU expression, enhanced MCU-mediated Ca2+ uptake, altered mitochondrial matrix Ca2+ concentration responses to agonist stimulation, suppression of inactivating-phosphorylation of pyruvate dehydrogenase and a modest increase of mitochondrial respiration. Genetic MCU deletion inhibited growth of HEK293T cells and transformed fibroblasts in mouse xenograft models, associated with reduced proliferation and delayed cell-cycle progression. MCU deletion inhibited cancer stem cell-like spheroid formation and cell invasion in vitro, both predictors of metastatic potential. Surprisingly, mitochondrial matrix [Ca2+], membrane potential, global dehydrogenase activity, respiration and ROS production were unaffected. In contrast, MCU deletion elevated glycolysis and glutaminolysis, strongly sensitized cell proliferation to glucose and glutamine limitation, and altered agonist-induced cytoplasmic Ca2+ signals. Conclusion: Our results reveal a dependence of tumorigenesis on MCU, mediated by a reliance on MCU for cell metabolism and Ca2+ dynamics necessary for cell-cycle progression and cell proliferation.

Low testosterone levels as an independent risk factor for mortality in male patients with COVID-19: Report of a Single-Center Cohort Study in Mexico.

INTRODUCTION AND OBJECTIVES: Throughout the coronavirus disease 2019 (COVID-19) pandemic, a greater severity and lethality of the disease has been highlighted in male patients, so we set out to evaluate the prognostic role of serum testosterone levels in the clinical results of this population. METHODS: In this single-center and cross-sectional design, we included male patients admitted to our hospital with COVID-19 confirmed diagnosis. The biochemical analysis included lymphocytes, lactate dehydrogenase (LDH), total testosterone (TT), dehydroepiandrosterone, follicle-stimulating hormone, and luteinizing hormone. Receiver operating characteristic curves, univariate and bivariate analysis, and binary logistic regression for multivariate analysis were performed. A p value<0.05 was consider significant. RESULTS: From 86 men included, 48.8% died. TT levels were lower in non-survivor patients than in survivor patients (4.01nmol/L [0.29-14.93] vs 5.41 (0.55-25.08) nmol/L, p=0.021). The independent risk factors that increased the relative risk (RR) of dying from COVID-19 were: age>59 years (RR 3.5 [95% IC 1.0-11.6], p=0.045), TT levels<4.89nmol/L (RR 4.0 [95% IC 1.2-13.5], p=0.027) and LDH levels>597IU/L (RR 3.9 [95% IC 1.2-13.1], p=0.024). Patients who required mechanical ventilation (p=0.025), had lymphopenia (p=0.013) and LDH levels>597IU/L (p=0.034), had significantly lower TT levels compared to those who did not present these conditions. There were no differences in TT levels between patients who had or did not have comorbidities. CONCLUSIONS: A TT level<4.89nmol/L increase four times the RR of death from COVID-19 in men, regardless of age or presence of comorbidities.

In Silico and In Vivo Evaluation of the Maqui Berry (Aristotelia chilensis (Mol.) Stuntz) on Biochemical Parameters and Oxidative Stress Markers in a Metabolic Syndrome Model.

Metabolic syndrome (MetS) is a complex disease that includes metabolic and physiological alterations in various organs such as the heart, pancreas, liver, and brain. Reports indicate that blackberry consumption, such as maqui berry, has a beneficial effect on chronic diseases such as cardiovascular disease, obesity, and diabetes. In the present study, in vivo and in silico studies have been performed to evaluate the molecular mechanisms implied to improve the metabolic parameters of MetS. Fourteen-day administration of maqui berry reduces weight gain, blood fasting glucose, total blood cholesterol, triacylglycerides, insulin resistance, and blood pressure impairment in the diet-induced MetS model in male and female rats. In addition, in the serum of male and female rats, the administration of maqui berry (MB) improved the concentration of MDA, the activity of SOD, and the formation of carbonyls in the group subjected to the diet-induced MetS model. In silico studies revealed that delphinidin and its glycosylated derivatives could be ligands of some metabolic targets such as α-glucosidase, PPAR-α, and PPAR-γ, which are related to MetS parameters. The experimental results obtained in the study suggest that even at low systemic concentrations, anthocyanin glycosides and aglycones could simultaneously act on different targets related to MetS. Therefore, these molecules could be used as coadjuvants in pharmacological interventions or as templates for designing new multitarget molecules to manage patients with MetS.

Prostate Cancer Cells Are Sensitive to Lysosomotropic Agent Siramesine through Generation Reactive Oxygen Species and in Combination with Tyrosine Kinase Inhibitors.

BACKGROUND: Prostate cancer is the most common cancer affecting men often resulting in aggressive tumors with poor prognosis. Even with new treatment strategies, drug resistance often occurs in advanced prostate cancers. The use of lysosomotropic agents offers a new treatment possibility since they disrupt lysosomal membranes and can trigger a series of events leading to cell death. In addition, combining lysosomotropic agents with targeted inhibitors can induce increased cell death in different cancer types, but prostate cancer cells have not been investigated. METHODS: We treated prostate cancer cells with lysosomotropic agents and determine their cytotoxicity, lysosome membrane permeabilization (LMP), reactive oxygen species (ROS) levels, and mitochondrial dysfunction. In addition, we treated cells with lysosomotropic agent in combination with tyrosine kinase inhibitor, lapatinib, and determined cell death, and the role of ROS in this cell death. RESULTS: Herein, we found that siramesine was the most effective lysosomotropic agent at inducing LMP, increasing ROS, and inducing cell death in three different prostate cancer cell lines. Siramesine was also effective at increasing cell death in combination with the tyrosine kinase inhibitor, lapatinib. This increase in cell death was mediated by lysosome membrane permeabilization, an increased in ROS levels, loss of mitochondrial membrane potential and increase in mitochondrial ROS levels. The combination of siramesine and lapatinib induced apoptosis, cleavage of PARP and decreased expression of Bcl-2 family member Mcl-1. Furthermore, lipid peroxidation occurred with siramesine treatment alone or in combination with lapatinib. Treating cells with the lipid peroxidation inhibitor alpha-tocopherol resulted in reduced siramesine induced cell death alone or in combination with lapatinib. The combination of siramesine and lapatinib failed to increase cell death responses in normal prostate epithelial cells. CONCLUSIONS: This suggests that lysomotropic agents such as siramesine in combination with tyrosine kinase inhibitors induces cell death mediated by ROS and could be an effective treatment strategy in advanced prostate cancer.

Importance of Insulin Resistance in the COVID-19 Era: A Retrospective Analysis of a Single Center in Mexico.

Introduction and objectives Type 2 diabetes mellitus (T2DM) has been one of the main risk factors associated with mortality from the coronavirus disease 2019 (COVID-19). Insulin resistance (IR) is a preceding and underlying condition of T2DM, which has been thought that it could increase mortality from COVID-19 since it favors the entry of severe acute respiratory syndrome coronavirus type 2 in the host cell. This article reports a biochemical study that estimated the prevalence of IR in COVID-19 patients and non-diabetic patients without COVID-19 history. It also assesses the prognostic role of IR in the evolution of patients with COVID-19. Materials and methods In this single-center, retrospective and cross-sectional design, we included patients with severe and critical COVID-19 and non-diabetic patients without COVID-19 history. We calculated the Homeostatic Model Assessment Insulin Resistance (HOMA-IR) and defined IR with a HOMA-IR >2.6. We estimated the prevalence of IR in both groups and used x 2 to assess the association between IR and mortality from severe and critical COVID-19. Results One hundred and twenty-three COVID-19 patients were included with a mean age of 53±15 years: 77 (62.6%) were men and 46 (37.4%) were women. Eighty (65%) patients were critical while the rest were severe. Forty-three (35%) patients died. Seventy-one (57.7%) patients had IR; there was no evidence of an association between IR and mortality from severe or critical COVID-19. Fifty-five non-diabetic patients without COVID-19 history were included with a median age of 40 (26-60) years; 35 (63.6%) were men and 20 (36.4%) were women. Nineteen (34.5%) people had IR. Conclusion IR was more prevalent in patients with severe and critical COVID-19 than in non-diabetic patients without COVID-19 history. Our results showed no evidence of the association between IR and mortality from severe and critical COVID-19.

A survivor woman after three years of a cardiac tamponade.

Primary pericardial mesothelioma is an extremely rare tumor, of unclear etiology, nonspecific presentation, with a delay in diagnosis, and a poor prognosis. We present the case of a woman with pericardial mesothelioma, whose main manifestation was cardiac tamponade, currently alive three years after diagnosis and undergoing chemotherapy treatment. .

Identification and evaluation of boronic compounds ameliorating cognitive deficit in orchiectomized rats.

BACKGROUND: Boron is a trace element with increasing importance in drug design. In this sense, boronic acids are emerging as therapeutic agents for several diseases. METHODS: Herein, 3- and 4- acetamidophenylboronic acids and 4-acetamidophenylboronic acid pinacol ester were identified as potential inhibitors of acetylcholinesterase through docking assays on eel, rat, and human acetylcholinesterases indicating binding on the gorge region of the target enzymes. Then, these compounds were evaluated in vitro and in vivo. RESULTS: It was found these compounds showed ability to inhibit acetylcholinesterase as competitive and non-competitive inhibitors. But also, these compounds were non-toxic to PC12 cells at micromolar concentration, and they have the ability to protect those cells against damage by amyloid-beta. CONCLUSIONS: Noticeably, intraperitoneal administration of these boronic compounds to rats with the cognitive deficit induced by orchiectomy provided ameliorative effects on disrupted behavior and neuronal damage induced by hormonal deprivation. Additional approaches are required to evaluate the possibility of multiple mechanisms of action for the observed effects in the central nervous system.

Development and validation of a 6-point grading scale in patients undergoing correction of nasolabial folds with a collagen implant.

BACKGROUND: Various scoring techniques prone to subjective interpretation have been used to evaluate soft tissue augmentation of nasolabial folds (NLFs). OBJECTIVE: To design and validate a reliable wrinkle assessment scoring scale. MATERIALS AND METHODS: Six photographed wrinkles of varying severity were electronically copied onto the same facial image to become a 6-point grading scale (GGS). A pilot training program (13 investigators) determined reliability, and a 12-week multicenter survey study validated the GGS scoring method. RESULTS: Pilot study inter- and intrarater scoring reliability were high (weighted kappa scores of 0.85 and 0.86, respectively). Seventy-five percent of survey investigators and independent review panel (IRP) members considered a GGS score difference of 0.5 to be a minimally perceivable difference. Interrater weighted kappa scores were 0.91 for the IRP and 0.80 for investigators. Intrarater agreements after repeat testing were 0.91 and 0.89, respectively. The baseline "live" assessment GGS mean score was 3.34, and the baseline blinded photographic assessment GGS mean score was 2.00 for the IRP and 2.16 for the investigators. CONCLUSIONS: The GGS is a reproducible method of grading the severity of NLF wrinkles. Treatment effectiveness of a dermal filler can be reliably evaluated using the GGS by comparing "live" assessments with the standard GGS photographic panel.

Novel hyaluronic acid dermal filler: dermal gel extra physical properties and clinical outcomes.

BACKGROUND: Dermal gel extra (DGE) is a new, tightly cross-linked hyaluronic acid (HA)-based dermal filler containing lidocaine engineered to resist gel deformation and degradation. OBJECTIVES: To develop a firmer gel product (DGE) and compare the efficacy and safety of DGE with nonanimal stabilized HA (NASHA) for correction of nasolabial folds (NLFs). METHODS: DGE physical properties were characterized, and 140 subjects with moderate to deep NLFs were treated with DGE and NASHA in a randomized, multicenter, split-face design study. Efficacy, pain, and satisfaction were measured using appropriate standard instruments. Adverse events were monitored throughout the study. RESULTS: DGE has a higher modulus and a higher gel:fluid ratio than other HA fillers. Similar optimal correction was observed with DGE and NASHA through 36 weeks (9 months). Study subjects required less volume (p<.001) and fewer touch-ups (p=.005) and reported less injection pain (p<.001) with DGE treatment. Most adverse events were mild to moderate skin reactions. CONCLUSIONS: DGE is a firm HA gel that required significantly less volume and fewer touch-ups to provide equivalent efficacy to NASHA for NLF correction; both dermal gels were well tolerated. DGE will provide a comfortable and cost-effective dermal filler option for clinicians and patients.