Classification of early tuberculosis states to guide research for improved care and prevention: an international Delphi consensus exercise.

The current active-latent paradigm of tuberculosis largely neglects the documented spectrum of disease. Inconsistency with regard to definitions, terminology, and diagnostic criteria for different tuberculosis states has limited the progress in research and product development that are needed to achieve tuberculosis elimination. We aimed to develop a new framework of classification for tuberculosis that accommodates key disease states but is sufficiently simple to support pragmatic research and implementation. Through an international Delphi exercise that involved 71 participants representing a wide range of disciplines, sectors, income settings, and geographies, consensus was reached on a set of conceptual states, related terminology, and research gaps. The International Consensus for Early TB (ICE-TB) framework distinguishes disease from infection by the presence of macroscopic pathology and defines two subclinical and two clinical tuberculosis states on the basis of reported symptoms or signs of tuberculosis, further differentiated by likely infectiousness. The presence of viable Mycobacterium tuberculosis and an associated host response are prerequisites for all states of infection and disease. Our framework provides a clear direction for tuberculosis research, which will, in time, improve tuberculosis clinical care and elimination policies.

The Asociación Mexicana de Gastroenterología consensus on the diagnosis and treatment of acute pancreatitis in children and adolescents.

Acute pancreatitis (AP) and recurrent acute pancreatitis (RAP) are conditions, whose incidence is apparently on the rise. Despite the ever-increasing evidence regarding the management of AP in children and adults, therapeutic actions that could potentially affect having a poor prognosis in those patients, especially in the pediatric population, continue to be carried out. Therefore, the Asociación Mexicana de Gastroenterología convened a group of 24 expert pediatric gastroenterologists from different institutions and areas of Mexico, as well as 2 pediatric nutritionists and 2 specialists in pediatric surgery, to discuss different aspects of the epidemiology, diagnosis, and treatment of AP and RAP in the pediatric population. The aim of this document is to present the consensus results. Different AP topics were addressed by 6 working groups, each of which reviewed the information and formulated statements considered pertinent for each module, on themes involving recommendations and points of debate, concerning diagnostic or therapeutic approaches. All the statements were presented and discussed. They were then evaluated through a Delphi process, with electronic and anonymous voting, to determine the level of agreement on the statements. A total of 29 statements were formulated, all of which reached above 75% agreement in the first round of voting.

Ultra-processed diet, systemic oxidative stress, and breach of immunologic tolerance.

In recent years, consumption of ultra-processed food around the world has been increasing. The nutritional profile of an ultra-processed diet is associated with the development of cellular alterations that lead to oxidative stress. The chronic prooxidative state leads to an environment that influences the proliferation, apoptosis, and signaling pathways of immune cells. Likewise, the decrease in the transcription factor NRF2, owing to exacerbated production of reactive oxygen species, leads to changes in immune function and response to infections. This review aims to analyze the connection between an ultra-processed diet, systemic oxidative stress, and immune tolerance, as a contribution to the scientific evidence on the impact of oxidative stress on health and the possible risk of infections-an important consideration in the association of eating pattern and the immune response.

Molecular mechanisms from insulin-mimetic effect of vitamin D: treatment alternative in Type 2 diabetes mellitus.

Diabetes mellitus is a complex and multifactorial disease with a global prevalence that exceeds 425 million people. Type 2 diabetes mellitus (T2DM) is characterized by a state of insulin resistance, which leads to metabolic alterations that aggravate the state of health of people. Vitamin D deficiency appears to play an important role in the triggering mechanisms of insulin resistance. In this review, an analysis is made of the biochemical mechanisms associated with the insulin-mimetic effect of vitamin D, its supplementation being a possible nutritional strategy for the T2DM treatment. The current scientific evidence is extensive regarding the dose of vitamin D used for an insulin-mimetic effect. However, clinical trials and systematic reviews show statistical differences on glucose, insulin, and glycated hemoglobin levels of patients with T2DM, associated with activation mechanisms of transcription factors related to genes of the glucide metabolism and the insulin receptor, and the regulation of intracellular Ca2+ insulin concentrations. Likewise, an indirect mechanism associated with antioxidant and anti-inflammatory effects has been shown that also leads to sensitivity to the insulin receptor. The use of a specific dose of vitamin D could be an effective alternative in the T2DM treatment, which would reduce the risk of complications derived from hyperglycemia.

Neuroprotective Effect Of Peptide Fractions from Chia (Salvia hispanica) on H2O2-Induced Oxidative Stress-Mediated Neuronal Damage on N1E-115 Cell Line.

Neurodegenerative diseases (ND) affect around a billion people worldwide. Oxidative stress plays a critical role in the activation of neuronal death mechanisms, implicated in the ND etiology. In the present research, the neuroprotective effect of the S. hispanica protein derivatives is evaluated, on neuronal cells N1E-115, after the damage induction with H2O2. From the protein-rich fraction of S. hispanica, three peptide fractions were obtained (3-5, 1-3 y < 1 kDa) and its neuroprotective effect on neuronal cells N1E-115 was evaluated, through the antioxidant pathway. In the toxicity assay, the peptide fractions showed viability greater than 90%. When N1E-115 cells were incubated with 100 µM H2O2, fractions 1-3 and < 1 kDa, presented cell viability of 66.64% ± 3.2 and 67.32% ± 2.8, respectively. Fractions 1-3 and < 1 kDa reduced by 41.73% ± 3.2 and 40.87% ± 2.8, respectively, the ROS production compared to the control, without significant statistical difference between both fractions (p < 0.05), while F3-5 kDa, only reduced the ROS production by 21.95% ± 2.4. The protective effect observed in the < 3 kDa fractions could be associated with its antioxidant activity, which represents an important study target.

Neuroprotective effect from Salvia hispanica peptide fractions on pro-inflammatory modulation of HMC3 microglial cells.

Neuroinflammation plays a critical role in the neurodegenerative disease's development, where microglia's act an important role in the mechanisms of response to neuronal damage. In the present research, the neuroprotective effect from Salvia hispanica peptide fractions on the proinflammatory modulation on HMC3 microglial cells was evaluated. From the enzymatic hydrolysis of a protein-rich fraction from S. hispanica seeds, three peptide fractions (<1, 1-3 and 3-5 kDa) were obtained, from which its neuroprotective and anti-inflammatory effect was determined on the production of proinflammatory mediators on HMC3 cells. The F1-3 kDa exhibited the greatest protective effect (79.04%), associated with the decrease in ROS cell production (51.3 ± 2.3%). Likewise, F1-3 kDa at 50 µg/ml, presented the highest reduction percentages of NO (33.1 ± 2.30%), TNFα (26.4 ± 1.1%) and IL6 (17.36 ± 1.6%). F1-3 kDa exhibited a neuroprotective effect in HMC3 cells associated with its antioxidant and anti-inflammatory effect. PRACTICAL APPLICATIONS: Currently, neurodegenerative diseases represent a global health problem, so the search for bioactive compounds with neuroprotective effect is useful in the prevention and treatment of this group of diseases. Peptide research with an effect on the proinflammatory and prooxidant mediator's reduction presents a potential application in the functional food's development aimed at the treatment of chronic diseases, that have oxidative stress and inflammation as their etiological factor. The present research adds to the scientific evidence of the potential benefits of bioactive peptides obtained from chia seeds. The results correlate with the main health benefits of whole chia seed in humans, such as antioxidant, anti-inflammatory, hypoglycemic and hypotensive capacity. This relationship is associated with the protein and peptide composition of chia, which increases its added value as food.

Effect of ultra-processed diet on gut microbiota and thus its role in neurodegenerative diseases.

The current dietary pattern is characterized by high consumption of ultra-processed foods and lower consumption of fiber and vegetables, environmental factors that are associated directly with the current incidence of chronic metabolic diseases. Diet is an environmental factor that influences the diversity and functionality of the gut microbiota, where dietary changes have a direct action on their homeostasis. The environment created in the gut by ultra-processed foods, a hallmark of the Western diet that are recognized as trigger factors for low-grade systemic inflammatory and oxidative changes, favor the development of neurodegenerative diseases (NDs). From a systematic search, the present review analyzes the relationship and effect of the current feeding pattern, with the dysregulation of the microbiota and its influence on the development of cognitive decline. Because diagnosis of NDs is usually at late stages, this review highlights the importance of a search for stricter public health strategies regarding access to and development of ultra-processed foods.

Systemic Oxidative Stress: A key Point in Neurodegeneration - A Review.

Systemic oxidative stress (SOS) has an important role in the mechanisms activation of neuronal death, involved in the neurodegenerative disease (ND) etiology. Brain is susceptible to oxidative stress injuries due to its high energy and metabolic request, therefore minimal imbalances of the redox state, as occurs in mitochondrial dysfunction, favour tissue injury and neuroinflammatory mechanisms activation. ND affect around the world about a billion people, without distinction of sex, educational level and economic status. Public measures generation that prevent ND from the SOS are possible promising therapeutic targets that could reduce the ND incidence. We discuss here the effects and mechanisms of SOS derived neurodegeneration, as well as the neuroinflammation repercussions for some cerebral structures.

Peptides from Mucuna pruriens L., with protection and antioxidant in vitro effect on HeLa cell line.

BACKGROUND: Mucuna pruriens L. is a legume sown in the Mexican southeast with an important protein content. Studies have shown the potential use of by-products derived from Mucuna as a functional food because of the hypoglycemic and antihypertensive activities. Thus, this study aims to assess the antioxidant and protective effect of the peptide fractions derived from M. pruriens L., in vitro on the HeLa cell line. An enzymatic hydrolysis with pepsin-pancreatin was performed on the total protein concentrate, from which five peptide fractions were obtained. RESULTS: All protein derivatives from M. pruriens L., except F5-10 kDa, decreased the hydrogen peroxide production by more than 50%. The highest antioxidant activity was exhibited by F1-3 kDa, which lowered the intracellular reactive oxygen species by 207 ± 4.20%. No significant differences were found in the protective effects of the protein hydrolysate, F5-10 kDa, F3-5 kDa and F1-3 kDa relative to the N-acetylcysteine control group. CONCLUSION: This elucidated the potential action mechanisms of M. pruriens L. protein derivatives for future investigations and their role in the prevention and treatment of oxidative stress. © 2019 Society of Chemical Industry.

Effect of Enzymatic Digestion of Protein Derivatives Obtained from Mucuna pruriens L. on Production of Proinflammatory Mediators by BALB/c Mouse Macrophages.

Inflammation is considered to be a major risk factor for the pathogenesis of chronic non-communicable diseases. Macrophages are important immune cells, which regulate inflammation and host defense by secretion of proinflammatory mediators. Obtaining biopeptides by enzymatic hydrolysis adds value to proteins of vegetative origin, such as Mucuna pruriens L. The present study evaluated the effect of enzymatic digestion of protein derivatives obtained from M. pruriens L. on the production of proinflammatory mediators by BALB/c mouse macrophages. Five different molecular weight peptide fractions were obtained (F > 10, 5-10, 3-5, 1-3, and < 1 kDa, respectively). At 300 µg/mL, F5-10 kDa inhibited 50.26 and 61.00% NO and H2O2 production, respectively. Moreover, F5-10 kDa reduced the IL-6 and TNFα levels to 60.25 and 69.54%, respectively. After enzymatic digestive simulation, F5-10 kDa decreased the inflammatory mediators.

Initial development and validation of a fecal incontinence-specific quality of life measure.

BACKGROUND/PURPOSE: Fecal incontinence is a prevalent pediatric condition with psychosocial impacts on both children and their caregivers. We sought to develop and validate the Cincinnati Fecal Incontinence Scale (CINCY-FIS) as a psychometrically valid measure to assess the quality of life and caregiver impacts of pediatric fecal incontinence. METHODS: Items were generated through review of previous measures, expert consensus, and pilot testing with feedback from 8 families. Initial study measures were completed by 222 caregivers. Following item reduction, 18 items were subjected to confirmatory factor analysis. Convergent and criterion validity were assessed using correlation. Reliability was established using internal consistency statistics and test-retest reliability at baseline and 2-week follow-up. RESULTS: A five factor first-order structure with two higher-order factors demonstrated acceptable fit to the data, was consistent with a priori hypotheses, and was more parsimonious than the alternative model. Convergent validity and criterion-related validity were established for all of the CINCY-FIS scales. Reliability was high and consistent across both measurement occasions. CONCLUSIONS: The CINCY-FIS is a reliable and valid assessment of pediatric fecal incontinence-specific quality of life and parenting stress. The score is highly sensitive to patient changes making it suitable for both clinical and research purposes. TYPE OF STUDY: Prospective observational. LEVEL OF EVIDENCE: Study of Diagnostic Test Level II.

Normative Ranges of Transcranial Doppler Metrics.

OBJECTIVE: To determine normal ranges for traditional transcranial Doppler (TCD) measurements for two age groups (14-19 and 20-29 years) and compare to existing literature results. The development of a normal range for TCD measurements will be required for the development of diagnostic and prognostic tests in the future. MATERIALS AND METHODS: We performed TCD on the middle cerebral artery on 147 healthy subjects aged 18.9 years (SD = 2.1) and calculated mean cerebral blood flow velocity (mCBFV) and pulsatility index (PI). The study population was divided into two age populations (14-19 and 20-29 years). RESULTS: There was a significant decrease in PI (p = 0.015) for the older age group with no difference in mCBFV. CONCLUSION: Age-related, normal data are a prerequisite for TCD to continue to gain clinical acceptance. Our correlation of age-related TCD findings with previously published results as the generally accepted "gold standard" underlines the validity and sensitivity of this ultrasound method.

Biopeptides with antioxidant and anti-inflammatory potential in the prevention and treatment of diabesity disease.

Diabesity is the leading cause of modern, chronic disease. In 2012, diabetes killed 1.2 million people worldwide and its global prevalence exceeded 347 million people, and it is expected that it will increase to 540 million by 2030. Because of this health imperative, it is also linked to increasing obesity. The role of the inflammatory process and oxidative stress in the pathophysiology of these diseases is widely documented. This paper review, using data from major databases, the role of biopeptides with antioxidant and anti-inflammatory activity as a potential aid for the prevention and treatment of diabesity, since the mechanisms of action mentioned directly affect oxidative stress and the characteristic imbalance of the inflammatory process of this disease. Some of these studies have demonstrated beneficial results in relation to oxidative stress and proinflammatory markers. However, the role of biopeptides, in relation to oxidative stress and inflammatory biomarkers, remains unclear and represents a potentially fruitful area for further research in the health area.

Spontaneous Rupture of Splenic Hemangioma in a Neonate.

Spleen vascular tumors such as hemangiomas, albeit rare, can present during neonatal period with unexplained circulatory shock. We present a case of a newborn with refractory hypovolemic shock and acute abdomen that underwent emergency splenectomy due to spontaneous rupture of a splenic hemangioma.

Surgical outcomes, bowel habits and quality of life in young patients after ileoanal anastomosis for ulcerative colitis.

PURPOSE: We aim to investigate the postoperative outcomes, bowel habits and quality of life (QoL) of younger pediatric ulcerative colitis (UC) patients following surgical intervention compared to an older pediatric population. METHODS: Medical records of UC patients after colectomy with ileoanal reconstruction (2002-2013) at our institution were reviewed. Patients/parents completed a QoL, bowel habits and disease course questionnaire. Surgical outcomes, bowel habits and QoL were reported comparing the younger (≤11years old, n=26) to older (>11years old, n=38) cohorts. RESULTS: The mean age at colectomy was 7.04±0.63years vs 14.71±0.32years in the two groups. Patients had a significant (P<0.001) reduction in stooling frequency after surgery in both age groups and had favorable rates of fecal continence. The frequency of pouchitis and postoperative small bowel obstruction was similar in both cohorts. Dehydration was slightly increased in the younger population but not significant. Anastomotic leak and stricture rates were slightly reduced in younger patients. Postoperative QoL was favorable and similar regardless of age at surgery. CONCLUSIONS: Colectomy with ileoanal anastomosis for young children (≤11years old) with UC is without increased complications relative to older patients and maintains a postoperative QoL and stool patterns.

The association of the severity of anorectal malformations and intestinal malrotation.

INTRODUCTION: Intestinal malrotation is a known association of anorectal malformations (ARM). Exact incidence, prognosis and surgical implications related to ARM are unknown. The aim of this study was to identify relevant associations between ARM and the presence of malrotation. METHODS: Records of patients from two referral centers were retrospectively analyzed looking for malrotation associated to ARM and its management, as well as factors for functional prognosis. RESULTS: 40 patients out of 2572 with ARM (1.6%) were found to have malrotation. Females were more commonly affected, and severe malformations were more frequent (cloaca, covered cloacal exstrophy in females and rectoprostatic and rectobladder neck fistula in males). Factors significantly associated with malrotation included Müllerian or Wolffian duct anomalies (P<0.05), while fecal continence status, presence of constipation, and use of laxatives or enemas were not. Detecting and correcting malrotation early on or at the time of colostomy creation represented a protective factor against additional surgeries for bowel obstruction and volvulus (P<0.001). Removal of the appendix during malrotation treatment required constructing a neoappendicostomy using a cecal flap in 9 out of 14 patients needing antegrade enema administration. CONCLUSIONS: Malrotation presence in patients with ARM has the same frequency as in the general population, but it is more common in severe malformations. Surgeons treating these patients should address the malrotation at the time of colostomy opening if detected. The appendix should be preserved for potential future use as an appendicostomy for antegrade administration of enemas.

Health-Related Quality of Life and Parental Stress in Children With Fecal Incontinence: A Normative Comparison.

OBJECTIVE: The aim of the present study was to describe the quality of life and parenting stress associated with a child with fecal incontinence (FI). METHODS: Female caregivers (n = 170) of children of 3 to 12 years age with FI completed a broad and general measure of quality of life and a measure of parenting stress. Results were compared with proxy reports for a normative sample of healthy children. RESULTS: Caregivers of children with FI reported significantly impaired quality of life for their children and increased parenting stress in all of the respective domains relative to healthy controls. Impairments reported by caregivers were large in magnitude. Similarly, rates of parenting stress were at or greater than the 98th percentile for caregivers of children with FI. CONCLUSIONS: Children with fecal incontinence and their families are in need of interventions targeting their quality of life and the stress associated with caregiving. FI appears to be particularly stressful for caregivers who may be in need of support beyond medical management of their child's bowel. Moreover, additional refinements in disease-specific quality of life assessment are needed in this population. Such refinement would allow for more precise measurement of the quality of life processes that are unique to FI.

Enterolito de sulfato de bario en una paciente con malformación anorrectal. Notas sobre el colostograma distal apropiado / Barium sulfate enterolith in a patient with anorectal malformation. Remarks on the appropriate distal colostogram

Resumen: Presentación del caso: Paciente femenino de 2 años de edad con malformación Anorrectal y fístula rectovestibular a quién se realizó colostograma distal con sulfato de bario provocando concreción lítica de bario en el fondo de saco del colon distal al no enjuagar el contenido. Ante la imposibilidad de retirar el enterolito a través del estoma disfuncional de la derivación intestinal decidimos realizar la extracción al momento de hacer la anorrectoplastía sagital posterior con riesgo aumentado de infección, dehiscencia de herida y lesión de estructuras adyacentes. Enfatizamos la necesidad de recordar a la comunidad médica radiológica y pediátrica de la adecuada realización de este tipo de estudios siempre con medio de contraste hidrosoluble, y aprovechamos para recapitular la técnica de realización del mismo.

Abstract: Case presentation: 2 year-old female patient with anorectal malformation with recto-vestibular fistula to whom a distal colostogram with barium sulfate was done, thus provoking lithic concretion in the distal sac. Since it was deemed impossible to extract the enterolith trough de distal stoma we decided to perform the anorectoplasty and extract the lit at that moment knowing the increased surgical risks such as infection, dehiscence and damage of adjacent structures. We stress the need to remind the radiological and pediatric medical communities to always perform this kind of imaging studies with water-soluble contrast agents and we also annotate the technique for doing so.

Laparoscopic approach in the management of anorectal malformations.

Seventeen years have passed since the first description of the laparoscopic approach for anorectal malformation and approximately 68 articles have been published on the subject. In this review article, we aim to describe the advantages as well as the indications and contraindications of this approach when dealing with each specific type of anorectal malformation, according to what has been described in the literature and to our own experience. The ideal and undisputable indication for laparoscopy remains for cases in which the abdomen needs to be entered to repair the malformation. Only 10% of male patients with anorectal malformation are born with a recto-bladder neck fistula that requires an abdominal approach, this represents an ideal indication for laparoscopy. In females, only the complex cloacae with a common channel length greater than 3 cm are the ones that require a laparotomy; they represent about 30% of the cloacae. However, the repair of this type of cloacae also requires sophisticated and technically demanding maneuvers that have never been done laparoscopically. In cases of recto-urethral prostatic fistulas the malformation can be repaired either way: laparoscopically or posterior sagitally. In all other malformations: recto-perineal fistula, recto-urethral bulbar fistula, anorectal malformation without fistula, rectal atresia, recto-vestibular fistula; no justification for laparoscopy could be found; and in some cases, laparoscopy is contraindicated. In the published reports, there is no evidence supporting the idea that laparoscopic repair results in better functional results when compared with non-laparoscopic operation; there is a tendency to omit information relevant to bowel control such as the characteristics of the sacrum and the presence or absence of tethered cord; and most authors do not compare results between comparable malformations.