Early Disturbances Research Articles

Abstract 17204: Asymmetric Patterns of Cerebral Cortical Development in Fetuses With Complex Congenital Heart Disease

Introduction: Neurodevelopmental disabilities are common among infants with complex congenital heart disease (CHD). While hemispheric asymmetries in normal fetal brain size and shape have been reported, the effect of CHD on hemispheric development of the developing fetal brain remains unknown. Hypothesis: We hypothesized that emerging cerebral hemispheric asymmetries of the fetal CHD brain would differ compared to healthy controls using in vivo MRI tools. Methods: A total of 252 pregnant women were recruited (164 controls; 88 CHD fetuses), in which 328 fetal MRI scans were performed. Single shot fast spin echo T2-weighted images were acquired on a 1.5T GE MRI scanner. High-resolution 3D models of the fetal brain were reconstructed using slice-to-volume registration method for motion correction and Draw-EM algorithm for automatic segmentation. Volumetric analysis of brain tissues was conducted, and cortical folding measures of brain lobes were evaluated. Mixed effects regression was utilized to compare the brain features between right and left hemispheres for healthy controls and CHD fetuses. Results: The mean gestational age of all fetal MRI studies was 32.1±3.7 weeks (range: 24.0-39.4). For healthy fetuses, the volume of cortical gray matter was higher in the left hemisphere; however, this pattern was diminished in CHD fetuses. Gyrification indices were higher in the parietal and occipital lobes of the right hemisphere for controls, but not for CHD fetuses. Similarly, Gaussian curvature was higher in the right frontal lobe for controls only. Conversely, the surface area of the left occipital lobe was lower in CHD fetuses, but not in healthy fetuses. Conclusions: We report for the first time early disturbances in emerging hemispheric asymmetric patterns of the fetal brain in CHD compared to controls. The extent to which these lateralization differences reflect genetic, epigenetic and/or hemodynamic disturbances in CHD fetuses is under investigation.

Clinical characteristics and outcomes after pulmonary vein isolation in atrial fibrillation patients with complete right bundle branch block

Abstract Background Complete right bundle branch block (CRBBB) is one of the most frequent alterations of the electrocardiogram (ECG). Several studies have shown that CRBBB was a risk factor for cardiovascular diseases and the appearance of CRBBB in patients hospitalized for exacerbated heart failure (HF) was associated with a worse prognosis. Various alternations of ECG such as early repolarization pattern and intraventricular conduction disturbance were associated with high recurrence ratio of atrial fibrillation (AF) after pulmonary vein isolation (PVI). However clinical outcome after PVI in patients with CRBBB remains unclear. Methods We enrolled consecutive AF patients who underwent PVI from September 2014 to November 2018 rom Osaka Rosai Atrial Fibrillation (ORAF) registry. We excluded patients with other wide QRS (left bundle branch block, ventricular pacing and unclassified intraventricular conduction disturbance) and divided into 2 groups; CRBBB (QRS duration ≥120msec) group and no-CRBBB (QRS duration <120) group. We compared the clinical characteristics including age, gender, hypertension, diabetes mellitus, history of heart failure, history of stroke, CHADS2Vasc score, paroxysmal AF (PAF), renal function, plasma brain natriuretic peptide (BNP) level and echocardiographic parameters including left ventricular end-diastolic diameter (LVDd), left ventricular end-systolic diameter (LVDs), left atrial diameter (LAD) and left ventricular ejection fraction (LVEF) between the 2 groups. We also compared the incidence of late recurrence of AF/atrial tachycardia (AT) between the 2 groups. We investigated whether CRBBB was an independent predictor of late recurrence of AF/AT after PVI by multivariate Cox analysis. Results We enrolled 736 consecutive AF patients who underwent PVI. CRBBB patients comprised 55 patients (7.5%). There were no significant differences of age, gender, hypertension, diabetes mellitus, history of heart failure, history of stroke, CHADS2Vasc score, PAF, renal function, plasma BNP level and echocardiographic parameters (LVDd, LVDs, LVEF and LAD) between the 2 groups. Incidence of AF/AT recurrence after PVI was significantly higher in CRBBB group than no-CRBBB group (Figure). CRBBB was an independently and significantly associated with late recurrence of AF/AT after PVI by multivariate Cox analysis (hazard ratio: 1.923, 95% CI: 1.190–2.961, p=0.009) in addition to female (p<0.001), no-PAF (p=0.005) and left atrial diameter (p=0.042). Conclusion CRBBB may be a strong predictor of AF/AT late recurrence after PVI. AF/Ar recurrence after PVI Funding Acknowledgement Type of funding source: None

Effects of tobacco addiction on links between early life adversities, sleep disturbance, and depression: A moderated mediation approach.

Despite the well-established relationship between early life adversities (ELA) and depression, the underlying mechanisms for this link remain less clear and need to be developed. The aim of this study was to advance our understanding of this link by testing the mediating role of sleep disturbances and the moderating role of tobacco use in this mediation. A total of 579 smokers and non-smokers were recruited in two US communities (Duluth and Minneapolis, MN). Simple and moderated mediation analyses were performed using the PROCESS macro for SPSS, with the number of ELA as an independent variable, depression symptoms assessed by the Patient Health Questionnaire-9 (PHQ-9) as a dependent variable, sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI) as a mediator, and smoking status as a moderator variable. The study demonstrated that ELA and depressive symptoms were positively correlated; and sleep quality fully mediated this relationship. This mediation was moderated by tobacco use (index of moderated mediation = 0.10, 95%CI [0.03; 0.19]) and was more pronounced among smokers (b = 0.14, 95%CI [0.07; 0.23]) than non-smokers (b = 0.04, 95%CI [0.0002; 0.10]). Subsequent mediation analyses run separately for each component of the PSQI suggested that individuals who experienced ELA and who were smokers had greater delays in sleep onset and were more likely to sleep for a shorter duration, both of which predicted greater depressive symptoms. Sleep quality is therefore a promising ELA-related target for preventive and therapeutic interventions as well as for further research in depression and tobacco addiction.

Maternal resistance to diet-induced obesity partially protects newborn and post-weaning male mice offspring from metabolic disturbances.

The rising rate of childhood overweight follows the increase in maternal obesity, since perinatal events impact offspring in a diversity of metabolic disorders. Despite many studies that have linked dietary consumption, overnutrition, or maternal obesity as the mediators of fetal metabolic programming, there are gaps regarding the knowledge about the contribution of different maternal phenotypes to the development of metabolic disturbances in offspring. This study aimed to investigate whether maternal high-fat diet (HFD) consumption without the development of the obese phenotype would protect offspring from metabolic disturbances. Female mice were fed standard chow diet or a HFD for 4 weeks before mating. HFD females were classified into obesity-resistant (OR) or obesity-prone (OP), according to weight gain. OP females presented with higher adiposity, fasting serum glucose and insulin, cholesterol and non-esterified fatty acid (NEFA). Newborn offspring from OP dams showed higher serum glucose and insulin and alteration in hepatic gene expression that may have contributed to the rise in hepatic fat content and decline of glycogen levels in the liver. Despite offspring from OR and OP females having showed similar growth after the day of delivery, offspring from OP females had higher caloric intake, fasting glucose, serum triglycerides and altered hepatic gene expression, as well as glucose and pyruvate intolerance and lower insulin sensitivity at d28 compared with offspring from OR females. Maternal pre-pregnancy serum glucose, insulin, and NEFA positively correlated with serum glucose and fat liver content and negatively correlated with hepatic glycogen in offspring. In conclusion, our results show that maternal resistance to diet-induced obesity partially protects offspring from early metabolic disturbances.

Surface-based morphometry study of the brain in benign childhood epilepsy with centrotemporal spikes

BackgroundThe study aimed to explore cortical morphology in benign childhood epilepsy with centrotemporal spikes (BECTS) and the relationship between cortical characteristics and age of onset and intelligence quotient (IQ).MethodsCortical morphometry with surface-based morphometry (SBM) was used to compare changes in cortical thickness, gyrification, sulcal depth, and fractal dimension of the cerebral cortex between 25 BECTS patients and 20 healthy controls (HCs) with two-sample t-tests [P<0.05, family-wise error (FWE) corrected]. Relationships between abnormal cortical morphological changes and age of onset and IQ, which included verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ), and full-scale intelligence quotient (FIQ) were investigated with Spearman correlation analysis (P<0.05, uncorrected).ResultsThe BECTS patients showed extensive cortical thinning predominantly in bilateral frontal, temporal regions, and limbic system. Cortical gyrification increased in the left hemisphere and partial right hemisphere, and the decreased cortical gyrification was only in the left hemisphere. The increased sulcal depth was the left fusiform gyrus. There are no statistically significant differences in the fractal dimension. Correlation analysis revealed the negative correlation between age of onset and cortical thickness in the right precentral gyrus. It also revealed the negative correlation between the age of onset and cortical gyrification in the left inferior parietal gyrus. Also, there was negative correlation between VIQ and cortical gyrification in the left supramarginal gyrus of BECTS patients.ConclusionsThis study reveals aberrant cortical thickness, cortical gyrification, and sulcal depth of BECTS in areas related to cognitive functions including language, attention and memory, and the correlation between some brain regions and VIQ and age of onset, providing a potential marker of early neurodevelopmental disturbance and cognitive dysfunction in BECTS.

Adult patients' wellbeing and disturbances during early recovery in the post anaesthesia care unit. A cross-sectional study

ObjectivesAssessment of patients’ wellbeing in the post anaesthesia care unit and how much each disturbance influences it. Furthermore, assessment of the incidence of the correlated disturbances and whether there are gender-specific aspects. Design/SettingObservational anonymised survey with a validated questionnaire in a university hospital in central Europe. Main Outcome MeasuresIncidence rates of wellbeing and disturbances in the post anaesthesia care unit. ResultsThe patients’ most frequently reported early postsurgical disturbances (n = 349) were i) dry mouth (35.4%), ii) pain in the surgical area (12.7%) and iii) hunger (12.2%). Every other disturbance was below 10% (e.g. nausea). Subjective wellbeing was reported by 57.2% of our patients. There were weak correlations between wellbeing and physical discomfort, pain in the surgical area, sleepiness and nausea. The strongest correlation was with physical discomfort. Female patients showed more feelings of cold, nausea and headache. ConclusionEven in hospitals repeatedly certified in pain management, a high percentage of patients still claim early postoperative discomfort. We see the necessity for an increased focus on this topic and the need for investigations regarding patients' perception. The most frequent claims were related to pain in the surgical area and a dry mouth.

Disease-specific gait deviations in pediatric patients with X-linked hypophosphatemia

BackgroundX-linked hypophosphatemia (XLH) represents the most common genetic form of rickets featuring profound hypophosphatemia with associated skeletal and non-skeletal manifestations. Early onset gait disturbances contribute strongly to the burden of disease. However, no study has comprehensively characterized naturally occurring gait deviations in pediatric patients with XLH. Research questionsCan disease-specific gait deviations and potentially influencing factors be identified by gait analysis in non-surgically treated children with XLH? MethodsGait laboratory assessments of 12 pediatric patients with XLH without previous long bone surgery was retrospectively analyzed and compared to age-matched healthy controls. Radiologic and clinical parameters of XLH patients were correlated with kinematic gait variables and gait scores. ResultsReduced external knee rotation and increased external hip orientation was ubiquitous in children with XLH. Increased lateral trunk lean, or “waddling gait”, occurred in five children and was associated with varus knee deformities. Overall, children with XLH showed a reduced Gait Deviation Index (GDI) compared to controls. Radiologic and gait analysis revealed complex combined frontal and torsional deformity of the lower limbs as a common feature in XLH. Higher Body Mass Index (BMI) was associated with both lateral trunk lean and impaired GDI. SignificanceGait analysis is feasible to quantify gait deviations and lower limb deformities in pediatric patients with XLH. Specific gait characteristics including internal knee rotation and external hip rotation are common among patients with XLH and contribute to impaired gait scores. Our data suggest the use of gait and deformity data assessment as outcome parameters in future observational and interventional studies. Standardized assessment might contribute to targeted treatments to improve life quality in XLH patients.

Evaluation of early relational disturbance in high-risk populations: Borderline personality disorder features, maternal mental state, and observed interaction.

Despite the longstanding theoretical association in the attachment literature between maternal trauma history and disturbances in the mother-infant interaction, few studies have investigated mechanisms of transmission of traumatogenic relational patterns in high-risk mother-infant dyads. This study investigated interrelationships among maternal trauma history, distorted maternal representations (DMRs, i.e. disturbed thoughts and feelings about the infant and self-as-parent), maternal mentalisation (i.e. capacity to conceive of self and other's intentions in terms of mental states including thoughts, feelings, and desires), and quality of interaction in a clinical sample of mothers with Borderline Personality Disorder (BPD) features and their infants (N=61). Measures used included the Childhood Trauma Questionnaire, Parent Development Interview, Mother-Infant Relationship Scale, Borderline Symptom Checklist-23, and the Emotional Availability Scales. The results indicated BPD features mediated the relationship between maternal trauma history and DMRs predicting disturbance in interaction. In addition, analyses showed that maternal mentalisation had a buffering effect between DMRs and maternal non-hostility and yet the severity of BPD features moderated the relationship between mentalisation and DMRs. The findings suggest postpartum borderline pathology may adversely impact the experience of being a parent for women with a relational trauma history including deficits in mentalisation (i.e. hypermentalising) and disturbances in the mother-infant interaction. Implications for research and clinical practice are discussed.

Proteome-wide assessment of diabetes mellitus in Qatari identifies IGFBP-2 as a risk factor already with early glycaemic disturbances

BackgroundProteomics is expected to provide novel insights in the underlying pathophysiology of type 2 diabetes mellitus. In the present study, we aimed to identify and biochemically characterize proteins associated with diabetes mellitus in a Qatari population. MethodsIn a diabetes case-control study (175 cases, 164 controls; Arab, South Asian and Philippine ethnicities), we conducted a discovery study to screen 1141 blood protein levels for associations with diabetes mellitus. Additional analyses were done in controls in relation to Hb1Ac, and biochemical characterization of the main findings was performed with metabolomics (501 metabolites). We performed two-sample Mendelian Randomization to provide evidence of potential causality using data from European descent of the DIAGRAM consortium (74,124 cases of diabetes mellitus and 824,006 controls) for the identified proteins for T2D and Hb1Ac. ResultsAfter accounting for multiple testing, 30 protein levels were different (p-values<8.6e−5) between cases and controls. Of these, a higher Hb1Ac in controls was associated with a lower IGFBP-2 level (p-value = 4.1e−6). IGFBP-2 protein level was found lower among cases compared with controls across all ethnicities. In controls, IGFBP-2 was associated with 21 metabolite levels, but specifically connected to the metabolite citrulline in network analyses. We observed no evidence, however, that the association between IGFBP-2 and diabetes mellitus was causal. ConclusionsWe specifically identified IGFBP-2 to be associated with diabetes mellitus, although with no evidence for causality, which was specifically connected to citrulline metabolism.

Perinatal exposure to omega-3 fatty acid imbalance leads to early behavioral alterations in rat pups

Polyunsaturated long-chain omega-3 fatty acids (n3-PUFAs) are crucially involved in brain development and function. Inadequate n3-PUFA intake in rats during the perinatal period leads to behavioral deficits in adulthood, but early behavioral changes have not yet been investigated. The present study aimed to investigate potential behavioral alterations in neonatal rats exposed to a perinatal n3-PUFA imbalance. Female Sprague Dawley rats were fed an n3-PUFA–enriched or an n3-PUFA–deficient diet throughout mating, pregnancy, and lactation. Controls were fed an n6/n3-PUFA–balanced diet. We observed maternal behavior from postnatal day (PND) 2 to PND 13 and tested pups in the isolation-induced ultrasonic vocalization (USV) emission task at PNDs 3, 5, 9 and 13 to evaluate the impact of perinatal n3-PUFA on early emotional traits. Both the n3-PUFA–enriched and n3-PUFA–deficient diets profoundly decreased maternal behavior. At PNDs 3 and PND 5, pups of the n3-PUFA–deficient or –enriched diet groups emitted significantly fewer USVs compared with control pups. Further, the sonographic pattern of the USVs was altered in the test pups compared with the control pups at PND 9 and PND 13. The present findings indicate that both n3-PUFA deficiency and supplementation induce alterations in mother-infant interaction and early behavioral disturbances in the offspring.

Physicochemical and microbial properties of urban park soils of the cities of Marrakech, Morocco and Toruń, Poland: Human health risk assessment of fecal coliforms and trace elements

The public green space (PGS) in urban areas presents an image of nature and its animal and plant biodiversity in the city. Due to intense urbanization in the world, pollutants such as trace elements (TE) or pathogenic microorganisms are continually emitted into the environment and pose a threat to ecosystems. The aim of this work was to assess the soil quality of PGS in the cities of Marrakech (Morocco) and Toruń (Poland) through physicochemical and microbiological approaches and to assess related health risks. Eighteen soils from the most visited historic parks in Marrakech and Toruń were sampled and analyzed. The results showed that content of Total Organic Carbon (TOC) in Toruń urban soils is about three times higher than that measured in Marrakech urban park soils. These differences are related to the naturally higher content of organic matter in the soils of temperate climate regions than in Mediterranean soils. The concentrations of trace element (TE) showed a similar trend in both cities, except for Pb in one Marrakech site, which exhibited a high concentration (400 mg Pb Kg−1 in Bab Rab Park). Soil enzymes present a high sensitivity to anthropogenic disturbances and can be used as tool to evaluate early disturbance of urban soils. The alkaline phosphatase (APHa) and urease (URa) activities are less affected by anthropogenic pressure than dehydrogenase (DHa). Slight sensitivity to TE was observed in the microbial community in the order fungi < actinomycetes < bacteria. Total and fecal coliforms (TC, FC) were present in all soil samples, with higher concentrations in Marrakech sites. Based on estimated FC risk, the highest percentage did not exceed 11% of the guideline limit set by International Commission on Microbiological Specifications for Foods. Hazard index showed no health risk for adults caused by studied TE concentrations in the park soils of Marrakech and Toruń, but potential adverse non-cancer health effects for children. Their safety depends on their own behavior and the ways by adults supervise them.

Thinner Medial Orbital Frontal Cortex is Associated With Early PTSD Symptoms, Sleep Disturbance, and Mental Health Problems that May Contribute to PTSD Development After Acute Trauma

Thinner Medial Orbital Frontal Cortex is Associated With Early PTSD Symptoms, Sleep Disturbance, and Mental Health Problems that May Contribute to PTSD Development After Acute Trauma

Hippocampal-Amygdala Resting State Functional Connectivity Serves as Resilience Factor for Short- and Long-Term Stress Exposure

Stressful experiences modulate neuro-circuitry function, and the temporal trajectory of these alterations, elapsing from early disturbances to late recovery, heavily influences resilience for psychopathology. In our previous work, we found that sustainability of subjective stress feeling following an acute social stressor, corresponded to neural stress response as indicated by resting-state functional connectivity (rsFC). In particular, we found that sustained enhancement of amygdala-hippocampus rsFC, for as long as 2 hours following lab stress induction, anti-correlated with faster recovery in stress feelings (Vaisvaser et al., 2013, 2016). Nevertheless, it is yet unknown if such acute rsFC changes could also mark long-term recovery from traumatic life stress.

A procedure to extract functional isolated mitochondria from small-sized human atrial samples. Application to obesity with a partial characterisation of the organelles

Evaluating the activity of cardiac mitochondria is probably the best way to estimate early cellular damage in chronic pathology. Early diagnosis allows rapid therapeutic intervention thus increasing patient survival rate in a number of diseases. However, data on human cardiac mitochondria are scarce in the international literature. Here, we describe a method to extract and study functional mitochondria from the small-sized right atrial aliquots (minimum of 400 mg) obtained during extracorporeal circulation and usually considered as surgical waste products. The mitochondria were purified through several mechanical processes (fine myocardial cutting, tissue grinding and potter Elvehjem homogenising), an enzymatic proteolytic action (subtilisin) and differential centrifugations. In chronic pathologies, including obesity, early disturbances of mitochondrial function can occur. The effects of obesity on the rate of mitochondrial oxygen consumption and H2O2 release were thus determined with three different substrates (glutamate/malate, succinate/rotenone and palmitoylcarnitine/malate). The human atrial mitochondria were of high quality from a functional viewpoint, compared to rat ventricle organelles, but the extraction yield of the human mitochondria was twice lower than that of rat mitochondria. Tests showed that glutamate/malate-related ADP-stimulated respiration was strongly increased in obese subjects, although the oxidation of the other two substrates was unaffected. Reactive oxygen species (ROS) production by the isolated mitochondria was low in comparison with that of the lean subjects. These results confirm those found in one of our previous studies in the ventricles of rats fed a high-fat diet. In conclusion, the described method is simple, reliable and sensitive. It allows for the description of the impact of obesity on the function of atrial mitochondria while using only a small patient sampling (n = 5 in both the lean and the obese groups).

Endothelial dysfunction and myocardial injury after major emergency abdominal surgery: a prospective cohort study

BackgroundPreoperative endothelial dysfunction is a predictor of myocardial injury and major adverse cardiac events. Non-cardiac surgery is known to induce acute endothelial changes. The aim of this explorative cohort study was to assess the extent of systemic endothelial dysfunction after major emergency abdominal surgery and the potential association with postoperative myocardial injury.MethodsPatients undergoing major emergency abdominal surgery were included in this prospective cohort study. The primary outcome was the change in endothelial function expressed as the reactive hyperemia index from 4-24 h after surgery until postoperative day 3–5. The reactive hyperemia index was assessed by non-invasive digital pulse tonometry. Secondary outcomes included changes in biomarkers of nitric oxide metabolism and bioavailability. All assessments were performed at the two separate time points in the postoperative period. Clinical outcomes included myocardial injury within the third postoperative day and major adverse cardiovascular events within 30 days of surgery.ResultsBetween October 2016 and June 2017, 83 patients were included. The first assessment of the endothelial function, 4–24 h, was performed 15.8 (SD 6.9) hours after surgery and the second assessment, postoperative day 3–5, was performed 83.7 (SD 19.8) hours after surgery. The reactive hyperemia index was suppressed early after surgery and did not increase significantly; 1.64 (95% CI 1.52–177) at 4–24 h after surgery vs. 1.75 (95% CI 1.63–1.89) at postoperative day 3–5, p = 0.34. The L-arginine/ADMA ratio, expressing the nitric oxide production, was reduced in the perioperative period and correlated significantly with the reactive hyperemia index. A total of 16 patients (19.3%) had a major adverse cardiovascular event, of which 11 patients (13.3%) had myocardial injury. The L-arginine/ADMA ratio was significantly decreased at 4–24 h after surgery in patients suffering myocardial injury.ConclusionThis explorative pathophysiological study showed that acute systemic endothelial dysfunction was present early after major emergency abdominal surgery and remained unchanged until day 3–5 after the procedure. Early postoperative disturbances in the nitric oxide bioavailability might add to the pathogenesis of myocardial injury. This pathophysiological link should be confirmed in larger studies.Trial registrationclinicaltrials.gov no. NCT03010969.

Metabolomics analyses in non-diabetic middle-aged individuals reveal metabolites impacting early glucose disturbances and insulin sensitivity

IntroductionSeveral plasma metabolites have been associated with insulin resistance and type 2 diabetes mellitus.ObjectivesWe aimed to identify plasma metabolites associated with different indices of early disturbances in glucose metabolism and insulin sensitivity.MethodsThis cross-sectional study was conducted in a subsample of the Leiden Longevity Study comprising individuals without a history of diabetes mellitus (n = 233) with a mean age of 63.3 ± 6.7 years of which 48.1% were men. We tested for associations of fasting glucose, fasting insulin, HOMA-IR, Matsuda Index, Insulinogenic Index and glycated hemoglobin with metabolites (Swedish Metabolomics Platform) using linear regression analysis adjusted for age, sex and BMI. Results were validated internally using an independent metabolomics platform (Biocrates platform) and replicated externally in the independent Netherlands Epidemiology of Obesity (NEO) study (Metabolon platform) (n = 545, mean age of 55.8 ± 6.0 years of which 48.6% were men). Moreover, in the NEO study, we replicated our analyses in individuals with diabetes mellitus (cases: n = 36; controls = 561).ResultsOut of the 34 metabolites, a total of 12 plasma metabolites were associated with different indices of disturbances in glucose metabolism and insulin sensitivity in individuals without diabetes mellitus. These findings were validated using a different metabolomics platform as well as in an independent cohort of non-diabetics. Moreover, tyrosine, alanine, valine, tryptophan and alpha-ketoglutaric acid levels were higher in individuals with diabetes mellitus.ConclusionWe found several plasma metabolites that are associated with early disturbances in glucose metabolism and insulin sensitivity of which five were also higher in individuals with diabetes mellitus.

Cortical and Striatal Circuits in Huntington's Disease.

Huntington’s disease (HD) is a hereditary neurodegenerative disorder that typically manifests in midlife with motor, cognitive, and/or psychiatric symptoms. The disease is caused by a CAG triplet expansion in exon 1 of the huntingtin gene and leads to a severe neurodegeneration in the striatum and cortex. Classical electrophysiological studies in genetic HD mouse models provided important insights into the disbalance of excitatory, inhibitory and neuromodulatory inputs, as well as progressive disconnection between the cortex and striatum. However, the involvement of local cortical and striatal microcircuits still remains largely unexplored. Here we review the progress in understanding HD-related impairments in the cortical and basal ganglia circuits, and outline new opportunities that have opened with the development of modern circuit analysis methods. In particular, in vivo imaging studies in mouse HD models have demonstrated early structural and functional disturbances within the cortical network, and optogenetic manipulations of striatal cell types have started uncovering the causal roles of certain neuronal populations in disease pathogenesis. In addition, the important contribution of astrocytes to HD-related circuit defects has recently been recognized. In parallel, unbiased systems biology studies are providing insights into the possible molecular underpinnings of these functional defects at the level of synaptic signaling and neurotransmitter metabolism. With these approaches, we can now reach a deeper understanding of circuit-based HD mechanisms, which will be crucial for the development of effective and targeted therapeutic strategies.

Temporal Occurrence of Arrhythmic Complications After Alcohol Septal Ablation.

The temporal occurrence of arrhythmic complications after alcohol septal ablation (ASA) is unclear. As a result, the appropriate time to monitor patients after ASA is controversial. The purpose of this study is to determine the temporal occurrence of complete heart block (CHB) and ventricular tachyarrhythmia (VT) after ASA to better understand when patients can be safely discharged. Consecutive patients treated with ASA for hypertrophic cardiomyopathy from 2003 to 2019 at a tertiary referral center were reviewed retrospectively. The incidence and timing of CHB or sustained VT within 30 days post-ASA were assessed. A total of 243 patients were included in this study. Mean maximal septal thickness was 19.0±3.9 mm, and total volume of ethanol injected was 1.7±0.6 mL. CHB occurred in 59 (24.3%) patients, including transient CHB in 33 (13.6%) and permanent in 26 (10.7%). The initial episode of CHB occurred within 24 hours post-ASA in 51 (21.0%) patients, between 24 and 48 hours in 3 (1.2%), between 48 and 72 hours in 3 (1.2%), and after 72 hours in 2 (0.8%). New permanent pacemaker was placed in 46 (18.3%). Presence of baseline bundle branch block and age ≥70 were significantly associated with CHB but not CHB presenting after 24 hours. VT occurred in 3 (1.2%) patients, including 1 (0.4%) within 24 hours, 1 (0.4%) between 24 and 48 hours, and 1 (0.4%) after 72 hours. VT required cardioversion in 2 patients and new implantable cardioverter-defibrillator placement in 2. The incidence of CHB or VT presenting after 72 hours post-ASA was low. These findings suggest that timely discharge of patients without evidence of early conduction disturbances after ASA can be considered as a potentially safe management strategy, especially in patients without preexisting conduction abnormalities.

Hormonal changes and reproductive health issues in females with tuberculosis

Background/aimsThe association between tuberculosis (TB) and female reproductive health issues usually remains unaddressed. TB is considered as one of the major causes of infertility in India. Because of the associated stigma, the suffering females do not discuss the problems they are facing. This may lead to disturbances in serum hormone levels also.Hence, a study was planned to find abnormalities in menstrual patterns and fertility in women in childbearing age, who were suffering from TB, and evaluate disturbances in serum hormone levels of LH, FSH, Prolactin and testosterone, if any. It also aimed to evaluate if hormone levels, or some early disturbances in menstrual cycle, can serve as a predictor for infertility in future lives. Materials and methods25 female patients each of child bearing age group from OPD/IPD: of pulmonary TB (PTB), extra pulmonary non genital TB (EPTB), extra pulmonary genital TB (GTB) and healthy controls were enrolled. Thus, a total of 75 patients with TB and 25 healthy controls were taken into the study.Patients were questioned for any abnormalities of menstrual cycle. If married, fertility status, total number of live children, abortions etc and previous history of any reproductive health issues was asked. Serum FSH, LH, Prolactin and testosterone levels on the 3rd day of the menstrual cycle were done. Data so obtained was tabulated and statistically analyzed. ResultsTB patients (75/100) and healthy controls (25/100) were matched with respect to age, marital status and rural/urban background. Menstrual abnormalities, infertility and adverse events related to pregnancy were higher in patients with TB than healthy controls (p = 0.176, 0.571 and 0.005 respectively). TB patients had significantly higher levels of Testosterone and significantly lower levels of Prolactin than healthy controls (p=<0.001). Levels of FSH and LH were lower in TB patients than healthy controls (p = 0.428 and 0.274 respectively).On categorization into different types of TB, the sub-groups were matched with respect to rural/urban background. GTB was significantly higher in patients who were married (p = 0.020). Significantly higher GTB patients (10/25) reported menstrual abnormalities (p < 0.001). All the 3 infertile patients reported in the study belonged to GTB sub-group (p = 0.044). GTB had higher number of adverse events related to pregnancy followed by EPTB and PTB.Levels of FSH, LH, Testosterone and Prolactin in the three sub-groups of TB patients did not show any significant difference (p = 0.683, 0.817, 0.781, and 0.187).Since the total number of infertile patients in our study was only 3, relationship of menstrual abnormalities or serum hormone levels as a predictor of infertility could not be assessed. ConclusionFemales suffering from TB experience significantly higher adverse events related to pregnancy than healthy controls. Menstrual abnormalities, infertility and adverse events related to pregnancy were more pronounced in females suffering from GTB than PTB/EPTB.Female patients suffering from any form of TB need to be comprehensively managed. Because of highly sensitive issues related to infertility and reproductive health in today's era, it is imperative that any future complications of the same are kept into consideration in female patients with TB.

Experimental Evaluation of the Influence of Early Disturbance on the Performance of Basalt Fiber Concrete

By applying early disturbance to the concrete, the influence of the disturbance on the macroscopic mechanical properties of basalt fiber concrete during the period from the initial setting to the final setting is explored, and the influence mechanism is revealed. Also, the influence of this disturbance on the process of sulfate erosion of concrete is evaluated by the sulfate erosion test and by the ultrasonic data acquisition of its damage process. The experimental results show that the flexural strength of basalt fiber concrete is increased after the concrete has been disturbed in the early stage of condensation but is decreased in the middle stage of condensation and is not affected in the later stage. When the condensation and hardening processes are disturbed, damage is caused inside the concrete, which is greater with the increase in the condensation degree until the penetration resistance reaches about 15 MPa, which then is more and more reduced. The durability of basalt fiber concrete is reduced by disturbance, which has a significant effect on it when the penetration resistance is between 7 MPa and 16 MPa.