Diarrhea In Adults Research Articles

Escherichia coli diarrhoea among the adults – prospective research

Introduction: Eschrichia coli is common diarrhea causing agent. This study aimed to identify the bacterial pathogens responsible for diarrhea and abdominal pain in adults. Foodborne illnesses remain a significant public health concern, with Escherichia coli. Methods: The study, conducted from January to May 2021 at GSL Medical College, included adults with diarrhea and abdominal pain. Stool samples were collected, processed, and cultured on selective media to identify bacterial pathogens. Statistical analysis was performed to assess pathogen prevalence and its association with symptoms, using descriptive statistics for findings interpretation. Results: Among 100 adults with diarrhea and abdominal pain, 52% were male, and the majority (40%) were aged 31–45 years. Abdominal pain (80%) and diarrhea (75%) were the most common symptoms. Escherichia coli was the leading isolate (30%), followed by Salmonella spp. (25%) and Staphylococcus aureus (20%). Conclusion: In conclusion, this study highlights Escherichia coli as the primary bacterial cause of diarrhea among adults, followed by Salmonella spp. and Staphylococcus aureus. These findings underscore the importance of targeted food safety measures and public health interventions to address foodborne pathogens and prevent related illnesses in communities. Key words: Escherichia coli, Diarrhea, Foodborne pathogens, Abdominal pain, Bacterial isolation

ReNeu: A Pivotal, Phase IIb Trial of Mirdametinib in Adults and Children With Symptomatic Neurofibromatosis Type 1-Associated Plexiform Neurofibroma.

Pharmacologic therapies for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PNs) are limited; currently, none are US Food and Drug Administration-approved for adults. ReNeu is an open-label, multicenter, pivotal, phase IIb trial of mirdametinib in 58 adults (≥18 years of age) and 56 children (2 to 17 years of age) with NF1-PN causing significant morbidities. Patients received mirdametinib capsules or tablets for oral suspension (2 mg/m2 twice daily, maximum 4 mg twice daily), regardless of food intake, in 3 weeks on/1 week off 28-day cycles. The primary end point was confirmed objective response rate (ORR; proportion of patients with a ≥20% reduction of target PN volume from baseline on consecutive scans during the 24-cycle treatment phase) assessed by blinded independent central review (BICR) of volumetric magnetic resonance imaging. Twenty-four of 58 adults (41%) and 29 of 56 children (52%) had a BICR-confirmed objective response during the 24-cycle treatment phase; in addition, two adults and one child had confirmed responses during long-term follow-up. Median (range) target PN volumetric best response was -41% (-90 to 13) in adults and -42% (-91 to 48) in children. Both cohorts reported significant and clinically meaningful improvement in patient- or parent proxy-reported outcome measures of worst tumor pain severity, pain interference, and health-related quality of life (HRQOL) that began early and were sustained during treatment. The most commonly reported treatment-related adverse events were dermatitis acneiform, diarrhea, and nausea in adults and dermatitis acneiform, diarrhea, and paronychia in children. In ReNeu, the largest multicenter NF1-PN trial reported to date, mirdametinib treatment demonstrated significant confirmed ORRs by BICR, deep and durable PN volume reductions, and early, sustained, and clinically meaningful improvement in pain and HRQOL. Mirdametinib was well-tolerated in adults and children.

The effect of blended tube feeding compared to conventional formula on clinical outcomes in adults: A systematic review.

To explore the effect of blended tube feeding compared to conventional formulas on nutritional status, quality of life, anthropometry, diarrhoea and tube blockages in adults receiving tube feeding. The protocol was registered (PROSPERO CRD42022372443). Five databases (MEDLINE, EMBASE, CINAHL, Scopus, CENTRAL) were searched from commencement of database to 14th June 2023 to identify studies comparing blended tube feeding to conventional formulas in adults receiving tube feeding. Certainty assessment was conducted using the Cochrane Risk of Bias Tools and the Grading of Recommendations, Assessment, Development and Evaluations framework, and a narrative synthesis of results is provided. From 4227 studies screened, eight were included (total n = 763 patients, 9-215 patients). Three studies were hospital-based and five were home-based with duration from 8 days-8 months. Blended tube feeding and conventional formulas were nutritionally equivalent in only three studies; energy and protein concentration of formulas ranged from 1.7-7.1 kJ/mL and 21-68.5 g/L for the blended tube feeding groups, and 4.2-6.7 kJ/mL and 39-100 g/L for the conventional groups. No studies assessed nutrition status or quality of life using validated measures. Blended tube feeding was associated with a clinically relevant reduction in diarrhoea with a low level of certainty. For remaining outcomes, there were inconclusive findings and an overall very low certainty of evidence for each. The effect of blended tube feeding compared to conventional formulas on all outcomes remains uncertain. Blended tube feeding may reduce the incidence of diarrhoea. Future research using nutritionally equivalent comparisons and validated outcome measures is required.

The current riboswitch landscape in Clostridioides difficile.

Riboswitches are 5' RNA regulatory elements that are capable of binding to various ligands, such as small metabolites, ions and tRNAs, leading to conformational changes and affecting gene transcription or translation. They are widespread in bacteria and frequently control genes that are essential for the survival or virulence of major pathogens. As a result, they represent promising targets for the development of new antimicrobial treatments. Clostridioides difficile, a leading cause of antibiotic-associated nosocomial diarrhoea in adults, possesses numerous riboswitches in its genome. Accumulating knowledge of riboswitch-based regulatory mechanisms provides insights into the potential therapeutic targets for treating C. difficile infections. This review offers an in-depth examination of the current state of knowledge regarding riboswitch-mediated regulation in C. difficile, highlighting their importance in bacterial adaptability and pathogenicity. Particular attention is given to the ligand specificity and function of known riboswitches in this bacterium. The review also discusses the recent progress that has been made in the development of riboswitch-targeting compounds as potential treatments for C. difficile infections. Future research directions are proposed, emphasizing the need for detailed structural and functional analyses of riboswitches to fully harness their regulatory capabilities for developing new antimicrobial strategies.

Postbiotics: A new member in the biotics family.

Postbiotics were defined in 2021 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) as a "preparation of inanimate microorganisms and/or their cellular components that confers a health benefit to the host." The field of postbiotics is a new area within the biotics family; numerous products have already been developed for clinical applications, such as immune stimulation, the management of diarrhea in children and adults, the management of irritable bowel syndrome, and 3 infant formulas. In particular, infant formulas with postbiotics obtained from milk fermented with Bifidobacteriumbreve C50 and Streptococcusthermophilus O65 -and their metabolites-, including the oligosaccharide 3'-GL, have demonstrated to be safe and to contribute to the development of the gut microbiota and the gutassociated immune system. These modifications help to prevent and manage functional gastrointestinal disorders in infants.

The role of pharmaceutical care in the use of rifaximin for the treatment of diarrhea

the management of diarrhea represents a prevalent issue within the realm of healthcare. Rifaximin is recommended to treat traveler's diarrhea and irritable bowel syndrome. At the same time, it is important to rationally use an antimicrobial drug to prevent the development of antimicrobial resistance. Aim: to evaluate the role of pharmaceutical care in using rifaximin to treat diarrhea, based on a questionnaire. A questionnaire survey was done among 55 pharmacy professionals and 42 pharmacy visitors regarding the dispensing and use of rifaximin for diarrhea treatment. The survey of pharmacy visitors revealed that rifaximin was used for the treatment of small intestinal bacterial overgrowth syndrome (32 cases), traveler's diarrhea (7 cases), and irritable bowel syndrome with diarrhea (3 cases). Patients did not undergo stool culture before rifaximin prescription, which could have prevented antimicrobial resistance and ruled out other causes of diarrhea. It was found that 14% of respondents reported improvement the next day, while 83.3% reported improvement within three days. Pharmacists can educate visitors about the importance of completing the treatment course. Five percent of respondents reported nausea as an adverse reaction. Pharmacists dispensed rifaximin for the treatment of diarrhea in adults almost three times more often than in children. The tablet form of the drug was used in 94.5% of cases, while the oral suspension was used in 5.5% of cases. The majority of pharmacy visitors (89.0%) received rifaximin with a doctor's prescription, and 10.9% without a prescription, which emphasizes the importance of pharmaceutical care to prevent irrational use of the drug. The results of the study show that 92.7% of pharmacists provide recommendations on the safety of rifaximin use, and 78.2% recommend abstaining from alcohol during treatment. Only 21.8% of pharmacists warn about the possible staining of urine, which can cause concern for patients. The majority of pharmacists (89.1%) systematically ask women about possible pregnancy, which indicates their awareness of safe pharmacotherapy. Pharmacists also clarify the simultaneous use of rifaximin with other drugs: 32.7% ask about taking oral contraceptives, 7.3% – antiarrhythmic drugs, and 3.6% – warfarin. mailto:https://meshb.nlm.nih.gov/record/ui?ui=D002648Pharmacists can enhance the effectiveness of rifaximin treatment by preventing its uncontrolled use, emphasizing the importance of completing the treatment course and informing about possible adverse reactions. When providing pharmaceutical care to visitors taking rifaximin, pharmacists should educate them about potential changes in urine color. Additionally, pharmaceutical workers advise women taking oral contraceptives to use additional contraceptive methods while taking rifaximin.

Adherence to Clinical Practice Guidelines on the Management of Acute Infectious Gastroenteritis in Children as a Measure of Quality of Care Delivered by a Primary Care Facility in Rural Philippines: A Descriptive Retrospective Study.

This study aimed to describe the pattern of prescription and laboratory use in the management of infectious acute gastroenteritis (AGE) in children seen in a rural service delivery network (SDN) and to determine their adherence to the 2019 Clinical Practice Guidelines on the Management of Acute Infectious Diarrhea in Children and Adults from the Department of Health (DOH). A descriptive retrospective study was done using the electronic medical records (EMR) of patients less than 19 years old seen by the rural SDN from April 2019-2021 and diagnosed with infectious AGE. Data were extracted on diagnostic and therapeutic management. Adherence to strong CPG recommendations focusing on rehydration, zinc supplementation, rational laboratory use, and antibiotic prescription was chosen as indicator of quality of care. Adherence of less than 70% was defined as low. There were 227 infectious AGE cases, with 72% diagnosed under non-specific infectious AGE. Fifty two percent (52%) were prescribed with low-osmolarity oral rehydration solutions (ORS), while 74% were given zinc. Stool analysis was done in 25% of cases while CBC was done in 20%. Top antibiotics given were metronidazole at 44% and cotrimoxazole at 33%. There was low adherence to prescribing low-osmolarity ORS for rehydration (52%) and to deferring routine antibiotic prescription for non-specific infectious AGE cases (24%). Adherence to deferring routine stool analysis and CBC were relatively high at 73% and 70%, respectively while adherence to antibiotic use for indicated cases was high at 95%. Frequency of diagnostics ordered were low resulting to high adherence rates to recommendations concerning judicious laboratory use. Prescription frequency of appropriate antibiotics and interventions for AGE were low, leading to low adherence rates to recommendations concerning rational antibiotic use and prescription of cornerstone therapies for infectious AGE.

Effects of postbiotics on chronic diarrhea in young adults: a randomized, double-blind, placebo-controlled crossover trial assessing clinical symptoms, gut microbiota, and metabolite profiles.

Chronic diarrhea has a considerable impact on quality of life. This randomized, double-blind, placebo-controlled crossover intervention trial was conducted with 69 participants (36 in Group A, 33 in Group B), aiming to investigate the potential of postbiotics in alleviating diarrhea-associated symptoms. Participants received postbiotic Probio-Eco® and placebo for 21 days each in alternating order, with a 14-day washout period between interventions. The results showed that postbiotic intake resulted in significant improvements in Bristol stool scale score, defecation frequency, urgency, and anxiety. Moreover, the postbiotic intervention increased beneficial intestinal bacteria, including Dysosmobacter welbionis and Faecalibacterium prausnitzii, while reducing potential pathogens like Megamonas funiformis. The levels of gut Microviridae notably increased. Non-targeted metabolomics analysis revealed postbiotic-driven enrichment of beneficial metabolites, including α-linolenic acid and p-methoxycinnamic acid, and reduction of diarrhea-associated metabolites, including theophylline, piperine, capsaicin, and phenylalanine. Targeted metabolomics confirmed a significant increase in fecal butyric acid after postbiotic intervention. The levels of aromatic amino acids, phenylalanine and tryptophan, and their related metabolites, 5-hydroxytryptophan and kynurenine, decreased after the postbiotic intervention, suggesting diarrhea alleviation was through modulating the tryptophan-5-hydroxytryptamine and tryptophan-kynurenine pathways. Additionally, chenodeoxycholic acid, a diarrhea-linked primary bile acid, decreased substantially. In conclusion, postbiotics have shown promise in relieving chronic diarrhea.

Lactiplantibacillus plantarum P9 for chronic diarrhea in young adults: a large double-blind, randomized, placebo-controlled trial

Current treatments for chronic diarrhea have limited efficacy and several side effects. Probiotics have the potential to alleviate symptoms of diarrhea. This randomized, double-blind, placebo-controlled trial evaluates the effects of administering the probiotic Lactiplantibacillus plantarum P9 (P9) strain in young adults with chronic diarrhea (Clinical Trial Registration Number: ChiCTR2000038410). The intervention period lasts for 28 days, followed by a 14-day post-intervention period. Participants are randomized into the P9 (n = 93) and placebo (n = 96) groups, with 170 individuals completing the double-blind intervention phase (n = 85 per group). The primary endpoint is the diarrhea symptom severity score. Both intention-to-treat (n = 189) and per-protocol (n = 170) analyses reveal a modest yet statistically significant reduction in diarrhea severity compared to the placebo group (20.0%, P = 0.050; 21.4%, P = 0.048, respectively). In conclusion, the results of this study support the use of probiotics in managing chronic diarrhea in young adults. However, the lack of blood parameter assessment and the short intervention period represent limitations of this study.

Relationship between dietary fiber intake and chronic diarrhea in adults.

Dietary fiber is essential for human health and can help reduce the symptoms of constipation. However, the relationship between dietary fiber and diarrhea is, poorly understood. To evaluate the relationship between dietary fiber and chronic diarrhea. This retrospective study was conducted using data from the United States National Health and Nutrition Examination Survey, conducted between 2005 and 2010. Participants over the age of 20 were included. To measure dietary fiber consumption, two 24-hour meal recall interviews were conducted. The independent relationship between the total amount of dietary fiber and chronic diarrhea was evaluated with multiple logistic regression and interaction analysis. Data from 12829 participants were analyzed. Participants without chronic diarrhea consumed more dietary fiber than participants with chronic diarrhea (29.7 vs 28.5, P = 0.004). Additionally, in participants with chronic diarrhea, a correlation between sex and dietary fiber intake was present: Women who consume more than 25 g of dietary fiber daily can reduce the occurrence of chronic diarrhea. Dietary fiber can reduce the occurrence of chronic diarrhea.

Infectious etiologies of persistent and chronic diarrhea in Asian developing countries: A systematic review and meta-analysis.

Infectious causes of diarrhea contribute significantly to morbidity in Asia. We conducted a systematic review and meta-analysis of the prevalence of infectious etiologies of persistent and chronic diarrhea in Asian adults. Searches were performed on PubMed and Scopus for studies from January 1, 1970, to May 30, 2023. Sixteen studies were identified and included. The meta-analysis was conducted with the random-effects method, estimating the pooled prevalence of groups of infectious pathogens as causes of persistent and chronic diarrhea among Asian adults. The findings were highly heterogeneous and indicative of publication bias. The majority of studies were conducted on persons living with human immunodeficiency virus infection (PLHIV). The studies were predominantly from low-income and middle-income Asian countries. The most common cause was parasitic, with a pooled prevalence of 0.52 (95% confidence interval 0.28-0.65, I2=99%, Cochran's Q=1027.44, P<0.01), followed by bacterial, fungal, and viral causes, which were substantially rarer. Negative microbiological testing was also common, with a pooled prevalence for a negative test being 0.37 (95% confidence interval 0.17-0.52, I2=99%, Cochran's Q=1027.44, P<0.01). Subgroup analyses of studies conducted among PLHIV, from year 2000 and among those conducted in Southeast Asia showed a similar prevalence of parasitic causes of diarrhea. In conclusion, inAsian adults with persistent and chronic diarrhea, parasitic causes were most prevalent. However, the estimate of true prevalence is limited by significant heterogeneity among the available studies. More study in this field is required, especially examining PLHIV in the post-antiretroviral therapy era and from high-income countries.

Abstract PO3-13-01: ONTARGET: Phase 3 randomized, double-blind, placebo-controlled trial evaluating crofelemer for the prophylaxis of diarrhea in adult patients with solid tumors receiving targeted therapies with or without standard chemotherapy

Abstract Background: Cancer therapy-related diarrhea (CTD) can result in fluid and electrolyte losses, malnutrition, unexpected hospitalization, and poor quality of life (QoL) of patients with cancer. CTD can also limit response to cancer therapy due to treatment interruption, discontinuations, or dose modifications. CTD is a common side effect of targeted therapies (TTx) (e.g., inhibitors of tyrosine kinases, EGFR, CDK4/6, VEGFR) with or without concomitant chemotherapy (ChemoRx) for treating various solid tumors, including breast cancer (BRCA). TTx induce CTD by increasing intracellular cAMP or Ca++ leading to activation of two intestinal Cl- channels, CFTR and CaCC, increasing luminal secretion of Cl- and accompanying loss of Na+ and fluids. For most patients with cancer, CTD management with dietary modifications and antimotility agents is suboptimal. New drugs are needed to prevent or mitigate CTD, a huge unmet medical need. Since the mechanism of CTD is mostly secretory, we hypothesized that crofelemer (CRO) an oral botanical drug purified from the latex of the Croton lechleri tree that modulates both intestinal Cl- ion channels, CFTR and CaCC, may benefit preventing CTD. CRO is negligibly absorbed orally and is FDA-approved for symptomatic relief of noninfectious diarrhea in adults with HIV/AIDS on antiretroviral therapy. In a phase 2 study in 51 women with BRCA receiving THP/TCHP (HALT-D), CRO given daily, compared to standard of care (SOC), for 2 cycles resulted in grade ≥2 diarrhea in significantly fewer subjects (9.0% vs. 33.3%, p=0.0361) in cycle 2 and was 1.8 times more likely to resolve diarrhea (p=0.0425) (Pohlmann et al. 2022; NCT02910219) Methods: ONTARGET (NCT04538625) is a randomized, multicenter, international, double-blind, placebo-controlled pivotal trial evaluating CRO for the prophylaxis of diarrhea in adults with solid tumors receiving 1 of 24 diarrheagenic TTx known to cause any grade diarrhea in ≥50% of patients. This study is designed to show a 40% reduction in loose/watery (LW) stools in patients randomized 1:1 CRO to placebo (1-sided α=0.025) and stratified by tumor type (lung, breast, other) and TTx type (CDK4/6i, TKIs, or other). Eligible patients require a new TTx, ECOG 0-2, lack baseline diarrhea and can complete patient-reported outcome (PRO) diary using a mobile device. Key exclusions include immunotherapy, neratinib or irinotecan (due to required SOC antimotility prophylaxis), colitis/ostomy/abdominal surgery ≤3 months, or antidiarrheal/laxative/antibiotic use ≤7 days. Oral CRO 125 mg or a matching placebo is administered twice daily concomitant with TTx initiation and continued for 12 weeks, with the option to continue blinded treatment through 24 weeks. Rescue antidiarrheal medication is permitted when participants have ≥4 LW stools and can continue thereafter. PRO diaries capture clinical and QoL outcomes. The primary endpoint is the mean weekly number of LW stools over 12 weeks based on PRO diary using the Bristol Stool Form Scale. Key secondary endpoints include time to TTx/ChemoRx dose reduction or discontinuation, time to ≥4 LW stools for 2 consecutive days, fecal incontinence episodes, and time to durable responder status (≤7 LW stools/week). PRO diaries capture: 1) LW stool frequency daily; 2) TTx/ChemoRx dose reduction/discontinuation, use of antimotility drugs, fecal incontinence daily; and 3) CTD’s impact on QoL weekly. Results: Enrollment is complete with 287 patients from 46 sites in 5 countries from 8/2020 through 5/2023. Primary cancer diagnoses were breast (183; 64%), lung (37; 13%), renal (36; 12.5%), liver (12; 4%) and other (19; 6.5%). Most frequent TTx were CDK 4/6 and EGFR inhibitors. To our knowledge this trial evaluating CRO is the first prospective, randomized double blind study for prevention of targeted therapy CTD. Topline results for the study are expected in Q4 2023 and will be reported at the meeting. Funded by Napo Pharmaceuticals (a Jaguar Health Co.) Citation Format: Lee Schwartzberg, Pablo Okhuysen, Eric Roeland, Gregory Vidal, Kathleen Harnden, Richard Zuniga, Snezana Bosnjak, Sreedevi Daggubati, Daliborka Bursac. ONTARGET: Phase 3 randomized, double-blind, placebo-controlled trial evaluating crofelemer for the prophylaxis of diarrhea in adult patients with solid tumors receiving targeted therapies with or without standard chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-13-01.

Cryo-EM structure of rotavirus B NSP2 reveals its unique tertiary architecture.

Rotavirus (RV) NSP2 is a multifunctional RNA chaperone that exhibits numerous activities that are essential for replication and viral genome packaging. We performed an in silico analysis that highlighted a distant relationship of NSP2 from rotavirus B (RVB) to proteins from other human RVs. We solved a cryo-electron microscopy structure of RVB NSP2 that shows structural differences with corresponding proteins from other human RVs. Based on the structure, we identified amino acid residues that are involved in RNA interactions. Anisotropy titration experiments showed that these residues are important for nucleic acid binding. We also identified structural motifs that are conserved in all RV species. Collectively, our data complete the structural characterization of rotaviral NSP2 protein and demonstrate its structural diversity among RV species.IMPORTANCERotavirus B (RVB), also known as adult diarrhea rotavirus, has caused epidemics of severe diarrhea in China, India, and Bangladesh. Thousands of people are infected in a single RVB epidemic. However, information on this group of rotaviruses remains limited. As NSP2 is an essential protein in the viral life cycle, including its role in the formation of replication factories, it may be a target for future antiviral strategy against viruses with similar mechanisms.

Prevalence and Correlates of Infectious Diarrhoea in Adults at Livingstone University Teaching Hospital, Zambia

Diarrhoea – defined as loose or watery stools for more than three times per day, is a common clinical problem. Worldwide, diseases causing infectious diarrhoea remain a major public health threat. Infectious diarrhoea in adults has been a major concern in developing countries, including Zambia. No study was conducted so far to estimate the infectious diarrhoeal load in the southern province of Zambia. Hence, the study aimed to determine the prevalence and factors associated with infectious diarrhoea in adults at Livingstone University Teaching Hospital. This cross-section study was conducted from January 2019 to December 2020 using a structured data collection tool and random sampling technique to select participants for the research. Of the 4,977 participants that were recorded, 7.9% reported having episodes of diarrhoea. The prevalence of diarrhoea was significantly more in females (55.2%) compared to males (44.8%). Additionally, a slightly high prevalence of patients with diarrhoea did not know their HIV status (35.9%), and more of these patients were from the rural areas (52.7%), and a significantly higher prevalence had no other underlying medical conditions (81.2%). This study concluded that diarrheal diseases are significantly prevalent among adult patients reporting at Livingstone University Teaching Hospital. Age was highly associated with infectious diarrhoea.

Anti-S-layer monoclonal antibodies impact Clostridioides difficile physiology

ABSTRACT Clostridioides difficile (C. difficile), a gram-positive anaerobic and spore-forming bacterium, is the leading cause of nosocomial antibiotic-associated diarrhea in adults which is characterized by high levels of recurrence and mortality. Surface (S)-layer Protein A (SlpA), the most abundantly expressed protein on the bacterial surface, plays a crucial role in the early stages of infection although the nature of its involvement in C. difficile physiology is yet to be fully understood. Anti-S-layer antibodies have been identified in the sera of convalescent patients and have been correlated with improved outcomes of C. difficile infection (CDI). However, the precise mechanisms by which anti-S-layer antibodies confer protection to the host remain unknown. In this study, we report the first monoclonal antibodies (mAbs) targeting the S-layer of reference strain 630. Characterization of these mAbs unraveled important roles for the S-layer protein in growth, toxin secretion, and biofilm formation by C. difficile, with differential and even opposite effects of various anti-SlpA mAbs on these functions. Moreover, one anti-SlpA mAb impaired C. difficile growth and conferred sensitivity to lysozyme-induced lysis. The results of this study show that anti-S-layer antibody responses can be beneficial or harmful for the course of CDI and provide important insights for the development of adequate S-layer-targeting therapeutics.

A monoclonal antibody collection for C. difficile typing ?

Clostridioides difficile is the leading cause of antibiotic-associated diarrhea and pseudomembranous colitis in adults. Various C. difficile strains circulate currently, associated with different outcomes and antibiotic resistance profiles. However, most studies still focus on the reference strain 630 that does not circulate anymore, partly due to the lack of immunological tools to study current clinically important C. difficile PCR ribotypes. The goal of this study was to generate monoclonal antibodies recognizing various epidemic ribotypes of C. difficile. To do so, we immunized mice expressing human variable antibody genes with the Low Molecular Weight (LMW) subunit of the surface layer protein SlpA from various C. difficile strains. Monoclonal antibodies purified from hybridomas bound LMW with high-affinity and whole bacteria from current C. difficile ribotypes with different cross-specificities. This first collection of anti-C. difficile mAbs represent valuable tools for basic and clinical research.

Associations of thyroid hormones with chronic diarrhea and constipation in euthyroid individuals.

Abnormalities in thyroid function affect bowel health. However, the relationships between thyroid hormone concentrations and the risk of developing chronic diarrhea and constipation remain unclear. Thus, the aim of this study was to investigate the relationships between thyroid hormone concentrations and the risk of developing chronic diarrhea and constipation in euthyroid US adults. The data for this population-based study were taken from the National Health and Nutrition Examination Survey (NHANES) 2007-2010 datasets. The relationships between thyroid hormone concentrations and the risk of developing chronic diarrhea and constipation were examined via multivariate regression. Smoothed curve fitting and threshold effects analysis were used to test for nonlinear relationships and inflection points. This study involved 4999 participants ranging in age from 20 to 80 years. Multivariate logistic regression analysis revealed a significant positive correlation between FT3 concentrations and the risk of developing chronic diarrhea [1.37 (1.00, 1.88), P=0.049]. Multivariate linear regression analysis revealed a significant positive correlation between FT3 concentrations and the number of bowel movements [0.84 (0.39, 1.28), P<0.001]. Using smoothed curve fitting and the two-stage regression model, we found a nonlinear relationship between FT4 concentrations and chronic diarrhea, with a breakpoint of 0.79 ng/dl. There were associations between thyroid hormone concentrations and abnormal bowel habits, particularly between FT3 concentrations and the risk of developing chronic diarrhea. A higher FT3 level was associated with an increased risk of developing chronic diarrhea and more frequent bowel movements. To validate our results, further large-scale prospective studies are needed.

Effects of &lt;i&gt;Lactobacillus delbrueckii&lt;/i&gt; TS1-06 probiotic strain on the size of myocardial infarction in Wistar rats with systemic inflammatory response syndrome

Experimental medicine provides the scientific community with a plethora of information on therapeutic efficacy of probiotic strains. However, from the point of view of evidence-based medicine, the list of disorders controlled by probiotics is limited to antibiotic-associated diarrhea in adults and children, Clostridium difficile-associated diarrhea, acute infectious diarrhea in children and adults, eradication therapy, ulcerative colitis and irritable bowel syndrome. Recently, these indications are also amended by well-validated clinical guidelines for the usage of probiotic preparations, in order to modulate immunity. Given the permeability of gastrointestinal and immune system barriers for pathogenic and opportunistic microbiota, it seems logical to assume the effectiveness of probiotics as potential symbiotic regulators of nervous and cardiovascular systems. It should also be taken into account that metabolic disorders, e.g., obesity, with a low-intensity inflammatory response and characteristic cytokine pattern, are acquired as a gain of human civilization. In this regard, we propose a scientific hypothesis about the effectiveness of probiotic microbial strains in increasing myocardial resistance to ischemic-reperfusion injury, due to their ability to block individual links of the cytokine cascade during the development of inflammatory response, for its subsequent translation into clinical practice.The development and validation of a new experimental model of systemic inflammatory response syndrome (SIRS) in male Wistar rats, including obesity, acute inflammatory process of the colon, and antibiotic-induced dysbiosis, became basic to the study of efficacy of probiotic drugs in terms of myocardial resistance to ischemicreperfusion injury (IRI). Rats with SIRS showed a significantly increased size of the infarction area (+28%) upon experiments with isolated perfused heart under global ischemia-reperfusion conditions. Significant changes in the leukocyte formula and immunological parameters associated with SIRS were corrected by introduction of a mixture of probiotic strains L. acidophilus (LA-5) and B. animalis subsp. lactis (BB-12), and the isolated strain L. delbrueckii TS1-06. In both groups with probiotic correction, there was a decrease in the infarction area compared to the SIRS group. General and specific changes in IL-2, transforming growth factor-b (TGF-b) and tumor necrosis factor-a (TNFa) were noted. The reduction of myocardial infarction by probiotics may be related to the blocking of first-order cytokines, which leads to a «break» of proinflammatory cascade. A need for in-depth study of cardioprotective mechanisms mediated by probiotics was confirmed due to their potential usage as a symbiotic alternative to biological drugs which block the main pro-inflammatory cytokines.

An Unusual Case of Loperamide Toxicity in a Neonate - A Case Report

Introduction: Loperamide is an antidiarrheal agent approved by the Food and Drug Administration for the treatment of various forms of diarrhea in adults, including traveler’s diarrhea, irritable bowel syndrome associated with chronic diarrhea, and acute nonspecific diarrhea in patients 2 years of age and older, and reducing ileostomy output. The drug has, however, been shown to be toxic at therapeutic doses and causes serious cardiac adverse reactions, central nervous system (CNS) effects such as decreased level of consciousness, coordination abnormality, muscular hypertonia, miosis, respiratory depression, urinary retention, paralytic ileus, abdominal distension, and fecal impaction in infants and toddlers. Methods: We report an unusual case of suspected loperamide toxicity in a 22-day-old baby who presented with respiratory and CNS depression after consuming a single therapeutic dose of loperamide. Results: The neonate’s respiratory depression was attributed to ingestion of loperamide, prescribed by a local quack, as all other causes were ruled out. There was a significant improvement in the baby’s respiratory efforts after IV naloxone, an effective antidote. Conclusion: Special caution should be taken when administering loperamide to pediatric patients due to their greater variability in response. Loperamide is often given by local quacks as a nonprescription medicine for immediate relief, even to infants and toddlers, without complete knowledge about its potential side effects at therapeutic doses. To address this, it is imperative that strict measures should be taken.

Province clustering based on the percentage of communicable disease using the BCBimax biclustering algorithm.

Indonesia needs to lower its high infectious disease rate. This requires reliable data and following their temporal changes across provinces. We investigated the benefits of surveying the epidemiological situation with the imax biclustering algorithm using secondary data from a recent national scale survey of main infectious diseases from the National Basic Health Research (Riskesdas) covering 34 provinces in Indonesia. Hierarchical and k-means clustering can only handle one data source, but BCBimax biclustering can cluster rows and columns in a data matrix. Several experiments determined the best row and column threshold values, which is crucial for a useful result. The percentages of Indonesia's seven most common infectious diseases (ARI, pneumonia, diarrhoea, tuberculosis (TB), hepatitis, malaria, and filariasis) were ordered by province to form groups without considering proximity because clusters are usually far apart. ARI, pneumonia, and diarrhoea were divided into toddler and adult infections, making 10 target diseases instead of seven. The set of biclusters formed based on the presence and level of these diseases included 7 diseases with moderate to high disease levels, 5 diseases (formed by 2 clusters), 3 diseases, 2 diseases, and a final order that only included adult diarrhoea. In 6 of 8 clusters, diarrhea was the most prevalent infectious disease in Indonesia, making its eradication a priority. Direct person-to-person infections like ARI, pneumonia, TB, and diarrhoea were found in 4-6 of 8 clusters. These diseases are more common and spread faster than vector-borne diseases like malaria and filariasis, making them more important.