Untreated Female Patients Research Articles

Sex differences in intracranial plaque burden in patients with type 2 diabetes mellitus with acute ischemic cerebrovascular disease: a pilot study based on high-resolution MRI

BackgroundAtherosclerosis (AS) is the main cause of macrovascular disease. Previous studies have found sex differences in the prevalence of type 2 diabetes mellitus (T2DM) and its associated macrovascular disease outcomes. However, the relationship between sex differences, T2DM, and AS is not fully understood. This study attempts to explore possible associations between sex, treatment, and the burden of intracranial atherosclerosis (ICAS) in patients with T2DM who have experienced an acute ischemic cerebrovascular disease.MethodsWe focused on patients with T2DM with acute ischemic stroke or transient ischemic attack due to intracranial atherosclerotic stenosis. ICAS was assessed by 3T cardiovascular magnetic resonance vascular wall imaging. Plaque counts of the total, proximal, and distal intracranial arteries were used to assess plaque burden. Patients with a history of T2DM and currently taking hypoglycemic drugs were defined as being treated. Poisson regression models or negative binomial regression models were used to analyze the interaction between sex and treatment in relation to plaque burden.ResultsA total of 495 plaques were detected in 120 patients (75 male; mean age, 60.77 ± 11.01 years), including 311 proximal and 184 distal plaques. The intracranial culprit plaque was located proximal to the artery in both male (85.3%) and female (88.9%) patients. The adjusted total and proximal intracranial plaque burdens were 1.261 times (95% confidence interval [CI], 1.050–1.515, P=0.013) and 1.322 times (95%CI, 1.055–1.682, P=0.016) higher in male than in female patients. The risk ratio for proximal plaque burden in untreated male versus female patients was 0.966 (95%CI, 0.704–1.769). However, the proximal plaque risk ratio for treated male versus female patients was 1.530 (95%CI, 1.076–2.174). The interaction of sex and treatment significantly affected the proximal plaque burden.ConclusionMale patients with T2DM and acute cerebrovascular disease have a significantly higher adjusted risk of total and proximal intracranial plaque burden compared to female patients. Female patients undergoing antidiabetic treatment have a significantly reduced risk of proximal plaque to males. Considering that culprit plaques tend to accumulate in the proximal arteries, understanding how to reduce the burden of proximal plaques may help reduce the risk of adverse cerebrovascular events.

Transcriptomic Profiling of Peripheral B Cells in Antibody Positive Sjogren's Patients Reveals Interferon Signature.

Sjögren's disease (SjD) is a common systemic autoimmune disease that affects mainly women. Key pathologic features include the infiltration of exocrine glands by lymphocytes and the activation of B lymphocytes with the production of autoantibodies. We aimed to analyze the transcriptome of circulating B cells from patients with SJD and healthy controls to decipher the B-cell-specific contribution to SJD. RNA from peripheral blood B cells of five untreated female patients with SjD and positive ANA, positive anti-SSA (both Ro-52 and Ro-60), positive anti-SSB and positive rheumatoid-factor, and five healthy controls was subjected to whole-transcriptome sequencing. A false discovery rate of < 0.1 was applied to define differentially expressed genes (DEG). RNA-sequencing identified 56 up and 23 down DEG. Hierarchal clustering showed a clear separation between the two groups. Ingenuity pathway analysis revealed that these genes may play a role in interferon signaling, chronic mycobacterial infection, and transformation to myeloproliferative disorders. We found upregulated expression of type-I and type-II interferon (IFN)-induced genes, as well as genes that may contribute to other concomitant conditions, including infections and a higher risk of myeloproliferative disorders. This adds insight into the autoimmune process and suggests potential targets for future functional and prognostic studies.

Outcomes of pregnancy in Wilson's disease: a population-based study from multiple centres of the Han population in China.

Wilson's disease is an autosomal recessive disorder related to copper metabolism which mostly patients occurs in adolescents, fertility has become a problem that WD needs to face. A 21 years retrospective follow up study was conducted and a total of 220 female patients were included to identify patients with outcomes of pregnancy. Untreated female patients with WD had a spontaneous abortion rate of 44%. During the study period, 146 female patients with WD from multicenter, 75 patients (51.4%) had successful outcomes of pregnancy. Notably, urinary copper levels below 616 μg/24 h were strongly associated with successful pregnancy. The nomogram built on these variables were age, urinary copper, haemoglobin and Child-Pugh classification, internally validated and showed good performance. The spontaneous abortion rate was 44% in untreated females with WD and developed a four-variable risk prediction model to accurately predict the likelihood of a successful pregnancy.

Downregulation of lncRNA XIST may promote Th17 differentiation through KDM6A-TSAd pathway in neuromyelitis optica spectrum disorders.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease with significant female preponderance. X inactive specific transcript (XIST) is a long non-coding RNA (lncRNA) and a key regulator of X-chromosome inactivation which is related to the sex-bias of autoimmunity. And Th17 cell proportion was significantly elevated in NMOSD according to our previous study. This study aimed to explore the expression levels of lncRNA XIST-KDM6A-TSAd pathway in lymphocytes of female NMOSD patients, and investigate its possible relationship with pathogenesis of NMOSD. The study enrolled 30 acute-phase untreated female NMOSD patients and 30 age-matched female healthy controls, their lymphocytes were collected for experiments. Microarray as well as validation experiments showed lncRNA XIST was significantly downregulated in the NMOSD group. And the levels of lysine demethylase 6A (KDM6A) decreased in NMOSD and showed significant positive correlation with XIST. The levels of T cell-specific adapter (TSAd) mRNA and protein levels were significantly lower in NMOSD. And Chromatin immunoprecipitation assay demonstrated that NMOSD had more H3K27me3 modification than control at TSAd promoter region. The present study introduced a potential pathway that following lncRNA XIST downregulation, which process may promote Th17 differentiation in NMOSD. These findings shed new light on the immune regulation mechanism about lncRNA XIST and related epigenetic features, which may contribute to develop female-specific treatment plans.

Prevalence and clinical correlates of psychotic symptoms in first-episode untreated female chinese patients with major depressive disorder

BackgroundRecent studies have reported that psychotic symptoms are common in patients with major depressive disorder (MDD). However, few studies have reported the relationship between thyroid function, lipid metabolism and clinical profiles in female MDD patients. Thus, this study aimed to investigate the prevalence of psychotic depression (PD) and its risk factors in first-episode and drug naive (FEDN) depression among the female population in China.MethodsThis was a cross-sectional study involving a representative probability sample of 1,130 FEDN female outpatients with MDD (aged 18 years or older) in China. We collected information relating to socio-demographic characteristics, clinical data and blood samples. The Hamilton Depression Rating Scale 17-item version (HAMD-17), Hamilton Anxiety Rating Scale 14-item version (HAMA-14), and Positive and Negative Syndrome Scale (PANSS) were used to evaluate depressive, anxiety, and psychotic symptoms.ResultsThe prevalence of psychotic symptoms in female MDD patients was 10.97%. The findings revealed significant differences between MDD female patients with psychotic symptoms and non-PD female patients in the following areas: higher HAMD scores, higher HAMA scores, more severe anxiety and an increased risk of suicide attempts. Further logistic regression analysis showed that psychotic symptoms were associated with higher thyroid-stimulating hormone (TSH) levels and an odds ratio of 1.168.ConclusionsOur findings supported the hypothesis that higher TSH levels were correlated with psychotic symptoms in female MDD patients. Therefore, serum TSH levels may be a potential biomarker of PD in female MDD patients. In addition, we found that PD was closely associated with suicide attempts and lipid levels, but did not reach statistical significance.

Oral Microbiota Signatures in the Pathogenesis of Euthyroid Hashimoto's Thyroiditis.

One of the most prevalent autoimmune illnesses in the world is Hashimoto's thyroiditis, whose pathogenesis is still unknown. The gut-thyroid axis is frequently examined, and although oral health affects thyroid functions, there are limited data on how oral microbiota is linked to Hashimoto's thyroiditis. The study aims to identify the oral microbiota from saliva samples taken from treated (with levothyroxine) and untreated female euthyroid Hashimoto's thyroiditis patients as well as healthy controls who were age- and sex-matched to compare the oral microbiota across the groups and to contribute preliminary data to the literature. This study was designed as a single-center cross-sectional observational study. Sixty (60) female patients with euthyroid Hashimoto's thyroiditis (HT) and eighteen (18) age- and gender-matched healthy controls were included in this study. Unstimulated saliva samples were collected. After DNA isolation, sequencing was performed by targeting the V3-V4 gene regions of the 16S rRNA on the MiSeq instrument. R scripts and SPSS were used for bioinformatic and statistical analysis. No significant differences were found in the diversity indices. However, Patescibacteria phylum showed a significantly higher abundance (3.59 vs. 1.12; p = 0.022) in the oral microbiota of HT patients compared to HC. In the oral microbiota, the euthyroid HT group had approximately 7, 9, and 10-fold higher levels of the Gemella, Enterococcus, and Bacillus genera levels than healthy controls, respectively. In conclusion, the results of our study demonstrated that Hashimoto's thyroiditis causes changes in the oral microbiota, whereas the medicine used to treat the condition had no such effects. Therefore, revealing the core oral microbiota and long-term follow-up of the HT process by conducting extensive and multicenter studies might provide some important data for understanding the pathogenesis of the disease.

Hypermethylation of the serotonin transporter gene and paternal parenting styles in untreated anorexia nervosa patients: A pilot study

PurposeIt has been reported that serotonergic systems and parenting styles are involved in the pathogenesis of anorexia nervosa (AN). The present study made attempts to examine the DNA methylation profiles in the promoter region of serotonin transporter (5-HTT) encoding gene SLC6A4, and explore the association between the methylation level and severity of symptoms, 5-HTT linked polymorphic region (5-HTTLPR) genotypes and parenting styles in untreated Chinese Han AN patients. MethodsNinety-one untreated female AN patients (ANs) and eighty-seven matched healthy controls (HCs) were analyzed for DNA methylation status at CpG islands in the promoter region of SLC6A4 using MassARRY EpiTYPER, and genotypes of 5-HTTLPR using PCR-RFLP. The severity of eating disorder (ED) symptoms was evaluated by body mass index (BMI) and Questionnaire Version of the Eating Disorders Examination (EDE-Q 6.0), and part of participants were assessed parenting styles using the short Chinese Egna Minnen av Barndoms Uppfostra (s-EMBU-C). ResultsANs had greater methylation levels at CpG26.27.28, CpG 31.32, and CpG 37 than HCs (P = 0.039, 0.042, 0.018 respectively). A positive association of methylation level at CpG26.27.28 with ED symptoms detected by EDEQ-6.0 was discovered in AN group (r = 0.216, P = 0.047). Methylation level at CpG26.27.28 was showed to be or tend to be positively correlated with the parenting styles of paternal rejection (r = 0.425, P = 0.038) and paternal overprotection (r = 0.362, P = 0.062) in ANs. No significant differences were found in SLC6A4 promoter region methylation levels among 5-HTTLPR genotypes in our samples (P > 0.05) and no interaction effect between 5-HTTLPR genotypes and parenting styles on SLC6A4 promoter region methylation was observed (P > 0.05). ConclusionsThis study suggested that hypermethylation of SLC6A4 promoter region may be implicated in the pathological mechanisms of untreated Chinese Han female ANs, which is possibly associated with poor parenting styles. This finding may provide a direction for the epigenetic and family treatments for ANs and further investigation with larger samples is warranted.

MO028: Kidney biopsy in females with Fabry disease is an important tool to establish the indication for Fabry-specific therapy

Abstract BACKGROUND AND AIMS Fabry disease (FD) is a rare lysosomal storage disease causing progressive kidney, nervous system and heart disorders. Specific therapy may stop or mitigate disease progression, but is very expensive and results depend significantly on early initiation of treatment. Thus, clear criteria for treatment options are necessary. Kidney biopsy in FD has important diagnostic, prognostic and therapeutically implications. Some countries already decided to include as a criterion for reimbursement of FD-specific therapy in presence of renal biopsy evidence related to FD. National criteria for starting FD specific therapy according to renal involvement include eGFR &amp;lt;80 mL/min/1.73 m2 and/or proteinuria &amp;gt;300 mg/day. METHOD The aim of our retrospective study is to evaluate clinical and histological aspects of renal involvement in untreated female patients diagnosed with FD by genetic test between 2015 and 2021 in our center. Biological renal manifestations using serum creatinine, albumin creatinine ratio and proteinuria. Also, presence of neurological involvement was assessed by clinical exam, electroneurographic exam and brain magnetic resonance, and heart manifestations were assessed by echocardiography, electrocardiogram (ECG), ECG Holter and cardiac magnetic resonance. Kidney biopsy specimens were analyzed by light and electron microscopy. Specific renal FD lesions, as well as general lesions of progression, were evaluated according to the International Study Group of Fabry Nephropathy Score Sheet. RESULTS From a total of 25 female patients, we enrolled 11 female patients in which kidney biopsy was performed. The mean age at diagnosis was 47.7 ± 12 years (range 30–65 years), although mean age of symptoms onset was 36.1 years. The mean eGFR was 72.7 ± 19.8 mL/min/1.72 m2 while mean proteinuria was 0.72 ± 1.3 mg/day. Average Mainz score was 16.6 ± 11.5. Heart involvement was found in five patients (45.5%), and neurological manifestations were present in five patients. Co-morbidities were as follows: arterial hypertension in six patients, diabetes mellitus in one patient and obesity in two patients. All kidney biopsies showed lysosomal accumulation in the podocytes, in the parietal cells of the Bowman capsule and in the tubules, while vascular inclusions were found in nine cases. Also, we observed segmental glomerular sclerosis in four cases and global glomerular sclerosis in three cases, interstitial fibrosis in six cases, tubular atrophy in five cases, arteriosclerosis in four cases and arteriolar hyalinosis in five cases. Considering national criteria for initiation of FD therapy, five patients (54.6%) fulfilled the renal criteria, three patients (27.3%) presented criteria for other organs involvement, while three patients (mean age 37.7 years) did not fulfill any criteria. We emphasize that, even in our six patients without renal criteria for FD therapy, kidney biopsy showed FD-specific lesions (lysosomal accumulation) in all cases, associated with segmental glomerular sclerosis in one case, interstitial fibrosis in four cases, tubular atrophy in three cases, arteriosclerosis in one case and arteriolar hyalinosis in three cases. Thus, in our three patients without clinical, biological and imaging criteria for FD therapy, evidence of specific FD lesions in kidney biopsy supported our recommendation to initiate FD treatment. CONCLUSION The data from our small cohort of females with Fabry disease underline the importance of kidney biopsy for detection of early kidney involvement and provide additional support to the consideration of early initiation of FD-specific therapy, potentially improving long-term outcome. Thus, proof of specific FD renal lesions as revealed by kidney biopsy could become a distinct criterion for initiation of FD therapy, in the absence of other criteria according to current guidelines. Future studies are necessary in order to specify the role of renal histology in the establishment of the proper timing to start the FD treatment, especially in young patients.

Increased resting-state cerebellar-cortical connectivity in breast cancer survivors with cognitive complaints after chemotherapy

Cognitive complaints after chemotherapy are common in breast cancer patients, but the neural bases for these complaints remain unclear. This pilot study explored resting-state functional connectivity (FC) as a marker of subtle cognitive changes in breast cancer patients who experience cognitive complaints. Chemotherapy-treated (n = 20, at least 6 months off therapy) and untreated (n = 17, disease-control) female breast cancer patients with cognitive complaints and healthy controls (n = 20) were recruited. The FC of the right dorsolateral prefrontal cortex was calculated, and any correlations between this FC and neuropsychological assessments were determined. Chemotherapy-treated patients with cognitive complaints displayed increased FC between the right dorsolateral prefrontal cortex and both the contralateral cerebellar lobule VII and the cerebellar vermis XI, compared to the disease-control and healthy-control groups, despite unimpaired neuropsychological performance. The increased FC was negatively correlated with executive function and attention in breast cancer survivors with cognitive complaints. Our pilot study findings provide evidence that cerebellar-cortical FC changes may be a pathophysiological basis for chemotherapy-related cognitive complaints. In addition, the FC changes have the potential to reflect minor or compensated cognitive function impairment in breast cancer patients.

Spontaneous clearance of Chlamydia trachomatis accounting for bacterial viability in vaginally or rectally infected women (FemCure)

ObjectivesSpontaneous clearance of Chlamydia trachomatis (CT) infections can occur between diagnosis and treatment. We followed CT patients to assess clearance using a conventional definition (no total CT-DNA, assessed by routine...

MRI activity in MS and completed pregnancy: Data from a tertiary academic center.

ObjectiveTo evaluate postpartum MRI activity in patients with MS and a completed pregnancy and to compare these results to an age-matched untreated nonpregnant MS cohort.MethodsPatient with MS from a tertiary care MS center between 2006 and 2015, with prepartum and postpartum neurologic follow-ups and MRI scans were analyzed. Clinical activity and inflammatory brain MRI activity (new T2-hyperintense or gadolinium-enhancing [Gd+] lesions) were assessed peripartum. The results were compared with untreated reproductive-age patients with MS from the placebo arm of the clinical trials.ResultsA total of 123 pregnancies in 123 women (median Expanded Disability Status Scale 1.0) were analyzed. Approximately 7.2% relapsed during pregnancy and 48.7% relapsed postpartum. Of pregnancies with prepartum and postpartum gadolinium (Gd)-enhanced MRI (n = 112), 8% had Gd+ lesions prepartum and 33% had new Gd+ lesions postpartum. Overall, 54.4% had either new T2 or Gd+ lesions postpartum. Seventy-nine percent of subjects with postpartum relapse had new MRI activity compared with 37.1% without relapse (p < 0.001). Twenty-five percent had both clinical and radiographic activity and only 24.9% maintained no evidence of disease activity status postpartum. There was no association between postpartum MRI activity and disease-modifying treatments (DMTs) (p > 0.5). MRI and clinical outcomes were also assessed for 126 nonpregnant untreated female patients with MS. Comparing pregnancy and no pregnancy groups, there was no difference in MRI activity at follow-up.ConclusionsThere was a high level of inflammatory radiographic disease activity which was related to relapses in postpartum patients with MS. Further studies are needed to determine whether hormonal fluctuations vs extended time off DMTs may be the underlying cause of our observations.

Assessment of Maximum Voluntary Ventilation (MVV) in Female Hypothyroids and Its Relationships with Serum TSH and FT4 Levels

Background: Hypothyroidism is a common hormonal disorder affecting various organs including lungs and pulmonary dysfunction in hypothyroid patients has been noted.&#x0D; Objective: To observe maximum voluntary ventilation (MVV) in hypothyroid female patients.&#x0D; Materials and method: This cross-sectional study was carried out in the Department of Physiology, BSMMU, Dhaka, Bangladesh, from 1st July 2008 to 30th June 2009 on 60 hypothyroid female patients of 30-50 years old. Based on treatment, hypothyroid patients were divided into B1 (untreated patients on their 1st day of diagnosis) and B2 (patients treated for at least 12-18 months). For comparison, 30 age and BMI matched apparently healthy subjects (Group A) were also studied. The study group was selected from the Out Patient Department of Endocrinology, BSMMU, Dhaka, Bangladesh, and the control group was selected by personal contact. Serum TSH and serum FT4 levels were measured by Microparticle Enzyme Immunoassay (MEIA) principle in AxSYM system. Maximum voluntary ventilation (MVV), which is a lung function parameter, was measured by a digital MicroDL spirometer. Data were analyzed by one way ANOVA test, independent sample t-test and Pearson’s correlation coefficient test.&#x0D; Results: The mean percentage of predicted values of lung function parameter of MVV in control subjects and treated hypothyroids were within normal ranges. However, this value was significantly lower in untreated hypothyroid subjects in comparison to those of control and treated hypothyroid subjects. In addition, MVV showed negative correlation with serum TSH level and positive correlation with serum FT4 level and these relationships were statistically significant in control group and treated hypothyroid subjects.&#x0D; Conclusion: This study reveals that MVV may be lower in untreated hypothyroid female patients compared to control and treated hypothyroids and the deterioration may be positively correlated with serum FT4 level and negatively correlated with serum TSH level. Treatment of hypothyroids may reverse these changes.&#x0D; Delta Med Col J. Jul 2020;8(2): 55-60

SAINT: Results of an expanded phase II study using safe amounts of ipilimumab (I), nivolumab (N), and trabectedin (T) as first-line treatment of advanced soft tissue sarcoma [NCT03138161

11520 Background: Sarcoma cells are most immunogenic earlier in the disease. Hypothesis: Immune checkpoint inhibitors would be most effective when given as first-line therapy. Methods: Eligible patients include previously untreated male or female patients, ≥ 18 years of age with locally advanced unresectable or metastatic soft tissue sarcoma (STS), with measurable disease by RECIST v1.1. Immune checkpoint inhibitors I (1 mg/kg i.v. q 12 weeks) and N (3 mg/kg i.v. q 2 weeks) were given with T (1.2 mg/m2 i.v. q 3 weeks), a tumoricidal agent that depletes growth-promoting macrophages in the tumor microenvironment. Primary endpoint: Objective response rate by RECIST v1.1; Secondary endpoints: (1) Progression-free survival (PFS) at 6 months, (2) Overall survival (OS) at 6, 9, 12, 24, and 48 months, and (3) Incidence of adverse events. Results: Efficacy analysis: There were forty-one evaluable subjects. Best overall response rate was 19.5%; disease control rate 87.8%. The median OS was &gt;12.5 months; median PFS was &gt;6.0 months (6-month OS rate: 75%; 6-month PFS rate: 50%). Safety analysis: Grade 3 TRAEs include fatigue (n = 5), increased TSH (n = 3), decreased TSH (n = 1), adrenal insufficiency (n = 1), hyperglycemia (n = 1), dehydration (n = 1), hyponatremia (n = 2), bipedal edema (n = 2), increased AST (n = 8), increased ALT (n = 19), increased ALP (n = 2), increased CPK (n = 3), port site infection (n = 2), psoriasis exacerbation (n = 1), anemia (n = 6), thrombocytopenia (n = 2), and neutropenia (n = 2). Grade 4 TRAES include neutropenia (n = 1), thrombocytopenia (n = 2), and increased CPK (n = 2). Conclusions: These data suggest that combinatorial therapy with Ipilimumab, Nivolumab and Trabectedin (1) may have synergistic activity in achieving disease control, and (2) is safe with manageable toxicity for patients with previously untreated STS. Clinical trial information: NCT03138161 . [Table: see text]

Circulating miRNAs in Untreated Breast Cancer: An Exploratory Multimodality Morpho-Functional Study.

The aim of this study was to identify new disease-related circulating miRNAs with high diagnostic accuracy for breast cancer (BC) and to correlate their deregulation with the morpho-functional characteristics of the tumour, as assessed in vivo by positron emission tomography/magnetic resonance (PET/MR) imaging. A total of 77 untreated female BC patients underwent same-day PET/MR and blood collection, and 78 healthy donors were recruited as negative controls. The expression profile of 84 human miRNAs was screened by using miRNA PCR arrays and validated by real-time PCR. The validated miRNAs were correlated with the quantitative imaging parameters extracted from the primary BC samples. Circulating miR-125b-5p and miR-143-3p were upregulated in BC plasma and able to discriminate BC patients from healthy subjects (miR-125-5p area under the receiver operating characteristic ROC curve (AUC) = 0.85 and miR-143-3p AUC = 0.80). Circulating CA15-3, a soluble form of the transmembrane glycoprotein Mucin 1 (MUC-1) that is upregulated in epithelial cancer cells of different origins, was combined with miR-125b-5p and improved the diagnostic accuracy from 70% (CA15-3 alone) to 89% (CA15-3 plus miR-125b-5p). MiR-143-3p showed a strong and significant correlation with the stage of the disease, apparent diffusion coefficient (ADCmean), reverse efflux volume transfer constant (Kepmean) and maximum standardized uptake value (SUVmax), and it might represent a biomarker of tumour aggressiveness. Similarly, miR-125b-5p was correlated with stage and grade 2 but inversely correlated with the forward volume transfer constant (Ktransmean) and proliferation index (Ki67), suggesting a potential role as a biomarker of a relatively more favourable prognosis. In situ hybridization (ISH) experiments revealed that miR-143-3p was expressed in endothelial tumour cells, miR-125-5p in cancer-associated fibroblasts, and neither in epithelial tumour cells. Our results suggested that miR-125-5p and miR-143-3p are potential biomarkers for the risk stratification of BC, and Kaplan-Maier plots confirmed this hypothesis. In addition, the combined use of miR-125-b-5p and CA15-3 enhanced the diagnostic accuracy up to 89%. This is the first study that correlates circulating miRNAs with in vivo quantified tumour biology through PET/MR biomarkers. This integration elucidates the link between the plasmatic increase in these two potential circulating biomarkers and the biology of untreated BC. In conclusion, while miR-143-3b and miR-125b-5p provide valuable information for prognosis, a combination of miR-125b-5p with the tumour marker CA15-3 improves sensitivity for BC detection, which warrants consideration by further validation studies.

Transcription profiling of peripheral B cells in antibody-positive primary Sjögren's syndrome reveals upregulated expression of CX3CR1 and a type I and type II interferon signature.

B cells play a key role in the pathogenesis of primary Sjögren's syndrome (pSS). The aim of this study was to analyse the transcriptome of CD19+ B cells from patients with pSS and healthy controls to decipher the B cell-specific contribution to pSS. RNA from purified CD19+ B cells from 12 anti-SSA antibody-positive untreated female patients with pSS and 20 healthy blood donors was subjected to whole transcriptome sequencing. A false discovery rate corrected significance threshold of α<0.05 was applied to define differential gene expression. As validation, gene expression in B cells from 17 patients with pSS and 16 healthy controls was analysed using a targeted gene panel. RNA-sequencing identified 4047 differentially expressed autosomal genes in pSS B cells. Upregulated expression of type I and type II interferon (IFN)-induced genes was observed, establishing an IFN signature in pSS B cells. Among the top upregulated and validated genes were CX3CR1, encoding the fractalkine receptor involved in regulation of B-cell malignancies, CCL5/RANTES and CCR1. Increased expression of several members of the TNF superfamily was also identified; TNFSF4/Ox40L, TNFSF10/TRAIL, TNFSF13B/BAFF, TNFRSF17/BCMA as well as S100A8 and -A9/calprotectin, TLR7, STAT1 and STAT2. Among genes with downregulated expression in pSS B cells were SOCS1 and SOCS3, CD70 and TNFAIP3/A20. We conclude that B cells from patients with anti-SSA antibody-positive pSS display immune activation with upregulated expression of chemokines, chemokine receptors and a prominent type I and type II IFN signature, while suppressors of cytokine signalling are downregulated. This adds insight into the autoimmune process and suggests potential targets for future functional studies.

Increased Serum Leptin Levels in New-Onset, Untreated Female Patients with Coronary Artery Disease and Positively Associated with Inflammatory Markers

Background/Aims: Previous studies have suggested that leptin was associated with atherosclerosis and involved in inflammation. Gender differences between leptin and inflammatory markers have been evaluated less in untreated patients with stable coronary artery disease (CAD). Methods: In this study, a total of 394 consecutive Chinese patients who received coronary artery angiography were enrolled, including 243 patients with CAD and 151 non-CAD controls. The baseline clinical characteristics were collected and serum leptin levels were determined using ELISA. Results: The relation of serum leptin levels to inflammatory markers was found only in female patients. Leptin and white blood cell count (WBCC) as well as its subsets were significantly higher in female patients than female controls. In female patients, leptin was positively associated with C-reactive protein (CRP; r = 0.28, p = 0.016), WBCC (r = 0.261, p = 0.02), neutrophil, r = 0.268, p = 0.018, and monocyte, r = 0.228, p = 0.044. Multivariable regression analysis revealed that leptin was significantly and independently associated with CRP (β = 0.317, p = 0.004), WBCC (β = 0.278, p = 0.020), neutrophil (β = 0.262, p = 0.032), and monocyte (β = 0.245, p = 0.032). Conclusions: The serum leptin levels were higher in female patients and independently associated with CRP, WBCC, and its subsets, suggesting a potential interaction between leptin and inflammation in female CAD patients.

Association of Dyslipidemia, Increased Insulin Resistance, and Serum CA 15-3 with Increased Risk of Breast Cancer in Urban Areas of North and Central India.

Objective:This study aims to determine the association of dyslipidemia and increased insulin resistance (IR) with increased breast cancer (BC) risk.Materials and Methods:The study group comprised 110 premenopausal and 143 postmenopausal, untreated female BC patients in the age range of 29–72 years. Control group consisted of 117 premenopausal and 141 postmenopausal healthy females in the age range of 23–75. Approximately 8-ml blood samples were drawn to measure various biochemical parameters. Serum glucose, total cholesterol, triglyceride (TG), and high-density lipoprotein-cholesterol were measured. Very low-density lipoprotein-cholesterol (VLDL-C) and LDL-C were calculated using Friedewald's formula. Serum insulin and serum CA 15-3 were estimated by immune enzymatic assay. IR was assessed using homeostasis model assessment IR index (HOMA-IR).Results:Clinical variables in the case and control groups were compared using the unpaired Student's t-test. The crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by binary logistic regression analysis. Pearson's correlation analysis was used to determine the association between CA 15-3 and variables of interest. Total cholesterol, TG, LDL, VLDL, serum glucose, serum insulin, HOMA-IR, and serum CA 15-3 were significantly higher (P < 0.001) in BC patients compared to those in controls. Significant adjusted ORs with 95% CI were found to be fasting glucose, total cholesterol, and TGs. We also found a significant positive correlation between total cholesterol, TG, LDL, serum glucose, serum insulin, HOMA-IR, and serum CA 15-3.Conclusion:This study confirms the association between dyslipidemia, IR, and increased BC risk.

CircHLA-C Plays an Important Role in Lupus Nephritis by Sponging miR-150.

Circular RNAs (circRNAs) participate in the pathogenesis of various diseases by sponging microRNAs (miRs). However, the roles of circRNAs remain unreported in glomerular diseases. We previously reported that miR-150 positively correlated with renal chronicity index in patients with lupus nephritis (LN). We aimed to investigate renal circRNA profiling and the interaction between circRNAs and miR-150 in LN patients. Six renal biopsies from untreated female patients with LN class IV and five normal kidney tissues from urology patients were used for circRNA sequencing. 171 circRNAs with 2-fold differential expression were identified in LN compared with normal control. Ten selected circRNAs were validated by real-time qPCR, and seven circRNAs showed the same significant increases as the sequencing results. circHLA-C positively correlated with proteinuria (R = 0.92, p < 0.01), serum creatinine (R = 0.76, p = 0.08), renal activity index (R = 0.88, p < 0.05), and crescentic glomeruli (R = 0.93, p < 0.01). Renal circHLA-C increased 2.72-fold, and miR-150 decreased 66% in LN compared with normal control (p < 0.05). Bio-informatic analysis predicted miR-150 was regulated by circHLA-C and displayed one perfect match seed between circHLA-C and miR-150. The renal miR-150 showed a tendency of negative correlation with circHLA-C in LN patients. In conclusion, circHLA-C may play an important role in the pathogenesis of lupus nephritis by sponging miR-150.

Reduction of quality-adjusted life years (QALYs) in patients with premenstrual dysphoric disorder (PMDD)

Premenstrual dysphoric disorder (PMDD) refers to the depression that occurs during the premenstrual phase and remits soon after the onset of menses. It affects the quality of life (QOL) of patients with PMDD. Therefore, this preliminary survey from chart recordings aimed to understand the symptom appearance and QOL reduction patterns in patients with PMDD, and to examine the extent of the loss of their quality-adjusted life years (QALYs). Participants were 66 untreated female patients with PMDD. Data on symptom appearance and QOL reduction during the menstrual cycle, and the EuroQoL-5D (EQ-5D) scores during the premenstrual phase and immediately after the completion of a menstrual period were collected. The mean EQ-5D score of the 66 patients with PMDD was 0.795±0.120 (range 0.362-0.949), indicating that their expected mean loss of QALYs was about 0.14years. If untreated, PMDD is expected to cause a mean loss of QALYs of about 0.14years. However, on accounting for the period from disease development to menopause, and subtracting the menstruation-free periods such as pregnancy and breastfeeding, patients with untreated PMDD are expected to experience a QALY loss of about 3years during their lifetime.

Evaluate the effects of long-term valproic acid treatment on metabolic profiles in newly diagnosed or untreated female epileptic patients: A prospective study

PurposeExcessive weight gain associated with sodium valproate (VPA) may predispose patients with epilepsy to other health problems such as insulin resistance. We prospectively evaluated the long-term impact of VPA monotherapy compared with lamotrigine (LTG) monotherapy on anthropometric and metabolic parameters in women with epilepsy. Our primary objective is to understand the underlying mechanism responsible for VPA-induced obesity. MethodsSixty-six female patients with newly diagnosed or untreated epilepsy were included in the study. Thirty-four patients with VPA and thirty-two patients with LTG were treated for a period of one year in our center. Anthropometric and clinical data were collected at 5 time points: before, at 6th week, 3rd month, 6th month, 9th month and 12th month (last visit). Biochemical and hormonal data were collected 2 time points: before and last visit. ResultsSubjects in the VPA group had significantly higher body weight than LTG-treated subjects (64.88±3.25 vs. 58.28±2.43, P<0.001). HOMA-IR level was significantly increased (2.76 vs. 1.35, P<0.05), and adiponectin levels were significantly lower in the VPA group (3.46 vs. 6.22, P<0.05). Triglycerides levels were significantly increased (118 vs. 96, P<0.05), and HDL-C levels were significantly lower in the VPA group. Both the VPA-treated group and the LTG-treated group showed no significant difference in term of total cholesterol, LDL-C, fasting blood glucose and serum leptin levels. ConclusionsBased on the findings of this study, we proposed that VPA induced hypoadiponectinemia which correlates significantly with insulin resistance. These two factors may be responsible for weight gain, possible by stimulating appetite. Valproic acid appears to be use cautionally in obese females with epilepsy.