Search Results (680)

The stomach has been a highly conserved organ throughout vertebrate evolution; however, there are now over 20 lineages composed of monotremes, lungfish and teleost fish displaying a secondary loss of stomach function and morphology. This “agastric phenotype” has evolved convergently and is typified by a loss of gastric glands and gastric acid secretion and a near-to-complete loss of storage capacity of the stomach. All agastric species have lost the genes for gastric enzymes (Pga and Pgc) and proton pump subunits (Atp4a and Atp4b), and gastrin (Gast) has been lost in monotremes. As a key gastric hormone, the conservation of gastrin has not yet been investigated in the lungfish or agastric teleosts, and it is unclear how the loss of gastrin affects the evolution and selection of the native receptor (Cckbr), gastrin-releasing peptide (Grp) and gastrin-releasing peptide receptor (Grpr) in vertebrates. Furthermore, there are still many genes implicated in gastric development and function which have yet to be associated with the agastric phenotype. We analysed the evolution, selection and conservation of the gastrin pathway and a novel gastric gene repertoire (Gkn1, Gkn2, Tff1, Tff2, Vsig1 and Anxa10) to determine the correlation with the agastric phenotype. We found that the loss of gastrin or its associated genes does not correlate with the agastric phenotype, and their conservation is due to multiple pleiotropic roles throughout vertebrate evolution. We found a loss of the gastric gene repertoire in the agastric phenotype, except in the echidna, which retained several genes (Gkn1, Tff2 and Vsig1). Our findings suggest that the gastrin physiological pathway evolved differently in pleiotropic roles throughout vertebrate evolution and support the convergent evolution of the agastric phenotype through shared independent gene-loss events. Full article

Background: Studies have demonstrated a positive correlation between high body mass index (BMI) and an increased risk of Clostridioides difficile infection (CDI), independent of antibiotic usage or healthcare exposures. Aim: To compare the outcomes of obese (BMI ≥ 30 kg/m²) and non-obese (BMI < 30 kg/m²) hospitalized patients with CDI. Methods: This retrospective cohort study included patients with CDI hospitalized in Beilinson hospital between January 2013 and January 2020. The primary outcome was 90-day all-cause mortality. Secondary outcomes included 30-day mortality, colectomy, intensive care unit (ICU) admission and length of hospital stay (LOS). Multivariate analysis was performed to identify the risk factors independently associated with 90-day mortality. Results: The study included 889 patients: 131 (15%) obese and 758 (85%) non-obese. The obese group was younger (median age 65 years vs. 73 years (p < 0.01)) and with a higher rate of diabetes mellitus (57/131 (44%) vs. 180/758 (24%) (p < 0.01)). The 90-day mortality was lower in the obese group: 19/131 (15%) vs. 170/752 (23%) (p = 0.04). The 30-day mortality was 8/131 (6%) vs. 96/757 (13%) (p = 0.03). ICU admission was 9/131 (7%) vs. 23/758 (3%) (p = 0.03), and median LOS was 19 vs. 12 days (p < 0.01) in obese and non-obese groups, respectively. In the multivariable analysis, after adjustment for age, Charlson’s comorbidity index ≥3, assistance in activities of daily living, treatment with proton pump inhibitors and severity of illness, obesity was not a significant risk factor for 90-day mortality (OR = 0.65, 95% CI: 0.38–1.01; p = 0.1). Conclusions: In this study, obesity was not significantly associated with 90-day mortality after adjustment for other risk factors; however, ICU admission was higher and LOS longer in this group. Full article

To further enhance the economic performance of fuel cell vehicles (FCVs), this study develops a model-adaptive model predictive control (MPC) strategy. This strategy leverages the dynamic relationship between proton exchange membrane fuel cell (PEMFC) output characteristics and temperature to track its optimal operating temperature (OOT), addressing challenges of temperature control accuracy and high energy consumption in the PEMFC thermal management system (TMS). First, PEMFC and TMS models were developed and experimentally validated. Subsequently, the PEMFC power–temperature coupling curve was experimentally determined under multiple operating conditions to serve as the reference trajectory for TMS multi-objective optimization. For MPC controller design, the TMS model was linearized and discretized, yielding a predictive model adaptable to different load demands for stack temperature across the full operating range. A multi-constrained quadratic cost function was formulated, aiming to minimize the deviation of the PEMFC operating temperature from the OOT while accounting for TMS parasitic power consumption. Finally, simulations under Worldwide Harmonized Light Vehicles Test Cycle (WLTC) conditions evaluated the OOT tracking performance of both PID and MPC control strategies, as well as their impact on stack efficiency and TMS energy consumption at different ambient temperatures. The results indicate that, compared to PID control, MPC reduces temperature tracking error by 33%, decreases fan and pump speed fluctuations by over 24%, and lowers TMS energy consumption by 10%. These improvements enhance PEMFC operational stability and improve FCV energy efficiency. Full article

Background and Clinical Significance: Sarcina ventriculi is a rare Gram-positive coccus that thrives in acidic environments such as the human stomach. It has been increasingly identified in individuals with delayed gastric emptying and has been reported in association with various gastric disorders. However, its exact pathogenic role is not fully understood and remains controversial. Case Presentation: We present two cases of patients, one with a small bowel obstruction and the other with epigastric pain, both diagnosed with Sarcina ventriculi infection by histological examination of gastric biopsies. The patients were managed with a combination of antibiotics and a proton pump inhibitor, resulting in symptom resolution and clearance of Sarcina ventriculi upon follow-up examinations. Conclusions: This report explores the pathogenicity of Sarcina ventriculi by documenting its presence in symptomatic patients without other identifiable pathogens and demonstrating complete symptom resolution following targeted therapy. These findings raise the possibility of Sarcina ventriculi’s pathogenic potential under specific clinical conditions, suggesting it may act as more than a benign colonizer. Full article

Hypomagnesemia is a frequent and often underrecognized electrolyte disturbance with important clinical consequences, especially in hospitalized and critically ill patients. This multifactorial condition arises from impaired intestinal absorption, renal magnesium wasting, and the effects of various medications. Magnesium, the second most abundant intracellular cation, is crucial in enzymatic and physiological processes; its deficiency is associated with neuromuscular, cardiovascular, and metabolic complications. This narrative review focuses on the mechanisms and clinical consequences of drug-induced hypomagnesemia, highlighting the major drug classes involved such as diuretics, antibiotics, antineoplastic agents, and immunosuppressants. Management strategies include magnesium supplementation and adjunctive therapies like amiloride and SGLT2 inhibitors to reduce renal magnesium losses. Recognizing and addressing drug-induced hypomagnesemia is essential to improve patient outcomes and prevent long-term complications. Full article

Background and objectives: Life expectancies have increased globally, including in Romania, leading to an aging population and thus increasing the burden of chronic diseases. Over 80% of individuals over 65 have more than three chronic conditions, with many exceeding ten and often requiring multiple medications and supplements. This widespread polypharmacy raises concerns about drug interactions, side effects, and inappropriate prescribing. This review examines the impact of polypharmacy in older adult patients, focusing on the physiological changes affecting drug metabolism and the potential risks associated with excessive medication use. Special attention is given to proton pump inhibitors (PPIs), a commonly prescribed drug class with significant benefits but also risks when misused. The aging process alters drug absorption and metabolism, necessitating careful prescription evaluation. Methods: We conducted literature research on polypharmacy and PPIs usage in the older adult population and the risk associated with this practice, synthesizing 217 articles within this narrative review. Results: The overuse of medications, including PPIs, may lead to adverse effects and increased health risks. Clinical tools such as the Beers criteria, the STOPP/START Criteria, and the FORTA list offer structured guidance for optimizing pharmacological treatments while minimizing harm. Despite PPIs’ well-documented safety and efficacy, inappropriate long-term use has raised concerns in the medical community. Efforts are being made internationally to regulate their consumption and reduce the associated risks. Conclusions: Physicians across all specialties must assess the risk–benefit balance when prescribing medications to older adult patients. A personalized treatment approach, supported by evidence-based prescribing tools, is essential to ensure safe and effective pharmacotherapy. Addressing inappropriate PPI use is a priority to prevent potential health complications. Full article

Background: Spinal muscular atrophy type 1 (SMA1) is a severe neuromuscular disorder characterized by progressive muscle weakness and atrophy, including the muscles of the oral cavity and esophagus. Eosinophilic esophagitis (EoE), a chronic, allergic disease, presents with eosinophilic infiltration of the esophagus, leading to esophageal dysmotility. Feeding difficulties may occur in both conditions. So far, the coexistence of EoE and SMA1 has not been described; we present the first such case. Case presentation: The patient was a girl with SMA1 diagnosed shortly after birth, treated with nusinersen and onasemnogene abeparvovec, and fed a standard industrial diet through a gastrostomy. In her second year of life, she developed increasing symptoms: distress during feeding, regurgitation, vomiting, and weight loss. She was treated with proton pump inhibitors without clinical improvement. Gastroscopy was performed, revealing superficial epithelial damage with bleeding in the proximal esophagus. Histopathology showed chronic inflammation with up to 150 eosinophils per high-power field, microabscesses, spongiosis, and basal layer hypertrophy. The girl was diagnosed with EoE. Her diet was switched from a standard industrial formula to an amino acid-based formula, which led to marked clinical improvement, the resolution of symptoms, and appropriate weight gain. Conclusions: This case report highlights the challenges of diagnosing EoE in SMA1 patients and emphasizes the need for multidisciplinary approaches and further investigation of allergic manifestations in SMA1 patients. Full article

The separation of three proton pump inhibitors (omeprazole, lansoprazole, and rabeprazole) as exemplified molecules containing chiral sulfoxide groups was investigated in polar organic liquid chromatographic mode on seven different polysaccharide stationary phases (Chiralcel OD and OJ; Chiralpak AD, AS, and IA; Lux Cellulose-2 and -4). Different alcohols, such as methanol, ethanol, 1-propanol, 2-propanol, and their combinations, were used as eluents. After method optimization, semi-preparative enantioseparation was successfully applied for the three proton pump inhibitors to collect the individual enantiomers. A detailed investigation was conducted into elution order reversal, thermodynamic parameters, the effect of eluent mixtures, and the hysteresis of retention time and selectivity. Using Chiralpak AS, containing the amylose tris[(S)-α-methylbenzylcarbamate] chiral selector, the separation of the investigated enantiomers was achieved in all four neat eluents, with methanol providing the best results. In many cases, a reversal of the enantiomer elution order was observed. In addition to chiral-selector-dependent reversal, eluent-dependent reversal was also observed. Notably, even replacing methanol with ethanol altered the enantiomer elution order. Both enthalpy- and entropy-controlled enantioseparation were also observed in several cases; however, temperature-dependent elution order reversal was not. The hysteresis of retention and selectivity was further investigated on amylose-type columns in methanol–2-propanol and methanol–ethanol eluent mixtures. The phenomenon was observed on all amylose columns regardless of the eluent mixtures employed. Hystereticity ratios were calculated and used to compare the hysteresis behaviors of different systems. Multivariate statistical analysis revealed that Chiralpak AS exhibited the most distinct enantioselective behavior among the tested columns, likely due to the absence of a direct connection between the carbamate moiety and the aromatic substituent. The present study aided in understanding the mechanisms leading to enantiomer recognition, which is crucial for developing new chiral stationary phases and chiral HPLC method development in general. Full article

Background: Magnesium (Mg) is an essential mineral that plays a vital role in various physiological processes, including enzyme regulation, neuromuscular function, and cardiovascular health. Dysmagnesemia has been associated with arrhythmias, neuromuscular dysfunction, and poor outcomes in intensive care unit (ICU) settings, representing diagnostic and therapeutic challenges. However, the relationship between dysmagnesemia and health outcomes in the ICU remains inadequately defined. Aim/Objective: This study aimed to assess the prevalence of dysmagnesemia and evaluate the correlation between total (tMg) and ionized magnesium (iMg) levels in a cohort of ICU and high dependency unit (HDU) patients. It also sought to evaluate patient characteristics and relevant health outcomes by comparing both concentrations of iMg and tMg. Methods: This prospective study was conducted among adult patients admitted to the ICU and the high dependency unit (HDU). Results: Among the 134 included patients, the median age was 63.5 years (IQR: 52.0–77.0). The majority, 91.0%, required mechanical ventilation. Additionally, 50.0% were diagnosed with diabetes, 28.4% had chronic kidney disease, and proton pump inhibitors (PPIs) were administered to 67.2% of the patients. The prevalence of hypomagnesemia, as measured by iMg, was 6.7%, while hypermagnesemia was at 39.6%. When measured by tMg, hypomagnesemia and hypermagnesemia were observed at rates of 14.9% and 22.4%, respectively. The iMg measurements showed an association between the incidence of atrial fibrillation and hypomagnesemia (p = 0.015), whereas tMg measurements linked hypomagnesemia with longer hospital stays. Notably, only a few patients identified with iMg-measured hypomagnesemia received magnesium replacement during their ICU stay. Conclusions: Dysmagnesemia is prevalent among critically ill patients, with discordance between iMg and tMg measurements. iMg appears more sensitive in detecting arrhythmia risk, while tMg correlates with length of stay. These findings support the need for larger studies and suggest considering iMg in magnesium monitoring and replacement strategies. Full article

Background: The European League Against Rheumatism (EULAR), in collaboration with the European Scleroderma Trial and Research group (EUSTAR), published the first set of treatment recommendations for systemic sclerosis (SSc) in 2009, with subsequent updates in 2016 and 2023. Objectives: This study aimed to evaluate how rheumatologists’ clinical approaches to the treatment of SSc evolved following the 2016 update of the clinical management guidelines. Methods: Medication use for SSc was analyzed in a cohort of 378 patients. The patients were stratified based on enrollment before (233 patients) and after (145 patients) the guideline update, and medication usage was compared between the two groups. Results: Although all patients presented with Raynaud’s phenomenon (RP), only 35% received calcium channel blockers. Medications such as iloprost, phosphodiesterase type 5 (PDE-5) inhibitors, fluoxetine, and bosentan, recommended for the treatment of RP and digital ulcers, were not approved for SSc by the Republic Health Insurance Fund. Treatment for pulmonary arterial hypertension (PAH) was administered to only 16 patients (4.2%), including 2 who received bosentan, 10 who received PDE-5 inhibitors, and 4 who were treated with riociguat. The use of PDE-5 inhibitors increased following the 2016 update of the guidelines. Cyclophosphamide was consistently prescribed for interstitial lung disease (ILD), with an increased frequency observed after the guideline update. No significant differences were observed in the use of methotrexate for skin involvement, ACE inhibitors for scleroderma renal crisis, or antibiotics for gastrointestinal symptoms. Proton pump inhibitors (PPIs) were prescribed to 87.3% of patients with gastrointestinal involvement, with an increase in use of both PPIs and prokinetic agents following the guideline update. Conclusions: Rheumatologists’ adherence to the EULAR/EUSTAR guidelines varied considerably, with 25% to 100% of eligible patients receiving the recommended treatments. Concordance improved in the management of PAH, ILD, and gastrointestinal involvement after the 2016 guideline update. Full article

Proton pump inhibitors (PPIs) are widely prescribed medications primarily used to treat gastroesophageal reflux disease, peptic ulcer disease, and upper gastrointestinal bleeding. Despite clear therapeutic benefits in appropriate contexts, widespread overprescribing and extended use without clear indications have prompted significant concerns about associated risks. Accumulating evidence, predominantly from observational studies, suggests that long-term PPI use may lead to complications such as vitamin and mineral deficiencies, increased risks of infections, dysbiosis, renal dysfunction, bone fractures, cardiovascular disease, and certain malignancies. This narrative review not only synthesizes the current evidence surrounding PPI-related harms and existing deprescribing guidelines but also offers a novel perspective on how stewardship principles can be applied to promote responsible PPI prescribing. In particular, we propose a stewardship-oriented deprescribing framework rooted in implementation science, focusing on provider behavior, patient engagement, and health system-level integration. Recognizing these potential harms, evidence-based deprescribing strategies such as tapering, intermittent dosing, and transitions to alternative therapies are critical to mitigate unnecessary patient exposure. Effective implementation of deprescribing requires addressing patient, provider, and institutional barriers through educational initiatives, policy support, and structured monitoring. By promoting judicious PPI prescribing and proactive stewardship practices, clinicians can significantly reduce medication-related harm and improve patient safety. Full article

SNX11, a sorting nexin protein localized on the endosomal membrane, is an important protein closely related to protein sorting and endosomal trafficking. Previously, through a genome-wide CRISPR screening, we identified SNX11 as a critical protein for the entry of Dabie bandavirus. SNX11 deletion significantly inhibits the replication of Dabie bandavirus. We further discovered that the loss of SNX11 alters endosomal pH, potentially affecting the release process of Dabie bandavirus from endosomes to the cytoplasm. However, the mechanism by which SNX11 modulates endosomal pH and whether SNX11 deletion similarly inhibits other viruses remain to be elucidated. This study reveals that SNX11 can interact with the V1 subunit of the endosomal proton pump V-ATPase, affecting the expression level of this subunit on the endosomal membrane and thereby disrupting the assembly of V-ATPase. Additionally, we found that SNX11 deletion significantly inhibits the replication of dengue virus, hantavirus, and influenza virus. These findings suggest that SNX11 may be a key protein in the process of viral infection and could serve as a broad-spectrum antiviral target. Full article

Background/Objectives: Inflammatory bowel disease (IBD) patients face elevated gastrointestinal (GI) infection risks due to immune dysregulation and gut dysbiosis. While steroids and immunosuppressants are known to increase infection risk, data on biologics and proton pump inhibitors (PPIs) remain limited, particularly for non-Clostridioides difficile (C.diff) infections. Methods: This retrospective cohort study analyzed 9849 hospitalized IBD patients (2013–2023) from the Northwell Inpatient Database. Patients were categorized into four groups: biologics-only, PPIs-only, both, or neither. GI infections were identified via C.diff PCR, GI PCR, and chart review. Multivariate logistic regression adjusted for demographics, BMI, and IBD type. Results: GI infections occurred in 1.75% of patients, with significantly higher odds in those on biologics alone (OR 21.5, 95% CI 11.7–39.4) or with PPIs (OR 16.6, 95% CI 10.2–26.8) versus untreated patients. Non-C.diff infections were strongly associated with biologics (OR 20.7, 95% CI 10.2–41.9). PPIs alone increased slightly the risk of GI infections (OR 1.6, 95% CI 1.1–2.4). Vedolizumab and adalimumab had the highest infection risks among biologics (26.8% and 22.7%, respectively). Bacterial pathogens, such as E. coli and Salmonella, predominated, with no significant difference in causative agents across treatment groups. Conclusions: Biologic therapy greatly increases GI infection risk in IBD patients independent of PPI use. Clinicians should weigh infection risks when prescribing biologics, particularly in high-risk populations. Further studies are needed to assess risks by biologic subtype and the interplay with PPIs. Full article

Background: Up to one-third of patients with gastroesophageal reflux disease (GERD) have persistent symptoms despite proton-pump inhibitor (PPI) therapy. E-Gastryal^® + MgAlg (Aurora Biofarma, Italy) is a mucosal protective agent that enhances barrier function against acid and non-acidic reflux. This study assessed its efficacy in combination with omeprazole versus omeprazole alone and as maintenance therapy. Methods: Patients with symptomatic GERD and Grade A reflux esophagitis confirmed by endoscopy were randomized to receive omeprazole 20 mg plus E-Gastryal^® + MgAlg or omeprazole 20 mg alone. The primary endpoint was the number of rescue medications used over 28 days. Secondary endpoints included symptom relief and quality-of-life assessments using the Reflux Symptom Index (RSI), Gastroesophageal Reflux Disease Impact Scale (GIS), GERD-Health-Related Quality of Life (GERD-HRQL), and Global Assessment of Performance (IGAP). Results: Ninety-six patients were included. The combination group used significantly fewer rescue medications (mean: 21 vs. 40.9 tablets; p = 0.002). At week 4, the combination group showed greater improvement in RSI, GIS, and GERD-HRQL scores (p < 0.001). Symptom relief was sustained during weeks 5–26 with E-Gastryal^® + MgAlg alone. Conclusions: E-Gastryal^® + MgAlg combined with omeprazole improves symptom control compared to PPI monotherapy. Continued use as maintenance therapy supports its role in long-term GERD management (NCT04130659). Full article

Background: Local audits of Helicobacter pylori (H. pylori) prescriptions and outcomes are necessary to assess guideline awareness among clinicians and treatment effectiveness. Aims: The aims were to investigate first-line prescriptions and effectiveness over a 10-year period in Ireland and evaluate the influence of the 2017 Irish consensus guidelines on these trends. Methods: Data were collected at e-CRF AEG-REDCap from the European Registry on H. pylori management (Hp-EuReg) and quality reviewed from 2013 to 2022. All treatment-naïve cases were assessed for effectiveness by modified intention-to-treat (mITT) analysis. Multivariate analysis was also performed. Results: Data from 1000 patients (mean age 50 ± 15 years; 54% female) were analyzed. Clarithromycin (C) and amoxicillin (A) triple therapy represented 88% of treatments, followed by sequential C, A, and metronidazole (M) therapy (4.3%) and triple C + M (2.7%). Bismuth quadruple therapy was prescribed in 1.7% of cases. Treatment durations of 14, 10, and 7 days accounted for 87%, 4.5%, and 8.5% of prescriptions, respectively. High-, standard-, and low-dose proton pump inhibitors (PPIs; 80 mg, 40 mg, and 20 mg omeprazole equivalent b.i.d.) were used in 86%, 0.9%, and 13% of cases, respectively. The overall eradication rate was 80%, while it was 81% for triple C + A. Good compliance and high-dose PPI were associated with higher overall mITT eradication rates (OR 4.5 and OR 1.9, respectively) and triple C + A eradication rates (OR 4.2 and OR 1.9, respectively). Overall eradication rates increased from 74% pre-2017 to 82% (p < 0.05) by the end of 2022. Similarly, the triple C + A eradication rates increased from 76% to 83% (p < 0.05). Conclusions: While first-line treatment effectiveness improved in clinical practice over time, cure rates remain below 90%. Alternative first-line strategies are required in Ireland. Full article