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1.
Cell Stress Chaperones ; 28(6): 1053-1067, 2023 11.
Article in English | MEDLINE | ID: mdl-37587350

ABSTRACT

Metazoan 70 kDa heat shock protein (HSP70) genes have been classified into four lineages: cytosolic A (HSP70cA), cytosolic B (HSP70cB), endoplasmic reticulum (HSP70er), and mitochondria (HSP70m). Because previous studies have identified no HSP70cA genes in vertebrates, we hypothesized that this gene was lost on the evolutionary path to vertebrates. To test this hypothesis, the present study conducted a comprehensive database search followed by phylogenetic and synteny analyses. HSP70cA genes were found in invertebrates and in two of the three subphyla of Chordata, Cephalochordata (lancelets) and Tunicata (tunicates). However, no HSP70cA gene was found in the genomes of Craniata (another subphylum of Chordata; lamprey, hagfish, elephant shark, and coelacanth), suggesting the loss of the HSP70cA gene in the early period of vertebrate evolution. Synteny analysis using available genomic resources indicated that the synteny around the HSP70 genes was generally conserved between tunicates but was largely different between tunicates and lamprey. These results suggest the presence of dynamic chromosomal rearrangement in early vertebrates that possibly caused the loss of the HSP70cA gene in the vertebrate lineage.


Subject(s)
Evolution, Molecular , Vertebrates , Animals , Phylogeny , Vertebrates/genetics , Genome/genetics , Genomics
2.
Eur J Clin Pharmacol ; 79(8): 1023-1029, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37344679

ABSTRACT

Proton pump inhibitors (PPIs) are a mainstay treatment for acid peptic disorders such as gastroesophageal reflux disease (GERD). Although PPIs are considered first-line medications for acid suppression, they have notable limitations such as requiring acid-mediated activation, short half-life and duration of action, and metabolic variability. Fexuprazan is a newly developed potassium-competitive acid blocker (P-CAB), which inhibits acid generation and secretion in a competitive and reversible manner. Fexuprazan, like other P-CABs, has significantly different pharmacodynamic and pharmacokinetic properties than PPIs with potential advantages including rapid, robust, and durable acid suppression, lack of CYP2C19 metabolism, independence from food intake, and no requirement for activation into an active form. Completed clinical trials of fexuprazan have demonstrated comparable efficacy to PPIs for the healing of erosive esophagitis and relief of GERD-related esophageal symptoms without concerning safety signals. Ongoing clinical trials are evaluating fexuprazan for the prevention of NSAID-induced peptic ulcer disease, non-erosive GERD, and acute and chronic gastritis, as well as healing efficacy and maintenance of erosive esophagitis (EE). Fexuprazan is approved in South Korea for the treatment of EE and at the time of this writing is being considered for regulatory approval in several other countries. In this article, we summarize and discuss the pharmacology, efficacy, and safety of fexuprazan.


Subject(s)
Esophagitis , Gastroesophageal Reflux , Peptic Ulcer , Humans , Gastroesophageal Reflux/drug therapy , Proton Pump Inhibitors/pharmacology , Proton Pump Inhibitors/therapeutic use , Pyrroles/therapeutic use , Peptic Ulcer/drug therapy , Esophagitis/drug therapy
3.
J Affect Disord ; 320: 590-594, 2023 01 01.
Article in English | MEDLINE | ID: mdl-36181915

ABSTRACT

BACKGROUND: In the United States, suicide is one of the serious public health problems and a major cause of death. Several researchers and clinical settings use the patient health questionnaires (PHQ-9) to gauge depression and psychological distress among adults and to predict suicide and death. This study aimed to assess the sensitivity, specificity, and predictive potential of suicide Q9 of the PHQ-9 compared to the Columbia-suicide severity rating scale (C-SSRS). METHODS: Adults aged 19 or older, identified with a primary mood disorder diagnosis during their initial clinic visit between 2012 and 2020 from the National Network of Depression Centers, were included in the study. The accuracy of the PHQ-9 suicide item was compared with the gold standard, the C-SSRS. RESULTS: Out of 2677 study participants, 31.6 % (n = 846) and 11.65 % (n = 312) had positive responses to the PHQ-9 suicide item and C-SSRS response, respectively. The sensitivity of the PHQ-9 compared to the C-SSR was 74.7 % (95%CI: 69.6 %-79.2 %), specificity 74.1 % (95%CI: 72.3 %-75.8 %), positive predictive value 27.5 % (95%CI: 24.6 %-30.6 %), and negative predictive value 95.7 % (95%CI: 94.7 %-96.5 %). The secondary analysis results showed better validity results of the PHQ-9 suicide item when compared to the suicide ideation item of the C-SSRS. LIMITATIONS: This study is among mood disorder patients so additional research would be necessary among populations with different conditions. CONCLUSION: For initial suicide screening, the PHQ-9 suicide item would over identify patients as at risk for suicide and the C-SSRS should be used mood disorder clinics to identify suicide risk.


Subject(s)
Depression , Patient Health Questionnaire , Humans , Adult , United States , Psychiatric Status Rating Scales , Depression/psychology , Mood Disorders/diagnosis , Outpatients , Suicidal Ideation , Surveys and Questionnaires , Reproducibility of Results
4.
Arch Plast Surg ; 49(4): 494-500, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35919555

ABSTRACT

Background Seroma formation is the most common donor site complication following autologous breast reconstruction, along with hematoma. Seroma may lead to patient discomfort and may prolong hospital stay or delay adjuvant treatment. The aim of this study was to compare seroma rates between the deep inferior epigastric perforator (DIEP), transverse musculocutaneous gracilis (TMG), and superior gluteal artery perforator (SGAP) donor sites. Methods The authors conducted a retrospective single-center cohort study consisting of chart review of all patients who underwent microsurgical breast reconstruction from April 2018 to June 2020. The primary outcome studied was frequency of seroma formation at the different donor sites. The secondary outcome evaluated potential prognostic properties associated with seroma formation. Third, the number of donor site seroma evacuations was compared between the three donor sites. Results Overall, 242 breast reconstructions were performed in 189 patients. Demographic data were found statistically comparable between the three flap cohorts, except for body mass index (BMI). Frequency of seroma formation was highest at the SGAP donor site (75.0%), followed by the TMG (65.0%), and DIEP (28.6%) donor sites. No association was found between seroma formation and BMI, age at surgery, smoking status, diabetes mellitus, neoadjuvant chemotherapy, or DIEP laterality. The mean number of seroma evacuations was significantly higher in the SGAP and the TMG group compared with the DIEP group. Conclusion This study provides a single center's experience regarding seroma formation at the donor site after microsurgical breast reconstruction. The observed rate of donor site seroma formation was comparably high, especially in the TMG and SGAP group, necessitating an adaption of the surgical protocol.

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