Search

Autistic adults often experience difficulties in taking the perspective of others, potentially undermining their social interactions. We evaluated a quick, forced-choice version of the Adult Theory of Mind (A-ToM) test, which was designed to assess such difficulties and comprehensively evaluated by Brewer et al. (2017). The forced-choice version (the A-ToM-Q) demonstrated discriminant, concurrent, convergent and divergent validity using samples of autistic (N = 96) and non-autistic adults (N = 75). It can be administered in a few minutes and machine-scored, involves minimal training and facilitates large-scale, live, or web-based testing. It permits measurement of response latency and self-awareness, with response characteristics on both measures enhancing understanding of the nature and extent of perspective taking difficulties in autistic individuals.

Eyewitness researchers recommend that "not present" and "don't know" response options should be presented with police lineups. Although it is important that witnesses--most of whom are unlikely to be familiar with the identification task--are fully cognizant of all response options available to them, an understanding of how explicit non-identification options affect performance is lacking. Across four experiments, including 3,633 participants and 8 different stimulus sets, we tested the effects of including non-identification options in computer-administered lineups. When explicit non-identification options were presented, target-present and -absent choosing decreased. This decrease in choosing was characterized by a shift from filler identifications to lineup rejections. ROC analyses revealed that there was no overall difference in discriminability between guilty and innocent suspects depending on response option condition. On balance, the findings suggest that, in addition to informing witnesses about acceptable responses, displaying non-identification response options does not undermine identification performance.

Purpose: Prostate cancer (PCa) screening can lead to potential over-diagnosis/over-treatment of indolent cancers. There is a need to optimize practices to better risk-stratify patients. We examined initial longitudinal outcomes of mid-life men with an elevated baseline prostate-specific antigen (PSA) following initiation of a novel screening program within a system-wide network. Materials and Methods: We assessed our primary care network patients ages 40 to 49 years with a PSA measured following implementation of an electronic health record screening algorithm from 2/2/2017–2/21/2018. The multidisciplinary algorithm was developed taking factors including age, race, family history, and PSA into consideration to provide a personalized approach to urology referral to be used with shared decision-making. Outcomes of men with PSA ≥1.5 ng/mL were evaluated through 7/2021. Statistical analyses identified factors associated with PCa detection. Clinically significant PCa (csPCa) was defined as Gleason Grade Group (GGG) ≥2 or GGG1 with PSA ≥10 ng/mL. Results: The study cohort contained 564 patients, with 330 (58.5%) referred to urology for elevated PSA. Forty-nine (8.7%) underwent biopsy; of these, 20 (40.8%) returned with PCa. Eleven (2.0% of total cohort and 55% of PCa diagnoses) had csPCa. Early referral timing (odds ratio [OR], 4.58) and higher PSA (OR, 1.07) were significantly associated with PCa at biopsy on multivariable analysis (both p<0.05), while other risk factors were not. Referred patients had higher mean PSAs (2.97 vs. 1.98, p=0.001). Conclusions: Preliminary outcomes following implementation of a multidisciplinary screening algorithm identified PCa in a small, important percentage of men in their forties. These results provide insight into baseline PSA measurement to provide early risk stratification and detection of csPCa in patients with otherwise extended life expectancy. Further follow-up is needed to possibly determine the prognostic significance of such mid-life screening and optimize primary care physician-urologist coordination. [ABSTRACT FROM AUTHOR]

Purpose: β2-sympathomimetics are used in obstetrics as tocolytic agents, despite a remarkable profile of side effects. Recently, the β2-sympathomimetic tocolytic drug hexoprenaline was identified as an independent risk factor for the development of infantile hemangioma (IH) in preterm infants. The aim of this study was to evaluate whether this observed effect was applicable to other β2-mimetic tocolytic agents like fenoterol.Methods: Clinical prospectively collected data of all infants born between 2001 and 2012 and admitted to the neonatal intensive care unit (NICU) at Heidelberg University Hospital and respective maternal data were merged. For the current retrospective cohort study, cases (IH) were matched to controls (no IH) at a ratio of 1:4, adjusting for birth weight, gestational age, gender and multiple gestations. Prenatal exposure to fenoterol and perinatal outcome were analyzed in the total cohort and in subgroups.Results: N = 5070 infants were admitted to our neonatal department, out of which n = 172 infants with IH were identified and compared to n = 596 matched controls. Exposure to fenoterol was not associated with a higher rate of IH in the total matched population (OR 0.926, 95% CI 0.619-1.384) or in a subgroup of neonates < 32 weeks of gestation or with a birth weight < 1500 g (OR 1.127, 95% CI 0.709-1.791). In the total matched population, prenatal exposure to glucocorticoids was associated with a reduced occurrence of IH (OR 0.566, 95% CI 0.332-0.964) and neonates with IH showed a prolonged total hospital stay compared to controls (69 vs. 57 days, p = 0.0033). Known risk factors for IH were confirmed by our large study cohort and included female gender, low birth weight, preterm birth and multiple gestations (all p < 0.005).Conclusions: Exposure to fenoterol during pregnancy does not increase the occurrence of IH. Further studies are needed to explore differences in the risk profiles of different β2-sympathomimetic tocolytic drugs. [ABSTRACT FROM AUTHOR]

The epidemic of Zika virus (ZIKV) has resulted in a surge of newborns with microcephaly and brain abnormalities. In this report, we describe the first case, to our knowledge, of congenital Zika syndrome with concomitant critical congenital heart disease. The mother had a confirmed ZIKV infection in the first trimester of pregnancy. Fetal ultrasonography at 31 weeks of gestation revealed cerebral cortical calcifications and hypoplastic left heart syndrome. The severity of brain involvement was assessed by postnatal magnetic resonance imaging and echocardiogram, and palliative surgery was performed. The ethical dimensions of this infant's clinical management are discussed. ZIKV is known to affect neural progenitor cells, but whether it could have a tropism for other tissues remains unclear. [ABSTRACT FROM AUTHOR]

R2884 --> 605.11 --> Background: Pulmonary arterial hypertension (PAH), is a progressive disease that seriously compromises quality of life due to dyspnea and fatigue on exertion that worsens over time such that patients are ultimately immobile. Although hemodynamic compromise is the main contributor to exercise intolerance in PAH, accumulating evidence supports that intrinsic skeletal muscle dysfunction also occurs and may contribute to this symptomatology. We previously showed that treatment with the carbonic anhydrase inhibitor Acetazolamide (ACTZ) ameliorates the hemodynamic components of experimental PAH but its effects on skeletal muscle function and exercise tolerance are unknown. Our objective is to characterize the mechanisms of skeletal muscle dysfunction in a preclinical model of severe PAH and evaluate the effect of ACTZ treatment. Hypotheses: We hypothesized that reduced exercise endurance in experimental PAH is associated with increased proportion of fast glycolytic (Type II) fibers to slow oxidative (Type I) fibers, and sarcomeric dysfunction in skeletal muscles and that treatment with ACTZ, alters muscle fiber specificity, improves skeletal muscle contractile properties and exercise tolerance. Methods: We used the adult rat Sprague Dawley sugen/hypoxia (Su/Hx) model of severe pulmonary hypertension and performed hemodynamic and exercise tolerance studies (treadmill). We evaluated the abundance of Type I and Type II fiber specific markers and sarcomeric organization in muscles from Su/Hx and ACTZ treated rats and measured twitch and tetanic forces, contraction and relaxation times in diaphragm, soleus and extensor digitorum longus (EDL). We used the rat myoblast cell line (L6) to evaluate the molecular mechanisms of muscle fiber switch using immunofluorescence, RNA and protein expression studies. Results: We found that diaphragm and soleus muscle from the adult rat sugen/hypoxia (Su/Hx) model of severe PAH have increased abundance of type II fiber markers and thick sarcomeric aggregates and these changes are accompanied by decreased twitch and tetanic forces, contraction and half‐relaxation time and exercise endurance despite absence of muscle atrophy. Acetazolamide (ACTZ), treatment restored the above derangements. In vitro rat myotube differentiation was associated with a predominance of type II fiber markers in conjunction with increased abundance of the transcription factor FoxO1. This pattern of increased abundance of FoxO1 and increased type II markers was also seen in Su/Hx soleus muscles and was reversed in response to ACTZ treatment. Conclusions: We conclude that a shift in skeletal muscle fiber type specification may underlie skeletal muscle dysfunction in experimental PAH and that treatment with ACTZ may ameliorate skeletal muscle dysfunction through an inhibitory effect on FoxO1‐mediated fiber type specification. [ABSTRACT FROM AUTHOR]

Objective: Defense attorneys sometimes suggest that social-cognitive difficulties render autistic individuals vulnerable to involvement in crime, often arguing that theory of mind (ToM) difficulties that undermine inferences about others' intentions underpin this vulnerability. We examined autistic adults' ability to respond adaptively to criminal intent during interactions and whether difficulties were associated with poor ToM., Hypotheses: Compared with nonautistic adults, autistic adults were expected to be less likely to respond adaptively to another's criminal intent and less likely to do so early in interactions, with poorer performance associated with ToM difficulties., Method: We developed the Suspicious Activity Paradigm, in which autistic ( n = 102) and nonautistic ( n = 95) adults listened (as if participating in an interaction) to audio scenarios in which cues suggesting their impending involvement in a crime gradually emerged. At periodic intervals, they were required to indicate how they would react toward the other person's behavior, with response coding reflecting detection of, and adaptive responding to, suspicious activity., Results: We observed similar patterns of suspicion and adaptive responses in autistic and nonautistic adults as the scenarios progressed. Regardless of diagnostic status, pronounced ToM difficulties and low verbal ability were independently associated with a lower likelihood of reporting suspicion and responding adaptively., Conclusions: Our results do not support the perspective that autistic adults are uniquely vulnerable to crime involvement due to an inability to recognize and respond adaptively to suspicious behavior. The potential for heightened criminal vulnerability was associated with significant ToM difficulties (and verbal ability) regardless of autism diagnostic status, although such difficulties were more prevalent in the autistic sample. The finding that pronounced ToM difficulties may heighten criminal vulnerability for both autistic and nonautistic individuals challenges the validity of a generalized "autism" legal defense based on assumed rather than measured ToM difficulties. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Pulmonary hypertension (PH) is a serious disease with pulmonary arterial fibrotic remodeling and limited responsiveness to vasodilators. Our data suggest that mild acidosis induced by carbonic anhydrase inhibition could ameliorate PH, but the vascular mechanisms are unclear. We tested the hypothesis that carbonic anhydrase inhibition ameliorates PH by improving pulmonary vascular reactivity and relaxation mechanisms. Male Sprague-Dawley rats were either control normoxic (Nx), or injected with Sugen 5416 (20 mg/kg, sc) and subjected to hypoxia (9% O 2 ) (Su + Hx), or Su + Hx treated with acetazolamide (ACTZ, 100 mg/kg/day, in drinking water). After measuring the hemodynamics, right ventricular hypertrophy was assessed by Fulton's Index; vascular function was measured in pulmonary artery, aorta, and mesenteric arteries; and pulmonary arteriolar remodeling was assessed in lung sections. Right ventricular systolic pressure and Fulton's Index were increased in Su + Hx and reduced in Su + Hx + ACTZ rats. Pulmonary artery contraction to KCl and phenylephrine were reduced in Su + Hx and improved in Su + Hx + ACTZ. Acetylcholine (ACh)-induced relaxation and nitrate/nitrite production were reduced in pulmonary artery of Su + Hx and improved in Su + Hx + ACTZ. ACh relaxation was blocked by nitric oxide (NO) synthase and guanylate cyclase inhibitors, supporting a role of NO-cGMP. Sodium nitroprusside (SNP)-induced relaxation was reduced in pulmonary artery of Su + Hx, and ACTZ enhanced relaxation to SNP. Contraction/relaxation were not different in aorta or mesenteric arteries of all groups. Pulmonary arterioles showed wall thickening in Su + Hx that was ameliorated in Su + Hx + ACTZ. Thus, amelioration of pulmonary hemodynamics during carbonic anhydrase inhibition involves improved pulmonary artery reactivity and NO-mediated relaxation and may enhance responsiveness to vasodilator therapies in PH.

Pulmonary vasoreactivity could determine the responsiveness to vasodilators and, in turn, the prognosis of pulmonary hypertension (PH). We hypothesized that pulmonary vasoreactivity is impaired, and we examined the underlying mechanisms in the Sugen-hypoxia rat model of severe PH. Male Sprague-Dawley rats were injected with Sugen (20 mg/kg s.c.) and exposed to hypoxia (9% O 2 ) for 3 weeks, followed by 4 weeks in normoxia (Su/Hx), or treated with Sugen alone (Su) or hypoxia alone (Hx) or neither (Nx). After hemodynamic measurements, the heart was assessed for right ventricular hypertrophy (Fulton's index); the pulmonary artery, aorta, and mesenteric arteries were isolated for vascular function studies; and contractile markers were measured in pulmonary arteries using quantitative polymerase chain reaction (PCR). Other rats were used for morphometric analysis of pulmonary vascular remodeling. Right ventricular systolic pressure and Fulton's index were higher in Su/Hx versus Su, Hx, and Nx rats. Pulmonary vascular remodeling was more prominent in Su/Hx versus Nx rats. In pulmonary artery rings, contraction to high KCl (96 mM) was less in Su/Hx versus Nx and Su, and phenylephrine-induced contraction was reduced in Su/Hx versus Nx, Hx, and Su. Acetylcholine (ACh)-induced relaxation was less in Su/Hx versus Nx and Hx, suggesting reduced endothelium-dependent vasodilation. ACh relaxation was inhibited by nitric oxide synthase (NOS) and guanylate cyclase blockade in all groups, suggesting a role of the NO-cGMP pathway. Nitrate/nitrite production in response to ACh was less in Su/Hx versus Nx, supporting reduced endothelial NO production. Sodium nitroprusside (10 -8 M) caused less relaxation in Su/Hx versus Nx, Hx, and Su, suggesting a decreased responsiveness of vascular smooth muscle (VSM) to vasodilators. Neither contraction nor relaxation differed in the aorta or mesenteric arteries of all groups. PCR analysis showed decreased expression of contractile markers in pulmonary artery of Su/Hx versus Nx. The reduced responsiveness to vasoconstrictors and NO-mediated vasodilation in the pulmonary, but not systemic, vessels may be an underlying mechanism of severe PH in Su/Hx rats and appears to involve attenuation of the NO relaxation pathway and a switch of pulmonary VSM cells to a synthetic less reactive phenotype., (Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.)