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Thyroid hormones are essential for metabolism and growth in almost all tissues. In reproduction, thyroid hormones affect steroidogenesis, ovulation, implantation, placental vascularisation and the maintenance of pregnancy and neurocognitive development of the child. The thyroid and reproductive axis are closely intertwined. Prior to describing early-pregnant thyroid physiology, non-pregnant thyroid physiology and its environmental influences, the interaction of the hypothalamic-pituitary-thyroid- and -ovarian axis and the action of thyroid hormones on the reproductive organs are described. In the foetus, the thyroid is the first endocrine gland to develop from 5 weeks of gestation, with a functional pituitary axis around week 20, but only fully mature at birth. For the rapid neuronal proliferation and growth, thyroid hormone receptors are present in the fetal brain from around 8-9 weeks of gestation. The foetus depends on the mothers thyroid hormone supply until 20 weeks of gestation.
The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.
Design:
The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance.
Methods:
MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.
Results:
Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O3.
Conclusions:
MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.
To examine the factors that are associated with changes in depression in people with type 2 diabetes living in 12 different countries.
Methods
People with type 2 diabetes treated in out-patient settings aged 18–65 years underwent a psychiatric assessment to diagnose major depressive disorder (MDD) at baseline and follow-up. At both time points, participants completed the Patient Health Questionnaire (PHQ-9), the WHO five-item Well-being scale (WHO-5) and the Problem Areas in Diabetes (PAID) scale which measures diabetes-related distress. A composite stress score (CSS) (the occurrence of stressful life events and their reported degree of ‘upset’) between baseline and follow-up was calculated. Demographic data and medical record information were collected. Separate regression analyses were conducted with MDD and PHQ-9 scores as the dependent variables.
Results
In total, there were 7.4% (120) incident cases of MDD with 81.5% (1317) continuing to remain free of a diagnosis of MDD. Univariate analyses demonstrated that those with MDD were more likely to be female, less likely to be physically active, more likely to have diabetes complications at baseline and have higher CSS. Mean scores for the WHO-5, PAID and PHQ-9 were poorer in those with incident MDD compared with those who had never had a diagnosis of MDD. Regression analyses demonstrated that higher PHQ-9, lower WHO-5 scores and greater CSS were significant predictors of incident MDD. Significant predictors of PHQ-9 were baseline PHQ-9 score, WHO-5, PAID and CSS.
Conclusion
This study demonstrates the importance of psychosocial factors in addition to physiological variables in the development of depressive symptoms and incident MDD in people with type 2 diabetes. Stressful life events, depressive symptoms and diabetes-related distress all play a significant role which has implications for practice. A more holistic approach to care, which recognises the interplay of these psychosocial factors, may help to mitigate their impact on diabetes self-management as well as MDD, thus early screening and treatment for symptoms is recommended.
Cognitive disturbances are common and disabling features of major depressive disorder (MDD). Previous studies provide limited insight into the co-occurrence of hot (emotion-dependent) and cold (emotion-independent) cognitive disturbances in MDD. Therefore, we here map both hot and cold cognition in depressed patients compared to healthy individuals.
Methods
We collected neuropsychological data from 92 antidepressant-free MDD patients and 103 healthy controls. All participants completed a comprehensive neuropsychological test battery assessing hot cognition including emotion processing, affective verbal memory and social cognition as well as cold cognition including verbal and working memory and reaction time.
Results
The depressed patients showed small to moderate negative affective biases on emotion processing outcomes, moderate increases in ratings of guilt and shame and moderate deficits in verbal and working memory as well as moderately slowed reaction time compared to healthy controls. We observed no correlations between individual cognitive tasks and depression severity in the depressed patients. Lastly, an exploratory cluster analysis suggested the presence of three cognitive profiles in MDD: one characterised predominantly by disturbed hot cognitive functions, one characterised predominantly by disturbed cold cognitive functions and one characterised by global impairment across all cognitive domains. Notably, the three cognitive profiles differed in depression severity.
Conclusion
We identified a pattern of small to moderate disturbances in both hot and cold cognition in MDD. While none of the individual cognitive outcomes mapped onto depression severity, cognitive profile clusters did. Overall cognition-based stratification tools may be useful in precision medicine approaches to MDD.
OBJECTIVES/SPECIFIC AIMS: The aims of this study are 2-fold: (1) to determine if maternal schistosomiasis affects maternal immunity to tetanus and/or transplacental transfer of antitetanus toxoid (TT) immunoglobulin G (IgG) from mother to infant and (2) determine the influence of maternal schistosomiasis on infant BCG vaccine immunogenicity. METHODS/STUDY POPULATION: The study will utilize blood samples from a historic cohort of 100 mother-infant pairs from Kisumu, Kenya, a schistosomiasis-endemic area. For the first aim, we will evaluate maternal schistosomal circulating anodic antigen, which has improved sensitivity and specificity to detect active schistosomiasis from serum, and antisoluble egg antigen IgG positivity compared with quantitative maternal anti-TT IgG at delivery and anti-TT IgG cord blood to maternal blood ratio (cord:maternal ratio). For the second aim, we will evaluate association between maternal schistosomiasis as detected by circulating anodic antigen and antisoluble egg antigen IgG at delivery and infant BCG-specific Th1-cytokine positive CD4+ cells at 10 weeks following BCG vaccination at birth. RESULTS/ANTICIPATED RESULTS: We hypothesize that active maternal schistosomiasis will be associated with decreased maternal anti-TT IgG and reduced efficiency of transplacental transfer, as measured by infant cord blood to maternal blood ratio of anti-TT IgG. We also expect that maternal schistosomiasis will be associated with decreased infant immunogenicity to BCG vaccine. DISCUSSION/SIGNIFICANCE OF IMPACT: This is a formative study on infant vaccine immunity using laboratory methodology not previously applied. Understanding infant immunity in the setting of maternal schistosomiasis will inform vaccination strategies and tailor vaccine development in schistosome-endemic areas such as Kenya, where neither TB nor neonatal tetanus have been eradicated. Additionally, our results will inform public health policies to consider integration of antischistosomal agents in antenatal care.
Day hospital mentalization-based treatment (MBT-DH) is a promising treatment for borderline personality disorder (BPD) but its evidence base is still limited. This multi-site randomized trial compared the efficacy of MBT-DH delivered by a newly set-up service v. specialist treatment as usual (S-TAU) tailored to the individual needs of patients, and offered by a well-established treatment service.
Methods
Two mental healthcare institutes in The Netherlands participated in the study. Patients who met DSM-IV criteria for BPD and had a score of ⩾20 on the borderline personality disorder severity index (BPDSI) were randomly allocated to MBT-DH (N = 54) or S-TAU (N = 41). The primary outcome variable was the total score on the BPDSI. Secondary outcome variables included symptom severity, quality of life, and interpersonal functioning. Data were collected at baseline and every 6 months until 18-month follow-up, and were analyzed using multilevel analyses based on intention-to-treat principles.
Results
Both treatments were associated with significant improvements in all outcome variables. MBT-DH was not superior to S-TAU on any outcome variable. MBT-DH was associated with higher acceptability in BPD patients compared v. S-TAU, reflected in significantly higher early drop-out rates in S-TAU (34%) v. MBT-DH (9%).
Conclusions
MBT-DH delivered by a newly set-up service is as effective as specialist TAU in The Netherlands in the treatment of BPD at 18-month follow-up. Further research is needed to investigate treatment outcomes in the longer term and the cost-effectiveness of these treatments.
Data on gender-specific profiles of cognitive functions in patients with Parkinson's disease (PD) are rare and inconsistent, and possible disease-confounding factors have been insufficiently considered.
Method
The LANDSCAPE study on cognition in PD enrolled 656 PD patients (267 without cognitive impairment, 66% male; 292 with mild cognitive impairment, 69% male; 97 with PD dementia, 69% male). Raw values and age-, education-, and gender-corrected Z scores of a neuropsychological test battery (CERAD-Plus) were compared between genders. Motor symptoms, disease duration, l-dopa equivalent daily dose, depression - and additionally age and education for the raw value analysis - were taken as covariates.
Results
Raw-score analysis replicated results of previous studies in that female PD patients were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.03), while men outperformed women in visuoconstruction (p = 0.002) and figural memory (p = 0.005). In contrast, gender-corrected Z scores showed that men were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.02; recognition, p = 0.04), while no difference was found for visuospatial tests. This picture could be observed both in the overall analysis of PD patients as well as in a differentiated group analysis.
Conclusions
Normative data corrected for gender and other sociodemographic variables are relevant, since they may elucidate a markedly different cognitive profile compared to raw scores. Our study also suggests that verbal memory decline is stronger in women than in men with PD. Future studies are needed to replicate these findings, examine the progression of gender-specific cognitive decline in PD and define different underlying mechanisms of this dysfunction.
Increased substitution of marine ingredients by terrestrial plant products in aquafeeds has been proven to be suitable for Atlantic salmon farming. However, a reduction in n-3 long-chain PUFA is a consequence of this substitution. In contrast, relatively little attention has been paid to the effects of fishmeal and oil substitution on levels of micronutrients such as Se, considering fish are major sources of this mineral for human consumers. To evaluate the effects of dietary marine ingredient substitution on tissue Se distribution and the expression of Se metabolism and antioxidant enzyme genes, Atlantic salmons were fed three feeds based on commercial formulations with increasing levels of plant proteins (PP) and vegetable oil. Lipid content in flesh did not vary at any sampling point, but it was higher in the liver of 1 kg of fish fed higher PP. Fatty acid content reflected dietary input and was related to oxidation levels (thiobarbituric acid-reactive substances). Liver had the highest Se levels, followed by head kidney, whereas the lowest contents were found in brain and gill. The Se concentration of flesh decreased considerably with high levels of substitution, reducing the added value of fish consumption. Only the brain showed significant differences in glutathione peroxidase, transfer RNA selenocysteine 1-associated protein 1b and superoxide dismutase expression, whereas no significant regulation of Se-related genes was found in liver. Although Se levels in the diets satisfied the essential requirements of salmon, high PP levels led to a reduction in the supply of this essential micronutrient.
To examine the association between urinary excretion of isoflavonoids and risk of type 2 diabetes (T2D), we conducted a nested case–control study among 1111 T2D pairs identified during 1995–2008 in the Nurses’ Health Study (NHS) and NHSII, who were free of diabetes, CVD and cancer at urine sample collection. Urinary excretion of daidzein and genistein, as well as their metabolites O-desmethylangolensin (O-DMA), dihydrogenistein (DHGE) and dihydrodaidzein (DHDE) was assayed using liquid chromatography MS. Self-reported T2D incident cases were confirmed using a validated questionnaire. Higher urinary excretion of daidzein and genistein was associated with a lower risk of T2D in the combined cohorts. Comparing extreme tertiles of the urinary markers, the OR of T2D were 0·71 (95 % CI 0·55, 0·93) for daidzein and 0·74 (95 % CI 0·56, 0·97) for genistein, although the test for linear trend was not significant for genistein (Ptrend=0·03 and 0·15, respectively). DMA, DHDE and DHGE were non-significantly associated with a lower T2D risk. The inverse association of daidzein with T2D risk was stronger among post-menopausal women who did not use hormone replacement therapy (Pinteraction=0·001): the OR was 0·58 (95 % CI 0·34, 0·97) comparing extreme tertiles among these women. In conclusion, urinary excretion of isoflavones was associated with a lower T2D risk in US women, especially among post-menopausal women who did not use hormone. Further research is warranted to replicate these observations among western populations with similarly low overall isoflavone intake.
Patients with a lower respiratory tract infection (LRTI) might be at risk for long-term impaired health status. We assessed whether LRTI patients without Q fever are equally at risk for developing long-term symptoms compared to LRTI patients with Q fever. The study was a cross-sectional cohort design. Long-term health status information of 50 Q fever-positive and 32 Q fever-negative LRTI patients was obtained. Health status was measured by the Nijmegen Clinical Screening Instrument. The most severely affected subdomains of the Q fever-positive group were ‘general quality of life’ (40%) and ‘fatigue’ (40%). The most severely affected subdomains of the Q fever-negative group were ‘fatigue’ (64%) and ‘subjective pulmonary symptoms’ (35%). Health status did not differ significantly between Q fever-positive LRTI patients and Q fever-negative LRTI patients for all subdomains, except for ‘subjective pulmonary symptoms’ (P = 0·048).
The hydrogenation of metals often leads to changes in optical properties in the visible range. This allows for fundamental studies of the hydrogenation process, as well as the exploration of various applications using these optical effects. Here, we focus on recent developments in metal hydride-based optical fiber and plasmonic sensors and smart windows. Both applications benefit from the existence of a reflective metallic state, which is lost on hydrogenation and allows for large reversible optical changes. In this article, we review the status of both technologies and their prospects for applications.
The seasonality hypothesis states that climates characterized by large annual cycles select for large body sizes. In order to study the effects of seasonality on the evolution of body size, we use a model that is based on physiological rules and first principles. At the ecological time scale, our model results show that both larger productivity and seasonality may lead to larger body sizes. Our model is the first dynamic and process-based model to support the seasonality hypothesis and hence demonstrates the importance of basing models on physiological processes. We focus not only on variability at the ecological time scale, but also on the temporal variations in seasonality existing at geological time scales. A particularly strong forcing of seasonality exists on the scale of 20,000-400,000 years, the scale of Milankovitch cycles. Therefore, we simulated the evolutionary response of body size to a Milankovitch-type of forcing of climate and food density. Results illustrate that for a given level of investment in reserves body size may track climatic cycles, and that below a certain seasonality threshold the body size will decrease rapidly, leading to extinction.
In The Netherlands, a national programme for the surveillance of zoonotic bacteria in farm animals has been operative since 1997. We describe the results of the surveillance of Salmonella spp. in flocks of laying hens and broilers and of Campylobacter spp. in broiler flocks in the period 1999–2002. The prevalence of Salmonella spp. in laying-hen flocks has significantly decreased from 21·1% in 1999 to 13·4% in 2002. This decreasing trend might indicate that the control measures taken by the poultry industry were effective. S. Enteritidis was the predominant serovar in laying hens accounting for one third of the positive flocks. Although prevalence estimates for Salmonella spp. in broiler flocks did not yield a significant decreasing trend in 1999–2002, a decrease in Salmonella prevalence to 11% was measured in 2002. During the study period, S. Paratyphi B var. Java emerged in broilers to become the predominant serovar in 2002 accounting for one third of the positive flocks. The prevalence of Campylobacter spp. in broiler flocks did not increase nor decrease continuously between 1999 and 2002, which roughly corresponds with the monitoring results from the poultry industry. In this period, the estimated flock prevalence roughly averaged around 20%, with C. jejuni being the predominant species. The approach of monitoring presented in this paper can serve as a blueprint for monitoring schemes in farm animal populations to be developed in the context of the EC Zoonoses Directive.
The body condition of the gilt at first mating may have a significant effect upon its lifetime reproductive performance. (Gueblez et al, 1985). Gaughan et al (1995), have recently demonstrated that gilts with low backfat thickness (9- 13mm) had fewer litters and weaned fewer piglets than gilts with medium (14-16mm) and high (>17mm) levels. The extent to which variations in both body weight and backfat thickness of gilts at first mating influence long-term reproductive efficiency has been further investigated in a commercial trial at the JSR Commercial Development Unit, Catwick. The overall objective of the trial was to assess the long-term performance of modern pig genotypes under commercial conditions.
We provide evidence that non-stoichiometric ablation of YBa2Cu3O7δ at low fluences is due to a phase separation of the target surface. On the other hand, in SrTiO3 we find at low fluences evidence for preferential ablation which is assisted by volume-diffusion. As a result, the Sr/Ti ratio of the ablated films can be tuned by choosing the appropriate fluence.
Weaning is a considerable challenge to the young piglet and represents the beginning of a critical period in its life. It is also the period which has a significant effect upon both short- and long-term growth and development. Rapid early growth results in higher and more efficient growth in the subsequent growing and finishing periods. Indeed, it is a common commercial experience that the ability to produce quality lean carcases from fast-growing modern genotypes is enhanced by rapid post-weaning growth. The objective of the current trial was to measure the performance and growth potential of modern pig genotypes in the 5-week post-weaning period, when offered non-limiting diets under commercial conditions.
There is evidence to suggest that individual pigs can differentiate and choose successfully between diets on the basis of their nutrient composition and change the proportion of the diet consumed to meet their changing nutritional requirements. Choice feeding may therefore provide an effective means of meeting the differing nutritional requirements of individual animals within a group and offers considerable productivity, dietary, managemental, welfare and environmental advantages. The present trial was therefore developed to establish the ability of young piglets to select their diet in the 5-week period following weaning and to examine the potential of choice feeding as a method of feeding piglets under commercial conditions.
The resistive transition of a preferentially oriented thin film of Y2Ba4Cu8O16‐δ has been measured in fields up to 20 T oriented parallel to the c‐axis. The data can be analysed in terms of thermally activated flux flow and flux pinning due to dislocation lines. The analysis yields the upper critical field Bc2 which shows an unusual upward curvature at low temperatures. Furthermore an estimate can be made of the correlation length Lc of the flux line lattice in the field direction. Lc is found to be very small, however, remaining larger than the Cu02 plane distance.
High Tc superconducting thin films were prepared by DC triode sputtering and laser ablation. With both deposition methods we were able to fabricate thin films on SrTiO3 which show an onset at Tcf=92 K. The superconductive transition is complete at Tcf=86 K. On other substrates like Al2O3, MgO and ZrO2 relatively poor results were obtained.