Perceived Anxiety in Family Caregivers of Individuals with Autism Spectrum Disorder, Down Syndrome and Williams Syndrome during the Lockdown of the First COVID-19 Wave in Spain.

The lockdown during the first wave of COV- ID-19 in Spain has been related to higher levels of anxiety in the general population. However, the emotional impact on Spanish caregivers of individuals with neurodevelopmental disorders (NDD) has not been studied so far.

Ansiedad percibida en familiares cuidadores de personas con trastorno del espectro autista, síndrome de Down y síndrome de Williams durante el confinamiento de la primera ola por COVID-19 en España / perceived anxiety in family caregivers of individuals with autism spectrum disorder, down syndrome and williams syndrome during the lockdown of the first COVID-19 wave in Spain

Antecedentes. El confinamiento durante la primera oleada de COVID-19 en España se ha relacionado con niveles mayores de ansiedad en la población general. Sin embargo, no se ha estudiado el impacto emocional en los cuidadores de personas con trastornos del neurodesarrollo (TND).Método. Se distribuyó un cuestionario a las organizaciones que prestan apoyo a las personas con TND y sus familias. Se analizaron los datos de los cuidadores de personas con trastorno del espectro autista (TEA) (N=17), síndrome de Down (N=25) y síndrome de Williams (N=18).Resultados. Los cuidadores informaron de preocupaciones relacionadas con la situación de pandemia y confinamiento. Los cuidadores de personas con TEA mostraron mayor preocupación sobre los conflictos familiares. Los tres grupos informaron de niveles de ansiedad más altos durante el confinamiento. Predijeron la ansiedad el trastorno de ansiedad previo y el diagnóstico del hijo/a. Conclusiones. Los predictores de ansiedad en los cuidadores de individuos con TND difieren de los reportados previamente en la población general española. Los resultados sugieren que el confinamiento fue especialmente duro paralas familias de personas con TEA. Las políticas públicas deberían considerar las necesidades de las personas con TND y sus cuidadores para minimizar las consecuencias negativas de la pandemia. (AU)

Background. The lockdown during the first wave of COVID-19 in Spain has been related to higher levels of anxietyin the general population. However, the emotional impact on Spanish caregivers of individuals with neurodevelopmental disorders (NDD) has not been studied so far. Methods. An online questionnaire was distributed to Spanish organisations providing support to individuals with NDD and their families. Data from caregivers of individuals with autism spectrum disorder (ASD) (N = 17), Down syndrome (DS)(N = 25) and Williams syndrome (WS) (N = 18) were analysed. Results. All caregivers reported concerns directly related to the pandemic and lockdown situation. Caregivers of individuals with ASD showed higher level of concern about the possibility of family conflict. All three groups reported higher levels of anxiety during the lockdown. Anxiety was predicted by previous anxiety disorder and the child’s diagnosis. Conclusions. Predictors of anxiety in caregivers of individuals with NDD differ from those previously reported in the general Spanish population. The results suggest that confinement in Spain was especially demanding for families of individuals with ASD. Public policies should consider the particular needs of people with NND and their caregivers to minimise the negative consequences of the ongoing pandemic.(AU)

Anxiety and Worries of Individuals with Down Syndrome During the COVID-19 Pandemic: A Comparative Study in the UK.

The present study explored the effects of the pandemic on individuals with Down Syndrome (DS; n = 67) compared to other groups with Special Education Needs and Disabilities (SEND; n = 48) and their Typically Developing Siblings (TDS; n = 56). In total, 115 caregivers reported on their own anxiety and worries and of their children. Anxiety levels for individuals with DS appeared to be lower compared to other SEND populations and to TDS. In terms of worries, individuals with DS worried more about social-related worries but worried less about family-related aspects compared to the other groups. In sum, individuals with DS might show less anxiety but still worried more about specific aspects related to the impact of COVID-19 pandemic on their lives.

The Impact of COVID-19 on Anxiety and Worries for Families of Individuals with Special Education Needs and Disabilities in the UK.

COVID-19 has affected people across the world. The current study examined anxiety and worries during the first UK national lockdown in March 2020. Parents (n = 402) reported on their own anxiety and worries as well as that of their son/daughter with Special Education Needs and Disabilities (SEND) and typically developing (TD) child (n = 186) at three time points. Although both groups showed increased anxiety across the three time points, levels of anxiety in the SEND group, but not the TD siblings, were predicted by awareness about COVID-19. In addition, worries differed between the groups showing that COVID-19 impacts the wellbeing of those with SEND differently to that of their TD siblings.

A molecular modeling analysis of diethylstilbestrol conformations and their similarity to estradiol-17 beta.

Crystallographic and computer modeling studies throughout the last 25 years have shown the structure of diethylstilbestrol (DES) to exist in two symmetrical or one asymmetrical conformation. As a result of specific comparisons to estradiol-17 beta (E2), the asymmetrical DES conformer has been suggested as the geometry possessing estrogenic activity. In the present study, a more complete set of DES conformations has been elucidated through the use of computer modeling. All previously defined DES geometries were found within this new set of ten structural forms. Differences between the molecular mechanics heat of formation energies of the ten conformers, as well as the transition energies separating them from each other, were found to be less than 1 kcal/mol. Additionally, a computer-based molecular alignment method was employed to quantitatively compare the steric and electrostatic molecular features of each DES conformer relative to E2. All ten DES structures were found to have shape relationships similar to E2. Thus, a model for the estrogen action of DES is presented whereby this stilbene can favorably interact with the estrogen receptor regardless of the conformation or orientation of the initial ligand-receptor association.

Cyclosporin A in refractory idiopathic nephrotic syndrome: 5 years clinical experience.

The use of cyclosporin A (Cy A) in idiopathic nephrotic syndrome, particularly lesions of focal segmental glomerular sclerosis, is controversial. A retrospective study of 10 adult patients with nephrotic syndrome treated with Cy A was performed. Histological diagnosis was established in all patients: focal segmental glomerular sclerosis (n = 6), focal global sclerosis (n = 1), mesangial proliferative glomerulonephritis (n = 1), focal proliferative glomerulonephritis (n = 1) and minimal change disease (n = 1). All patients had previously received immunosuppressive therapy (duration of steroids 1-76 months; 35.0 +/- 12.1, mean +/- SEM). Cy A in a dose of 3-5 mg/kg/day, reduced proteinuria from 16.85 +/- 6.67 to 3.37 +/- 1.48 g/24 hours (P = 0.008), with an associated increase in serum albumin from 15.2 +/- 2.6 to 34.3 +/- 2.5 g/l (P < 0.001). In six patients steroid therapy was discontinued. Cy A was well tolerated for up to 5 years. There was no significant nephrotoxicity. In conclusion, Cy A was effective treatment of refractory idiopathic nephrotic syndrome, including those cases with focal segmental glomerular sclerosis.

Regulation of iron absorption in iron loaded subjects with end stage renal disease: effects of treatment with recombinant human erythropoietin and reduction of iron stores.

The effects on iron absorption of variation in erythroid activity, haemoglobin and iron stores were studied in six anaemic dialysis-dependent subjects in whom iron stores were increased from previous red cell transfusions. Gastrointestinal mucosal uptake and whole body retention of oral iron were measured at the beginning of the study, after starting treatment with recombinant erythropoietin (but before significant increase in haemoglobin), after partial correction of anaemia, after further reduction of iron stores by repeated phlebotomy, and when erythropoiesis decreased from the discontinuation of treatment with erythropoietin. Between successive measurements, valid comparisons were made in five subjects. Correction of anaemia decreased whole body retention of iron through decreased mucosal uptake (P = 0.032). Further reduction in iron stores through repeated phlebotomy whilst the increase in haemoglobin was maintained by treatment with erythropoietin, tended to increase whole body retention of iron through an increase in mucosal transfer (P = 0.010). With initial enhancement of erythropoiesis in anaemic iron-loaded subjects there was no change in any measured component of iron absorption. However, after correction of anaemia and reduction of iron stores, a decrease in erythropoiesis was associated with decreased whole body iron retention in all subjects through decreased mucosal transfer (P = 0.028). The data suggest that anaemia upregulates mucosal iron uptake, and that erythroid activity upregulates mucosal transfer but that this latter effect may be counter-balanced by iron overload which downregulates mucosal transfer.

Surgical correction of hyperopia following radial keratotomy.

BACKGROUND: No effective treatment for hyperopia following radial keratotomy has been described. A new surgical technique of two purse-string intrastromal sutures was investigated for correction of this hyperopia. METHODS: Eighteen radial keratotomy patients who were unhappy with uncorrected vision and who were unsatisfied with contact lens or spectacle correction, after informed consent, underwent corneal suturing. The 19 hyperopic eyes included 5 original overcorrections, 5 overcorrections after reoperation, and 9 progressive hyperopes. The refractive error ranged from +1.25 to +5.75 diopters spherical equivalent (mean +3.47 D). Presuturing uncorrected visual acuity ranged from 20/50 to 20/400 with 11 eyes (58%) 20/100 or worse. RESULTS: The follow up after double purse-string suturing averaged 24 months (range, 12 to 47 months). All patients had follow up of at least 1 year; 14 patients (74%) had follow up of 2 years or more. The change in refractive spherical equivalent following surgery averaged -3.30 D (range, -1.00 to -7.50 D). The steepening in average keratometry was 4.10 D (range, 1.00 to 8.00 D). The refraction after suturing averaged -1.12 D (range, +2.50 to -3.50 D). Uncorrected visual acuity after suturing was 20/40 or better in 14 eyes (74%), and 20/50 to 20/80 in 5 eyes (36%). There were no significant intraoperative, early or late postoperative complications. Seventeen eyes were either the same or gained 1 line of acuity; 2 eyes gained 2 lines of acuity; no eyes lost any lines of refractive Snellen acuity. CONCLUSIONS: The placement of two purse-string intrastromal sutures appears to provide significant steepening of the central cornea following excessive flattening after radial keratotomy. The steepening effect appears to remain stable with greater than 1-year follow up. This surgical technique offers an alternative to symptomatic hyperopic postradial keratotomy patients who cannot be corrected with spectacles or contact lenses.

Do beta-adrenoceptor blocking drugs cause retroperitoneal fibrosis?

The aetiology of retroperitoneal fibrosis is unknown. From time to time different drugs have been suggested as a cause, including beta adrenoceptor blocking agents. The notes of 100 hospital inpatients in whom retroperitoneal fibrosis had been diagnosed were surveyed to identify the date of onset of symptoms, the drugs prescribed before then, and the blood pressures on admission. Seventy one patients had diastolic pressures on admission of 90 mm Hg or more and 53 of these had pressures of at least 100 mm Hg despite 14 of the patients taking anti-hypertensive drugs at the time. Six patients had received beta-adrenoceptor blocking agents before the onset of symptoms and a further 24 received them subsequently. In particular, three patients continued treatment for at least six years after the diagnosis was made and surgery performed, without suffering a recurrence of retroperitoneal fibrosis. Besides beta-adrenoceptor drugs, diuretics and other hypotensive drugs were taken in amounts reflecting the pattern of drug use among hypertensive patients generally. Rather than being causal agents, the antihypertensive drugs were probably being used to treat hypertension associated with the retroperitoneal fibrosis, and our findings suggest that beta-adrenoceptor blocking agents do not cause retroperitoneal fibrosis.

Subtype specificity of alpha-adrenergic receptors in rat heart.

Recent studies suggest that two subtypes of alpha-adrenergic receptors (alpha 1 and alpha 2) can be distinguished on the basis of the differential affinities of certain adrenergic ligands for each subtype. We have investigated the binding characteristics of several such ligands for alpha-adrenergic receptors in membrane preparations derived from rat heart. alpha-Adrenergic antagonists competed for binding sites identified by the nonsubtype selective alpha-adrenergic ligand [3H]dihydroergocryptine (DHE) in the order of potency expected for alpha 1-receptors, namely, prazosin (EC50 = 0.35 nM) greater than phentolamine (EC50 = 37 nM) greater than yohimbine (EC50 = 918 nM). Furthermore, the nonsubtype selective radioligand [3H]DHE identified a quantitatively similar number of specific binding sites in rat cardiac membranes as the alpha 1-selective radioligand [3H]prazosin (33 and 36 fmoles/mg protein, respectively), while the alpha 2-selective ligand [3H]clonidine at concentrations up to 20 nM demonstrated negligible specific binding. We conclude that the alpha-adrenergic receptors of rat heart homogenates demonstrate binding characteristics typical of alpha 1-receptors. While we cannot exclude the presence of small numbers of alpha-2 receptors, the similar number of binding sites identified at saturation for the alpha 1-specific ligand [3H]prazosin and for the nonsubtype selective ligand [3H]DHE supports the hypothesis that the alpha-receptors of rat heart are predominantly of the alpha 1-subtype.

Distinctive protein profiles obtained from extracts of normal and atherosclerotic human aorta.

Specific areas of fourteen autopsied abdominal aortas were layer-dissected, histologically graded and solubilzed with SDS, dilute saline or SDS-urea and beta-mercaptoethanol. Comparisons were made between intima, media, lesions of progressive severity and an in-vivo thrombus. Apparent molecular weights were calculated from the Coomassie blue stained gels of these extracts extracts and each band's contribution estimated by integrative densitometry. Four minor high moleucular weight bands and six medium to low molecular weight bands were detected in the arterial extracts. Band intensity stain patterns of normal intima are easily distinguished from normal media. Extracts of minor lesions resemble normal media; higher grade lesions demonstrate increased amounts of characteristic initmal bands. The major medial band is also seen on gels of thrombus extracts. Both of the bands most characteristic of atherosclerotic lesions stain for carbohydrate. Isolation and characterization of these (glyco)proteins will provide material for binding studies. Quantitation of characteristic lesion proteins may provide insights into the proliferative phase of this disease.

Coenzyme A derivatives of bile acids-chemical synthesis, purification, and utilization in enzymic preparation of taurine conjugates.

Synthesis of the coenzyme A derivatives of bile acids by the mixed anyhydride method results in a product that is contaminated by unreacted CoASH and bile acid. These compounds can be purified by Sephadex LH-20 chromatography. In each case, the purified product is free of starting materials and exhibits an equimolar ratio of bile acid, coenzyme A, and thioester bond. Millimolar extinction coefficients were calculated for these compounds as A259 nm, 15.03 +/- 0.58; A232 nm, 7.60 +/- 0.17; and A232 nm for the thioester bond, 4.12 +/- 0.17. These CoA derivatives were hydrolyzed in strongly alkaline solution, but were stable at physiologic temperature and pH. Utilization of these compounds in the enzymic preparation of taurine conjugates of bile acids indicated 94% activity. These purified CoA derivatives may be useful in studying the enzymic conjugation of bile acids.

Dialysis procedures in acute liver coma.

9 haemodialyses against fluids designed to reduce plasma abnormality were used in four patients with acute liver failure in an attempt to maintain consciousness and buy time for liver regeneration. Dialysis had little effect in two patients. In the third patient spontaneous movements and response to commands were seen during the second dialysis. Arousal occurred during both dialyses in the fourth patient who eventually recovered.