Human Papillomavirus Infection and Cervical Dysplasia in a Subset of Arab American Women

Background: With limited health data on Arab Americans (AAs), we sought to describe the health-seeking behaviors, prevalence of abnormal cervical cytology and high-risk human papillomavirus (HPV) serotypes, and the relationship with socioeconomic factors among a subset of AA women. Methods: Retrospective observational cohort study of women undergoing routine cancer screening at the Arab-American Center for Economic and Social Services clinic. Data collected included demographics, tobacco use, gross monthly income, prior Papanicolaou (Pap) smear history, and results of cervical cytology and high-risk HPV testing. Results: Of 430 women, 74 (17%) reported that they had never had a Pap smear. Three hundred eighty-eight (90%) women had cervical cytology interpreted as negative for intraepithelial lesion, the remaining 42 (10%) women had abnormal results. Thirteen (3%) women reported prior abnormal Pap smear, which was significantly associated with additional abnormal Pap smear on multivariable analyses (odds ratio 65.46; 95% confidence interval [CI] 17.01-338.62; p \u3c 0.001). One hundred twenty-five (29%) women were tested for high-risk HPV serotypes; 106 (91%) had negative results, 4 (3%) were positive for HPV-16, 7 (6%) were positive for other high-risk serotypes, and 8 results were not recorded. A negative HPV screen was significantly associated with a negative Pap smear (Fisher\u27s exact test p = 0.006). There was no significant association between abnormal cervical cytology and evaluated socioeconomic factors. Conclusions: Additional population based-studies to determine cervical dysplasia/cancer and HPV prevalence in women of Middle Eastern descent are needed

Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate and high-risk early stage triple negative breast cancer.

BACKGROUND: Post-treatment detection of circulating tumour DNA (ctDNA) in early-stage triple negative breast cancer (TNBC) patients predicts high risk of relapse. c-TRAK-TN assessed the utility of prospective ctDNA surveillance in TNBC and the activity of pembrolizumab in patients with ctDNA detected (ctDNA+). PATIENTS AND METHODS: c-TRAK-TN, a multi-centre phase II trial, with integrated prospective ctDNA surveillance by digital PCR, enrolled patients with early-stage TNBC and residual disease following neoadjuvant chemotherapy, or, stage II/III with adjuvant chemotherapy. ctDNA surveillance comprised three monthly blood sampling to 12 months (18 months if samples were missed due to COVID), and ctDNA+ patients were randomised 2:1; intervention:observation. ctDNA results were blinded unless patients were allocated to intervention, when staging scans were done and those free of recurrence were offered pembrolizumab. A protocol amendment (16/09/2020) closed the observation group; all subsequent ctDNA+ patients were allocated to intervention. Co-primary endpoints were i) ctDNA detection rate ii) sustained ctDNA clearance rate on pembrolizumab (NCT03145961). RESULTS: 208 patients registered between 30/01/18 - 06/12/19, 185 had tumour sequenced, 171 (92·4%) had trackable mutations, and 161 entered ctDNA surveillance. Rate of ctDNA detection by 12 months was 27·3% (44/161,95%CI:20·6-34·9). Seven patients relapsed without prior ctDNA detection. 45 patients entered the therapeutic component (intervention n=31; observation n=14; 1 observation patient was re-allocated to intervention following protocol amendment). Of patients allocated intervention, 72% (23/32) had metastases on staging at time of ctDNA+, and 4 patients declined pembrolizumab. Of the five patients who commenced pembrolizumab, none achieved sustained ctDNA clearance. CONCLUSION: c-TRAK-TN is the first prospective study to assess whether ctDNA assays have clinical utility in guiding therapy in TNBC. Patients had a high rate of metastatic disease on ctDNA detection. Findings have implications for future trial design, emphasising the importance of commencing ctDNA testing early, with more sensitive and/or frequent ctDNA testing regimes

Polyunsaturated fatty acid intake and prevalence of eczema and rhinoconjunctivitis in Japanese children: The Ryukyus Child Health Study

<p>Abstract</p> <p>Background</p> <p>The recent increase in the prevalence of allergic disorders might be a consequence of increased intake of n-6 polyunsaturated fatty acids (PUFAs) and reduced intake of n-3 PUFAs. The current cross-sectional study examined the association between intake levels and the prevalence of eczema and rhinoconjunctivitis in Japanese children.</p> <p>Methods</p> <p>Subjects were 23,388 schoolchildren aged 6-15 years residing in Okinawa. The presence of eczema and/or rhinoconjunctivitis was determined according to the criteria of the International Study of Asthma and Allergies in Childhood. A brief diet history questionnaire for children and adolescents was administered to acquire information on dietary factors. Adjustment was made for age, sex, residential municipality, number of siblings, smoking in the household, body mass index, paternal and maternal history of allergic diseases, and paternal and maternal educational level.</p> <p>Results</p> <p>The prevalences of eczema and rhinoconjunctivitis in the previous 12 months were 7.0% and 8.0%, respectively. Consumption of PUFAs, n-3 PUFAs, α-linolenic acid, n-6 PUFAs, and linoleic acid was positively associated with the prevalence of eczema: the adjusted odds ratios (ORs) between extreme quintiles (95% confidence intervals [CIs], <it>P </it>for trend) were 1.26 (1.07-1.48, 0.04), 1.31 (1.11-1.54, 0.009), 1.31 (1.12-1.55, 0.003), 1.26 (1.07-1.48, 0.01), and 1.27 (1.08-1.49, 0.01), respectively. Arachidonic acid intake was independently inversely related to eczema: the adjusted OR between extreme quintiles was 0.81 (0.69-0.95, 0.0008). Eczema was not associated with eicosapentaenoic or docosahexaenoic acid intake, or with the ratio of n-3 to n-6 PUFA intake. Only arachidonic acid intake was statistically significantly related to the prevalence of rhinoconjunctivitis, showing a clear inverse linear trend: the adjusted OR between extreme quintiles was 0.86 (0.74-0.997, 0.03).</p> <p>Conclusions</p> <p>Consumption of n-3 and n-6 PUFAs, especially α-linolenic acid and linoleic acid, may be positively associated with eczema. Arachidonic acid intake may be inversely related to eczema and rhinoconjunctivitis.</p

Upregulation of Hemoglobin Expression by Oxidative Stress in Hepatocytes and Its Implication in Nonalcoholic Steatohepatitis

Recent studies revealed that hemoglobin is expressed in some non-erythrocytes and it suppresses oxidative stress when overexpressed. Oxidative stress plays a critical role in the pathogenesis of non-alcoholic steatohepatitis (NASH). This study was designed to investigate whether hemoglobin is expressed in hepatocytes and how it is related to oxidative stress in NASH patients. Analysis of microarray gene expression data revealed a significant increase in the expression of hemoglobin alpha (HBA1) and beta (HBB) in liver biopsies from NASH patients. Increased hemoglobin expression in NASH was validated by quantitative real time PCR. However, the expression of hematopoietic transcriptional factors and erythrocyte specific marker genes were not increased, indicating that increased hemoglobin expression in NASH was not from erythropoiesis, but could result from increased expression in hepatocytes. Immunofluorescence staining demonstrated positive HBA1 and HBB expression in the hepatocytes of NASH livers. Hemoglobin expression was also observed in human hepatocellular carcinoma HepG2 cell line. Furthermore, treatment with hydrogen peroxide, a known oxidative stress inducer, increased HBA1 and HBB expression in HepG2 and HEK293 cells. Importantly, hemoglobin overexpression suppressed oxidative stress in HepG2 cells. We concluded that hemoglobin is expressed by hepatocytes and oxidative stress upregulates its expression. Suppression of oxidative stress by hemoglobin could be a mechanism to protect hepatocytes from oxidative damage in NASH

Complete gonadal dysgenesis 46,XY (Swyer syndrome) in two sisters and their mother's maternal aunt with a female phenotype.

OBJECTIVE: To present a familial case of Swyer syndrome. DESIGN: Case report. SETTING: Academic medical center. PATIENT(S): Two sisters with a main complaint of primary amenorrhea and another case, their mother's maternal aunt with the same history of primary amenorrhea but married with no consanguinity and no children. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The patients were studied from clinical, endocrinologic, and genetic perspectives. RESULT(S): Chromosome analyses revealed a 46,XY male karyotype with no detectable mosaicism in both sisters and their mother's maternal aunt. Molecular studies of sex-determining region Y and molecular investigation undertaken for the two sisters revealed SRY negativity. CONCLUSION(S): Gonadal dysgenesis can also be inherited as an X-linked disorder, and evidence exists from familial studies of perhaps autosomal inheritance

their mother's maternal aunt with a female phenotype

Objective: To present a familial case of Swyer syndrome.Design: Case report.Setting: Academic medical center.Patient(s): Two sisters with a main complaint of primary amenorrhea and another case, their mother's maternal aunt with the same history of primary amenorrhea but married with no consanguinity and no children.Intervention(s): None.Main Outcome Measure(s): The patients were studied from clinical, endocrinologic, and genetic perspectives.Result(s): Chromosome analyses revealed a 46, XY male karyotype with no detectable mosaicism in both sisters and their mother's maternal aunt. Molecular studies of sex-determining region Y and molecular investigation undertaken for the two sisters revealed SRY negativity.Conclusion(s): Gonadal dysgenesis can also be inherited as an X-linked disorder, and evidence exists from familial studies of perhaps autosomal inheritance. (Fertil Steril (R) 2011; 95: 1786. e1-e3. (C) 2011 by American Society for Reproductive Medicine.

Food and fatty acid intake and atopic disease in adults.

The aim of the study was to assess the relationship between dietary intake of selected foods and fatty acids with atopic disease prevalence in adults. Data from the European Community Respiratory Health Survey in Erfurt, combined with a 3‐day weighed records dietary survey, was used. Complete data was available from 469 males and 333 females aged 20&ndash;64 yrs. Multiple logistic regression was applied comparing the highest with the lowest quartile of dietary exposures and linear trends were tested stratified by sex. In males, margarine intake and a high ratio of omega‐6 to omega‐3 fatty acids were positively associated with hay fever. In females, a high intake of total fat, palmitoleic and oleic acids were positively associated with sensitisation. A high total fat, high monounsaturated fatty acid and high oleic acid consumption were positively associated with hay fever. Whilst an excessive intake of fat or imbalance in fat intake, particular of monounsaturated fatty acids, increased the risk for hay fever and allergic sensitisation in females, mostly no significant associations were found for males. Dietary factors were mostly not related with prevalence rates of bronchial hyperresponsiveness and atopic eczema either in males or in females