Lacticaseibacillus rhamnosus HA-114 and Bacillus subtilis R0179 Prolong Lifespan and Mitigate Amyloid-ß Toxicity in C. elegans via Distinct Mechanisms.

Background: Recent advances linking gut dysbiosis with neurocognitive disorders such as Alzheimer's disease (AD) suggest that the microbiota-gut-brain axis could be targeted for AD prevention, management, or treatment. Objective: We sought to identify probiotics that can delay Aß-induced paralysis. Methods: Using C. elegans expressing human amyloid-ß (Aß)1-42 in body wall muscles (GMC101), we assessed the effects of several probiotic strains on paralysis. Results: We found that Lacticaseibacillus rhamnosus HA-114 and Bacillus subtilis R0179, but not their supernatants or heat-treated forms, delayed paralysis and prolonged lifespan without affecting the levels of amyloid-ß aggregates. To uncover the mechanism involved, we explored the role of two known pathways involved in neurogenerative diseases, namely mitophagy, via deletion of the mitophagy factor PINK-1, and fatty acid desaturation, via deletion of the Δ9 desaturase FAT-5. Pink-1 deletion in GMC101 worms did not modify the life-prolonging and anti-paralysis effects of HA-114 but reduced the protective effect of R0179 against paralysis without affecting its life-prolonging effect. Upon fat5 deletion in GMC101 worms, the monounsaturated C14:1 and C16:1 FAs conserved their beneficial effect while the saturated C14:0 and C16:0 FAs did not. The beneficial effects of R0179 on both lifespan and paralysis remained unaffected by fat-5 deletion, while the beneficial effect of HA-114 on paralysis and lifespan was significantly reduced. Conclusions: Collectively with clinical and preclinical evidence in other models, our results suggest that HA-114 or R0179 could be studied as potential therapeutical adjuncts in neurodegenerative diseases such as AD.

Sedation practices in gastrointestinal endoscopy-A survey from southern India.

Gastrointestinal endoscopies can cause an unpleasant experience for the patient. In India, most endoscopists follow a common institutional policy for sedation. The aim of this study was to analyze the sedation practices in various endoscopy centers across southern India. Data were collected with the help of a structured questionnaire given to a senior endoscopist of the center. Data from the completed questionnaire were later analyzed. Data were obtained from 19 centers across southern India. All endoscopy suites had central oxygen supply and emergency cart. A defibrillator was available in 12 centers (63.2%). Common criteria followed for administering sedation included therapeutic procedures (84.2%), patients who requested sedation (63.2%), children (63.2%), high-risk procedures (57.9%), and uncooperative patients (57.9%). Monitoring methods included pulse oximetry alone in six centers (31.6%), pulse oximetry with blood pressure monitoring in five centers (26.3%), and pulse oximetry, blood pressure, and electrocardiography (ECG) monitoring in eight centers (42.1%). For advanced procedures like endoscopic ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP), sedation was universally used. An anesthesiologist was available in the endoscopy suite in eight centers (42.1%). Five endoscopists administered propofol sedation without anesthesiologist's presence (26.3%). Thirteen centers had a written protocol for pre-procedure risk assessment (68.4%). A dedicated post-procedure observation area was available in seventeen centers (89.5%). Seven centers followed a written post-sedation discharge protocol (36.8%). Significant variations exist in the practice of sedation among endoscopists in southern India. There is an urgent need to formulate guidelines by endoscopy societies for ensuring better patient outcomes in endoscopy.

The cooperation of enamelin and amelogenin in controlling octacalcium phosphate crystal morphology.

Enamel matrix proteins, including the most abundant amelogenin and lesser amounts of enamelin, ameloblastin, and proteinases, play vital roles in controlling crystal nucleation and growth during enamel formation. The cooperative action between amelogenin and the 32-kDa enamelin is critical to regulating the growth morphology of octacalcium phosphate crystals. Using biophysical methods, we investigated the interaction between the 32-kDa enamelin and recombinant pig amelogenin 148 (rP148) at pH 6.5 in phosphate-buffered saline (PBS). Dynamic light scattering results showed a trend of increasing particle size in the mixture with the addition of enamelin to amelogenin. Upon addition of the 32-kDa enamelin, the shift and intensity decrease in the ellipticity minima of rP148 in the circular dichroism spectra of rP148 illustrated a direct interaction between the 2 proteins. In the fluorescence spectra, the maximum emission of rP148 was blue shifted from 335 to 333 nm in the presence of enamelin as a result of complexation of the 2 proteins. Our results demonstrate that the 32-kDa enamelin has a close association with amelogenin at pH 6.5 in PBS buffer. Our present study provides novel insights into the possible cooperation between enamelin and amelogenin in macromolecular coassembly and in controlling enamel mineral formation.

Imatinib-induced pancreatitis.

Drug-induced pancreatitis is a rare but serious complication of many drugs, some of which have been well documented. Here we present a case of a middle-aged man with chronic myeloid leukemia who developed acute pancreatitis after being initiated on imatinib mesylate. The case history, the pharmacodynamics, uses, and adverse effects of imatinib mesylate are discussed in detail.

Immunogenic potential of Enterococcus faecalis biofilm under simulated growth conditions.

INTRODUCTION: The aim of this study was to evaluate the effect of growth modes (planktonic and biofilms) of Enterococcus faecalis on the intracellular survival and ability to produce tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-6 after interacting with monocytes/in vitro-differentiated macrophages. METHODS: In vitro biofilms of three E. faecalis strains (ATCC-29212, OG1RF, and FA2-2) were grown on dentin under simulated nutrient-rich and nutrient-deprived conditions. Biofilm-derived E. faecalis cells were incubated with monocytes/in vitro-differentiated human macrophages. A fluorometric assay was used to quantify the surface adherent bacteria, whereas an antibiotic protection assay was used to quantify the internalized E. faecalis cells 6 to 48 hours after interaction with macrophages. TNF-alpha and IL-6 produced during this interaction were quantified by an enzyme-linked immunosorbent assay. RESULTS: The surface adherence and intracellular survival of E. faecalis within macrophages was significantly higher in biofilm bacteria when compared with planktonic cells (p 0.05). CONCLUSION: Biofilm cells of E. faecalis interacting with macrophages showed higher potential for surface adherence, intracellular survival and produced lesser amounts of IL-6 and TNF-alpha when compared to planktonic cells. Further experiments are required to understand the clinical implication of the intracellular survival of E. faecalis biofilm.

Influence of irrigation regimens on the adherence of Enterococcus faecalis to root canal dentin.

Enterococcus faecalis is frequently associated with post-treatment endodontic infections. Because adherence of bacteria to a substrate is the earliest stage in biofilm formation, eliciting the factors that links adherence of this bacterium to dentin would help in understanding its association with treatment-failed root canals. This investigation aimed to study the effects of endodontic irrigants on the adherence of E. faecalis to dentin. The bacteria adherence assay was conducted by using fluorescence microscopy, and the adhesion force was measured by using atomic force microscopy. There were significant increases in adherence and adhesion force after irrigation of dentin with ethylenediaminetetraacetic acid (EDTA), whereas sodium hypochlorite (NaOCl) reduced it. With the use of chlorhexidine (CHX), the force of adhesion increased, but the adherence assay showed a reduction in the number of adhering bacteria. The irrigation regimen of EDTA, NaOCl, and CHX resulted in the least number of adhering E. faecalis cells. This study highlighted that chemicals that alter the physicochemical properties of dentin will influence the nature of adherence, adhesion force, and subsequent biofilm formation of E. faecalis to dentin.