Retrospective epidemiological analysis of SARS-CoV-2 wastewater surveillance and case notifications data - New South Wales, Australia, 2020.

This epidemiological study analysed SARS-CoV-2 wastewater surveillance and case notifications data to inform evidence-based public health action in NSW. We investigated measures of association between SARS-CoV-2 RNA fragments detected in wastewater samples (n = 100) and case notifications (n = 1,367, as rates per 100,000 population) within wastewater catchment areas (n = 6); and evaluated the performance of wastewater testing as a population-level diagnostic tool. Furthermore, we modelled SARS-CoV-2 RNA fragment detection in wastewater given the case notification rate using logistic regression. The odds of a viral detection in wastewater samples increased by a factor of 5.68 (95% CI: 1.51-32.1, P = 0.004) with rates of one or more notified cases within a catchment. The diagnostic specificity of wastewater viral detection results was 0.88 (95% CI: 0.69-0.97); the overall diagnostic sensitivity was 0.44 (95% CI: 0.33-0.56). The probability of a viral detection result in wastewater exceeded 50% (95% CI: 36-64%) once the case rate within a catchment exceeded 10.5. Observed results suggest that in a low prevalence setting, wastewater viral detections are a more reliable indicator of the presence of recent virus shedding cases in a catchment, than non-detect results are of the absence of cases in a catchment.

Application of QMRA to prioritise water supplies for Cryptosporidium risk in New South Wales, Australia.

A Quantitative Microbial Risk Assessment (QMRA) framework was applied to assess 312 drinking water supply systems across regional New South Wales (NSW). The framework was needed to support the implementation of a recommendation in the Australian Drinking Water Guidelines (ADWG) for appropriate treatment barriers to be operating in systems 'at risk' for Cryptosporidium. The objective was to prioritise systems so that those with the highest risk could be identified and addressed first. The framework was developed in a pilot study of 30 systems, selected to represent the range of water supplies across regional NSW. From these, source water categories were defined to represent local conditions with reference to the literature and Cryptosporidium risk factors. Values for Cryptosporidium oocyst concentration were assigned to the categories to allow quantification of the health risk from those water sources. The framework was then used to assess the risks in all 312 regional drinking water supply systems. Combining the disciplined approach of QMRA with simple catchment and treatment information and categorical risk outputs provided a useful and transparent method for prioritising systems for further investigation and potential risk management intervention. The risk rankings for drinking water supplies from this QMRA process have been used to set priorities for a large State Government funding program.

The relation between measures of explicit shame and borderline personality features in adolescent inpatients.

BACKGROUND: Shame is a highly negative emotion frequently experienced by individuals with borderline personality disorder (BPD) as well as those with internalizing or externalizing psychopathology. However, few studies have examined whether shame is related to BPD above and beyond other psychopathology. Further, although feelings of shame peak during adolescence, coinciding with the onset of BPD, very few studies have examined the relationship between shame and BPD in adolescence. Therefore, the current study examined (1) whether levels of shame differ between adolescent psychiatric inpatients with and without BPD and (2) whether borderline personality pathology accounts for additional variance in the experience of shame above and beyond internalizing and externalizing psychopathology. METHODS: Adolescent psychiatric inpatients (n = 184, 67% female, M age = 15.26) completed clinical interviews and self-report measures as well as self-report measures of three types of explicit shame: state-shame, shame-proneness, and trait-shame. RESULTS: T-tests revealed that adolescents with BPD reported significantly higher levels of each type of explicit shame. In hierarchical regression models, borderline personality features explained significant additional variance in shame-proneness and trait-shame while controlling for age, gender, and internalizing and externalizing psychopathology. LIMITATIONS: Our sample was limited by a lack of demographic diversity and healthy control group, and the study did not examine relations with unique internalizing/externalizing disorders or features of BPD. CONCLUSIONS: Our findings contribute to growing evidence that shame is an important component of BPD, particularly during adolescence, and suggest that shame should be addressed in treatment.

Contraceptive method use among HIV-positive women in a US urban outpatient clinic: an exploratory cross-sectional study.

OBJECTIVE(S): Effective contraceptive method use is important for HIV-positive women to meet fertility goals, prevent unintended pregnancy and reduce risk of vertical HIV transmission. Our objective was to evaluate factors associated with HIV-positive women's contraceptive method use at last coitus defined as more effective [Tier 1 and 2 methods (T1/2)] versus less effective [Tier 3 or no method (T3/none)] by the US Medical Eligibility Criteria for contraception use. STUDY DESIGN: HIV-positive women, recruited from an HIV clinic in Atlanta, Georgia, between 2013 and 2014, completed a survey of demographic, clinical and reproductive health characteristics surrounding contraception. We examined the relationship between survey responses and contraceptive method use at last coitus using χ2 tests and multivariate logistic regression. RESULTS: Thirty-one percent of this HIV-positive and predominantly African-American (90%) cohort reported usage of T1/2 methods. T1/2 methods use was higher among younger women [adjusted odds ratio (aOR)=.90, p=.008] and those in noncommitted relationships (aOR =.32, p=.027). Only 21% reported dual method use at last intercourse. Fifty-three percent and 31% reported having heard of the intrauterine device and implant, respectively. Misconceptions about contraception were common. CONCLUSIONS: The use of T1/2 methods was more common in this cohort than in the general African-American population, but overall use and dual method use can still be improved, particularly among older women and those in noncommitted relationships. IMPLICATIONS: As this population had low awareness and usage of T1/2 methods and expressed many misconceptions, reoccurring contraceptive counseling may be helpful. Providers should address patient-level barriers, pregnancy intentions, and the importance of dual method and T1/2 method use.

A Systematic Review of the Current Status of Safer Conception Strategies for HIV Affected Heterosexual Couples in Sub-Saharan Africa.

We conducted a systematic review of safer conception strategies (SCS) for HIV-affected couples in sub-Saharan Africa to inform evidence-based safer conception interventions. Following PRISMA guidelines, we searched fifteen electronic databases using the following inclusion criteria: SCS research in HIV-affected couples; published after 2007; in sub-Saharan Africa; primary research; peer-reviewed; and addressed a primary topic of interest (SCS availability, feasibility, and acceptability, and/or education and promotion). Researchers independently reviewed each study for eligibility using a standardized tool. We categorize studies by their topic area. We identified 41 studies (26 qualitative and 15 quantitative) that met inclusion criteria. Reviewed SCSs included: antiretroviral therapy (ART), pre-exposure prophylaxis, timed unprotected intercourse, manual/self-insemination, sperm washing, and voluntary male medical circumcision (VMMC). SCS were largely unavailable outside of research settings, except for general availability (i.e., not specifically for safer conception) of ART and VMMC. SCS acceptability was impacted by low client and provider knowledge about safer conception services, stigma around HIV-affected couples wanting children, and difficulty with HIV disclosure in HIV-affected couples. Couples expressed desire to learn more about SCS; however, provider training, patient education, SCS promotions, and integration of reproductive health and HIV services remain limited. Studies of provider training and couple-based education showed improvements in communication around fertility intentions and SCS knowledge. SCS are not yet widely available to HIV-affected African couples. Successful implementation of SCS requires that providers receive training on effective SCS and provide couple-based safer conception counseling to improve disclosure and communication around fertility intentions and reproductive health.

Parent-adolescent concordance on the Revised Diagnostic Interview for Borderlines (DIB-R) and the Childhood Interview for Borderline Personality Disorder (CI-BPD).

While the degree of concordance between parent and adolescent self-report of internalizing and externalizing pathology is well studied, virtually nothing is known about concordance in borderline pathology and the implication of parent-adolescent discrepancies for outcomes. The present study aimed to (1) examine discrepancies between parents and adolescents on two interview-based measures of borderline personality disorder (BPD)-the Revised Diagnostic Interview for Borderlines (DIB-R22 ) and the Childhood Interview for Borderline Personality Disorder (CI-BPD23 ); and (2) investigate the implications of discrepancies for clinical outcomes. Diagnostic concordance on the DIB-R and CI-BPD showed rates of 82% and 94% respectively, with lower concordance demonstrated for dimensionally scored variables. Standardized difference scores between adolescent and parent reports on both borderline measures were significantly correlated with few interview-based axis I diagnoses as reported by parents, but not adolescents themselves. Implications regarding the use of each measure for the assessment and diagnosis of borderline personality disorder are discussed. Copyright © 2017 John Wiley & Sons, Ltd.

Transcript analysis in two alfalfa salt tolerance selected breeding populations relative to a non-tolerant population.

With the growing limitations on arable land, alfalfa (a widely cultivated, low-input forage) is now being selected to extend cultivation into saline lands for low-cost biofeedstock purposes. Here, minerals and transcriptome profiles were compared between two new salinity-tolerant North American alfalfa breeding populations and a more salinity-sensitive western Canadian alfalfa population grown under hydroponic saline conditions. All three populations accumulated two-fold higher sodium in roots than shoots as a function of increased electrical conductivity. At least 50% of differentially expressed genes (p < 0.05) were down-regulated in the salt-sensitive population growing under high salinity, while expression remained unchanged in the saline-tolerant populations. In particular, most reduction in transcript levels in the salt-sensitive population was observed in genes specifying cell wall structural components, lipids, secondary metabolism, auxin and ethylene hormones, development, transport, signalling, heat shock, proteolysis, pathogenesis-response, abiotic stress, RNA processing, and protein metabolism. Transcript diversity for transcription factors, protein modification, and protein degradation genes was also more strongly affected in salt-tolerant CW064027 than in salt-tolerant Bridgeview and salt-sensitive Rangelander, while both saline-tolerant populations showed more substantial up-regulation in redox-related genes and B-ZIP transcripts. The report highlights the first use of bulked genotypes as replicated samples to compare the transcriptomes of obligate out-cross breeding populations in alfalfa.

Factors associated with sterilization among HIV-positive US women in an urban outpatient clinic.

This cross-sectional study sought to determine factors associated with sterilization among HIV-positive US women. HIV-positive women aged 18-45 completed an Audio Computer Assisted Self Interview (ACASI) questionnaire. Chi-square tests and multivariable logistic regression evaluated factors associated with sterilization. The median age of the 187 participants was 37, the majority had at least a high school education, and 88% were African American. Nearly a quarter (22%) of women had undergone sterilization at an average age of 25; of these women, 71% cited their HIV-positive status as an important factor in deciding to have a tubal ligation, 22% expressed desire for future children, 32% reported sterilization regret, and 20% reported feeling pressure to undergo sterilization. In multivariable analysis, factors significantly associated with sterilization included non-African American race, no desire for future pregnancy, having heard of any birth control methods making it harder to get pregnant in the future, belief that women should take a break from hormonal methods every few years, and having had a child born with HIV. While almost a quarter of this HIV-positive group was sterilized, many during the height of the early HIV epidemic, a large proportion of sterilized women expressed sterilization regret. Counseling messages for sterilized HIV-positive women should be sensitive to the fact that women may have regret regarding a decision that, in some cases, may historically have been part of provider recommendations to prevent vertical transmission of HIV. Improved knowledge about contraceptive options such as the IUD and implant is needed among HIV-positive women.

Growth of elaborate microbial pinnacles in Lake Vanda, Antarctica.

Microbial pinnacles in ice-covered Lake Vanda, McMurdo Dry Valleys, Antarctica, extend from the base of the ice to more than 50 m water depth. The distribution of microbial communities, their photosynthetic potential, and pinnacle morphology affects the local accumulation of biomass, which in turn shapes pinnacle morphology. This feedback, plus environmental stability, promotes the growth of elaborate microbial structures. In Lake Vanda, all mats sampled from greater than 10 m water depth contained pinnacles with a gradation in size from <1-mm-tall tufts to pinnacles that were centimeters tall. Small pinnacles were cuspate, whereas larger ones had variable morphology. The largest pinnacles were up to ~30 cm tall and had cylindrical bases and cuspate tops. Pinnacle biomass was dominated by cyanobacteria from the morphological and genomic groups Leptolyngbya, Phormidium, and Tychonema. The photosynthetic potential of these cyanobacterial communities was high to depths of several millimeters into the mat based on PAM fluorometry, and sufficient light for photosynthesis penetrated ~5 mm into pinnacles. The distribution of photosynthetic potential and its correlation to pinnacle morphology suggests a working model for pinnacle growth. First, small tufts initiate from random irregularities in prostrate mat. Some tufts grow into pinnacles over the course of ~3 years. As pinnacles increase in size and age, their interiors become colonized by a more diverse community of cyanobacteria with high photosynthetic potential. Biomass accumulation within this subsurface community causes pinnacles to swell, expanding laminae thickness and creating distinctive cylindrical bases and cuspate tops. This change in shape suggests that pinnacle morphology emerges from a specific distribution of biomass accumulation that depends on multiple microbial communities fixing carbon in different parts of pinnacles. Similarly, complex patterns of biomass accumulation may be reflected in the morphology of elaborate ancient stromatolites.

[Evaluation of sulfur status in dairy cows in Germany]. / Untersuchungen zur Schwefelversorgung von Milchkühen in Deutschland.

OBJECTIVE: Sulfur deficiency and toxicity in livestock is associated with decreased performance and diseases. However, little is known about the diagnostics of sulfur status in dairy herds. The objectives of this study were to describe sulfur concentrations in feed rations in German dairy herds, to assess associations between feed sulfur concentrations and health and milk yield, to determine suitable laboratory diagnostic methods of sulfur status, and to propose reference values for the assessment of sulfur status in different sample media. MATERIALS AND METHODS: Between 2006 and 2014, a total of 569 dairy herds were visited. Blood, urine, and hair samples were obtained from 10 animals per group in the groups -3 to 0, 0 to 1, 3 to 5, and 15 to 18 weeks post partum (p. p.) (farms > 200 animals) or -3 to 0, 0 to 5, and 6 to 20 weeks p. p. (farms ≤ 200 animals). Pooled whole blood, serum, plasma, urine, and hair samples (n = 5663) were analyzed by ICP-OES. The sulfur content of the total mixed ration (TMR) of the group -3 to 0 weeks p. p. was determined in a certified feed laboratory (n = 625). Data analyses were performed using ANOVA, Chi-squared test and Spearman-correlation. Reference values were determined using the 2.5% and 97.5% percentiles. RESULTS: Median sulfur concentration in the feed rations was 2.3 g/kg dry matter (DM). Deficiency (< 1.6 g/kg DM; 31% of farms) and oversupply (> 4.0 g/kg DM; 11% of farms) of sulfur in feed rations were regularly diagnosed. Sulfur deficiency was associated with reduced milk yield (p  <   0.001), retained placenta (OR  =   1.74; p  =  0.037), milk fever (OR  =  2.68; p  <  0.001) and silent heat (OR  = 2.56; p   =  0.014). Positive correlations were found between sulfur concentration in feed rations and sulfur content in urine (r  =  0.50), serum (r  =  0.17), plasma (r  =  0.18) and whole blood (r = 0.16). Reference values for sulfur diagnostics in dairy herds were proposed. CONCLUSION AND CLINICAL RELEVANCE: Diagnostics of sulfur status in dairy herds is relevant for veterinary practitioners and can be performed using TMR analysis and clinical laboratory parameters. Urine can be considered a short-term parameter, serum, plasma, and whole blood as intermediate parameters, and hair as a long-term parameter for the evaluation of the sulfur status.

Acceptance of treatment for latent tuberculosis infection: prospective cohort study in the United States and Canada.

SETTING: An estimated 300 000 individuals are treated for latent tuberculosis infection (LTBI) in the United States and Canada annually. Little is known about the proportion or characteristics of those who decline treatment. OBJECTIVE: To define the proportion of individuals in various groups who accept LTBI treatment and to identify factors associated with non-acceptance of treatment. DESIGN: Persons offered LTBI treatment at 30 clinics in 12 Tuberculosis Epidemiologic Studies Consortium sites were prospectively enrolled. Multivariate regression models were constructed based on manual stepwise assessment of potential predictors. RESULTS: Of 1692 participants enrolled from March 2007 to September 2008, 1515 (89.5%) accepted treatment and 177 (10.5%) declined. Predictors of acceptance included believing one could personally spread TB germs, having greater TB knowledge, finding clinic schedules convenient and having low acculturation. Predictors of non-acceptance included being a health care worker, being previously recommended for treatment and believing that taking medicines would be problematic. CONCLUSION: This is the first prospective multisite study to examine predictors of LTBI treatment acceptance in general clinic populations. Greater efforts should be made to increase acceptance among health care workers, those previously recommended for treatment and those who expect problems with LTBI medicines. Ensuring convenient clinic schedules and TB education to increase knowledge could be important for ensuring acceptance.

Azacitidine fails to eradicate leukemic stem/progenitor cell populations in patients with acute myeloid leukemia and myelodysplasia.

Epigenetic therapies demonstrate significant clinical activity in acute myeloid leukemia (AML) and myelodysplasia (MDS) and constitute an important new class of therapeutic agents. However hematological responses are not durable and disease relapse appears inevitable. Experimentally, leukemic stem/progenitor cells (LSC) propagate disease in animal models of AML and it has been postulated that their relative chemo-resistance contributes to disease relapse. We serially measured LSC numbers in patients with high-risk AML and MDS treated with 5'-azacitidine and sodium valproate (VAL-AZA). Fifteen out of seventy-nine patients achieved a complete remission (CR) or complete remission with incomplete blood count recovery (CRi) with VAL-AZA therapy. There was no significant reduction in the size of the LSC-containing population in non-responders. While the LSC-containing population was substantially reduced in all patients achieving a CR/CRi it was never eradicated and expansion of this population antedated morphological relapse. Similar studies were performed in seven patients with newly diagnosed AML treated with induction chemotherapy. Eradication of the LSC-containing population was observed in three patients all of whom achieved a durable CR in contrast to patients with resistant disease where LSC persistence was observed. LSC quantitation provides a novel biomarker of disease response and relapse in patients with AML treated with epigenetic therapies. New drugs that target this cellular population in vivo are required.

A quantitative descriptive study of the prevalence of carriage (colonisation) of haemolytic streptococci groups A, B, C and G in pregnancy.

Invasive group B streptococcus (GBS) disease is a leading cause of neonatal death. There is no UK national screening programme for GBS in pregnancy, hence colonisation rates are unknown. Intrapartum antibiotic prophylaxis is given during labour to colonised women to reduce neonatal GBS transmission and subsequent invasive infection. Data about prevalence of other haemolytic streptococci in pregnancy, including group A streptococcus (GAS), are uncommon despite increasing importance. This study investigated colonisation in 100 pregnant women using conventional culture methods; 19% had GBS. This suggests that GBS carriage is common in the UK. The role of other ß-haemolytic streptococci remains undefined.

Increased fat mass and cardiac septal hypertrophy in newborn infants of mothers with well-controlled diabetes during pregnancy.

BACKGROUND: Improved glycaemic control during pregnancy in mothers with type 1 diabetes (T1DM) and gestational diabetes (GDM) has resulted in a marked reduction of perinatal mortality and morbidity, but the prevalence of macrosomia is usually high. OBJECTIVE: We used non-invasive anthropometric methods to estimate the body composition and the thickness of the interventricular heart septum in 18 infants of mothers with well-controlled T1DM, 10 infants of mothers with GDM and 28 infants of healthy control mothers matched for gestational age and mode of delivery. METHODS: Skinfold measurements were obtained with a Harpenden calliper within 48 h after delivery. Echocardiography was also performed to measure the thickness of the interventricular septum. Cord blood was sampled for assays of C-peptide, leptin and IGF-I. RESULTS: The rates of macrosomia (gestational age-adjusted birth weight >2 standard deviation score, SDS) were 56 and 30% in infants of mothers with T1DM and GDM, respectively, compared to 10% in control infants. The body fat content was 40% (0.2 kg) higher and the interventricular heart septum thickness was increased by 20% in both groups of infants of diabetic mothers. We found no associations between maternal levels of HbA1c during pregnancy and body composition or interventricular heart septum thickness. Cord levels of C-peptide and leptin were significantly higher in infants of T1DM mothers than in control infants. Cord leptin level was associated with birth weight SDS and percent body fat in infants of T1DM mothers. IGF-I was associated with percent body fat in infants of GDM mothers and control mothers. A multiple-regression analysis showed that 50% of the variation in body weight SDS could be determined, with IGF-I, leptin and C-peptide as independent variables. CONCLUSION: Both fat mass and cardiac septal thickness are increased in newborn infants of women with T1DM and GDM in spite of efforts to achieve good glycaemic control during pregnancy.

Formal selection of measures for a composite index of NICU quality of care: Baby-MONITOR.

OBJECTIVE: To systematically rate measures of care quality for very low birth weight infants for inclusion into Baby-MONITOR, a composite indicator of quality. STUDY DESIGN: Modified Delphi expert panelist process including electronic surveys and telephone conferences. Panelists considered 28 standard neonatal intensive care unit (NICU) quality measures and rated each on a 9-point scale taking into account pre-defined measure characteristics. In addition, panelists grouped measures into six domains of quality. We selected measures by testing for rater agreement using an accepted method. RESULT: Of 28 measures considered, 13 had median ratings in the high range (7 to 9). Of these, 9 met the criteria for inclusion in the composite: antenatal steroids (median (interquartile range)) 9(0), timely retinopathy of prematurity exam 9(0), late onset sepsis 9(1), hypothermia on admission 8(1), pneumothorax 8(2), growth velocity 8(2), oxygen at 36 weeks postmenstrual age 7(2), any human milk feeding at discharge 7(2) and in-hospital mortality 7(2). Among the measures selected for the composite, the domains of quality most frequently represented included effectiveness (40%) and safety (30%). CONCLUSION: A panel of experts selected 9 of 28 routinely reported quality measures for inclusion in a composite indicator. Panelists also set an agenda for future research to close knowledge gaps for quality measures not selected for the Baby-MONITOR.

Floral transmission of Erwinia tracheiphila by cucumber beetles in a wild Cucurbita pepo.

Cucumber beetles, Acalymma vittatum (F.) and Diabrotica undecipunctata howardi (Barber), are specialist herbivores of cucurbits and the vector of Erwinia tracheiphila (E.F. Smith) Holland, the causative agent of wilt disease. Cucumber beetles transmit E. tracheiphila when infected frass falls onto leaf wounds at the site of beetle feeding. We show that E. tracheiphila also can be transmitted via the floral nectaries of Cucurbita pepo ssp. texana L. Andres (Texas gourd). Under field conditions, we found that beetles aggregate in flowers in the late morning, that these beetles chew the anther filaments that cover the nectaries in male flowers thereby exposing the nectary, and that beetle frass accumulates on the nectary. We use real-time polymerase chain reaction to show that most of the flowers produced during the late summer possess beetle frass containing E. tracheiphila. Greenhouse experiments, in which cultures of E. tracheiphila are deposited onto floral nectaries, show that Texas gourds can contract wilt disease through the floral nectaries. Finally, we use green fluorescent protein-transformed E. tracheiphila to document the movement of E. tracheiphila through the nectary into the xylem of the pedicel before the abscission of the flower. Together, these data show that E. tracheiphila can be transmitted through infected frass that falls on or near the floral nectaries. We hypothesize that the concentration of frass from many beetles in the flowers increases both exposure to and the concentration of E. tracheiphila and plays a major role in the dynamics of wilt disease in both wild populations and cultivated squash fields.

Carbohydrate-deficient transferrin in vitreous humour: a marker of possible withdrawal-related death in alcoholics.

The possibility of performing reliable post-mortem analysis of carbohydrate-deficient transferrin (CDT) concentration in vitreous humour (VH) by using a commercial assay designed for serum analysis (CDTect(TM)) as well as the usefulness of VH-CDT as a marker of alcohol misuse and possible withdrawal-related death were evaluated in a forensic sample. Detectable VH-CDT was found in 20 of 21 alcoholic subjects and in two of seven controls. By using the detection limit of the CDTect(TM) method (VH-CDT = 5 U/l) as cut-off level for a positive test, the alcoholic group was significantly separated from the control group (P = 0.0024, Fisher's exact test). The sensitivity and specificity of the test was 95% and 71%, giving a positive and a negative predictive value of 91% and 83%, respectively. Time-dependent changes of VH-CDT in the dead body could not unequivocally be excluded, which must be considered when selecting cases suitable for VH-CDT analysis. We conclude that adding VH-CDT analysis to ordinary alcohol tests may become useful in forensic medicine for establishing the so-called 'alcoholic state', which may provide a tool in research dealing with the relation between alcohol withdrawal and various causes of death in alcoholics.

Quality of life 20 and 30 years after surgery in patients operated on for tetralogy of Fallot and for atrial septal defect.

Follow-up studies on patients operated on for congenital heart defects have shown good anatomical results and long-term survival. To date, there have been few studies on such patients with regard to long-term psychosocial outcome and quality of life. In this study, two cohorts of patients operated on before the age of 15 years, one for tetralogy of Fallot (TOF) and the other for atrial septal defect (ASD), were investigated 20 and 30 years after operation regarding quality of life. The combined cohort had a higher educational level than average. There was no connection between quality of life and physical health as judged from the New York Heart Association classification. The TOF group rated their quality of life higher than the ASD group, but both groups had lower figures at the 30-year than at the 20-year follow-up. Fewer patients in the TOF than in the ASD group considered that their lives were affected by the heart disease. It is concluded that the severity of the heart disease is not necessarily congruent with estimated quality of live and that mild heart defects, such as ASD, can have a considerable impact on later life quality. Surprisingly few TOF patients were affected negatively, a finding which might reflect development of a specific coping strategy in these patients during childhood.

Dose-response of retinoic acid induced stress protein synthesis and teratogenesis in mice.

Stress proteins are synthesized in response to a variety of stressors, including several teratogenic agents. However, their role, if any, in the teratogenic process is unknown. We have previously demonstrated that all-trans-retinoic acid administered to pregnant CD-1 mice on gestational day 11 or 13 produced limb defects and cleft palate near term in a dose-responsive manner. This chemical also induced the synthesis of several nuclear stress proteins in embryonic tissues within several hours of dosing. The stress proteins were only observed in tissues that eventually became malformed and not in tissues that appeared normal at term. In the current work, we examined the stress response in embryonic target tissues after several different doses of retinoic acid. The nuclear stress proteins were synthesized in a dose-related manner and at a lower retinoic acid dose than doses producing malformations in the corresponding tissue at birth. Each individual stress protein and the total stress protein response were highly correlated, across dose, with the respective malformations observed at term.