ABSTRACT
Viral respiratory infections are an important public health concern due to their prevalence, transmissibility, and potential to cause serious disease. Disease severity is the product of several factors beyond the presence of the infectious agent, including specific host immune responses, host genetic makeup, and bacterial coinfections. To understand these interactions within natural infections, we designed a longitudinal cohort study actively surveilling respiratory viruses over the course of 19 months (2016 to 2018) in a diverse cohort in New York City. We integrated the molecular characterization of 800+ nasopharyngeal samples with clinical data from 104 participants. Transcriptomic data enabled the identification of respiratory pathogens in nasopharyngeal samples, the characterization of markers of immune response, the identification of signatures associated with symptom severity, individual viruses, and bacterial coinfections. Specific results include a rapid restoration of baseline conditions after infection, significant transcriptomic differences between symptomatic and asymptomatic infections, and qualitatively similar responses across different viruses. We created an interactive computational resource (Virome Data Explorer) to facilitate access to the data and visualization of analytical results.
Subject(s)
Coinfection , Virus Diseases , Viruses , Humans , Coinfection/genetics , Virome , Longitudinal Studies , Viruses/genetics , Virus Diseases/genetics , Virus Diseases/epidemiology , Bacteria/genetics , Gene Expression ProfilingABSTRACT
BACKGROUND: MicroRNA (miR)-214-3p is emerging as an important tumor suppressor in esophageal cancer. In this study, we examined the interaction between miR-214-3p and RAB14, a membrane trafficking protein shown to exert oncogenic functions in other malignancies, in esophageal cancer cells. METHODS: Studies were performed in a human esophageal epithelial cell line and a panel of esophageal cancer cell lines, as well in human specimens. MiR-214-3p expression was measured by digital PCR. Biotinylated RNA pull-down and luciferase reporter assays assessed binding. The xCELLigence RTCA system measured cell migration and invasion in real time. A lentiviral expression vector was used to create an esophageal cancer cell line stably expressing miR-214-3p. RESULTS: MiR-214-3p expression was decreased in esophageal cancer cell lines and human specimens compared to non-malignant controls. RAB14 mRNA stability and protein expression were decreased following miR-214-3p overexpression. Binding between miR-214-3p and RAB14 mRNA was observed. Either forced expression of miR-214-3p or RAB14 silencing led to a marked decrease in cellular migration and invasion. Esophageal cancer cells stably expressing miR-214-3p demonstrated decreased growth in a subcutaneous murine model. CONCLUSIONS: These results further support the tumor-suppressive role of miR-214-3p in esophageal cancer cells by demonstrating its ability to regulate RAB14 expression.
Subject(s)
Esophageal Neoplasms , MicroRNAs , rab GTP-Binding Proteins , Animals , Humans , Mice , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Genes, Tumor Suppressor , MicroRNAs/genetics , MicroRNAs/metabolism , rab GTP-Binding Proteins/genetics , rab GTP-Binding Proteins/metabolismABSTRACT
OBJECTIVES: Lung ultrasound (LUS) may help determine illness severity in children with acute lower respiratory tract infections (LRTI) but limited pediatric studies exist. Our objective was to determine the association between LUS findings and illness severity in children with LRTI. METHODS: We conducted a prospective study of patients <20 years with LRTI. Trained investigators performed standardized LUS examinations of 12 regions. Blinded sonologists reviewed examinations for individual pathologic features and also calculated a Quantified Lung Ultrasound Score (QLUS). We defined focal severity as QLUS of ≥2 in ≥1 region, and diffuse severity as QLUS of ≥1 in ≥3 regions. The primary outcome was the Respiratory component of the Pediatric Early Warning Score (RPEWS), a 14-item scale measuring respiratory illness severity. Secondary outcomes included hospital admission, length of stay, supplemental oxygen, and antibiotic use. RESULTS: We enrolled 85 patients with LRTIs, 46 (54%) whom were hospitalized (5.4% intensive care). Median RPEWS was 1 (interquartile range 2). Neither individual features on ultrasound nor total QLUS were associated with RPEWS, hospitalization, length of stay, or oxygen use. Mean RPEWS was similar for participants regardless of focal (1.46 versus 1.26, P = .57) or diffuse (1.47 versus 1.21, P = .47) severity findings, but those with focal or diffuse severity, or isolated consolidation, had greater antibiotic administration (P < .001). CONCLUSIONS: In children with LRTI, neither individual features nor QLUS were associated with illness severity. Antibiotics were more likely in patients with either focal or diffuse severity or presence of consolidation on ultrasound.
Subject(s)
Respiratory Tract Infections , Humans , Child , Prospective Studies , Respiratory Tract Infections/diagnostic imaging , Lung/diagnostic imaging , Emergency Service, Hospital , Patient Acuity , Anti-Bacterial Agents/therapeutic use , OxygenABSTRACT
BACKGROUND: Treatment of multiple myeloma with daratumumab (DARA) is increasing fast. Unfortunately, this antibody also attaches to red blood cells (RBCs) and mimics an autoantibody's panreactivity during pre-transfusion testing, necessitating specialized techniques, (e.g. dithiothreitol (DTT)) for alloantibody detection. Many hospitals use a reference lab for such testing, increasing both cost and turn-around time (TAT). Herein, we compare the cost and TAT, pre and post-implementation of an in-house DTT protocol. METHODS: We designed a validation of our in-house DTT protocol from Nov to Dec 2017 with full implementation on January 1, 2018. We retrospectively reviewed all pre-transfusion tests on DARA patients from Feb 2016 to April 2018, pre and post-implementation of in-house DTT testing. Descriptive statistics were used for patient demographics and a Student t-test was used to compare cost and TATs (pre and post-implementation). RESULTS: We identified 49 patients on DARA treatment requiring transfusion. Samples from these patients were sent to the reference lab 104 times and were tested in-house 28 times. The average TAT for the reference lab was 19h25 m compared to our in-house TAT of 5h9m (an average time-savings of 14h16 m). We spent approximately $33,800 ($325 per test) for 104 reference lab samples versus $806.12 (Ë$28.79 per test) for in-house testing of 28 samples. CONCLUSION: We provide an easily implementable DTT protocol for pre-transfusion testing community hospitals and beyond. As more monoclonal antibodies are developed and approved for clinical use, the lessons learned with DARA will expand to deal with interference from future targeted therapies.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Dithiothreitol/therapeutic use , Home Care Services/standards , Hospitals, Community/standards , Tertiary Care Centers/standards , Antibodies, Monoclonal/pharmacology , Cost-Benefit Analysis , Dithiothreitol/pharmacology , Female , Humans , Male , Reproducibility of Results , Retrospective StudiesABSTRACT
High-risk human papillomaviruses (HPVs) are causative agents of anogenital cancers and a fraction of head and neck cancers. The mechanisms involved in the progression of HPV neoplasias to cancers remain largely unknown. Here, we report that O-linked GlcNAcylation (O-GlcNAc) and O-GlcNAc transferase (OGT) were markedly increased in HPV-caused cervical neoplasms relative to normal cervix, whereas O-GlcNAcase (OGA) levels were not altered. Transduction of HPV16 oncogene E6 or E6/E7 into mouse embryonic fibroblasts (MEFs) up-regulated OGT mRNA and protein, elevated the level of O-GlcNAc, and promoted cell proliferation while reducing cellular senescence. Conversely, in HPV-18-transformed HeLa cervical carcinoma cells, inhibition of O-GlcNAc with a low concentration of a chemical inhibitor impaired the transformed phenotypes in vitro. We showed that E6 elevated c-MYC via increased protein stability attributable to O-GlcNAcylation on Thr58. Reduction of HPV-mediated cell viability by a high concentration of O-GlcNAc inhibitor was partially rescued by elevated c-MYC. Finally, knockdown of OGT or O-GlcNAc inhibition in HeLa cells or in TC-1 cells, a mouse cell line transformed by HPV16 E6/E7 and activated K-RAS, reduced c-MYC and suppressed tumorigenesis and metastasis. Thus, we have uncovered a mechanism for HPV oncoprotein-mediated transformation. These findings may eventually aid in the development of effective therapeutics for HPV-associated malignancies by targeting aberrant O-GlcNAc.
Subject(s)
Carcinogenesis , N-Acetylglucosaminyltransferases/physiology , Oncogene Proteins, Viral/physiology , Repressor Proteins/physiology , Uterine Cervical Neoplasms/etiology , Animals , Cell Line, Tumor , Female , Genes, myc , Humans , Mice , Mice, Inbred C57BL , Papillomavirus E7 Proteins/physiology , Uterine Cervical Neoplasms/virologyABSTRACT
Background: Brain-derived neurotrophic factor is implicated in the pathophysiology of major depressive disorder and suicide. Both are partly caused by early life adversity, which reduces brain-derived neurotrophic factor protein levels. This study examines the association of brain-derived neurotrophic factor Val66Met polymorphism and brain brain-derived neurotrophic factor levels with depression and suicide. We hypothesized that both major depressive disorder and early life adversity would be associated with the Met allele and lower brain brain-derived neurotrophic factor levels. Such an association would be consistent with low brain-derived neurotrophic factor mediating the effect of early life adversity on adulthood suicide and major depressive disorder. Methods: Brain-derived neurotrophic factor Val66Met polymorphism was genotyped in postmortem brains of 37 suicide decedents and 53 nonsuicides. Additionally, brain-derived neurotrophic factor protein levels were determined by Western blot in dorsolateral prefrontal cortex (Brodmann area 9), anterior cingulate cortex (Brodmann area 24), caudal brainstem, and rostral brainstem. The relationships between these measures and major depressive disorder, death by suicide, and reported early life adversity were examined. Results: Subjects with the Met allele had an increased risk for depression. Depressed patients also have lower brain-derived neurotrophic factor levels in anterior cingulate cortex and caudal brainstem compared with nondepressed subjects. No effect of history of suicide death or early life adversity was observed with genotype, but lower brain-derived neurotrophic factor levels in the anterior cingulate cortex were found in subjects who had been exposed to early life adversity and/or died by suicide compared with nonsuicide decedents and no reported early life adversity. Conclusions: This study provides further evidence implicating low brain brain-derived neurotrophic factor and the brain-derived neurotrophic factor Met allele in major depression risk. Future studies should seek to determine how altered brain-derived neurotrophic factor expression contributes to depression and suicide.
Subject(s)
Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , Brain/metabolism , Depressive Disorder, Major/genetics , Depressive Disorder, Major/metabolism , Suicide , Adult , Adult Survivors of Child Adverse Events , Alleles , Brain/pathology , Depressive Disorder, Major/pathology , Female , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Polymorphism, Single NucleotideABSTRACT
The significance of discontinuous growth (DG) of the tumor to include tumor deposits and intramural metastasis in esophageal adenocarcinoma (EAC) is unclear. Esophagectomy specimens from 151 treatment-naïve and 121 treated patients with EAC were reviewed. DG was defined as discrete (≥2 mm away) tumor foci identified at the periphery of the main tumor in the submucosa, muscularis propria, and/or periadventitial tissue. Patients' demographics, clinicopathologic parameters, and oncologic outcomes were compared between tumors with DG versus without DG. DGs were identified in 16% of treatment-naïve and 29% of treated cases ( P =0.01). Age, gender, and tumor location were comparable in DG+ and DG- groups. For the treatment-naïve group, DG+ tumors were larger with higher tumor grade and stage and more frequent extranodal extension, lymphovascular/perineural invasion, and positive margin. Patients with treated tumors presented at higher disease stages with higher rates of recurrence and metastasis compared with treatment-naïve patients. In this group, DG was also associated with TNM stage and more frequent lymphovascular/perineural spread and positive margin, but not with tumor size, grade, or extranodal extension. In multivariate analysis, in all patients adjusted for tumor size, lymphovascular involvement, margin, T and N stage, metastasis, neoadjuvant therapy status, treatment year, and DG, DG was found to be an independent adverse predictor of survival outcomes in EAC. DG in EAC is associated with adverse clinicopathologic features and worse patient outcomes. DG should be considered throughout the entire clinicopathologic evaluation of treatment-naïve and treated tumors as well as in future staging systems.
Subject(s)
Adenocarcinoma , Esophageal Neoplasms , Humans , Prognosis , Clinical Relevance , Extranodal Extension/pathology , Esophageal Neoplasms/surgery , Adenocarcinoma/pathology , Retrospective Studies , Neoplasm StagingABSTRACT
AIMS: Current guidelines offer limited strategies for managing recurrent/persistent oesophageal adenocarcinoma (EAC). Salvage endoscopic mucosal/submucosal resection (ER) shows promise in oesophageal squamous cell carcinoma, however its success in EAC is limited. We aimed to elucidate histological characteristics influencing salvage ER success in patients with low-stage, pretreated EAC. METHODS: We retrospectively reviewed 272 EAC tumours postoesophagectomy from five US centres and collected clinicopathological data including discontinuous growth (DG), defined as separate tumour foci ≥2 mm from the main tumour. We selected 101 patients with low-stage disease and divided them into treatment-naïve (n=70) and neoadjuvant therapy (n=31) groups. We compared the two groups and differences in clinical, histological and outcome characteristics were identified. RESULTS: In the entire cohort (n=272), DGs were identified in 22% of cases. Multivariate analysis revealed DGs as an independent prognostic factor for recurrence and positive oesophagectomy margins. Lymphovascular invasion (LVI) and background intestinal metaplasia predicted DG presence and absence, respectively. Compared with the treatment-naïve low T-stage subgroup, the pretreated subgroup exhibited higher incidence of poorly differentiated carcinoma (16% vs 46%, p=0.007), larger tumours (14 vs 30 mm, p<0.001), higher tumour, node, metastases stage (7% vs 30%, p=0.004), more nodal disease (7% vs 36%, p<0.001) and frequent DGs (1% vs 13%, p=0.030). CONCLUSIONS: In treated low T-stage EACs, DGs may contribute to suboptimal outcomes following salvage ER. Presence of LVI (as a surrogate for DGs) and poor differentiation in the absence of intestinal metaplasia in biopsy samples may serve as histological poor prognosticators in treated patients with EAC being considered for salvage ER.
ABSTRACT
Inborn errors of immunity lead to autoimmunity, inflammation, allergy, infection, and/or malignancy. Disease-causing JAK1 gain-of-function (GoF) mutations are considered exceedingly rare and have been identified in only four families. Here, we use forward and reverse genetics to identify 59 individuals harboring one of four heterozygous JAK1 variants. In vitro and ex vivo analysis of these variants revealed hyperactive baseline and cytokine-induced STAT phosphorylation and interferon-stimulated gene (ISG) levels compared with wild-type JAK1. A systematic review of electronic health records from the BioME Biobank revealed increased likelihood of clinical presentation with autoimmunity, atopy, colitis, and/or dermatitis in JAK1 variant-positive individuals. Finally, treatment of one affected patient with severe atopic dermatitis using the JAK1/JAK2-selective inhibitor, baricitinib, resulted in clinically significant improvement. These findings suggest that individually rare JAK1 GoF variants may underlie an emerging syndrome with more common presentations of autoimmune and inflammatory disease (JAACD syndrome). More broadly, individuals who present with such conditions may benefit from genetic testing for the presence of JAK1 GoF variants.
Subject(s)
Colitis , Dermatitis , Hypersensitivity , Humans , Autoimmunity , Colitis/genetics , Inflammation , Janus Kinase 1/geneticsABSTRACT
Fetal hemoglobin (HbF) is a potent genetic modifier of ß-thalassemia phenotype. B-cell lymphoma 11A ( BCL11A ) gene results in significant silencing of HbF. The aim of this study was to assess the prevalence of different BCL11A genotypes among a cohort of Egyptian children with ß-thalassemia and to correlate them to HbF and clinical severity score. Eighty-two children with ß-thalassemia (aged 12.95 ± 3.63 years) were recruited from the Pediatric Hematology Clinic, Ain Shams University. They were divided based on the clinical severity of ß-thalassemia into three subgroups: 20 mild (24.4%), 24 moderate (29.3%), and 38 severe (46.3%). Age, gender, age of diagnosis, initial HbF level, transfusion history, and history of splenectomy were assessed. Anthropometric measures, signs of anemia and hemosiderosis, and the severity score were determined. Laboratory investigations such as complete blood picture, ferritin, and single gene polymorphism genotyping of the rs11886868 were also performed. Our findings showed that 16 children had CC genotype (19.5%), 38 had TC genotype (46.3%), and 28 had TT genotype (34.1%) of the rs#. ß-thalassemia children with TT genotype had significantly higher severity scoring than the other two groups ( p < 0.001). Moreover, mean initial HbF was found to be lower in children with TT genotype followed by TC and CC genotypes ( p < 0.001). Increased γ-globin expression associated with BCL11A gene polymorphism is associated with better clinical severity of ß-thalassemia.
ABSTRACT
CALFAN syndrome is an extremely rare disease consisting of recurrent pediatric acute liver failure (PALF), neurodegenerative diseases, and skeletal abnormalities associated with SCYL1 gene mutation. To date, three of 18 patients reported underwent liver transplantation in infancy and early childhood (7-23 months). Here, we report a case of CALFAN syndrome with infantile onset, recurrent jaundice/PALF requiring liver transplantation in early adulthood. At the most recent follow-up, 3 years after transplantation, the patient is doing well.
ABSTRACT
CONTEXT.: Primary breast carcinomas constitute a divergent group of neoplasms. The classification of breast tumors has been evolving. Recent advances in molecular genetic techniques have enhanced our understanding of these diseases. Integration of state-of-the-art knowledge from research and practice has resulted in the recognition of novel entities as primary carcinomas of the breast with therapeutic and prognostic significance. OBJECTIVE.: To provide an overview of current concepts in the classification and diagnosis of selective salivary-type carcinomas of the breast, focusing on their salient histologic and immunophenotypic characteristics and recent molecular genetic advancements. DATA SOURCES.: Data were obtained from review of pertinent English-language literature and firsthand experience of the authors as practicing breast pathologists. CONCLUSIONS.: The cutting-edge knowledge has led us to further understand a growing number of uncommon types of breast carcinoma that demonstrate morphologic and immunophenotypic resemblance to those more frequently encountered in other organ systems, particularly salivary glands. Some of them also harbor identical molecular genetic alterations to those in their salivary gland counterparts. Yet they typically have diverse prognostic outcomes, thus warranting different clinical management. Accurate diagnosis of these tumors necessitates recognition of salient histologic features and judicious assessment of ancillary studies in the pursuit of precision medicine.
Subject(s)
Breast Neoplasms , Carcinoma , Salivary Gland Neoplasms , Humans , Female , Diagnosis, Differential , Biomarkers, Tumor/genetics , Salivary Gland Neoplasms/diagnosis , Salivary Gland Neoplasms/genetics , Salivary Gland Neoplasms/pathology , Salivary Glands/pathology , Carcinoma/diagnosis , Carcinoma/genetics , Carcinoma/pathology , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Breast Neoplasms/pathologyABSTRACT
Cisplatin is one of the most widely used chemotherapeutic drugs across the world. However, the serious ototoxic effects, leading to permanent hair cell death and hearing loss, significantly limit the utility of cisplatin. In zebrafish, the functional mechanotransduction channel is required for cisplatin ototoxicity. However, it is still unclear the extent to which the mechanotransduction channel is involved in cisplatin uptake and ototoxicity in mammalian hair cells. Herein, we show that genetically disrupting mechanotransduction in mouse partially protects hair cells from cisplatin-induced hair cell death. Using a fluorescent-dye conjugated cisplatin, we monitored cisplatin uptake in cochlear explants and found that functional mechanotransduction is required for the uptake of cisplatin in murine hair cells. In addition, cimetidine, an inhibitor of the organic cation transporter, also partially protects hair cells from cisplatin ototoxicity. Notably, the otoprotective effects of cimetidine do not require mechanotransduction. These findings suggest that both the mechanotransduction channel and the organic cation transporter are critical for cisplatin ototoxicity in murine hair cells.
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INTRODUCTION: The role of DNA methylation in metabolic dysregulation is emerging. However, the functional role of methylation in obesity and metabolic dysregulation is poorly understood. AIM: The aim of this study was to compare DNA methyltransferase-3A (DNMT3A) and ten-eleven translocase-2 (TET2) levels in children and adolescents with obesity to normal-weighed children and adolescents and to correlate them to various metabolic parameters. METHODS: Fifty children and adolescents with obesity were compared to 50 matched normal-weighed children and adolescents. Participants underwent assessment for anthropometric measurements, Tanner staging, acanthosis nigricans, and mean blood pressure percentile on three different occasions. TET2, DNMT3A, fasting lipids, and insulin were measured with calculation of the homeostatic model assessment insulin resistance (HOMA-IR). RESULTS: The median BMI SDS of the studied children and adolescents with obesity was 3.40, their mean TET2 was 178.40 ng/mL, and their mean DNMT3A was 2.18 ng/mL. TET2 is significantly lower (p = 0.009), while DNMT3A is significantly higher (p < 0.001) in children and adolescents with obesity than controls. Children and adolescents with obesity and insulin resistance have significantly lower TET2 (p = 0.012) and significantly higher DNMT3A (p = 0.013) than those without insulin resistance. Diastolic blood pressure percentile and HOMA-IR are positively correlated to DNMT3A (p < 0.001) and negatively correlated to TET-2 (p < 0.001). Multivariate logistic regression analysis revealed that TET2 and DNMT3A are independently associated with diastolic blood pressure percentile (p = 0.03 and p = 0.014, respectively) and HOMA-IR (p = 0.003 and p = 0.001, respectively). CONCLUSIONS: Children and adolescents with obesity have significantly higher DNMT3A and significantly lower TET2 than controls. This is more evident in those having insulin resistance than those without. DNMT3A and TET2 are independently associated with systemic hypertension and insulin resistance in children with obesity.
Subject(s)
DNA Methyltransferase 3A , DNA-Binding Proteins , Dioxygenases , Insulin Resistance , Pediatric Obesity , Adolescent , Blood Glucose/metabolism , Body Mass Index , Child , DNA Methylation , DNA Methyltransferase 3A/genetics , DNA-Binding Proteins/genetics , Dioxygenases/genetics , Humans , Insulin Resistance/genetics , Pediatric Obesity/complications , Pediatric Obesity/geneticsABSTRACT
Background: Toll-like receptor (TLR)-4 plays a vital role in recognizing viral particles, activating the innate immune system, and producing pro-inflammatory cytokines. Objectives: This cross-sectional study aimed to compare COVID-19 severity, progression, and fate according to TLR-4 (Asp299Gly) polymorphism in Egyptian patients. Methods: A total of 145 COVID-19 patients were included in this study. TLR-4 (Asp299Gly) genotyping was done using the PCR restriction fragment length polymorphism (PCR-RFLP) approach. Results: The most commonly encountered TLR-4 genotype in relation to the amino acid at position 299 was the wild-type AA (73.1%); meanwhile, the homozygous mutant GG genotype (8.3%) was the least encountered. At hospital admission, 85.8% of the AA group had free (with no ground glass opacities) chest computed tomography (CT) examination, and 16.0% were asymptomatic. On the other hand, of the AG and GG groups, 81.5% and 83.3%, respectively showed bilateral ground-glass opacities in chest CT, as well as 25.9% and 75.0%, respectively were dyspneic. Values of the total leucocytic count, C-reactive protein (CRP), ferritin, and D dimer increased in the AA
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Background: In clinical practice, distinguishing disease activity in patients with rheumatological illnesses is challenging. Objectives: We aimed to investigate clinical associations of hemogram-derived indices, namely: red cell distribution width (RDW), mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) with disease activity in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS). Methods: In 250 patients with rheumatological disease and 100 healthy age-matched controls, we investigated disease activity scores and indicators and evaluated their association with hemogram-derived indices values. Results: Compared with the control group, RDW, MPV, and PLR significantly increased (P < .001) in the three studied disorders (RA, SLE, and AS), but LMR dramatically decreased. SII was considerably higher in RA and AS patients compared with controls but not in SLE patients. On the other hand, NLR rose dramatically in SLE patients compared with controls (P = .043), but did not change much in RA and AS patients (P > .05). RDW and MPV showed significant changes (P < .001) in the three studied diseases (RA, SLE, and AS) according to disease activity. They significantly increased across worsening activity scores. Only in the SLE group, PLR was significantly increased with disease activity (P < .001), while LMR showed a significant decrease (P = .016). Conclusions: Clinicians must pay close attention to complete blood count (CBC) analysis and its various derived ratios to better characterize the activity of rheumatological disorders and anticipate the disease course and prognosis.
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PURPOSE: The Women Aware with Their Children study was created because prospective data are required to accurately guide prevention programmes for intimate partner violence (IPV) and to improve the mental health and resettlement trajectories of women from refugee backgrounds in Australia. PARTICIPANTS: 1335 women (685 consecutively enrolled from refugee backgrounds and 650 randomly selected Australian-born) recruited during pregnancy from three public antenatal clinics in Sydney and Melbourne, Australia. The mean age was 29.7 years among women from refugee backgrounds and 29.0 years among women born in the host nation. Main measures include IPV, mood, panic, post-traumatic stress disorder, disability and living difficulties. FINDINGS TO DATE: Prevalence of IPV at all three time points is significantly higher for refugee-background women. The trend data showed that reported IPV rates among Australian-born women increased from 25.8% at time 1 to 30.1% at time 3, while for refugee-background women this rate declined from 44.4% at time 1 to 42.6% at time 3. Prevalence of major depressive disorder (MDD) at all three time points is higher for refugee-background women. MDD among Australian-born women significantly declined from 14.5% at time 1 to 9.9% at time 3, while for refugee-background women it fluctuated from 25.1% at time 1 to 17.3% at time 2 and to 19.1% at time 3. FUTURE PLANS: We are currently examining trajectories of IPV and mental disorder across four time points. Time 4 occurred during the COVID-19 pandemic, enabling a unique opportunity to examine the impacts of the pandemic over time. Time 5 started in August 2021 and time 6 will begin approximately 12 months later. The children at time 5 are in the early school years, providing the capacity to examine behaviour, development and well-being of the index child.
Subject(s)
COVID-19 , Depressive Disorder, Major , Intimate Partner Violence , Refugees , Adult , Australia/epidemiology , Child , Cohort Studies , Depressive Disorder, Major/epidemiology , Female , Humans , Intimate Partner Violence/psychology , Male , Mental Health , Pandemics , Pregnancy , Prospective Studies , Refugees/psychologyABSTRACT
BACKGROUND: The incidence of colorectal cancer (CRC) has risen worldwide, with increasing prevalence in the UAE and GCC during the last few decades. Dietary and lifestyle behaviors play a pivotal role in the development and prevention of sporadic, with knowledge and awareness considered the first line of defence. Knowledge, awareness, and practices have been examined in different parts of the world, with scarce research have been conducted in the GCC countries and the UAE in particular. This study explored the UAE university student's knowledge and awareness toward the role of dietary and lifestyle behaviors in CRC. METHODS: A cross-sectional study was conducted, using an online multi-component self-reported questionnaire. Descriptive and analytical statistics were used. RESULTS: A total of 1213 students participated in the study, with the vast majority (92.7%) of the surveyed students reported good knowledge scores toward CRC risk factors. Significant differences (P<0.05) were found between the two sexes regarding dietary and lifestyle factors associated with CRC. Females consumed more vegetables compared to males, had lower intakes of red and processed meats, and were found to be fewer smokers. Being single (P= 0.0001), undergraduate (P=0.005), with medium to low income (P=0.026) all were significantly associated with increased risk of having poor knowledge about CRC, while being a medical student was significantly associated (P= 0.0001) with a 55% lower risk of having poor knowledge. CONCLUSION: Despite the good knowledge, university students' dietary and lifestyle behaviors necessities improvement, with barriers that require to be addressed.
Subject(s)
Colorectal Neoplasms , Students, Medical , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/prevention & control , Cross-Sectional Studies , Female , Health Knowledge, Attitudes, Practice , Humans , Life Style , Male , UniversitiesABSTRACT
Tumor necrosis factor receptor-associated factor 3 (TRAF3) is a central regulator of immunity. TRAF3 is often somatically mutated in B cell malignancies, but its role in human immunity is not defined. Here, in five unrelated families, we describe an immune dysregulation syndrome of recurrent bacterial infections, autoimmunity, systemic inflammation, B cell lymphoproliferation, and hypergammaglobulinemia. Affected individuals each had monoallelic mutations in TRAF3 that reduced TRAF3 expression. Immunophenotyping showed that patients' B cells were dysregulated, exhibiting increased nuclear factor-κB 2 activation, elevated mitochondrial respiration, and heightened inflammatory responses. Patients had mild CD4+ T cell lymphopenia, with a reduced proportion of naïve T cells but increased regulatory T cells and circulating T follicular helper cells. Guided by this clinical phenotype, targeted analyses demonstrated that common genetic variants, which also reduce TRAF3 expression, are associated with an increased risk of B cell malignancies, systemic lupus erythematosus, higher immunoglobulin levels, and bacterial infections in the wider population. Reduced TRAF3 conveys disease risks by driving B cell hyperactivity via intrinsic activation of multiple intracellular proinflammatory pathways and increased mitochondrial respiration, with a likely contribution from dysregulated T cell help. Thus, we define monogenic TRAF3 haploinsufficiency syndrome and demonstrate how common TRAF3 variants affect a range of human diseases.
Subject(s)
Neoplasms , TNF Receptor-Associated Factor 3 , Autoimmunity/genetics , B-Lymphocytes , Humans , Mutation , Neoplasms/pathology , TNF Receptor-Associated Factor 3/genetics , TNF Receptor-Associated Factor 3/metabolismABSTRACT
BACKGROUND: Various musculoskeletal and autoimmune manifestations have been described in patients with coronavirus disease 2019 (COVID-19). Objectives: This study aims to investigate the prevalence and etiology of arthritis in post-COVID Egyptian patients. Methods: We included 100 post-COVID Egyptian patients who recovered 6 months ago and assessed several inflammatory and autoimmune markers. Results: The prevalence of post-COVID arthritis was 37%. Ankle, knee, and wrist were the most commonly affected joints. Old age (P = 0.010), smoking (P = 0.001), and arthralgia (P = 0.049) were all linked with post-COVID arthritis. Levels of pretreatment (baseline) interleukin (IL)-6 (46.41 ± 3.67 vs. 24.03 ± 2.46; P = 0.001), as well as 6-month post-COVID C-reactive protein (CRP; 98.49 ± 67.55 vs. 54.32 ± 65.73; P = 0.002), and erythrocyte sedimentation rate (ESR; 109.08 ± 174.91 vs. 58.35 ± 37.87; P = 0.029) were significantly higher in patients with arthritis compared to those without. On the other hand, complement C3 (P = 0.558) and C4 (P = 0.192), anti-nuclear antibodies (P = 0.709), and anti-cyclic citrullinated peptides (anti-CCP; P = 0.855) did not show significant differences. Only pretreatment IL-6 level was the significant single predictor of post-COVID arthritis with an odds ratio (95% confidence interval) of 3.988 (1.460-10.892) and a P-value of 0.007. CONCLUSION: The strong association observed with inflammatory markers (ESR and CRP) and the insignificant association with serologic markers of autoimmunity (ANA and anti-CCP) in our study support the notion that the underlying mechanism of post-COVID-19 arthritis is primarily due to the hyperinflammatory process associated with COVID-19 infection, and not the result of an autoimmune reaction. IL-6 levels before therapy can predict post-COVID arthritis allowing for early management.