Mechanotransduction's impact on animal development, evolution, and tumorigenesis.

Mechanotransduction translates mechanical signals into biochemical signals. It is based on the soft-matter properties of biomolecules or membranes that deform in response to mechanical loads to trigger activation of biochemical reactions. The study of mechanotransductive processes in cell-structure organization has been initiated in vitro in many biological contexts, such as examining cells' response to substrate rigidity increases associated with tumor fibrosis and to blood flow pressure. In vivo, the study of mechanotransduction in regulating physiological processes has focused primarily on the context of embryogenesis, with an increasing number of examples demonstrating its importance for both differentiation and morphogenesis. The conservation across species of mechanical induction in early embryonic patterning now suggests that major animal transitions, such as mesoderm emergence, may have been based on mechanotransduction pathways. In adult animal tissues, permanent stiffness and tissue growth pressure contribute to tumorigenesis and appear to reactivate such conserved embryonic mechanosensitive pathways.

CDK1-Cyclin B1 Activates RNMT, Coordinating mRNA Cap Methylation with G1 Phase Transcription.

The creation of translation-competent mRNA is dependent on RNA polymerase II transcripts being modified by addition of the 7-methylguanosine (m7G) cap. The factors that mediate splicing, nuclear export, and translation initiation are recruited to the transcript via the cap. The cap structure is formed by several activities and completed by RNMT (RNA guanine-7 methyltransferase), which catalyzes N7 methylation of the cap guanosine. We report that CDK1-cyclin B1 phosphorylates the RNMT regulatory domain on T77 during G2/M phase of the cell cycle. RNMT T77 phosphorylation activates the enzyme both directly and indirectly by inhibiting interaction with KPNA2, an RNMT inhibitor. RNMT T77 phosphorylation results in elevated m7G cap methyltransferase activity at the beginning of G1 phase, coordinating mRNA capping with the burst of transcription that occurs following nuclear envelope reformation. RNMT T77 phosphorylation is required for the production of cohort of proteins, and inhibiting T77 phosphorylation reduces the cell proliferation rate.

Violence and aggression against nurses during the COVID-19 pandemic in Latin America. From the emerging leaders program of the Interamerican Society of Cardiology (SIAC).

INTRODUCTION: During the Coronavirus (COVID-19) pandemic, healthcare providers have overcome difficult experiences such as workplace violence. Nurses are particularly vulnerable to workplace violence. The objective of this study was to characterize violence and aggression against nurses during the COVID-19 pandemic in Latin America. METHODS: An electronic cross-sectional survey was conducted in 19 Latin American countries to characterize the frequency and type of violent actions against front-line healthcare providers. RESULTS: Of the original 3544 respondents, 16% were nurses (n = 567). The mean age was 39.7 ± 9.0 years and 79.6% (n = 2821) were women. In total, 69.8% (n = 2474) worked in public hospitals and 81.1% (n = 2874) reported working regularly with COVID-19 patients. Overall, about 68.6% (n = 2431) of nurses experienced at least one episode of workplace aggression during the pandemic. Nurses experienced weekly aggressions more frequently than other healthcare providers (45.5% versus 38.1%, p < .007). Nurses showed a trend of lower reporting rates against the acts of aggression suffered (p = .076). In addition, nurses were more likely to experience negative cognitive symptoms after aggressive acts (33.4% versus 27.8%, p = .028). However, nurses reported considering changing their work tasks less frequently compared to other healthcare providers after an assault event (p = .005). CONCLUSION: Workplace violence has been a frequent problem for all healthcare providers during COVID-19 pandemic in Latin America. Nurses were a particularly vulnerable subgroup, with higher rates of aggressions and cognitive symptoms and lower rate of complaints than other healthcare providers who suffered from workplace violence. It is imperative to develop strategies to protect this vulnerable group from aggressions during their tasks.

Pathogen reduction with methylene blue does not have an impact on the clinical effectiveness of COVID-19 convalescent plasma.

BACKGROUND AND OBJECTIVES: There is a concern about a possible deleterious effect of pathogen reduction (PR) with methylene blue (MB) on the function of immunoglobulins of COVID-19 convalescent plasma (CCP). We have evaluated whether MB-treated CCP is associated with a poorer clinical response compared to other inactivation systems at the ConPlas-19 clinical trial. MATERIALS AND METHODS: This was an ad hoc sub-study of the ConPlas-19 clinical trial comparing the proportion of patients transfused with MB-treated CCP who had a worsening of respiration versus those treated with amotosalen (AM) or riboflavin (RB). RESULTS: One-hundred and seventy-five inpatients with SARS-CoV-2 pneumonia were transfused with a single CCP unit. The inactivation system of the CCP units transfused was MB in 90 patients (51.4%), RB in 60 (34.3%) and AM in 25 (14.3%). Five out of 90 patients (5.6%) transfused with MB-treated CCP had worsening respiration compared to 9 out of 85 patients (10.6%) treated with alternative PR methods (p = 0.220). Of note, MB showed a trend towards a lower rate of respiratory progressions at 28 days (risk ratio, 0.52; 95% confidence interval, 0.18-1.50). CONCLUSION: Our data suggest that MB-treated CCP does not provide a worse clinical outcome compared to the other PR methods for the treatment of COVID-19.

A systematic review of EEG neurofeedback in fibromyalgia to treat psychological variables, chronic pain and general health.

This paper is the first up-to-date review of the various EEG-neurofeedback treatments for fibromyalgia patients and their psychological, physiological and general health consequences. Searches were made of the PubMed, PsycNet, Google Scholar and Scopus databases according to PRISMA guidelines for empirical peer-reviewed articles on EEG-neurofeedback treatment of fibromyalgia, yielding a final selection of 17 studies that met the inclusion criteria: (1) published articles and doctoral theses; (2) conducted between 2000 and 2022; (3) reporting empirical and quantitative data. These articles show that there is a wide range of protocols with different designs and procedures to treat fibromyalgia using EEG-neurofeedback techniques. The main symptoms that showed improvement were anxiety, depression, pain, general health and symptom severity, whilst the most commonly used method was traditional EEG neurofeedback based on a sensorimotor rhythm protocol. It may be concluded from the review that the lack of consistency and uniqueness of the protocols makes it very difficult to generalise results, despite the individual improvements identified. This review provides instructions and information that could guide future research and clinical practise, with the data extracted helping to gain a deeper understanding of the state of the art and the needs of the technique for this population group.

Mechanical induction of the tumorigenic ß-catenin pathway by tumour growth pressure.

The tumour microenvironment may contribute to tumorigenesis owing to mechanical forces such as fibrotic stiffness or mechanical pressure caused by the expansion of hyper-proliferative cells. Here we explore the contribution of the mechanical pressure exerted by tumour growth onto non-tumorous adjacent epithelium. In the early stage of mouse colon tumour development in the Notch(+)Apc(+/1638N) mouse model, we observed mechanistic pressure stress in the non-tumorous epithelial cells caused by hyper-proliferative adjacent crypts overexpressing active Notch, which is associated with increased Ret and ß-catenin signalling. We thus developed a method that allows the delivery of a defined mechanical pressure in vivo, by subcutaneously inserting a magnet close to the mouse colon. The implanted magnet generated a magnetic force on ultra-magnetic liposomes, stabilized in the mesenchymal cells of the connective tissue surrounding colonic crypts after intravenous injection. The magnetically induced pressure quantitatively mimicked the endogenous early tumour growth stress in the order of 1,200 Pa, without affecting tissue stiffness, as monitored by ultrasound strain imaging and shear wave elastography. The exertion of pressure mimicking that of tumour growth led to rapid Ret activation and downstream phosphorylation of ß-catenin on Tyr654, imparing its interaction with the E-cadherin in adherens junctions, and which was followed by ß-catenin nuclear translocation after 15 days. As a consequence, increased expression of ß-catenin-target genes was observed at 1 month, together with crypt enlargement accompanying the formation of early tumorous aberrant crypt foci. Mechanical activation of the tumorigenic ß-catenin pathway suggests unexplored modes of tumour propagation based on mechanical signalling pathways in healthy epithelial cells surrounding the tumour, which may contribute to tumour heterogeneity.

Overexpression of LeNHX4 improved yield, fruit quality and salt tolerance in tomato plants (Solanum lycopersicum L.).

The function of the tomato K+, Na+/H+ antiporter LeNHX4 has been analyzed using 35S-driven gene construct for overexpressing a histagged LeNHX4 protein in Solanum lycopersicum L. Compared to wild-type plants, the expression of LeNHX4 was enhanced in most of plants transformed with a gene construct for LeNHX4 overexpression although some plants showed a decreased LeNHX4 expression. Overexpression of LeNHX4 was associated to an increased fruit size while silencing of this gene was related to a decreased fruit size. We have investigated the effect of LeNHX4 overexpression on fruit production and quality and we have also evaluated salt tolerance in two different overexpression lines by measuring proline, protein and glucose concentrations in tomato leaves grown either under control (0 mM NaCl) or saline (125 mM NaCl) conditions. Plants overexpressing LeNHX4 showed a higher amount of fruits than WT plants and accumulated higher contents of sugars and cations (Na+ and K+). The application of 125 mM NaCl, affected negatively fruit production and quality of WT plants. However the transgenic lines overexpressing LeNXH4 increased fruit quality and yield. In relation to salt tolerance, overexpression lines showed higher levels of leaf proline, glucose and proteins under NaCl treatment. The overexpression of LeNHX4 in tomato plants, improved salinity tolerance and increased fruit yield and quality under both normal and salinity stress conditions.

Socioeconomic position and the health gradient in Cuba: dimensions and mechanisms.

BACKGROUND: To throw light on the under-researched association between socioeconomic position (SEP) and health in Cuba, this study examined SEP gradients in health and their underlying mechanisms among urban Cuban adults aged 18-65. METHODS: By applying linear regressions to data from the 2010 National Survey on Risk Factors and Chronic Diseases, the analysis explored the SEP-health gradient along three SEP dimensions - education, occupation, and skin colour - using ten health measures: self-reported health (SRH), general and abdominal obesity, hypertension, high glucose, high cholesterol, high triglycerides, low high-density lipoprotein cholesterol, metabolic syndrome, and cumulative risk factors. Regressions also included behaviours and health-related risk perceptions (tobacco and alcohol consumption, diet, physical activity, and risk-related behaviours). It thus investigated the SEP-health gradient and its underlying mechanisms via both behaviours and health-related risk perceptions. RESULTS: Once controlling for gender, age, marital status, region and provincial dummies, the analysis detected educational gradients in SRH (estimated coefficient [95% CI]: middle-level education = 3.535 [1.329, 5.741], p < 0.01; high-level education = 5.249 [3.050, 7.448], p < 0.01) that are partially explainable by both health-affecting behaviours (tobacco and alcohol consumption, diet, physical and sedentary activity) and risk perceptions. Using objective measures of health, however, it found no SEP-health gradients other than hypertension among people identified as having Black skin color (adjusted for demographic variables, 0.060 [0.018, 0.101], p < 0.01) and high cholesterol among those identified as having Mulatto or Mestizo skin color (adjusted for demographic variables, - 0.066 [- 0.098, - 0.033], p < 0.01). CONCLUSIONS: In terms of objective health measures, the study provides minimal evidence for an SEP-health gradient in Cuba, results primarily attributable to the country's universal healthcare system - which offers full coverage and access and affordable medications - and its highly developed education system.

Immunization with recombinant rHc23 partially protects lambs against trickle infections by Haemonchus contortus.

BACKGROUND: Haemonchosis is one of the most economically important parasitic diseases affecting small ruminants all over the world. Chemotherapeutic control has several shortcomings (limited anthelmintic arsenal, frequent resistance) and is hardly affordable by many farm economies. A recombinant antigen (rHc23) was shown to induce significant protection in vaccination trials with single dose challenges and different adjuvants. RESULTS: Lambs were vaccinated with 100 µg rHc23/dose + bacterial immunostimulant (BI) (LPS from Escherichia coli + Propionibacterium acnes extract) (days - 2, 0, 7 and 14) and subjected to a trickle infection with two dosages [6x, 1000 infective larvae (L3) or 6x, 2000 L3]. Vaccinated lambs showed a significant antibody response against rHc23 and Haemonchus contortus soluble extract as assessed by ELISA and Western blot (WB). Fecal egg counts (epg) along the experiment of vaccinated and BI treated lambs were significantly reduced. All vaccinated animals showed total egg output and abomasal helminth burdens (median, average) lower than those from unvaccinated or BI-treated animals lambs although differences were not statistically significant. CONCLUSIONS: Vaccination with 100 µg rHc23/dose + BI against H.contortus trickle infections apparently induced lower epg values and helminth burdens at the end of the experiment. Intragroup individual variations did not allow to obtain conclusive results and more research is needed including adjuvants and larger groups of animals to validate the potential value of rHc23 as candidate to develop a recombinant vaccine for lambs haemonchosis.

[Esophagitis dissecans superficialis: two cases of the same rare entity]. / Esofagitis disecante superficial: dos casos de una misma entidad poco frecuente.

Esophagitis dissecans superficialis (EDS) is a rare disease characterized by sloughing of the superficial esophageal mucosa and, histologically, by the bitonal appearance of the squamous epithelium secondary to necrosis of the most superficial layers. Etiology is uncertain, however, it has been associated with some medications, autoimmune diseases, esophageal stasis and endoscopic procedures. Here, two cases are presented, one of them which appeared in a woman after an episode of dysphagia and another one which occurred to a man with comorbidities and epigastric pain. This entity should be considered due to its self-limiting clinical course, compared to other entities with a more torpid evolution or that require more specific treatment.

Purification and characterization of chymotrypsin from viscera of vermiculated sailfin catfish, Pterygoplichthys disjunctivus, Weber, 1991.

Pterygoplichthys disjunctivus viscera chymotrypsin was purified by fractionation with ammonium sulfate (30-70 % saturation), gel filtration, affinity, and ion exchange chromatography. Chymotrypsin molecular weight was approximately 29 kDa according to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), shown a single band in zymogram. Electrofocusing study suggested being an anionic enzyme (pI ≈ 3.9), exhibiting maximal activity at pH 9 and 50 °C, using Suc-Ala-Ala-Pro-Phe-p-nitroanilide (SAAPNA) as substrate. Enzyme was effectively inhibited by phenyl methyl sulfonyl fluoride (PMSF) (99 %), and N-tosyl-L-phenylalanine chloromethyl ketone (TPCK) (94 %). Enzyme activity was affected by the following ions in decreasing order: Hg(2+), Fe(2+), Cu(2+), Li(1+), Mg(2+), K(1+), Mn(2+), while Ca(2+) had no effect. Chymotrypsin activity decreased continuously as NaCl concentration increased (from 0 to 30 %). K m and V max values were 0.72 ± 1.4 mM and 1.15 ± 0.06 µmol/min/mg of protein, respectively (SAAPNA as substrate). Results suggest the enzyme has a potential application where low processing temperatures are needed, such as in fish sauce production.

Comparative Infections of Zika, Dengue, and Yellow Fever Viruses in Human Cytotrophoblast-Derived Cells Suggest a Gating Role for the Cytotrophoblast in Zika Virus Placental Invasion.

The Zika virus (ZIKV) is teratogenic and considered a TORCH pathogen (toxoplasmosis [Toxoplasma gondii], rubella, cytomegalovirus, herpes simplex virus [HSV], and other microorganisms capable of crossing the blood-placenta barrier). In contrast, the related flavivirus dengue virus (DENV) and the attenuated yellow fever virus vaccine strain (YFV-17D) are not. Understanding the mechanisms used by ZIKV to cross the placenta is necessary. In this work, parallel infections with ZIKV of African and Asian lineages, DENV, and YFV-17D were compared for kinetics and growth efficiency, activation of mTOR pathways, and cytokine secretion profile using cytotrophoblast-derived HTR8 cells and monocytic U937 cells differentiated to M2 macrophages. In HTR8 cells, ZIKV replication, especially the African strain, was significantly more efficient and faster than DENV or YFV-17D. In macrophages, ZIKV replication was also more efficient, although differences between strains were reduced. Greater activation of the mTORC1 and mTORC2 pathways in HTR8 cells infected with ZIKV than with DENV or YFV-17D was observed. HTR8 cells treated with mTOR inhibitors showed a 20-fold reduction in ZIKV yield, versus 5- and 3.5-fold reductions for DENV and YFV-17D, respectively. Finally, infection with ZIKV, but not DENV or YFV-17D, efficiently inhibited the interferon (IFN) and chemoattractant responses in both cell lines. These results suggest a gating role for the cytotrophoblast cells in favoring entry of ZIKV, but not DENV and YFV-17D, into the placental stroma. IMPORTANCE Zika virus acquisition during pregnancy is associated with severe fetal damage. The Zika virus is related to dengue virus and yellow fever virus, yet fetal damage has not been related to dengue or inadvertent vaccination for yellow fever during pregnancy. Mechanisms used by the Zika virus to cross the placenta need to be deciphered. By comparing parallel infections of Zika virus strains belonging to the African and Asian lineages, dengue virus, and the yellow fever vaccine virus strain YFV-17D in placenta-derived cytotrophoblast cells and differentiated macrophages, evidence was found that Zika virus infections, especially by the African strains, were more efficient in cytotrophoblast cells than dengue virus or yellow fever vaccine virus strain infections. Meanwhile, no significant differences were observed in macrophages. Robust activation of the mTOR signaling pathways and inhibition of the IFN and chemoattractant response appear to be related to the better growth capacity of the Zika viruses in the cytotrophoblast-derived cells.

Prevalence of Anemia and Iron Deficiency in Women of Reproductive Age in Cuba and Associated Factors.

This study aims to evaluate the prevalence of anemia and iron deficiency in women of reproductive age and the association with inflammation, global overweight, adiposity, and menorrhagia. A sample design of women of reproductive age from the Eastern, Central, and Havana Regions was carried out. Biochemical determinations of hemoglobin, serum ferritin, soluble transferrin receptors, leukocytes, C-reactive protein, alpha-1 acid glycoprotein, and homocysteine were performed. Serum ferritin was also adjusted by inflammation. Nutritional status was assessed, and menstrual characteristics were collected by survey. A total of 742 women were studied. The prevalence of anemia was 21.4%, iron storage deficiency at 16.0%, and erythropoietic dysfunction at 5.4%, with inflammation at 47.0% and elevated homocysteine at 18.6%. Global overweight was 46.2% and increased adiposity at 58.4%. Anemia is associated with iron deposition deficiency (OR = 3.023 (1.816-5.033)) and with erythropoietic deficiency (OR = 5.62 (3.03-10.39)), but not with inflammation, global overweight, and adiposity. Global overweight was found to be associated with inflammation (OR = 2.23 (1.41-3.53)). Anemia was associated with heavy menstrual bleeding (OR = 1.92 (1.34-2.76)). Homocysteine was associated with inflammation (OR = 2.05 (1.08-3.90)), but not with anemia. In conclusion, anemia in Cuba is classified as a moderate public health problem, but not iron deficiency. A high prevalence of overweight and obesity was found, associated with inflammation, but not with anemia or iron deficiency. Heavy menstrual bleeding is a factor associated with anemia.

Mechano-biochemical marine stimulation of inversion, gastrulation, and endomesoderm specification in multicellular Eukaryota.

The evolutionary emergence of the primitive gut in Metazoa is one of the decisive events that conditioned the major evolutionary transition, leading to the origin of animal development. It is thought to have been induced by the specification of the endomesoderm (EM) into the multicellular tissue and its invagination (i.e., gastrulation). However, the biochemical signals underlying the evolutionary emergence of EM specification and gastrulation remain unknown. Herein, we find that hydrodynamic mechanical strains, reminiscent of soft marine flow, trigger active tissue invagination/gastrulation or curvature reversal via a Myo-II-dependent mechanotransductive process in both the metazoan Nematostella vectensis (cnidaria) and the multicellular choanoflagellate Choanoeca flexa. In the latter, our data suggest that the curvature reversal is associated with a sensory-behavioral feeding response. Additionally, like in bilaterian animals, gastrulation in the cnidarian Nematostella vectensis is shown to participate in the biochemical specification of the EM through mechanical activation of the ß-catenin pathway via the phosphorylation of Y654-ßcatenin. Choanoflagellates are considered the closest living relative to metazoans, and the common ancestor of choanoflagellates and metazoans dates back at least 700 million years. Therefore, the present findings using these evolutionarily distant species suggest that the primitive emergence of the gut in Metazoa may have been initiated in response to marine mechanical stress already in multicellular pre-Metazoa. Then, the evolutionary transition may have been achieved by specifying the EM via a mechanosensitive Y654-ßcatenin dependent mechanism, which appeared during early Metazoa evolution and is specifically conserved in all animals.

Coping strategies used by health-care workers during the SARS-COV2 crisis. A real-world analysis.

The aim of this paper is to analyze the main coping strategies used by frontline teams during the first days of the COVID pandemic confinement in Spain. This information could be necessary in order to carry out training programs that allow a better handling of future emergency situations, as well as acting more effectively and with less negative emotional impact. A questionnaire was used to identify different psychological profiles for coping, and in turn, other relevant variables were analyzed. The most used strategies by health professionals were problem solving, desiderative thinking and social support. Emotional expression and social support were used more by women. Significantly different behaviors were found in desiderative thinking (lower in people of 35-50 years old, and social support, higher in people 35 years old). The symptoms most commonly experienced by medical personnel were: sleep disorders, anxiety, tension, depressive symptoms, gastrointestinal symptoms and general somatic muscular symptoms. A relationship could be determined between the age/gender of the workers and the participants' overall assessment of their ability to cope with the COVID-19 stress situation they had experienced (men 50 years old and women between 35 and 50 years old, who felt able or very able to cope with the stress caused by the health emergency. However, women <35 years old and >50 years old believed they were able to cope poorly with the circumstances. The advantage of specific training plans in order to help with some stress symptoms could be suggested, aimed at the acquisition of tools based on problem solving, and emotional management in stressful and emergency situations.

Ret kinase-mediated mechanical induction of colon stem cells by tumor growth pressure stimulates cancer progression in vivo.

How mechanical stress actively impacts the physiology and pathophysiology of cells and tissues is little investigated in vivo. The colon is constantly submitted to multi-frequency spontaneous pulsatile mechanical waves, which highest frequency functions, of 2 s period, remain poorly understood. Here we find in vivo that high frequency pulsatile mechanical stresses maintain the physiological level of mice colon stem cells (SC) through the mechanosensitive Ret kinase. When permanently stimulated by a magnetic mimicking-tumor growth analogue pressure, we find that SC levels pathologically increase and undergo mechanically induced hyperproliferation and tumorigenic transformation. To mimic the high frequency pulsatile mechanical waves, we used a generator of pulsed magnetic force stimulation in colonic tissues pre-magnetized with ultra-magnetic liposomes. We observed the pulsatile stresses using last generation ultra-wave dynamical high-resolution imaging. Finally, we find that the specific pharmacological inhibition of Ret mechanical activation induces the regression of spontaneous formation of SC, of CSC markers, and of spontaneous sporadic tumorigenesis in Apc mutated mice colons. Consistently, in human colon cancer tissues, Ret activation in epithelial cells increases with tumor grade, and partially decreases in leaking invasive carcinoma. High frequency pulsatile physiological mechanical stresses thus constitute a new niche that Ret-dependently fuels mice colon physiological SC level. This process is pathologically over-activated in the presence of permanent pressure due to the growth of tumors initiated by pre-existing genetic alteration, leading to mechanotransductive self-enhanced tumor progression in vivo, and repressed by pharmacological inhibition of Ret.

The human COP9 signalosome protects ubiquitin-conjugating enzyme 3 (UBC3/Cdc34) from beta-transducin repeat-containing protein (betaTrCP)-mediated degradation.

The COP9 signalosome (CSN) is an essential multisubunit complex that regulates the activity of cullin-RING ubiquitin ligases by removing the ubiquitin-like peptide NEDD8 from cullins. Here, we demonstrate that the CSN can affect other components of the ubiquitination cascade. Down-regulation of human CSN4 or CSN5 induced proteasome-mediated degradation of the ubiquitin-conjugating enzyme UBC3/Cdc34. UBC3 was targeted for ubiquitination by the cullin-RING ubiquitin ligase SCF(betaTrCP). This interaction required the acidic C-terminal extension of UBC3, which is absent in ubiquitin-conjugating enzymes of the UBCH5 family. Conversely, the UBC3 acidic domain was sufficient to impart sensitivity to SCF(betaTrCP)-mediated ubiquitination to UBCH5 enzymes. Our work indicates that the CSN is necessary to ensure the stability of selected ubiquitin-conjugating enzymes and uncovers a novel pathway of regulation of ubiquitination processes.

Association of abnormal pulmonary vasculature on CT scan for COVID-19 infection with decreased diffusion capacity in follow up: A retrospective cohort study.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is a respiratory viral illness causing pneumonia and systemic disease. Abnormalities in pulmonary function tests (PFT) after COVID-19 infection have been described. The determinants of these abnormalities are unclear. We hypothesized that inflammatory biomarkers and CT scan parameters at the time of infection would be associated with abnormal gas transfer at short term follow-up. METHODS: We retrospectively studied subjects who were hospitalized for COVID-19 pneumonia and discharged. Serum inflammatory biomarkers, CT scan and clinical characteristics were assessed. CT images were evaluated by Functional Respiratory Imaging with automated tissue segmentation algorithms of the lungs and pulmonary vasculature. Volumes of the pulmonary vessels that were ≤5mm (BV5), 5-10mm (BV5_10), and ≥10mm (BV10) in cross sectional area were analyzed. Also the amount of opacification on CT (ground glass opacities). PFT were performed 2-3 months after discharge. The diffusion capacity of carbon monoxide (DLCO) was obtained. We divided subjects into those with a DLCO <80% predicted (Low DLCO) and those with a DLCO ≥80% predicted (Normal DLCO). RESULTS: 38 subjects were included in our cohort. 31 out of 38 (81.6%) subjects had a DLCO<80% predicted. The groups were similar in terms of demographics, body mass index, comorbidities, and smoking status. Hemoglobin, inflammatory biomarkers, spirometry and lung volumes were similar between groups. CT opacification and BV5 were not different between groups, but both Low and Normal DLCO groups had lower BV5 measures compared to healthy controls. BV5_10 and BV10 measures were higher in the Low DLCO group compared to the normal DLCO group. Both BV5_10 and BV10 in the Low DLCO group were greater compared to healthy controls. BV5_10 was independently associated with DLCO<80% in multivariable logistic regression (OR 1.29, 95% CI 1.01, 1.64). BV10 negatively correlated with DLCO% predicted (r = -0.343, p = 0.035). CONCLUSIONS: Abnormalities in pulmonary vascular volumes at the time of hospitalization are independently associated with a low DLCO at follow-up. There was no relationship between inflammatory biomarkers during hospitalization and DLCO. Pulmonary vascular abnormalities during hospitalization for COVID-19 may serve as a biomarker for abnormal gas transfer after COVID-19 pneumonia.

Frequency of Iatrogenic Sexual Dysfunction Associated with Antihypertensive Compounds.

Iatrogenic sexual dysfunction (SD) caused by antihypertensive (AH) compounds, provoking sexual desire, orgasm or arousal dysfunction, is a common clinical adverse event. Unfortunately, it is often underestimated and underreported by clinicians and prescribers in clinical practice, deteriorating the adherence and patient quality of life. The objective of this study was to investigate the frequency of SD in patients treated with different antihypertensive compounds; a real-life naturalistic and cross-sectional study in patients receiving AH treatment was carried out. Method: A total of 256 patients were included in the study (188 males and 68 females who met the inclusion and exclusion criteria). The validated Psychotropic-Related Sexual Dysfunction Questionnaire (PRSexDQ-SALSEX) was transversally applied once at least every two months following the onset of the treatment in order to measure possible AH-related SD. Although the spontaneous reporting of SD was very low (6.81% females/24.8% males), 66.40% of the patients reported impaired sexual function through the SALSEX questionnaire after the treatment onset, as follows: decreased desire (55.8% females/54.2% males), delayed orgasm (42.6%/45.7%), anorgasmia (42.6%/43.6%) and arousal difficulties (53%/59.6%). The average frequency of moderate to severe iatrogenic SD was 66.4% with AH in monotherapy as follows: angiotensin II receptor antagonists (ARBs), 29.8%; calcium antagonists, 40%; diuretics, 42.9%; beta blockers, 43.8%; and angiotensin-converting enzyme (ACE) inhibitors, 77.8%. Combined treatments showed a higher percentage of main SD (70.3%): diuretic + ACE inhibitor, 42.3%; ARB + calcium antagonist, 55.6%; diuretic + calcium antagonist, 68.8%; and diuretic + ARB, 74.2%. The greatest risk factors associated with SD were poor general health, age over 60 with a comorbid coronary or musculoskeletal disease, mood disorder and diuretic +ARB combined therapy. Conclusion: SD is common in patients treated with antihypertensive drugs, and it is still underreported. The most harmful treatment deteriorating sexual function was the combination of diuretic +ARB, while the least harmful was monotherapy with ARBs. More research is needed on the clinical management of this problem to preserve the quality of life of patients and their partners.

Production of Protein Hydrolysates Using Marine Catfish Bagre panamensis Muscle or Casein as Substrates: Effect of Enzymatic Source and Degree of Hydrolysis on Antioxidant and Biochemical Properties.

Protein hydrolysates from fishery byproducts have resulted to be nutraceutical ingredients with potential to be applied in human nutrition; however, critical quality attributes are dependent on some process parameters such as enzyme source and degree of hydrolysis. This study analyzed the biochemical properties and in vitro antioxidant activity (using DPPH, ABTS, and FRAP assays), of protein hydrolysates at 10, 20, and 30% degree of hydrolysis (DH), measured by pH-STAT and prepared from sea catfish (Bagre panamensis) muscle and casein as protein sources by treatment with alcalase (ALC) and a semi-purified protease extract (SPE) from B. panamensis intestinal tissues as enzyme sources. With SPE, the DH was reached faster than ALC regardless of the protein substrate used. Sea catfish muscle (MUSC) hydrolysate made with SPE at 30% DH showed the highest antioxidant activity (DPPH: 118.8 µmoles TE/mg; ABTS: EC50 of 1.5 mg/mL). In FRAP assay, the MUSC hydrolysates produced with SPE or ALC at 20% DH showed the higher activity (0.38 and 0.40 µmoles TE/mg, respectively). MUSC hydrolysates made with SPE contained the highest proportion of peptides with MW < 1.35 kDa and had a high protein content (72 to 78%), and almost 50% of the amino acids were essential. These results suggest that intestinal proteases and muscle of marine catfish represent a potential source to elaborate antioxidant protein hydrolysates. Our results promote the full utilization of this fish species and offer a biotechnological strategy for the management and valorization of its byproducts.