Insights into estrogen impact in oral health & microbiome in COVID-19.

BACKGROUND: COVID-19 emerged in late 2019 and has occasioned more than 765 millions cumulative cases and 6.9 millions of deaths globally. Notably, around 70% of patients with severe COVID-19 are men. Therefore, it is to be presumed that women have a hormonal protector factor in inflammation and ACE2 expression. On the other hand, oral health status, and local microbiome can be key factors to respiratory viral infections control. Nevertheless, it has been poorly investigated. In our study 20 premenopausal, 18 postmenopausal and 22 men with COVID-19 were included. Oral health status, viral load, lingual ACE2 expression, as well as microbiome, estrogens and cytokines in saliva were analyzed. RESULTS: Our results showed a lower expression of ACE2 in tongue cells of postmenopausal compared with premenopausal (p = 0.05), and a strong negative correlation between saliva estrogen and viral load (r = -0.76; p = 0.001). Respect to IFN-γ (p = 0.05), IL-1ß, TNF-α, IL-18, and IL-23 levels were increased in postmenopausal. Oral microbiome signature of premenopausal was characterized by Prevotella melaninogenica (Log2 = 26.68; p = 1.34e-10), Haemophilus (Log2 = 23.99; p = 2.96e-9), and Alloprevotella (Log2 = 7.92; p = 0.0001). On the other hand, Leptotrichia (Log2 = -18.74; p = 0.001), Tanerella (Log2 = -17.08; p = 0.004), and Clostridiales (Log2 = -2.88; p = 0.04) represented the poor oral health group compared with the adequate group which was enriched with the commensal microorganism Neisseria perflava (Log2 = 26.70; p = 1.74e-7). Furthermore, the high viral load group was characterized by Prevotella nanceiensis (Log2 = 19.60; p = 6.06e-8), Prevotella melaninogenica (Log2 = 21.45; p = 9.59e-6), Alloprevotella (Log2 = 23.50; p = 2.70e-7) and bacteria from the red complex Porphyromonas endodentalis (Log2 = 21.97; p = 1.38e-7). CONCLUSIONS: Postmenopausal and men have a poor oral health status which could be related to a detrimental progression of COVID-19 also linked to a lower expression of ACE2, lower saliva estrogen levels and oral dysbiosis. Nevertheless, functional studies are required for a deeper knowledge.

Engineering properties and optimization of the dehulling process for hairless canary seed.

 This work aimed to determine the engineering properties of hairless canary seeds (Phalaris canariensis L.) of the variety "CDC Maria" and the optimum combination of operating conditions of the dehulling process with a pilot-scale centrifugal dehuller. The engineering properties analyzed in this study were the principal dimensions, length (4.8 mm), width (1.95 mm) and thickness (1.41 mm); geometric mean diameter (2.36 mm); the sphericity (49.2%); apparent and true densities (752 and 1191.47 kg/m3, respectively); the porosity (0.37); 1000 grains weight (7.28 g); angle of repose (15.89°) and the static coefficient of friction (galvanized steel, 0.325; plywood, 0.372; aluminium, 0.316). For the process optimization, a two-variable Doehlert design was used, analyzing the effect of impact dehuller rotor speed (peripheral speed 30.4 to 47.1 m/s) and seed moisture content (10 to 14% d.b.) by maximizing the dehulling ability (DA) and maintaining the production of fines by 3%. Under the experimental conditions of 36.7 m/s (peripheral speed) and 10% d.b. (seed moisture), with a double pass through the dehuller, the optimum value of DA (94%) was obtained, with a fine production of 3%. The optimized dehulling process allows removing a large percentage (98%) of the canary seed hull.

Longitudinal transkingdom gut microbial approach towards decompensation in outpatients with cirrhosis.

OBJECTIVE: First decompensation development is a critical milestone that needs to be predicted. Transkingdom gut microbial interactions, including archaeal methanogens, may be important targets and predictors but a longitudinal approach is needed. DESIGN: Cirrhosis outpatients who provided stool twice were included. Group 1: compensated, group 2: 1 decompensation (decomp), group 3: >1 decompensationwere followed and divided into those who remained stable or decompensated. Bacteria, viral and archaeal presence, α/ß diversity and taxa changes over time adjusted for clinical variables were analysed. Correlation networks between kingdoms were analysed. RESULTS: 157 outpatients (72 group 1, 33 group 2 and 52 group 3) were followed and 28%-47% developed outcomes. Baseline between those who remained stable/developed outcome: While no α/ß diversity differences were seen, commensals were lower and pathobionts were higher in those who decompensated. After decompensation: those experiencing their first decompensation showed greater decrease in α/ß-diversity, bacterial change (↑Lactobacillus spp, Streptococcus parasanguinis and ↓ beneficial Lachnospiraceae and Eubacterium hallii) and viral change (↑Siphoviridae, ↓ Myoviridae) versus those with further decompensation. Archaea: 19% had Methanobacter brevii, which was similar between/within groups. Correlation networks: Baseline archaeal-viral-bacterial networks were denser and more homogeneous in those who decompensated versus the rest. Archaea-bacterial correlations collapsed post first decompensation. Lactobacillus phage Lc Nu and C2-like viruses were negatively linked with beneficial bacteria. CONCLUSION: In this longitudinal study of cirrhosis outpatients, the greatest transkingdom gut microbial changes were seen in those reaching the first decompensation, compared with subsequent decompensating events. A transkingdom approach may refine prediction and provide therapeutic targets to prevent cirrhosis progression.

Non-fitness status of peripheral NK cells defined by decreased NKp30 and perforin, and increased soluble B7H6, in cervical cancer patients.

The NKp30 receptor is one of the three natural cytotoxic receptors reported in NK cells. This receptor is codified by the NCR3 gene, which encodes three isoforms, a consequence of the alternative splicing of exon 4. A greater expression of the three isoforms (A, B, and C), along with low levels of the NKp30 ligand B7H6, has been reported as a positive prognostic factor in different cancer types. Here, in patients with cervical cancer and precursor lesions, we report an altered immune-phenotype, characterized by non-fitness markers, that correlated with increased disease stage, from CIN 1 to FIGO IV. While overall NK cell numbers increased, loss of NKp30+ NK cells, especially in the CD56dim subpopulation, was found. Perforin levels were decreased in these cells. Decreased expression of the NKp30 C isoform and overexpression of soluble B7H6 was found in cervical cancer patients when compared against healthy subjects. PBMCs from healthy subjects downregulated NKp30 isoforms after co-culture with B7H6-expressing tumour cells. Taken together, these findings describe a unique down-modulation or non-fitness status of the immune response in cervical cancer, the understanding of which will be important for the design of novel immunotherapies against this disease.

Impact of bacterial infections and spontaneous bacterial peritonitis prophylaxis on phage-bacterial dynamics in cirrhosis.

BACKGROUND AND AIMS: Gut microbiota, including bacteria and phages, are altered in cirrhosis, but their role during infections and spontaneous bacterial peritonitis (SBP) prophylaxis is unclear. Our aim was determine metagenomic changes in gut bacteria; phages and their linkages centered around Gram-negative and Gram-positive pathobionts in patients with cirrhosis with/without infections or SBP prophylaxis. APPROACH AND RESULTS: We included uninfected (n = 231) and infected (n = 30, SBP n = 19 and urinary tract infection n = 11 before antibiotics) patients who gave stool for bacterial and phage metagenomics. We matched uninfected to infected patients 1:1 on a model for end-stage liver disease (MELD). We also analyzed subgroups of patients with ascites matched on an MELD (n = 73) to patients on SBP prophylaxis (n = 7) and then to SBP infection. Phage and bacterial taxa differences (DESeq2) and correlation networks centered around Escherichia coli and Enterococcus faecium were analyzed. Infections were mostly due to Enterobacteriaceae and Enterococcus spp. On metagenomics, higher fold changes of Enterobacteriaceae members, Enterococcus and Streptococcus spp., and Escherichia phages were seen in infected patients. Correlation networks showed more complex bacteria-phage linkages in infected patients compared with uninfected ones overall and centered around E. coli and E. faecium. SBP prophylaxis induced higher Gram-positive bacteria. In SBP, Enterococcus and Escherichia were higher versus ascites. Correlation networks around E. coli were complex in ascites but sparse with SBP prophylaxis, whereas the reverse was seen with E. faecium. Lytic phages and those associated with antibiotic resistance were correlated with E. faecium. CONCLUSION: In cirrhosis, there are significant changes in phage-bacterial linkages in infected patients and those on SBP prophylaxis compared to the remaining patients. SBP prophylaxis enriches complexity of E. faecium-centered but induces a collapse in E. coli-centered phage-bacterial correlations.

[Public, private, and public-private partnerships to implement One Health as an action to address antimicrobial resistance in ColombiaParcerias públicas, privadas e público-privadas para a implementação da Saúde Única como uma ação contra a resistência a antimicrobianos na Colômbia]. / Alianzas públicas, privadas y público-privadas para implementar Una Salud como acción contra la resistencia antimicrobiana en Colombia.

This article describes the importance of public-private partnerships (PPPs) and public-private coordination to address antimicrobial resistance (AMR) through the One Health approach. These partnerships are developed between governmental actors, private companies, and social organizations to build agendas, decision-making, and the management of projects of common interest. A case study from Colombia is presented. It describes examples of response from the public sector when the World Health Organization (WHO) reported a colistin resistance alert in 2016; from the animal protein production sector under an industry partnership for the rational use of antimicrobials; and, finally, from a public-private partnership in the swine sector, with governmental institutions and international cooperation, to take action to mitigate the risk of AMR. In Colombia, the establishment of partnerships with organizations representing agricultural producers has generated impactful actions such as strengthening ongoing communication channels between the public and private sectors; characterizing the conditions of the agricultural production chain; establishing mechanisms for consultation and validation of health policies related to AMR; obtaining a baseline of indicator pathogens and identification of possible flows of AMR spread; and, finally, achieving knowledge transfer and capacity-building with national and international experts, with actions to raise awareness about the problem of AMR and its impact on public health. The strategic model developed in Colombia through public-private collaboration can inspire other low- and middle-income countries to optimize their use of resources to obtain results that contribute to the national AMR mitigation plan.

Este artigo descreve a importância das parcerias públicas e das parcerias privadas (PPP) e da articulação público-privada no enfrentamento da resistência a antimicrobianos (RAM) utilizando a abordagem de Saúde Única. Essas parcerias são formadas entre atores governamentais, empresas privadas e organizações sociais para elaborar agendas, tomar decisões e gerir projetos de interesse comum. Este artigo apresenta um estudo de caso da Colômbia, no qual são apresentados exemplos do setor público diante do alerta de resistência à colistina emitido pela Organização Mundial da Saúde (OMS) em 2016, a formação de uma aliança intersetorial pelos setores de produção de proteína animal para promover o uso racional de antimicrobianos e, por último, a formação de uma parceria público-privada composta pelo setor suinícola e por instituições governamentais e cooperação internacional para que a implementação de medidas de mitigação do risco de RAM. Na Colômbia, a criação de parcerias com organizações representantes dos setores de produção agropecuária geraram ações de impacto, como o fortalecimento de canais permanentes de comunicação entre os setores público e privado, a caracterização das condições da cadeia de produção agropecuária, o estabelecimento de mecanismos de consulta e validação das políticas de saúde voltadas para a RAM, a obtenção de uma linha de base de patógenos indicadores e identificação de possíveis fluxos de propagação de RAM e, por fim, a transferência de conhecimentos e capacitação envolvendo especialistas nacionais e internacionais, com ações de conscientização sobre o problema e seu impacto na saúde pública. O modelo estratégico desenvolvido na Colômbia por meio da colaboração público-privada pode inspirar outros países de baixa e média renda a obter resultados, pela otimização de recursos, que contribuam para o plano nacional de mitigação da RAM.

Association of serum metabolites and gut microbiota at hospital admission with nosocomial infection development in patients with cirrhosis.

Cirrhosis is complicated by a high rate of nosocomial infections (NIs), which result in poor outcomes and are challenging to predict using clinical variables alone. Our aim was to determine predictors of NI using admission serum metabolomics and gut microbiota in inpatients with cirrhosis. In this multicenter inpatient cirrhosis study, serum was collected on admission for liquid chromatography-mass spectrometry metabolomics, and a subset provided stool for 16SrRNA analysis. Hospital course, including NI development and death, were analyzed. Metabolomic analysis using analysis of covariance (ANCOVA) (demographics, Model for End-Stage Liver Disease [MELD] admission score, white blood count [WBC], rifaximin, and infection status adjusted) and random forest analyses for NI development were performed. Additional values of serum metabolites over clinical variables toward NI were evaluated using logistic regression. Stool microbiota and metabolomic correlations were compared in patients with and without NI development. A total of 602 patients (231 infection admissions) were included; 101 (17%) developed NIs, which resulted in worse inpatient outcomes, including intensive care unit transfer, organ failure, and death. A total of 127 patients also gave stool samples, and 20 of these patients developed NIs. The most common NIs were spontaneous bacterial peritonitis followed by urinary tract infection, Clostridioides difficile, and pneumonia. A total of 247 metabolites were significantly altered on ANCOVA. Higher MELD scores (odds ratio, 1.05; p < 0.0001), admission infection (odds ratio, 3.54; p < 0.0001), and admission WBC (odds ratio, 1.05; p = 0.04) predicted NI (area under the curve, 0.74), which increased to 0.77 (p = 0.05) with lower 1-linolenoyl-glycerolphosphocholine (GPC) and 1-stearoyl-GPC and higher N-acetyltryptophan and N-acetyl isoputreanine. Commensal microbiota were lower and pathobionts were higher in those who developed NIs. Microbial-metabolite correlation networks were complex and dense in patients with NIs, especially sub-networks centered on Ruminococcaceae and Pseudomonadaceae. NIs are common and associated with poor outcomes in cirrhosis. Admission gut microbiota in patients with NIs showed higher pathobionts and lower commensal microbiota. Microbial-metabolomic correlations were more complex, dense, and homogeneous among those who developed NIs, indicating greater linkage strength. Serum metabolites and gut microbiota on admission are associated with NI development in cirrhosis.

Stool microbiota show greater linkages with plasma metabolites compared to salivary microbiota in a multinational cirrhosis cohort.

BACKGROUND AND AIMS: Cirrhosis is associated with changes in gut microbiota in both saliva and stool. The relative linkage patterns of stool versus saliva microbiota with systemic metabolomics are unclear and may differ across countries. We hypothesized that stool microbiota have greater linkages with plasma metabolites than saliva microbiota, which may depend on country of origin. METHODS: Age-balanced controls and outpatient patients with cirrhosis, compensated and decompensated, from the USA and Mexico (MX) underwent plasma collection and dietary recall. Plasma metabolomics were analysed using nuclear magnetic resonance spectroscopy. Microbiota in stool and saliva samples were analysed using 16S rRNA analyses. Correlation network differences between both saliva and stool gut microbiota and plasma metabolites were compared between subject groupings and within/between countries. RESULTS: A total of 313 age-balanced subjects-135 USA (47 control, 48 compensated and 40 decompensated) and 178 MX (71 control, 56 compensated and 51 decompensated)-were enrolled. Cirrhosis severity, including lactulose and rifaximin use, were comparable. Plasma metabolites differed with advancing cirrhosis, between countries and according to 90-day hospitalizations. Correlation networks demonstrated more microbiome-metabolite linkages in stool compared to saliva in both populations, although there were no salivary correlation metrics across decompensated subjects in either country. Stool Lactobacillus showed a positive correlation to plasma lactate in decompensated cirrhosis from MX but not USA. CONCLUSIONS: Stool microbiota were more extensively linked with systemic metabolites than were saliva microbiota, irrespective of cirrhosis severity and country. These changes were more prominent in decompensated cirrhosis and were centred around plasma lactate, which might reflect the interaction of diet and lactulose therapy.

Integration of persuasive elements into exergames: Application in the development of a novel gait rehabilitation system for children with musculoskeletal conditions.

The main contribution of this paper is the application of the Persuasive System Design (PSD) model for the analysis and development of exergame systems to stimulate pediatric patients to adhere to short-term gait rehabilitation. It resulted in a novel therapy consisting of a video gaming and virtual reality (VG/VR) biofeedback system for treadmill gait rehabilitation, including a method for progressing the rehabilitation settings. During gait rehabilitation (GR) sessions, therapy settings need to be adjusted by physiotherapists, based on their clinical experience, to address the deficiencies of individuals while maximizing their motor functioning and maintaining their motivation. The system integrates persuasive elements, adjusted when physiotherapists progress the therapeutic settings, such as the treadmill speed, auditory feedback, and game challenges. We followed a scenario-based design method to develop the system, which comprised an observational study of conventional GR sessions and evaluations with 6 and 9 rehabilitation specialists who provided feedback about the system design. They perceived that the proposed method was valuable for physiotherapists to adapt the rehabilitation based on the children's performance. Also, they remarked that the system's visual and auditory stimulus would help engage the children in the therapy.

Gut microbiota from Mexican patients with metabolic syndrome and HIV infection: An inflammatory profile.

AIM: A remarkable increase in metabolic syndrome (MetS) has occurred in HIV-infected subjects. Gut dysbiosis is involved in the pathogenesis of metabolic disorders. Therefore, the aim is to explore the profile of the gut microbiota in Mexican population with HIV infection and MetS. METHODS AND RESULTS: In all, 30 HIV-infected patients with MetS were compared to a group of 30 patients without MetS, treated with integrase inhibitors and undetectable viral load were included in the study. Stool samples were analysed by 16S rRNA next-generation sequencing. High-sensitivity C-reactive protein >3 mg L-1 and higher scores in cardiometabolic indices were associated with MetS. The group with MetS was characterized by a decrease in α-diversity, higher abundance of Enterobacteriaceae and Prevotella, as well as a dramatic decrease in bacteria producing short-chain fatty acids. Prevotella negatively correlated with Akkermansia, Lactobacillus and Anaerostipes. Interestingly, the group without MetS presented higher abundance of Faecalibacterium, Ruminococcus, Anaerofilum, Oscillospira and Anaerostipes. Functional pathways related to energy metabolism and inflammation were increased in the group with MetS. CONCLUSIONS: HIV-infected patients with MetS present a strong inflammatory microbiota profile; therefore, future strategies to balance intestinal dysbiosis should be implemented.

An Upgrade on the Surveillance System of SARS-CoV-2: Deployment of New Methods for Genetic Inspection.

SARS-CoV-2 variants surveillance is a worldwide task that has been approached with techniques such as Next Generation Sequencing (NGS); however, this technology is not widely available in developing countries because of the lack of equipment and limited funding in science. An option is to deploy a RT-qPCR screening test which aids in the analysis of a higher number of samples, in a shorter time and at a lower cost. In this study, variants present in samples positive for SARS-CoV-2 were identified with a RT-qPCR mutation screening kit and were later confirmed by NGS. A sample with an abnormal result was found with the screening test, suggesting the simultaneous presence of two viral populations with different mutations. The DRAGEN Lineage analysis identified the Delta variant, but there was no information about the other three mutations previously detected. When the sequenced data was deeply analyzed, there were reads with differential mutation patterns, that could be identified and classified in terms of relative abundance, whereas only the dominant population was reported by DRAGEN software. Since most of the software developed to analyze SARS-CoV-2 sequences was aimed at obtaining the consensus sequence quickly, the information about viral populations within a sample is scarce. Here, we present a faster and deeper SARS-CoV-2 surveillance method, from RT-qPCR screening to NGS analysis.

Acute meningoencephalitis associated with SARS-CoV-2 infection in Colombia.

We present the case of a patient in the third decade of life, with asthma as comorbidity, who presented to the emergency department due to odynophagia, dyspnea, and cough of 2 days of evolution, later developing acute ventilatory failure requiring orotracheal intubation. The high-resolution chest tomography study showed consolidation due to a pneumonic process towards the posterior segment of the right lower lobe with areas of ground-glass infiltrates with a peripheral distribution. During the clinical course, the patient presented multiple seizure episodes that met the criteria for status epilepticus with MRI compatible with changes due to leptomeningitis. Given symptoms and thorax imaging, tests for SARS-CoV-2 ensued, with both positive RT-PCR in bronchoalveolar lavage and cerebrospinal fluid for the virus also positive. RT-PCR multiplex panel of meningitis/encephalitis results negative for 14 common organisms. A diagnosis of acute meningoencephalitis associated with COVID-19 was considered, with an adequate response to corticosteroid management; to our knowledge, this is the first adult patient with CNS involvement and CSF positive test in Latin America.

Performance evaluation of a lateral flow assay for nasopharyngeal antigen detection for SARS-CoV-2 diagnosis.

BACKGROUND: SARS-CoV-2 has become a global pandemic due to its capacity for rapid transmission. In this context, an early and rapid diagnosis of infected patients that do not require expensive equipment or highly trained personnel is crucial in order to reduce the contagious rate. The aim of this study was to evaluate a chromatographic immunoassay's performance for the rapid diagnosis of SARS-CoV-antigen. METHODS: A cross-sectional study included 369 adults from Western México with diagnosis or suspicion of SARS-CoV-2 infection. Two samples were collected; a naso-oropharyngeal was used for a molecular determination of SARS-CoV-2 RNA. The molecular analysis was carried out using DeCoV19 Kit Triplex (Genes2life S.A.P.I.) based on the CDC diagnostic panel for N1, N2, and N3 regions. The second sample was retrieved from a nasopharyngeal rub and used for the rapid diagnosis of SARS-CoV-2 antigen employing the commercial STANDARD™ Q COVID-19 Ag Test (SD BIOSENSOR). RESULTS: Overall, in 28.2% of the patients was detected the SARS-CoV-2 RNA, and 21.4% were positive for antigen detection. The rapid antigen test showed a sensitivity and specificity of 75.9% and 100%, respectively, with a positive predictive and negative values of 100% and 91%. Symptoms as anosmia presented a high OR for the positive diagnosis for both test, reverse transcription-polymerase chain reaction (RT-PCR), and the rapid antigen test of 8.86 (CI = 4.91-16) and 6.09 (CI = 3.42-10.85), respectively. CONCLUSION: SD BIOSENSOR is a useful assay, but some caveats must be considered before the general implementation.

Stimulating the Involvement of Family Members in the Medication Management Activities of Older Adults Through Ambient Displays: Qualitative Study.

Little attention has been paid to how medication management technologies, designed for older adults, modify the participation of family caregivers. We developed a tablet-based ambient display that provides external cues to remind and motivate older adults to take their medications. This study aimed to understand the effect of ambient displays on the involvement of family members in the elderly's medication management. We conducted a 10-week study consisting of interviews administered weekly to nine elderly-caregivers. We identify that new involvement patterns of the family caregivers were provoked through external cues, which made them aware of older adults' medication adherence and encouraged younger relatives to help older adults.

Mexico's 2018 Report Card on Physical Activity for Children and Youth: Full report.

OBJECTIVES: Mexico's 2018 Report Card evaluates the opportunities available for Mexican children and youth to reach healthy levels of physical activity, sleep, and sedentary behavior. METHODS: The Report Card is a surveillance system that gathers data from national surveys, censuses, government documents, websites, grey literature, and published studies to evaluate 16 indicators in four categories: Daily Behaviors; Physical Fitness; Settings and Sources of Influence; and Strategies and Investments. Data were compared to established benchmarks. Each indicator was assigned a grade from 1 - 10 (< 6 is a failing grade) or "incomplete" if data was insufficient/unavailable. RESULTS: Daily Behavior grades were: Overall Physical Activity, 4; Organized Sport Participation, 5; Active Play, 3; Active Transportation, 5; Sleep, 7; and Sedentary Behavior, 3. Physical Fitness, received a 7. Settings and Sources of Influence grades were: Family and Peers, incomplete; School, 3; and Community and Environment, 4. Strategies and Investments were: Government Strategies, 6; and Non-Government Organizations, 2. CONCLUSION: Low grades in 11 of the 16 indicators indicate that schools, families, communities, and government need to work together to improve physical activity opportunities for children and youth in Mexico.

Back to the clinic. Methods II. The Architecture of Clinical Research. Subject interaction, maneuvers and disease throughout time.

Medicine is characterized by the application of the scientific method through clinical judgment, by correct interpretation and use of the clinical course and/or natural history of the disease; its best description is observed in the architecture of clinical research. Through a temporal sequence, this model explains the phenomenon of causality with three sections: baseline status, maneuver, and outcome. The baseline status assesses who the patient is, where does he come from, his general conditions, the diagnosis, stage and aggressiveness of the pathology, complications, previous therapies, socioeconomic-cultural level, habits, therapeutic indications or contraindications, and the expected evolution is anticipated. In the maneuver, risk or prognostic factors, specific or symptomatic treatment, and general measures can be evaluated. In the outcome, early and late evolution are monitored. The model also allows the causes of follow-up loss to be determined. Anticipating patient evolution by recognizing his condition, disease, and expected effect of medical decisions allows acting in advance, since waiting for the manifestations of the evolutionary process of disease results in detriment to the patient.

La medicina se caracteriza por la aplicación del método científico a través del juicio clínico, por la correcta interpretación y el uso del curso clínico o historia natural de la enfermedad; su descripción más lograda la observamos en la arquitectura de la investigación clínica. A través de una secuencia temporal, este modelo explica el fenómeno de causalidad con tres apartados: estado basal, maniobra y desenlace. En el estado basal se evalúa quién es el paciente, de donde proviene, sus condiciones generales, el diagnóstico, el estadio y la agresividad de la patología, las complicaciones, terapias previas, nivel socioeconómi­co-cultural, hábitos, indicaciones o contraindicaciones terapéuticas y se prevé la evolución esperada. De la maniobra se pueden evaluar los factores de riesgo o pronóstico, tratamiento específico, sintomático y medidas generales. En el desenlace se vigila la evolución temprana y tardía. El modelo también permite determinar las causas de pérdida de seguimiento. Anticipar la evo­lución del paciente al reconocer su condición, enfermedad y efecto esperado de la decisiones médicas permite actuar antici­padamente, ya que esperar las manifestaciones del proceso evolutivo de la enfermedad resulta en detrimento del paciente.

Small bowel transit time of capsule endoscopy as a factor for the detection of lesions in potential small bowel bleeding.

BACKGROUND: the relationship between small bowel transit time (SBTT) of the capsule endoscopy (CE) and the diagnosis of small bowel bleeding (SBB) is controversial. OBJECTIVE: to evaluate the relationship between SBTT and CE and the identification of SBB. MATERIAL AND METHODS: CE was divided according to SBTT into < 4 hours and ≥ 4 hours. RESULTS: CE with SBTT ≥ 4 hours identified more angioectasias (p = 0.023), single lesions (p = 0.029) and jejunal lesions (p = 0.001) with an OR of 3.13 (95% CI, 1.61-6.10, p = 0.001) to identify the cause of SBB. CONCLUSIONS: CE SBTT of ≥ 4 hours increases the diagnosis of SBB.

De vuelta a la clínica. Métodos I. Diseños de investigación. Mayor calidad de información, mayor certeza a la respuesta.

Research designs refer to the way information is obtained and are limited by ethical, economic and temporal viability. Research designs are standardized strategies to reduce biases, which in the architectural model of research are identified in the baseline state, the maneuver and the outcome; hence, there are no specific designs for each question. The design with the lowest probability of bias is the clinical trial, followed by cohort and case-control studies and, finally, by cross-sectional surveys. Among the main characteristics that give merit to research designs are the following: population inquiry, which refers to the situation of the population in relation to the clinical course/natural history of the disease; the maneuver, or action that is expected to modify the baseline state, which can be observational or experimental; follow-up, or documented monitoring that is given to each subject, which can be longitudinal or cross-sectional; and directionality, which can prolective or retrolective and refers to the timing of data collection for research purposes. It will always be better having a valuable question, even when answered with a design with higher risk of bias, than a question that is irrelevant or has no applicability.

Los diseños de investigación se refieren a la forma como se obtiene la información y están limitados por viabilidad ética, económica y temporal. Son estrategias estandarizadas para disminuir los sesgos que en el modelo arquitectónico de la investigación se identifican en el estado basal, maniobra y desenlace; de ahí que no hay diseños específicos para cada pregunta. El diseño con menor probabilidad de sesgos es el ensayo clínico, seguido de la cohorte, el estudio de casos y controles y, finalmente, la encuesta transversal. Entre las principales características que dan mérito a los diseños están las siguientes: la pesquisa de la población, que se refiere a la ubicación de la población en relación con el curso clínico o historia natural de la enfermedad; la maniobra, o acción que se espera modifique la condición basal, que puede ser observacional o experimental; el seguimiento, o monitoreo documentado que se le da a cada sujeto, que puede ser longitudinal o transversal; y la direccionalidad, prolectiva o retrolectiva, que alude al tiempo de recopilación de la información con fines de investigación. Siempre será mejor tener una pregunta valiosa, incluso cuando se responda con un diseño con mayor riesgo de sesgos, que una pregunta irrelevante o sin aplicabilidad.

De vuelta a la clínica: sin justificación no existe pregunta de investigación que valga.

A clinical research question requires the concurrence of clinical experience and knowledge on methodology and statistics in that who formulates it. Initially, a research question should have a structure that clearly establishes what is that which is being sought (consequence or outcome), in whom (baseline status), and by action of what (maneuver). Subsequently, its reasoning must explore four aspects: feasibility and reasonableness of the questioning, lack of a prior answer, relevance of the answer to be obtained, and applicability. Once these aspects are satisfactorily covered, the question can be regarded as being "clinically relevant", which is different from being statistically significant, which refers to the probability of the result being driven by chance, which does not reflect the relevance of the question or the outcome. One should never forget that every maneuver entails adverse events that, when serious, discredit good results. It is imperative to have the possible answer estimated from within the structure of the question. The function of clinical research is to corroborate or reject a hypothesis, rather than to empirically test to find out what the outcome is.

La formulación de una pregunta de investigación clínica requiere la concurrencia de experiencia clínica y conocimiento en metodología y estadística. Inicialmente, la pregunta de investigación debe contar con una estructura que deje claro qué se busca (consecuencia o desenlace), en quién (estado basal) y por acción de qué (maniobra). Posteriormente, su argumentación debe explorar cuatro aspectos: factibilidad y sensatez del cuestionamiento, ausencia de respuesta previa, relevancia de la respuesta a obtener y aplicabilidad. Una vez que estos aspectos han sido cubiertos en forma satisfactoria puede considerarse que la pregunta es "clínicamente relevante", que es diferente a significancia estadística (la probabilidad de que el resultado se deba al azar y que no refleja la relevancia de la pregunta ni de los resultados). Nunca se debe olvidar que toda maniobra conlleva eventos adversos, que cuando son graves demeritan los buenos resultados. Es imperativo estimar la posible respuesta desde la estructura de la pregunta; la función de la investigación clínica es corroborar o rechazar una hipótesis, no probar empíricamente para ver qué resulta.

Impact of Systemic Antibiotics on Staphylococcus aureus Colonization and Recurrent Skin Infection.

Background: Staphylococcus aureus colonization poses risk for subsequent skin and soft tissue infection (SSTI). We hypothesized that including systemic antibiotics in the management of S. aureus SSTI, in conjunction with incision and drainage, would reduce S. aureus colonization and incidence of recurrent infection. Methods: We prospectively evaluated 383 children with S. aureus SSTI requiring incision and drainage and S. aureus colonization in the anterior nares, axillae, or inguinal folds at baseline screening. Systemic antibiotic prescribing at the point of care was recorded. Repeat colonization sampling was performed within 3 months (median, 38 days; interquartile range, 22-50 days) in 357 participants. Incidence of recurrent infection was ascertained for up to 1 year. Results: Participants prescribed guideline-recommended empiric antibiotics for purulent SSTI were less likely to remain colonized at follow-up sampling (adjusted hazard ratio [aHR], 0.49; 95% confidence interval [CI], .30-.79) and less likely to have recurrent SSTI (aHR, 0.57; 95% CI, .34-.94) than those not receiving guideline-recommended empiric antibiotics for their SSTI. Additionally, participants remaining colonized at repeat sampling were more likely to report a recurrent infection over 12 months (aHR, 2.37; 95% CI, 1.69-3.31). Clindamycin was more effective than trimethoprim-sulfamethoxazole (TMP-SMX) in eradicating S. aureus colonization (44% vs 57% remained colonized, P = .03) and preventing recurrent SSTI (31% vs 47% experienced recurrence, P = .008). Conclusions: Systemic antibiotics, as part of acute SSTI management, impact S. aureus colonization, contributing to a decreased incidence of recurrent SSTI. The mechanism by which clindamycin differentially affects colonization and recurrent SSTI compared to TMP-SMX warrants further study.