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Genome Biology May 2024In dinoflagellates, a unique and extremely divergent genomic and nuclear organization has evolved. The highly unusual features of dinoflagellate nuclei and genomes...
BACKGROUND
In dinoflagellates, a unique and extremely divergent genomic and nuclear organization has evolved. The highly unusual features of dinoflagellate nuclei and genomes include permanently condensed liquid crystalline chromosomes, primarily packaged by proteins other than histones, genes organized in very long unidirectional gene arrays, a general absence of transcriptional regulation, high abundance of the otherwise very rare DNA modification 5-hydroxymethyluracil (5-hmU), and many others. While most of these fascinating properties are originally identified in the 1970s and 1980s, they have not yet been investigated using modern genomic tools.
RESULTS
In this work, we address some of the outstanding questions regarding dinoflagellate genome organization by mapping the genome-wide distribution of 5-hmU (using both immunoprecipitation-based and basepair-resolution chemical mapping approaches) and of chromatin accessibility in the genome of the Symbiodiniaceae dinoflagellate Breviolum minutum. We find that the 5-hmU modification is preferentially enriched over certain classes of repetitive elements, often coincides with the boundaries between gene arrays, and is generally correlated with decreased chromatin accessibility, the latter otherwise being largely uniform along the genome. We discuss the potential roles of 5-hmU in the functional organization of dinoflagellate genomes and its relationship to the transcriptional landscape of gene arrays.
CONCLUSIONS
Our results provide the first window into the 5-hmU and chromatin accessibility landscapes in dinoflagellates.
Topics: Dinoflagellida; Chromatin; Pentoxyl; Genome, Protozoan
PubMed: 38711126
DOI: 10.1186/s13059-024-03261-3 -
BMC Medical Research Methodology May 2024During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies.
OBJECTIVE
To describe the conduct of an international randomized trial of stress ulcer prophylaxis (Re-Evaluating the Inhibition of Stress Erosions in the ICU [REVISE]) during the pandemic, addressing enrolment patterns, center engagement, informed consent processes, data collection, a COVID-specific substudy, patient transfers, and data monitoring.
METHODS
REVISE is a randomized trial among mechanically ventilated patients, comparing pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important upper gastrointestinal bleeding and the primary safety outcome of 90-day mortality. We documented protocol implementation status from March 11th 2020-August 30th 2022.
RESULTS
The Steering Committee did not change the scientific protocol. From the first enrolment on July 9th 2019 to March 10th 2020 (8 months preceding the pandemic), 267 patients were enrolled in 18 centers. From March 11th 2020-August 30th 2022 (30 months thereafter), 41 new centers joined; 59 were participating by August 30th 2022 which enrolled 2961 patients. During a total of 1235 enrolment-months in the pandemic phase, enrolment paused for 106 (8.6%) months in aggregate (median 3 months, interquartile range 2;6). Protocol implementation involved a shift from the a priori consent model pre-pandemic (188, 58.8%) to the consent to continue model (1615, 54.1%, p < 0.01). In one new center, an opt-out model was approved. The informed consent rate increased slightly (80.7% to 85.0%, p = 0.05). Telephone consent encounters increased (16.6% to 68.2%, p < 0.001). Surge capacity necessitated intra-institutional transfers; receiving centers continued protocol implementation whenever possible. We developed a nested COVID-19 substudy. The Methods Centers continued central statistical monitoring of trial metrics. Site monitoring was initially remote, then in-person when restrictions lifted.
CONCLUSION
Protocol implementation adaptations during the pandemic included a shift in the consent model, a sustained high consent rate, and launch of a COVID-19 substudy. Recruitment increased as new centers joined, patient transfers were optimized, and monitoring methods were adapted.
Topics: Humans; COVID-19; Pantoprazole; SARS-CoV-2; Intensive Care Units; Pandemics; Female; Respiration, Artificial; Male; Clinical Protocols; Middle Aged; Gastrointestinal Hemorrhage; Anti-Ulcer Agents
PubMed: 38704520
DOI: 10.1186/s12874-024-02233-2 -
Medicine May 2024Success in eradication of H. pylori is decreasing due to increasing resistant strains. In particular, side-effects due to 4-agent treatment multiple drug use are...
Success in eradication of H. pylori is decreasing due to increasing resistant strains. In particular, side-effects due to 4-agent treatment multiple drug use are observed and treatment compliance decreases. The aim of this study was to evaluate the efficacy, reliability, and side-effect profile of the combination of amoxicillin and rabeprazole with gemifloxacin, which is a new generation quinolone, in the treatment of H. pylori infection. This study was conducted on 71 naive patients who received H. pylori eradication. All the patients were administered treatment of Amoxicillin (1000 mg twice a day) + Gemifloxacin (320 mg once a day) + rabeprazole (20 mg twice a day) for 7 days. Drug compliance and treatment tolerance were evaluated after finishing the treatment. At 1 month after the end of the treatment, H. pylori eradication was evaluated in all the patients by examining H. pylori antigen in the feces. In the evaluation after treatment, H. pylori eradication was obtained in 63 (88.7%) patients and eradication was not obtained in 8 (11.3%) patients. The treatment was not completed by 2 patients because of side-effects and noncompliance, so after exclusion of these 2 patients, successful H. pylori eradication was obtained in 63 (91.3%) of 69 patients who completed the treatment. Side-effects were seen in a total of 9 (12.7%) patients. Diarrhea, bloating, abdominal pain, and nausea-vomiting were seen in some patients, but no reflux, constipation, skin rash, listlessness-fatigue, headache, dizziness, palpitations, dry mouth, or weight loss was seen in any patient. In regions with high resistance to clarithromycin and metronidazole in particular, the combination of gemifloxacin with amoxicillin and rabeprazole can be considered for use in first-stage treatment as both the efficacy and tolerability are high.
Topics: Humans; Rabeprazole; Amoxicillin; Helicobacter Infections; Male; Gemifloxacin; Female; Pilot Projects; Helicobacter pylori; Drug Therapy, Combination; Anti-Bacterial Agents; Middle Aged; Adult; Fluoroquinolones; Treatment Outcome; Aged
PubMed: 38701320
DOI: 10.1097/MD.0000000000038012 -
In Vivo (Athens, Greece) 2024Recent research has increasingly demonstrated an association between proton pump inhibitors (PPIs) and serious adverse events. This study aimed to evaluate the...
BACKGROUND/AIM
Recent research has increasingly demonstrated an association between proton pump inhibitors (PPIs) and serious adverse events. This study aimed to evaluate the association between PPI and rhabdomyolysis (RM), examining its time-to-onset profiles using the Japanese Adverse Drug Event Report (JADER) database.
PATIENTS AND METHODS
Data spanning from April 2004 to March 2022 were used. The association between PPIs and RM was evaluated using the reporting odds ratio (ROR), adjusted for sex and age. Subsequent analyses were conducted after excluding cases involving concomitant use of statins or fibrates. Furthermore, the onset time of RM and Weibull distribution parameters were calculated to evaluate the expression profile of RM, and the outcomes were examined.
RESULTS
RM was associated with the use of esomeprazole, omeprazole, and rabeprazole, even in the absence of concomitant statin or fibrate use. The median time to RM onset varied among PPIs, ranging from 6.5 to 127 d. The Weibull distribution parameters indicated that the hazard types of nearly all orally administered PPIs were classified as early failure or close to random failure. Regarding outcomes, cases of death were reported for all PPIs except vonoprazan.
CONCLUSION
The findings suggest the need for vigilant monitoring of RM during PPI administration, particularly in the early stages, considering the varying onset times.
Topics: Humans; Proton Pump Inhibitors; Rhabdomyolysis; Male; Female; Pharmacovigilance; Middle Aged; Aged; Adult; Adverse Drug Reaction Reporting Systems; Databases, Factual; Aged, 80 and over; Young Adult; Adolescent; Esomeprazole
PubMed: 38688634
DOI: 10.21873/invivo.13567 -
Gut Microbes 2024Inulin, an increasingly studied dietary fiber, alters intestinal microbiota. The aim of this study was to assess whether inulin decreases intestinal colonization by...
Inulin, an increasingly studied dietary fiber, alters intestinal microbiota. The aim of this study was to assess whether inulin decreases intestinal colonization by multidrug resistant and to investigate its potential mechanisms of action. Mice with amoxicillin-induced intestinal dysbiosis mice were inoculated with extended spectrum beta-lactamase producing (ESBL-). The combination of inulin and pantoprazole (IP) significantly reduced ESBL- fecal titers, whereas pantoprazole alone did not and inulin had a delayed and limited effect. Fecal microbiome was assessed using shotgun metagenomic sequencing and qPCR. The efficacy of IP was predicted by increased abundance of 74 taxa, including two species of Adlercreutzia. Preventive treatments with or also reduced ESBL- fecal titers. Fecal microbiota of mice effectively treated by IP was enriched in genes involved in inulin catabolism, production of propionate and expression of beta-lactamases. They also had increased beta-lactamase activity and decreased amoxicillin concentration. These results suggest that IP act through production of propionate and degradation of amoxicillin by the microbiota. The combination of pantoprazole and inulin is a potential treatment of intestinal colonization by multidrug-resistant . The ability of prebiotics to promote propionate and/or beta-lactamase producing bacteria may be used as a screening tool to identify potential treatments of intestinal colonization by multidrug resistant Enterobacterales.
Topics: Animals; Inulin; Mice; Gastrointestinal Microbiome; Escherichia coli; Feces; Amoxicillin; Pantoprazole; Drug Resistance, Multiple, Bacterial; beta-Lactamases; Dysbiosis; Anti-Bacterial Agents; Escherichia coli Infections; Female; Prebiotics
PubMed: 38685762
DOI: 10.1080/19490976.2024.2347021 -
BMJ Open Apr 2024To compare the efficacy and safety of seven Chinese patent medicines (CPMs) combined with conventional triple/quadruple therapy (T/Q) for -positive peptic ulcers. (Meta-Analysis)
Meta-Analysis
Efficacy and safety of seven Chinese patent medicines combined with conventional triple/quadruple therapy for -positive peptic ulcers: a systematic review and network meta-analysis.
OBJECTIVES
To compare the efficacy and safety of seven Chinese patent medicines (CPMs) combined with conventional triple/quadruple therapy (T/Q) for -positive peptic ulcers.
DESIGN
A systematic review and network meta-analysis.
DATA SOURCES
China National Knowledge Infrastructure, VIP database, Wanfang database, ScienceDirect, EBSCO, EMBASE, Web of Science, Cochrane Library and PubMed were searched through 1 June 2022.
ELIGIBILITY CRITERIA
Randomised controlled trials (RCTs) testing CPMs combined with T/Q for -positive peptic ulcers were included. The CPMs included Anweiyang capsule, Jianweiyuyang tablets/capsule/granule, Jinghuaweikang capsule, Kangfuxin liquid, Puyuanhewei capsule, Weifuchun tablets/capsule and Weisu granule. At least one of the following outcome indicators was recorded: complete ulcer healing rate (CUHR), effective rate (ER), eradication rate (ER), rate of peptic ulcer recurrence (RPUR) and incidence of adverse reactions (IAR).
DATA EXTRACTION AND SYNTHESIS
Two researchers independently conducted the study selection and extracted data for included studies. The risk of bias was assessed using the Cochrane risk of bias tool. A pairwise meta-analysis was performed using RevMan V.5.3. Network meta-analysis was performed using STATA/MP V.15.0. Confidence in the evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluation.
RESULTS
A total of 36 RCTs involving 3620 patients were included. Compared with T/Q alone, Weisu+T/Q, Weifuchun+T/Q and Puyuanhewei+T/Q had the highest CUHR, ER and ER, respectively. Weisu+T/Q and Jianweiyuyang+T/Q had the lowest RPUR and IAR, respectively. The cluster analysis results showed Jianweiyuyang+T/Q might be the best choice concerning efficacy and safety simultaneously, followed by Kangfuxin+T/Q.
CONCLUSION
Among the combination therapies with the CPMs, Jianweiyuyang+T/Q might be the most favourable option for -positive peptic ulcers, followed by Kangfuxin+T/Q. Considering the limited quantity and quality of the included RCTs, the results should be interpreted with caution.
PROSPERO REGISTRATION NUMBER
CRD42022327687.
Topics: Humans; Helicobacter Infections; Drug Therapy, Combination; Helicobacter pylori; Network Meta-Analysis; Drugs, Chinese Herbal; Peptic Ulcer; Anti-Bacterial Agents; Randomized Controlled Trials as Topic; Proton Pump Inhibitors; Anti-Ulcer Agents; Treatment Outcome; Nonprescription Drugs
PubMed: 38684278
DOI: 10.1136/bmjopen-2023-074188 -
Nutrients Apr 2024The excessive activation of glutamate in the brain is a factor in the development of vascular dementia. γ-Oryzanol is a natural compound that has been shown to enhance...
The excessive activation of glutamate in the brain is a factor in the development of vascular dementia. γ-Oryzanol is a natural compound that has been shown to enhance brain function, but more research is needed to determine its potential as a treatment for vascular dementia. This study investigated if γ-oryzanol can delay or improve glutamate neurotoxicity in an in vitro model of differentiated HT-22 cells and explored its neuroprotective mechanisms. The differentiated HT-22 cells were treated with 0.1 mmol/L glutamate for 24 h then given γ-oryzanol at appropriate concentrations or memantine (10 µmol/L) for another 24 h. Glutamate produced reactive oxygen species and depleted glutathione in the cells, which reduced their viability. Mitochondrial dysfunction was also observed, including the inhibition of mitochondrial respiratory chain complex I activity, the collapse of mitochondrial transmembrane potential, and the reduction of intracellular ATP levels in the HT-22 cells. Calcium influx triggered by glutamate subsequently activated type II calcium/calmodulin-dependent protein kinase (CaMKII) in the HT-22 cells. The activation of CaMKII-ASK1-JNK MAP kinase cascade, decreased Bcl-2/Bax ratio, and increased Apaf-1-dependent caspase-9 activation were also observed due to glutamate induction, which were associated with increased DNA fragmentation. These events were attenuated when the cells were treated with γ-oryzanol (0.4 mmol/L) or the N-methyl-D-aspartate receptor antagonist memantine. The results suggest that γ-oryzanol has potent neuroprotective properties against glutamate excitotoxicity in differentiated HT-22 cells. Therefore, γ-oryzanol could be a promising candidate for the development of therapies for glutamate excitotoxicity-associated neurodegenerative diseases, including vascular dementia.
Topics: Glutamic Acid; Phenylpropionates; Animals; Neuroprotective Agents; Mice; Cell Line; Reactive Oxygen Species; Mitochondria; Oryza; Membrane Potential, Mitochondrial; Cell Differentiation; Cell Survival; Memantine; Apoptosis; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Neurons
PubMed: 38674927
DOI: 10.3390/nu16081237 -
Toxins Apr 2024Snakebite envenomation (SBE) causes diverse toxic effects in humans, including disability and death. Current antivenom therapies effectively prevent death but fail to...
BACKGROUND
Snakebite envenomation (SBE) causes diverse toxic effects in humans, including disability and death. Current antivenom therapies effectively prevent death but fail to block local tissue damage, leading to an increase in the severity of envenomation; thus, seeking alternative treatments is crucial.
METHODS
This study analyzed the potential of two fucoidan sulfated polysaccharides extracted from brown seaweeds (FVF) and (UPF) against the fibrinogen or plasma coagulation, proteolytic, and phospholipase A (PLA) activities of , , and venom. The toxicity of FVF and UPF was assessed by the hemocompatibility test.
RESULTS
FVF and UPF did not lyse human red blood cells. FVF and UPF inhibited the proteolytic activity of , , and venom by approximately 25%, 50%, and 75%, respectively, while all venoms led to a 20% inhibition of PLA activity. UPF and FVF delayed plasma coagulation caused by the venoms of and but did not affect the activity of venom. FVF and UPF blocked the coagulation of fibrinogen induced by all these Bothropic venoms.
CONCLUSION
FVF and UPF may be of importance as adjuvants for SBE caused by species of , which are the most medically relevant snakebite incidents in South America, especially Brazil.
Topics: Animals; Antivenins; Blood Coagulation; Bothrops; Bothrops jararaca; Crotalid Venoms; Edible Seaweeds; Fucus; Phospholipases A2; Polysaccharides; Proteolysis; Seaweed; Undaria; Venomous Snakes
PubMed: 38668613
DOI: 10.3390/toxins16040188 -
The Korean Journal of Gastroenterology... Apr 2024() is the most prevalent infection in the world and is strongly associated with gastric adenocarcinoma, lymphoma and gastric or duodenal ulcers. Different regimens have... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND/AIMS
() is the most prevalent infection in the world and is strongly associated with gastric adenocarcinoma, lymphoma and gastric or duodenal ulcers. Different regimens have been used for eradication. We aimed to compare the efficacy of two different regimens as first-line eradication regimens, in an area with high antibiotic resistance.
METHODS
In this RCT, we assigned 223 patients with infection, who were naïve to treatment. They were randomly divided into two groups to receive either 12-day concomitant quadruple therapy (consisting of pantoprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg every 12 hours) or 14-day high dose dual therapy (consisting of esomeprazole 40 mg and amoxicillin 1 g TDS). eradication was assessed eight weeks after the end of treatment.
RESULTS
eradication rate by PP analysis for 12-day concomitant quadruple therapy and 14-day high dose dual therapy were 90.4% and 79.1%, respectively (p=0.02). According to ITT analysis, the eradication rates were 86.2% and 76.3%, respectively (p=0.06). Adverse drug reactions were 12.3% in high dose dual therapy and 36.8% in concomitant quadruple therapy (p<0.001).
CONCLUSIONS
Twelve-day concomitant therapy seems to be an acceptable regimen for first-line eradication in Iran, a country with a high rate of antibiotic resistance. Although, high dose dual therapy did not result in an ideal eradication rate, but it had fewer drug side effects than the 12-day concomitant regimen.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Amoxicillin; Anti-Bacterial Agents; Clarithromycin; Drug Administration Schedule; Drug Therapy, Combination; Esomeprazole; Helicobacter Infections; Helicobacter pylori; Metronidazole; Pantoprazole; Proton Pump Inhibitors; Treatment Outcome
PubMed: 38659251
DOI: 10.4166/kjg.2024.012 -
Chinese Medical Journal Apr 2024Erosive esophagitis (EE) is a gastroesophageal reflux disease characterized by mucosal breaks in the esophagus. Proton pump inhibitors are widely used as maintenance... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Erosive esophagitis (EE) is a gastroesophageal reflux disease characterized by mucosal breaks in the esophagus. Proton pump inhibitors are widely used as maintenance therapy for EE, but many patients still relapse. In this trial, we evaluated the noninferiority of vonoprazan vs. lansoprazole as maintenance therapy in patients with healed EE.
METHODS
We performed a double-blind, double-dummy, multicenter, phase 3 clinical trial among non-Japanese Asian adults with endoscopically confirmed healed EE from April 2015 to February 2019. Patients from China, South Korea, and Malaysia were randomized to vonoprazan 10 mg or 20 mg once daily or lansoprazole 15 mg once daily for 24 weeks. The primary endpoint was endoscopically confirmed EE recurrence rate over 24 weeks with a noninferiority margin of 10% using a two-sided 95% confidence interval (CI). Treatment-emergent adverse events (TEAEs) were recorded.
RESULTS
Among 703 patients, EE recurrence was observed in 24/181 (13.3%) and 21/171 (12.3%) patients receiving vonoprazan 10 mg or 20 mg, respectively, and 47/184 (25.5%) patients receiving lansoprazole (differences: -12.3% [95% CI, -20.3% to -4.3%] and -13.3% [95% CI, -21.3% to -5.3%], respectively), meeting the primary endpoint of noninferiority to lansoprazole in preventing EE recurrence at 24 weeks. Evidence of superiority (upper bound of 95% CI <0%) was also observed. At 12 weeks, endoscopically confirmed EE recurrence was observed in 5/18, 2/20, and 7/20 of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. TEAEs were experienced by 66.8% (157/235), 69.0% (156/226), and 65.3% (158/242) of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. The most common TEAE was upper respiratory tract infection in 12.8% (30/235) and 12.8% (29/226) patients in vonoprazan 10 mg and 20 mg groups, respectively and 8.7% (21/242) patients in lansoprazole group.
CONCLUSION
Vonoprazan maintenance therapy was well-tolerated and noninferior to lansoprazole for preventing EE recurrence in Asian patients with healed EE.
TRIAL REGISTRATION
https://clinicaltrials.gov; NCT02388737.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Asian People; Double-Blind Method; Esophagitis; Esophagitis, Peptic; Lansoprazole; Proton Pump Inhibitors; Pyrroles; Sulfonamides; East Asian People; China; Republic of Korea; Malaysia
PubMed: 38654422
DOI: 10.1097/CM9.0000000000003068