The clinical significance of medial arterial calcification in end-stage renal disease in women.

Medial arterial calcification is common in advanced kidney disease but its impact on cardiovascular disease is uncertain because imaging techniques used to date cannot reliably distinguish it from atherosclerotic calcification. We have previously shown that breast arterial calcification (BAC) is exclusively medial and is a marker of generalized medial calcification in end-stage renal disease (ESRD). Therefore, the presence of BAC on mammograms in 202 women with ESRD (mean duration 4.1 years) was correlated with cardiovascular events to determine the clinical significance of medial arterial calcification. BAC was found in 58% of the study participants and was significantly associated with age, diabetes, and ESRD duration. Both coronary artery (27 vs. 15%) and peripheral arterial disease (PAD; 19 vs. 4%) were more likely in patients with BAC but only the latter persisted after accounting for other factors (odds ratio 4.6; 95% confidence interval 1.2-15). In 142 women without clinical events before mammography, BAC was associated with a greater incidence of new PAD events (13 vs. 3%) but not coronary artery disease events (11 vs. 11%). Thus, BAC is strongly and independently associated with PAD in women with ESRD and may be predictive of clinical events. This suggests that medial arterial calcification is a clinically significant lesion that may contribute to the accelerated PAD in ESRD.

Electrospun cellulose nanofibers immobilized with anthocyanin extract for colorimetric determination of bacteria.

A novel smart biochromic textile sensor was developed by immobilizing anthocyanin extract into electrospun cellulose acetate nanofibers to detect bacteria for numerous potential uses, such as healthcare monitoring. Red-cabbage was employed to extract anthocyanin, which was then applied to cellulose acetate nanofibers treated with potassium aluminum sulfate as a mordant. Thus, nanoparticles (NPs) of mordant/anthocyanin (65-115 nm) were generated in situ on the surface of cellulose acetate nanofibrous film. The pH of a growing bacterial culture medium is known to change when bacteria multiply. The absorbance spectra revealed a bluish shift from 595 nm (purple) to 448 nm (green) during the growth of Gram-negative bacteria (E. coli) owing to the discharge of total volatile basic amines as secretion metabolites. On the other hand, the absorption spectra of a growing bacterial culture containing Gram-positive bacteria (L. acidophilus) showed a blue shift from 595 nm (purplish) to 478 nm (pink) as a result of releasing lactic acid as a secretion metabolite. Both absorbance spectra and CIE Lab parameters were used to determine the color shifts. Various analytical techniques were utilized to study the morphology of the anthocyanin-encapsulated electrospun cellulose nanofibers. The cytotoxic effects of the colored cellulose acetate nanofibers were tested.

The development of candidate composite disease activity and responder indices for psoriatic arthritis (GRACE project).

OBJECTIVE: To develop new composite disease activity indices for psoriatic arthritis (PsA). METHODS: Data from routine clinic visits at multiple centres were collected in a systematic manner. Data included all domains identified as important in randomised controlled trials in PsA. Decisions to change treatment were used as surrogates for high disease activity. New indices were developed by multiple linear regression (psoriatic arthritis disease activity score: PASDAS) and empirically, utilising physician-defined cut-offs for disease activity (arithmetic mean of desirability functions: AMDF). These were compared with existing composite measures: Composite Psoriatic arthritis Disease Activity Index (CPDAI), Disease Activity for PSoriatic Arthritis (DAPSA), and Disease Activity Score for rheumatoid arthritis (DAS28). RESULTS: 161/503 (32%) subjects had treatment changes. Although all measures performed well, compared with existing indices, PASDAS was better able to discriminate between high and low disease activity (area under receiver operating curves (ROC)) curve with 95% CI: PASDAS 0.773 (0.723, 0.822); AMDF 0.730 (0.680, 0.780); CPDAI 0.719 (0.668, 0.770); DAPSA 0.710 (0.654, 0.766); DAS28 0.736 (0.680, 0.792). All measures were able to discriminate between disease activity states in patients with oligoarthritis, although area under the receiver operating curves (AUC) were generally smaller. In patients with severe skin disease (psoriasis area and severity index>10) both nonparametric and AUC curve statistics were nonsignificant for all measures. CONCLUSIONS: Two new composite measures to assess disease activity in PsA have been developed. Further testing in other datasets, including comparison with existing measures, is required to validate these instruments.

Identification and validation of a novel long non-coding RNA (LINC01465) in ovarian cancer.

Epithelial Ovarian Cancer (EOC) is a heterogeneous disease usually diagnosed at advanced stages. Therefore, early detection is crucial for better survival. Despite the advances in ovarian research, mechanisms underlying EOC carcinogenesis are not elucidated. We performed chromatin immunoprecipitation sequencing to identify genes regulated by E2F5, a transcription factor involved in ovarian carcinogenesis. Results revealed several putative candidate genes (115 protein-coding genes, 20 lncRNAs, 6 pseudogenes, and 4 miRNAs). A literature review and bioinformatics analysis of these genes revealed a novel lncRNA candidate (LINC01465) in EOC. We validated LINC01465 by quantifying its expression in EOC cell lines and selected OVSAHO and SKOV3 as a model with high LINC01465 levels. We silenced LINC01465 and performed proliferation, wound healing, invasion, and drug resistance assays. Knocking-down LINC01465 resulted in reduced migration, suggesting potential involvement in EOC. Furthermore, to identify the significance of LINC01465 in chemoresistance, we assessed the LINC01465 levels in A2780 S cells treated with malformin, which revealed higher LINC01465 expression as compared to untreated A2780S cells implying the involvement of LINC01465 in cell death. Thus, this study unraveled the repertoire of E2F5 regulated candidate genes and suggested a putative role of LINC01465 in malformin-induced cell death in EOC.

Assessing the Efficacy of a 28-Day Comprehensive Online Prostate Cancer Patient Empowerment Program (PC-PEP) in Facilitating Engagement of Prostate Cancer Patients in Their Survivorship Care: A Qualitative Study.

A 28-day Prostate Cancer-Patient Empowerment Program (PC-PEP) developed through patient engagement was successful at promoting mental and physical health. Thirty prostate cancer patients from Halifax, Canada participated in the 28-day PC-PEP intervention in early 2019. PC-PEP encompassed daily patient education and empowerment videos, prescribed physical activities (including pelvic floor exercises), a mostly plant-based diet, stress reduction techniques, intimacy education, social connection, and support. Quantitative exit surveys and semi-structured interviews (conducted in focus groups of ten) were used to assess perceived factors that facilitated or impeded adherence to the program. The program received high praise from the patients and was deemed extremely useful by the participating men, who rated it 9 out of 10. Patients expressed that the multifaceted, online, home-based nature of the program helped them adhere to it better than they would have had to a single or less comprehensive intervention. Feedback from the participants indicated that the program, when viewed as a whole, was perceived as greater than the sum of its individual parts. Furthermore, the program addressed various issues, including emotional vulnerability and distress, physical fitness, urinary incontinence, challenges in expressing emotions, perceived lack of control over healthcare decisions, emotional fragility, and hesitancy to discuss prostate cancer-related matters in social settings. Patients highly (9.6/10) endorsed integrating the program into the standard care regimen from the very beginning of diagnosis. However, challenges such as work commitments were noted. Patients' high endorsement of PC-PEP suggests that its implementation into the standard of care from day one of diagnosis may be warranted.

Comprehensive description of the prevalence, serological and clinical characteristics, and visceral involvement of systemic sclerosis (scleroderma) in a large cohort from the United Arab Emirates Systemic Sclerosis Registry.

Systemic sclerosis is an autoimmune condition characterized by a wide range of clinical presentations. Registries may serve to expand understanding about systemic sclerosis and aid in patient care and follow-up. The objective of this study was to analyze the prevalence of systemic sclerosis in a large cohort from the United Arab Emirates Systemic Sclerosis Registry and find the significant similarities and differences between the different subsets. All scleroderma patients in the United Arab Emirates were included in this multicenter national retrospective analysis. Data on demographics, comorbidities, serological characteristics, clinical aspects, and treatment were collected and analyzed, highlighting the most common traits identified. A total of 167 systemic scleroderma patients from diverse ethnic backgrounds were enrolled. Overall, 54.5% (91/167) of the patients were diagnosed with diffuse cutaneous systemic sclerosis, and 45.5% (76/167) with limited cutaneous systemic sclerosis. The prevalence of systemic sclerosis was 1.66 per 100,000 for the total registry and 7.78 per 100,000 for United Arab Emirates patients. Almost all patients in the diffuse cutaneous systemic sclerosis and limited cutaneous systemic sclerosis groups tested positive for the immunofluorescence antinuclear antibody. Antibodies against Scl-70 were significantly more associated with diffuse cutaneous systemic sclerosis, whereas anticentromere antibodies were significantly more associated with the limited cutaneous systemic sclerosis group (p < 0.001). Sclerodactyly, shortness of breath, and digital ulcers were more common in diffuse cutaneous systemic sclerosis patients compared with the limited cutaneous systemic sclerosis subtype in terms of clinical symptoms and organ involvement. Telangiectasia was much more common in the limited cutaneous systemic sclerosis group. Furthermore, diffuse cutaneous systemic sclerosis patients had more lung fibrosis (interstitial lung disease) than limited cutaneous systemic sclerosis patients (70.5% vs 45.7%), and pulmonary arterial hypertension was twice as common in limited cutaneous systemic sclerosis patients as it was in diffuse cutaneous systemic sclerosis patients. Local registries are paramount to understanding the clinical/serological characteristics of scleroderma. This study emphasizes the importance of raising disease awareness and distinguishing between the various systemic sclerosis subsets to implement patient-tailored strategies for early detection, better management, and higher quality of care.

Screening and Identification of Human Endogenous Retrovirus-K mRNAs for Breast Cancer Through Integrative Analysis of Multiple Datasets.

Objective: Human endogenous retroviruses (HERVs) make up 8% of the human genome. HERVs are biologically active elements related to multiple diseases. HERV-K, a subfamily of HERVs, has been associated with certain types of cancer and suggested as an immunologic target in some tumors. The expression levels of HERV-K in breast cancer (BCa) have been studied as biomarkers and immunologic therapeutic targets. However, HERV-K has multiple copies in the human genome, and few studies determined the transcriptional profile of HERV-K copies across the human genome for BCa. Methods: Ninety-one HERV-K indexes with entire proviral sequences were used as the reference database. Nine raw sequencing datasets with 243 BCa and 137 control samples were mapped to this database by Salmon software. The differential proviral expression across several groups was analyzed by DESeq2 software. Results: First, the clustering of each dataset demonstrated that these 91 HERV-K proviruses could well cluster the BCa and control samples when the normal controls were normal cells or healthy donor tissues. Second, several common HERV-K proviruses that are closely related with BCa risk were significantly differentially expressed (p adj < 0.05 and absolute log2FC > 1.5) in the tissues and cell lines. Additionally, almost all the HERV-K proviruses had higher expression in BCa tissue than in healthy donor tissue. Notably, we first found the expression of 17p13.1 provirus that located with TP53 should regulate TP53 expression in ER+ and HER2+ BCa. Conclusion: The expression profiling of these 91 HERV-K proviruses can be used as biomarkers to distinguish individuals with BCa and healthy controls. Some proviruses, especially 17p13.1, were strongly associated with BCa risk. The results suggest that HERV-K expression profiles may be appropriate biomarkers and targets for BCa.

Thyroid hormones profile among obese pregnant Sudanese women.

BACKGROUND: Previous studies evaluating thyroid function among obese pregnant women failed to demonstrate a consistent pattern of thyroid hormones profile, probably due to the variations in biological/environmental determinants of thyroid function in different countries. AIM: The aim of the study was to evaluate thyroid hormones profile in Sudanese pregnant women with varying degrees of obesity. PATIENTS AND METHODS: Obstetric/sociodemographic characteristics were gathered from 178 singleton pregnant Sudanese women using questionnaires. Weight and height were measured; body mass index (BMI) was calculated and categorized into four groups: Underweight (BMI <18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obese (≥30 kg/m2). Free triiodothyronine (FT3), free thyroxin (FT4), and thyroid-stimulating hormone (TSH) were measured. RESULTS: Of the 178 enrolled women, 9 (5.1%), 52 (29.2%), 73 (41.0%), and 44 (24.7%) were underweight, normal BMI, overweight, and obese, respectively. FT3 level was significantly higher in obese women compared with normal BMI (P=0.004) as well as overweight women (P=0.015). Higher FT3 levels were significantly associated with obesity (odds ratio [OR]=9.5, 95% confidence interval [CI] =3.1-29.0, P<0.001). Lower levels of FT4 were significantly associated with overweight (OR=0.06, 95% CI=0.007-0.58, P=0.015) and obesity (OR=0.048, 95% CI=0.004-0.5, P=0.018). Based on linear regression analysis, BMI was positively associated with FT3 (4.7 pmol/l, P<0.001) and negatively associated with FT4 (-8.26 pmol/l, P=0.001). CONCLUSIONS: BMI correlates with FT3 differently compared to FT4. Pregnant women with higher BMI are likely to have higher levels of FT3, but lower FT4. In contrast, TSH levels were comparable in different BMI groups. RELEVANCE FOR PATIENTS: Increased iodothyronine 5´deiodinase (5´D) activity associated with obesity may give an explanation for thyroid profile in those with higher BMI. High 5´ activity increases FT3 at the expense of FT4. Alternatively, high FT3 and low FT4 are expected to feedback differently on TSH, which explains the loss of positive correlation between BMI and TSH.

Helicobacter pylori and Chlamydia trachomatis in Sudanese women with preeclampsia.

Background: Helicobacter pylori and Chlamydia trachomatis infections are associated with many complications of pregnancy including preeclampsia. The association between H. pylori and C. trachomatis with preeclampsia needs to be further explored.Methods: A case-control study was conducted at Saad Abualila Hospital, Khartoum, Sudan during the period of February to August 2015 to investigate the association between H. pylori or C. trachomatis with preeclampsia. The cases were women with preeclampsia and healthy pregnant women were the controls. The obstetrics and clinical history were gathered using questionnaires. Weight and height were measured and were used to compute body mass index (BMI). H. pylori and C. trachomatis antibodies (IgG) were determined by their specific enzyme-linked immunosorbent assays (ELISAs), respectively.Results: There was no significant difference in the age, parity, gestational age, BMI, and hemoglobin between the two groups (93 women in each arm). In all, 31 and 62 cases were severe and mild preeclampsia, respectively. H. pylori seropositivity (IgG) was significantly higher in the preeclamptic women compared with their respective controls (80/93 [86.0%] versus 52/93 [55.9%], p < 0.001). In binary logistic regression, H. pylori seropositivity (adjusted odds ratio [AOR] = 4.933, 95% confidence interval [CI] = 2.082-11.692) was associated with preeclampsia. No C. trachomatis seropositive women were detected in the studied subjects.Conclusion: The current study confirmed that H. pylori, but not C. trachomatis, is associated with preeclampsia.

School performance and long-term outcomes of very preterm children conceived via in vitro fertilization.

OBJECTIVE: To assess the impact of in vitro fertilization (IVF) on school performance and long-term outcomes in very preterm children aged 8-16 years. METHODS: Seventy-nine children born after IVF were compared with 79 randomly selected matched controls born after spontaneous conception (SC). Information was obtained from parents via a questionnaire administered through telephone interviews looking into school performance, including preschool education, repeated grades, extra lessons, special education needs, and learning difficulties; long-term status, including incidence of attention deficit hyperactivity disorder and autism; and family profile. Gross motor function was assessed against the gross motor function classification system based on information given by the subjects' families. RESULTS: Mothers of IVF children were more likely to have a high educational level than mothers of SC children. Moreover, a greater proportion of IVF children had received preschool education than SC children. After adjusting for potential confounders, there was no difference in the school performance or long-term outcomes between IVF and SC children. CONCLUSION: In our study, the school performance and long-term outcomes of very preterm children born after IVF and of their spontaneously conceived peers were comparable. This information can help provide guidance to families and educators.

Oral Mucosal Stem Cells, Human Immature Dental Pulp Stem Cells and Hair Follicle Bulge Stem Cells as Adult Stem Cells Able to Correct Limbal Stem Cell Deficiency.

BACKGROUND: Adult stem cells are somatic stem cells distributed all over the body. They represent a promising future for regenerative medicine because of their multiple advantages as they are widely available, accessible, easily stored and manipulated to a wide range of cells and with minimal invasive extraction. OBJECTIVE: This review describes three examples of adult stem cells: oral mucosal epithelial stem cells, human immature dental pulp stem cells and hair follicle bulge stem cells that show an ability to correct limbal stem cell deficiency, their isolation and cultivation methods, feeder layers, carriers, markers expressed, successfulness to regenerate the ocular surface and mimic the corneal function in LSCD. CONCLUSION: Although hair follicle bulge stem cells and human immature dental pulp stem cells are a promising adult stem cell source to correct limbal stem cell deficiency, but the published research evaluating this ability is limited. Therefore, this article emphasize further research in this area.

Maternal Heart Rate Variability during the First Stage of Labor.

Labor necessitates continuous adjustments of cardiac autonomic reflexes by alternate activation of the sympathetic and parasympathetic nervous systems. The division of the autonomic nervous system (ANS) that predominates during the first stage of labor is unclear and needs to be further investigated. The study aimed to compare heart rate variability (HRV) in pregnant women in the third trimester with those during the first stage of labor. We conducted a case-control study at Saad Abul Ela Maternity Hospital, Khartoum, Sudan. Forty-five women with singleton, live neonates in the first stage of labor and 45 women in the third trimester (but not in labor) were enrolled as case and control groups, respectively. Data on the medical history, obstetrics history, and clinical examinations that were performed in all of the studied women were obtained using prearranged questionnaires. Cardiac autonomic modulation (CAM) of the heart was examined in both groups based on time and frequency domain HRV indices. There were no significant differences in age, parity, body mass index, and hemoglobin levels between the two groups. Pregnant women in labor had significantly higher LnSDNN, LnRMSSD, LnTP, LnVLF, LnLF, LnHF, LF Norm, and LnLF/HF ratio, but lower HF Norm compared with controls (P < 0.001). These findings remained unchanged when possible confounders were controlled for using regression analysis. Our findings suggest a significant increase in indictors of sympathetic CAM, namely LF Norm and LnLF/HF, during labor. Sympathetic hypertonia associated with labor is unlikely to increase the risk of cardiac events because sympathetic CAM simultaneously increases with global HRV. Increased HRV during labor may be explained by parasympathetic activation as indicated by higher LnHF and LnRMSSD at the time of delivery.

Higher Rate of Iron Deficiency in Obese Pregnant Sudanese Women.

AIM: To assess the association between obesity and iron deficiency (ID). MATERIAL AND METHODS: Pregnant women were recruited from Saad Abualila Hospital, Khartoum, Sudan, during January-April 2015. Medical history (age, parity, gestational age) was gathered using questionnaire. Weight and height were measured, and body mass index (BMI) was calculated. Women were sub-grouped based on BMI into underweight (< 18.5 kg/m^2), normal weight (18.5-24.9 kg/m^2), overweight (25-29.9 kg/m^2) and obese (≥ 30 kg/m^2). Serum ferritin and red blood indices were measured in all studied women. RESULTS: Two (0.5%), 126 (29.8%), 224 (53.0%) and 71 (16.8%) out of the 423 women were underweight, normal weight, overweight and obese, respectively. Anemia (Hb <11 g/dl), ID (ferritin <15µg/l) and iron deficiency anemia (IDA) were prevalent in 57.7%, 21.3% and 12.1%, respectively. Compared with the women with normal BMI, significantly fewer obese women were anemic [25 (35.2%) vs. 108 (85.7%), P < 0.001] and significantly higher number of obese women [25 (35.2) vs. 22 (17.5, P = 0.015] had iron deficiency. Linear regression analysis demonstrated a significant negative association between serum ferritin and BMI (- 0.010 µg/, P= 0.006). CONCLUSION: It is evident from the current findings that prevalence of anaemia and ID showed different trends about BMI of pregnant women.

The risk for medial arterial calcification in CKD.

BACKGROUND AND OBJECTIVES: CKD is a risk factor for medial artery calcification, but the CKD stage at which this risk begins is unknown. Because breast arterial calcification (BAC) is a marker of generalized medial arterial calcification, mammography was used to detect medial arterial calcification in women with different CKD stages. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective, cross-sectional study of women with and without CKD matched for age and diabetes and identified from mammograms obtained in 2006-2011. BAC was scored as present or absent per visual inspection. RESULTS: A total of 146 women with stage 3 CKD and 54 with stage 4/5 CKD were identified. An additional 21 patients with ESRD were identified and added to a previous cohort of 71 patients. Mean age was 64 years for CKD 3, 63 for CKD 4, and 59 for ESRD. Half of each group had diabetes. Compared with controls, the odds ratios for BAC were 1.44 in CKD 3 (95% confidence interval [CI], 0.82-2.53), 2.69 in CKD 4 (95% CI, 1.14-6.33), and 7.19 in ESRD (95% CI, 3.77-13.7) and did not differ with diabetic status or race. In a multivariable logistic model, age (P<0.001) and estimated GFR (P=0.005) were independent predictors of BAC. The odds ratio for BAC increased 4% for each milliliter per minute per 1.73 m(2) decrease in estimated GFR. The prevalence of BAC in CKD was increased in each decade of age over 49 years. CONCLUSIONS: CKD is an independent risk factor for medial arterial calcification.

Differential roles of uPAR in peritoneal ovarian carcinomatosis.

Epithelial ovarian cancer is the fourth leading cause of death from gynecologic malignancies in the United States. Most cases are diagnosed at late stages, with the solid tumor masses growing as peritoneal implants, or floating within the ascitic fluid (peritoneal ovarian carcinomatosis). Despite aggressive surgical "debulking," recurrence of recalcitrant disease is frequent with poor patient survival. Efforts to improve survival rates are hindered by lack of biomarkers that can detect and effectively treat ovarian cancer in its early stages. Urokinase plasminogen activator receptor (uPAR) is a multifunctional receptor involved in a myriad of tumor cell processes. However, the role of host uPAR in ovarian cancer is still elusive. To define the potential proinflammatory role of uPAR in ovarian cancer, first, using a syngeneic murine model in uPAR(-/-) mice, we found that ablation of uPAR restrained tumor take and peritoneal implants and prolonged the survival of uPAR(-/-) mice compared with their uPAR(+/+) counterparts. Ascitic fluid accumulation was significantly decreased in uPAR(-/-) mice with decreased macrophage infiltration. Second, in vitro mechanistic studies revealed that host uPAR is involved in the multiple steps of peritoneal metastatic cascade. Third, we evaluated the prognostic utility of tumor and stromal uPAR in human ovarian cancer tissue microarray. In summary, our studies indicated that uPAR plays a significant role in ovarian cancer cell-stromal crosstalk and contributes to increased vascular permeability and inflammatory ovarian cancer microenvironment. This provides a rationale for targeting the uPAR with either specific neutralizing antibodies or targeting its downstream inflammatory effectors in patients with ovarian cancer.