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Background: Transgender women sex workers (TWSWs) and men sex workers (MSWs) are especially vulnerable to acquiring hepatitis B virus (HBV) infection. We aimed to describe HBV prevalence (hepatitis B surface antigen [HBsAg] and core antibody [HBcAb]) and associated risk factors for HBV exposure (HBcAb), to assess vaccination status and risk factors for no prior vaccination, and to compare HBV prevalence and vaccination status between TWSWs and MSWs. Methods: The SexCohort study was advertised to TWSWs and MSWs through several communication channels. At cohort entry through 2 community-based organizations in Barcelona, the study population was screened for HBV and other sexually transmitted infections, and an epidemiological questionnaire was administered (n = 271). Results: Overall, 93.0% of participants were migrants, mostly from South and Central American countries. HBsAg prevalence was 1.9% (TWSWs, 2.4%; vs MSWs, 0.9%; P = .42), and previous exposure to HBV was 31.8% (TWSWs, 38.5%; vs MSWs, 20.8%; P = .002). Over 5 years of sex work (adjusted odds ratio [aOR], 9.35), prior exposure to Treponema pallidum (aOR, 3.49), and treatment with anxiolytic drugs (aOR, 3.23) were associated with HBV exposure. Overall, 33.7% of participants exhibited immunity from vaccination (TWSWs, 30.8%; vs MSWs, 38.61%; P < .001), while 34.4% were candidates to HBV vaccination (TWSWs, 30.8%; vs MSWs, 40.6%; P < .001). Never having been on pre-exposure prophylaxis for HIV (odds ratio [OR], 4.23) and non-Spanish origin (OR, 5.00) were associated with no prior HBV vaccination. Conclusions: There is a need to reinforce screening and vaccination programs aimed at TWSWs and MSWs as integrated services offered at the community centers commonly accessed by these populations.
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BACKGROUND: Patients afflicted by type 1 diabetes (T1D) exhibit polyautoimmunity (PolyA). However, the frequency and distribution of PolyA in T1D is still unknown. OBJECTIVE: We conducted a systematic review and meta-analysis to define the prevalence of latent and overt PolyA in individuals with T1D. METHODS: Following PRISMA guidelines, a comprehensive search across medical databases identified studies on latent and overt PolyA in T1D. Two researchers independently screened, extracted data, and assessed study quality. A random effects model was utilized to calculate the pooled prevalence, along with its corresponding 95 % confidence interval (CI), for latent PolyA and overt PolyA. Meta-regression analysis was conducted to study the effect of study designs, age, sex, and duration of disease on pooled prevalence. RESULTS: A total of 158 articles, encompassing a diverse composition of study designs were scrutinized. The analysis included 270,890 individuals with a confirmed diagnosis of T1D. The gender was evenly distributed (50.30 % male). Notably, our analysis unveiled an overt PolyA prevalence rate of 8.50 % (95 % CI, 6.77 to 10.62), with North America having the highest rates (14.50 %, 95 % CI, 7.58 to 24.89). This PolyA profile was further characterized by a substantial incidence of concurrent autoimmune thyroid disease (7.44 %, 95 % CI, 5.65 to 9.74). Moreover, we identified a notable prevalence of latent PolyA in the T1D population, quantified at 14.45 % (95 % CI, 11.17 to 18.49) being most frequent in Asia (23.29 %, 95 % CI, 16.29 to 32.15) and Oceania (21.53 %, 95 % CI, 16.48 to 27.62). Remarkably, this latent PolyA phenomenon primarily featured an array of autoantibodies, including rheumatoid factor, followed by Ro52, thyroid peroxidase antibodies, and thyroglobulin antibodies. Duration of the disease was associated with a highest frequency of latent (ß: 0.0456, P-value: 0.0140) and overt PolyA (ß: 0.0373, P-value: 0.0152). No difference in the pooled prevalence by study design was observed. CONCLUSION: This meta-analysis constitutes a substantial advancement in the realm of early detection of PolyA in the context of T1D. Individuals with T1D should regularly undergo assessments to identify potential concurrent autoimmune diseases, especially as they age.
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Three-dimensional cell cultures have improved the evaluation of drugs for cancer therapy, due to their high similarity to solid tumors. In melanoma, autophagy appears to show a dual role depending on the progression of the disease. p62 protein has been proposed for the evaluation of autophagic flux since its expression is an indicator of the state of autophagy. Pentoxifylline (PTX) and Norcantharidin (NCTD) are drugs that have been shown to possess anticancer effects. In this work, we used B16F1 mouse melanoma cells in two-dimensional (2D) monolayer cultures and three-dimensional (3D) spheroids to test the effect of PTX and NCTD over the p62 expression. We analyzed the effect on p62 expression through Western blot and immunofluorescence assays. Our results indicate that PTX decreases p62 expression in both cell culture models, while Norcantharidin increases its expression in 3D cultures at 24 h. Therefore, these drugs could have a potential therapeutic use for the regulation of autophagy in melanoma, depending on the state of evolution of the disease.
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Autofagia , Compuestos Bicíclicos Heterocíclicos con Puentes , Pentoxifilina , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Animales , Ratones , Pentoxifilina/farmacología , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Melanoma Experimental/metabolismo , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/patología , Técnicas de Cultivo de Célula , Proteína Sequestosoma-1/metabolismo , Proteína Sequestosoma-1/genética , Antineoplásicos/farmacología , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/metabolismoRESUMEN
BACKGROUND: A paucity of predictive models assessing risk factors for COVID-19 mortality that extend beyond age and gender in Latino population is evident in the current academic literature. OBJECTIVES: To determine the associated factors with mortality, in addition to age and sex during the first year of the pandemic. DESIGN: A case-control study with retrospective revision of clinical and paraclinical variables by systematic revision of clinical records was conducted. Multiple imputations by chained equation were implemented to account for missing variables. Classification and regression trees (CART) were estimated to evaluate the interaction of associated factors on admission and their role in predicting mortality during hospitalisation. No intervention was performed. SETTING: High-complexity centre above 2640 m above sea level (masl) in Colombia. PARTICIPANTS: A population sample of 564 patients admitted to the hospital with confirmed COVID-19 by PCR. Deceased patients (n=282) and a control group (n=282), matched by age, sex and month of admission, were included. MAIN OUTCOME MEASURE: Mortality during hospitalisation. MAIN RESULTS: After the imputation of datasets, CART analysis estimated 11 clinical profiles based on respiratory distress, haemoglobin, lactate dehydrogenase, partial pressure of oxygen to inspired partial pressure of oxygen ratio, chronic kidney disease, ferritin, creatinine and leucocytes on admission. The accuracy model for prediction was 80.4% (95% CI 71.8% to 87.3%), with an area under the curve of 78.8% (95% CI 69.63% to 87.93%). CONCLUSIONS: This study discloses new interactions between clinical and paraclinical features beyond age and sex influencing mortality in COVID-19 patients. Furthermore, the predictive model could offer new clues for the personalised management of this condition in clinical settings.
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COVID-19 , Humanos , Estudios de Casos y Controles , SARS-CoV-2 , Estudios Retrospectivos , Oxígeno , Mortalidad HospitalariaRESUMEN
BACKGROUND: Dual point-of-care tests (POCTs) for the simultaneous detection of antibodies to HIV and syphilis have been developed. Since community-based organisations (CBO) are effective providers of HIV and syphilis testing among men who have sex with men (MSM), evaluation of the utility of these dual tests at CBO testing services is a high priority. The aim of this study is to determine the feasibility of performing dual HIV-syphilis POCT testing among both users and providers at these non-clinical sites. METHODS: This evaluation assessed the utility of two lateral flow immunochromatographic antibody technologies for dual screening for HIV/syphilis among MSM seeking testing in four CBO testing services in Spain, Slovenia, Latvia, and Ukraine. The study's conceptual framework divides the concept of feasibility into two inter-related domains, acceptability, and usability and further breaks it down into six subdomains: learnability, willingness, suitability, satisfaction, efficacy, and effectiveness. The feasibility analysis was performed by calculating the median score in 3 stages (for individual questions, subdomains, and domains), using a summated scores method. RESULTS: The final sample included 844 participants, 60 of which were found to be HIV test positive (7.1%) and 61 (7.2%) positive on testing for syphilis. There was a small difference (1.1%) when comparing the results of the two dual POCTs under evaluation to the tests routinely used at each site. The inter-rater agreement showed a high concordance between two independent readings. The analysis of the feasibility for the users of the services indicated good satisfaction, suitability, and willingness. In addition, among 18 providers the total mean score showed good acceptability and usability, good willingness, easy learnability, high suitability, and good efficacy, but lower satisfaction and effectiveness. The operational characteristics of both dual study POCTs were well evaluated by providers. CONCLUSIONS: The introduction of dual HIV and syphilis POCTs in CBO testing services for screening of MSM is feasible, with a high acceptability and usability both for users and providers. Implementation of dual POCTs for HIV and syphilis in CBO testing services is an opportunity for scaling up integrated HIV/syphilis testing for MSM.
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Infecciones por VIH , Minorías Sexuales y de Género , Sífilis , Masculino , Humanos , Sífilis/diagnóstico , Homosexualidad Masculina , Infecciones por VIH/diagnóstico , Tamizaje Masivo/métodos , Pruebas en el Punto de AtenciónRESUMEN
Laboratory automation in microbiology improves productivity and reduces sample turnaround times (TATs). However, its full potential can be unlocked through the optimization of workflows by adopting lean principles. This study aimed to explore the relative impact of laboratory automation and continuous improvement events (CIEs) on productivity and TATs. Laboratory automation took place in November 2020 and consisted of the introduction of WASPLab and VITEK MS systems. CIEs were run in May and September 2021. Before the conversion, the laboratory processed about ~492 samples on weekdays and had 10 full-time equivalent (FTE) staff for a productivity of 49 samples/FTE/day. In March 2021, after laboratory automation, the caseload went up to ~621 while the FTEs decreased to 8.5, accounting for productivity improvement to 73 samples/FTE/day. The hypothetical productivity went up to 110 samples/FTE/day following CIEs, meaning that the laboratory could at that point deal with a caseload increase to ~935 with unchanged FTEs. Laboratory conversion also led to an improvement in TATs for all sample types. For vaginal swabs and urine samples, median TATs decreased from 70.3 h [interquartile range (IQR): 63.5-93.1] and 73.7 h (IQR: 35.6-50.7) to 48.2 h (IQR: 44.8-67.7) and 40.0 h (IQR: 35.6-50.7), respectively. Automation alone was responsible for 37.2% and 75.8% of TAT reduction, respectively, while the remaining reduction of 62.8% and 24.2%, respectively, was achieved due to CIEs. The laboratory reached productivity and TAT goals predefined by the management after CIEs. In conclusion, automation substantially improved productivity and TATs, while the subsequent implementation of lean management further unlocked the potential of laboratory automation.IMPORTANCEIn this study, we combined total laboratory automation with lean management to show that appropriate laboratory work organization enhanced the benefit of the automation and substantially contributed to productivity improvements. Globally, the rapid availability of accurate results in the setting of a clinical microbiology laboratory is part of patient-centered approaches to treat infections and helps the implementation of antibiotic stewardship programs backed by the World Health Organization. Locally, from the point of view of laboratory management, it is important to find ways of maximizing the benefits of the use of technology, as total laboratory automation is an expensive investment.
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Automatización de Laboratorios , Laboratorios , Femenino , Humanos , Automatización de Laboratorios/métodos , Factores de TiempoRESUMEN
PURPOSE: This systematic review represents an update to previous reviews of the literature addressing behavioral management of respiratory/phonatory dysfunction in individuals with dysarthria due to neurodegenerative disease. METHOD: Multiple electronic database searches and hand searches of prominent speech-language pathology journals were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards. RESULTS: The search yielded 1,525 articles, from which 88 met inclusion criteria and were reviewed by two blinded co-investigators. A large range of therapeutic approaches have been added to the evidence base since the last review, including expiratory muscle strength training, singing, and computer- and device-driven programs, as well as a variety of treatment modalities, including teletherapy. Evidence for treatment in several different population groups-including cerebellar ataxia, myotonic dystrophy, autosomal recessive spastic ataxia of Charlevoix-Saguenay, Huntington's disease, multiple system atrophy, and Lewy body dementia-were added to the current review. Synthesis of evidence quality provided strong evidence in support of only one behavioral intervention: Lee Silverman Voice Treatment Program (LSVT LOUD) in people with Parkinson's disease. No other treatment approach or population included in this review demonstrated more than limited evidence, reflecting that these approaches/populations require urgent further examination. CONCLUSION: Suggestions about where future research efforts could be significantly strengthened and how clinicians can apply research findings to their practice are provided. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24964473.
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Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Humanos , Enfermedades Neurodegenerativas/complicaciones , Enfermedades Neurodegenerativas/terapia , Disartria/diagnóstico , Disartria/etiología , Disartria/terapia , Logopedia , Entrenamiento de la Voz , Enfermedad de Parkinson/complicacionesRESUMEN
INTRODUCTION: The incidence of cochlear implantation failure is rare; however, complications can arise in which revision surgery becomes necessary. The purpose of this study is to review our institutional experience with revision cochlear implantation to further understand the surgical and audiological outcomes after cochlear implant failure. METHODS: This is a retrospective review of patients who underwent revision cochlear implantation from 2014 to 2022 at a single institution. RESULTS: Twenty-one patients required reimplantation within the 8-year study period. During this time frame, a total of 202 cochlear implants were implanted in 171 pediatric patients, resulting in a reimplantation rate of 5.9 %. Our reimplantation patient population were majority white (61.9 %), female (52.4 %), and insured by Medicaid (61.9 %). The average age at implantation was 54.8 months ±47.5 months and the average age at reimplantation was 100.1 months ±55.9 months. The average time between initial implantation and reimplantation was 46.2 months ±30.2 months. The most common sign of failure was abnormal impedances (47.6 %). Reimplantation was required more often for hard failure (76.2 %), which occurred secondary to trauma in 56.3 % of patients, and occurred more frequently in those ages 5-7. Operative findings were unremarkable in 81 % of patients. Those with audiologic data were noted to have stable or improved thresholds after their revision surgery. Three of the 21 patients discontinued use of their processor on the revised ear. Of these, two had known trauma associated with implant failure that was not immediately addressed. CONCLUSION: We noted increased rates of hard failure, most commonly secondary to trauma. We noted that majority of those who discontinued use of their implant after revision surgery had associated traumatic injuries that ultimately delayed their presentation and surgery.
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Implantación Coclear , Implantes Cocleares , Niño , Humanos , Femenino , Implantación Coclear/efectos adversos , Falla de Prótesis , Estudios Retrospectivos , ReoperaciónRESUMEN
We aimed to evaluate the feasibility of an online self-sampling pilot intervention for HIV testing addressed to gay, bisexual, and other men who have sex with men (GBMSM) and trans women (TW) users of dating apps in Spain. The website https://www.testate.org/ was designed to offer self-sampling kits for HIV testing and online consultation of the results. It was advertised on gay dating apps. Participants requested the delivery of a saliva self-sampling kit by mail and a postage-paid envelope to send the sample to the reference laboratory. An anonymous acceptability survey was conducted. The cascade of care was estimated. From November 2018 to December 2021, 4623 individual users ordered self-sampling kits, 3097 returned an oral fluid sample to the reference laboratory (67.5% return rate). 87 reactive results were detected. 76 were confirmed to be HIV-positive, we estimated an HIV prevalence of 2.45% (95% CI 1.9-3.0%). 100% of those referred to specialized care are in treatment. 45.8% of participants took more than one test. 23 incident cases were detected among repeat testers, of which 20 were confirmed. The estimated incidence was 1.00 confirmed case per 100 individual-years of follow-up. 98.01% of participants would recommend it to a friend. The most identified advantages were convenience and privacy. We demonstrated that the online offer of oral self-sampling kits for HIV detection and reporting results online among GBMSM and TW users of dating apps is feasible. The intervention counted with a high acceptability and high efficacy (in terms of reactivity, confirmation and linkage to care rates).
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Infecciones por VIH , Minorías Sexuales y de Género , Masculino , Humanos , Femenino , Homosexualidad Masculina , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , España/epidemiología , Conducta SexualRESUMEN
OBJECTIVE: To describe healthcare resource utilization (HCRU) and costs, in patients with newly diagnosed heart failure (HF) according to ejection fraction (EF) in Spain. METHODS: Retrospective cohort study that analyzed anonymized, integrated and computerised medical records in Spain. Patients with ≥ 1 new HF diagnosis between January 2013 and September 2019 were included and followed-up during a 4-year period. Rates per 100 person-years of HCRU and costs were estimated. RESULTS: Nineteen thousand nine hundred sixty-one patients were included, of whom 43.5%, 26.3%, 5.1% and 25.1% had HF with reduced, preserved, mildly reduced and unknown EF, respectively. From year 1 to 4, HF rates of outpatient visits decreased from 1149.5 (95% CI 1140.8-1159.3) to 765.5 (95% CI 745.9-784.5) and hospitalizations from 61.7 (95% CI 60.9-62.7) to 15.7(14.7-16.7) per 100 person-years. The majority of HF-related healthcare resource costs per patient were due to hospitalizations (year 1-4: 63.3-38.2%), followed by indirect costs (year 1-4: 12.2-29.0%), pharmacy (year 1-4: 11.9-19.9%), and outpatient care (year 1-4: 12.6-12.9%). Mean (SD) per patient HF-related costs decreased from 2509.6 (3518.5) to 1234.6 (1534.1) Euros (50% cost reduction). At baseline, 70.1% were taking beta-blockers, 56.3% renin-angiotensin system inhibitors, 11.8% mineralocorticoid receptor antagonists and 8.9% SGLT2 inhibitors. At 12 months, these numbers were 72.3%, 65.4%, 18.9% and 9.8%, respectively. CONCLUSIONS: Although the economic burden of HF decreased over time since diagnosis, it is still substantial. This reduction could be partially related to a survival bias (sick patients died early), but also to a better HF management. Despite that, there is still much room for improvement.
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Estrés Financiero , Insuficiencia Cardíaca , Humanos , Valsartán , Volumen Sistólico , España/epidemiología , Estudios Retrospectivos , Tetrazoles , Combinación de Medicamentos , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/terapia , Antagonistas de Receptores de AngiotensinaRESUMEN
In this work, we extracted chitosan from marine amphipods associated with aquaculture facilities and tested its use in crop protection. The obtained chitosan was 2.5 ± 0.3% of initial ground amphipod dry weight. The chemical nature of chitosan from amphipod extracts was confirmed via Raman scattering spectroscopy and Fourier transform infrared spectroscopy (FTIR). This chitosan showed an 85.7-84.3% deacetylation degree. Chitosan from biofouling amphipods at 1 mg·mL-1 virtually arrested conidia germination (ca. sixfold reduction from controls) of the banana wilt pathogenic fungus Fusarium oxysporum f. sp cubense Tropical Race 4 (FocTR4). This concentration reduced (ca. twofold) the conidia germination of the biocontrol fungus Pochonia chlamydosporia (Pc123). Chitosan from amphipods at low concentrations (0.01 mg·mL-1) still reduced FocTR4 germination but did not affect Pc123. This is the first time that chitosan is obtained from biofouling amphipods. This new chitosan valorizes aquaculture residues and has potential for biomanaging the diseases of food security crops such as bananas.
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Anfípodos , Quitosano , Fusarium , Musa , Animales , Musa/microbiología , Quitosano/farmacología , Enfermedades de las Plantas/prevención & control , Enfermedades de las Plantas/microbiología , HongosRESUMEN
Introduction: Systemic sclerosis (SSc) is a chronic autoimmune disease, marked by an unpredictable course, high morbidity, and increased mortality risk that occurs especially in the diffuse and rapidly progressive forms of the disease, characterized by fibrosis of the skin and internal organs and endothelial dysfunction. Recent studies suggest that the identification of altered metabolic pathways may play a key role in understanding the pathophysiology of the disease. Therefore, metabolomics might be pivotal in a better understanding of these pathogenic mechanisms. Methods: Through a systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA), searches were done in the PubMed, EMBASE, Web of Science, and Scopus databases from 2000 to September 2022. Three researchers independently reviewed the literature and extracted the data based on predefined inclusion and exclusion criteria. Results: Of the screened studies, 26 fulfilled the inclusion criteria. A total of 151 metabolites were differentially distributed between SSc patients and healthy controls (HC). The main deregulated metabolites were those derived from amino acids, specifically homocysteine (Hcy), proline, alpha-N-phenylacetyl-L-glutamine, glutamine, asymmetric dimethylarginine (ADMA), citrulline and ornithine, kynurenine (Kyn), and tryptophan (Trp), as well as acylcarnitines associated with long-chain fatty acids and tricarboxylic acids such as citrate and succinate. Additionally, differences in metabolic profiling between SSc subtypes were identified. The diffuse cutaneous systemic sclerosis (dcSSc) subtype showed upregulated amino acid-related pathways involved in fibrosis, endothelial dysfunction, and gut dysbiosis. Lastly, potential biomarkers were evaluated for the diagnosis of SSc, the identification of the dcSSc subtype, pulmonary arterial hypertension, and interstitial lung disease. These potential biomarkers are within amino acids, nucleotides, carboxylic acids, and carbohydrate metabolism. Discussion: The altered metabolite mechanisms identified in this study mostly point to perturbations in amino acid-related pathways, fatty acid beta-oxidation, and in the tricarboxylic acid cycle, possibly associated with inflammation, vascular damage, fibrosis, and gut dysbiosis. Further studies in targeted metabolomics are required to evaluate potential biomarkers for diagnosis, prognosis, and treatment response.
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BACKGROUND: Mitochondrial membrane protein-associated neurodegeneration (MPAN) is caused by mutations in the C19orf12 gene. MPAN typically appears in the first two decades of life and presents with progressive dystonia-parkinsonism, lower motor neuron signs, optic atrophy, and abnormal iron deposits predominantly in the basal ganglia. MPAN, initially considered as a strictly autosomal recessive disease (AR), turned out to be also dominantly inherited (AD). OBJECTIVES: Our aim was to better characterize the clinical, molecular, and functional spectra associated with such dominant pathogenic heterozygous C19orf12 variants. METHODS: We collected clinical, imaging, and molecular information of eight individuals from four AD-MPAN families and obtained brain neuropathology results for one. Functional studies, focused on energy and iron metabolism, were conducted on fibroblasts from AD-MPAN patients, AR-MPAN patients, and controls. RESULTS: We identified four heterozygous C19orf12 variants in eight AD-MPAN patients. Two of them carrying the familial variant in mosaic displayed an atypical late-onset phenotype. Fibroblasts from AD-MPAN showed more severe alterations of iron storage metabolism and autophagy compared to AR-MPAN cells. CONCLUSION: Our data add strong evidence of the realness of AD-MPAN with identification of novel monoallelic C19orf12 variants, including at the mosaic state. This has implications in diagnosis procedures. We also expand the phenotypic spectrum of MPAN to late onset atypical presentations. Finally, we demonstrate for the first time more drastic abnormalities of iron metabolism and autophagy in AD-MPAN than in AR-MPAN. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Mosaicismo , Trastornos del Movimiento , Humanos , Proteínas Mitocondriales/genética , Hierro/metabolismo , Mutación/genética , Proteínas de la Membrana/genética , FenotipoRESUMEN
Biallelic variants in the mitochondrial form of the tryptophanyl-tRNA synthetases (WARS2) can cause a neurodevelopmental disorder with movement disorders including early-onset tremor-parkinsonism syndrome. Here, we describe four new patients, who all presented at a young age with a tremor-parkinsonism syndrome and responded well to levodopa. All patients carry the same recurrent, hypomorphic missense variant (NM_015836.4: c.37T>G; p.Trp13Gly) either together with a previously described truncating variant (NM_015836.4: c.797Cdel; p.Pro266ArgfsTer10), a novel truncating variant (NM_015836.4: c.346C>T; p.Gln116Ter), a novel canonical splice site variant (NM_015836.4: c.349-1G>A), or a novel missense variant (NM_015836.4: c.475A>C, p.Thr159Pro). We investigated the mitochondrial function in patients and found increased levels of mitochondrially encoded cytochrome C Oxidase II as part of the mitochondrial respiratory chain as well as decreased mitochondrial integrity and branching. Finally, we conducted a literature review and here summarize the broad phenotypical spectrum of reported WARS2-related disorders. In conclusion, WARS2-related disorders are diagnostically challenging diseases due to the broad phenotypic spectrum and the disease relevance of a relatively common missense change that is often filtered out in a diagnostic setting since it occurs in ~0.5% of the general European population.
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Trastornos Parkinsonianos , Triptófano-ARNt Ligasa , Humanos , Temblor , Mitocondrias/genética , Mutación MissenseRESUMEN
INTRODUCTION: In 2020 the pandemic caused by SARS-COV-2 demanded an enormous number of healthcare resources in order to guarantee adequate treatment and support for those patients. This study aims to assess caloric and protein intake and evaluate its associations with relevant clinical outcomes in critically ill with coronavirus disease (COVID-19) patients. METHODS: A nationwide, multicentre prospective observational study including twelve Argentinian intensive care units (ICUs,) was conducted between March and October 2020. INCLUSION CRITERIA: Adult ICU patients>18 years admitted to the ICU with COVID-19 diagnosis and mechanical ventilation for at least 48h. Statistical analysis was carried out using IBM-SPSS© 24 programme. RESULTS: One hundred and eighty-five patients were included in the study. Those who died had lower protein intake (0.73g/kg/day (95% confidence interval (CI) 0.70-0.75 vs 0.97g/kg/day (CI 0.95-0.99), P<0.001), and lower caloric intake than those who survived (12.94kcal/kg/day (CI 12.48-13.39) vs 16.47kcal/kg/day (CI 16.09-16.8), P<0.001). A model was built, and logistic regression showed that factors associated with the probability of achieving caloric and protein intake, were the early start of nutritional support, modified NUTRIC score higher than five points, and undernutrition (Subjective Global Assessment B or C). The patients that underwent mechanical ventilation in a prone position present less caloric and protein intake, similar to those with APACHE II>18. CONCLUSIONS: Critically ill patients with COVID-19 associated respiratory failure requiring mechanical ventilation who died in ICU had less caloric and protein intake than those who survived. Early start on nutritional support and undernutrition increased the opportunity to achieve protein and caloric goals, whereas the severity of disease and mechanical ventilation in the prone position decreased the chance to reach caloric and protein targets.
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COVID-19 , Desnutrición , Adulto , Humanos , Enfermedad Crítica/terapia , Argentina , Prueba de COVID-19 , SARS-CoV-2 , Desnutrición/epidemiología , Desnutrición/etiología , Desnutrición/terapiaRESUMEN
OBJECTIVE: The objective of this study was to describe the rates of adverse clinical outcomes, including all-cause mortality, heart failure (HF) hospitalization, myocardial infarction, and stroke, in patients newly diagnosed with HF to provide a comprehensive picture of HF burden. METHODS: This was a retrospective and observational study, using the BIG-PAC database in Spain. Adults, newly diagnosed with HF between January 2013 and September 2019 with ≥1 HF-free year of enrolment prior to HF diagnosis, were included. RESULTS: A total of 19,961 patients were newly diagnosed with HF (43.5% with reduced ejection fraction (EF), 26.3% with preserved EF, 5.1% with mildly reduced EF, and 25.1% with unknown EF). The mean age was 69.7 ± 19.0 years; 53.8% were men; and 41.0% and 41.5% of patients were in the New York Heart Association functional classes II and III, respectively. The baseline HF treatments included beta-blockers (70.1%), renin-angiotensin system inhibitors (56.3%), mineralocorticoid receptor antagonists (11.8%), and SGLT2 inhibitors (8.9%). The post-index incidence rates of all-cause mortality, HF hospitalization, and both combined were 102.2 (95% CI 99.9-104.5), 123.1 (95% CI 120.5-125.7), and 182 (95% CI 178.9-185.1) per 1000 person-years, respectively. The rates of myocardial infarction and stroke were lower (26.2 [95% CI 25.1-27.4] and 19.8 [95% CI 18.8-20.8] per 1000 person-years, respectively). CONCLUSIONS: In Spain, patients newly diagnosed with HF have a high risk of clinical outcomes. Specifically, the rates of all-cause mortality and HF hospitalization are high and substantially greater than the rates of myocardial infarction and stroke. Given the burden of adverse outcomes, these should be considered targets in the comprehensive management of HF. There is much room for improving the proportion of patients receiving disease-modifying therapies.
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We present the case of an 82-year-old woman with subacute altered mental status, oculomotor disturbances, and ataxia. On examination, she exhibited bilateral ptosis, complete horizontal ophthalmoplegia, and limited vertical eye movements during upgaze associated with prominent truncal ataxia. Cerebral MRI showed a mild hyperintensity on T2 and fluid-attenuated inversion recovery sequences in the posterior brainstem extending to the upper cervical cord, without gadolinium enhancement. Clinical and radiologic features suggested an encephalomyelitis with prominent brainstem involvement. We summarize the comprehensive differential diagnosis in patients with subacute brainstem encephalitis, which includes infectious paraneoplastic syndromes and inflammatory disorders. This case highlights the relevance of performing a wide methodical screening for malignancy in case of negative initial workup.
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Ataxia Cerebelosa , Oftalmoplejía , Femenino , Humanos , Anciano de 80 o más Años , Medios de Contraste , Gadolinio , Ataxia , Oftalmoplejía/diagnóstico , Oftalmoplejía/etiología , Razonamiento ClínicoRESUMEN
Individuals infected with the SARS-CoV-2 virus present with a wide variety of symptoms ranging from asymptomatic to severe and even lethal outcomes. Past research has revealed a genetic haplotype on chromosome 3 that entered the human population via introgression from Neanderthals as the strongest genetic risk factor for the severe response to COVID-19. However, the specific variants along this introgressed haplotype that contribute to this risk and the biological mechanisms that are involved remain unclear. Here, we assess the variants present on the risk haplotype for their likelihood of driving the genetic predisposition to severe COVID-19 outcomes. We do this by first exploring their impact on the regulation of genes involved in COVID-19 infection using a variety of population genetics and functional genomics tools. We then perform a locus-specific massively parallel reporter assay to individually assess the regulatory potential of each allele on the haplotype in a multipotent immune-related cell line. We ultimately reduce the set of over 600 linked genetic variants to identify four introgressed alleles that are strong functional candidates for driving the association between this locus and severe COVID-19. Using reporter assays in the presence/absence of SARS-CoV-2, we find evidence that these variants respond to viral infection. These variants likely drive the locus' impact on severity by modulating the regulation of two critical chemokine receptor genes: CCR1 and CCR5. These alleles are ideal targets for future functional investigations into the interaction between host genomics and COVID-19 outcomes.
Asunto(s)
COVID-19 , Hombre de Neandertal , Virosis , Humanos , Animales , COVID-19/genética , Hombre de Neandertal/genética , SARS-CoV-2/genética , Genética de PoblaciónRESUMEN
Amphipods are one of the dominant epifaunal groups in seagrass meadows. However, our understanding of the biogeographical patterns in the distribution of these small crustaceans is limited. In this study, we investigated such patterns and the potential drivers in twelve Cymodocea nodosa meadows within four distinctive biogeographical areas across 2000 Km and 13° of latitude in two ocean basins (Mediterranean Sea and Atlantic Ocean). We found that species abundances in the assemblage of seagrass-associated amphipods differed among areas following a pattern largely explained by seagrass leaf area and epiphyte biomass, while the variation pattern in species presence/absence was determined by seagrass density and epiphyte biomass. Seagrass leaf area was also the most important determinant of greater amphipod total density and species richness, while amphipod density also increased with algal cover. Overall, our results evidenced that biogeographical patterns of variation in amphipod assemblages are mainly influenced by components of the habitat structure, which covary with environmental conditions, finding that structurally more complex meadows harboring higher abundance and richness of amphipods associated.