The sensor of the bacterial histidine kinase CpxA is a novel dimer of extracytoplasmic Per-ARNT-Sim domains.

Histidine kinases are key bacterial sensors that recognize diverse environmental stimuli. While mechanisms of phosphorylation and phosphotransfer by cytoplasmic kinase domains are relatively well-characterized, the ways in which extracytoplasmic sensor domains regulate activation remain mysterious. The Cpx envelope stress response is a conserved Gram-negative two-component system which is controlled by the sensor kinase CpxA. We report the structure of the Escherichia coli CpxA sensor domain (CpxA-SD) as a globular Per-ARNT-Sim (PAS)-like fold highly similar to that of Vibrio parahaemolyticus CpxA as determined by X-ray crystallography. Because sensor kinase dimerization is important for signaling, we used AlphaFold2 to model CpxA-SD in the context of its connected transmembrane domains, which yielded a novel dimer of PAS domains possessing a distinct dimer organization compared to previously characterized sensor domains. Gain of function cpxA∗ alleles map to the dimer interface, and mutation of other residues in this region also leads to constitutive activation. CpxA activation can be suppressed by mutations that restore inter-monomer interactions, suggesting that inhibitory interactions between CpxA-SD monomers are the major point of control for CpxA activation and signaling. Searching through hundreds of structural homologs revealed the sensor domain of Pseudomonas aeruginosa sensor kinase PfeS as the only PAS structure in the same novel dimer orientation as CpxA, suggesting that our dimer orientation may be utilized by other extracytoplasmic PAS domains. Overall, our findings provide insight into the diversity of the organization of PAS sensory domains and how they regulate sensor kinase activation.

[Scores obtained by physicians in the national health services admission contest between 2016 and 2020]. / Resultados del sistema de puntuación del Concurso Nacional de Ingreso a los Servicios de Salud entre 2016 y 2020.

BACKGROUND: Medical specialists are an essential resource for the functioning of the health system and in Chile there is a growing deficit of these specialists. To address this shortage, the government has strategies for training health professionals, such as a national public contest for medical scholarships, named CONISS, which stands out for its high capacity to produce medical specialists. The scoring system of this contest is used for the allocation of training resources to the best candidates. AIM: To describe the results of the CONISS scoring system between 2016 and 2020. MATERIAL AND METHODS: Analysis of public registries of physicians participating in the CONISS contest between 2016 and 2020. RESULTS: During the study period 7,373 physicians participated in this contest (49% females). Annual participation increased progressively. The participants graduated from 21 Chilean universities and a variable number from foreign universities. The scores obtained by participants improved by 1.47 points between the first and last year of the study period. CONCLUSIONS: Interpretation of these results is complicated by the characteristics and limitations of the measurements of the CONISS scoring system. This precludes establishing whether this system effectively filters out the best candidates for medical specialization programs.

Limosilactobacillus balticus sp. nov., Limosilactobacillus agrestis sp. nov., Limosilactobacillus albertensis sp. nov., Limosilactobacillus rudii sp. nov. and Limosilactobacillus fastidiosus sp. nov., five novel Limosilactobacillus species isolated from the vertebrate gastrointestinal tract, and proposal of six subspecies of Limosilactobacillus reuteri adapted to the gastrointestinal tract of specific vertebrate hosts.

Ten strains, BG-AF3-AT, pH52_RY, WF-MT5-AT, BG-MG3-A, Lr3000T, RRLNB_1_1, STM3_1T, STM2_1, WF-MO7-1T and WF-MA3-C, were isolated from intestinal or faecal samples of rodents, pheasant and primate. 16S rRNA gene analysis identified them as Limosilactobacillus reuteri. However, average nucleotide identity and digital DNA-DNA hybridization values based on whole genomes were below 95 and 70 %, respectively, and thus below the threshold levels for bacterial species delineation. Based on genomic, chemotaxonomic and morphological analyses, we propose five novel species with the names Limosilactobacillus balticus sp. nov. (type strain BG-AF3-AT=DSM 110574T=LMG 31633T), Limosilactobacillus agrestis sp. nov. (type strain WF-MT5-AT=DSM 110569T=LMG 31629T), Limosilactobacillus albertensis sp. nov. (type strain Lr3000T=DSM 110573T=LMG 31632T), Limosilactobacillus rudii sp. nov. (type strain STM3_1T=DSM 110572T=LMG 31631T) and Limosilactobacillus fastidiosus sp. nov. (type strain WF-MO7-1T=DSM 110576T=LMG 31630T). Core genome phylogeny and experimental evidence of host adaptation of strains of L. reuteri further provide a strong rationale to consider a number of distinct lineages within this species as subspecies. Here we propose six subspecies of L. reuteri: L. reuteri subsp. kinnaridis subsp. nov. (type strain AP3T=DSM 110703T=LMG 31724T), L. reuteri subsp. porcinus subsp. nov. (type strain 3c6T=DSM 110571T=LMG 31635T), L. reuteri subsp. murium subsp. nov. (type strain lpuph1T=DSM 110570T=LMG 31634T), L. reuteri subsp. reuteri subsp. nov. (type strain F 275T=DSM 20016T=ATCC 23272T), L. reuteri subsp. suis subsp. nov. (type strain 1063T=ATCC 53608T=LMG 31752T) and L. reuteri subsp. rodentium subsp. nov. (type strain 100-23T=DSM 17509T=CIP 109821T).

Effect of photobiomodulation therapy on performance and running economy in runners: A randomized double-blinded placebo-controlled trial.

The objective of this study was to evaluate effects of photobiomodulation therapy (PBMT) on the 3000 m running performance (primary outcome), running economy (RE), metabolic cost and ratings of perceived exertion during running (secondary outcomes). Twenty male endurance athletes performed 4-min treadmill rectangular test at 12 km.h-1 monitored by a gas analyser. After that, PBMT or placebo in each lower limb was applied, followed performed a maximum test of 3000 m. Immediately after 3000 m test, the athletes repeated the treadmill test. Another application of PBMT/placebo was done after the treadmill test, and athletes went back to the laboratory 24 h later to repeat the treadmill test. After a 72 h interval, athletes repeated all procedures with another treatment intervention (PBMT/placebo). Athletes performed the 3000 m running test ~7s faster when treated with PBMT with similar effort score compared placebo condition. The RE remains unchanged immediately post 3000 m running test, nonetheless RE measured post-24 h improved by 5% with PBMT application without changes in metabolic cost. The PBMT pre- and post-conditioning enhanced the 3000 m running performance and improved RE 24 h following the 3000 m test. However, no changes on ratings of perceived exertion and metabolic cost with the application of PBMT.

Genetic differentiation in East African ethnicities and its relationship with endurance running success.

Since the 1960s, East African athletes, mainly from Kenya and Ethiopia, have dominated long-distance running events in both the male and female categories. Further demographic studies have shown that two ethnic groups are overrepresented among elite endurance runners in each of these countries: the Kalenjin, from Kenya, and the Oromo, from Ethiopia, raising the possibility that this dominance results from genetic or/and cultural factors. However, looking at the life history of these athletes or at loci previously associated with endurance athletic performance, no compelling explanation has emerged. Here, we used a population approach to identify peaks of genetic differentiation for these two ethnicities and compared the list of genes close to these regions with a list, manually curated by us, of genes that have been associated with traits possibly relevant to endurance running in GWAS studies, and found a significant enrichment in both populations (Kalenjin, P = 0.048, and Oromo, P = 1.6x10-5). Those traits are mainly related to anthropometry, circulatory and respiratory systems, energy metabolism, and calcium homeostasis. Our results reinforce the notion that endurance running is a systemic activity with a complex genetic architecture, and indicate new candidate genes for future studies. Finally, we argue that a deterministic relationship between genetics and sports must be avoided, as it is both scientifically incorrect and prone to reinforcing population (racial) stereotyping.

[Indications and results of liver retransplantation: experience with 1181 patients at the University Hospital La Fe]. / Indicaciones y resultados de retrasplante hepático: experiencia del hospital universitario La Fe (1.181 pacientes).

UNLABELLED: Liver retransplantation (LrT) is the only therapeutic option for irreversible failure of a hepatic graft and accounts for 2.9%-24.0% of all liver transplantations (LT). It is technically difficult and has a high level of immediate morbidity and a lower survival than primary LT. Our aim was to determine the rate of LrT and its indications, morbidity, post-operative mortality and actuarial survival in the retransplanted patient. PATIENTS AND METHOD: A historical cohort study of 1181 patients transplanted between 1991 and 2006. RESULTS: Of the 1260 LT performed, 79 were LrT. At the time of the first LT there were no differences between those patients and those that did not require an LrT. The LrT rate was 6.3% and the most frequent causes were: hepatic artery thrombosis (31.6%), recurrence of cirrhosis due the HVC (30.4%) and primary graft (21.5%). The ischemia times, perfusion syndrome and hepatic congestion were no different between the primary LT and the LrT. On the other hand, red cell transfusions were higher in LrT (6.3+/-4.9 vs. 3.5+/-3.0 units, P<0.001). The post-operative morbidity and morbidity (up to 30 days after the LT) was higher in retransplanted patients (68.4% vs. 57.0%, P=0.04 and 25.3% vs. 10.9%, P<0.001; respectively). The actuarial survival at 1 and 5 years was 83% and 69% in those without LrT, 71% and 61% in early LrT and 64% and 34% in delayed LrT (P<0.001). CONCLUSIONS: Despite the increased morbidity and mortality of LrT, it appears that this treatment alternative is still valid in those patients with an early loss of the liver graft. On the other hand, when the graft loss is delayed, it needs to be defined, what would be the minimum acceptable results to indicate LrT and which patients could benefit from this treatment.

Expanded criteria for liver transplantation in patients with cirrhosis and hepatocellular carcinoma.

Orthotopic liver transplantation (OLT) selection for patients with hepatocellular carcinoma (HCC) is a matter of debate. The Milan criteria (MC) have been largely adopted by the international community. The main aim of this study was to evaluate the survival rates and recurrence probabilities of a new proposal for criteria (up to 3 tumors, each no larger than 5 cm, and a cumulative tumor burden

Resultados del sistema de puntuación del Concurso Nacional de Ingreso a los Servicios de Salud entre 2016 y 2020 / Scores obtained by physicians in the national health services admission contest between 2016 and 2020

BACKGROUND: Medical specialists are an essential resource for the functioning of the health system and in Chile there is a growing deficit of these specialists. To address this shortage, the government has strategies for training health professionals, such as a national public contest for medical scholarships, named CONISS, which stands out for its high capacity to produce medical specialists. The scoring system of this contest is used for the allocation of training resources to the best candidates. AIM: To describe the results of the CONISS scoring system between 2016 and 2020. MATERIAL AND METHODS: Analysis of public registries of physicians participating in the CONISS contest between 2016 and 2020. RESULTS: During the study period 7,373 physicians participated in this contest (49% females). Annual participation increased progressively. The participants graduated from 21 Chilean universities and a variable number from foreign universities. The scores obtained by participants improved by 1.47 points between the first and last year of the study period. CONCLUSIONS: Interpretation of these results is complicated by the characteristics and limitations of the measurements of the CONISS scoring system. This precludes establishing whether this system effectively filters out the best candidates for medical specialization programs.

Diagnostic properties of a symptoms scale for diagnosing reflux esophagitis.

OBJECTIVE: To the objective of the study was to determine accuracy and predictive values of a symptoms scale for diagnosing reflux esophagitis (RE). STUDY DESIGN AND SETTING: Standard criterion study. All recruited patients from two centers in Chile underwent both digestive endoscopy (reference standard) and a symptoms scale known to be valid and reliable for diagnosing gastroesophageal reflux disease. The RE variable was dealt with dichotomously. A receiver operating characteristic curve was constructed. Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of the scale were calculated. RESULTS: Two hundred and thirty eight (238) subjects (57.6% female), with an average age of 44.2+/-13.0 years were included. Of these, 57.1% presented with RE. With a cut-off score of six, association was confirmed between the symptoms scale and RE with an odds ratio of 7.26 and a correct classification i.e. diagnostic accuracy of 73.1%. Sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, of 74.3%, 71.6%, 77.7%, 67.6%, 2.61, and 0.36 respectively, were obtained. CONCLUSION: A seven-item symptoms scale when compared to endoscopy as gold standard was useful for diagnosing RE. Using a cutoff of six points, the diagnostic accuracy of the scale was 73.1%.

[Liver transplant in patients with hepatocellular carcinoma]. / Trasplante hepático en pacientes con carcinoma hepatocelular.

Liver transplant in patients with cirrhosis and hepatocellular carcinoma is indicated in the early stages of the disease, which can be achieved with early detection programs using liver ultrasound. Dynamic imaging techniques (ultrasound with contrast, magnetic resonance and tomography) are essential in the diagnosis of this tumour, being able to type the lesion clearly, and, in the majority of cases, lead to the therapy to follow. Surgery is the treatment of choice in these patients, and liver transplant, from a theoretical point of view, is the best. Currently, the size and number of nodes play an important role in the indication of a transplant. The best liver transplant results are obtained in these patients using the Milan criteria, with survivals that exceed 70% and recurrence indices of 15%, at 5 years. Nowadays we have the possibility of using neo-adjuvant treatments to transplant, such as arterial chemoembolisation, percutaneous ablation techniques, and even liver resection as a bridging technique. The survival of patients transplanted due to liver cancer is similar to that obtained for other non-tumour diseases. In Spain it is 1, 3 and 5 years and 82%, 70% and 60%, respectively. The recurrence is between 6.4% and 16%, micro- and macrovascular invasion being its highest risk variable.

[Liver transplantation in patients with benign hepatic lesions]. / Trasplante hepático en pacientes con lesiones hepáticas benignas.

Benign hepatic lesions are rare and liver transplantation in these cases is exceptional. We present a review of the subject, commenting on the aspects that have been subsidiary to liver transplantation, of which are highlighted: adenomatosis, polycystosis and hepatic epithelioid haemangioendothelioma (although this process may be a low to intermediate malignant grade). We assessed specific epidemiological, aetiopathogenic, clinical, diagnostic, therapeutic and aspects of the lesions as well as indication for transplantation, and the experiences of different authors on these pathologies.

Iniciativas disponibles para el reporte de resultados en investigación biomédica con diferentes tipos de diseño / Initiatives for reporting biomedical research results with different types of designs

La calidad del reporte de los resultados de una investigación no es óptima, razón por la cual, se han desarrollado numerosas iniciativas tendientes a mejorar este aspecto a lo largo de los años. El objetivo de este artículo es mencionar y describir las iniciativas existentes para el reporte de resultados de investigación biomédica en diversos escenarios de investigación clínica y situaciones especiales. Se realizó una búsqueda en las bases de datos THE COCHRANE LIBRARY, MEDLINE, SciELO y Redalyc; y en los buscadores Clinical Evidence, TRIP database, Fisterra, Rafabravo, EQUATOR Network, portal de BIREME y Programa HINARI; para obtener las listas de verificación existentes. Los documentos recuperados fueron agrupados de la siguiente forma: relacionados con escenarios de terapia, diagnóstico, pronóstico, evaluaciones económicas y misceláneas. La búsqueda generó un total de 31 documentos. Doce para escenarios de terapia (CONSORT, QUOROM, MOOSE, STRICTA, TREND, MINCIR-Terapia, RedHot, REHBaR, PRISMA, REFLECT, Ottawa y SPIRIT), 5 para diagnóstico (STARD, QUADAS, QAREL, GRRAS y MINCIR-Diagnóstico), 3 para pronóstico (REMARK, MINCIR-Pronóstico y GRIPS), 4 para evaluaciones económicas (NHS-HTA, CHEERS, ISPOR RCT-CEA y NICE-STA,); y 7 misceláneos (STROBE, COREQ, GRADE, SQUIRE, STREGA, ORION y MINCIR-EOD). Existen diversas iniciativas y declaraciones. Estas deben ser conocidas y utilizadas por escritores, revisores y editores de revistas biomédicas; de forma tal de incrementar la calidad del reporte de resultados de la investigación biomédica.

Quality of results reporting is not perfect, many initiatives tending to improve this aspect of clinical research have been developed in the last decade. The aim of this manuscript is to mention and describe the existent initiatives for reporting biomedical research results in different scenarios and special situations. To obtain check-lists, a search in THE COCHRANE LIBRARY, MEDLINE, SciELO y Redalyc; Clinical Evidence, TRIP database, Fisterra, Rafabravo, EQUATOR Network, BIREME and HINARI Program was developed. Identified documents were grouped in relation with clinical research scenarios (therapy, diagnosis, prognosis and economic evaluations) and miscellaneous. The search allows finding 31 documents. Twelve for therapy (CONSORT, QUOROM, MOOSE,STRICTA, TREND, MINCIR-Therapy, RedHot, REHBaR, PRISMA,REFLECT, Ottawa and SPIRIT), 5 for diagnosis (STARD, QUADAS, QAREL, GRRAS and MINCIR-Diagnosis), 3 for prognosis (REMARK, MINCIR-Prognosis and GRIPS), 4 for economic evaluations (NHS-HTA, CHEERS, ISPOR RCT-CEA and NICE-STA,) and 7 miscellaneous (STROBE, COREQ, GRADE, SQUIRE, STREGA, ORION and MINCIR-EOD). Different initiatives and statements were found. These must be noted and used by writers, reviewers and editors of biomedical journals, in order to improve the quality of reporting results.

[Indications and results of liver retransplantations]. / Indicaciones y resultados del retrasplante hepático.

Liver retransplantation (re-LT) is the only therapeutic option for irreversible failure of the graft. It currently makes up 2.9% to 24.0% of all liver transplants. It is technically very difficult and has a high index of immediate complications, underlined by the fact that 50% of the deaths after this procedure occur in the first three months; and that in general, the results of re-LT are worse than those of primary LT. Re-LT can be early (when it is performed during the first 30 days) or delayed. The reasons for early re-LT are: loss of primary function of the graft, complications for technical reasons, acute resistant rejection and infection problems of biliary origin. Those of delayed are: chronic rejection, liver arterial thrombosis, biliary complications and recurrence of the primary disease. In general, when a patient has an irreversible rejection of the graft, the indication for a re-LT is indisputable, but there are discrepancies on whether or not the aetiology of the basic disease has to have a bearing on this. If we take into account the MELD scoring system, when considering the indications for re-LT, this only allows us to predict mortality, but not to give priority on a waiting list. Patients must be retransplanted early, in good physical condition, with a low bilirubin and creatine level; and the donors must be young. Taking into account the continuing increase in mortality as a direct result of the imbalance between the growing number of potential candidates and the number of donors, it seems necessary to define what are the minimally accepted results to indicate a re-LT and thus arrive at a consensus that will help us decide which subject is a candidate to receive it.