bluuebunny/crossref_metadata_2025 huggingface dataset:
Micronuclei as Biomarkers of Carcinogen Exposure in Populations Exposed to Arsenic Through Drinking Water in West Bengal, India: A Comparative Study in Three Cell Types
Authors: Basu Anamika , Ghosh Pritha , Das Jayanta K. , Banerjee Apurba , Ray Kunal , Giri Ashok K.
Published: June 2022

Contamination of groundwater by arsenic, a paradoxical human carcinogen, has become a cause of global public health concern. In West Bengal, India, the groundwater in 9 of 18 districts is heavily contaminated with arsenic. Various adverse health effects including cancer have been reported from these districts and are associated with prolonged arsenic exposure. A cross-sectional biomarker study was conducted to evaluate and compare the frequencies of micronuclei in peripheral blood lymphocytes, oral mucosa cells, and urothelial cells from the inhabitants of North 24 Parganas, one of the arsenic-affected districts. The three cell types were collected from 163 residents exposed to high levels of arsenic in drinking water (214.7213 ± 9.0273 μg/l) and from 154 unexposed subjects residing in the unaffected East Midnapur district with very little or no exposure to arsenic through drinking water (9.2017 ± 0.3157 μg/l). Our analysis revealed that micronuclei frequencies in the exposed group were significantly elevated to 5.33-fold over unexposed levels for lymphocytes, 4.63-fold for oral mucosa cells, and 4.71-fold for urothelial cells (increases in micronuclei frequencies significant at P < 0.01). The results indicate that chronic ingestion of arsenic in drinking water by the exposed subjects is linked to the enhanced incidence of micronuclei in all the three cell types, slightly higher level of micronuclei being observed in lymphocytes compared with oral mucosa and urothelial cells.
Effects of Reduced Cigarette Smoking on Levels of 1-Hydroxypyrene in Urine
Authors: Hecht Stephen S. , Carmella Steven G. , Le Ky-Anh , Murphy Sharon E. , Li Y. Shelby , Le Chap , Jensen Joni , Hatsukami Dorothy K.
Published: June 2022

We investigated the effects of smoking fewer cigarettes/day (CPD) on urinary levels of 1-hydroxypyrene (1-HOP), a biomarker of carcinogenic polycyclic aromatic hydrocarbon (PAH) uptake. We randomly assigned 151 smokers to either a reduction group or a waitlist group. In the reduction group, we measured urinary 1-HOP at two baseline intervals. Then, the smokers were expected to reduce their CPD by 25% in weeks 0–2, 50% in weeks 2–4, and 75% in weeks 4–6 and to maintain reduced smoking through week 26. In the waitlist group, four baseline measurements were taken and then the smokers joined the reduction group. Urinary 1-HOP was quantified at weeks 4, 6, 8, 12, and 26 after baseline. Statistically significant reductions in urinary 1-HOP were observed at most time points examined in groups of smokers who reduced to different extents. Reductions in the waitlist group were also generally significantly greater than baseline levels. The reductions in 1-HOP were usually modest (ranging from 14% to 35% in all groups and time points examined), which partially reflects the fact that there are sources of pyrene exposure other than cigarette smoke. Thus, cessation of smoking would only be expected to result in partial reductions of 1-HOP. The observed reductions in 1-HOP were not fully consistent with reductions in CPD probably due to uncontrolled dietary factors. Collectively, the results demonstrate that some smokers can achieve substantial reductions in 1-HOP, reflecting reduced uptake of polycyclic aromatic hydrocarbons, by reducing CPD, but there was not a consistent relationship between these parameters.
Predictors of Participation in Psychosocial Telephone Counseling following Genetic Testing for BRCA1 and BRCA2 Mutations
Authors: Halbert Chanita Hughes , Wenzel Lari , Lerman Caryn , Peshkin Beth N. , Narod Steven , Marcus Alfred , Corio Camille , Demarco Tiffani , Bellamy Scarlett
Published: June 2022

Although adjunctive educational and psychosocial programs are now being developed for BRCA1 and BRCA2 (BRCA1/2) mutation carriers, limited information is available about whether mutation carriers will want to receive such programs or about the characteristics of individuals who participate. The goals of the present study were to describe rates of completing a psychosocial telephone counseling (PTC) intervention that was offered to female BRCA1/2 mutation carriers and to identify sociodemographic and psychological factors associated with decisions to complete the intervention. Subjects were 66 BRCA1/2 mutation carriers who were randomized to receive a PTC intervention following receipt of genetic test results. Sociodemographic and psychological factors were evaluated before notification of assignment to the PTC intervention. Completion of the intervention was determined from study records. Overall, 75.8% of subjects completed the PTC intervention. Compared to unaffected subjects, those affected with breast and/or ovarian cancer were 76% less likely to complete the intervention [odds ratio (OR) = 0.24, 95% confidence interval (CI) = 0.06, 0.98, P = 0.05]. In addition, subjects with higher levels of cancer-specific distress [OR = 4.74, 95% CI = 1.02, 22.03, P = 0.05] and those with greater perceptions of social support [OR = 5.81, 95% CI = 1.29, 26.16, P = 0.02] were also most likely to complete the intervention. The results of this study suggest that while most BRCA1/2 mutation carriers are likely to complete an adjunctive psycho-educational program, personal history of cancer, cancer-specific distress, and perceptions of social support are likely to influence participation.
Methylated DNA Collected by Tampons—A New Tool to Detect Endometrial Cancer
Authors: Fiegl Heidi , Gattringer Conny , Widschwendter Andreas , Schneitter Alois , Ramoni Angela , Sarlay Daniela , Gaugg Inge , Goebel Georg , Müller Hannes M. , Mueller-Holzner Elisabeth , Marth Christian , Widschwendter Martin
Published: June 2022

This proof of principle study aimed to define a new and simple strategy for detection of endometrial cancer using epigenetic markers. We investigated DNA isolated from vaginal secretion collected from tampon for aberrant methylation of five genes (CDH13, HSPA2, MLH1, RASSF1A, and SOCS2) using MethyLight in 15 patients with endometrial cancer and 109 patients without endometrial cancer. All endometrial cancer patients revealed three or more methylated genes, whereas 91% (99 of 109) of the patients without endometrial cancer had no or fewer than three genes methylated in their vaginal secretion. The methods developed in this study provide the basis for a prospective clinical trial to screen asymptomatic women who are at high risk for endometrial cancer.
Polymorphisms in PTGS1 (=COX-1) and Risk of Colorectal Polyps
Authors: Ulrich Cornelia M. , Bigler Jeannette , Sparks Rachel , Whitton John , Sibert Justin G. , Goode Ellen L. , Yasui Yutaka , Potter John D.
Published: June 2022

Two isoforms of prostaglandin H synthase (PTGS = COX) are key enzymes in prostaglandin synthesis and primary targets for aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs). Use of aspirin or other NSAIDs is associated with a lower risk and reduced recurrence of colorectal adenomas, established precursors of adenocarcinoma. This study investigated risk of colorectal adenomatous and hyperplastic polyps associated with several polymorphisms in the coding region of PTGS1. Within the Minnesota polyp case-control study, patients with colorectal adenomatous (n = 521) or hyperplastic (n = 194) polyps and n = 621 polyp-free controls were genotyped for four PTGS1 polymorphisms (R8W, L15-L16del, P17L, L237M); these had been predicted to affect protein function based on sequence-homology software. Age- and sex-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed. Whereas there was no appreciable difference in adenoma or hyperplastic polyp risk associated with R8W, P17L, and L237M, an increased risk was observed for individuals heterozygous for the L15-L16del polymorphism (OR = 3.6, 95% CI 1.2–11.2). The variant L15-L16del allele appeared to be associated with a stronger increase in adenoma risk among nonusers of aspirin/other NSAIDs. The reduced risk observed with aspirin/other NSAID use was limited to those wild type for P17L [PP users: OR = 0.6 (0.5–0.8) versus PP nonusers: 1.0 (referent) (P interaction = 0.03)]. To our knowledge, this study represents the first investigation of polymorphisms in PTGS1 and risk of colorectal polyps. The L15-L16del variant allele may result in an increased risk of colorectal adenomas, whereas P17L may be relevant to the pharmacogenetics of aspirin. These preliminary findings require confirmation in larger studies of colorectal neoplasia.
Preliminary Communication: Glycated Hemoglobin, Diabetes, and Incident Colorectal Cancer in Men and Women: A Prospective Analysis from the European Prospective Investigation into Cancer–Norfolk Study
Authors: Khaw Kay-Tee , Wareham Nicholas , Bingham Sheila , Luben Robert , Welch Ailsa , Day Nicholas
Published: June 2022

Background: Increasing evidence suggests that abnormal glucose metabolism may be associated with increased risk of colorectal cancer. Methods: We examined the relationship between known diabetes and glycated hemoglobin (HbA1c) concentrations measured in 1995 to 1997 and subsequent incident colorectal cancer after 6 years follow-up in 9,605 men and women ages 45 to 79 years in the European Prospective Investigation into Cancer–Norfolk Study. Results: Among individuals not known to have cancer at the baseline survey, there were 67 incident colorectal cancers. HbA1c concentration appeared continuously related to incident colorectal cancer risk, with lowest rates observed in those with HbA1c below 5%. Known diabetes was also associated with incident colorectal cancer, with relative risk (RR) 3.18 and 95% confidence interval (CI) 1.36-7.40 (P < 0.01) adjusting for age and sex and RR 2.78 and 95% CI 1.10-7.00 (P = 0.03) adjusting for age, sex, body mass index, and smoking compared with those without known diabetes. The RR (95% CI) of incident colorectal cancer per 1% absolute increase in HbA1c was 1.34 (1.12-1.59; P < 0.001). HbA1c concentrations appeared to explain the increased colorectal cancer risk associated with diabetes in multivariate models. Conclusions: Known diabetes was associated with ∼3-fold risk of colorectal cancer in this analysis; this increased risk was largely explained by HbA1c concentrations, which appears continuously related to colorectal cancer risk across the population distribution.
Cell Proliferation and Apoptotic Indices Predict Adenoma Regression in a Placebo-Controlled Trial of Celecoxib in Familial Adenomatous Polyposis Patients
Authors: Sinicrope Frank A. , Half Elizabeth , Morris Jeffrey S. , Lynch Patrick M. , Morrow Jason D. , Levin Bernard , Hawk Ernest T. , Cohen Deborah S. , Ayers Gregory D. , Stephens L. Clifton ,   Familial Adenomatous Polyposis Study Group
Published: June 2022

Background: Celecoxib was shown to regress colorectal adenomas in familial adenomatous polyposis (FAP) patients relative to placebo. To address the mechanism of polyp regression, we determined whether celecoxib can modulate cell proliferation, apoptosis, and prostaglandin E2 (PGE2) levels in colorectal epithelia from FAP trial participants and whether such alterations correlate with observed reductions in polyp number. Materials and Methods: Colorectal mucosal biopsies were obtained at baseline and on last day of celecoxib (100 or 400 mg twice daily) or placebo administration (6 months). Residual paraffin-embedded adenomas and normal mucosa from the same patients (n = 17) or normal tissue alone (n = 15) were analyzed. Immunoperoxidase staining for Ki-67 was performed and apoptotic cells were identified by their morphology. Ki-67 and apoptotic labeling indices and their ratios were calculated in superficials (s) and nonsuperficial (ns) regions of adenomas and normal mucosa, and baseline to 6-month differences were calculated. PGE2 levels were analyzed by mass spectroscopy (normal, n = 64; adenoma, n = 56). Biomarkers were analyzed by treatment arm and correlated with previously determined mean percentage reductions in colorectal polyp number. Results: In adenomas, a reduction in the superficial proliferative activity i.e., Ki-67s labeling index, accompanied polyp regression (r = −0.76, P = 0.006). An increase in the apoptotic ratio [i.e., superficial apoptotic index (AIs)/nonsuperficial apoptotic index (AIns)] was found to correlate with reduced polyp counts in that higher apoptotic ratios correlated with better response to celecoxib (r = 0.71, P = 0.004). Furthermore, the AIs/Ki-67s ratio (r = 0.58, P = 0.026) accompanied polyp regression. In normal mucosa, a trend toward increased AIs (r = 0.33, P = 0.053) and polyp regression was found. PGE2 levels did not significantly correlate with polyp regression. Changes in biomarker levels (baseline to 6 months) were correlated in adenomas and normal mucosa (AIs, r = 0.29, P = 0.024; AIns, r = 0.34, P = 0.009; PGE2, r = 0.50, P = 0.059) within individual patients. Conclusion: Suppression of cell proliferation and an increased apoptotic ratio, as well as the ratio of apoptosis to cell proliferation, accompany polyp regression in a chemoprevention trial in FAP patients. These findings suggest potential mechanisms for the efficacy of celecoxib and warrant further study of these biomarkers as intermediate endpoints in FAP patients.
Variation in Estradiol, Estradiol Precursors, and Estrogen-related Products in Nipple Aspirate Fluid from Normal Premenopausal Women
Authors: Chatterton Robert T. , Geiger Angela S. , Khan Seema A. , Helenowski Irene B. , Jovanovic Borko D. , Gann Peter H.
Published: June 2022

The purpose of the study was to measure the concentrations of estradiol, its primary precursors, and factors with which it interacts in the breast, and determine their sources of variation. Nipple aspirate fluid (NAF) was collected from premenopausal women during the mid-luteal phase of the menstrual cycle. The fluid was diluted and unconjugated steroids were extracted. Estradiol was further purified by a solvent partition into aqueous NaOH. Androgens were measured in the non-phenolic fraction. Water-soluble, conjugated steroids and proteins were measured in the aqueous residue. All analytes were measured by immunoassays. Permutation methods were used to determine the correlations over multiple periods of time. The average concentration of estradiol in NAF was 435 pmol/L after purification but was many times higher when assayed without purification. Estrone and dehydroepiandrosterone (DHEA) sulfates were present in 3.7 and 75 μmol/L concentrations, respectively, while unconjugated androstenedione and DHEA were present in nanomole per liter concentrations. Lack of the steroid sulfates in NAF in 19% of subjects had no effect on NAF estradiol levels but was associated with a 77% lower concentration of unconjugated DHEA. Progesterone was present in concentrations that were 3- to 4-fold higher than normal serum concentrations (mean: 291 nmol/L). Cathepsin D, epidermal growth factor, and interleukin 6 had average values of 3.4 μg/mL, 424 ng/mL, and 1.7 ng/mL, respectively. Correlations between breasts were between 0.57 and 0.84 for the several analytes; correlations over time ranged from 0.64 and 0.93 with estrone sulfate highest in both categories. The lower correlation between breasts than within breasts indicates that local factors play an important role in determining the levels of many of these analytes in the breast. The high stability of the concentrations of several analytes over time indicates that fluctuations in environmental factors have little immediate effect on levels in the breast, and portends their utility as surrogate breast cancer risk markers.
Cancer Prevention Services and Physician Consensus in Primary Care Group Practices
Authors: Love Richard R. , Baumann Linda C. , Brown Roger L. , Fontana Susan A. , Clark Caroline C. , Sanner Louis A. , Davis James E.
Published: June 2022

Background: We conducted a randomized clinical trial of interventions to achieve physician consensus, practice changes, and patient activation designed to help primary care group practices enhance the delivery of cancer prevention and screening services. Methods: In each of 42 primary care practices in 1991 to 1994, we studied approximately 60 patients per physician who were between the ages 53 and 64. Data sources included patient and physician questionnaires, medical record audits of consenting patients for evidence of 11 cancer prevention services during the previous 3 years, and telephone interviews with key practice personnel. Results: None of the interventions was associated with significant changes in frequency of services or procedures received or provided. Increased frequencies of services overall and of specific activities were associated with HMO membership or insurance coverage for six screening procedures. Patient reports of clinic staff recommendations to have each of six screening procedures were specifically associated with higher frequencies of services (P = 0.001). Conclusions: Demonstration of intervention impact may have been limited because the rates of prevention services were significantly higher in this study than have been reported elsewhere. These results might be explained by selection biases inherent in studying patients with a regular provider, overall practice trends for changes in provision of the studied services, and the study methods.
Endogenous Hormones and Ovarian Cancer: Epidemiology and Current Hypotheses
Authors: Lukanova Annekatrin , Kaaks Rudolf
Published: June 2022

The effect of major epidemiologic risk factors for ovarian cancer has been reviewed in the light of several hormonal hypotheses, including the gonadotropin, androgens, progesterone, estrogens, insulin-like growth factor-I, and insulin hypotheses. The role of inclusion cyst formation and Mullerian epithelium differentiation in the pathology of the disease are also briefly outlined. Although based on limited data, the observed tendency in current evidence suggests possible etiologic roles for elevated androgens and estrogens and decreased progesterone in the pathogenesis of ovarian cancer. A direct effect of gonadotropins cannot be entirely ruled out, but it is plausible that their effect on ovarian cancer risk is mediated by stimulation of ovarian steroidogenesis. Insulin-like growth factor-I also emerges as a hormone that may be directly involved in the pathogenesis of the disease, but thus far only one prospective study has examined this association. Hyperinsulinemia is an unlikely risk factor for ovarian cancer. The observed tendency for an increased risk with androgens from ovarian origin (in premenopausal women), the lack of association with adrenal androgens, and the relatively weak associations observed with obesity, hormonal replacement therapy use, and endogenous hormones after menopause suggest that ovarian synthesis of sex steroids rather than their circulating levels may be etiologically important. More data from prospective studies will be crucial to improve our understanding of the etiologic role of endogenous hormones in the pathogenesis of ovarian cancer. Such data will ultimately provide opportunities for research targeted; at early detection and preventive interventions.
Effect of Blood Groups on Clinical Presentations and Treatment Outcomes in Immune Thrombotic Thrombocytopenic Purpura Patients with Severe ADAMTS13 Deficiency: A Multi-Center Experience
Authors: Yıldırım Murat , Sayın Selim , Güneş Ahmet Kürşad , Reis Aras Merih , Safak Yılmaz Esra , Albayrak Murat , Özet Gülsüm , Aylı Meltem
Published: June 2022

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by accumulation of ultra-large von Willebrand factor (vWF) due to the significantly reduced activity ADAMTS13. Limited studies have been published examining the blood group as an epidemiological factor that can contribute to development of TTP. It has been suggested that due to low vWF levels, the distribution of the “O” blood group among TTP patients may be lower than anticipated compared to the blood group distribution rates in the normal population. The aim of this study was to explore the relationship between blood groups and the clinical outcome of immune TTP (iTTP). Methods: Thirty patients with iTTP with severe ADAMTS13 deficiency were enrolled. Data collection commenced in January 2011 and was completed by June 2020. It was analyzed whether there was a difference between the blood groups in terms of frequency of iTTP, response to treatment, frequency of relapse, and clinical and laboratory results. Results and Conclusions: The distribution of group “A” among patients with iTTP was higher than expected. Although not statistically significant, patients with blood group “O” required more TPE for the treatment and relapse rate was statistically higher than other blood groups. Mortality rate in all patients was 6.7%. Although blood group “A” is a risk factor for iTTP, the frequency of relapse is higher in the blood group “O.”
Beware the Retrobulbar Optic Neuritis Diagnosis
Authors: McElhinney Kealan , Rhatigan Maedbh , Tsvetanova Zornitsa , O’Keane Conor , Logan Patricia
Published: June 2022

A 48-year-old gentleman presented to the ophthalmology department with progressive monocular vision loss, a relative afferent-pupillary defect, decreased color perception, headache, proptosis, and retro-orbital pain. This particular patient’s demographics and disease course did not suggest a “typical” retro-bulbar optic neuritis and highlights the importance of avoiding presumptive steroid treatment in such “atypical” cases. Further investigations revealed a compressive optic neuropathy secondary to an orbital tumor (B-cell non-Hodgkin’s lymphoma) and were subsequently treated by a multi-disciplinary approach. Early detection and commencement of treatment is a crucial determining factor in orbital lymphoma prognosis and is therefore an important differential diagnosis for an ophthalmologist to consider when evaluating patients with “atypical” optic neuropathies.
Struktur von kindlicher Verhaltensauffälligkeit und assoziierter Elternbelastung in Familiensituationen
Authors: Lauth Morena , Panagl Mariella , Lauth Gerhard
Published: June 2022

Alle drei Kardinalsymptome der Aufmerksamkeitsdefizit-Hyperaktivitätsstörung (ADHS) beschreiben die mangelnde Verhaltenswirksamkeit vorausgehender Umweltreize. Daher benötigen betroffene Kinder mehr und nachdrücklichere Verhaltenshinweise der sozialen Umwelt und erhöhen elterliches Stresserleben. Zwar manifestieren sich Selbststeuerungsdefizite und Elternstress situations- bzw. anforderungsabhängig mit intra-individueller Variabilität. Gängige Maße von Verhaltensauffälligkeit und Elternstress zielen aber auf generalisierte Eindrücke. Forschungsrationale: Zur Erfassung intra-individueller Auffälligkeits- und Belastungsunterschiede liegt ein Familiensituationsinventar mit Ratingskalen vor. Es handelt sich um eine deutschsprachige und eng am Original ausgerichtete Adaptation des Home Situation Questionnaire (HSQ) mit ergänzter Elternbelastungsskala. Aus der untersuchungsbedürftigen Frage nach faktorieller Validität ergibt sich das Forschungsrationale für eine explorative Faktorenanalyse. Methode: In der Gesamtstichprobe waren Eltern von Kindern mit (m. = 204, w. = 33; Mittelwert = 8,6 J.) und ohne gesicherte ADHS (m. = 206, w.= 155; Mittelwert = 7,6 J.) eingeschlossen. Sie sollten 16 Familiensituationen auf das Ausmaß kindlicher Verhaltensauffälligkeiten und ihrer damit verbundenen Belastung hin beurteilen. In der klinischen Stichprobe wurde die externe Validität der ermittelten Faktorenstruktur korrelationsanalytisch anhand dreier etablierter Skalen überprüft. Ergebnisse: Beide HSQ-Skalen teilen eine Zweifaktorenstruktur mit zufriedenstellender Varianzaufklärung (56,02–60,38%) und akzeptabler externer und diskriminanter Validität. „Häusliche Aufgabenerledigung“ (Faktor 2) unterscheidet stärker als „soziales Auftreten“ (Faktor 1) zwischen Kindern mit und ohne ADHS. Diskussion: „Häusliche Aufgabenerledigung“ beinhaltet Verhalten in regelmäßig wiederkehrenden Familiensituationen und erfordert Regel- bzw. Instruktionsbefolgung. Mit ADHS diagnostizierte Kinder befolgen geltende Regeln selten von sich aus (beispielsweise mit Selbstinstruktionen). Bei der mit Verhaltensauffälligkeiten assoziierten Elternbelastung in Familiensituationen handelt es sich daher eher um Regulation Load statt Mental Load.
Initial eGFR Changes with Ertugliflozin and Associations with Clinical Parameters: Analyses from the VERTIS CV Trial
Authors: Cherney David Z.I. , Cosentino Francesco , Dagogo-Jack Samuel , McGuire Darren K. , Pratley Richard E. , Frederich Robert , Maldonado Mario , Liu Chih-Chin , Pong Annpey , Cannon Christopher P. ,   on behalf of the VERTIS CV Investigators
Published: June 2022

Introduction: Using data from the ertugliflozin cardiovascular outcomes trial in patients with type 2 diabetes mellitus (VERTIS CV; NCT01986881), associations between the initial estimated glomerular filtration rate (eGFR) “dip” with eGFR slope, glucosuria/natriuresis-related measures, and safety were investigated. Methods: Patients were categorized into tertiles based on change in eGFR at week 6: >+1.00 mL/min/1.73 m2 (tertile 1), >−5.99 and ≤+1.00 (tertile 2), and ≤−6.00 (tertile 3). eGFR slope after week 6 and week 18 was assessed by tertile. Glucosuria/natriuresis-related measures were also determined. Adverse events (AEs) were analyzed in the acute (baseline–week 6) and chronic periods (week 6–30 days after last dose of trial medication). Results: In the ertugliflozin group, chronic eGFR slopes (95% CI, mL/min/1.73 m2/year; weeks 6–156) were −0.76 (−1.03, −0.50), −0.29 (−0.51, −0.07), and −0.05 (−0.26, 0.17) in tertiles 1, 2, and 3, respectively (p value <0.001), and approximately −1.5 mL/min/1.73 m2/year across tertiles in the placebo group (p value = 0.79). At week 18, least squares mean (LSM) changes from baseline in glycated hemoglobin (%) were −0.77, −0.71, and −0.67 in tertiles 1, 2, and 3, respectively, in the ertugliflozin group; a similar tertile-associated trend was observed for uric acid. At week 18, LSM changes from baseline in hematocrit (%) were 2.07, 2.33, and 2.55 in tertiles 1, 2, and 3, respectively, in the ertugliflozin group; similar tertile-associated trends were observed for blood pressure. All pinteraction values were <0.0001 for glucosuria- and natriuresis-related measures. Kidney-related AEs were reported more frequently in tertiles 3 and 2 in the chronic period for both placebo- and ertugliflozin-treated groups. In both periods and in all tertiles, incidences of AEs did not differ between placebo- and ertugliflozin-treated groups. Conclusion: With ertugliflozin, the tertile with the largest initial dip in eGFR had a slower rate of chronic eGFR decline. Initial eGFR changes were associated with changes in both glucosuria- and natriuresis-related measures.
Is Splitting Related to Resistance to Proactive Interference? A Process-Oriented Study of Kernberg’s Conceptualization of Splitting
Authors: Gagnon Jean , Quansah Joyce Emma , Saleh Gasser , Levin Charles
Published: June 2022

Introduction: Splitting, as a defense mechanism in Kernberg’s theory, plays a significant role in the development and maintenance of polarized and oscillating representations of self/other characteristics of borderline personality disorder (BPD). Although the notion of splitting can be considered from a structural and a functional point of view, almost all empirical studies to date have focused on the former elements to the detriment of related cognitive processes. Methods: To further investigate the cognitive processes related to splitting, 60 participants were administered the Splitting Index and indexes of resistance to proactive interference (PI) using the interpersonal recent negative task with words that reflect negative or positive interactions compared to neutral words. Results: The use of splitting was uniquely and significantly predicted by a higher capacity to resist PI and a lower capacity to consistently maintain this resistance when presented with negative words, above and beyond BPD traits, primitive defenses, and the presentation of neutral words. Results showed no evidence of a relationship between splitting and resistance to PI with positive words. Conclusion: Results appear compatible with Kernberg’s conceptualization of splitting as an active defense process that relates to an unstable capacity to inhibit negative representations of the object from entering working memory.
Criminal and Civil Responsibility of the Donor in a Case of Transmission of Malaria by a Blood Transfusion in a Nonendemic Country
Authors: Wagner Thomas , Stadlbauer Vanessa , Stöger Karl , Schorna Karin , Zink Michael
Published: June 2022

Introduction: The blood donation process is strictly regulated by law. The process includes the necessity of a medical history taken to determine if a donor is suitable to donate, which shall guarantee both donor and recipient safety. Supplementary screening for a limited number of infections is performed by antibody (HIV, HCV, syphilis) or antigen (HBV) tests or NAT (HIV, HCV, HBV). Case Presentation: With regard to a possible infection due to (sexual) risk behavior or foreign travel, blood donation facilities are predominantly dependent on information provided by the donor. This is especially true for malaria in nonendemic areas such as Europe. Transmission of malaria by a blood transfusion in a nonendemic country that led to fulminant septic shock and death of the patient happened. Discussion: From a legal perspective, the donor thus assumes a high level of responsibility with regard to the accuracy and completeness of the information provided on the donor questionnaire. Incorrect information may, as in this Austrian case reported, result in civil or criminal responsibility of the donor.
Human Ocular Thelaziasis: A Case Report from Indonesia
Authors: Harlimton Liem Meysie Kristi , Wahyuni Sitti , Reza Alif , Sirajuddin Junaedi , Eka Hasnah B. , Islam Itzar Chaidir , Ichsan Andi Muhammad
Published: June 2022

Thelaziasis is a parasitic disease caused by a nematode of genus Thelazia, which is rare in the world, including Indonesia. The definitive hosts for Thelazia are canids, felids, mustelids, and other mammals, while the vector is drosophila flies. Consequently, this study reported an uncommon occurrence of human ocular thelaziasis in Indonesia. Based on the patient’s complaints and physical examination, we found a living worm that move actively in the anterior chamber; then documentation is carried out both during the examination at the polyclinic and in the operating room. The surgery was performed using topical anaesthesia, clear corneal incision, and removing worm through the main port. Morphological examination from the parasitology laboratory showed that the worm was Thelazia callipaeda species. Following this intervention, the patient was given an oral anti-helminthics drug, topical and oral antibiotics, topical steroid, and surgical treatment. There was no recurrence or appearance of any other symptoms reported in 2 months of follow-up.
Paraganglioma of the Fallopian Tube Presenting as Isolated Fallopian Tube Torsion
Authors: Takeda Akihiro , Watanabe Kazuko , Koike Wataru , Tsuge Shiori
Published: June 2022

A 32-year-old woman with no previous disease history was presented with worsening right-lower abdominal pain, which lasted for 4 days. On magnetic resonance imaging, a solid mass measuring 48 mm in longitudinal diameter connected with a tortuous structure that appeared to be a fallopian tube was identified in the right-lower abdomen. Because the right ovary was identified at a slightly distant location, isolated fallopian tube torsion with heterogeneous mass was suspected. The isolated fallopian tube torsion without ovarian involvement was laparoscopically confirmed. After detorsion, solid necrotized mass in the distal portion of the right fallopian tube near the fimbrial end became evident, followed by uneventful right salpingectomy with ovarian preservation. The pathological diagnosis was paraganglioma of the fallopian tube with positive cells for neural cell adhesion molecule, neuron-specific enolase, and S-100 protein in the viable peripheral foci of the massively necrotized hemorrhagic mass. Recurrence was not observed after 1.5 years.
Listening to Individuals with Differences in Sex Development or Intersex and Their Families: “Not Doing Surgery Does Not Mean Doing Nothing”
Authors: Magritte Ellie , Williams Jo , Amyot Emma , Usipuik Megan , Sanders Caroline
Published: June 2022

Informed decision-making and considerations of the child’s best interest offer a starting place for building informed and lifelong discussions that promote the long-term interests and the well-being of individuals experiencing differences in sex development (DSD) or intersex traits. Parents require sufficient information and support to understand what “doing something and doing nothing” really means when learning about nonsurgical options. This may take the form of health literacy support, asking how parents are given access to meaningful and understandable information, as well as psychosocial support and psychological care. Timely psychological assessment and interventions that support informed decision-making actions are an essential aspect of holistic care for children and youth with DSD and their parents. Without actionable tools or approaches, parents cannot make informed decisions about their child’s health and, as such, health literacy is a key attribute to aid decision making for both parents and children. As individuals with DSD become increasingly adept at building resourcefulness and gathering and applying knowledge about their bodies, limiting irreversible surgeries in childhood can afford wider life choices. To this end, an educated and informed comprehensive and helpful multidisciplinary group understands and embodies, as a whole team, the need for compassionate, emotionally supportive, and validating care in all interactions with parents of children and individuals with DSD. The paper draws on the primary author’s experiences working with the charity, dsdfamilies, concluding with actionable approaches that include supporting personal knowledge through health literacy, examining team-based psychological care, and psychosocial approaches across the lifespan.
Virtual Venues and International Negotiations: Lessons from the COVID-19 Pandemic
Authors: Bjola Corneliu , Coplen Michaela
Published: June 2022

The COVID-19 pandemic has altered international diplomacy, with many negotiations now conducted in ‘virtual venues’ facilitated by videoconferencing platforms such as Zoom, Microsoft Teams, Webex, and Interprefy. Drawing on a survey of diplomats with experience in virtual venue negotiation, we analyze respondents’ perceptions of efficacy, tactics, and legitimacy in these venues. We find that virtual venues not only affect the format, but also the substance of negotiations. In general, perceptions of efficacy are related to diplomats’ ability to ‘read the room’. Virtual venues also impact negotiations at the tactical level. We find that coercive approaches (including novel tactics) are more common than persuasive approaches. Overall, these venues are afforded the same legitimacy as face-to-face negotiations. We conclude that, as virtual venues will be a feature of international diplomacy for the foreseeable future, further research is required to inform increased diplomatic adaptation and hybridity.
Deconstructing the Relation between Law and Authoritarianism: How Law Consolidated Authoritarianism in Post-2011 Egypt
Authors: Elgohari Mohamed
Published: June 2022

This article argues that law and legal mechanisms in Egypt have not simply reinforced authoritarianism but have also been the avenue through which embryonic moves toward the rule of law have been halted and even reversed. The political regime has utilized law to consolidate its rule, boost its legitimacy, crack down on opposition and dissent, and restrict freedoms and rights. In Egypt, law and authoritarianism have not only co-existed but also have intersected and been mutually supportive. The political regime has used laws to legalize its autocratic policies and practices as a pretext to restore order and stability and fight terrorism. Since 2013, the law has been a tool not simply for authoritarianism in general but also for the ruling regime and military institution to assert control over society, to place themselves out of reach of legal/constitutional mechanisms and accountability either by issuing new laws and executive orders or altering existing ones.
Foliar cuticles of species of Persea subg. Eriodaphne (Lauraceae)
Authors: MORAES PEDRO LUÍS RODRIGUES DE , DELTREGGIA TRINCA MAYRA
Published: June 2022

The American species of Persea are divided in two subgenera, Persea subg. Persea and P. subg. Eriodaphne, which form a monophyletic group. In this study we analysed leaf cuticle characters of 220 collections of 54 species of Persea, 48 of them belonging to the P. subg. Eriodaphne, two belonging to the P. subg. Persea, and another four formally unplaced. A dichotomous identification key was built from a matrix of eight leaf cuticle qualitative characters and 30 states, most of them illustrated here for the first time by light and scanning electron microscopy, which allowed us to distinguish these taxa.
The Agrarian Roots of Divergent Development: A Case Study of Twentieth-Century Brazil
Authors: Carlson Chris
Published: June 2022

The literature on development has long highlighted the role of international trade and developmental states as key factors in explaining divergent processes of economic development. A country’s position in the world economy and its state’s capacity to promote industrialization are seen as fundamental to understanding its development path. Yet, these approaches are often inadequate for explaining the actual contours of industrial and economic growth across the Global South. In this study, an in-depth case study of Brazil reveals the limits of the mainstream approaches and illustrates the centrality of the underlying agrarian economy for understanding the country’s development path. Archival and quantitative data show that both the timing and location of industrialization in Brazil are better explained by the agrarian dynamics that unfolded in the country in the twentieth century. This has broader implications for understanding development processes throughout the Global South.
The implementation of a whole school approach to mental health and well-being promotion in the Irish primary school context
Authors: Higgins Edel , Booker Roger
Published: June 2022

Background:

Schools are well recognised as critical contexts for the promotion of mental health and well-being and offer the potential to reach a large number of children at an early age, at a time when they are developing important attitudes and behaviours that may influence their future health. Ensuing from a number of large-scale epidemiological studies which have found that young Irish people are significantly struggling with their mental health and well-being, the Government of Ireland has committed to prioritising mental health promotion in schools through a multicomponent, preventive, whole school approach.

Objectives:

To obtain a detailed and integrated account of the implementation of a whole school approach to mental health and well-being promotion in the Irish primary school context.

Method:

A qualitative case study approach was undertaken employing in depth semi-structured interviews, document analysis and field notes. Thematic analysis was applied to all interview data and emerging themes were mapped on to the Theoretical Domains Framework (TDF) domains.

Setting:

Three Irish primary schools.

Results:

Facilitators and barriers that emerged from the data related primarily to the schools’ economic and political context, organisational context, and internal and external partnerships and relationships.

Conclusion:

This study has demonstrated that the implementation process in ‘real-world’ practice settings, such as schools, is dynamic, complex and exists within a multi-level system and requires careful consideration of the numerous ecological factors that can influence implementation.
Benchmarking Deep Learning Models for Tooth Structure Segmentation
Authors: Schneider L. , Arsiwala-Scheppach L. , Krois J. , Meyer-Lueckel H. , Bressem K.K. , Niehues S.M. , Schwendicke F.
Published: June 2022

A wide range of deep learning (DL) architectures with varying depths are available, with developers usually choosing one or a few of them for their specific task in a nonsystematic way. Benchmarking (i.e., the systematic comparison of state-of-the art architectures on a specific task) may provide guidance in the model development process and may allow developers to make better decisions. However, comprehensive benchmarking has not been performed in dentistry yet. We aimed to benchmark a range of architecture designs for 1 specific, exemplary case: tooth structure segmentation on dental bitewing radiographs. We built 72 models for tooth structure (enamel, dentin, pulp, fillings, crowns) segmentation by combining 6 different DL network architectures (U-Net, U-Net++, Feature Pyramid Networks, LinkNet, Pyramid Scene Parsing Network, Mask Attention Network) with 12 encoders from 3 different encoder families (ResNet, VGG, DenseNet) of varying depth (e.g., VGG13, VGG16, VGG19). On each model design, 3 initialization strategies (ImageNet, CheXpert, random initialization) were applied, resulting overall into 216 trained models, which were trained up to 200 epochs with the Adam optimizer (learning rate = 0.0001) and a batch size of 32. Our data set consisted of 1,625 human-annotated dental bitewing radiographs. We used a 5-fold cross-validation scheme and quantified model performances primarily by the F1-score. Initialization with ImageNet or CheXpert weights significantly outperformed random initialization ( P < 0.05). Deeper and more complex models did not necessarily perform better than less complex alternatives. VGG-based models were more robust across model configurations, while more complex models (e.g., from the ResNet family) achieved peak performances. In conclusion, initializing models with pretrained weights may be recommended when training models for dental radiographic analysis. Less complex model architectures may be competitive alternatives if computational resources and training time are restricting factors. Models developed and found superior on nondental data sets may not show this behavior for dental domain-specific tasks.
Application of Terror Management Theory to End-Of-Life Care Decision-Making: A Narrative Literature Review
Authors: Perry Laura M. , Mossman Brenna , Lewson Ashley B. , Gerhart James I. , Freestone Lily , Hoerger Michael
Published: June 2022

Patients with serious illnesses often do not engage in discussions about end-of-life care decision-making, or do so reluctantly. These discussions can be useful in facilitating advance care planning and connecting patients to services such as palliative care that improve quality of life. Terror Management Theory, a social psychology theory stating that humans are motivated to resolve the discomfort surrounding their inevitable death, has been discussed in the psychology literature as an underlying basis of human decision-making and behavior. This paper explores how Terror Management Theory could be extended to seriously ill populations and applied to their healthcare decision-making processes and quality of care received.
Enhancing Surveillance Protocols for Acute Hepatitis C Virus Infection, Utah, 2014-2019
Authors: Lewis Nathaniel M. , Eason Jeff , Barbeau Bree , Boulton Rachelle , Nakashima Allyn K. , Dunn Angela C.
Published: June 2022

During 2014-2019, the Utah Department of Health (UDOH) enhanced its surveillance program for acute hepatitis C virus (HCV) infections by mandating electronic reporting of negative HCV test results in 2015 and liver function test results in 2016. UDOH also engaged with blood and plasma donation centers beginning in 2014 and syringe exchange programs in 2018 to encourage manual reporting of negative HCV test results from facilities without electronic reporting capabilities. UDOH hepatitis surveillance staff also provided training for case investigations in 2017. The number of cases detected increased 14-fold, from 9 during 2012 to 127 during 2019. In 2019, of 127 cases, 55% (n = 70) were detected through negative HCV test results reported electronically before positive test results (ie, recent seroconversions), 25% (n = 32) through positive HCV test results and elevated liver function test results, 18% (n = 23) through manually reported negative HCV test results, and 2% (n = 2) through positive HCV test results and clinical evidence. Challenges to surveillance included accessing patients for investigations and engaging donation centers in reporting negative test results. Utah’s experience demonstrates practical considerations for improving surveillance of acute HCV infections.
Temporal Trends in Tobacco Product Use Among US Middle and High School Students: National Youth Tobacco Survey, 2011-2020
Authors: Jebai Rime , Osibogun Olatokunbo , Li Wei , Gautam Prem , Bursac Zoran , Ward Kenneth D. , Maziak Wasim
Published: June 2022

Objectives:

Despite significant declines in cigarette smoking during the past decade, other tobacco products gained popularity among middle and high school students. This study examined temporal trends in exclusive and concurrent use of tobacco products among middle and high school students in the United States from 2011 through 2020.

Methods:

We used multiple annual datasets from the National Youth Tobacco Survey from 2011 through 2020 (N = 193 350) to examine trends of current (past 30 days) exclusive, dual, and poly use of tobacco products (ie, cigarettes, electronic cigarettes [e-cigarettes], cigars, hookahs, and smokeless tobacco). We used joinpoint regression models to calculate log-linear trends in annual percentage change (APC).

Results:

During 2011-2020, exclusive use of any tobacco product decreased significantly, except for e-cigarettes, which increased significantly at an APC of 226.8% during 2011-2014 and 14.6% during 2014-2020. This increase was more pronounced among high school students (APC = 336.6% [2011-2014] and 15.7% [2014-2020]) than among middle school students (APC = 10.4% [2014-2020]) and among male students (APC = 252.8% [2011-2014] and 14.8% [2014-2020]) than among female students (APC = 13.6% [2014-2020]). During 2011-2020, we also found upward trends in dual use of e-cigarettes and cigarettes (APC = 17.3%). Poly use of e-cigarettes, cigarettes, and any other tobacco products increased significantly at an APC of 57.1% during 2011-2014.

Conclusions:

The emergence of new tobacco products such as e-cigarettes in the US market has shifted the landscape of tobacco use among adolescents in the last decade toward poly product use, in which e-cigarettes are a prominent component. Our findings underscore the increasing complexity of tobacco use among adolescents in the United States and the need for strong policies and regulations adapted to evolving trends in cigarette and noncigarette tobacco products.