Neural Tube Defects in Pregnancies Among Women With Diagnosed HIV Infection - 15 Jurisdictions, 2013-2017.

In May 2018, a study of birth defects in infants born to women with diagnosed human immunodeficiency virus (HIV) infection in Botswana reported an eightfold increased risk for neural tube defects (NTDs) among births with periconceptional exposure to antiretroviral therapy (ART) that included the integrase inhibitor dolutegravir (DTG) compared with other ART regimens (1). The World Health Organization* (WHO) and the U.S. Department of Health and Human Services† (HHS) promptly issued interim guidance limiting the initiation of DTG during early pregnancy and in women of childbearing age with HIV who desire pregnancy or are sexually active and not using effective contraception. On the basis of additional data, WHO now recommends DTG as a preferred treatment option for all populations, including women of childbearing age and pregnant women. Similarly, the U.S. recommendations currently state that DTG is a preferred antiretroviral drug throughout pregnancy (with provider-patient counseling) and as an alternative antiretroviral drug in women who are trying to conceive.§ Since 1981 and 1994, CDC has supported separate surveillance programs for HIV/acquired immunodeficiency syndrome (AIDS) (2) and birth defects (3) in state health departments. These two surveillance programs can inform public health programs and policy, linkage to care, and research activities. Because birth defects surveillance programs do not collect HIV status, and HIV surveillance programs do not routinely collect data on occurrence of birth defects, the related data have not been used by CDC to characterize birth defects in births to women with HIV. Data from these two programs were linked to estimate overall prevalence of NTDs and prevalence of NTDs in HIV-exposed pregnancies during 2013-2017 for 15 participating jurisdictions. Prevalence of NTDs in pregnancies among women with diagnosed HIV infection was 7.0 per 10,000 live births, similar to that among the general population in these 15 jurisdictions, and the U.S. estimate based on data from 24 states. Successful linking of data from birth defects and HIV/AIDS surveillance programs for pregnancies among women with diagnosed HIV infection suggests that similar data linkages might be used to characterize possible associations between maternal diseases or maternal use of medications, such as integrase strand transfer inhibitors used to manage HIV, and pregnancy outcomes. Although no difference in NTD prevalence in HIV-exposed pregnancies was found, data on the use of integrase strand transfer inhibitors in pregnancy are needed to understand the safety and risks of these drugs during pregnancy.

Primary central nervous system posttransplantation lymphoproliferative disorder after heart and lung transplantation.

Primary central nervous system posttransplantation lymphoproliferative disorder (PCNS-PTLD) is uncommon, especially after heart or lung transplantation. Database analysis from a single heart and lung transplantation centre and a literature review pertaining to PCNS-PTLD was performed. In this study, the prevalence of PCNS-PTLD was 0.18% after heart and/or lung transplants. Of 1674 transplants, three cases of PCNS-PTLD developed 14 months, 9 years and 17 years posttransplant, and all were Epstein-Barr virus driven malignancies. Literature review of the topic revealed predominantly retrospective studies, with most reported cases after renal transplantation. The overall survival is poor, and it may be improved by early diagnosis and treatment. There are no published guidelines on the management of PCNS-PTLD; immune-chemotherapy in conjunction with reduction of immune suppression is preferred based on available evidence.

Hepatosplenic T-cell lymphoma, immunosuppressive agents and biologicals: what are the risks?

We present three cases of the rare hepatosplenic T-cell lymphoma (HSTCL); two patients suffering from Crohn disease who developed HSTCL on azathioprine without exposure to biologicals, and a third patient who had psoriasis treated using etanercept, cyclosporine and methotrexate. The evidence for an association between HSTCL and immunosuppressive drugs and biologicals is reviewed. We argue for improved pharmacovigilance processes to help determine the benefit to risk ratios for the use of these and other new agents.

Comparing Job Satisfaction Among Healthcare Workers at Emergency Departments and Primary Healthcare Units During the COVID-19 Pandemic.

Background The primary healthcare professionals' work description changed during the COVID-19 pandemic, as was the case of all other healthcare departmental operation systems. Objectives This investigation compares job satisfaction between emergency department (ED) and primary healthcare professionals during the COVID-19 pandemic to ascertain the possible effect of the pandemic on healthcare providers. Methods A cross-sectional online self-assessment questionnaire consisting of 36 questions was distributed using available social media to target all frontline healthcare workers (HCWs) in emergency departments and primary healthcare centres in Riyadh. The inclusive criterion was that the respondents should have been frontline HCWs during the pandemic era. The questionnaire was validated by a pre-test of responses of 10 frontline HCWs. This was to ensure the comprehensibility and validity of the questions. Thereafter, necessary corrections were made to the final questionnaire. Responses were collected with an Excel sheet (Microsoft Corp., Redmond, WA), while data were analysed with SPSS version 23 (IBM Corp., Armonk, NY) and GraphPad Prism version 9.2.0 (GraphPad Software, San Diego, CA). Results The targeted sample size was 400; however, 159 HCWs responded to the questionnaire and were thus included in the investigation. There were more male (60.4%) than female (39.6%) respondents, the majority of whom were Saudi nationals (86.6%) while the remaining were non-Saudi nationals working in the Kingdom. Also, 67% of the respondents were emergency medical service professionals while the remaining (23%) were primary healthcare professionals. Significantly, 71.8% of the respondents (p < 0.05) disagreed with adequate enumeration, rewards, and chances of promotion compared to those who agreed (28.2%) during the COVID-19 pandemic. Job satisfaction was not significantly correlated to gender or the work departments (p > 0.05). Respondents significantly (p < 0.05) agreed to the competence of their supervisors, and liked their colleagues and work environment. Conclusion The study has shown that although supervision during the pandemic era was with competence; however, hours of work put in by these frontline emergency professionals were not adequately remunerated. Also, the services they provide seemed not to have been appreciated and hence did not lead to promotion either. Therefore, there was job satisfaction. As expected, the workload was huge while chances of promotion were lacking. These observations could lead to a substandard service should there be another pandemic. There is a need for all stakeholders to look into this more cautiously should there be another pandemic.

The association between sports participation and athletic identity with eating pathology among college-aged males and females.

The current study examined associations among sports participation (SP), athletic identity (AI), weight status, and eating pathology, and whether these relations differed by gender. Data come from male and female first-year college students who participated in the Tufts Longitudinal Health Study (TLHS) between 1999-2007 (N=712). Relations among SP, AI, actual and perceived weight statuses, Eating Disorders Inventory (EDI) subscale scores, and indices of body shape concern and restrictive eating were examined with hierarchical ordinary least squares (OLS) regression. Associations between SP and eating pathology among females were moderated by perceived weight status. By contrast, relations between males' EDI subscales scores and SP were moderated by ethnicity, as well as by actual weight status. Our findings support that sports participation alone neither promotes nor protects against eating pathology among males and females.

Pathway-Based Approaches for Assessing Biological Hazards of Complex Mixtures of Contaminants: A Case Study in the Maumee River.

Assessment of ecological risks of chemicals in the field usually involves complex mixtures of known and unknown compounds. We describe the use of pathway-based chemical and biological approaches to assess the risk of chemical mixtures in the Maumee River (OH, USA), which receives a variety of agricultural and urban inputs. Fathead minnows (Pimephales promelas) were deployed in cages for 4 d at a gradient of sites along the river and adjoining tributaries in 2012 and during 2 periods (April and June) in 2016, in conjunction with an automated system to collect composite water samples. More than 100 industrial chemicals, pharmaceuticals, and pesticides were detected in water at some of the study sites, with the greatest number typically found near domestic wastewater treatment plants. In 2016, there was an increase in concentrations of several herbicides from April to June at upstream agricultural sites. A comparison of chemical concentrations in site water with single chemical data from vitro high-throughput screening (HTS) assays suggested the potential for perturbation of multiple biological pathways, including several associated with induction or inhibition of different cytochrome P450 (CYP) isozymes. This was consistent with direct effects of water extracts in an HTS assay and induction of hepatic CYPs in caged fish. Targeted in vitro assays and measurements in the caged fish suggested minimal effects on endocrine function (e.g., estrogenicity). A nontargeted mass spectroscopy-based analysis suggested that hepatic endogenous metabolite profiles in caged fish covaried strongly with the occurrence of pesticides and pesticide degradates. These studies demonstrate the application of an integrated suite of measurements to help understand the effects of complex chemical mixtures in the field. Environ Toxicol Chem 2021;40:1098-1122. © 2020 SETAC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Phosphatidylinositol 3,5-bisphosphate and Fab1p/PIKfyve underPPIn endo-lysosome function.

PtdIns(3,5)P(2) is one of the seven regulatory PPIn (polyphosphoinositides) that are ubiquitous in eukaryotes. It controls membrane trafficking at multiple points in the endosomal/lysosomal system and consequently regulates the size, shape and acidity of at least one endo-lysosomal compartment. PtdIns(3,5)P(2) appears to exert this control via multiple effector proteins, with each effector specific for a subset of the various PtdIns(3,5)P(2)-dependent processes. Some putative PtdIns(3,5)P(2) effectors have been identified, including Atg18p-related PROPPIN [beta-propeller(s) that bind PPIn] proteins and the epsin-like proteins Ent3p and Ent5p, whereas others remain to be defined. One of the principal functions of PtdIns(3,5)P(2) is to regulate the fission/fragmentation of endo-lysosomal sub-compartments. PtdIns(3,5)P(2) is required for vesicle formation during protein trafficking between endo-lysosomes and also for fragmentation of endo-lysosomes into smaller compartments. In yeast, hyperosmotic stress accelerates the latter process. In the present review we highlight and discuss recent studies that reveal the role of the HOPS-CORVET complex and the vacuolar H(+)-ATPase in the process of endo-lysosome fission, and speculate on connections between these machineries and the Fab1p pathway. We also discuss new evidence linking PtdIns(3,5)P(2) and PtdIns5P to the regulation of exocytosis.

Children's understanding of promising, lying, and false belief.

Understanding promising and lying requires an understanding of intention and the ability to interpret mental states. The author examined (a) the extent to which 4- to 6-year-olds focus on the sincerity of the speaker's intention when the 4-to 6-year-olds make judgments about promises and lies and (b) whether false-belief reasoning skills are related to understanding promising and lying. Participants watched videotaped stories and made promise and lie judgments from their own perspective and from the listener-character's perspective. Children also completed false-belief reasoning tasks. Older children made more correct promise judgments from both perspectives. All children made correct lie judgments from the listener's perspective. The author found that Ist-order false-belief reasoning was related to making judgments from the participant's perspective; 2nd-order false-belief reasoning was related to making judgments from the listener-character's perspective. Results suggest that children's understanding of promising and lying moves from a focus on outcome toward a focus on the belief that each utterance is designed to create.

CD200 is a useful diagnostic marker for identifying atypical chronic lymphocytic leukemia by flow cytometry.

INTRODUCTION: Immunophenotyping by flow cytometry is routinely employed in distinguishing between chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). Inclusion of CD200 has been reported to contribute to more reliable differentiation between CLL and MCL. We investigated the value of CD200 in assessment of atypical CLL cases. METHODS: CD200 expression on mature B cell neoplasms was studied by eight-color flow cytometry in combination with a conventional panel of flow cytometry markers. The study included 70 control samples, 63 samples with CLL or atypical CLL phenotype, 6 MCL samples, and 40 samples of other mature B cell neoplasms. RESULTS: All CLL samples were positive for CD200, whereas MCL samples were dim or negative for CD200. Of the CLL samples, 7 were atypical by conventional flow cytometry, with Matutes scores ≤3. These cases were tested for evidence of a t(11;14) translocation, characteristic of MCL, and all were negative, consistent with their classification as atypical CLL. All these atypical CLL samples were strongly positive for CD200. CONCLUSION: CD200 proved to be a useful marker for differentiation between CLL and MCL by flow cytometry. In particular, CD200 was useful in distinguishing CLL samples with atypical immunophenotypes from MCL.

Prenatal diagnosis of congenital myotonic dystrophy and counseling of the pregnant mother: case report and literature review.

The molecular basis of the myotonic dystrophy (MD) kinase gene is expansion of the CTG repeat at the 3'-untranslated region of the MD gene. Variability of the CTG repeat size in different tissues of affected individuals has been demonstrated. The objective of this report was to examine and review the feasibility of prenatal diagnosis of congenital myotonic dystrophy (CMD) in pregnant women with MD using CTG repeat sizes in amniocytes or villi. We present a case of a pregnant woman with MD who underwent prenatal diagnosis of MD using amniocytes. The repeat size in the amniocytes was smaller than the repeat size in the maternal leukocytes and smaller than the repeat size in the infant blood. The infant had CMD. We also reviewed the literature for reports on MD cases that were prenatally tested for CTG repeat size using amniocytes or chorionic villi. Data were tabulated based on the number of maternal CTG repeats, prenatal procedure [amniocentesis or chorionic villus sampling (CVS)], CTG repeat size in fetal tissue, fetal/infant blood, and pregnancy outcome. Twenty-seven pregnancies at risk for MD that underwent prenatal diagnosis were reported. Eleven (40.7%) of the 27 pregnancies underwent amniocentesis, and 16 (59.3%) underwent CVS. Fourteen patients (61%) demonstrated an increase in CTG repeat size in the amniocytes or villi compared with the maternal repeat size. Nine (33%) of the 27 pregnancies were terminated because of CMD risk. The outcomes of 11 (40.7%) pregnancies were consistent with diagnosis of CMD. CMD was diagnosed in fetuses demonstrating expansion or contraction of the CTG mutation in the amniocytes. Prenatal diagnosis of MD is possible by using mutation analysis on maternal and fetal DNA and detection of the CTG repeat expansion. Prenatal diagnosis of CMD is more complex. The possible lack of correlation between CTG repeat size in amniocytes, villi, and other fetal tissues is a potential limitation in prenatal diagnosis and counseling of CMD using CTG repeat size. Thus, prenatal diagnosis of CMD should be based on a combination of factors, including maternal pregnancy history, clinical findings, and cautious interpretation of maternal and fetal DNA analysis.

Lenograstim administration to HLA-identical donor-recipient pairs to accelerate marrow recovery post-transplant.

In an attempt to accelerate marrow recovery after HLA-identical sibling bone marrow transplantation, the donors of 12 patients with haematological malignancy were given recombinant human granulocyte colony-stimulating factor (rHuG-CSF; lenograstim; Granocyte) 5 micrograms/kg/day for seven doses prior to marrow harvest. All 12 recipients also received lenograstim 5 micrograms/kg/day from the day of transplant until their neutrophil count was 1.0 x 10(9)/1. In addition to lenograstim post-transplant and lenograstim-stimulated donor bone marrow the first six recipients also received donor peripheral blood stem cells that had been enriched for CD34+ stem/progenitor cells and T cell depleted on an immune absorption column (cohort 1). The second six patients (cohort 2) received lenograstim post-transplant and lenograstim-stimulated donor marrow only. All 12 patients showed a marked elevation of their circulating white blood cell count (predominantly neutrophils) on day 1 post-transplant. Compared to carefully matched historical control patients the rate of neutrophil engraftment was significantly accelerated in both patient cohorts and platelet engraftment was accelerated in cohort 2.

Ultrasonography in the diagnosis and monitoring of ascites in acute abdominal attacks of hereditary angioneurotic oedema.

BACKGROUND: Hereditary angioneurotic oedema (HAE) is a rare cause of ascites. As acute abdominal attacks of the disease can mimic surgical emergencies, prompt and accurate diagnosis is essential. This study was undertaken to evaluate the usefulness of serial abdominal ultrasound (US) examinations. PATIENTS AND METHODS: Seventy patients with HAE were followed up for almost a decade. All patients presenting with an acute oedematous attack underwent abdominal US, which was then repeated 24 and 48 h after appropriate therapy. RESULTS: Twenty-two acute oedematous attacks with abdominal complaints severe enough to justify hospital admission occurred in the study population. Abdominal US performed during the attack showed oedematous thickening of the intestinal wall in 80% of cases and invariably demonstrated the presence of free peritoneal fluid in all patients. Rapid symptomatic relief achieved by treatment was accompanied by the significant regression of US abnormalities. CONCLUSIONS: Transitory ascites demonstrated by abdominal US is a clue to the diagnosis of an acute abdominal attack of HAE. The possibility of HAE should always be considered whenever unexplained abdominal pain recurs with or without ascites.

[What can family physicians contribute to health promotion in schools?]. / Welchen Beitrag können niedergelassene Arzte zur Gesundheitsförderung an Schulen leisten?

Although several German schools have developed and tested concepts of a goal-directed health education, a stable and continuous implementation is missing. In this field free-practising physicians can support public health efforts. In the area Bruchsal/Ostringen it is demonstrated, that especially those primary care physicians, who work according to the "Three-Level-Concept of Free-Practising Physicians", can successfully use their geographical and social proximity to schools in their neighbourhood for a log-lasting implementation of recurring health-related activities. Within ten years 1389 students in schools, further ca. 500 outside schools, were directly included in interactive learning in the framework of preventive measures, e.g. during school health days. 10 physicians (4 of them continuously) cooperated in these activities, which had been planned in close collaboration with teachers and parents, considering the different age groups. From the very beginning--although sometimes limited in scale--each activity was evaluated. Pupils in the age group 10-12 years generally showed the highest interest in health-related diet, 17-26% were physically more active. Promising are the results with respect to smoking: one fifth of the smoking students intended to quit as a consequence of the health activities in their schools.

Fludarabine Melphalan reduced-intensity conditioning allotransplanation provides similar disease control in lymphoid and myeloid malignancies: analysis of 344 patients.

This was an Australasian Bone Marrow Transplant Recipient Registry (ABMTRR)-based retrospective study assessing the outcome of Fludarabine Melphalan (FluMel) reduced-intensity conditioning between 1998 and 2008. Median follow-up was 3.4 years. There were 344 patients with a median age of 54 years (18-68). In all, 234 patients had myeloid malignancies, with AML (n=166) being the commonest indication. There were 110 lymphoid patients with non-hodgkins lymphoma (NHL) (n=64) the main indication. TRM at day 100 was 14% with no significant difference between the groups. OS and disease-free survival (DFS) were similar between myeloid and lymphoid patients (57 and 50% at 3 years, respectively). There was no difference in cumulative incidence of relapse or GVHD between groups. Multivariate analysis revealed four significant adverse risk factors for DFS: donor other than HLA-identical sibling donor, not in remission at transplant, previous autologous transplant and recipient CMV positive. Chronic GVHD was associated with improved DFS in multivariate analysis predominantly due to a marked reduction in relapse (HR:0.44, P=0.003). This study confirms that FluMel provides durable and equivalent remissions in both myeloid and lymphoid malignancies. Disease stage and chronic GVHD remain important determinants of outcome for FluMel allografting.

An especial skill in elite wheelchair basketball players.

We aimed to investigate whether an especial skill is present in elite wheelchair basketball players when taking twenty shots with a regular basketball from five different distances (11 ft, 13 ft, 17 ft, & 19 ft) from the basket including the free throw line (15 ft). Twelve elite male basketball players participated. The results showed that as distance increased shot accuracy decreased in line with force by variability predictions for the 11 ft, 13 ft, 17 ft, & 19 ft distances. However, shot performance at the free throw line where players are more familiar with practicing free throw shots did not follow this trend. A linear regression line was drawn to predict performance at the free throw line based on nearer (11 ft & 13 ft) and farer (17 ft & 19 ft) distances to the basket, this was then compared to actual performance. A significant difference between actual and predicted scores was found (p<.05) supporting the presence of an especial skill. Significant positive correlations were found for the 11 ft and 17 ft distance, age, years of playing, and accumulated practice hours with performance at the 15 ft line (p<.05). These correlations imply the operation of generalization in the especial skill. This observation received support from applying a model in which shot accuracy as a function of distance was approximated by two regression lines.

Acute effects of prostaglandin E1 and E2 on vascular reactivity and blood flow in situ in the chick chorioallantoic membrane.

The chick chorioallantoic membrane (CAM) subserves gas exchange in the developing embryo and shell-less culture affords a unique opportunity for direct observations over time of individual blood vessels to pharmacologic interventions. We tested a number of lipids including prostaglandins PGE(1&2) for vascular effects and signaling in the CAM. Application of PGE(1&2) induced a decrease in the diameter of large blood vessels and a concentration-dependent, localized, reversible loss of blood flow through small vessels. The loss of flow was also mimicked by misoprostol, an agonist for 3 of 4 known PGE receptors, EP(2-4), and by U46619, a thromboxane mimetic. Selective receptor antagonists for EP(3) and thromboxane each partially blocked the response. This is a first report of the effects of prostaglandins on vasoreactivity in the CAM. Our model allows the unique ability to examine simultaneous responses of large and small vessels in real time and in vivo.

Allogeneic hematopoietic SCT as treatment option for patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): a consensus conference proposal for a standardized approach.

Allogeneic hematopoietic SCT (HSCT) has been proposed as a treatment for patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). HSCT has been performed in nine patients using different protocols with varying success. Based on this preliminary experience, participants of the first consensus conference propose a common approach to allogeneic HSCT in MNGIE. Standardization of the transplant protocol and the clinical and biochemical assessments will allow evaluation of the safety and efficacy of HSCT as well as optimization of therapy for patients with MNGIE.