Search Results (534)

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 stretch film production is highly energy intensive. The components of the technological line are powered by electrical energy, and the heat is used to change the physical state of the raw material (granules). The raw material is poured into FCR (the first calender roller). To solidify the liquid raw material, the calendar must be cooled. The low-temperature heat, treated as waste heat, has dissipated in the atmosphere. Technological innovations were proposed: (a) the raw material comprises raw material (primary) and up to 80% recyclate (waste originating mainly from agriculture), (b) the use of low-temperature waste heat (the cooling of FCR in the process of foil stretch production). A heat recovery line based on two compressor heat pumps (HP, hydraulically coupled) was designed. The waste heat (by low-temperature HP) was transformed into high-temperature heat (by high-temperature HP) and used to prepare the raw material. The proposed technological line enables the management of difficult-to-manage post-production waste (i.e., agriculture and other economic sectors). It reduces energy consumption and raw materials from non-renewable sources (CO₂ and other greenhouse gas emissions are reducing). It implements a closed-loop economy based on renewable energy sources (according to the European Green Deal). Full article

Background and Objectives: Alzheimer’s disease (AD) has become a serious health problem. Agomelatine (Ago) is a neuroprotective antidepressant. This study aimed to assess how Ago influences behavioral outcomes in AD-like rat model. Materials and Methods: Forty-eight Wistar albino rats were allocated into four groups: Control (C), Alzheimer’s disease-like model (AD), Alzheimer’s disease-like model treated with Ago (ADAgo), and Ago alone (Ago). Physiological saline was injected intrahippocampally in C and Ago animals, whereas Aβ peptide was delivered similarly in AD and ADAgo rats. On day 15, 0.9% NaCl was administered to the C and AD groups, and Agomelatine (1 mg/kg/day) was infused into ADAgo and Ago rats via osmotic pumps for 30 days. Behavioral functions were evaluated using Open Field (OF), Forced Swim (FST), and Morris Water Maze (MWM) tests. Brain tissues were examined histopathologically. Neuritin, Nestin, DCX, NeuN, BDNF, MASH1, MT1, and MT2 transcripts were quantified by real-time PCR. Statistical analyses were performed in R 4.3.1, with p < 0.05 deemed significant. Results: In the FST, swimming, climbing, immobility time, and mobility percentage differed significantly among groups (p < 0.05). In the MWM, AD rats exhibited impaired learning and memory that was ameliorated by Ago treatment (p < 0.05). DCX expression decreased in AD rats but was elevated by Ago (p < 0.05). Nestin levels differed significantly between control and AD animals; MT1 expression varied between control and AD cohorts; and MT2 transcript levels were significantly lower in AD, ADAgo, and Ago groups compared to C (all p < 0.05). Conclusions: Ago exhibits antidepressant-like activity in this experimental AD model and may enhance cognitive function via mechanisms beyond synaptic plasticity and neurogenesis. Full article

We present a miniaturized, inexpensive, and user-friendly microfluidic platform to support biological applications. The system integrates a mini-incubator providing controlled environmental conditions and housing a microfluidic device for long-term cell culture experiments. The incubator is designed to be compatible with standard inverted optical microscopes and Raman spectrometers, allowing for the non-invasive imaging and spectroscopic analysis of cell cultures in vitro. The microfluidic device, which reproduces a dynamic environment, was optimized to sustain a passive, gravity-driven flow of medium, eliminating the need for an external pumping system and reducing mechanical stress on the cells. The platform was tested using Raman analysis and adherent tumoral cells to assess proliferation prior and subsequent to hydrogen peroxide treatment for oxidative stress induction. The results demonstrated a successful adhesion of cells onto the substrate and their proliferation. Furthermore, the platform is suitable for carrying out optical monitoring of cultures and Raman analysis. In fact, it was possible to discriminate spectra deriving from control and hydrogen peroxide-treated cells in terms of DNA backbone and cellular membrane modification effects provoked by reactive oxygen species (ROS) activity. The 800–1100 cm⁻¹ band highlights the destructive effects of ROS on the DNA backbone’s structure, as its rupture modifies its vibration; moreover, unpaired nucleotides are increased in treated sample, as shown in the 1154–1185 cm⁻¹ band. Protein synthesis deterioration, led by DNA structure damage, is highlighted in the 1257–1341 cm⁻¹, 1440–1450 cm⁻¹, and 1640–1670 cm⁻¹ bands. Furthermore, membrane damage is emphasized in changes in the 1270, 1301, and 1738 cm⁻¹ frequencies, as phospholipid synthesis is accelerated in an attempt to compensate for the membrane damage brought about by the ROS attack. This study highlights the potential use of this platform as an alternative to conventional culturing and analysis procedures, considering that cell culturing, optical imaging, and Raman spectroscopy can be performed simultaneously on living cells with minimal cellular stress and without the need for labeling or fixation. 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

Objectives: To assess the long-term survival outcomes of patients undergoing no-touch aorta, total arterial off-pump coronary artery bypass grafting (OPCAB) using a left internal mammary artery (LIMA)–radial artery (RA) Y-graft configuration. This approach was applied uniformly to all-comers undergoing isolated CABG between 2004 and 2021, irrespective of preoperative risk profile. Methods: We included all patients treated with total arterial OPCAB using the LIMA–RA Y-graft without additional concomitant procedures. Patients were stratified into five age groups (<50, 50–59, 60–69, 70–79, and >80 years). Survival at 5 years was analyzed using Kaplan–Meier curves and Cox regression analysis. Results: A total of 2174 patients were analyzed, with a median follow-up of 3266 days. In-hospital mortality was 0.6%, whereas postoperative stroke was 0.3% without residual trauma and 0.2% with residual trauma, respectively, without differences between age groups. The mean number of grafts per patient was 3.7, with no significant variation between age groups (p = 0.09). Overall, 5-year survival was 90% (n = 1767), ranging from 98% in the youngest group to 65% in the oldest (log-rank p < 0.0001). Conclusions: No-touch aorta, total arterial OPCAB using the LIMA–RA Y-graft is a safe and effective revascularization strategy for a broad spectrum of patients, including those with advanced age and comorbidities. 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

Background: Intra-aortic balloon pump (IABP) augments coronary perfusion during high-risk percutaneous coronary interventions (PCI). We sought to identify patients who benefited from prophylactic IABP (P-IABP) compared to rescue-IABP (R-IABP). Methods: All consecutive non-cardiogenic shock patients undergoing high-risk PCI with IABP support at Ulm University Hospital, Germany, between 2012 and 2020 were grouped based on the timing of IABP insertion in the pre-interventional P-IABP or peri-interventional R-IABP group. We compared the primary endpoint peri-interventional high-sensitivity Troponin T (hsTnT) increase, sought baseline characteristics associated with the endpoint in the R-IABP group, and compared their correlation strengths between the groups. Results: Interventional outcomes of 44 patients with P-IABP implantation were compared with those of 15 patients with R-IABP implantation. P-IABP was associated with a lower peri-interventional hsTnT increase (p = 0.008, r = 0.390). In the R-IABP group, the presence of ST-segment elevation (p = 0.037, r = 0.631), low systolic blood pressure (RRsyst) (p = 0.007, r = 0.893 (inverse correlation)), and elevated NT-proBNP levels (p < 0.001, r = 0.953) were associated with higher hsTnT increases. HsTnT increase was significantly smaller in the P-IABP group in patients with low RRsyst (IZI = 2.6) and high NT-proBNP levels (IZI = 3.36). Patients with RRsyst < 120 mmHg (p = 0.007) and NT-proBNP levels ≥ 900 pg/mL (Cohen’s d = 0.70, respectively 1.17 for ≥5000 pg/mL and 5.01 for ≥10,000 pg/mL) showed lower peri-interventional hsTnT increase when treated with P-IABP compared to R-IABP, while patients with NT-proBNP levels < 900 pg/mL showed a contrary effect (Cohen’s d = −0.90). Cox regression analysis showed that a high peri-interventional hsTnT increase was significantly associated with a shorter survival time (p = 0.046). Conclusions: P-IABP use in high-risk PCI was associated with reduced peri-interventional myocardial injury, as measured by lower hsTnT increase, which was associated with improved survival in patients with low systolic blood pressure and elevated NT-proBNP levels. Thus, these conditions should be considered for indicating P-IABP. Full article

Background/Objectives: Ceftiofur hydrochloride (CEF) is a third-generation cephalosporin widely used in cattle to treat various disease. The recommended dosage was 1.1 to 2.2 mg/kg BW for 3 to 5 consecutive days by intramuscular or subcutaneous injection. Incomplete treatment, overuse, or misuse, often observed in clinical practice, are major contributors to resistance development. This study aims to explore how different concentrations, durations, and dosing frequencies affect susceptibility and bactericidal efficacy of Staphylococcus aureus to optimize CEF dosage regimens. Methods: First, CEF was intermittently administered at 1/2 × minimum inhibitory concentration (MIC), 2 × MIC, 6 × MIC, and 100 × MIC for 30 cycles. Second, CEF was continuously administered for 48, 72, 96, 120, 144, and 168 h. Bacterial susceptibility, regrowth, survival rate, and the emergence of persisters or tolerant phenotypes were assessed. Genetic mutations were identified by whole-genome resequencing. Membrane permeability, integrity, and efflux pump activity were analyzed to elucidate the mechanism of CEF. Results: After 30 cycles, the MIC increased eight-fold in the 2 × MIC group. No significant MIC increase was found in other groups, but a progression from susceptibility to persistence and then to tolerance was observed in the 100 × MIC intermittent group. The survival rate increased both in the 2 × MIC and 100 × MIC groups. With continuous exposure to ≥6 × MIC over 120 h, strains were completely eradicated without MIC increase. Resistance-associated single-nucleotide polymorphism (SNP) mutations were detected only in strains of the 2 × MIC and 100 × MIC intermittent groups. CEF altered the membrane hydrophobicity, damaging membrane integrity after 30 cycles. Conclusions: These findings suggest that high-dose, prolonged exposure is more effective for eliminating Staphylococcus aureus and avoiding resistance, whereas intermittent dosing may promote persistence, tolerance, and resistance evolution. 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

Background/Objectives: Small intestinal bacterial overgrowth (SIBO) is frequently observed in patients treated with proton pump inhibitors (PPIs), yet the role of treatment duration in modulating SIBO risk remains unclear. This meta-analysis aims to evaluate the temporal association between PPI use duration and SIBO risk. Methods: Following the PRISMA 2020 guidelines, a systematic search was conducted across MEDLINE/PubMed, EMBASE, the Cochrane Library, the Russian Science Citation Index, and Google Scholar from 1985 to June 2025 and was previously registered in PROSPERO under the registration number CRD420251031719. Eligible studies included observational designs or clinical trials assessing SIBO in adult PPI users. Results: Twenty-nine studies (n = 3682 PPI patients; n = 2907 controls) were included. The pooled SIBO prevalence among PPI-treated patients was 36.839% (95% CI: 29.703–44.277), significantly higher than that among controls (19.887%; 95% CI: 12.027–29.399). PPI use was associated with increased SIBO risk (OR = 2.143; 95% CI: 1.446–3.175), with high heterogeneity (I² = 77.61%). A duration-dependent trend was observed: our meta-regression analysis demonstrated a significant positive association between PPI treatment duration and SIBO prevalence with the regression coefficient 4.265% (95% CI: 1.827–6.384; p = 0.0024), indicating that each additional month of PPI therapy was associated with a 4.265 percentage increase in SIBO risk. Conclusions: PPI use significantly increases the risk of SIBO, with longer treatment durations associated with higher odds. Full article

Background/Objective: Platelet concentrates (PCs) are used in transfusion medicine to treat bleeding disorders. Staphylococcus aureus, a predominant PC contaminant, has been implicated in several adverse transfusion reactions. The aim of this study was to investigate the impact of PC storage on S. aureus resistance to quinolones, which are commonly used to treat S. aureus infections. Methods/Results: Four transfusion-relevant S. aureus strains (TRSs) were subjected to comparative transcriptome analyses when grown in PCs vs. trypticase soy broth (TSB). Results of these analyses revealed differentially expressed genes involved in antibiotic resistance. Of interest, the norB gene (encodes for the NorB efflux pump, which is implicated in quinolone resistance and is negatively regulated by MgrA) was upregulated (1.2–4.7-fold increase) in all PC-grown TRS compared to TSB cultures. Minimal Bactericidal Concentration (MBC) of ciprofloxacin and norfloxacin in PC-grown TRS compared to TSB showed increased resistance to both quinolones in PC cultures. Complementary studies with non-transfusion-relevant strains S. aureus RN6390 and its norB and mgrA deletion mutants were conducted. MBC of ciprofloxacin and norfloxacin and RT-qPCR assays of these strains showed that not only norB, but also norA and norC may be involved in enhanced quinolone resistance in PC-grown S. aureus. The role of norB in S. aureus virulence was also tested using the silkworm Bombyx mori animal model; lethal dose 50 (LD₅₀) assays revealed slightly higher virulence in larvae infected with the wild-type strain compared to the norB mutant. Conclusions: The PC storage environment enhances quinolone resistance in S. aureus and induces differential expression of efflux pump nor genes. Furthermore, our preliminary data of the involvement of NorB in virulence of S. aureus using a silkworm model merit further investigation with other systems such as a mammal animal model. Our results provide mechanistic insights to aid clinicians in the selection of antimicrobial treatment of patients receiving transfusions of S. aureus-contaminated PCs. Full article

Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor, is released pre-prandially and during periods of negative energy balance, exhibiting anti-fertility properties. In this study, twenty ewes were divided into two groups: a ghrelin-treated group receiving 1.25 μg/kg body weight (BW) of ghrelin per day via mini-pumps for 28 days and an untreated control group. Estrus was synchronized, superovulation was induced with FSH, and embryos and follicular fluid were collected six days post-estrus. Blood samples were taken to measure LH, progesterone, and anti-Müllerian hormone (AMH) concentrations. Results indicated that in treated animals, preovulatory LH surge was weaker, and progesterone levels were lower than in controls. Differences were observed in the superovulatory response and the number of collected embryos, both being higher in controls. While AMH levels did not differ between groups at the beginning of the experiment, they were lower in treated animals at the time of FSH administration. Treated ewes exhibited a reduced number of small follicles, and their follicular fluid contained lower AMH concentrations than the controls. These findings suggest that ghrelin plays a direct role in regulating LH secretion from the pituitary and in controlling ovarian follicle development, highlighting the strong interaction between nutrition and fertility. Full article

Background and Aims: Non-variceal upper gastrointestinal bleeding (NVUGIB) is a common cause of hospitalizations, with proton pump inhibitors (PPIs) being the mainstay treatment. However, there is a lack of high-level evidence to show if adjunctive medical therapy (somatostatin and its analogs) can improve outcomes. This systematic review and meta-analysis aim to evaluate the outcomes of PPIs with adjunctive therapy versus PPI monotherapy in treating NVUGIB in an in-patient setting. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, major databases were systematically searched to retrieve English-only, original studies, published from 1 January 2000 to 31 December 2023, investigating NVUGIB only. The primary outcomes included the mortality rate within 7 days of therapy, rebleeding rate within 7 days of therapy, and length of hospital stay. Results: Seven studies with 789 patients had a pooled mortality rate of 2.0% (95% CI, 0–4.0%), and the pooled risk ratio was 1.11 (95% CI, 0.50–2.48; p = 0.79) between PPI monotherapy and PPIs with adjunctive medical therapy. The pooled rebleeding rate was 13% (95% CI, 6–20%) and the risk ratio was 1.04 (95% CI, 0.73–1.48; p = 0.83). The pooled average length of stay in the hospital was 5.47 days (95% CI, 3.72–7.21 days), with insignificant weighted differences between the two groups. No statistically significant differences were noted in surgical management risk ratios or amount of blood transfusion. Conclusions: Among patients with NVUGIB, adjunctive medical therapy offered no clinical benefits given the statistically insignificant differences in the primary outcomes. However, this conclusion is limited by the considerable variability in treatment protocols, weak control of confounding variables, and missing clinical information in the original studies. Therefore, better-quality, large-scale randomized controlled trials are needed, ideally using standardized somatostatin dosing, timing, delivery routes, and clearly defined inclusion criteria to more accurately evaluate the role of somatostatin in NVUGIB management. Full article

Eosinophilic Esophagitis (EoE) is a chronic, immune-mediated disorder that is characterized by symptoms of esophageal dysfunction and the presence of increased eosinophils in the esophageal mucosa. It is becoming increasingly prevalent among children and adults and its pathogenesis arises from the complex interaction of genetic predisposition and environmental triggers, both which contribute to esophageal inflammation. Current societal guidelines recommend the use of proton pump inhibitors, topical steroids, and dietary interventions such as elimination diets as first-line treatments, however, the recent approval of Dupliumab has provided an additional therapeutic avenue. There are a number of investigational biologic agents targeting other immune pathways which are making their way through the pipeline of pharmacologic options in treating this chronic disorder. Full article