-
American Journal of Obstetrics and... Jun 2024To investigate the association between actual and planned modes of delivery, neonatal mortality, and short-term outcomes among preterm pregnancies ≤32 weeks of gestation. (Review)
Review
Cesarean delivery is associated with lower neonatal mortality among breech pregnancies - a systematic review and meta-analysis of preterm deliveries ≤32 weeks of gestation.
OBJECTIVE
To investigate the association between actual and planned modes of delivery, neonatal mortality, and short-term outcomes among preterm pregnancies ≤32 weeks of gestation.
DATA SOURCES
A systematic literature search was conducted in three main databases (PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to November 16, 2022. The protocol was registered in advance in the International Prospective Register of Systematic Reviews (CRD42022377870).
STUDY ELIGIBILITY CRITERIA
Eligible studies examined pregnancies ≤ 32nd gestational week. All infants received active care, and the outcomes were reported separately by different modes of delivery. Singleton and twin pregnancies at vertex and breech presentations were included. Studies that included pregnancies complicated with preeclampsia and abruptio placentae were excluded. Primary outcomes were neonatal mortality and intraventricular hemorrhage.
STUDY APPRAISAL AND SYNTHESIS METHODS
Articles were selected by title, abstract, and full text, and disagreements were resolved by consensus. Random effects model-based odds ratios with corresponding 95% confidence intervals were calculated for dichotomous outcomes. ROBINS-I was used to assess the risk of bias.
RESULTS
A total of nineteen observational studies were included involving a total of 16,042 preterm infants in this systematic review and meta-analysis. Actual cesarean delivery improves survival (odds ratio, 0.62; 95% confidence interval, 0.42 to 0.9) and decreases the incidence of intraventricular hemorrhage (odds ratio, 0.70; confidence interval, 0.57 to 0.85) compared to vaginal delivery. Planned cesarean delivery does not improve the survival of very and extremely preterm infants compared to vaginal delivery (odds ratio, 0.87; 95% confidence interval, 0.53 to 1.44). Subset analysis found significantly lower odds of death for singleton breech preterm deliveries born by both planned (odds ratio, 0.56; 95% confidence interval, 0.32 to 0.98) and actual (odds ratio, 0.34; 95% confidence interval, 0.13 to 0.88) cesarean delivery.
CONCLUSION
Cesarean delivery should be the mode of delivery for preterm ≤32 weeks of gestation breech births due to the higher mortality in preterm infants born via vaginal delivery.
PubMed: 38908650
DOI: 10.1016/j.ajog.2024.06.015 -
Biochimie Jun 2024Amyloidosis forms a large family of pathologies associated with amyloid deposit generated by the formation of amyloid fibrils or plaques. The amyloidogenic proteins and...
Amyloidosis forms a large family of pathologies associated with amyloid deposit generated by the formation of amyloid fibrils or plaques. The amyloidogenic proteins and peptides involved in these processes are targeted against almost all organs. In brain they are associated with neurodegenerative disease, and the Translocator Protein (TSPO), overexpressed in these inflammatory conditions, is one of the target for the diagnostic. Moreover, TSPO ligands have been described as promising therapeutic drugs for neurodegenerative diseases. Type 2 diabetes, another amyloidosis, is due to a beta cell mass decrease that has been linked to hIAPP (human islet amyloid polypeptide) fibril formation, leading to the reduction of insulin production. In the present study, in a first approach, we link overexpression of TSPO and inflammation in potentially prediabetic patients. In a second approach, we observed that TSPO deficient rats have higher level of insulin secretion in basal conditions and more IAPP fibrils formation compared with wild type animals. In a third approach, we show that diabetogenic conditions also increase TSPO overexpression and IAPP fibril formation in rat beta pancreatic cell line (INS-1E). These data open the way for further studies in the field of type 2 diabetes treatment or prevention.
PubMed: 38908539
DOI: 10.1016/j.biochi.2024.06.007 -
Medicina 2024
Topics: Humans; Pancreatic Diseases; Male; Cholangiopancreatography, Endoscopic Retrograde
PubMed: 38907986
DOI: No ID Found -
BMC Medical Genomics Jun 2024Collagen (COL) genes, play a key role in tumor invasion and metastasis, are involved in tumor extracellular matrix (ECM)-receptor interactions and focal adhesion...
BACKGROUND
Collagen (COL) genes, play a key role in tumor invasion and metastasis, are involved in tumor extracellular matrix (ECM)-receptor interactions and focal adhesion pathways. However, studies focusing on the diagnostic value of the COL4 family in stomach adenocarcinoma (STAD) are currently lacking.
METHODS
The TCGA database was employed to retrieve the clinical features and RNA sequencing expression profiles of patients with STAD. We conducted an investigation to examine the expression disparities between STAD and adjacent normal tissues. Kaplan-Meier survival analysis was utilized to assess their prognostic significance, while Spearman correlation analysis was employed to determine their association with immune checkpoint genes and immunomodulatory molecules. Furthermore, GO and KEGG analyses were performed on the COL4s-related genes, revealing potential biological pathways through gene set enrichment analysis (GSEA). Subsequently, we explored the extent of immune infiltration of the COL4 family in STAD using the TIMER database. Lastly, the expression levels of the COL4 family in STAD were further validated through quantitative PCR (qPCR) and western blot techniques.
RESULTS
The expression levels of COL4A1/2 were significantly upregulated, while COL4A5/6 were conspicuously downregulated in STAD. The survival analysis revealed that the upregulated COL4s indicated poorer overall survival, first progression and post-progression survival outcomes. Additionally, our findings demonstrated a positive correlation between the expressions of COL4A1/2/3/4 and the infiltration of immune cells, including CD8 + T cells, dendritic cells, macrophages, neutrophils and CD4 + T cells. Further correlation analysis uncovered a favorable association between the expression of COL4A1/2/3/4 and various crucial immunomodulatory molecules, immunological checkpoint molecules, and chemokines. Quantitative PCR analysis confirmed that the expression patterns of COL4A1/3/4/6 genes aligned with the finding from the TCGA database. However, gastric cancer cells exhibited downregulation of COL4A2. Consistently, the protein level of COL4A1 was elevated, whereas the protein level of COL4A2 was reduced in the gastric cancer cell lines.
CONCLUSION
COL4s could potentially serve as biomarkers for diagnosing and predicting the prognosis of STAD.
Topics: Stomach Neoplasms; Humans; Adenocarcinoma; Prognosis; Collagen Type IV; Gene Expression Regulation, Neoplastic; Male; Female; Biomarkers, Tumor; Middle Aged; Kaplan-Meier Estimate
PubMed: 38907304
DOI: 10.1186/s12920-024-01934-3 -
Biomedicine & Pharmacotherapy =... Jun 2024Macropinocytosis is a cellular process that enables cells to engulf extracellular material, such as nutrients, growth factors, and even whole cells. It is involved in...
Macropinocytosis is a cellular process that enables cells to engulf extracellular material, such as nutrients, growth factors, and even whole cells. It is involved in several physiological functions as well as pathological conditions. In cancer cells, macropinocytosis plays a crucial role in promoting tumor growth and survival under nutrient-limited conditions. In particular KRAS mutations have been identified as main drivers of macropinocytosis in pancreatic, breast, and non-small cell lung cancers. We performed a high-content screening to identify inhibitors of macropinocytosis in pancreatic ductal adenocarcinoma (PDAC)-derived cells, aiming to prevent nutrient scavenging of PDAC tumors. The screening campaign was conducted in a well-known pancreatic KRAS-mutated cell line (MIAPaCa-2) cultured under nutrient deprivation and using FITC-dextran to precisely quantify macropinocytosis. We assembled a collection of 3584 small molecules, including drugs approved by the Food and Drug Administration (FDA), drug-like molecules against molecular targets, kinase-targeted compounds, and molecules designed to hamper protein-protein interactions. We identified 28 molecules that inhibited macropinocytosis, with potency ranging from 0.4 to 29.9 μM (EC). A few of them interfered with other endocytic pathways, while 11 compounds did not and were therefore considered specific "bona fide" macropinocytosis inhibitors and further characterized. Four compounds (Ivermectin, Tyrphostin A9, LY2090314, and Pyrvinium Pamoate) selectively hampered nutrient scavenging in KRAS-mutated cancer cells. Their ability to impair albumin-dependent proliferation was replicated both in different 2D cell culture systems and 3D organotypic models. These findings provide a new set of compounds specifically targeting macropinocytosis, which could have therapeutic applications in cancer and infectious diseases.
PubMed: 38906021
DOI: 10.1016/j.biopha.2024.116991 -
Medicine Jun 2024To explore the relationships between gastrointestinal radiation injuries of pancreatic cancer patients treated with TOMO and dose-volume histogram parameters... (Observational Study)
Observational Study
To explore the relationships between gastrointestinal radiation injuries of pancreatic cancer patients treated with TOMO and dose-volume histogram parameters prospectively. Seventy patients with pancreatic cancer who underwent TOMO were enrolled in this prospective study from February 2015 to May 2020. The clinical and dose-volume histogram parameters of the patients were collected. The optimal dose parameters for gastrointestinal radiation ulcers were confirmed based on the receiver operating characteristic curve (ROC) and the area below the ROC curve. Acute gastrointestinal tract toxic and side effect and injury grading correlation analyzed by Kruskal-Wallis rank sum test. Gastrointestinal injury often occurs during radiotherapy for pancreatic cancer, as observed using gastroscopy. The main adverse reactions were radioactive gastrointestinal inflammation (58.5%), radioactive gastrointestinal ulcers (41.4%), active bleeding (10%), newly-developed gastric retention (8.6%), and gastric varices (5.7%). As for the stomach, Dmean and V10 were related to radiation ulcer injury. ROC curve indicated that for stomach a Dmean of 13.39 Gy (area under ROC curves = 0.74, P = .048) and a V10 of 72.21% (area = 0.74, P = .048) was the tolerated dose for the injury of stomach radiation ulcer. As for duodenum, aV20 and aV25 are related to radiation ulcer injury. ROC curve indicated that aV20 of 22.82 cm3 (area = 0.68, P = .025) and aV25 of 32.04 cm3 (area = 0.66, P < .047) was the tolerated dose for the injury of duodenum radiation ulcer. The acute gastrointestinal tract toxic and side effects have no significant correlation with injury grading under gastroscope. Dmean > 13.39 Gy and V10 > 72.21% were the key dosimetric indices for predicting radiation-induced gastric ulcer, and aV20 > 22.82 cm3 and aV25 > 32.04 cm3 were for duodenal. Gastrointestinal reactions cannot be used as an overall basis for the diagnosis of gastrointestinal injury, and gastroscopy is recommended as a review item after radiotherapy.
Topics: Humans; Male; Female; Pancreatic Neoplasms; Middle Aged; Prospective Studies; Aged; Radiation Injuries; Gastroscopy; Radiotherapy Dosage; Radiotherapy, Intensity-Modulated; Adult; ROC Curve; Aged, 80 and over
PubMed: 38905414
DOI: 10.1097/MD.0000000000038469 -
Medicine Jun 2024walled-off pancreatic necrosis (WOPN) is one of the complications of acute pancreatitis (AP) with high mortality. A method to predict the development of WOPN in AP... (Observational Study)
Observational Study
The success of SII, MII-1, MII-2, MII-3, and QT dispersion in predicting the walled-off pancreatic necrosis development in acute pancreatitis in the emergency department: An observational study.
walled-off pancreatic necrosis (WOPN) is one of the complications of acute pancreatitis (AP) with high mortality. A method to predict the development of WOPN in AP patients admitted to the emergency department may guide life-saving practices such as early initiation of antibiotic therapy and, when necessary, referral of the patient to a center where necrosectomy can be performed. This study is a prospective observational study. One hundred eleven AP patients who applied to the emergency department were included in the study. The mean of QT interval (QT) dispersion, systemic immune-inflammation Index (SII), multi-inflammatory index-I (MII-1), multi-inflammatory index-II (MII-2), and multi-inflammatory index-III (MII-3) were compared between patients who developed WOPN and patients who did not develop WOPN during their hospitalization. In the study, the mean of QT dispersion, SII, MII-1, MII-2, and MII-3 were significantly lower in the patient group who developed WOPN compared to those who did not develop WOPN. In the receiver operating characteristic analysis, all methods except SII were found to be successful in predicting WOPN. QT dispersion, SII, MII-1, MII-2, and MII-3 are valuable tools that provide rapid results and successfully predict the development of WOPN in AP. However, MII-2 and QT dispersion appears to be slightly more successful than the others.
Topics: Humans; Male; Female; Middle Aged; Prospective Studies; Emergency Service, Hospital; Pancreatitis, Acute Necrotizing; Adult; Electrocardiography; Severity of Illness Index; Aged; Predictive Value of Tests; ROC Curve; Pancreatitis
PubMed: 38905406
DOI: 10.1097/MD.0000000000038599 -
Medicine Jun 2024This study aimed to evaluate the significance of serum salusin beta (SAL-β) levels in predicting the severity of acute pancreatitis (AP) in patients diagnosed with this... (Observational Study)
Observational Study
BACKGROUND
This study aimed to evaluate the significance of serum salusin beta (SAL-β) levels in predicting the severity of acute pancreatitis (AP) in patients diagnosed with this condition and to assess its relationship with disease and prognosis.
METHODS
Sixty-four patients between 18 and 100 years of age diagnosed with AP, were included in the study. Patients were categorized into 3 groups based on the Revised Atlanta Classification: mild, moderate, and severe AP. Eighteen healthy adults were included as the control group. Sex, age, height, weight, presence of additional diseases, laboratory results, imaging findings, levels of white blood cells, neutrophil-lymphocyte ratio, mean platelet volume, amylase, lipase, sensitive C-reactive protein, sedimentation, and serum SAL-β were measured and recorded. SAL-β levels were reevaluated on the third day of hospitalization.
RESULTS
The average age of the patients included in the study was 62.66 ± 17.67. Gallstones were present in 64.1% of the patients. The difference in the SAL-β averages on the 1st and 3rd days was statistically significant (P < .05). On the first day, the SAL-β averages of those with severe Atlanta scores were higher than those with mild and moderate Atlanta severity. Similarly, on the third day, the SAL-β averages of those with severe Atlanta scores were higher than those with mild and moderate Atlanta severity. According to receiver operating characteristic analysis using the Youden index, the cutoff value for SAL-β for severe pancreatitis was 178.8 pg/mL on the 1st day and 207.5 pg/mL on the 3rd day.
CONCLUSION
SAL-β can be used to detect and monitor severe pancreatitis. Further extensive clinical studies with larger case series are needed.
Topics: Humans; Male; Female; Middle Aged; Pancreatitis; Severity of Illness Index; Adult; Aged; Intercellular Signaling Peptides and Proteins; Aged, 80 and over; Young Adult; Biomarkers; Adolescent; Prognosis; Acute Disease; Case-Control Studies
PubMed: 38905397
DOI: 10.1097/MD.0000000000038685 -
PLoS Pathogens Jun 2024Histone demethylase JMJD2D (also known as KDM4D) can specifically demethylate H3K9me2/3 to activate its target gene expression. Our previous study has demonstrated that...
Histone demethylase JMJD2D (also known as KDM4D) can specifically demethylate H3K9me2/3 to activate its target gene expression. Our previous study has demonstrated that JMJD2D can protect intestine from dextran sulfate sodium (DSS)-induced colitis by activating Hedgehog signaling; however, its involvement in host defense against enteric attaching and effacing bacterial infection remains unclear. The present study was aimed to investigate the role of JMJD2D in host defense against enteric bacteria and its underlying mechanisms. The enteric pathogen Citrobacter rodentium (C. rodentium) model was used to mimic clinical colonic infection. The responses of wild-type and JMJD2D-/- mice to oral infection of C. rodentium were investigated. Bone marrow chimeric mice were infected with C. rodentium. JMJD2D expression was knocked down in CMT93 cells by using small hairpin RNAs, and Western blot and real-time PCR assays were performed in these cells. The relationship between JMJD2D and STAT3 was studied by co-immunoprecipitation and chromatin immunoprecipitation. JMJD2D was significantly up-regulated in colonic epithelial cells of mice in response to Citrobacter rodentium infection. JMJD2D-/- mice displayed an impaired clearance of C. rodentium, more body weight loss, and more severe colonic tissue pathology compared with wild-type mice. JMJD2D-/- mice exhibited an impaired expression of IL-17F in the colonic epithelial cells, which restricts C. rodentium infection by inducing the expression of antimicrobial peptides. Accordingly, JMJD2D-/- mice showed a decreased expression of β-defensin-1, β-defensin-3, and β-defensin-4 in the colonic epithelial cells. Mechanistically, JMJD2D activated STAT3 signaling by inducing STAT3 phosphorylation and cooperated with STAT3 to induce IL-17F expression by interacting with STAT3 and been recruited to the IL-17F promoter to demethylate H3K9me3. Our study demonstrates that JMJD2D contributes to host defense against enteric bacteria through up-regulating IL-17F to induce β-defensin expression.
PubMed: 38905308
DOI: 10.1371/journal.ppat.1012316 -
Therapeutic Advances in Respiratory... 2024Cystic fibrosis (CF) is an autosomal recessive disease caused by the inheritance of two mutant cystic fibrosis transmembrane conductance regulator (CFTR) alleles, one...
Identification and structural analysis for the first mutation in the cystic fibrosis transmembrane conductance regulator protein in Iran: case report and developmental insight using microsatellite markers.
Cystic fibrosis (CF) is an autosomal recessive disease caused by the inheritance of two mutant cystic fibrosis transmembrane conductance regulator (CFTR) alleles, one from each parent. Autosomal recessive disorders are rarely associated with germline mutations or mosaicism. Here, we propose a case of paternal germline mutation causing CF. The subject also had an identifiable maternal mutant allele. We identified the compound heterozygous variants in the proband through Sanger sequencing, and studies predicted functional effects on the protein. Also, short tandem repeat markers revealed the nature of the mutation. The maternal mutation in the CFTR gene was c.1000C > T. The mutation was c.178G > A, p.Glu60Lys. This mutation is located in the lasso motif of the CFTR protein and, according to structural analysis, disrupts the interaction of the lasso motif and R-domain, thus influencing protein function. This first reported case of mutation in Asia has notable implications for molecular diagnostics, genetic counseling, and understanding the genetic etiology of recessive disorders in the Iranian population.
Topics: Female; Humans; Male; Computer Simulation; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; DNA Mutational Analysis; Genetic Predisposition to Disease; Germ-Line Mutation; Iran; Microsatellite Repeats; Phenotype; Child, Preschool; Infant
PubMed: 38904297
DOI: 10.1177/17534666241253990