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Objectives: Hemodynamic abnormalities and brain development disorders have been reported previously in fetuses and infants with transposition of the great arteries and intact ventricular septum (TGA‐IVS). A ventricular septal defect (VSD) is thought to be an additional risk factor for adverse neurodevelopment, but literature describing this population is sparse. The objectives of this study were to assess fetal cardiac hemodynamics throughout pregnancy, to monitor cerebral hemodynamics and oxygen metabolism in neonates, and to compare these data between patients with TGA‐IVS, those with TGA‐VSD and age‐matched controls. Methods: Cardiac hemodynamics were assessed in TGA‐IVS and TGA‐VSD fetuses and compared with healthy controls matched for gestational age (GA) during three periods: ≤ 22 + 5 weeks (GA1), 27 + 0 to 32 + 5 weeks (GA2) and ≥ 34 + 5 weeks (GA3). Left (LVO), right (RVO) and combined (CVO) ventricular outputs, ductus arteriosus flow (DAF, sum of ante‐ and retrograde flow in systole and diastole), diastolic DAF, transpulmonary flow (TPF) and foramen ovale diameter were measured. Aortic (AoF) and main pulmonary artery (MPAF) flows were derived as a percentage of CVO. Fetal middle cerebral artery and umbilical artery (UA) pulsatility indices (PI) were measured and the cerebroplacental ratio (CPR) was derived. Bedside optical brain monitoring was used to measure cerebral hemoglobin oxygen saturation (SO2) and an index of microvascular cerebral blood flow (CBFi), along with peripheral arterial oxygen saturation (SpO2), in TGA‐IVS and TGA‐VSD neonates. Using hemoglobin (Hb) concentration measurements, these parameters were used to derive cerebral oxygen delivery and extraction fraction (OEF), as well as an index of cerebral oxygen metabolism (CMRO2i). These data were acquired in the early preoperative period (within 3 days after birth and following balloon atrial septostomy) and compared with those of age‐matched healthy controls, and repeat measurements were collected before discharge when vital signs were stable. Results: LVO was increased in both TGA groups compared with controls throughout pregnancy. Compared with controls, TPF was increased and diastolic DAF was decreased in TGA‐IVS fetuses throughout pregnancy, but only during GA1 and GA2 in TGA‐VSD fetuses. Compared with controls, DAF was decreased in TGA‐IVS fetuses throughout pregnancy and in TGA‐VSD fetuses at GA2 and GA3. At GA2, AoF was higher in TGA‐IVS and TGA‐VSD fetuses than in controls, while MPAF was lower. At GA3, RVO and CVO were higher in the TGA‐IVS group than in the TGA‐VSD group. In addition, UA‐PI was lower at GA2 and CPR higher at GA3 in TGA‐VSD fetuses compared with TGA‐IVS fetuses. Within 3 days after birth, SpO2 and SO2 were lower in both TGA groups than in controls, while Hb, cerebral OEF and CMRO2i were higher. Preoperative SpO2 was also lower in TGA‐VSD neonates than in those with TGA‐IVS. From preoperative to predischarge periods, SpO2 and OEF increased in both TGA groups, but CBFi and CMRO2i increased only in the TGA‐VSD group. During the predischarge period, SO2 was higher in TGA‐IVS than in TGA‐VSD neonates, while CBFi was lower. Conclusions: Fetal cardiac and neonatal cerebral hemodynamic/metabolic differences were observed in both TGA groups compared with controls. Compared to those with TGA‐IVS, fetuses with TGA‐VSD had lower RVO and CVO in late gestation. A higher level of preoperative hypoxemia was observed in the TGA‐VSD group. Postsurgical cerebral adaptive mechanisms probably differ between TGA groups. Patients with TGA‐VSD have a specific physiology that warrants further study to improve neonatal care and neurodevelopmental outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Synapse loss occurs early and correlates with cognitive decline in Alzheimer's disease (AD). Synaptotoxicity is driven, at least in part, by amyloid-beta oligomers (Aβo), but the exact synaptic components targeted by Aβo remain to be identified. We here tested the hypotheses that the post-synaptic protein Neuroligin-1 (NLGN1) is affected early in the process of neurodegeneration in the hippocampus, and specifically by Aβo, and that it can modulate Aβo toxicity. We found that hippocampal NLGN1 was decreased in patients with AD in comparison to patients with mild cognitive impairment and control subjects. Female 3xTg-AD mice also showed a decreased NLGN1 level in the hippocampus at an early age (i.e., 4 months). We observed that chronic hippocampal Aβo injections initially increased the expression of one specific Nlgn1 transcript, which was followed by a clear decrease. Lastly, the absence of NLGN1 decreased neuronal counts in the dentate gyrus, which was not the case in wild-type animals, and worsens impairment in spatial learning following chronic hippocampal Aβo injections. Our findings support that NLGN1 is impacted early during neurodegenerative processes, and that Aβo contributes to this effect. Moreover, our results suggest that the presence of NLGN1 favors the cognitive prognosis during Aβo-driven neurodegeneration.

Background: The well-being of mothers of infants requiring Neonatal Intensive Care Unit (NICU) hospitalization may be affected by the architectural design of the unit. A few recent studies suggest there may be some drawbacks of single-family rooms (SFRs) for infants and their mothers, such as isolation of mothers and reduced exposure to auditory stimulation for infants., Purpose: To compare NICU-stress, symptoms of depression, perceptions of nurse-parent support and family-centered care, sleep disturbances, breastfeeding self-efficacy and readiness for discharge in mothers of infants cared for in an open ward (OW) to those cared for in a unit that includes both pods and SFRs., Methods: A pre-post quasi-experimental study was conducted in a Canadian level 3 unit before and after transitioning to a new unit of 6-bed pods and SFRs. OW data were collected in 2014 and pod/SFR data 1 year after the transition in 2017 to 2018. Mothers of infants hospitalized for at least 2 weeks completed questionnaires about stress, depressive symptoms, support, family-centered care, and sleep disturbances. In the week prior to discharge, they responded to breastfeeding self-efficacy and readiness for discharge questionnaires. They described their presence in the NICU at enrollment and again prior to discharge., Results: Pod/SFR mothers reported significantly less NICU-stress compared to OW mothers. OW mothers had greater sights and sounds stress and felt more restricted in their parental role. Pod/SFR mothers reported greater respect from staff. Controlling for maternal education, pod/SFR mothers perceived their infant's readiness for discharge to be greater than OW mothers. There were no significant differences between groups in depressive symptoms, nurse-parent support, sleep disturbances, and breastfeeding self-efficacy. At enrollment and again in the weeks preceding discharge, pod/SFR mothers were present significantly more hours per week than OW mothers, controlling for maternal education., Conclusions: Further study of small pods is indicated as these units may be less stressful for parents, and enhance family-centered care, as well as maternal presence, compared to OWs.

Drosophila suzukii Matsumura (Diptera: Drosophilidae) is a significant invasive pest in soft-skin fruits and berries in Asia, Europe, and North and South America. Many herbivorous insects use multiple cues for host selection, particularly olfactory and visual stimuli. The visual system of closely-related Drosophila melanogaster is well-documented, expressing strong sensitivity to short-wavelength colors (ultraviolet to green) and only limited sensitivity to long-wavelength colors (red to infrared). Our results suggest that D. suzukii have limited ability to distinguish red consistent with visual sensitivity range within the melanogaster subgroup. We propose that color contrast rather than color appearance may be of greater importance in orientation and attraction. We propose that differences in reflectance between light wavelengths important for color opponency are key to color discrimination to provide color contrast between foreground and background, as occurs between fruit and foliage, during host-finding.

Background: When a newborn requires neonatal intensive care unit (NICU) hospitalization, parent and infant experience an unusual often prolonged separation. This critical care environment poses challenges to parent-infant closeness. Parents desire physical contact and holding and touching are particularly important. Evidence shows that visitation, holding, talking, and skin to skin contact are associated with better outcomes for infants and parents during hospitalization and beyond. Thus, it would be important to understand closeness in this context. The purpose of this study was to explore from nurses' perspective, what do parents and nurses do to promote parent-infant closeness or provoke separation., Methods: Qualitative methods were utilized to attain an understanding of closeness and separation. Following ethics approval, purposive sampling was used to recruit nurses with varying experience working different shifts in NICUs in two countries. Nurses were loaned a smartphone over one work shift to record their thoughts and perceptions of events that occurred or experiences they had that they considered to be closeness or separation between parents and their hospitalized infant. Sample size was determined by saturation (18 Canada, 19 Finland). Audio recordings were subjected to inductive thematic analysis. Team meetings were held to discuss emerging codes, refine categories, and confirm these reflected data from both sites. One overarching theme was elaborated., Results: Balancing closeness and separation was the major theme. Both parents and nurses engaged in actions to optimize closeness. They sought closeness by acting autonomously in infant caregiving, assuming decision-making for their infant, seeking information or skills, and establishing a connection in the face of separation. Parents balanced their desire for closeness with other competing demands, such as their own needs. Nurses balanced infant care needs and ability to handle stimulation with the need for closeness with parents. Nurses undertook varied actions to facilitate closeness. Parent, infant and NICU-related factors influenced closeness. Consequences, both positive and negative, arose for parents, infants, and nurses., Conclusion: Findings point to actions that nurses undertake to promote closeness and help parents cope with separation including: promoting parent decision-making, organizing care to facilitate closeness, and supporting parent caregiving.

Purpose: To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of acetazolamide (ACTZ) in peritoneal dialysis patients, ACTZ 500 mg was administered intravenously to 7 healthy subjects (HV) and 8 peritoneal dialysis patients (CAPD)., Methods: Population PK/PD modeling was performed with ACTZ serum (total and unbound), urine and dialysate concentrations, intra-ocular pressure (IOP) and covariates. A multi-compartment PK model (accounting for non-linear protein binding) and an inhibitory Emax (maximal change in IOP) PD model were selected., Results: As expected, renal clearance (which almost equals total body clearance) was severely decreased in CAPD (1.2 vs 80.3 L/h) and the elimination half-life of total ACTZ was prolonged (20.6 vs 3.4 hours). The protein binding was significantly altered with a mean free fraction 4.2% in HV and 8.6% in CAPD. Moreover protein binding of ACTZ was concentration dependent in both HV and CAPD. Despite a higher free fraction of ACTZ, the Emax was lower in CAPD: 4.4±1.4 vs 7.4±2.8 mmHg., Conclusion: Both PK and PD are significantly altered in dialysis patients.

Unlabelled: The Brugada syndrome (BS) is a clinical entity involving cardiac sodium channelopathy, typical electrocardiogram (ECG) changes and predisposition to ventricular arrhythmia. This syndrome is mainly recognized by specialized cardiologists and electrophysiologists. Data regarding BS largely come from multicentre registries or Asian countries. The present report describes the Quebec Heart Institute experience, including the clinical characteristics and prognosis of native French-Canadian subjects with the Brugada-type ECG pattern., Methods and Results: BS has been diagnosed in 35 patients (mean age 51 +/- 12 years) at the Quebec Heart Institute since 2001. Patients were referred from primary care physicians for ECG abnormalities, syncope or ventricular arrhythmia, or were diagnosed incidentally on an ECG obtained for other purposes. The abnormal ECG was recognized after a syncopal spell in four patients and during family screening in four patients. All of the others were incidental findings following a routine ECG. No patient had a family history of sudden cardiac death at younger than 45 years of age. In this population, right bundle branch block pattern with more than 2 mm ST segment elevation in leads V1 to V3 was recorded spontaneously in 25 patients and was induced by sodium blockers in 10 patients. The sodium channel blocker test was performed in 21 patients and was positive in 18 patients (86%). An electrophysiological study was performed in 20 of 35 patients, during which ventricular fibrillation was induced in five patients; three of the five patients were previously asymptomatic. An implantable cardioverter-defibrillator was implanted in six of 35 patients (17%), including three of four patients with a history of syncope. A loop recorder was implanted in three patients. After a mean follow-up of 36 +/- 18 months, one patient died from a noncardiac cause and one patient (with a history of syncope) received an appropriate shock from his implantable cardioverter-defibrillator. No event occurred in the asymptomatic population., Conclusions: BS is present in the French-Canadian population and is probably under-recognized. Long-term prognosis of individuals with BS, especially in sporadic, asymptomatic cases, needs to be clarified.

Objectives: This study examined the roles of myocardial perfusion and adenosine in warm-up angina., Background: In warm-up angina, neither the role of an adenosine-mediated mechanism, as is found in experimental ischemic preconditioning, nor of increased myocardial perfusion is well defined., Methods: In substudy A, a single-photon emission computed tomography (SPECT)-thallium-201 exercise test was performed by 12 subjects with ischemic heart disease on three occasions one week apart. The third test was preceded by a warm-up test. The extent of the thallium deficit and its intensity on the third test were compared with the baseline tests controlling for the heart rate-systolic blood pressure product (RPP) at thallium injection. In substudy B, 12 similar subjects did two successive exercise tests at two separate sessions and received the adenosine antagonist, aminophylline (intravenous 5 mg/kg bolus and 0.9 mg/kg/h infusion) at one session, and equivalent saline at the other session. Change in ischemic threshold (RPP at 1 mm ST segment depression) and in maximum ST depression adjusted for RPP were analyzed., Results: In substudy A, despite a significant attenuation of electrocardiogram indexes of myocardial ischemia between the baseline and third (warmed-up) tests, the thallium extent deficits (20.8 +/- 15.1% and 16.8 +/- 12.4%) and intensity deficits (41.2 +/- 12.6% and 39.3 +/- 12.6%) did not differ significantly. In substudy B, the increase in ischemic threshold on re-exercise was unaffected by aminophylline. Adjusted maximum ST depression even decreased to a greater extent on re-exercise with aminophylline (by 51 +/- 21%) than with saline (by 32 +/- 19%) (p = 0.012)., Conclusions: While warm-up angina is associated with a significant attenuation of exercise electrocardiogram indexes of ischemia, it is unaccompanied by significant changes in SPECT perfusion and does not appear to be mediated by an adenosine-dependent mechanism since it is not blocked by aminophylline. Thus, its mechanism, which appears distinct from experimental ischemic preconditioning, remains unidentified.

Objectives: This study characterized the attenuation of myocardial ischemia observed with re-exercise to determine whether: 1) a differing exercise intensity modifies this attenuation; 2) it could be explained by contractile down-regulation or stunning; 3) it is mediated by activation of ATP-sensitive potassium channels (K+-ATP)., Background: Subjects with ischemic heart disease (IHD) frequently note less angina with re-exercise after a brief rest. Potential mechanisms of this 'warm-up' phenomenon have been little explored., Methods: IHD subjects with a positive exercise test were studied. Groups I and II (12 subjects each) underwent 2 successive Naughton protocol exercise echocardiography tests (with 1 min instead of 2 min stages for Group II). Group D (10 subjects) had type II diabetes, were on > or =10 mg daily of the K+-ATP blocker, glibenclamide, and underwent the group I exercise protocol. The ischemic threshold or rate-pressure product at 1 mm ST segment depression, ST depression corresponding to the peak rate-pressure product of the first exercise (maximum ST depression equivalent), and left ventricular wall motion indexes before and immediately after each exercise were analyzed., Results: Exercise-induced myocardial ischemia with re-exercise was similarly attenuated in groups I, II, and D. The ischemic threshold was raised by nearly 20% with re-exercise (p=0.001, p=0.02, and p=0.02, respectively) and the maximum ST depression equivalent was nearly halved on re-exercise (p=0.005, p=0.006, and p=0.001, respectively). Exercise-induced wall motion dysfunction was attenuated with re-exercise. In group I, wall motion returned to the initial baseline score prior to exercise 2, whereas in the more intense protocol of group II, wall motion dysfunction persisted prior to exercise 2., Conclusions: Thus, the attenuation of myocardial ischemia observed with re-exercise appears to be independent of the intensity of the exercise protocol and is not explained by down-regulation of myocardial contractility induced by the initial ischemic stimulus. Since results were similar in diabetic subjects on robust doses of glibenclamide, this phenomenon does not appear to be mediated by K+-ATP activation.

A panel of 257 RFLP loci was selected on the basis of high heterozygosity in Caucasian DNA surveys and equivalent spacing throughout the human genome. Probes from each locus were used in a Southern blot survey of allele frequency distribution for four human ethnic groups: Caucasian, African American, Asian (Chinese), and American Indian (Cheyenne). Nearly all RFLP loci were polymorphic in each group, albeit with a broad range of differing allele frequencies (delta). The distribution of frequency differences (delta values) was used for three purposes: (1) to provide estimates for genetic distance (differentiation) among these ethnic groups, (2) to revisit with a large data set the proportion of human genetic variation attributable to differentiation within ethnic groups, and (3) to identify loci with high delta values between recently admixed populations of use in mapping by admixture linkage disequilibrium (MALD). Although most markers display significant allele frequency differences between ethnic groups, the overall genetic distances between ethnic groups were small (.066-.098), and < 10% of the measured overall molecular genetic diversity in these human samples can be attributed to "racial" differentiation. The median delta values for pairwise comparisons between groups fell between .15 and .20, permitting identification of highly informative RFLP loci for MALD disease association studies.

Increasingly, family physicians are expressing an interest in this facet of adolescent health care, realizing that a successful initial consultation offers tremendous educational opportunities. This article compares the use of a comprehensive questionnaire to a less formal approach. It describes various components of the pelvic examination that can teach adolescents to take responsibility for their health.