Rapid and cost-effective process based on insect larvae for scale-up production of SARS-COV-2 spike protein for serological COVID-19 testing.

Serology testing for COVID-19 is important in evaluating active immune response against SARS-CoV-2, studying the antibody kinetics, and monitoring reinfections with genetic variants and new virus strains, in particular, the duration of antibodies in virus-exposed individuals and vaccine-mediated immunity. In this study, recombinant S protein of SARS-CoV-2 was expressed in Rachiplusia nu, an important agronomic plague. One gram of insect larvae produces an amount of S protein sufficient for 150 determinations in the ELISA method herein developed. We established a rapid production process for SARS-CoV-2 S protein that showed immunoreactivity for anti-SARS-CoV-2 antibodies and was used as a single antigen for developing the ELISA method with high sensitivity (96.2%) and specificity (98.8%). Our findings provide an efficient and cost-effective platform for large-scale S protein production, and the scale-up is linear, thus avoiding the use of complex equipment like bioreactors.

Structure of the putative long tail fiber receptor-binding tip of a novel temperate bacteriophage from the Antarctic bacterium Bizionia argentinensis JUB59.

Tailed bacteriophages are one of the most widespread biological entities on Earth. Their singular structures, such as spikes or fibers are of special interest given their potential use in a wide range of biotechnological applications. In particular, the long fibers present at the termini of the T4 phage tail have been studied in detail and are important for host recognition and adsorption. Although significant progress has been made in elucidating structural mechanisms of model phages, the high-resolution structural description of the vast population of marine phages is still unexplored. In this context, we present here the crystal structure of C24, a putative receptor-binding tip-like protein from Bizionia argentinensis JUB59, a psychrotolerant bacterium isolated from the marine surface waters of Potter Cove, Antarctica. The structure resembles the receptor-binding tip from the bacteriophage T4 long tail fiber yet showing marked differences in its domain organization, size, sequence identity and metal binding nature. We confirmed the viral origin of C24 by induction experiments using mitomycin C. Our results reveal the presence of a novel uncharacterized prophage in the genome of B. argentinensis JUB59, whose morphology is compatible with the order Caudovirales and that carries the nucleotide sequence of C24 in its genome. This work provides valuable information to expand our current knowledge on the viral machinery prevalent in the oceans.

COVID-19 in elderly kidney transplant recipients.

The SARS-Cov-2 infection disease (COVID-19) pandemic has posed at risk the kidney transplant (KT) population, particularly the elderly recipients. From March 12 until April 4, 2020, we diagnosed COVID-19 in 16 of our 324 KT patients aged ≥65 years old (4.9%). Many of them had had contact with healthcare facilities in the month prior to infection. Median time of symptom onset to admission was 7 days. All presented with fever and all but one with pneumonia. Up to 33% showed renal graft dysfunction. At infection diagnosis, mTOR inhibitors or mycophenolate were withdrawn. Tacrolimus was withdrawn in 70%. The main treatment combination was hydroxychloroquine and azithromycin. A subset of patients was treated with anti-retroviral and tocilizumab. Short-term fatality rate was 50% at a median time since admission of 3 days. Those who died were more frequently obese, frail, and had underlying heart disease. Although a higher respiratory rate was observed at admission in nonsurvivors, symptoms at presentation were similar between both groups. Patients who died were more anemic, lymphopenic, and showed higher D-dimer, C-reactive protein, and IL-6 at their first tests. COVID-19 is frequent among the elderly KT population and associates a very early and high mortality rate.

Hypothalamic-pituitary axis response to a 0.25-MG dexamethasone test in women with fibromyalgia.

Fibromyalgia has been reported as having some clinical overlap with both depression and emotionally-unstable disorders, although both types of disorders present different cortisol suppression response to dexamethasone. In this study we investigated the hypothalamic-pituitary-adrenal system (HPA) in the fibromyalgic syndrome (FMS) using a dexamethasone suppression test (DST) of 0.25 mg designed to specifically detect cortisol hypersuppression. We studied 59 women (20 patients and 39 healthy controls) to whom the DST was administered together with a battery of psychometric tests. In our results, patients with FMS had significant lower levels of basal cortisol pre- and post-DST compared with control subjects. However, cortisol suppression rate in patients after DST was not significantly different than in controls. As other syndromes like post-traumatic stress disorder or emotionally unstable personality disorders, also related with high incidence of severe trauma, FMS patients presented significant low basal cortisol. However, they did not have cortisol hypersuppression as is commonly found in the mentioned disorders. The relation of FMS with lifetime traumas and with emotional instability should be further investigated in order to improve psychological treatment approaches for these patients.LAY SUMMARYPatients with fibromyalgic syndrome have basal hypocortisoism but no cortisol hypersuppression after dexamethasone infusion compared to control subjects, as other trauma-related syndromes.

Leap motion controlled video game-based therapy for upper limb rehabilitation in patients with Parkinson's disease: a feasibility study.

BACKGROUND: Non-immersive video games are currently being used as technological rehabilitation tools for individuals with Parkinson's disease (PD). The aim of this feasibility study was to evaluate the effectiveness of the Leap Motion Controller® (LMC) system used with serious games designed for the upper limb (UL), as well as the levels of satisfaction and compliance among patients in mild-to-moderate stages of the disease. METHODS: A non-probabilistic sampling of non-consecutive cases was performed. 23 PD patients, in stages II-IV of the Hoehn & Yahr scale, were randomized into two groups: an experimental group (n = 12) who received treatment based on serious games designed by the research team using the LMC system for the UL, and a control group (n = 11) who received a specific intervention for the UL. Grip muscle strength, coordination, speed of movements, fine and gross UL dexterity, as well as satisfaction and compliance, were assessed in both groups pre-treatment and post-treatment. RESULTS: Within the experimental group, significant improvements were observed in all post-treatment assessments, except for Box and Blocks test for the less affected side. Clinical improvements were observed for all assessments in the control group. Statistical intergroup analysis showed significant improvements in coordination, speed of movements and fine motor dexterity scores on the more affected side of patients in the experimental group. CONCLUSIONS: The LMC system and the serious games designed may be a feasible rehabilitation tool for the improvement of coordination, speed of movements and fine UL dexterity in PD patients. Further studies are needed to confirm these preliminary findings.

Cuff-Based Oscillometric Central and Brachial Blood Pressures Obtained Through ABPM are Similarly Associated with Renal Organ Damage in Arterial Hypertension.

BACKGROUND/AIMS: Central blood pressure (BP) has been suggested to be a better estimator of hypertension-associated risks. We aimed to evaluate the association of 24-hour central BP, in comparison with 24-hour peripheral BP, with the presence of renal organ damage in hypertensive patients. METHODS: Brachial and central (calculated by an oscillometric system through brachial pulse wave analysis) office BP and ambulatory BP monitoring (ABPM) data and aortic pulse wave velocity (PWV) were measured in 208 hypertensive patients. Renal organ damage was evaluated by means of the albumin to creatinine ratio and the estimated glomerular filtration rate. RESULTS: Fifty-four patients (25.9%) were affected by renal organ damage, displaying either microalbuminuria (urinary albumin excretion ≥30 mg/g creatinine) or an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Compared to those without renal abnormalities, hypertensive patients with kidney damage had higher values of office brachial systolic BP (SBP) and pulse pressure (PP), and 24-h, daytime, and nighttime central and brachial SBP and PP. They also had a blunted nocturnal decrease in both central and brachial BP, and higher values of aortic PWV. After adjustment for age, gender, and antihypertensive treatment, only ABPM-derived BP estimates (both central and brachial) showed significant associations with the presence of renal damage. Odds ratios for central BP estimates were not significantly higher than those obtained for brachial BP. CONCLUSION: Compared with peripheral ABPM, cuff-based oscillometric central ABPM does not show a closer association with presence of renal organ damage in hypertensive patients. More studies, however, need to be done to better identify the role of central BP in clinical practice.

Experience with fampridine in clinical practice: analysis of a possible marker of clinical response.

PURPOSE OF THE STUDY: Approximately 85% of patients with multiple sclerosis experience reduced mobility, which negatively affects quality of life. Fampridine is the first symptomatic treatment aimed at improving gait. We analyzed effectiveness and tolerance in clinical practice. We also sought a prevalent gait pattern in responders as a potential clinical response marker. MATERIAL AND METHODS: Six-month prospective study of fampridine in patients with multiple sclerosis. Response was evaluated using the Timed 25-Foot Walk Test (T25FW) and the 12-Item Multiple Sclerosis Walking Scale (MSWS-12). Response was defined as increased gait speed (≥20%) and decreased MSWS-12 score (≥4 points). RESULTS: Fifty-five patients (67.3% women; mean age, 51.7 [11.1] years) with a baseline Expanded Disability Status Scale (EDSS) score of 5.8. Gait pattern was paraparetic (40%), hemiparetic (21.8%) and ataxic (38.2%). Of all patients, 70.9% demonstrated clinical benefit based on response criteria established, at the 14-d follow-up, 61.8% at 3 months and 45.5% at 6 months. A similar response pattern was observed in the MSWS-12. A significant decrease in the mean (SD) EDSS score was observed in responders at 6 months (6.1 [0.9] vs. 5.64 [0.1], p < 0.05). Adverse effects were recorded in 50.9%, although most were mild-moderate and resolved completely. We did not identify a prevalent gait pattern among responders. After a washout period, some patients received fampridine a second time obtaining response recovery. CONCLUSIONS: In our patients' cohort, fampridine proved clinical benefit, being safe and well tolerated in most cases. We did not identify a gait pattern that was predictive of clinical response.

Dengue specific immunoglobulins M, A, and E in primary and secondary dengue 4 infected Salvadorian children.

El Salvador is a Central American country that has been affected by several dengue outbreaks. This study investigated the levels of IgM, IgA, and IgE anti-dengue antibodies in serum samples from children in El Salvador, with a clinical and serological diagnosis of dengue infection during the dengue 4 outbreak in 2002-2003. Seventy one serum samples were tested by ELISA and cases were classified in three groups: 13 primary dengue fever (PDF), 21 secondary dengue fever (SDF), and 37 secondary dengue hemorrhagic fever (SDHF). Also, the specificity of anti-dengue IgM for the different serotypes was tested. No significant differences in the IgM response were found between PDF and SDF, but these were detected between PDF and SDHF (P = 0.0053) and between SDF and SDHF (P = 0.0003). The IgA and IgE values showed a statistically significant difference between primary and secondary groups. The highest positivity percentage of IgA was between 95% (SDF) and 100% (SDHF) towards day 7 of onset of fever. All secondary cases were positive for IgE antibodies. The specificity of IgM was determined for DENV-4 virus in primary and secondary DF groups. This is the first study on dengue cases in Salvadorian children related to the immune response of different immunoglobulins to the type of infection and the clinical picture. Further prospective studies are needed to define if the pattern of immunoglobulins can determine early dengue infection and/or severity.

Indication, performance and outcomes of adrenal vein sampling in patients with primary hyperaldosteronism.

Primary hyperaldosteronism (PAH) is an important cause of secondary hypertension (HTN). The study of the same requires a high clinical suspicion in addition to a hormonal study that confirms hormonal hypersecretion. It is important to start the appropriate treatment once the diagnosis is confirmed, and for this is necessary to demonstrate whether the hormonal hypersecretion is unilateral (patients who could be candidates for surgical treatment) or bilateral (patients who are candidates for pharmacological treatment only). At the Hospital del Mar since 2016 there has been a multidisciplinary work team in which Nephrologists, Endocrinologists, Radiologists and Surgeons participate to evaluate cases with suspected hyperaldosteronism and agree on the best diagnostic-therapeutic approach for these patients, including the need for adrenal vein sampling, which is a technique that in recent years has become the gold standard for the study of PAH. In the present study we collect the experience of our centre in performing AVC and its usefulness for the management of these patients.

Dynamics of HLA and angiotensin II type 1 receptor antibodies during pregnancy.

BACKGROUND: Alloantibodies, especially anti-human leukocyte antigen antibodies (HLA antibodies), and autoantibodies, as angiotensin II type 1 receptor antibodies (AT1R antibodies), may complicate the access and the course of transplantation. Pregnancy is a known source of HLA antibodies, with most studies evaluating pregnancy-induced sensitization by complement-dependent cytotoxicity assays, mainly after childbirth. AT1R antibodies have been evaluated in the context of preeclampsia. We aimed to evaluate pregnancy as a natural source of HLA antibodies and AT1R antibodies, their dynamics along gestation and the potential factors involved in antibody appearance. METHODS: Serum samples from pregnant women were collected during the three trimesters of pregnancy (1T, 2T, 3T). Presence of HLA antibodies was assessed by screening beads on Luminex and AT1R antibodies by ELISA. RESULTS: A cohort of 138 pregnant women were included. Samples from all were tested in 1T, 127 in 2T and 102 in 3T. HLA antibodies increased from 29.7 % (1T) to 38.2 % (3T). AT1R antibodies were stable around 30 % along pregnancy. Up to 43.2 % multiparous women had HLA antibodies, with a similar proportion of class I and class II antibodies. In primiparous women HLA antibodies increased along pregnancy (from 17.6 % to 34.1 %), with predominance of class II HLA antibodies. AT1R antibodies were not different in primiparous and multiparous women. CONCLUSIONS: Pregnancy is a relevant source of HLA antibodies sensitization, but not of AT1R antibodies. HLA antibodies increased clearly in primiparous women with predominance of class II. The use of newer solid-phase techniques on Luminex evidence a higher degree of HLA sensitization during pregnancy.

Optimal Prone Position Duration in Patients With ARDS Due to COVID-19: The Omelette Pilot Trial.

BACKGROUND: Prone position (PP) has been widely used in the COVID-19 pandemic for ARDS management. However, the optimal length of a PP session is still controversial. This study aimed to evaluate the effects of prolonged versus standard PP duration in subjects with ARDS due to COVID-19. METHODS: This was a single-center, randomized controlled, parallel, and open pilot trial including adult subjects diagnosed with severe ARDS due to COVID-19 receiving invasive mechanical ventilation that met criteria for PP between March-September 2021. Subjects were randomized to the intervention group of prolonged PP (48 h) versus the standard of care PP (∼16 h). The primary outcome variable for the trial was ventilator-free days (VFDs) to day 28. RESULTS: We enrolled 60 subjects. VFDs were not significantly different in the standard PP group (18 [interquartile range [IQR] 0-23] VFDs vs 7.5 [IQR 0-19.0] VFDs; difference, -10.5 (95% CI -3.5 to 19.0, P = .08). Prolonged PP was associated with longer time to successful extubation in survivors (13.00 [IQR 8.75-26.00] d vs 8.00 [IQR 5.00-10.25] d; difference, 5 [95% CI 0-15], P = .001). Prolonged PP was also significantly associated with longer ICU stay (18.5 [IQR 11.8-25.3] d vs 11.50 [IQR 7.75-25.00] d, P = .050) and extended administration of neuromuscular blockers (12.50 [IQR 5.75-20.00] d vs 5.0 [IQR 2.0-14.5] d, P = .005). Prolonged PP was associated with significant muscular impairment according to lower Medical Research Council values (59.6 [IQR 59.1-60.0] vs 56.5 [IQR 54.1-58.9], P = .02). CONCLUSIONS: Among subjects with severe ARDS due to COVID-19, there was no difference in 28-d VFDs between prolonged and standard PP strategy. However, prolonged PP was associated with a longer ICU stay, increased use of neuromuscular blockers, and greater muscular impairment. This suggests that prolonged PP is not superior to the current recommended standard of care.

Economic Cost of Rehabilitation with Robotic and Virtual Reality Systems in People with Neurological Disorders: A Systematic Review.

Background: The prevalence of neurological disorders is increasing worldwide. In recent decades, the conventional rehabilitation for people with neurological disorders has been often reinforced with the use of technological devices (robots and virtual reality). The aim of this systematic review was to identify the evidence on the economic cost of rehabilitation with robotic and virtual reality devices for people with neurological disorders through a review of the scientific publications over the last 15 years. Methods: A systematic review was conducted on partial economic evaluations (cost description, cost analysis, description of costs and results) and complete (cost minimization, cost-effectiveness, cost utility and cost benefit) studies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The main data sources used were PubMed, Scopus and Web of Science (WOS). Studies published in English over the last 15 years were considered for inclusion in this review, regardless of the type of neurological disorder. The critical appraisal instrument from the Joanna Briggs Institute for economic evaluation and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) were used to analyse the methodological quality of all the included papers. Results: A total of 15 studies were included in this review. Ten papers were focused on robotics and five on virtual reality. Most of the studies were focused on people who experienced a stroke. The robotic device most frequently used in the papers included was InMotion® (Bionik Co., Watertown, MA, USA), and for those focused on virtual reality, all papers included used semi-immersive virtual reality systems, with commercial video game consoles (Nintendo Wii® (Nintendo Co., Ltd., Kyoto, Japan) and Kinect® (Microsoft Inc., Redmond, WA, USA)) being used the most. The included studies mainly presented cost minimization outcomes and a general description of costs per intervention, and there were disparities in terms of population, setting, device, protocol and the economic cost outcomes evaluated. Overall, the methodological quality of the included studies was of a moderate level. Conclusions: There is controversy about using robotics in people with neurological disorders in a rehabilitation context in terms of cost minimization, cost-effectiveness, cost utility and cost benefits. Semi-immersive virtual reality devices could involve savings (mainly derived from the low prices of the systems analysed and transportation services if they are applied through telerehabilitation programmes) compared to in-clinic interventions.

Women Refugee's Perceptions, Experiences and Coping Mechanisms in Situations of Sexual and Gender-Based Violence (SGBV): A Metasynthesis.

Women represent almost half of the 20 million refugees worldwide, and although they play a key role in their communities, their voices and needs are often missing from research and policies directed to this population. A qualitative systematic review, or metasynthesis, was conducted to examine the experiences, perceptions, coping mechanisms, and psychological discourses of women refugees in situations of sexual and gender-based violence (SGBV) that occur during the travel, interception, and destination migratory stages. A systematic search was conducted on five multidisciplinary databases and was complemented with a manual search, resulting on a total of 511 articles which were screened for eligibility. Only qualitative, peer-reviewed, and English-written research articles were selected, and they were required to (1) focus on women refugees above 15 years of age and (2) report on their experiences, perceptions, psychological discourses, and/or coping with SGBV during their migration across countries (international migration). Ultimately, a total of 14 qualitative research articles were selected for the review. Using the thematic synthesis approach as a guideline, the results were summarized in the following themes: experiences of SGBV, perception of SGBV, perception of the risk factors creating and perpetuating their vulnerability, coping with SGBV, barriers to help-seeking, and psychological consequences. Despite the broad search, only information about some types of SGBV experiences from Asian and African refugee communities was found. Nonetheless, the available qualitative information on this topic is effectively integrated, knowledge gaps are identified, and future research, interventions, and policies using an integrated and culturally sensitive framework are suggested.

Hypertensive mediated organ damage evolution in resistant hypertension patients after adding spironolactone.

INTRODUCTION: Resistant hypertension (RH) represents an important multi-organic impact and increases the morbi-mortality. We aimed to evaluate the evolution of hypertensive mediated organ damage in patients with RH after adding spironolactone. MATERIAL AND METHODS: Retrospective study of 58 patients with RH who started spironolactone (12.5-25mg daily). Office blood pressure, 24-h ambulatory blood pressure monitoring (24h-ABPM), urine albumin-to-creatinine ratio and echocardiographic parameters were analyzed prior to initiation of spironolactone and after 12 months of treatment. RESULTS: Thirty-six percent of patients were women and mean age was 67.3±10.1 years. We observed a decrease in urine albumin-to-creatinine ratio (median [RIQ25-75]) of 27.0 (7.5-255.4) to 11.3 (3.1-37.8)mg/g, p=0.009. This was more relevant in patients with albuminuria grade A2 and A3: 371.2 (139.5-797.4) to 68.4 (26.5-186.5)mg/g, p=0.02. The echocardiographic changes were: posterior wall thickness: -1.0±0.4mm (p<0.001), interventricular septal thickness: -0.6±0.5mm (p=0.01), left ventricular (LV) mass index: -14.7±10.2g/m2 (p=0.006), LV remodeling index: -0.04±0.036 (p=0.03), without statistically significant changes in LV ejection fraction, LV end-diastolic diameter, LV end-systolic diameter, left atrial diameter, relationship between early ventricular filling wave and atrial contraction and LV filling pressure index. Systolic/diastolic office blood pressure decreased -12.5±4.9/-4.9±3.0mmHg, p<0.001. In 24h-ABPM, systolic and diastolic BP had a significant decrease in diurnal and nocturnal periods and 38.1% of patients presented a favorable change in the circadian pattern, p<0.001. CONCLUSIONS: Adding spironolactone to patients with RH contributes to improve hypertensive mediated organ damage by reducing albuminuria levels and echocardiographic parameters of hypertensive heart disease.

Predictors of Preeclampsia in the First Trimester in Normotensive and Chronic Hypertensive Pregnant Women.

Preeclampsia (PE) is characterized by the new onset of hypertension (HT) and proteinuria beyond the 20th week of gestation. We aimed to find the best predictor of PE and find out if it is different in women with or without HT. Consecutively attended pregnant women were recruited in the first trimester of pregnancy and followed-up. Laboratory and office and 24 h-ambulatory blood pressure (BP) data were collected. PE occurred in 6.25% of normotensives (n = 124). Both office mean BP and 24 h-systolic BP in the first trimester were higher in women with versus those without PE (p ≤ 0.001). In women with chronic hypertension (cHT), PE occurred in 55%; office SBP (p = 0.769) and 24 h-SBP (p = 0.589) were similar between those with and those without PE. Regarding biochemistry, in cHT, plasma urea and creatinine were higher in PE women than in those without cHT (p = 0.001 and p = 0.004 for the differences in both parameters). These differences were not observed in normotensives. In normotensives, mean BP was the best predictor of PE [ROC curve = 0.91 (95%CI 0.82-0.99)], best cut-off = 80.3 mmHg. In cHT, plasma urea and creatinine were the best predictors of PE, with ROC curves of 0.94 (95%CI 0.84-1.00) and 0.93 (95%CI 0.83-1.00), respectively. In the first trimester of pregnancy, the strongest predictor of PE in normotensive women is office mean BP, while in cHT, renal parameters are the strongest predictors. Otherwise, office BP is non-inferior to 24 h ambulatory BP to predict PE.

Comparison of the first and sixth waves of the SARS-COV-2 coronavirus pandemic in patients with immune-mediated disease.

INTRODUCTION: Recent evidence shows that COVID-19 infection does not have a worse prognosis in patients with immune-mediated inflammatory diseases (IMID), although they develop a worse response to vaccination. OBJECTIVE: To compare the incidence of COVID-19 and clinical features in patients with IMID between the first and sixth waves. METHOD: Prospective observational study of two cohorts of IMID patients diagnosed with COVID-19. First cohort March to May 2020, and second cohort December/2021 to February/2022. Sociodemographic and clinical variables were collected and, in the second cohort, COVID-19 vaccination status. Statistical analysis established differences in characteristics and clinical course between the two cohorts. RESULTS: In total, 1627 patients were followed up, of whom 77 (4.60%) contracted COVID-19 during the first wave and 184 in the sixth wave (11.3%). In the sixth wave, there were fewer hospitalisations, intensive care unit admissions, and deaths than in the first wave (p=.000) and 180 patients (97.8%) had at least one dose of vaccine. CONCLUSION: Early detection and vaccination have prevented the occurrence of serious complications.

Natural Semantic Networks of the Neurorehabilitation Concept by Spanish Physiotherapists-A Qualitative Phenomenological Representational Study.

The Natural Semantic Networks (NSN) model is highly useful in analyzing the words that define a concept in terms of the value, strength, weight, or density that a specific population assigns to the construction of a learned concept. The main objective of this study was to describe the conceptualization of the concept of neurorehabilitation by Spanish physiotherapists specializing in this field using NSN. A phenomenological study is presented. The participants were physiotherapy professionals who graduated from three Spanish universities and were working in the field of neurorehabilitation. A questionnaire was administered via Google Forms, which was constructed using the NSN technique. A total of 191 physiotherapists participated in this study. The Spanish physiotherapists interviewed used a total of 1247 defining words for the concept of neurorehabilitation. The semantic core of the concept was mainly formed by the words 'treatment', 'recovery', 'functionality', 'neuroplasticity', and 'learning', which carried significant weight. Results were also presented taking into account the academic level and years of professional experience of the sample. The semantic network observed in this study allows us to elucidate the polysemy of the concept of neurorehabilitation, which is composed not only of certain associated words but also the meanings they imply.

Looking for the mechanism of arsenate respiration of Fusibacter sp. strain 3D3, independent of ArrAB.

The literature has reported the isolation of arsenate-dependent growing microorganisms which lack a canonical homolog for respiratory arsenate reductase, ArrAB. We recently isolated an arsenate-dependent growing bacterium from volcanic arsenic-bearing environments in Northern Chile, Fusibacter sp. strain 3D3 (Fas) and studied the arsenic metabolism in this Gram-positive isolate. Features of Fas deduced from genome analysis and comparative analysis with other arsenate-reducing microorganisms revealed the lack of ArrAB coding genes and the occurrence of two arsC genes encoding for putative cytoplasmic arsenate reductases named ArsC-1 and ArsC-2. Interestingly, ArsC-1 and ArsC-2 belong to the thioredoxin-coupled family (because of the redox-active disulfide protein used as reductant), but they conferred differential arsenate resistance to the E. coli WC3110 ΔarsC strain. PCR experiments confirmed the absence of arrAB genes and results obtained using uncouplers revealed that Fas growth is linked to the proton gradient. In addition, Fas harbors ferredoxin-NAD+ oxidoreductase (Rnf) and electron transfer flavoprotein (etf) coding genes. These are key molecular markers of a recently discovered flavin-based electron bifurcation mechanism involved in energy conservation, mainly in anaerobic metabolisms regulated by the cellular redox state and mostly associated with cytoplasmic enzyme complexes. At least three electron-bifurcating flavoenzyme complexes were evidenced in Fas, some of them shared in conserved genomic regions by other members of the Fusibacter genus. These physiological and genomic findings permit us to hypothesize the existence of an uncharacterized arsenate-dependent growth metabolism regulated by the cellular redox state in the Fusibacter genus.

Exploring Renal Changes after Bariatric Surgery in Patients with Severe Obesity.

Obesity-related hyperfiltration leads to an increased glomerular filtration rate (GFR) and hyperalbuminuria. These changes are reversible after bariatric surgery (BS). We aimed to explore obesity-related renal changes post-BS and to seek potential mechanisms. Sixty-two individuals with severe obesity were prospectively examined before and 3, 6 and 12 months post-BS. Anthropometric and laboratory data, 24 h-blood pressure, renin-angiotensin-aldosterone system (RAS) components, adipokines and inflammatory markers were determined. Both estimated GFR (eGFR) and albuminuria decreased from the baseline at all follow-up times (p-for-trend <0.001 for both). There was a median (IQR) of 30.5% (26.2-34.4) reduction in body weight. Plasma glucose, glycosylated hemoglobin, fasting insulin and HOMA-index decreased at 3, 6 and 12 months of follow-up (p-for-trend <0.001 for all). The plasma aldosterone concentration (median (IQR)) also decreased at 12 months (from 87.8 ng/dL (56.8; 154) to 65.4 (56.8; 84.6), p = 0.003). Both leptin and hs-CRP decreased (p < 0.001) and adiponectine levels increased at 12 months post-BS (p = 0.017). Linear mixed-models showed that body weight (coef. 0.62, 95% CI: 0.32 to 0.93, p < 0.001) and plasma aldosterone (coef. -0.07, 95% CI: -0.13 to -0.02, p = 0.005) were the independent variables for changes in eGFR. Conversely, glycosylated hemoglobin was the only independent variable for changes in albuminuria (coef. 0.24, 95% CI: 0.06 to 0.42, p = 0.009). In conclusion, body weight and aldosterone are the main factors that mediate eGFR changes in obesity and BS, while albuminuria is associated with glucose homeostasis.

Effect of CPAP treatment on BP in resistant hypertensive patients according to the BP dipping pattern and the presence of nocturnal hypertension.

High heterogeneity in the blood pressure (BP) response to continuous positive airway pressure (CPAP) exists in patients with resistant hypertension (RH). Only nondipper normotensive and hypertensive patients exhibited BP reductions when treated with CPAP; the baseline BP dipping pattern has been proposed as a predictor of BP response to CPAP but has never been explored in patients with RH. This study aimed to assess the effect of CPAP on BP in subjects with RH with respect to BP dipping pattern or nocturnal hypertension. This is an ancillary study of the SARAH study. RH subjects with an apnea/hypopnea index (AHI) ≥ 15/h and who received CPAP treatment for 1 year were included. Subjects underwent a sleep study and ambulatory BP monitoring (ABPM) at baseline and at the 1-year follow-up. Eighty-nine RH subjects were included. The subjects were mainly male (77.5%) and obese, with a mean age of 66 years (25th-75th percentile; 59.0; 70.0) and an AHI of 32.7/h (25th-75th percentile; 25.0; 54.7). A total of 68.5% of participants were nondippers, and 71.9% had nocturnal hypertension. After 1 year of CPAP, no significant differences in ABPM parameters were observed between dippers and nondippers. According to nighttime BP, subjects with nocturnal normotension did not show significant changes in ABPM parameters, while nocturnal hypertensive subjects achieved a significant reduction in mean nighttime BP of -4.38 mmHg (-7.10 to -1.66). The adjusted difference between groups was 3.04 (-2.25 to 8.34), which was not significant. This study shows that the BP response to CPAP in patients with RH does not differ according to the BP dipping pattern (dipper and nondipper) and suggests a differential response according to the presence of nocturnal hypertension (ClinicalTrials.gov: NCT03002558).