Potential efficacy of digital polymerase chain reaction for non-invasive prenatal screening of autosomal aneuploidies: a systematic review and meta-analysis.

BACKGROUND: Digital Polymerase Chain Reaction (dPCR) presents a promising approach for quantifying DNA and analyzing copy number variants, particularly in non-invasive prenatal testing. This method offers a streamlined and time-efficient procedure in contrast to the widely used next-generation sequencing for non-invasive prenatal testing. Studies have reported encouraging results for dPCR in detecting fetal autosomal aneuploidies. Consequently, this systematic review aimed to evaluate the effectiveness of dPCR in screening for trisomy 21, 18, and 13. METHODS: A systematic search was conducted in PubMed, Web of Sciences, and Embase for relevant articles published up to December 30, 2023. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was utilized for the quality assessment of the included articles. Furthermore, a bivariate random-effect regression model was used to conduct a meta-analysis on the utility of dPCR for trisomy 21 screening. RESULTS: A total of 9 articles were included in this review, with all of them assessing the utility of dPCR in trisomy 21 screening, and 2 and 1 studies conducting additional analysis on the screening abilities of dPCR for trisomy 18 and 13, respectively. A bivariate random-effects model calculated pooled sensitivity and specificity with a 95% confidence interval (CI). Meta-analysis of 6 studies comparing trisomy-21 screening with karyotyping demonstrated dPCR's pooled sensitivity of 98% [95% CI: 94 -100] and specificity of 99% [95% CI: 99 -100]. While conducting a meta-analysis for trisomy 13 and 18 proved impractical, reported values for sensitivity and specificity were favorable. CONCLUSIONS: These findings suggest that dPCR holds promise as an effective tool for non-invasive prenatal testing, presenting a less time-consuming and intricate alternative to next-generation sequencing. However, further research is necessary to evaluate dPCR's applicability in clinical settings and to delineate its specific advantages over next-generation sequencing. This study contributes valuable insights into the potential of dPCR for enhancing prenatal screening methodologies. TRIAL REGISTRATION: The protocol of this study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) on 7/3/2024, with a registration code of CRD42024517523.

Paradoxical air embolism in patients undergoing hysteroscopic surgery for cesarean scar pregnancy: A case report and review of the literatures.

Cesarean scar pregnancy cases who undergo hysteroscopic suction aspiration could be at higher risk of air emboli due to dilated, low-resistant, high-velocity blood vessels.

Severe fetal hemolytic disease due to anti-M alloimmunization: A case report and literature review.

Fetal hemolysis is caused by maternal antibodies that cross the placenta. Anti-M antibodies can rarely cause severe forms of alloimmunization in the fetus and newborn. We present a case of severe anti-M alloimmunization requiring a total of 8 intrauterine transfusions, in a patient with a prior poor obstetrical history. A 35-year-old Iranian pregnant woman with a prior obstetrical history of one abortion and two stillbirths was found to have had anti-M antibody titers 1:8 and accompanying elevated middle cerebral artery peak systolic velocity (MCA-PSV) of 1.9 MoM suggestive of severe fetal anemia at 17 weeks of gestation. Persistently elevated fetal MCA-PSV was noted despite intraperitoneal transfusion at 17, 19, and 22 weeks. Fetal blood sampling at 27 weeks confirmed severe fetal anemia (3 g/dL), which required additional intravascular and intraperitoneal blood transfusion. At 37 weeks, elective cesarean section was performed. Neonatal hemoglobin immediately after delivery was 10.1 g/dL. In addition to standard supportive care, the neonate required two additional transfusions and remained in the neonatal intensive care unit (NICU) for 23 days. Anti-M antibodies are a rare cause of severe alloimmunization. We present a case in order to improve management.

Molecular characterization of Staphylococcus aureus isolated from hospital-acquired infections in Ilam, Iran.

OBJECTIVE: This research study was undertaken to investigate antimicrobial resistance patterns and the prevalence of hospital-acquired infections (HAIs). The study focuses on common microorganisms responsible for HAIs and explores emerging challenges posed by antimicrobial drug-resistant isolates. METHODS: A comprehensive analysis of 123 patients with HAIs, hospitalized in surgical department and intensive care unit (ICU) at Imam Khomeini Hospital, Ilam, Iran, was conducted over a six-month period. Pathogenic bacterial isolates, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Staphylococcus aureus (VRSA), were isolated and subjected to antibiotic susceptibility testing. RESULTS: The study findings revealed a significant prevalence of multidrug-resistant (MDR) isolates, of which 73.3% were MRSA. Notably, 6.7% of S. aureus isolates exhibited resistance to vancomycin, indicating the emergence of VRSA. Respiratory infections were identified as the most prevalent HAI, constituting 34.67% of cases, often arising from extended ICU stays and invasive surgical procedures. Furthermore, patients aged 60 and above, particularly those associated with MDR, exhibited higher vulnerability to HAI. CONCLUSIONS: This research sheds light on the intricate interplay between drug resistance and HAI, highlighting the imperative role of rational antibiotic use and infection control in addressing this critical healthcare challenge.

Prevailing of HPV-16 and 52 genotype in 2022-2023 in Sanandaj, Iran.

INTRODUCTION: Human papillomavirus (HPV) presents a potential threat to the onset of carcinogenesis in the cervix, anogenital regions, and oropharynx. HPV encompasses over 200 types, with at least 12 having the potential to cause cancer, impacting the majority of sexually active individuals. In this current research, we explore the occurrence and spread of HPV genotypes. MATERIAL AND METHODS: During this cross-sectional study conducted in Sanandaj, Iran from Feb 2022 to Aug 2023, diverse samples including oral, vaginal, and genital were collected from individuals referred to private laboratories in Sanandaj, Iran. After sample collection and DNA extraction (FAVORGEN, Taiwan), they were subjected to PCR and genotyping (MehrViru, Iran). The subsequent statistical analysis unveiled infection rates across different demographics and age groups. STATA (version 17) were used for statistical analysis. We examined infection rates across demographics using t-tests and Odds Ratio. RESULTS: Overall, 26% (249) out of 950 cases tested positive for HPV, with 69% of these classified as high-risk. Among the examined population, 98% (933) were female, and 2% (17) were male. Females aged 31-40 exhibited the highest percentage of HPV prevalence (115/460) in the study with the majority of positive cases belonging to HR genotypes. The overall most frequent genotypes identified were 6, 16, 52, 53, 51, 58, and 56. HPV-16 exhibited the highest frequency among HR genotypes, accounting for 42 (17%) occurrences, followed by HPV-52 with a frequency of 32 (13%). CONCLUSION: Our findings emphasize the significant prevalence of HPV among females, particularly in the 21-30 age group. The identification of high-risk genotypes, underscores the importance of targeted interventions for specific age cohorts. The age-stratified analysis highlights a consistent predominance of high-risk HPV across age groups, indicating the need for age-specific preventive measures. These results contribute valuable information for designing effective screening and vaccination strategies, to alleviate the impact of diseases associated with HPV.

APOE and Alzheimer's disease: Pathologic clues from transgenic Drosophila melanogaster.

Alzheimer's disease (AD) is one of the most common forms of neurodegenerative diseases. Apolipoprotein E4 (ApoE4) is the main genetic risk factor in the development of late-onset AD. However, the exact mechanism underlying ApoE4-mediated neurodegeneration remains unclear. We utilized Drosophila melanogaster to examine the neurotoxic effects of various human APOE isoforms when expressed specifically in glial and neural cells. We assessed impacts on mitochondrial dynamics, ER stress, lipid metabolism, and bio-metal ion concentrations in the central nervous system (CNS) of the transgenic flies. Dachshund antibody staining revealed a reduction in the number of Kenyon cells. Behavioral investigations including ethanol tolerance and learning and memory performance demonstrated neuronal dysfunction in APOE4-expressing larvae and adult flies. Transcription level of marf and drp-1 were found to be elevated in APOE4 flies, while atf4, atf6, and xbp-1 s showed down regulation. Enhanced concentrations of triglyceride and cholesterol in the CNS were observed in APOE4 transgenic flies, with especially pronounced effects upon glial-specific expression of the gene. Spectrophotometry of brain homogenate revealed enhanced Fe++ and Zn++ ion levels in conjunction with diminished Cu++ levels upon APOE4 expression. To explore therapeutic strategies, we subjected the flies to heat-shock treatment, aiming to activate heat-shock proteins (HSPs) and assess their potential to mitigate the neurotoxic effects of APOE isoforms. The results showed potential therapeutic benefits for APOE4-expressing flies, hinting at an ability to attenuate memory deterioration. Overall, our findings suggest that APOE4 can alter lipid metabolism, bio metal ion homeostasis, and disrupt the harmonious fission-fusion balance of neuronal and glial mitochondria, ultimately inducing ER stress. These alterations mirror the main clinical manifestations of AD in patients. Therefore, our work underscores the suitability of Drosophila as a fertile model for probing the pathological roles of APOE and furthering our understanding of diverse isoform-specific functions.

Prediction of bleeding in placenta accrete spectrum with lacunar surface: a novel aspect.

PURPOSE: Diagnosing the placenta accreta spectrum is crucial to prevent morbidities and mortalities among women with the suspicion of this pathology. We aim to evaluate novel ultrasonography markers for these patients in diagnosing and predicting prognosis. METHODS: This cross-sectional study was performed in a referral academic hospital. The population was composed of 51 pregnant women with a suspect of placenta accreta spectrum who had scheduled C-sections. Their primary information and past medical histories were documented. Then the ultrasonography markers, including the most bulging volume behind the bladder (area, perimeter, and volume), the Lacune (diameter, length, number, and surface of the largest lacuna obtained by multiplying the length by the width), the most considerable thickness of placenta on the cervix in patients with placenta previa, the most considerable thickness of the placenta behind the bladder, the Jellyfish sign, and sponge cervix were evaluated. Their comparison to the severity of the bleeding, the rate of the hysterectomy, and the following pathology of the placenta accreta spectrum were analyzed. RESULTS: The results showed that 17 (33.3%) of patients had severe bleeding (more than 2500 cc). The diameter, length, and surface of the largest lacunae limited to women with severe bleeding were 13.50 (5.5-21) mm, 20.50 (11-56) mm, 273.00 (60-1176) mm2, and they were 11.00 (5-24) mm, 16.25 (10-39) mm, and 176.25 (50-744) mm2 for women without severe bleeding (P value = 0.039, 0.027, 0.021). 13 (76.5%) women with severe bleeding had Jellyfish signs,16 (94.2%) had bulging on the cervix, and 10(58.8%) had a sponge cervix (P value = 0.046, 0.036, 0.006). Also, 34 (66.66%) patients needed hysterectomy. The diameter, length, and surface of the largest lacunae limited to women with hysterectomy were 12.00 (5-24) mm, 18.00 (11-56) mm, 231.00 (60-1176) mm2, and they were 9.00 (5-18) mm, 15.00 (10-28) mm, and 136.00(50-504) mm2 for women without hysterectomy (P value = 0.012, 0.070, 0.021). 24(70.6%) women with hysterectomy had Jellyfish signs, 29 (85.3%) of them had bulging on the cervix, and 15 (44.1%) had sponge cervix (P value = 0.05, 0.036, 0.028). The cut-off associated with the Lacunar surface was 163.5 mm2. Its sensitivity was 80%, and its specificity was 48% (P value = 0.021). CONCLUSION: The presence of single large lacunae could be a suitable predictive factor for bleeding in the placenta accreta spectrum; Moreover, there are some other US criteria, including the presence of a sponge cervix or the Jellyfish sign that are valuable predictive factors for negative outcomes for this spectrum, including hysterectomy.

Conservative Management of Retroperitoneal Hematoma Expanded to Prerenal Space Due to Episiotomy in a Woman with Vaginal Delivery, a case report.

INTRODUCTION: Episiotomy is a procedure during vaginal delivery to facilitate a safer delivery. However, it can also have complications including hemorrhage, perineal tears, infections, and vaginal hematoma which should be managed and monitored carefully. PRESENTATION OF CASE: A 27-year-old woman with term pregnancy, had a normal vaginal delivery at 39 weeks of gestation, and a large episiotomy was performed due to the estimated neonate weight to prevent shoulder dystocia. She was complicated with a huge pelvic hematoma that was expanded to prerenal space. DISCUSSION: This complication was managed by conservative therapy, including antibiotic therapy, intensive observation of the patient's situation, and follow-up with a CT scan after consulting with a radiologist. The huge hematoma was reduced. CONCLUSION: Noninvasive management and close monitoring for pelvic hematoma due to episiotomy in a low-risk patient are successful; however, consulting with radiologists and experts and a multidisciplinary approach should be considered.

Burden and quality of care index of chronic kidney disease: Global Burden of Disease analysis for 1990-2019.

BACKGROUND: Chronic kidney disease (CKD) imposes a heavy obscure burden on individuals and health systems. Besides its burden, the quality of care of CKD is less well investigated. In this study, we aimed to explore the global, regional and national trends of CKD burden and quality of care. METHODS: The Global Burden of Disease Study 2019 data were used. Trends of incidence, prevalence, deaths and disability-adjusted life years were studied for the 1990-2019 period in the global aspect. By generating four secondary indices to assess different aspects of quality of care the quality of care index (QCI) was developed to explore the care provided for CKD. Inequities and disparities between various geographic, socio-demographic and age stratifications, and sex were studied using the QCI values. RESULTS: In 2019, there were 18 986 903 (95% uncertainty interval 17 556 535 to 20 518 156) incident cases of CKD, globally. The overall global QCI score had increased slightly from 78.4 in 1990 to 81.6 in 2019, and it was marginally better in males (QCI score 83.5) than in females (80.3). The highest QCI score was observed in the European region with a score of 92.5, while the African region displayed the lowest QCI with 61.7. Among the age groups, the highest QCI was for children aged between 5 and 9 years old (92.0), and the lowest was in the age group of 20-24 year olds (65.5). CONCLUSIONS: This study revealed that significant disparities remain regarding the quality of care of CKD, and to reach better care for CKD, attention to and care of minorities should be reconsidered. The evidence presented in this study would benefit health policymakers toward better and more efficient control of CKD burden alongside improving the care of this condition.

Mixed oral biofilms are controlled by the interspecies interactions of Fusobacterium nucleatum.

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) is an integral component of supra- and subgingival biofilms, especially more prevalent in subgingival areas during both periodontal health and disease. AIMS: In this review, we explore the physical, metabolic, and genetic interactions that influence the role of F. nucleatum in the formation of mixed oral biofilms. The role of F. nucleatum in antibiotic resistance in oral biofilms was discussed and some therapeutic strategies were proposed. METHODS: PubMed, Scopus, Google Scholar, and the Web of Science were extensively searched for English-language reports. RESULTS: F. nucleatum-derived proteins such as RadD, Fap2, FomA, and CmpA are involved in direct interactions contributing to biofilm formation, while autoinducer-2 and putrescine are involved in metabolic interactions. Both groups are essential for the formation and persistence of oral biofilms. This study highlights the clinical relevance of targeted interactions of F. nucleatum in supra- and subgingival oral biofilms. CONCLUSIONS: By focusing on these interactions, researchers and clinicians can develop more effective strategies to prevent biofilm-related disease and reduce the spread of antibiotic resistance. Further research in this area is warranted to explore the potential therapeutic interventions that can be derived from understanding the interactions of F. nucleatum in oral biofilm dynamics.

Evaluating the incidence of ampC-ß-lactamase genes, biofilm formation, and antibiotic resistance among hypervirulent and classical Klebsiella pneumoniae strains.

AIM: Both immunocompetent and healthy individuals can become life-threateningly ill when exposed to the hypervirulent (hvKp) strains of Klebsiella pneumoniae (Kp). The main objectives of this study were to evaluate the presence of ampC-lactamase genes, biofilm formation, and antibiotic resistance in clinical strains of hvKp and cKp (classical K. pneumoniae). MATERIALS AND METHODS: Kp strains were collected from patients referred to Shahidzadeh Hospital in Behbahan City, Khuzestan Province, Iran. Several techniques were used to identify hvKp. The hypermucoviscosity phenotype was determined using the string test. Isolates that developed dark colonies on tellurite agar were assumed to be hvKp strains. If any of the iucA, iutA, or peg-344 genes were detected, the isolates were classified as hvKp. Phenotypic and genotypic detection of AmpC ß-lactamases of hvKp strains was performed by the combined disk method and polymerase chain reaction, respectively. In addition, crystal violet staining was used to determine the biofilm formation of these isolates. RESULTS: For this study, 76 non-duplicative isolates of Kp were collected. Overall, 22 (28.94%) strains had positive string test results, and 31 (40.78%) isolates were grown in tellurite-containing medium. The genes iucA and iutA or peg-344 were found in 23.68% of all Kp strains and in 50% of tellurite-resistant isolates, respectively. The most effective antibiotics against hvKp isolates were tetracycline (85.52%) and chloramphenicol (63.15%). Using the cefoxitin disc diffusion method, we observed that 56.57% (43/76) of the strains were AmpC producer. A total of 30.26% (n = 23/76) of the isolates tested positive for at least one ampC gene, including blaDHA (52.63%, n = 40), blaCIT (40.78%, n = 31), blaACC (19.76%, n = 15), blaMOX (25%, n = 19), and blaFOX (43.42%, n = 33). Biofilm formation analysis revealed that most hvKp isolates were weak (n = 6, 40%) and moderate (n = 5, 33.33%) biofilm producers. CONCLUSION: Healthcare practitioners should consider the possibility of the existence and acquisition of hvKp everywhere. The exact mechanisms of bacterial acquisition are also unknown, and it is unclear whether the occurrence of infections is related to healthcare or not. Thus, there are still many questions about hvKp that need to be investigated.

Novel markers of Doppler ultrasonography in the placenta accreta spectrum to predict complications

Objective: Ultrasonography (US) is an acceptable tool to diagnose the placenta accreta spectrum (PAS) among pregnant women. However, the lack of a robust criteria for diagnosis and predicting the severity of the consequences facing pregnant women requires identification of novel biomarkers. Material and Methods: This prospective, cross-sectional study was performed on pregnant women with a probable diagnosis of PAS. Their demographic information, medical and surgical history, blood loss severity (severe ≥2500 mL) following hysterectomy, and the histopathology after the surgery were collected. In addition, the Doppler imaging of both uterine arteries, including the pulsatility index, resistance index, peak systolic velocity (PSV), the PSV of the posterior part of the bladder, cervix, the largest lacuna, and the posterior lacuna of the bladder were calculated by Doppler US. Data were analyzed to investigate the relationship between Doppler markers and the severity of PAS in terms of bleeding, hysterectomy, and histopathology. Results: Fifty-one women were enrolled with a mean age of 35.4±4.11 years and 17 (33.3%) had severe bleeding. There were significant differences between median (range) bladder PSV [57 (34-90) vs. 33 (20-64); p<0.001], cervix PSV [26 (0-63) vs. 18 (0-76); p=0.04] and left uterine artery [89 (81-135) vs. 68 (61-113); p=0.045] for women with and without severe bleeding, respectively. Thirty-four (66.66%) had hysterectomy. Comparison of bladder PSV, cervix PSV, and left uterine PSV for women with and without hysterectomy were 46 (20-90) vs. 39.5 (33-46) (p=0.005), 20 (0-76) vs. 20 (14-26) (p=0.013) and 68 (61-135) vs. 82 (63-101) (p=0.003), respectively. Conclusion: Bladder PSV, cervix PSV, and uterine PSV were significantly higher in pregnant women with PAS, and they may be useful diagnostic and prognostic markers.

Effect of ZnO nanoparticles on biofilm formation and gene expression of the toxin-antitoxin system in clinical isolates of Pseudomonas aeruginosa.

BACKGROUND: Biofilm formation by Pseudomonas aeruginosa (P. aeruginosa) is known to be characteristic of this organism. This bacterium is considered one of the most life-threatening bacteria and has been identified as a priority pathogen for research by WHO. Biofilm-producing P. aeruginosa is a concern in many parts of the world due to antibiotic resistance. Alginate also plays an important role in the biofilm formation of P. aeruginosa as well as the emergence of antibiotic resistance in biofilms. In addition, the systems of toxin-antitoxin( TA) play an important role in biofilm formation. Metal nanoparticle(NP) such as zinc oxide (ZnO) also have extensive biological properties, especially anti-biofilm properties. Therefore, this study was conducted in relation to the importance of zinc oxide nanoparticles (ZnO NPs) in biofilm formation and also the correlation of gene expression of TA systems in clinical isolates of P. aeruginosa. METHODS: A total of 52 P. aeruginosa isolates were collected from burns (n = 15), UTI (n = 31), and trachea (n = 6) in hospitals in Ilam between May 2020 and October 2020. Biofilm formation was assessed using a microtiter plate assay. MIC and sub-MIC concentrations of ZnO NPs (10-30 nm with purity greater than 99.8%) in P. aeruginosa were determined. Subsequently, biofilm formation was investigated using sub-MIC concentrations of ZnO NPs. Finally, total RNA was extracted and RT- qPCR was used to determine the expression levels of genes of mazEF, mqsRA, and higBA of TA systems. RESULTS: Six isolates of P. aeruginosa were found to form strong biofilms. The results showed that ZnO NPs were able to inhibit biofilm formation. In our experiments, we found that the sub-MIC concentration of ZnO NPs increased the gene expression of antitoxins mazE and mqsA and toxin higB of TA systems treated with ZnO NPs. CONCLUSIONS: In the present study, ZnO NPs were shown to effectively inhibit biofilm formation in P. aeruginosa. Our results support the relationship between TA systems and ZnO NPs in biofilm formation in P. aeruginosa. Importantly, the expression of antitoxins mazE and mqsA was high after treatment with ZnO NPs, but not that of antitoxin higA.

Breast Implant Illness as a Challenging Disorder in Clinics.

Breast augmentation is a common cosmetic procedure but may cause physical and psychological side effects, including malignancies and breast implant illness (BII). BII is a condition that can improve with implant removal. We present a challenging case with the diagnosis of BII that was appropriately managed, and we wanted to share this experience with you. A 41-year-old woman with bilateral breast augmentation presented with nonspecific symptoms like pain, fatigue, and brain fog. After doing all workups and ruling out other causes, she underwent implant removal surgery with the diagnosis of BII. The patient's symptoms disappeared after the surgical intervention to remove the breast implants. Overall, the case presented highlights the importance of considering breast implant illness (BII) as a potential cause of general and nonspecific symptoms in patients with breast implants. BII is a condition that can cause physical and psychological symptoms and can be challenging to diagnose due to its non-specific nature. This case underscores the importance of educating patients about breast augmentation's potential risks and side effects and obtaining informed consent before surgery. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The global prevalence of gastric cancer in Helicobacter pylori-infected individuals: a systematic review and meta-analysis.

BACKGROUND: Helicobacter pylori is a gastrointestinal pathogen that infects around half of the world's population. H. pylori infection is the most severe known risk factor for gastric cancer (GC), which is the second highest cause of cancer-related deaths globally. We conducted a systematic review and meta-analysis to assess the global prevalence of GC in H. pylori-infected individuals. METHODS: We performed a systematic search of the PubMed, Web of Science, and Embase databases for studies of the prevalence of GC in H. pylori-infected individuals published from 1 January 2011 to 20 April 2021. Metaprop package were used to calculate the pooled prevalence with 95% confidence interval. Random-effects model was applied to estimate the pooled prevalence. We also quantified it with the I2 index. Based on the Higgins classification approach, I2 values above 0.7 were determined as high heterogeneity. RESULTS: Among 17,438 reports screened, we assessed 1053 full-text articles for eligibility; 149 were included in the final analysis, comprising data from 32 countries. The highest and lowest prevalence was observed in America (pooled prevalence: 18.06%; 95% CI: 16.48 - 19.63; I2: 98.84%) and Africa (pooled prevalence: 9.52%; 95% CI: 5.92 - 13.12; I2: 88.39%). Among individual countries, Japan had the highest pooled prevalence of GC in H. pylori positive patients (Prevalence: 90.90%:95% CI: 83.61-95.14), whereas Sweden had the lowest prevalence (Prevalence: 0.07%; 95% CI: 0.06-0.09). The highest and lowest prevalence was observed in prospective case series (pooled prevalence: 23.13%; 95% CI: 20.41 - 25.85; I2: 97.70%) and retrospective cohort (pooled prevalence: 1.17%; 95% CI: 0.55 - 1.78; I 2: 0.10%). CONCLUSIONS: H. pylori infection in GC patients varied between regions in this systematic review and meta-analysis. We observed that large amounts of GCs in developed countries are associated with H. pylori. Using these data, regional initiatives can be taken to prevent and eradicate H. pylori worldwide, thus reducing its complications.

Site-specific transgene integration in chimeric antigen receptor (CAR) T cell therapies.

Chimeric antigen receptor (CAR) T cells and natural killer (NK) cells are genetically engineered immune cells that can detect target antigens on the surface of target cells and eliminate them following adoptive transfer. Recent progress in CAR-based therapies has led to outstanding clinical success in certain patients with leukemias and lymphomas and offered therapeutic benefits to those resistant to conventional therapies. The universal approach to stable CAR transgene delivery into the T/NK cells is the use of viral particles. Such approaches mediate semi-random transgene insertions spanning the entire genome with a high preference for integration into sites surrounding highly-expressed genes and active loci. Regardless of the variable CAR expression level based on the integration site of the CAR transgene, foreign integrated DNA fragments may affect the neighboring endogenous genes and chromatin structure and potentially change a transduced T/NK cell behavior and function or even favor cellular transformation. In contrast, site-specific integration of CAR constructs using recent genome-editing technologies could overcome the limitations and disadvantages of universal random gene integration. Herein, we explain random and site-specific integration of CAR transgenes in CAR-T/NK cell therapies. Also, we tend to summarize the methods for site-specific integration as well as the clinical outcomes of certain gene disruptions or enhancements due to CAR transgene integration. Also, the advantages and limitations of using site-specific integration methods are discussed in this review. Ultimately, we will introduce the genomic safe harbor (GSH) standards and suggest some appropriate safety prospects for CAR integration in CAR-T/NK cell therapies.

Emergency postpartum hysterectomy as a consequence of cervical varix during pregnancy; a case report and literature review.

INTRODUCTION AND IMPORTANCE: Vaginal bleeding might accrue during pregnancy and it has different causes due to the pregnancy trimester and the diagnosis and management would be crucial to prevent maternal-fetal life-threatening situations. In uncommon cases, varicose veins can emerge in the neck of the uterus, leading to a severe maternal hemorrhage. CASE PRESENTATION: We presented a pregnant woman with vaginal bleeding and spotting during pregnancy with the diagnosis of cervical varix at 22 weeks of gestation. Close monitoring and proper patient education led to a term delivery at 37 weeks of gestation. Otherwise, an emergency postpartum hysterectomy after a cesarean section was performed due to uncontrolled bleeding from cervical varix. CLINICAL DISCUSSION: Although rare, cervical varix should be included in the differential diagnosis in a pregnant patient who appears with extensive vaginal bleeding to reduce maternal and/or neonatal morbidity or fatality. The approved diagnosis for that is not clear. CONCLUSION: This case report showed that Doppler and transvaginal sonography could be suitable diagnostic tools. The best management for cervical varix needs further research.

TNF-α/STAT1/CXCL10 mutual inflammatory axis that contributes to the pathogenesis of experimental models of multiple sclerosis: A promising signaling pathway for targeted therapies.

BACKGROUND: Identifying mutual neuroinflammatory axis in different experimental models of multiple sclerosis (MS) is essential to evaluate the de- and re-myelination processes and improve therapeutic interventions' reproducibility. METHODS: The expression profile data set of EAE (GSE47900) and cuprizone (GSE100663) models were downloaded from the Gene Expression Omnibus database. The R package and GEO2R software processed these raw chip data. Gene Ontology (GO) functional analysis, KEGG pathway analysis, and protein-protein interaction network analysis were performed to investigate interactions between common differentially expressed genes (DEGs) in all models. Finally, the ELISA method assessed the protein level of highlighted mutual cytokines in serum. RESULTS: Our data introduced 59 upregulated [CXCL10, CCL12, and GBP6 as most important] and 17 downregulated [Serpinb1a, Prr18, and Ugt8a as most important] mutual genes. The signal transducer and activator of transcription 1 (STAT1) and CXCL10 were the most crucial hub proteins among mutual upregulated genes. These mutual genes were found to be mainly involved in the TNF-α, TLRs, and complement cascade signaling, and animal models shared 26 mutual genes with MS individuals. Finally, significant upregulation of serum level of TNF-α/IL-1ß/CXCL10 cytokines was confirmed in all models in a relatively similar pattern. CONCLUSION: For the first time, our study revealed the common neuroinflammatory pathway in animal models of MS and introduced candidate hub genes for better evaluating the preclinical efficacy of pharmacological interventions and designing prospective targeted therapies.

The interplay between tauopathy and aging through interruption of UPR/Nrf2/autophagy crosstalk in the Alzheimer's disease transgenic experimental models.

PURPOSE: Alzheimer's disease (AD) is the most common form of tauopathy that usually occursduring aging and unfolded protein response (UPR), oxidative stress and autophagy play a crucialrole in tauopathy-induced neurotoxicity. The aim of this study was to investigate the effects oftauopathy on normal brain aging in a Drosophila model of AD. METHOD: We investigated the interplay between aging (10, 20, 30, and 40 days) and human tauR406W (htau)-induced cell stress in transgenic fruit flies. RESULTS: Tauopathy caused significant defects in eye morphology, a decrease in motor function and olfactory memory performance (after 20 days), and an increase in ethanol sensitivity (after 30 days). Our results showed a significant increase in UPR (GRP78 and ATF4), redox signalling (p-Nrf2, total GSH, total SH, lipid peroxidation, and antioxidant activity), and regulatory associated protein of mTOR complex 1 (p-Raptor) activity in the control group after 40 days, while the tauopathy model flies showed an advanced increase in the above markers at 20 days of age. Interestingly, only the control flies showed reduced autophagy by a significant decrease in the autophagosome formation protein (dATG1)/p-Raptor ratio at 40 days of age. Our results were also confirmed by bioinformatic analysis of microarray data from tauPS19 transgenic mice (3, 6, 9, and 12 months), in which tauopathy increased expression of heme oxygenase 1, and glutamate-cysteine ligase catalytic subunit and promote aging in transgenic animals. CONCLUSIONS: Overall, we suggest that the neuropathological effects of tau aggregates may be accelerated brain aging, where redox signaling and autophagy efficacy play an important role.

Potential Role of Lactobacillus and Bifidobacterium for Preventing Kidney Stones.

BACKGROUND: A probiotic is a living microorganism that promotes host health when grown under appropriate conditions. Kidney stones are one of the universal agonizing diseases that have increased dramatically in recent years. One of the causes of this disease is hyperoxaluria (HOU), which is known to be an important factor in the formation of oxalate stones and is manifested by high levels of oxalate in the urine. In addition, about 80% of kidney stones contain oxalate, and decomposition of this material by microbes is one way to dispose of it. METHODS: Therefore, we examined a bacterial mixture containing Lactobacillus plantarum, Lactobacillus casei, Lactobacillus acidophilus, and Bifidobacterium longum to prevent of oxalate production in Wistar rats with kidney stones. We divided the rats into 6 groups defined in the method. RESULTS: The results of this study clearly show a decrease in urinary oxalate levels by exogenous means by L. plantarum, L. casei, L. acidophilus, and B. longum at the beginning of the experiment. Therefore, these bacteria can be used to control and prevent the formation of kidney stones. CONCLUSIONS: However, further studies should be conducted on the effects of these bacteria, and it is recommended to identify the gene responsible for the degradation of oxalate in order to develop a new probiotic.