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The herbicide atrazine is one of the most commonly applied pesticides in the world. As a result, atrazine is the most commonly detected pesticide contaminant of ground, surface, and drinking water. Atrazine is also a potent endocrine disruptor that is active at low, ecologically relevant concentrations. Previous studies showed that atrazine adversely affects amphibian larval development. The present study demonstrates the reproductive consequences of atrazine exposure in adult amphibians. Atrazine-exposed males were both demasculinized (chemically castrated) and completely feminized as adults. Ten percent of the exposed genetic males developed into functional females that copulated with unexposed males and produced viable eggs. Atrazine-exposed males suffered from depressed testosterone, decreased breeding gland size, demasculinized/feminized laryngeal development, suppressed mating behavior, reduced spermatogenesis, and decreased fertility. These data are consistent with effects of atrazine observed in other vertebrate classes. The present findings exemplify the role that atrazine and other endocrine-disrupting pesticides likely play in global amphibian declines.

Background Breastfeeding is associated with reduced risk of becoming overweight or obese later in life. Breastfed babies grow more slowly during infancy than formula-fed babies. Among offspring exposed in utero to maternal glucose intolerance, prospective data on growth during infancy have been unavailable. Thus, scientific evidence is insufficient to conclude that breastfeeding reduces the risk of obesity among the offspring of diabetic mothers (ODM). To address this gap, we devised the Study of Women, Infant Feeding and Type 2 Diabetes after GDM Pregnancy and Growth of their Offspring, also known as the SWIFT Offspring Study. This prospective, longitudinal study recruited mother-infant pairs from the SWIFT Study, a prospective study of women with recent gestational diabetes mellitus (GDM). The goal of the SWIFT Offspring Study is to determine whether breastfeeding intensity and duration, compared with formula feeding, are related to slower growth of GDM offspring during the first year life. This article details the study design, participant eligibility, data collection, and methodologies. We also describe the baseline characteristics of the GDM mother-infant pairs. Methods The study enrolled 466 mother-infant pairs among GDM deliveries in northern California from 2009–2011. Participants attended three in-person study exams at 6–9 weeks, 6 months and 12 months after delivery for infant anthropometry (head circumference, body weight, length, abdominal circumference and skinfold thicknesses), as well as maternal anthropometry (body weight, waist circumference and percent body fat). Mothers also completed questionnaires on health and lifestyle behaviors, including infant diet, sleep and temperament. Breastfeeding intensity and duration were assessed via several sources (diaries, telephone interviews, monthly mailings and in-person exams) from birth through the first year of life. Pregnancy course, clinical perinatal and newborn outcomes were obtained from health plan electronic medical records. Infant saliva samples were collected and stored for genetics studies. Discussion This large, racially and ethnically diverse cohort of GDM offspring will enable evaluation of the relationship of infant feeding to growth during infancy independent of perinatal characteristics, sociodemographics and other risk factors. The longitudinal design provides the first quantitative measures of breastfeeding intensity and duration among GDM offspring during early life.

Aims: This study examines factors potentially contributing to unattended mental health needs among primary care patients in Lebanon’s Shatila Palestinian Refugee Camp in order to understand the prevalence of such needs and improve clinical practice with refugees and other vulnerable groups. Methods: Data collection (2012-13) involved researcher administered structured surveys of primary healthcare-clinic patients (n = 254) using the K6, the PC-PTSD, and the Modified-MINI mental illness screens. Chi. Sq., ANOVA and Principal Component analysis evaluate associations and differences in sample characteristics; Logistic regression evaluates factors associated with unattended-positive-mental-health-screens. Results: The sample (n = 254) included 55% females and 45% males; aged 18 to 89, M = 40.4 (±13). About 51.6% (n = 132) screened positive for mental illness, for these individuals only 11.4% (15 of 132) spoke to their physician about mental illness or had an acknowledged record of psychological problems. Thus 88.6% (n = 117) of those who screened positive, had unattended positive-screens. Univariate tests indicated that patients with “negative-screens,” those with “attended positive-screens,” and those with “unattended positive-screens” differed in their social and psychological characteristics as well as their relationship with the primary care setting. Overall multivariable Logistic results indicated that patients with unattended positive-screens were 34% less likely to have higher SES scores for each step up in status [OR = 0.66; CI: 0.48-0.89] and 58% less likely to have access to a provider for advice or assistance [OR = 0.42; CI: 0.20-0.88]. They were 2.2 times more likely to be females [OR = 2.20; CI: 1.22-3.95], and 5.26 times more likely to attribute their mental illness to a physical illness [OR = 5.26; CI: 2.36-11.74]. Conclusion: Large numbers of patients screen positive for mental illness who do not have their mental health need addressed during their primary care visit. This seems an issue rooted in a lack of psychoeducation about what is mental versus physical illness, female specific access to care, stigma toward mental illness, and cross-SES-communication. Improved communication in primary care, especially as it serves vulnerable refugee populations might significantly reduce the prevalence of untreated mental illness.

Combination of chemotherapy with a tyrosine-kinase inhibitor is effective in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukaemia. Ponatinib is a more potent BCR-ABL1 inhibitor than all other tyrosine-kinase inhibitors and selectively suppresses the resistant T315I clones. We examined the activity and safety of combining chemotherapy with ponatinib for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia in this continuing phase 2 trial. In this single-centre, phase 2, single-arm trial, adult patients with previously untreated Philadelphia chromosome-positive acute lymphoblastic leukaemia were sequentially enrolled. Patients who had received fewer than two courses of previous chemotherapy with or without tyrosine-kinase inhibitors were also eligible. Patients had to be aged 18 years or older, have an Eastern Cooperative Oncology Group performance status of 2 or less, have normal cardiac function (defined by ejection fraction above 50%), and have adequate organ function (serum bilirubin ≤3·0 mg/dL and serum creatinine ≤3·0 mg/dL, unless higher concentrations were believed to be due to a tumour). Patients received eight cycles of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) alternating with high-dose methotrexate and cytarabine every 21 days. Ponatinib 45 mg was given daily for the first 14 days of cycle 1 then continuously for the subsequent cycles. Patients in complete remission received maintenance with ponatinib 45 mg daily with vincristine and prednisone monthly for 2 years followed by ponatinib indefinitely. The primary endpoint for this study was event-free survival. The trial is registered at ClinicalTrials.gov, number NCT01424982. 37 patients were enrolled and treated from Nov 1, 2011, to Sept 1, 2013. 2-year event-free survival rate was 81% (95% CI 64–90). Grade 3 or more toxic effects included infections during induction (20 [54%] patients), increased aspartate aminotransferase and alanine aminotransferase concentration (14 [38%] patients), thrombotic events (three [8%]), myocardial infarction (three [8%]), hypertension (six [16%]), skin rash (eight [22%]), and pancreatitis (six [16%] patients). Two patients died from from myocardial infarction potentially related to treatment; another patient also died from myocardial infarction related to sepsis. Two further patients died, one from bleeding and another from infection, both deemed unrelated to treatment. The first results of this ongoing trial indicate that the combination of chemotherapy with ponatinib is effective in achieving early sustained remissions in patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukaemia. New strategies, including dosing titration of ponatinib and optimised control of vascular risk factors, might further improve outcomes. ARIAD Pharmaceuticals Inc.

Cancer registries, epidemiological studies, national and international health-care initiatives, and clinical, translational, and basic biomedical research rely on this up-to-date classification. [...]it is a broad interdisciplinary, globally harmonised, and sustainable undertaking that reflects health-care systems in both low-income and high-income settings with substantial implications on educational, economic, and political fronts. [...]accurate tumour subtyping when interpreting molecular data, as shown through the current approach of the WCT, is needed to establish the response to specific drug treatment in separate organs. 5 Identification of the site of origin is important in the diagnostic process, even when a tumour has metastasised, as this helps to establish a differential diagnosis and improve treatment selection. The interpretation of molecular tests is influenced by various factors, including tumour heterogeneity, discovery of mutations with uncertain significance, and inaccurate or misinterpreted results. The WCT will build on the existing structural basis and robustly incorporate any clinically validated molecular data during edition revisions.

BACKGROUNDInterventions that interrupt Plasmodium vivax transmission or eliminate dormant P. vivax liver-stage parasites will be essential for malaria elimination. Development of these interventions has been hindered by the lack of P. vivax in vitro culture and could be accelerated by a safe and reproducible clinical model in malaria-naive individuals.METHODSHealthy, malaria-naive adults were enrolled in 2 studies to assess the safety, infectivity, and transmissibility of a new P. vivax isolate. Participants (Study 1, n = 2; Study 2, n = 24) were inoculated with P. vivax-infected red blood cells to initiate infection, and were treated with artemether-lumefantrine (Study 1) or chloroquine (Study 2). Primary endpoints were safety and infectivity of the new isolate. In Study 2, transmission to mosquitoes was also evaluated using mosquito feeding assays, and sporozoite viability was assessed using in vitro cultured hepatocytes.RESULTSParasitemia and gametocytemia developed in all participants and was cleared by antimalarial treatment. Adverse events were mostly mild or moderate and none were serious. Sixty-nine percent of participants (11/16) were infectious to Anopheles mosquitoes at peak gametocytemia. Mosquito infection rates reached 97% following membrane feeding with gametocyte-enriched blood, and sporozoites developed into liver-stage schizonts in culture.CONCLUSIONWe have demonstrated the safe, reproducible, and efficient transmission of P. vivax gametocytes from humans to mosquitoes, and have established an experimental model that will accelerate the development of interventions targeting multiple stages of the P. vivax life cycle.TRIAL REGISTRATIONACTRN12614000930684 and ACTRN12616000174482.FUNDING(Australian) National Health and Medical Research Council Program Grant 1132975 (Study 1). Bill and Melinda Gates Foundation (OPP1111147) (Study 2).

TRIAL REGISTRATION. ACTRN12614000930684 and ACTRN12616000174482.

To review the literature regarding the diagnosis and management of acromegaly during pregnancy. A systematic literature search was performed using MEDLINE including hand-searching reference lists from original articles. The diagnosis of acromegaly during pregnancy is made difficult due to the physiologic changes in pituitary GH secretion and IGF-1 production resulting from placental GH secretion and the inability of commercial assays to discriminate between pituitary and placental GH. Most patients with acromegaly during pregnancy do not have an increase in tumor size, metabolic complications are uncommon, and neonatal outcome is largely unaffected. IGF-1 levels tend to be stable in such patients possibly due to the high estrogen levels causing GH resistance. Dopamine agonists, somatostatin analogues, and a GH receptor antagonist have been reported to be safe during pregnancy. Patients with visual field defects should be considered for surgery, but in most cases this can be safely postponed until after delivery. Overall, pregnancy in acromegaly is uneventful and newborns unaffected. Dopamine agonists and somatostatin analogues have not been associated with major adverse effects to the fetus; however, more data are needed to validate their safety.

OBJECTIVEThe objective of this study was to compare morbidity and outcome following radical surgery with or without adjuvant radiation therapy (RT) in the treatment of stages IB1-IB2 cervical carcinoma. METHODSWe retrospectively identified 222 patients with stages IB1-IB2 cervical carcinoma treated initially with radical hysterectomy or radical trachelectomy with or without adjuvant RT from February 2000 to November 2009. All grade 3 or higher complications—those requiring interventional radiology, endoscopic evaluation, or operative intervention—were documented. RESULTSOne hundred fifty-eight patients (71%) underwent radical hysterectomy; 64 (29%) underwent radical trachelectomy. One hundred fifty-three patients (69%) underwent surgery alone; 69 (31%) received adjuvant radiation with or without chemosensitization. There was a statistically significant difference in the rate of total grades 1 to 5 late complications between the surgery-alone and surgery + RT groups (12% vs 32%, respectively; P < 0.001); however, the rate of grade 3 or higher complications was similar (5% vs 4%, respectively; P = 0.999). The progression-free and overall survival rates of the entire cohort were both 95%. The 5-year progression-free survival rates for the surgery-alone and surgery + RT groups were 93% and 90% (P = 0.172). The overall survival rates were 96% and 91%, respectively (P = 0.332). CONCLUSIONSThe majority of women with stages IB1-IB2 cervical cancer undergoing radical surgery do not require adjuvant RT, have excellent oncologic outcome, and have low severe complication rates. Nearly one third of our patients required postoperative radiation, with no statistically significant increase in severe complication rate and with similar oncologic outcomes compared with the surgery-only cohort. These data support the continued practice of radical surgery with individualized postoperative radiation for these patients.