Effect of Caffeine on Colonic Manometry in Children.

OBJECTIVES: Coffee and caffeinated products have been widely consumed for many centuries. Previous adult studies have suggested that both coffee and decaffeinated beverages induce colonic motility. However, no study has been conducted in pediatrics, and the role of caffeine alone in pediatric colonic motility needs to be explored. METHODS: A prospective study of pediatric patients undergoing standard colonic motility testing that were able to consume caffeinated coffee, decaffeinated coffee, and caffeine tablet during colonic manometry. Patients who had a gastrocolonic reflex and high amplitude propagated contractions (HAPCs) in response to intraluminal administration of bisacodyl in the colon were included in the final analyses. RESULTS: Thirty-eight patients were recruited, 22 of which were excluded, 11 due to abnormal studies (no HAPC seen in response to intraluminal response to bisacodyl), and 11 due to inability to consume all study agents or complete the study. Sixteen patients met criteria for final analyses. Intracolonic bisacodyl produced a larger area under the curve (AUC) compared to all other agents. Caffeinated coffee resulted in a higher AUC, motility index (MI), and time to HAPC compared with decaffeinated coffee ( P < 0.05). There was no significant difference between caffeinated coffee and caffeine tablet, or caffeine tablet and decaffeinated coffee. CONCLUSIONS: Caffeine is indeed a colonic stimulant; however, other components of caffeinated and non-caffeinated beverages likely induce colonic response and require further evaluation for possible use as a colonic stimulant.

Assessment of exocrine pancreatic function in children and adolescents with direct and indirect testing.

The exocrine pancreas plays an important role in digestion. Understanding of the physiology and regulation of exocrine function provides insight into disease processes and basis of functional testing. Specifically, exocrine pancreatic insufficiency (EPI) can cause maldigestion and thus a proper assessment of exocrine pancreatic function is important. There are indirect and direct methods for evaluating pancreatic function. Indirect methods are varied and include stool, serum, urine, and breath tests. Fecal elastase is a commonly used indirect test today. Direct methods involve stimulated release of pancreatic fluid that is collected from the duodenum and analyzed for enzyme activity. The most used direct test today is the endoscopic pancreatic function test. Indirect pancreatic function testing is limited in identifying cases of mild to moderate EPI, and as such in these cases, direct testing has higher sensitivity and specificity in diagnosing EPI. This review provides a comprehensive guide to indirect and direct pancreatic function tests as well as an in-depth look at exocrine pancreatic function including anatomy, physiology, and regulatory mechanisms.

Development of the human pancreas and its exocrine function.

The pancreas has both endocrine and exocrine function and plays an important role in digestion and glucose control. Understanding the development of the pancreas, grossly and microscopically, and the genetic factors regulating it provides further insight into clinical problems that arise when these processes fail. Animal models of development are known to have inherent issues when understanding human development. Therefore, in this review, we focus on human studies that have reported gross and microscopic development including acinar-, ductal-, and endocrine cells and the neural network. We review the genes and transcription factors involved in organ formation using data from animal models to bridge current understanding where necessary. We describe the development of exocrine function in the fetus and postnatally. A deeper review of the genes involved in pancreatic formation allows us to describe the development of the different groups (proteases, lipids, and amylase) of enzymes during fetal life and postnatally and describe the genetic defects. We discuss the constellation of gross anatomical, as well as microscopic defects that with genetic mutations lead to pancreatic insufficiency and disease states.

Efficacy of Probiotics-Based Interventions as Therapy for Inflammatory Bowel Disease: A Recent Update.

Probiotics such as Lactobacillus spp. play an important role in human health as they embark beneficial effect on the human gastrointestinal microflora composition and immune system. Dysbiosis in the gastrointestinal microbial composition has been identified as a major contributor to chronic inflammatory conditions, such as inflammatory bowel disease (IBD). Higher prevalence of IBD is often recorded in most of the developed Western countries, but recent data has shown an increase in previously regarded as lower risk regions, such as Japan, Malaysia, Singapore, and India. Although the IBD etiology remains a subject of speculation, the disease is likely to have developed because of interaction between extrinsic environmental elements; the host's immune system, and the gut microbial composition. Compared to conventional treatments, probiotics and probiotic-based interventions including the introduction of specific prebiotics, symbiotic and postbiotic products had been demonstrated as more promising therapeutic measures. The present review discusses the association between gut dysbiosis, the pathogenesis of IBD, and risk factors leading to gut dysbiosis. In addition, it discusses recent studies focused on the alteration of the gastrointestinal microbiome as an effective therapy for IBD. The impact of the COVID-19 pandemic and other viral infections on IBD are also discussed in this review. Clinical and animal-based studies have shown that probiotic-based therapies can restore the gastrointestinal microbiota balance and reduce gut inflammations. Therefore, this review also assesses the status quo of these microbial-based therapies for the treatment of IBD. A better understanding of the mechanisms of their actions on modulating altered gut microbiota is required to enhance the effectiveness of the IBD therapeutics.

A 1-minute blood test detects decreased immune function and increased clinical risk in COVID-19 patients.

Upon infection with SARS-CoV-2, the virus that causes COVID-19, most people will develop no or mild symptoms. However, a small percentage of the population will become severely ill, and some will succumb to death. The clinical severity of COVID-19 has a close connection to the dysregulation of the patient's immune functions. We previously developed a simple, nanoparticle-enabled blood test that can determine the humoral immune status in animals. In this study, we applied this new test to analyze the immune function in relation to disease severity in COVID-19 patients. From the testing of 153 COVID-19 patient samples and 142 negative controls, we detected a drastic decrease of humoral immunity in COVID-19 patients who developed moderate to severe symptoms, but not in patients with no or mild symptoms. The new test may be potentially used to monitor the immunity change and predict the clinical risk of patients with COVID-19.

The CHA2DS2-VASc Score for Risk Stratification of Stroke in Heart Failure With-vs-Without Atrial Fibrillation.

A recent study suggested that the CHA2DS2-VASc score can risk stratify heart failure (HF) patients without atrial fibrillation (AF) for stroke. We performed a retrospective analysis using the national Veteran Affairs database to externally validate the findings. Crude incidence rates of end points were calculated. A Cox proportional model was used to study the association between the CHA2DS2-VASc score and outcomes. In HF patients with AF (n = 17,481) and without AF (n = 36,935), the 1 year incidence rate for ischemic stroke, thromboembolism, thromboembolism (without MI), and death were 2.7 and 2.0%; 10.3 and 7.9%; 4.1 and 3.1%; and 19.2 and 26.0%, respectively, with higher rates with increasing CHA2DS2-VASc scores both with and without AF. CHA2DS2-VASc score predicted strokes in HF patients without AF (1-year C-statistic 0.62, 95% CI 0.60-0.64; NPV 85.4%, 95% CI 83.4-87.4%) with similar predictive ability to those with AF (C-statistic 0.59, 95% CI 0.56-0.62; NPV 86.4%, 95% CI 82.6-90.2%). Among patients with HF, there was an increased risk of stroke, thromboembolism, and death with increasing CHA2DS2-VASc scores regardless of AF status. Our findings support the use of the CHA2DS2-VASc score as a prognostic tool in HF.

Efficacy of Short Course of Preksha Dhyana for Functional Abdominal Pain Disorder in a Busy Pediatric Clinic.

Introduction: Mind body techniques such as meditation improve symptoms in children and adults with IBS. Typical courses, however, are lengthy and difficult to administer. We report our experience with a short course of Preksha Dhyana (PD), a child-friendly focused meditation with yoga. Method: Physicians deliver focused meditation while medical assistants taught yoga. Three sessions were administered biweekly with recommendations for daily practice. Pain severity Likert scores were compared with a treatment as usual (TAU) historical control. Anxiety scores were compared from baseline in the PD group. Results: Thirty PD patients aged 9-17 (20 female) and 52 consecutive TAU group aged 5-17 (33 female) were reviewed. The biweekly sessions had high (71%) completion rates. Utilization rates of PD were similar to TAU despite added sessions. The PD group had an average time of follow-up of 8.9 ± 9.4 vs. 6.0 ± 3.9 months in the TAU group (p = 0.522). Changes in pain scores from baseline showed improvement in the PD group, 0.67 ± 0.13 vs. TAU 1.39 ± 0.11 (p = 0.0003). In the PD group, anxiety scores improved significantly from baseline (0.5 vs. 1, P < 0.001). Pain improved in 93% (28/30) and resolved in 47% (14/30). Conclusion: A short course of PD was successfully embedded in a busy pediatric office without additional staffing. The approach proved cost-effective without increasing overall healthcare utilization and showed significant benefits over TAU. Pending RCT confirmation, this offers a cost-effective method to incorporate mind-body techniques into a pediatric office practice.

Perception of nursing students' on clinical experience in the National Referral Hospital of Bhutan.

BACKGROUND: This study has been carried out to study the usefulness of the clinical posting at the National Referral Hospital in Bhutan. It is important to know whether the clinical experience leads to gaining nursing skills, and nursing being a skill-oriented profession, clinical placement provides an opportunity, and education that carry a heavy weight in their wholesome nursing education. OBJECTIVE: The objective was to explore how nursing students commonly perceive their clinical experience. METHODS: A focus group discussion was conducted with eight to ten students/group from three levels of nursing education. The groups were 1st-, 2nd-, and 3rd-year students who expressed their clinical experiences during the focus group discussions. The data were analyzed by content analysis using a thematic analysis. RESULTS: Four themes emerged from the focus group discussion. The themes were "good exposure," "connect theory to practice," "anxiety and fear," and "learning by task participation and helping." CONCLUSION: The clinical environment is different to classroom. In clinical areas, the students experience stress and anxiety, and learning is through working together, moreover, it finds out that real situation is not what is taught in the classroom.

A Review of Tertiary Referrals for Management of Pediatric Esophageal Eosinophilia.

Background: Eosinophilic esophagitis is a chronic, immune-mediated disease characterized by symptoms of esophageal dysfunction and ≥15 eosinophils/high-powered field (eos/hpf). Proton pump inhibitor responsive esophageal eosinophilia (1) is an entity of esophageal eosinophilia that responds to PPI therapy and is thought to be clinically and histologically similar to EoE. Current guidelines suggest therapy with PPI prior to endoscopy and use of PPI as first line for esophageal eosinophilia. In order to gain a better understanding of community practice patterns and to try differentiate between these two entities, we sought to evaluate the clinical presentations, treatment and final diagnoses of patients presenting to our institution for second opinions of esophageal eosinophilia. Methods: A search of our electronic medical record yielded a list of patients presenting for a second opinion of esophageal eosinophilia. Charts were reviewed for clinical information. Results: A total of 187 charts were included. Patients ranged from 1-19 years old with 75% being male and 74% being Caucasian. Of the patients who had documentation of their medications at the time of initial endoscopy, 70% were not on any PPI prior to their endoscopy, and 94% were on <2 mg/kg/day. Of the 19 patients who had full response to PPI therapy and were diagnosed with PPI-REE, close to half had previously been treated with diet, steroids, or both. Patients with final diagnosis of EoE had significantly higher eos/hpf on initial endoscopy compared to those with diagnosis of PPI-REE (51.9 ± 30.6 v. 35.8 ± 16.4. p = 0.027), as well as higher likelihood of having IgE-mediated food allergy (79 v. 47%, p = 0.003). Conclusions: Diagnostic and therapeutic algorithms are needed for esophageal eosinophilia to prevent misdiagnosis and unnecessary procedures and therapies.

Development of pharmacophore similarity-based quantitative activity hypothesis and its applicability domain: applied on a diverse data-set of HIV-1 integrase inhibitors.

Quantitative pharmacophore hypothesis combines the 3D spatial arrangement of pharmacophore features with biological activities of the ligand data-set and predicts the activities of geometrically and/or pharmacophoric similar ligands. Most pharmacophore discovery programs face difficulties in conformational flexibility, molecular alignment, pharmacophore features sampling, and feature selection to score models if the data-set constitutes diverse ligands. Towards this focus, we describe a ligand-based computational procedure to introduce flexibility in aligning the small molecules and generating a pharmacophore hypothesis without geometrical constraints to define pharmacophore space, enriched with chemical features necessary to elucidate common pharmacophore hypotheses (CPHs). Maximal common substructure (MCS)-based alignment method was adopted to guide the alignment of carbon molecules, deciphered the MCS atom connectivity to cluster molecules in bins and subsequently, calculated the pharmacophore similarity matrix with the bin-specific reference molecules. After alignment, the carbon molecules were enriched with original atoms in their respective positions and conventional pharmacophore features were perceived. Distance-based pharmacophoric descriptors were enumerated by computing the interdistance between perceived features and MCS-aligned 'centroid' position. The descriptor set and biological activities were used to develop support vector machine models to predict the activities of the external test set. Finally, fitness score was estimated based on pharmacophore similarity with its bin-specific reference molecules to recognize the best and poor alignments and, also with each reference molecule to predict outliers of the quantitative hypothesis model. We applied this procedure to a diverse data-set of 40 HIV-1 integrase inhibitors and discussed its effectiveness with the reported CPH model.

Human umbilical cord blood cells induce neuroprotective change in gene expression profile in neurons after ischemia through activation of Akt pathway.

Human umbilical cord blood (HUCB) cell therapies have shown promising results in reducing brain infarct volume and most importantly in improving neurobehavioral function in rat permanent middle cerebral artery occlusion, a model of stroke. In this study, we examined the gene expression profile in neurons subjected to oxygen-glucose deprivation (OGD) with or without HUCB treatment and identified signaling pathways (Akt/MAPK) important in eliciting HUCB-mediated neuroprotective responses. Gene chip microarray analysis was performed using RNA samples extracted from the neuronal cell cultures from four experimental groups: normoxia, normoxia+HUCB, OGD, and OGD+HUCB. Both quantitative RT-PCR and immunohistochemistry were carried out to verify the microarray results. Using the Genomatix software program, promoter regions of selected genes were compared to reveal common transcription factor-binding sites and, subsequently, signal transduction pathways. Under OGD condition, HUCB cells significantly reduced neuronal loss from 68% to 44% [one-way ANOVA, F(3, 16)=11, p=0.0003]. Microarray analysis identified mRNA expression of Prdx5, Vcam1, CCL20, Alcam, and Pax6 as being significantly altered by HUCB cell treatment. Inhibition of the Akt pathway significantly abolished the neuroprotective effect of HUCB cells [one-way ANOVA, F(3, 11)=8.663, p=0.0031]. Our observations show that HUCB neuroprotection is dependent on the activation of the Akt signaling pathway that increases transcription of the Prdx5 gene. We concluded that HUCB cell therapy would be a promising treatment for stroke and other forms of brain injury by modifying acute gene expression to promote neural cell protection.

Peer-mediated multimodal intervention program for the treatment of children with ADHD in India: one-year followup.

The objective was to assess the efficacy of a one-year, peer-mediated interventional program consisting of yoga, meditation and play therapy maintained by student volunteers in a school in India. The population consisted of 69 students between the ages of 6 and 11 years, previously identified as having attention deficit hyperactivity disorder (ADHD). A program, known as Climb-Up, was initially embedded in the school twice weekly. Local high school student volunteers were then trained to continue to implement the program weekly over the period of one year. Improvements in ADHD symptoms and academic performance were assessed using Vanderbilt questionnaires completed by both parents and teachers. The performance impairment scores for ADHD students assessed by teachers improved by 6 weeks and were sustained through 12 months in 46 (85%) of the enrolled students. The improvements in their Vanderbilt scores assessed by parents were also seen in 92% (P < 0.0001, Wilcoxon). The Climb-Up program resulted in remarkable improvements in the students' school performances that were sustained throughout the year. These results show promise for a cost-effective program that could easily be implemented in any school.

Multimodal behavior program for ADHD incorporating yoga and implemented by high school volunteers: a pilot study.

A low-cost resource approach to ADHD therapy would be a practical approach to treating children in developing countries. Research has shown that ADHD is prevalent in all areas of the world, and yet treatment for children in more impoverished countries is still lacking. The approach taken was to combine yoga and meditation combined with multimodal behavioral therapy program for children ageing 6 to 11. The program was kept low cost by using trained high school volunteers and integrating the program within the public school. After 6 weeks of the program, 90.5% of children showed improvement as measured by their performance impairment score, a measurement of academic performance. Parent and Teacher evaluations of behavior also found improvement as 25 of the 64 children (39.1%) improved into the normal range as measured by the Vanderbilt questionnaire. Moreover, children could successfully learn both yoga and meditation from high school students irrespective of their age, ADHD type, or initial performance impairment. The results demonstrate efficacy of a multimodal behavioral program incorporating yoga and meditation. The use of high school volunteers from schools in the area demonstrates an effective low-cost and universally applicable approach.

Malaria in assam: a challenge.

RESEARCH QUESTION: What is the trend of malaria and proportion of Plasmodium falciparum infections amongst troops of the Army units deployed in Assam over the last 5 years? STUDY DESIGN: Retrospective cross -sectional descriptive study. SETTING: Army units deployed in the state of Assam over the last 5 years. PARTICIPANTS: Population of army units deployed in the state of Assam over the last 5 years. STATISTICAL ANALYSIS: Percentage, Chi square. RESULTS: Malaria contributed to 3.60% to 7% of all hospital admissions over the period of 5 years. The overall malaria incidence showed a significantly increasing trend during the study period. (Chi square for linear trend = 5.19; P = 0.023). Out of these, P falciparum contributed 86% to 98%. The proportion of P falciparum infections showed a significantly increasing trend from 2005 to 2006. (Yate's corrected Chi square = 7.123; P = 0.008).

The effect of ethnicity on the relationship between premature coronary artery disease and traditional cardiac risk factors among uninsured young adults.

Prior studies of premature coronary artery disease (CAD) in young adults did not address the association of race/ethnicity and risk factors. Therefore, the authors conducted a study of 400 patients 40 years and older undergoing coronary angiography at a large, urban public hospital that serves predominantly minority, uninsured populations. The prevalence of risk factors and their association with premature CAD varied markedly by ethnic group. Among blacks, dyslipidemia, diabetes, and smoking were independently associated with premature CAD. Among Hispanics, dyslipidemia, male sex, and family history of CAD were independently associated with premature CAD. Smoking was the only risk factor in whites, and no independent risk factor was identified in Asian Indians. Whites and Asian Indians had a higher prevalence of disease than blacks or Hispanics--before and after adjusting for risk factor imbalances across ethnic groups. In this ethnically diverse population, the authors' findings underscore the importance of identifying distinctive risk factors in various ethnic groups.