Unraveling the crystal structure of the HpaA adhesin: insights into cell adhesion function and epitope localization of a Helicobacter pylori vaccine candidate.

Helicobacter pylori is a bacterium that exhibits strict host restriction to humans and non-human primates, and the bacterium is widely acknowledged as a significant etiological factor in the development of chronic gastritis, peptic ulcers, and gastric cancers. The pathogenic potential of this organism lies in its adeptness at colonizing the gastric mucosa, which is facilitated by a diverse repertoire of virulence factors, including adhesins that promote the attachment of the bacteria to the gastric epithelium. Among these adhesins, HpaA stands out due to its conserved nature and pivotal role in establishing H. pylori colonization. Moreover, this lipoprotein holds promise as an antigen for the development of effective H. pylori vaccines, thus attracting considerable attention for in-depth investigations into its molecular function and identification of binding determinants. Here, we present the elucidation of the crystallographic structure of HpaA at 2.9 Å resolution. The folding adopts an elongated protein shape, which is distinctive to the Helicobacteraceae family, and features an apical domain extension that plays a critical role in the cell-adhesion activity on gastric epithelial cells. Our study also demonstrates the ability of HpaA to induce TNF-α expression in macrophages, highlighting a novel role as an immunoregulatory effector promoting the pro-inflammatory response in vitro. These findings not only contribute to a deeper comprehension of the multifaceted role of HpaA in H. pylori pathogenesis but also establish a fundamental basis for the design and development of structure-based derivatives, aimed at enhancing the efficacy of H. pylori vaccines. IMPORTANCE: Helicobacter pylori is a bacterium that can cause chronic gastritis, peptic ulcers, and gastric cancers. The bacterium adheres to the lining of the stomach using proteins called adhesins. One of these proteins, HpaA, is particularly important for H. pylori colonization and is considered a promising vaccine candidate against H. pylori infections. In this work, we determined the atomic structure of HpaA, identifying a characteristic protein fold to the Helicobacter family and delineating specific amino acids that are crucial to support the attachment to the gastric cells. Additionally, we discovered that HpaA can trigger the production of TNF-α, a proinflammatory molecule, in macrophages. These findings provide valuable insights into how H. pylori causes disease and suggest that HpaA has a dual role in both attachment and immune activation. This knowledge could contribute to the development of improved vaccine strategies for preventing H. pylori infections.

Neuropsychology of Generalized Anxiety Disorder in Clinical Setting: A Systematic Evaluation.

This research paper provides a systematic review of the neuropsychology of generalized anxiety disorder (GAD), examining relevant articles' methodologies and subject matter and highlighting key findings. It suggests potential cognitive deficits in GAD patients, such as subtle attention, executive function, and working memory deficiencies. It also discusses neural correlates of GAD, particularly the hyperactivity in the amygdala and insula, and the additional impact of comorbidity with other psychiatric disorders. The paper uses the PRISMA methodology and draws data from the PsycINFO, Scopus, PubMed, and Elsevier databases. Although the reviewed research has contributed to understanding GAD's cognitive and neural mechanisms, further research is required. Additionally, the paper mentions the clinical neuropsychology of GAD, including strategies and treatments, such as cognitive behavioral therapy (CBT), mindfulness, and medication. Lastly, the review identifies the limitations of the existing research and recommends future directions to enhance the understanding of GAD's underlying cognitive and neural mechanisms. The neural underpinnings of GAD encompass heightened activity within the amygdala and insula, which are brain regions implicated in processing adverse emotional reactions. Co-occurring psychiatric disorders, such as major depressive disorder (MDD), can also impact neuropsychological functioning. Additional investigation is warranted to better understand the intricate interplay between GAD, cognitive performance, and underlying neural processes.

Reduction of Instrumentation-Related Spine Surgical Site Infections After Optimization of Surgical Techniques. A Single Center Retrospective Analysis.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Although surgical risk factors for developing spine surgical site infections (S-SSI) have been identified, the impact of such knowledge in its prevention has not been demonstrated. METHODS: We evaluated in 500 patients undergoing spine surgery between 2011 and 2019 at Hospital 12 de Octubre the changes in S-SSI rates over time. Surgical variables independently related to S-SSI were analyzed by univariate and multivariate analysis using binary logistic regression models. A case-control sub-analysis (1:4), matched by the surgical variables identified in the overall cohort was also performed. RESULTS: Twenty cases of S-SSI were identified (4%), with a significant decrease in the incidence rate across consecutive time periods (6.6% [2011-2014] vs .86% [2015-2019]; P-value <.0001)). Multivariate analysis identified arthrodesis involving sacral levels (odds ratio [OR]: 2.57; 95% confidence interval [95%CI]: 1.02-6.47; P-value = .044) and instrumentation over 4-8 vertebrae (OR: 2.82; 95%CI: 1.1-7.1; P-value = .027) as independent risk factors for S-SSI. The reduction in the incidence of S-SSI concurred temporally with a reduction in instrumentations involving 4-8 vertebrae (55% vs 21.8%; P-value <.0001) and sacral vertebrae (46.9% vs 24.6%; P-value <.0001) across both periods. The case-control analysis matched by these surgical variables failed to identify other factors independently related to the occurrence of S-SSI. CONCLUSIONS: Spinal fusion of more than 4 levels and the inclusion of sacral levels were independently related to the risk of S-SSI. Optimization of surgical techniques by reducing these two types of instrumentation could significantly reduce S-SSI rates.

Trophic structure of benthic communities in a Chilean fjord (45°S) influenced by salmon aquaculture: Insights from stable isotopic signatures.

Benthic marine food webs, which recycle organic matter and sustain unique biodiversity, are an important component of estuarine Patagonian fjords; however, these may be heavily influenced by salmon farming activities. Under the above conditions, this study collected several food sources (sediment organic matter, suspended particulate organic matter, macroalgae) and 26 benthic invertebrate species, and analyzed them using a Bayesian mixing model. Briefly, carbon and nitrogen stable isotopes analyses revealed that the highly variable isotopic niche widths respond to food supplies from marine and terrestrial organic matter. In addition, particulate and dissolved waste from salmon farming activities were found to modify isotopic composition ratios in many suspension feeders. Particularly, our results indicate high δ15N values in the sponge Cliona chilensis and the encrusting coral Incrustatus comauensis, which appear to be potential ecological indicators for evaluating stoichiometry imbalances and trace organic pollution sources in fjord environments.

Population Pharmacokinetics of Vancomycin and Meropenem in Pediatric Extracorporeal Membrane Oxygenation Support.

Objective: Describe primary pharmacokinetic/pharmacodynamic (PK/PD) parameters of vancomycin and meropenem in pediatric patients undergoing ECMO and analyze utilized dosing to reach PK/PD target. Design: Prospective, multicentric, population PK analysis. Setting: Two hospitals with pediatric intensive care unit. Patients: Pediatric patients (1 month - 15 years old) receiving vancomycin and meropenem for empiric or definitive infection treatment while ECMO support. Measurements and Main Results: Four serum concentration were obtained for patients receiving vancomycin (n = 9) and three for meropenem (n = 9). The PK/PD target for vancomycin was a ratio of the area under the curve to the minimal inhibitory concentration (AUC/MIC) of >400, and for meropenem was 4 times above MIC for 50% of the dosing interval (fT50% > 4xMIC). Pharmacokinetic modeling was performed using PMetrics 1.5.0. We included nine patients, with 11 PK profiles for each antimicrobial. The median age of patients was 4 years old (2 months - 13 years) and 45% were male. Creatinine clearance (CL) was 183 (30-550) ml/min/1.73 m2. The median dose was 13.6 (range 10-15) mg/kg every 6-12 h and 40 mg/kg every 8-12 h for vancomycin and meropenem, respectively. Two compartment models were fitted. Weight was included as a covariate on volume of the central compartment (Vc) for meropenem. Weight was included as a covariate on both Vc and clearance (CL) and serum creatinine was also included as a covariate on CL for vancomycin. The pharmacokinetic parameters CL and Vc were 0.139 ± 0.102 L/h/kg and 0.289 ± 0.295 L/kg for meropenem and 0.060 ± 0.055 L/h/kg and 0.419 ± 0.280 L/kg for vancomycin, respectively. Across each dosing interval 91% of patients achieved the PK/PD targets for adequate exposure for meropenem and 63.6% for vancomycin. Conclusion: Pharmacokinetic/pharmacodynamic objectives for vancomycin were achieved partially with conventional doses and higher dosing with extended infusion were needed in the case of meropenem.

Guía de recomendaciones para el manejo de pacientes pediátricos con enfermedad severa por SARS-CoV-2 / Recommendations guide for the management of pediatric patients with severe SARS-CoV-2

Resumen: La aparición del SARS-CoV-2 a partir de diciembre de 2019 y su rápida expansión en el mundo alcanzando el estatus de Pandemia, se ha convertido en un gran desafío para los equipos de salud. Aunque la evidencia de la infección en niños aún es escasa comparada a la de los adultos, se ha hecho evidente que a nivel de la población pediátrica, la mayor parte de las veces la infección es asintomática o de curso leve, sin embargo no todos los pacientes tienen esta evolución, lo que ha motivado la discusión en los equipos de Cuidados Criticos Pediátricos respecto a cómo enfrentar estos pacientes con enfermedad grave. Este consenso es fruto del trabajo de la Rama de Cuidados Intensivos Pe diátricos de la Sociedad Chilena de Pediatría, recogiendo la evidencia disponible al momento de la revisión más la opinión de expertos nacionales en Cuidados Intensivos Pediátricos. El propósito de estas recomendaciones, es ofrecer a los equipos que atienden a pacientes críticos pediátricos, una guía para el diagnóstico y tratamiento de pacientes que evolucionen con COVID 19 grave, que puedan ser aplicadas en todas las UPC Pediátricas de nuestro país, haciendo especial énfasis en aquellas medidas que han demostrado mayor efectividad a nivel de estudios diagnósticos, tratamiento y cuidados del personal de salud.

Abstract: The appearance of SARS-CoV-2 from December 2019 and its rapid expansion in the world reaching Pandemic status, has become a great challenge for health teams. Although the evidence of infection in children is still scarce compared to that of adults, it has become evident that at the pediatric po pulation level, most of the time the infection is asymptomatic or mild, but not all the patients have this evolution, which has motivated the discussion in the Pediatric Critical Care teams regarding how to face these patients with a more serious disease. This consensus is the result of the work of the Pediatric Intensive Care Branch of the Chilean Society of Pediatrics, collecting the evidence available at the time of the review plus the opinion of national experts in Pediatric Intensive Care. The purpose of these recommendations is to offer teams that care for critically ill pediatric patients a guide for the diagnosis and treatment of patients who evolve with severe COVID 19, which can be applied in all Pediatric UPCs in our country, with special emphasis in those measures that have shown greater effectiveness at the level of diagnostic studies, treatment and care of health personnel.

Association of salivary alpha-amylase and salivary flow rate with working memory functioning in healthy children.

The aim of this study was to examine the association between auditory and visual working memory (WM) performance and salivary alpha-amylase (sAA) and salivary flow rate (SFR) in a sample of 63 children (38 boys). WM was assessed by means of WISC-V subtests: four auditory subtests (Digit Span and Letter-Number Sequencing) and one visual subtest (Picture Span). SAA activity, output, and SFR were measured at baseline (10 min prior to testing), one minute prior to testing, one minute after the end of the auditory WM subtests and one minute after the end of the visual WM subtest. Our statistical analyses showed an association among SAA activity, output and SFR levels and the number of recalled digits in the last attempt score in Letter-Number Sequencing subtest. Specifically, our results showed that working performance in this task was associated with a concurrent decrease in SFR (r(63) = -0.423, p < .05). This salivary measure was the best predictor of this specific index of working memory performance (ß = -0.423, p < .05). These results show that the changes in SFR, which represents changes in parasympathetic tone, could be employed in future studies as a noninvasive marker of working memory performance in child studies.

Association between Salivary Alpha-Amylase and Executive Functioning in Healthy Children.

The main aim of this study was to confirm the relationship between executive performance and salivary alpha-amylase (SAA) activity in a sample of 64 healthy children (39 boys), and compare it to the association of SAA output and salivary flow rate (SFR). Executive functioning was assessed via fluency, trail-making, rings and inhibition tasks from the Batería de Evaluación Neuropsicológica de la Función Ejecutiva en Niños [Battery of Neuropsychological Assessment for Executive Function in Children] (ENFEN), merged into an ENFEN total score. SAA activity, output, and SFR were measured at baseline, one minute before, and one minute after the end of a neuropsychological testing session. Our results confirmed a direct, linear and significant association between SAA activity and executive functioning, r(64) = .351, p < .05, and extended it to SAA output, r(64) =.431, p < .05. The mean level of SAA output was the best predictor of executive functioning (ß = .431, p < .05) and explained 18.2 % of the variance in ENFEN total score. In sum, and compared to SAA activity, measuring SAA output may be a more precise and indirect marker to assess executive functioning in children.

Association between salivary alpha-amylase and executive functioning in healthy children

The main aim of this study was to confirm the relationship between executive performance and salivary alpha-amylase (SAA) activity in a sample of 64 healthy children (39 boys), and compare it to the association of SAA output and salivary flow rate (SFR). Executive functioning was assessed via fluency, trail-making, rings and inhibition tasks from the Batería de Evaluación Neuropsicológica de la Función Ejecutiva en Niños [Battery of Neuropsychological Assessment for Executive Function in Children] (ENFEN), merged into an ENFEN total score. SAA activity, output, and SFR were measured at baseline, one minute before, and one minute after the end of a neuropsychological testing session. Our results confirmed a direct, linear and significant association between SAA activity and executive functioning, r(64) = .351, p < .05, and extended it to SAA output, r(64) =.431, p < .05. The mean level of SAA output was the best predictor of executive functioning (β = .431, p < .05) and explained 18.2 % of the variance in ENFEN total score. In sum, and compared to SAA activity, measuring SAA output may be a more precise and indirect marker to assess executive functioning in children

No disponible

A national telemedicine network for retinopathy of prematurity screening.

PURPOSE: To report the results of retinopathy of prematurity (ROP) screening by a telemedicine system in Chile and evaluate its usefulness for referring patients who require treatment. METHODS: Premature infants at risk of developing ROP from 11 neonatal intensive care units were included. Screening was performed on all infants born at a gestational age of <32 weeks and/or birth weight of <1500 g. A trained nonphysician operator used an imaging system to capture retinal images, which were reviewed by two independent ROP experts. All infants that required treatment were referred for further evaluation. RESULTS: The study included 2,048 eyes of 1,024 premature infants. Mean gestational age was 28.8 ± 2.2 weeks, and mean birth weight was 1128 ± 279 g. A total of 5,263 telemedicine examinations were performed and reported. The average number of image sets per patient was 2.6 ± 2.5. Of the 5,263 images, 4,903 (93%) were recorded to at least the end of zone II; 5,172 (98%) were graded as having good quality, allowing for staging of ROP disease. Forty-two infants (4%) were referred for treatment. Discharged patients with ROP type 2 that regressed did not present with any complications or adverse effects during 6 months' follow-up. CONCLUSIONS: Our study demonstrates the utility of telemedicine screening for ROP with ophthalmologist readers in a developing country. Telemedicine screening was able to detect treatment-requiring ROP. Most of the images had good quality and showed the end of zone II, two variables sufficient to discharge patients.

Utilização de enxerto ósseo proveniente de banco de ossos na Implantodontia / Use of bone graft of bone bank in Implantology

Muitas vezes é necessário o uso de enxerto ósseo em cirurgias para instalação de implantes. A utilização de ossos homógenos provenientes de banco de ossos passou a despertar interesse devido inúmeras vantagens em relação aos outros tipos de enxertos ósseos. O objetivo deste estudo foi realizar uma busca sistemática da literatura para avaliar a utilização de osso homógeno na reabilitação de pacientes com altura e espessura ósseas insuficientes para a instalação de implantes dentários. Os artigos foram procurados através de uma estratégia de busca nas bases de dados eletrônicas Pubmed - Biblioteca nacional de Medicina US, Bireme - Biblioteca virtual em saúde e Biblioteca Cochrane. Foram encontrados 594 estudos, destes 590 foram excluídos após a leitura de títulos de resumos, e 4 foram selecionados para leitura completa do artigo e incluídos. Todos os estudos incluídos foram avaliados em relação à qualidade dos estudos e todos foram classificados com alto risco de viés. Concluiu-se que a utilização de homoenxertos demonstra ser uma ferramenta bastante útil para a Odontologia, com a finalidade de regenerar o tecido ósseo perdido dos maxilares, no entanto, serão necessários estudos futuros com mais critérios metodológicos para verificar os riscos e benefícios em utilizar enxertos de ossos homógenos provenientes de bancos de ossos na instalação de implantes (AU).

Many times the use of bone graft in surgeries for implant placement is necessary. The use of homogenous bone from bone bank began to awaken interest due to numerous advantages over other types of bone grafts. The aim of this study was to perform a systematic literature search to assess the use of homogenous bone in the rehabilitation of patients with insufficient bone height and thickness for the installation of dental implants. Articles were sought through a searching strategy in PubMed electronic databases - National Library of Medicine US, Bireme - Virtual Library in Health and Cochrane Library. As a result, 594 studies were found, 590 were excluded after reading abstract titles, and 4 were selected for complete article reading and were included. All included studies were assessed for their quality and all them were classified as high risk of bias. It was concluded that the use of homografts proves to be a useful tool for Dentistry, in order to regenerate lost bone jaw, however, it will require future studies with more methodological criteria to verify the risks and benefits of using homogenous bone from bone banks in implant placement (AU).

Uso de Bio-Oss® como enxerto em elevação de seio maxilar para instalação de implantes û revisão sistemática / Use of Bio-Oss® as grafting in maxillary sinus elevation for installation of implants û systematic literature search

Muitas vezes para a reabilitação por implantes na região posterior da maxila se faz necessária a elevação do seio maxilar e vários biomateriais podem ser utilizados. Sendo assim, o objetivo do estudo é avaliar, através de uma busca sistemática da literatura, a utilização do Bio-Oss® puro em procedimentos de enxerto em elevação de seio maxilar. A busca sistemática da literatura foi realizada pelos pesquisadores nas bases de dados eletrônica PUBMED (Biblioteca Nacional de Medicina, US), Bireme (Biblioteca Virtual em Saúde) e Biblioteca Cochrane. Os artigos incluídos foram avaliados para grau de qualidade por dois pesquisadores independentes. Seiscentos e vinte e dois artigos foram avaliados, destes, 616 foram excluídos, permanecendo 6 artigos. Dos 6 artigos incluídos todos apresentaram alto viés no grau de qualidade dos estudos. Concluiu-se que apesar do alto viés dos artigos incluídos, devido diversas falhas metodológicas, a busca sistemática da literatura mostrou que o Bio-Oss® é um biomaterial adequado para cirurgias de aumento de seio maxilar...

In order to achieve the rehabilitation using implants in the posterior maxillary region a maxillary sinus elevation is required and for this purpose there are various biomaterials that can be used. Thus, the aim of this study is to evaluate, through a systematic literature search, the use of Bio-Oss® in pure grafting procedures in maxillary sinus elevation. A systematic literature search was conducted in the electronic databases PUBMED (National Library of Medicine, US), Virtual Library Bireme-health and the Cochrane Library. The included articles were assessed for level of quality by two independent researchers. Six hundred and twenty-two articles were evaluated, and 616 of those were excluded, remaining 6 articles. All six articles included showed high degree of bias in the quality of studies. It was concluded that despite the high bias of the articles due to several methodological flaws, this systematic literature search showed that Bio-Oss® is a suitable biomaterial for augmentation of the maxillary sinus surgeries...

Modification of epigenetic patterns in low birth weight children: importance of hypomethylation of the ACE gene promoter.

There is a growing body of evidence that epigenetic alterations are involved in the pathological mechanisms of many chronic disorders linked to fetal programming. Angiotensin-converting enzyme (ACE) appears as one candidate gene that brings new insights into the epigenetic control and later development of diseases. In this view, we have postulated that epigenetic modifications in the ACE gene might show different interactions between birth weight (BW), blood pressure levels, plasma ACE activity and ACE I/D polymorphism. To explore this hypothesis, we performed a cross-sectional study to evaluate the DNA methylation of 3 CpG sites using pyrosequencing within the ACE gene promoter of peripheral blood leukocytes from 45 LBW children compared with 70 NBW children. Our results have revealed that LBW children have lower methylation levels (P<0.001) in parallel with a higher ACE activity (P = 0.001). Adjusting for prematurity, gender, age, body mass index, and family history of cardiovascular disease did not alter these findings. We have also performed analyses of individual CpG sites. The frequency of DNA methylation was significantly different at two CpG sites (site 1: nucleotide position +555; and site 3: nucleotide position +563). In addition, we have found a significant inverse correlation between degree of DNA methylation and both ACE activity (P<0.001) and systolic blood pressure levels (P<0.001). We also observed that the methylation level was significantly lower in LBW children who are carriers of the DD genotype compared to NBW children with DD genotype (P<0.024). In conclusion, we are able to demonstrate that the hypomethylation in the 3 CpG sites of ACE gene promoter is associated with LBW in 6 to 12 year-old children. The magnitude of these epigenetic changes appears to be clinically important, which is supported by the observation that discrete changes in DNA methylation can affect systolic blood pressure and ACE protein activity levels.

Classification of the ecological quality of the Aysen and Baker Fjords (Patagonia, Chile) using biotic indices.

The AZTI's marine biotic index (AMBI), an ecological indicator for managing estuarine and coastal waters worldwide, was tested in two fjords in Chilean Patagonia. The Aysen Fjord (42° Lat. S) supports intensive salmon farming in coastal ecosystems, while the Baker Fjord (48° Lat. S) is currently just beyond the limit of the southern expansion of salmon concessions. The ecological status of the Aysen Fjord was classified as good, while the status of the Baker Fjord was classified as high and unbalanced. These differences were consistent with our expectations, illustrating the effect of local environmental conditions and human activities, combined with river inputs into semi-confined fjords. This method is appropriate for the evaluation of the ecological status of the fjords, but requires a sufficient amount of data for the robust environmental assessment as proposed by the Water Framework Directive (WFD).

Serie de pacientes con artritis reumatoidea tratados con el Sistema Integral de Salud Mokichi Okada / Case series of patients with rheumatoid arthritis treated with Mokichi Okada Style System of Health

Introducción: describir la evolución de siete pacientes con artritis reumatoidea (AR) tratados con el Sistema de Salud Mokichi Okada (SISMO) sumado al tratamiento de dicha entidad clínica...

Introduction: to describe the evolution of seven patients with rheumatoid arthritis (RA) treated with the Mokichi Okada Health System (SISMO) in addition to the treatment of this clinical entity...

Diagnóstico más frecuentemente reportado en estudios ultrasónicos en un centro privado de La Vega / Most frequently reported ultasonographic diagnosis at a private medical center in La Vega

Se realizó un estudio de tipo restrospectivo en pacientes que se le habían hecho estudios sonográficos durante el período 1991-1996 con fines de determinar los diagnósticos más frecuentemente reportados por los mismos, donde de 500 casos investigados el 65.2// resultaron anormales, 34.8// normales, 50.6// de los pacientes resultaron ser del sexo masculino y 49.4// del femenino, un 43// eran casados, los grupos estéreos a los que más se le realizó estudios sonográficos fueron 31-40 años 21//, 51-60 años 17.4//, 21-30 años 16.8//, los antecedentes patológicos familiares más frecuentes fueron enfermedades cardiovasculares 20.6// y enfermedades hepáticas 18//, los antecedentes patológicos personales más frecuentes fueron enfermedades cardiovasculares 18.7// y gastroduodenales 16.8//, los síntomas de presentación más frecuentes fueron: dolor abdominal 46// y flatulencia y/o acidez 16.4//. Los diagnósticos sonográficos más reportados fueron litiasis vesicular 23.9//, gastropatía aguda 22.1//, esteatosis hepática 14.7// y hepatomegalia 8.9//