Flourishing During the COVID-19 Pandemic: A Longitudinal Study in South Africa.

In this longitudinal study, we examine changes in psychological distress and multidimensional well-being from before to during the COVID-19 pandemic among South African adults. As a secondary purpose, we explore whether pre-pandemic flourishing is protective against subsequent psychological distress during the public health crisis. The analytic sample (n = 293; Mage = 44.27, SD = 14.28; female = 65.19%) completed measures of anxiety symptoms, depression symptoms, and well-being shortly before the stringent nationwide lockdown started in South Africa (T1). A follow-up assessment was completed approximately 6 months later (T2). Paired samples t-tests supported very small improvements in anxiety (d = -0.09) and depression symptoms (d = -0.13). For domains of well-being, small increases were found in close social relationships (d = 0.25) and financial and material stability (d = 0.19). Positive changes in the domains of character and virtue (d = 0.10) and meaning and purpose (d = 0.07) were very small. Changes in physical and mental health (d = -0.03) and life satisfaction and happiness (d = 0.02) were more negligible. Results from the generalized linear models indicated that continuous scores of secure flourishing assessed before the COVID-19 pandemic were associated with lower subsequent psychological distress (particularly depression symptoms) during the public health crisis. We discuss the implications of the findings for the development and delivery of interventions to promote and sustain human flourishing during public health crises, especially in contexts of social-structural vulnerability.

Gain of 20q11.21 in Human Pluripotent Stem Cells Impairs TGF-ß-Dependent Neuroectodermal Commitment.

Gain of 20q11.21 is one of the most common recurrent genomic aberrations in human pluripotent stem cells. Although it is known that overexpression of the antiapoptotic gene Bcl-xL confers a survival advantage to the abnormal cells, their differentiation capacity has not been fully investigated. RNA sequencing of mutant and control hESC lines, and a line transgenically overexpressing Bcl-xL, shows that overexpression of Bcl-xL is sufficient to cause most transcriptional changes induced by the gain of 20q11.21. Moreover, the differentially expressed genes in mutant and Bcl-xL overexpressing lines are enriched for genes involved in TGF-ß- and SMAD-mediated signaling, and neuron differentiation. Finally, we show that this altered signaling has a dramatic negative effect on neuroectodermal differentiation, while the cells maintain their ability to differentiate to mesendoderm derivatives. These findings stress the importance of thorough genetic testing of the lines before their use in research or the clinic.

An induction or flare of arthritis and/or sacroiliitis by vedolizumab in inflammatory bowel disease: a case series.

BACKGROUND: In inflammatory bowel disease (IBD), a new biological therapy has recently been approved. Vedolizumab is a humanised IgG1 monoclonal antibody to α4ß7 integrin that modulates gut lymphocyte trafficking. Although an exclusively local effect of vedolizumab could be expected based on the restricted presence of the α4ß7-mucosal vascular addressin cell adhesion molecule 1 complex in the gut, past combined success with anti-tumour necrosis factor, and previous demonstration of α4ß7 integrin in the joint, led to the expectation of a therapeutic efficacy in spondyloarthritis. Nonetheless, the effect of vedolizumab on extraintestinal manifestations-and especially the joint-has not been reported so far. CASE REPORT: A series of five patients with IBD who were treated with vedolizumab and promptly developed new onset or exacerbation of sacroiliitis or arthritis are reported. CONCLUSIONS: Vedolizumab therapy does not seem to show any efficacy in and might even induce arthritis and/or sacroiliitis. However, larger cohort studies are needed to provide information on the prevalence, the evolution and underlying mechanism.

Vemurafenib-associated Dupuytren- and Ledderhose palmoplantar fibromatosis in metastatic melanoma patients.

BACKGROUND: The BRAF-inhibitor vemurafenib, used in patients with metastatic melanoma, induces multiple cutaneous side-effects. OBJECTIVE: The aim of this work was to evaluate the development of palmoplantar fibromatosis in a population of patients treated with the BRAF inhibitor vemurafenib. METHODS: Between April 2011 and February 2013, we initiated a treatment with vemurafenib in 53 patients with an unresectable stage IIIC or stage IV melanoma. The patients were followed-up on a regular base to monitor possible side-effects. RESULTS: A plantar or palmar fibromatosis was observed in five of 53 patients treated with vemurafenib. In four of these patients other risk factors for the development of palmoplantar fibromatosis were absent. CONCLUSION: The BRAF-inhibitor vemurafenib might induce palmoplantar fibromatosis.

Derivation and characterization of a cytocompatible scaffold from human testis.

STUDY QUESTION: Is it possible to derive a scaffold from human testis for the purpose of tissue engineering and regenerative medicine? SUMMARY ANSWER: We developed a method to produce a cytocompatible decellularized testicular matrix (DTM) while maintaining the native tissue-specific characteristics and components. WHAT IS KNOWN ALREADY: The potential benefits of tissue-specific scaffolds consisting of naturally-derived extracellular matrix (ECM) have been demonstrated using a wide variety of animal and human tissue sources. However, so far, testis scaffolds have never been considered for constructive remodelling purposes. STUDY DESIGN, SIZE, DURATION: Human cadaveric testicular tissue was exposed for 24 or 48 h to 1% Triton X-100 and/or 1% sodium dodecyl sulphate (SDS). Acellular samples were used for further scaffold characterization purposes. PARTICIPANTS/MATERIALS, SETTING, METHODS: The extent of decellularization was evaluated by histology. Confirmation of cell removal in DTM was done by a DNA quantification technique. Retention of testicular tissue-specific characteristics was evaluated by mass spectrometry, immunohistochemistry, Alcian blue staining and scanning electron microscopy. Soluble toxicity and testicular cell attachment was assessed to check the cytocompatibility of DTM scaffolds. MAIN RESULTS AND THE ROLE OF CHANCE: Histological analysis showed that DTM could be obtained by mechanical agitation in 1% SDS for 24 h. The resulting DTM was found to be clear of cells while retaining the typical three-dimensional structure and the major components of the native tissue scaffold, including collagen type I and IV, fibronectin, laminin and glycosaminoglycans. In addition, using proteomic analysis, we revealed numerous additional ECM proteins in DTM, indicating its complex nature. The mass spectrometry data were deposited to the ProteomeXchange with identifier PXD001524. Importantly, we demonstrated that DTM scaffolds are not cytotoxic, as evidenced by MTT assay not showing an aberrant fibroblast proliferation activity after indirect exposure, and support testicular cell attachment and infiltration. LIMITATIONS, REASONS FOR CAUTION: The functionality of human testicular cells in DTM needs to be investigated. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that the insights into the molecular composition of the testicular ECM provide new clues for the unravelling of its important yet poorly understood role in regulating testicular function, and DTM-based bioscaffolds are promising components for the development of human in vitro spermatogenesis as a treatment for various types of male fertility disorders.

A liver-derived rat epithelial cell line from biliary origin acquires hepatic functions upon sequential exposure to hepatogenic growth factors and cytokines.

Withdrawal of promising drug candidates is often due to the detection of liver toxicity. In particular the parenchymal liver cells or hepatocytes are targeted since they are the major sites of drug transport and of metabolite formation and thus also the place where not only detoxification, but also activation of new chemical (NCE) and biological (NBE) entities may occur. Therefore, primary hepatocyte- based cultures are currently the preferred in vitro model to screen for liver toxicity. However, within a few days, they undergo dedifferentiation with loss of liver-specific functionality, including xenobiotic biotransformation capacity, making them only suitable for short-term applications. A plausible alternative to primary hepatocyte cultures that can be maintained for longer periods of time could be the use of liver-derived epithelial cell lines and their optimized derivatives. Therefore, in the present study, we evaluated the stability and the hepatic differentiation potential of a neonatal liver-derived rat epithelial cell line from biliary origin (rLEC). Undifferentiated rLEC stably express the hepatic progenitor markers CEBPA, FOXA2, GJA1, ONECUT1, KRT18 and KRT19 for at least 15 consecutive passages after cryopreservation. Upon sequential exposure to hepatogenic growth factors and cytokines, rLEC generate functional hepatic progeny, expressing mature hepatic markers including Alb, Ahr, Car, C/ebpα, Cx32, Foxa2, Hnf1α, Hnf1ß and Onecut1. Furthermore, an active polarization is observed for the hepatic drug transporters Oatp4 and Ntcp. rLEC-derived hepatic cells also acquire the ability to store glycogen, express genes encoding for key hepatic enzymes as shown by Affymetrix microarray data, and display stable CYP1A1/2- and CYP2B1/2-dependent activities for several weeks at levels comparable to those observed in cultured primary rat hepatocytes. The acquisition of such a stable and active biotransformation capacity is key for the applicability of liver-based in vitro models for long-term toxicity testing.

Repeatability and phenotypic correlations for body weight and reproduction in commercial ostrich breeding pairs.

1. Reproduction is an important aspect of ostrich farming, where income is mainly derived from hides and meat. No estimates of repeatability or phenotypic correlations for reproduction and body weight are currently available for commercial ostriches. 2. Means, standard deviations, repeatability coefficients and phenotypic correlations for and among reproductive traits and body weight were computed for the average yearly production of 42 to 67 mixed age ostrich breeding pairs maintained on the Klein Karoo Agricultural Development Centre from 1990 to 1994. The among-breeding-pair variance component was used in the repeatability estimations, as the pairing off of the same male:female combinations repeatedly resulted in the confounding of these effects. 3. Phenotypic correlations of male body weight with egg production performance (-0.20) and female body weight with hatchability percentage (-0.16) were negative. Correlations of egg production performance with infertility (-0.20) and hatchability (0.23) percentages were favourable. 4. The repeatability of annual adult body weight was 0.68 +/- 0.05 in male ostriches and 0.61 +/- 0.05 in females. 5. Ostrich reproduction traits were extremely variable. An appreciable portion of this variation could be attributed to the repeatable nature of breeding pair performance from year to year. All the reproduction traits analysed were moderately repeatable, ranging from 0.38 +/- 0.07 (hatchability percentage) to 0.51 +/- 0.06 (percentage of embryonic deaths). Egg production performance during the first breeding season of 17 breeding pairs for which data were available predicted subsequent performance satisfactorily, suggesting that selection decisions can be made at quite an early age.

[Parents' experience of the death of their baby with congenital disorder]. / Ouers se belewenis van die dood van 'n baba met kongenitale afwykings.

The purpose of this study is to determine the experiences of the parents after the death of a congenital abnormal baby. Parents who have lost a baby go through a process of grief. This also applies to parents of a baby with congenital abnormalities. Parents whose congenital abnormal baby dies, not only grieve because of the abnormality of their baby, but also because it died. Unstructured in-depth interviews were held with six couples within a year after the death of their babies. The experiences of the six couples were afterwards compared. A literature study was undertaken in order to determine what the conclusions of other researchers field were. The result of the literature study was compared with that of the present study. Recommendations are made at the end of this study on the practical applications, education and further research that can be undertaken on this subject.

Reflectance pulse oximetry measurements from the retinal fundus.

Conventional transmission pulse oximetry is a noninvasive technique for the continuous monitoring of arterial oxygen saturation (SaO2) from peripheral vascular beds such as the finger tip or earlobe. In this paper we propose to exploit the unique transparency of the ocular media to make reflectance pulse oximetry measurements on the retinal fundus. This technique potentially offers significant advantages over conventional pulse oximetry, primarily the ability to monitor cerebral, as opposed to peripheral, oxygen saturation. We have developed an in vitro system to stimulate the retinal circulation and ocular optics. This system consists of a flexible cuvette located in a model eye and an extracorporeal blood circuit to stimulate arterial blood flow. The system was used to investigate the relationship between SaO2 and the R/IR ratio in reflectance pulse oximetry. To enable in vivo measurements to be made, we also modified a standard haptic contact lens to hold the pulse oximeter probe in front of the pupil. In a preliminary study, the lens was fitted to an awake volunteer and cardiac-synchronous signals were detected by the retinal pulse oximeter.

Pulse oximetry: theoretical and experimental models.

In the paper a pulse oximetry model is developed using an approach which combines both theoretical and empirical modelling. The optical properties of whole blood are measured as a function of cuvette depth by transmission spectrophotometry using red (660 nm) and infra-red (950 nm) light-emitting diodes as light sources. Twersky's theoretical model gives the best fit to the experimental data. A simple theoretical model which takes into account the nonlinear relationship between optical density and cuvette depth is then used to obtain an expression for the R:IR ratio, which relates the measurement of transmission at the two wavelengths. The R:IR ratio is found to be more or less independent of cuvette depth (SD = 0.14 at 100 per cent SaO2). To validate the predictions of the theoretical model, the results of a previous experiment in which the relationship between SaO2 and the R:IR ratio was recorded using a flexible cuvette are used. The experimental values are found to lie within one standard deviation from the theoretical curve relating SaO2 and the R:IR ratio. It is argued that a reasonably accurate model for pulse oximetry which is based on whole blood and not haemoglobin solutions has been developed.

Determination of diclazuril in animal feed by liquid chromatography.

A method is described for the determination of diclazuril (Janssen Research Compound R64433; trademark Clinacox) in chicken feed at the mg kg(-1) level. Compound R062646, a structure analogous to diclazuril, was used as the interna standard. The drug was extracted from food with acidified methanol. Diclazuril was then isolated by means of solid-phase extraction with a cartridge containing a C18 phase. The eluate was evaporated and the residue redissolved in dimethylformamide. An aliquot was injected onto a reversed-phase high-performance liquid chromatographic column and the drug substance quantified at 280 nm by an ultraviolet detector. Extraction (absolute) recoveries of 85% for both internal standard and diclazuril were obtained. The method is suitable for diclazuril concentrations ranging from 0.1 to 1.5 mg kg(-1). Method validation data are presented.

Temperature dependence of led and its theoretical effect on pulse oximetry.

Ambient temperature is known to affect the emission spectrum of a light-emitting diode (LED). This study has investigated the effect of changes in ambient temperature on the emission spectra of two LED with peak emission wavelengths similar to those used in pulse oximetry. There was a 5.5-nm increase in the peak wavelength for a 660-nm LED, and a 7.8-nm increase in the peak wavelength for a 950-nm LED as temperature increased from 0 to 50 degrees C. Using a simple theoretical model based on the Beer-Lambert law, the effect of these shifts in wavelength on pulse oximeter accuracy was examined and found to be negligible over the temperature range studied.

The effect of varying LED intensity on pulse oximeter accuracy.

Most pulse oximeters automatically alter the intensity of their light-emitting diodes (LEDs) according to the absorption of the finger, toe or earlobe to which they are attached. This paper investigates the effect of changing LED intensity on pulse oximeter accuracy. Our results show that the peak wavelength of a red LED typically increases by 8 nm as its intensity is increased ten-fold. To determine whether this shift introduces a significant error, a simple theoretical model based on the Beer-Lambert law is used. The model predicts that a 10:1 change in LED intensity results in a 2.5% error at 50% arterial oxygen saturation (SpO2). At high saturations (SpO2 greater than or equal to 85%) the model predicts little loss of accuracy and thus any effect due to changes in LED intensity will be apparent only at low saturations.

In vitro investigation of the factors affecting pulse oximetry.

The effect of a number of physiological parameters on pulse oximetry accuracy has been investigated in an in vitro model. We have found that above 50% saturation, pulse oximeters will not be affected by variations in haematocrit, blood flow rate, tissue blood content and pulse amplitude. At low saturations, however, it is known that the accuracy of pulse oximeters decreases and our in vitro results suggest how this may be corrected.

A new perspective in the assessment of vitamin B-6 nutritional status during pregnancy in humans.

Plasma pyridoxal-5'-phosphate (PLP) concentration has been suggested as a valid indicator to assess vitamin B-6 nutritional status. Animal and human studies have shown that plasma PLP concentrations decrease progressively during pregnancy and large doses of vitamin B-6 supplementation are required to maintain plasma PLP at early or prepregnant levels. PLP is known to be hydrolyzed to pyridoxal (PL) by alkaline phosphatase (ALP), resulting in an inverse relationship between PLP and ALP. The object of this study was to compare the PLP-PL equilibrium in a group of healthy pregnant females with that of an age-matched nonpregnant control group from a similar socioeconomic background. The mean plasma PLP level was 37% lower, (P less than 0.0001), whereas the mean PL level was almost 90% higher (P less than 0.001) in the pregnant group than in the nonpregnant control group. The total amount of plasma PLP and PL levels, however, did not differ significantly (P greater than 0.24) between the two groups. Because the PL vitamer is regarded as the ultimate transport form of vitamin B-6, it may serve as a readily available source of vitamin B-6 to meet possible increased metabolic demands. Therefore, the estimation of plasma PLP alone does not permit an accurate assessment or understanding of the nutritional status and the physiology of vitamin B-6 in conditions associated with altered vitamin B-6 homeostases.

Nest microclimate and incubation water loss of eggs of the African ostrich (Struthio camelus var. domesticus).

The microclimate of the nest and the rates of egg water loss were studied at weekly intervals throughout the 41-day incubation period in six ostrich nests. Overall mean values were a central egg temperature of 34.9 degrees C associated with saturation vapor pressure of 42 torr, a mean nest vapor pressure of 11 torr, and an ambient vapor pressure of 8.4 torr. The egg water loss increased from 4,000 to 4,800 mg X day-1 over the incubation period, and the total water loss was equal to 13.2% of the initial egg mass of 1,368 gm. The mean rate of water loss (4,403 mg X day-1) divided by the water vapor conductance of the shell (147 mg X day-1 X torr-1) equals 30 torr. When this value is added to the nest vapor pressure of 11 torr, it predicts an egg saturation vapor pressure of 41 torr, similar to that derived from the central egg temperature.