Clinical impact of time to results from the microbiology laboratory in bloodstream infections caused by carbapenemase-producing Enterobacterales (TIME-CPE STUDY).

OBJECTIVES: To evaluate the impact of time to results (TTR) on the outcome of patients with carbapenemase-producing Enterobacterales bloodstream infections (CPE-BSI). METHODS: Times-series study conducted from January 2014 to December 2021, selecting patients with first CPE-BSI episodes. Periods of intervention were defined according to implementation of diagnostic bundle tests in the microbiology laboratory: pre-intervention (January 2014-December 2017) and post-intervention (January 2018-December 2021). TTR was defined as time elapsed from positivity time of the blood culture bottles to physicians' notification of CPE-BSI episodes, and was evaluated in patients who received inappropriate empirical and switched to appropriate targeted treatment (switch group). Analysis of a composite unfavourable outcome (mortality at Day 30 and/or persistent and/or recurrent bacteraemia) was performed for the total episodes and in the switch group. RESULTS: One hundred and nine episodes were analysed: 66 pre-intervention and 43 post-intervention. Compared with pre-intervention, patients in the post-intervention period were younger (68 versus 63 years, P = 0.04), had INCREMENT score > 7 (31.8% versus 53.5%, P = 0.02) and unfavourable outcome (37.9% versus 20.9%, P = 0.04). Proportion of TTR > 30 h was more frequent pre-intervention than post-intervention (61.7% versus 35.5%, P = 0.02). In multivariate analysis of the 109 episodes, source other than urinary or biliary (OR 2.76, 95% CI 1.11-6.86) was associated with unfavourable outcome, while targeted appropriate treatment trended to being protective (OR 0.17, 95% CI 0.03-1.00). Considering the switch group (n = 78), source other than urinary or biliary (OR 14.9, 95% CI 3.25-69.05) and TTR > 30 h (OR 4.72, 95% CI 1.29-17.22) were associated with unfavourable outcome. CONCLUSIONS: Decreased TTR in the post-intervention period was associated with the outcome in patients with CPE-BSI episodes.

Kinect v2-Assisted Semi-Automated Method to Assess Upper Limb Motor Performance in Children.

The interruption of rehabilitation activities caused by the COVID-19 lockdown has significant health negative consequences for the population with physical disabilities. Thus, measuring the range of motion (ROM) using remotely taken photographs, which are then sent to specialists for formal assessment, has been recommended. Currently, low-cost Kinect motion capture sensors with a natural user interface are the most feasible implementations for upper limb motion analysis. An active range of motion (AROM) measuring system based on a Kinect v2 sensor for upper limb motion analysis using Fugl-Meyer Assessment (FMA) scoring is described in this paper. Two test groups of children, each having eighteen participants, were analyzed in the experimental stage, where upper limbs' AROM and motor performance were assessed using FMA. Participants in the control group (mean age of 7.83 ± 2.54 years) had no cognitive impairment or upper limb musculoskeletal problems. The study test group comprised children aged 8.28 ± 2.32 years with spastic hemiparesis. A total of 30 samples of elbow flexion and 30 samples of shoulder abduction of both limbs for each participant were analyzed using the Kinect v2 sensor at 30 Hz. In both upper limbs, no significant differences (p < 0.05) in the measured angles and FMA assessments were observed between those obtained using the described Kinect v2-based system and those obtained directly using a universal goniometer. The measurement error achieved by the proposed system was less than ±1° compared to the specialist's measurements. According to the obtained results, the developed measuring system is a good alternative and an effective tool for FMA assessment of AROM and motor performance of upper limbs, while avoiding direct contact in both healthy children and children with spastic hemiparesis.

Upper Limb Movement Measurement Systems for Cerebral Palsy: A Systematic Literature Review.

Quantifying the quality of upper limb movements is fundamental to the therapeutic process of patients with cerebral palsy (CP). Several clinical methods are currently available to assess the upper limb range of motion (ROM) in children with CP. This paper focuses on identifying and describing available techniques for the quantitative assessment of the upper limb active range of motion (AROM) and kinematics in children with CP. Following the screening and exclusion of articles that did not meet the selection criteria, we analyzed 14 studies involving objective upper extremity assessments of the AROM and kinematics using optoelectronic devices, wearable sensors, and low-cost Kinect sensors in children with CP aged 4-18 years. An increase in the motor function of the upper extremity and an improvement in most of the daily tasks reviewed were reported. In the population of this study, the potential of wearable sensors and the Kinect sensor natural user interface as complementary devices for the quantitative evaluation of the upper extremity was evident. The Kinect sensor is a clinical assessment tool with a unique markerless motion capture system. Few authors had described the kinematic models and algorithms used to estimate their kinematic analysis in detail. However, the kinematic models in these studies varied from 4 to 10 segments. In addition, few authors had followed the joint assessment recommendations proposed by the International Society of Biomechanics (ISB). This review showed that three-dimensional analysis systems were used primarily for monitoring and evaluating spatiotemporal variables and kinematic parameters of upper limb movements. The results indicated that optoelectronic devices were the most commonly used systems. The joint assessment recommendations proposed by the ISB should be used because they are approved standards for human kinematic assessments. This review was registered in the PROSPERO database (CRD42021257211).

[Factors associated with tuberculosis mortality in Paraguay, 2015-2016Fatores associados à mortalidade por tuberculose no Paraguai, 2015-2016]. / Factores asociados a la mortalidad por tuberculosis en Paraguay, 2015-2016.

OBJECTIVE: To describe the socio-demographic and clinical-epidemiological characteristics and to determine the factors associated with the mortality of people diagnosed with tuberculosis (TB) in Paraguay. METHODS: Operational research with a retrospective cohort design of cases diagnosed with TB in Paraguay between 2015-2016. The database of the National Tuberculosis Control Program was used. Chi-square and relative risk (RR) tests with a 95% confidence interval (95% CI) were used to determine the factors associated with mortality; in addition, a robust Poisson multiple regression model was adjusted. A significance level of 5% was used. RESULTS: Five hundred and forty-one cases of TB were studied, of which 11.5% died. The factors increasing the risk of death were male sex (RR 1.26; 95% CI 1.1-1.50), infection with human immunodeficiency virus (RR 4.78; 95% CI 4.04-5.65) and chronic obstructive pulmonary disease (RR 1.70; 95% CI 1.19-2.42). Being deprived of one's liberty was a protective factor (RR 0.37; 95% CI 0.24-0.61). CONCLUSIONS: The highest risk of death is presented by men and people with TB/HIV coinfection and the lowest risk is presented by people deprived of liberty. There is a need to improve diagnosis and follow-up of TB cases, with effective implementation of directly observed treatment (DOTS) and timely management of associated diseases such as HIV and chronic obstructive pulmonary disease.

OBJETIVO: Descrever as características sociodemográficas e clínico-epidemiológicas e determinar os fatores associados à mortalidade de pessoas diagnosticadas com tuberculose (TB) no Paraguai. MÉTODOS: Pesquisa operacional com desenho de coorte retrospectivo de casos diagnosticados com TB no Paraguai entre 2015-2016. Foi utilizada a base de dados do Programa Nacional de Controle da Tuberculose. Testes de qui-quadrado e risco relativo (RR) com intervalo de confiança de 95% (IC95%) foram utilizados para determinar os fatores associados à mortalidade; além disso, um robusto modelo de regressão múltipla de Poisson foi ajustado. Foi utilizado nível de significância de 5%. RESULTADOS: Foram estudados quinhentos e quarenta e um casos de TB, dos quais 11,5% morreram. Os fatores que aumentaram o risco de morte foram sexo masculino (RR 1,26; IC95% 1,1-1,50), infecção por vírus da imunodeficiência humana (RR 4,78; IC95% 4,04-5,65) e doença pulmonar obstrutiva crônica (RR 1,70; 95 % CI 1,19-2,42). Ser privado de liberdade foi um fator protetor (RR 0,37; IC 95% 0,24-0,61). CONCLUSÕES: O maior risco de morte é apresentado por homens e pessoas com co-infecção TB / HIV e o menor risco é apresentado por pessoas privadas de liberdade. É necessário melhorar o diagnóstico e o acompanhamento dos casos de TB, com a implementação efetiva do tratamento diretamente observado (DOTS) e o gerenciamento oportuno de doenças associadas, como o HIV e a doença pulmonar obstrutiva crônica.

"Send & hold" clinical decision support rules improvement to reduce unnecessary testing of vitamins A, E, K, B1, B2, B3, B6 and C.

BACKGROUND: We assessed the impact of several "send & hold" clinical decision support rules (CDSRs) within the electronical request system for vitamins A, E, K, B1, B2, B3, B6 and C for all outpatients at a large health department. METHODS: When ordered through electronical request, providers (except for all our primary care physicians who worked as a non-intervention control group) were always asked to answer several compulsory questions regarding main indication, symptomatology, suspected diagnosis, vitamin active treatments, etc., for each vitamin test using a drop-down list format. After samples arrival, tests were later put on hold internally by our laboratory information system (LIS) until review for their appropriateness was made by two staff pathologists according to the provided answers and LIS records (i.e. "send & hold"). The number of tests for each analyte was compared between the 10-month period before and after CDSRs implementation in both groups. RESULTS: After implementation, vitamins test volumes decreased by 40% for vitamin A, 29% for vitamin E, 42% for vitamin K, 37% for vitamin B1, 85% for vitamin B2, 68% for vitamin B3, 65% for vitamin B6 and 59% for vitamin C (all p values 0.03 or lower except for vitamin B3), whereas in control group, the majority increased or remained stable. In patients with rejected vitamins, no new requests and/or adverse clinical outcome comments due to this fact were identified. CONCLUSIONS: "Send & hold" CDSRs are a promising informatics tool that can support in utilization management and enhance the pathologist's leadership role as tests specialist.

The importance of COVID-19 vaccination during lactation.

The World Health Organization strongly supports breastfeeding as the main source of infant feeding to ensure maternal and child health. Since its emergence, COVID-19 has become a disease affecting the health of the world's population, and vaccines have been developed to prevent it. However, the decision to license COVID-19 vaccines for infants under 6 months of age has been delayed. Different studies have shown that during the breastfeeding period, the benefit-risk balance is much higher in favor of the benefit, at the immunological level for the infant, due to its low perception of adverse effects and the low transmission of products such as mRNA from the mother to the child. Different organizations and societies recommend vaccination in breastfeeding women. COVID-19 vaccines have been shown to be safe and effective.

Measurement proprieties of the CROM instrument for assessing head posture, neck retraction and protraction.

BACKGROUND: The CROM instrument is widely used clinically and in research to measure neck range of motion. However, its measurement proprieties during the assessment of protraction and retraction movements were not examined so far. OBJECTIVE: To analyse the intra- and inter-rater reliability, the concurrent validity of the CROM for measuring head posture, retraction and protraction in healthy subjects. METHODS: Thirty-three asymptomatic subjects were recruited and assigned in a random order to one of two raters. After a 10-min break, they were examined by a second rater (Assessment 1). After a 30-min break, both raters repeated the examination (Assessment 2). The examination consisted of measuring the head posture, maximum head protraction and maximum retraction. Each movement was repeated 3 times and measured simultaneously with the CROM and with a 3D capture system laboratory. RESULTS: The intra-rater reliability of the CROM was excellent for both raters for head posture and all head movements (ICC>0.9, 95% CI: 0.82-0.99, p < 0.01). The inter-rater reliability was excellent for head posture (ICC>0.95, 95% CI: 0.92-0.98, p < 0.01) and good-to-excellent for all movements at both time-points (ICC = 0.73-0.98, 95%CI: 0.45-0.99, p < 0.01). The validity analysis showed moderate-to-strong correlation between instruments for the head posture and head movements [(r) = -0.47 to -0.78), 95% CI: 0.99 to -0.24, p < 0.01]. CONCLUSION: The CROM instrument has good-to-excellent reliability and adequate validity for measuring cervical position and displacement in the sagittal plane.

Mapping the concept of health care integration: A lexicographic analysis of scientific literature.

BACKGROUND: Systems fragmentation is a major challenge for an efficient organization, integration being a potential solution also proposed in health care field, including pharmacy as a player. However, the use of different terms and definitions in the literature hinders the comparison of different integration initiatives. OBJECTIVE: To identify and map the terms used in scientific literature regarding integration in health care and to characterize each emerging topic. METHODS: A lexicographic analysis of the integration of healthcare systems literature indexed in PubMed was conducted. Ten different systematic searches, four using only Medical Subject Headings (MeSH) and six using text words, were conducted in March 2023. Journal scattering was analyzed following Bradford's distribution using the Leimkuhler model. An overall text corpus was created with titles and abstracts of all the records retrieved. The corpus was lemmatized, and the most used bigrams were tokenized as single strings. To perform a topic modeling, the lemmatized corpus text was analyzed using IRaMuTeQ, producing descending hierarchic classification and a correspondence analysis. The 50 words with higher chi-square statistics in each class were considered as representative of the class. RESULTS: A total of 42,479 articles published from 1943 to 2023 in 4469 different journals were retrieved. The MeSH "Delivery of Health Care, Integrated", created in the 1996 MeSH update, was the most productive retrieving 33.7 % of the total articles but also retrieving 22.6 % of articles not retrieved in any other search. The text word "Integration" appeared in 15,357 (36.2 %) records. The lexicographic analysis resulted in 7 classes, named as: Evidence and implementation, Quantitative research, Professional education, Qualitative research, Governance and leadership, Clinical research, and Financial resources. Association between the classes and the searches or the text-words used ranged from moderate to weak demonstrating the lack of a standard pattern of use of terms in literature regarding healthcare integration. CONCLUSIONS: The term "integration" and the MeSH "Delivery of Health Care, Integrated" are the most used to represent the concept of integration in healthcare and should be the preferred terms in the literature.

Community pharmacy and primary health care - Types of integration and their applicability: A narrative review.

BACKGROUND: There is an urgent need for health care systems to be more efficient and efficacious. An approach to integrate public and private provider organizations such as community pharmacies and public primary health care (PHC) merits consideration. The objective of this review was to identify the types of integration in health care settings and discuss their applicability to the potential integration of community pharmacy and PHC. METHODS: A narrative review using Medline, Scopus and SciELO databases was performed in which terms related to health were combined with terms related to integration. Levels and Types of integration: 14 types of integration were identified (two in breadth, seven as enablers and five in system levels). A model was created which classifies and assigns the types of integration to the different levels of the health system and to the breadth, intensity, and enablers of the integration process. Due to the nature of community pharmacy and PHC system, a horizontal integration at the micro level, supported by meso and macro levels policy, is suggested. The different elements of intensity and enablers can significantly influence the process. CONCLUSION: The application of principles, concepts and types of integration suggest that it might be feasible and practical to integrate community pharmacies and PHC. However, the conflictive historical context would need to be overcome with appropriate policy and incentives.

IL-15/IL-15Rα in SJS/TEN: Relevant Expression of IL15 and IL15RA in Affected Skin.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a life-threatening hypersensitivity reaction to medications characterized by keratinocyte apoptosis and skin detachment. IL-15 serum levels have been associated with severity and prognosis of SJS/TEN. We have measured IL-15 concentrations in serum and blister fluid (BF) from patients with SJS/TEN by ELISA and used quantitative RT-PCR to analyze the expression of IL15 and IL15RA (encoding for IL-15 Receptor-α chain) genes in peripheral blood and BF cells, including isolated monocytes, and in affected skin. A positive correlation was found between IL-15 serum levels and a percent of detached skin. BF concentrations were higher, but no correlation was found. Higher IL15 and IL15RA gene expression levels were found in skin-infiltrating blister fluid cells compared to peripheral mononuclear cells. Moreover, IL15RA transcripts were barely detected in healthy skin, being the highest expression levels found in samples from two SJS/TEN patients who did not survive. The cutaneous expression of IL-15Rα in SJS/TEN may provide an explanation to the tissue-specific immune cytotoxic response in this clinical entity, and the results suggest that the effects of IL-15 in SJS/TEN patients may be dependent on the expression of its private receptor IL-15Rα in affected skin.

LTT and HLA testing as diagnostic tools in Spanish vancomycin-induced DRESS cases: A case-control study.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe T-cell-mediated off-target adverse reaction. DRESS cases caused by vancomycin have often been reported. The HLA-A*32:01 allele has been associated with genetic susceptibility to vancomycin-induced DRESS in US citizens of European descent. We have analyzed the association of the HLA-A*32:01 allele in 14 Spanish DRESS cases in which vancomycin was suspected as the culprit drug, and the lymphocyte transformation test (LTT) as an in vitro assay to evaluate vancomycin sensitization. The results were compared to vancomycin-tolerant control donors. LTT was performed in 12 DRESS cases with PBMCs from resolution samples available and in a group of 12 tolerant donors. ROC curves determined that LTT is a suitable tool to identify patients sensitized to vancomycin (AUC = 0.9646; p < 0.0001). When a stimulation index >3 was regarded as a positive result, contingency tables determined 91% sensitivity, 91.67% specificity, 91% positive predictive value, and 91.67% negative predictive value (p = 0.0001, Fisher's exact test). The HLA A*32:01 allele was determined by an allele-specific PCR assay in 14 cases and 25 tolerant controls. Among the DRESS cases, five carriers were identified (35.7%), while it was detected in only one (4%) of the tolerant donors, [odds ratio (OR) = 13.33; 95% CI: 1.364-130.3; p = 0.016]. The strength of the association increased when only cases with positive LTT to vancomycin were considered (OR = 24.0; 95% CI: 2.28-252.6; p = 4.0 × 10-3). Our results confirm the association of the risk allele HLA-A*32:01 with vancomycin-induced DRESS in Spanish cases, and support LTT as a reliable tool to determine vancomycin sensitization.

Integration of community pharmacy in primary health care: The challenge.

Community pharmacies and pharmacists predominantly operate in a retail environment independently of other health care providers, and they are not often viewed as an integral member of the healthcare team. Thus, they remain overlooked or excluded during integration processes of health care systems. At the same time, there are calls by the profession at national and international levels for community pharmacy to be integrated within primary care systems. The COVID-19 pandemic appears to have further stimulated this desire. When pressing for integration, various terms, such as integration, integrated care, or interprofessional collaboration, are used in an interchangeable manner leading to lack of clarity, ambiguity and confusion for health care policy makers, planners, and other healthcare professionals. The literature was reviewed to identify critical components for community pharmacy to consider for integration. From the five selected articles describing integration of community pharmacies, four different constructs were identified: consensus, connectivity, communication and trust. The integration of community pharmacy into the health system may translate into better access for patients to primary care services, contribute to cost effectiveness, and promulgate the sustainability of the system. However significant political, economic, social, and practice change would be required by all stakeholders. Further research is needed to underpin a consensus for a definition, the type of integration, and the model optimally suited to integrate community pharmacy into primary care. These models, specific and adaptable to each national health care system and political environment, would need to be consensus-based by principal stakeholders to overcome a variety of barriers, including government resistance. Mere calls or demands by the pharmaceutical profession, although laudable, will not be sufficient to overcome the historical, cultural, and economic challenges.

Differential pattern of glycogen accumulation after protein phosphatase 1 glycogen-targeting subunit PPP1R6 overexpression, compared to PPP1R3C and PPP1R3A, in skeletal muscle cells.

BACKGROUND: PPP1R6 is a protein phosphatase 1 glycogen-targeting subunit (PP1-GTS) abundant in skeletal muscle with an undefined metabolic control role. Here PPP1R6 effects on myotube glycogen metabolism, particle size and subcellular distribution are examined and compared with PPP1R3C/PTG and PPP1R3A/G(M). RESULTS: PPP1R6 overexpression activates glycogen synthase (GS), reduces its phosphorylation at Ser-641/0 and increases the extracted and cytochemically-stained glycogen content, less than PTG but more than G(M). PPP1R6 does not change glycogen phosphorylase activity. All tested PP1-GTS-cells have more glycogen particles than controls as found by electron microscopy of myotube sections. Glycogen particle size is distributed for all cell-types in a continuous range, but PPP1R6 forms smaller particles (mean diameter 14.4 nm) than PTG (36.9 nm) and G(M) (28.3 nm) or those in control cells (29.2 nm). Both PPP1R6- and G(M)-derived glycogen particles are in cytosol associated with cellular structures; PTG-derived glycogen is found in membrane- and organelle-devoid cytosolic glycogen-rich areas; and glycogen particles are dispersed in the cytosol in control cells. A tagged PPP1R6 protein at the C-terminus with EGFP shows a diffuse cytosol pattern in glucose-replete and -depleted cells and a punctuate pattern surrounding the nucleus in glucose-depleted cells, which colocates with RFP tagged with the Golgi targeting domain of ß-1,4-galactosyltransferase, according to a computational prediction for PPP1R6 Golgi location. CONCLUSIONS: PPP1R6 exerts a powerful glycogenic effect in cultured muscle cells, more than G(M) and less than PTG. PPP1R6 protein translocates from a Golgi to cytosolic location in response to glucose. The molecular size and subcellular location of myotube glycogen particles is determined by the PPP1R6, PTG and G(M) scaffolding.

Psychological Profile and Competitive Performance in Group Aesthetic Gymnastics.

The objective of the research was to evaluate the perceptions about the psychological variables of cohesion and motivational climate that AGG gymnasts have about the context created by the coaches in their teams and to analyze in the different categories the optimism and competitive anxiety they face in competitive situations. In an attempt to clarify the psychosocial training patterns in this sport and the influence they have on the well-being of its practitioners, competitive anxiety, motivational climate, team cohesion and level of optimism were taken as dependent variables. The sample was made up of 98 national and international junior and senior athletes in the aesthetic gymnastics group aged 13 to 27 (M = 17.1; SD = 2.8). The Perceived Motivational Climate in Sport Questionnaire for motivational climate, the Sport Anxiety Scale-2 for competitive anxiety, the Group Environment Questionnaire for cohesion and the Revised Life Orientation Test for optimism were used in the evaluation. The results obtained show a positive and statistically significant correlation between anxiety and ego involvement, while, for task involvement, high levels of cohesion are associated with high levels of optimism (p = 0.005). In conclusion, the data confirm that high levels of cohesion are associated with high levels of optimism, in addition high scores on task involvement show high scores on cohesion and optimism, however high scores on ego involvement are associated with low scores on cohesion and optimism.

Multicomponent Home-Based Training Program for Chronic Kidney Disease Patients during Movement Restriction.

Both intradialytic and out-of-clinic exercise programs (EP) have been proven to be a safe and effective way to increase fitness levels in end-stage chronic kidney disease (CKD) patients. The actual COVID-19 pandemic situation has forced the suspension of EP offered in hemodialysis centers in many countries; as well as all activities considered as "non-essential" (i.e., sport facilities and fitness centers). Therefore, there is a high risk that movement restrictions would promote physical inactivity and its associated diseases in CKD patients; especially those undergoing domiciliary confinement situations. Given the importance for CKD patients' overall health to maintain exercise levels and reach physical activity recommendations, the aim of this Protocol was to design a personalized, well-structured, multicomponent physical EP that CKD patients can safely follow at home. We also aimed to provide an initial fitness evaluation tool that allows patients to adapt the EP to their fitness level. Current general exercise recommendations for people living with chronic conditions have been analyzed to develop the present home-based EP proposal.

Spermidine Supplementation Protects the Liver Endothelium from Liver Damage in Mice.

Chronic liver diseases are multifactorial and the need to develop effective therapies is high. Recent studies have shown the potential of ameliorating liver disease progression through protection of the liver endothelium. Polyamine spermidine (SPD) is a caloric restriction mimetic with autophagy-enhancing properties capable of prolonging lifespan and with a proven beneficial effect in cardiovascular disease in mice and humans. We evaluated the use of dietary supplementation with SPD in two models of liver disease (CCl4 and CDAAH diet). We analyzed the effect of SPD on endothelial dysfunction in vitro and in vivo. C57BL/6J mice were supplemented with SPD in the drinking water prior and concomitantly with CCl4 and CDAAH treatments. Endothelial autophagy deficient (Atg7endo) mice were also evaluated. Liver tissue was used to evaluate the impact of SPD prophylaxis on liver damage, endothelial dysfunction, oxidative stress, mitochondrial status, inflammation and liver fibrosis. SPD improved the endothelial response to oxidative injury in vitro and improved the liver endothelial phenotype and protected against liver injury in vivo. SPD reduced the overall liver oxidative stress and improved mitochondrial fitness. The absence of benefits in the Atg7endo mice suggests an autophagy-dependent effect of SPD. This study suggests SPD diet supplementation in early phases of disease protects the liver endothelium from oxidative stress and may be an attractive approach to modify the chronic liver disease course and halt fibrosis progression.

Neurological Manifestations and Outcomes in a Retrospective Cohort of Mexican Inpatients with SARS-CoV-2 Pneumonia: Design of a Risk Profile.

We analyzed the neurological manifestations in Mexican patients hospitalized with pneumonia due to COVID-19 and investigated the association between demographic, clinical, and biochemical variables and outcomes, including death. A retrospective, analytical study was conducted using the electronic records of patients hospitalized between 1 April 2020 and 30 September 2020. Records of 1040 patients were analyzed: 31.25% died and 79.42% had neurological symptoms, including headache (80.62%), anosmia (32.20%), ageusia (31.96%), myopathy (28.08%), disorientation (14.89%), encephalopathy (12.22%), neuropathy (5.4%), stroke (1.3%), seizures (1.3%), cerebral hemorrhage (1.08%), encephalitis (0.84%), central venous thrombosis (0.36%), and subarachnoid hemorrhage (0.24%). Patients also had comorbidities, such as hypertension (42.30%), diabetes mellitus (38.74%), obesity (61.34%), chronic obstructive pulmonary disease (3.17%), and asthma (2.01%). Factors associated with neurological symptoms were dyspnea, chronic obstructive pulmonary disease, advanced respiratory support, prolonged hospitalization, and worsening fibrinogen levels. Factors associated with death were older age, advanced respiratory support, amine management, chronic obstructive pulmonary disease, intensive care unit management, dyspnea, disorientation, encephalopathy, hypertension, neuropathy, diabetes, male sex, three or more neurological symptoms, and obesity grade 3. In this study we designed a profile to help predict patients at higher risk of developing neurological complications and death following COVID-19 infection.

Comparative gene expression profiling between human cultured myotubes and skeletal muscle tissue.

BACKGROUND: A high-sensitivity DNA microarray platform requiring nanograms of RNA input facilitates the application of transcriptome analysis to individual skeletal muscle (SM) tissue samples. Culturing myotubes from SM-biopsies enables investigating transcriptional defects and assaying therapeutic strategies. This study compares the transcriptome of aneurally cultured human SM cells versus that of tissue biopsies. RESULTS: We used the Illumina expression BeadChips to determine the transcriptomic differences between tissue and cultured SM samples from five individuals. Changes in the expression of several genes were confirmed by QuantiGene Plex assay or reverse transcription real-time PCR. In cultured myotubes compared to the tissue, 1216 genes were regulated: 583 down and 633 up. Gene ontology analysis showed that downregulated genes were mainly associated with cytoplasm, particularly mitochondria, and involved in metabolism and the muscle-system/contraction process. Upregulated genes were predominantly related to cytoplasm, endoplasmic reticulum, and extracellular matrix. The most significantly regulated pathway was mitochondrial dysfunction. Apoptosis genes were also modulated. Among the most downregulated genes detected in this study were genes encoding metabolic proteins AMPD1, PYGM, CPT1B and UCP3, muscle-system proteins TMOD4, MYBPC1, MYOZ1 and XIRP2, the proteolytic CAPN3 and the myogenic regulator MYF6. Coordinated reduced expression of five members of the GIMAP gene family, which form a cluster on chromosome 7, was shown, and the GIMAP4-reduction was validated. Within the most upregulated group were genes encoding senescence/apoptosis-related proteins CDKN1A and KIAA1199 and potential regulatory factors HIF1A, TOP2A and CCDC80. CONCLUSIONS: Cultured muscle cells display reductive metabolic and muscle-system transcriptome adaptations as observed in muscle atrophy and they activate tissue-remodeling and senescence/apoptosis processes.

The Utilization of Linear Polylysine Coupled with Mechanic Forces to Extract Microbial DNA from Different Matrices.

Molecular approaches are powerful tools that are used for medical or environmental diagnoses. However, the main limitations of such a tools are that they extract low levels of DNA and they do not remove the inhibitors of polymerase chain reaction (PCR). Although the use of polycation to complex and purify DNA has been described in the literature, elution often requires a high ionic strength or pH levels not compatible with molecular analyses. In this paper, we described a new process that is based on the complexation of DNA with linear polylysine, followed by capturing the complex by a cation exchange resin. The originality of the process consisted of using mechanic force to elute DNA from the complex. The extraction method showed several advantages when compared to existing methods, such as being compatible with pH levels that range from 5 to 11, as well as high levels of DNA recovery and elimination of PCR inhibitors from complex samples. This method was successfully applied to different types of samples, such as environmental samples, beverage samples, and medical samples. Furthermore, it was proven to be a good solution for removing PCR inhibitors and assuring good DNA recovery yield.

Novel role of FATP1 in mitochondrial fatty acid oxidation in skeletal muscle cells.

Carnitine palmitoyltransferase 1 (CPT1) catalyzes the first step in long-chain fatty acid import into mitochondria, and it is believed to be rate limiting for beta-oxidation of fatty acids. However, in muscle, other proteins may collaborate with CPT1. Fatty acid translocase/CD36 (FAT/CD36) may interact with CPT1 and contribute to fatty acid import into mitochondria in muscle. Here, we demonstrate that another membrane-bound fatty acid binding protein, fatty acid transport protein 1 (FATP1), collaborates with CPT1 for fatty acid import into mitochondria. Overexpression of FATP1 using adenovirus in L6E9 myotubes increased both fatty acid oxidation and palmitate esterification into triacylglycerides. Moreover, immunocytochemistry assays in transfected L6E9 myotubes showed that FATP1 was present in mitochondria and coimmunoprecipitated with CPT1 in L6E9 myotubes and rat skeletal muscle in vivo. The cooverexpression of FATP1 and CPT1 also enhanced mitochondrial fatty acid oxidation, similar to the cooverexpression of FAT/CD36 and CPT1. However, etomoxir, an irreversible inhibitor of CPT1, blocked all these effects. These data reveal that FATP1, like FAT/CD36, is associated with mitochondria and has a role in mitochondrial oxidation of fatty acids.