Subsequent Onset Research Articles

Prevalence of infantile wheezing and eczema in a metropolitan city in Japan: A complete census survey.

Infantile wheezing and eczema are associated with the subsequent onset of asthma and other atopic diseases. However, there are no large population-based surveys on infantile allergic symptoms in Japan. The objective of the study was to determine the prevalence of wheezing and asthma in infants in Nagoya, Japan. This population-based cross-sectional study was performed in the metropolitan city of Nagoya, Japan. We surveyed parents to ascertain the prevalence of wheezing and eczema in infants who attended group health checkups at 3, 18, and 36 months of age. Their parents completed modified questionnaires from the International Study of Asthma and Allergies in Childhood. More than 90% of the approximately 40,000 children in each study group living in the target area were included in the survey. The prevalence of wheezing was 8%, 17%, and 13% at 3, 18, and 36 months, respectively, and was characterized by birth season. The prevalence of eczema was 24%, 30%, and 31%, at 3, 18, and 36 months, respectively. Participants born in autumn and winter had a higher incidence of eczema in each age group. Three-quarters of the children had a parental history of allergic conditions. Parental allergic diseases and male gender are risk factors for wheezing and eczema in children. This survey had a high response rate and covered almost the entire population of the target age groups in a large city. We believe that the results of this study, therefore, provide a much higher level of confidence regarding the prevalence of allergies in infants in Japan than that in previous studies with limited cohorts.

Prevalence of Contralateral Hip Abductor Tears and Factors Associated With Symptomatic Progression

Background: Patients with gluteus medius tendinopathy present with laterally based hip pain that can be diagnosed under the greater trochanteric pain syndrome diagnosis. Magnetic resonance imaging (MRI) can assist in diagnosing pathology of the symptomatic hip, and when a pelvic MRI that includes both hips, the clinician may identify asymptomatic tears in the nonsurgical hip. In patients who undergo unilateral gluteus medius repairs, little is known about the prevalence or subsequent onset of clinical symptoms in the nonsurgical hip. Purpose: To describe (1) the prevalence of asymptomatic contralateral gluteus medius tears in patients with unilateral symptoms, (2) the presentation and time before symptom onset, and (3) the morphological characteristics on MRI of future symptomatic tears. Study Design: Case series; Level of evidence, 4. Methods: A total of 51 consecutive patients who underwent gluteus medius tear surgery were reviewed for contralateral hip pathology; of these, 43 patients were 2 years out from index surgery with reviewable preoperative MRI scans. A musculoskeletal radiologist reviewed the MRI scans for tear size, tendon retraction, and fatty infiltration using the Goutallier-Fuchs grading system. Medical record review identified contralateral hips requiring subsequent treatment. Results: Of the original 43 patients, 10 (23%) had no contralateral tear, 19 (44%) had low-grade partial tears, 9 (20%) had high-grade partial tears, and 5 (11%) had full-thickness tears. Thirty-seven patients had unilateral symptoms; the other 6 had mild contralateral hip pain at enrollment. Of the 37 patients with unilateral symptoms, 27 (73%) had a contralateral tear; of those, 10 became symptomatic at an average of 24 months after index presentation (range, 6-50 months). In patients with symptomatic progression, 7 had low-grade partial tears, 1 had a high-grade partial tear, and 2 had full-thickness tears, with an average retraction of 17 mm. Tendon tear grade on MRI did not always correlate with symptoms or future presentation. All symptomatic progression remained mild to moderate. Seven patients required a corticosteroid injection, and none needed contralateral hip surgery within 2 years. Conclusion: Of patients who underwent surgery for a gluteus medius tear, 73% (27/37) had an incidental MRI-confirmed contralateral hip abductor tear. Of these, 37% (10/27) developed symptoms consistent with greater trochanteric pain syndrome during the 2-year study period.

Protein-losing enteropathy recurrence after pediatric heart transplantation: Multicenter case series.

Protein-losing enteropathy (PLE) is a devastating complication of the Fontan circulation. Although orthotopic heart transplantation (HTx) typically results in resolution of PLE symptoms, isolated cases of PLE relapse have been described after HTx. Patients with Fontan-related PLE who had undergone HTx at participating centers and experienced relapse of PLE during follow-up were retrospectively identified. Available data related to pre- and post-HTx characteristics and PLE events were collected. Eight patients from four different centers were identified. Median time from Fontan procedure to the development of PLE was 8years, and median age at HTx was 17years (range 7.7-21). In all patients, PLE resolved at a median time of 1month after HTx (0.3-5). PLE recurrences occurred at a median time of 7.5months after HTx (2-132). Each occurrence was associated with one or more significant clinical events; most commonly cellular- or antibody-mediated rejection; and less commonly graft dysfunction, infection, thrombosis, and posttransplant lymphoproliferative disease. PLE recurrences resolved after the successful treatment of the concomitant event, after a median time of 2months in seven cases, while persisted and recurred in one patient in association with atypical mycobacterium infection and subsequent PTLD onset and relapses. Six patients were alive during follow-up at a median time of 4years (1.3-22.5) after HTx. This is the largest series of PLE recurrence after HTx. All cases were associated with one or more concomitant and significant clinical events. PLE typically resolved after resolution of the inciting clinical event.

Can the First Fasting Plasma Glucose Test in Pregnancy Predict Subsequent Gestational Complications?

Objective To determine the best cut-off level of pregnant women's first fasting plasma glucose (FFPG) test results for the prediction of subsequent onset of gestational diabetes mellitus (GDM) and to examine the association between FFPG and maternal and neonatal outcomes in a large Caucasian population. Methods 1437 medical records of women with singleton pregnancies followed up between 2015 and 2018 were retrospectively analyzed. Data on FFPG tested in the first trimester and 75 g oral glucose tolerance test (OGTT) findings performed according to IADPSG criteria and Italian guidelines were collected and evaluated. The women's clinical and metabolic characteristics (age, prepregnancy body mass index (BMI), previous pregnancies complicated by GDM, timing of delivery, and gestational hypertension) were also recorded. The fetal variables considered were being large for gestational age (LGA) or small for gestational age (SGA), macrosomia, and hypoglycemia. Results Among the 1437 pregnant women studied, 684 had a normal glucose tolerance (NGT) and 753 developed GDM. In a univariate analysis FFPG ≥92 mg/dl predicts the risk of GDM with an OR = 2.36 (95% CI 1.930–3.186; p < 0.001). In multivariate analysis, after adjusting for principal risk factors of GDM (BMI, previous GDM, age >35 years, family history of diabetes) FFPG ≥92 mg/dl was associated with the risk of GDM (OR = 1.92; 95% CI 1.488–2.492; p < 0.001). In univariate analysis, FFPG ≥92 mg/dl predict the risk of insulin therapy in GDM women with a OR = 1.88 (95% CI 1.230–2.066; p < 0.001). As regards LGA, in a multivariate analysis, after adjusting for BMI, FFPG ≥92 mg/dl was associated with the risk of LGA only in NGT women (OR = 2.34; 95% CI 1.173–4.574; p=0.014), but not in GDM women. FFPG was not associated with other maternal or neonatal outcomes. Conclusions FFPG ≥92 mg/dl is related to GDM diagnosis and to the need of insulin therapy if GDM is diagnosed. An early diagnosis and a prompt start of insulin therapy are essential to prevent maternal and fetal complications.

Is early exposure to cannabis associated with bipolar disorder? Results from a Finnish birth cohort study.

Background and aimsThere are few longitudinal studies assessing the association of cannabis use and subsequent onset of bipolar disorder. We aimed to measure the association between early cannabis exposure and subsequent bipolar disorder.Design, Setting and ParticipantsObservational study linking a sample from the northern Finland birth cohort 1986 (n = 6325) to nation‐wide register data to examine the association of life‐time cannabis exposure at age 15/16 years and subsequent bipolar disorder until age 33 (until the end of 2018); 6325 individuals (48.8% males) were included in the analysis.MeasurementsCannabis exposure was measured via self‐report. Bipolar disorder was measured via bipolar disorder‐related diagnostic codes (ICD‐10: F30.xx, F31.xx) collected from the Care Register for Health Care 2001–18, the Register of Primary Health Care Visits 2011–18, the medication reimbursement register of the Social Insurance Institution of Finland 2001–05 and the disability pensions of the Finnish Center for Pensions 2001–16. Potential confounders included demographic characteristics, parental psychiatric disorders, emotional and behavioral problems and other substance use.FindingsThree hundred and fifty‐two adolescents (5.6%) reported any cannabis use until the age of 15–16 years. Of the whole sample, 66 (1.0%) were diagnosed with bipolar disorder. Adolescent cannabis use was associated with bipolar disorder [hazard ratio (HR) = 3.46; 95% confidence interval (CI) = 1.81–6.61]. This association remained statistically significant after adjusting for sex, family structure and parental psychiatric disorders (HR = 3.00; 95% CI = 1.47–6.13) and after further adjusting for adolescent emotional and behavioral problems (HR = 2.34; 95% CI = 1.11–4.94). Further adjustments for frequent alcohol intoxications, daily smoking and lifetime illicit drug use attenuated the associations to statistically non‐significant.ConclusionsIn Finland, the positive association between early cannabis exposure and subsequent development of bipolar disorder appears to be confounded by other substance use.

Optical Fingerprints of Nematicity in Iron-Based Superconductors

Nematicity, which refers to a phase of broken rotational but preserved translational symmetry, is underlined by the appearance of anisotropic properties and leaves remarkable fingerprints in all measurable physical quantities upon crossing the structural tetragonal-orthorhombic transition at Ts in several iron-based materials. Here, we review part of our own broadband optical investigations, addressing the impact of nematicity on the charge dynamics, as a function of temperature and of tunable applied stress, the latter acting as an external symmetry breaking field. We shall first focus our attention on FeSe, which undergoes a nematic (structural) transition without any subsequent onset of magnetic ordering below Ts. FeSe thus provides an opportunity to study nematicity without the limitations due to the reconstruction of the Fermi surface because of the spin-density-wave collective state in the orthorhombic phase, typical for several other iron-based superconductors. Our data reveal an astonishing anisotropy of the optical response in the mid-infrared-to-visible spectral range, which bears testimony of an important polarization of the underlying electronic structure in agreement with angle-resolved-photoemission-spectroscopy results. Our findings at high energy scales support models for the nematic phase resting on an orbital-ordering mechanism, supplemented by orbital selective band renormalization. The optical results at energies close to the Fermi level furthermore emphasize scenarios relying on scattering by anisotropic spin-fluctuations and shed new light on the origin of nematicity in FeSe. Moreover, the composition at which the associated Weiss temperature of the nematic susceptibility extrapolates to zero is found to be close to optimal doping (i.e., in coincidence with the largest superconducting transition temperature), boosting the debate to what extent nematic fluctuations contribute to the pairing-mechanism and generally affect the electronic structure of iron-based superconductors. The present review then offers a discussion of our optical data on the optimally hole-doped Ba0.6K0.4Fe2As2. We show that the stress-induced optical anisotropy in the infrared spectral range is reversible upon sweeping the applied stress and occurs only below the superconducting transition temperature. These findings demonstrate that there is a large electronic nematicity at optimal doping which extends right under the superconducting dome.

Association Between Acute Kidney Injury and Dementia in the Atherosclerosis Risk in Communities (ARIC) Study

Acute kidney injury (AKI) causes biochemical changes in the brain in animal models and is associated with adverse neurological complications in hospitalized patients. This study tested the association between AKI and incident dementia in a community-based cohort. Prospective cohort study. Adult participants in the Atherosclerosis Risk in Communities (ARIC) study who experienced hospitalized AKI compared with participants hospitalized for other reasons (primary analysis, mean follow-up period 4.3 years) or participants without hospitalized AKI (secondary analysis). Incident AKI, defined by ICD codes from hospital records. Incident dementia, diagnosed based on a combination of neurocognitive testing, informant interviews, ICD codes, and death certificates. In the primary analysis, we estimated the propensity for hospitalized AKI and matched these participants with those hospitalized for another reason to examine the association of AKI with subsequent onset of dementia (N= 1,708). In the secondary analysis, we estimated the association between time-varying hospitalized AKI and subsequent onset of dementia using multivariable Cox proportional hazards regression models, adjusted for age, sex, race/center, education, smoking status, body mass index, baseline estimated glomerular filtration rate, baseline urinary albumin-creatinine ratio, systolic blood pressure, coronary heart disease, diabetes, hypertension, apolipoprotein E (APOE) ε4 allele, and C-reactive protein. The mean age in the propensity-matched cohort was 76.1 ± 6.5 (SD) years, and 53.2% of the participants were women. People who were hospitalized with AKI had a higher risk of dementia (HR, 1.25 [95% CI, 1.02-1.52]; P= 0.03) compared with those without a hospitalization for AKI. The associations were slightly stronger in the time-varying analysis (HR, 1.69 [95% CI, 1.48-1.92]; P< 0.001). Other risk factors for dementia included older age, male sex, higher albuminuria, diabetes, current smoker status, and presence of the APOE risk alleles. Observational study, with AKI identified through diagnosis codes. Participants who experienced a hospitalization for AKI were at increased risk of dementia.

Longitudinal associations between e-cigarette use and onset of multiple modes of cannabis use among US adolescents

ObjectiveTo examine the prospective associations between e-cigarette use and subsequent onset of various modes of cannabis use during a 12-month follow-up period among US adolescents. MethodsData were from the Wave 4 (2017, baseline) and Wave 4.5 (12-month follow-up) surveys of the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative, longitudinal cohort study. Study population was cannabis-naïve US adolescents (12–16 years) at baseline who reported cannabis use status at follow-up (N = 9,692). Outcomes were modality-specific past-12-month cannabis use (vaping, blunting, smoking with hookah) and any cannabis use (past-12-month and past-30-day) at follow-up. Multivariate logistic regressions were used to estimate the weighted association between baseline past-30-day e-cigarette use and each outcome. ResultsBaseline e-cigarette use was significantly associated with onset of cannabis vaping (aOR = 4.00, 95% CI = 2.25–7.10), blunting (aOR = 5.30, 95% CI = 2.82–9.94), any cannabis use (aOR = 3.94, 95% CI = 2.35–6.62), and past-30-day cannabis use (aOR = 4.47, 95%CI = 2.64–7.58) at follow-up. Non-Hispanic blacks were more likely to report past-12-month blunting (aOR = 1.55, 95% CI = 1.07–2.24) and smoking cannabis with hookah (aOR = 3.13, 95% CI = 1.14–8.63) compared with non-Hispanic whites. Other tobacco use, alcohol use, perceiving e-cigarette use as having little or some harm, older age, high severity of externalizing mental health problems, and living in states legalized adult recreational cannabis use were significantly associated with future onset of cannabis vaping, blunting, and any cannabis use. ConclusionsThe association of e-cigarette use with cannabis vaping was not stronger than its association with other modes of cannabis use. Future studies are needed to explain the mechanisms linking e-cigarettes and cannabis use.

Risk Factors, Subsequent Disease Onset, and Prognostic Impact of Myocardial Infarction and Atrial Fibrillation.

BackgroundAlthough myocardial infarction (MI) and atrial fibrillation (AF) are frequent comorbidities and share common cardiovascular risk factors, the direction and strength of the association of the risk factors with disease onset, subsequent disease incidence, and mortality are not completely understood.Methods and ResultsIn pooled multivariable Cox regression analyses, we examined temporal relations of disease onset and identified predictors of MI, AF, and all‐cause mortality in 108 363 individuals (median age, 46.0 years; 48.2% men) free of MI and AF at baseline from 6 European population‐based cohorts. During a maximum follow‐up of 10.0 years, 3558 (3.3%) individuals were diagnosed exclusively with MI, 1922 (1.8%) with AF but no MI, and 491 (0.5%) individuals developed both MI and AF. Association of sex, systolic blood pressure, antihypertensive treatment, and diabetes appeared to be stronger with incident MI than with AF, whereas increasing age and body mass index showed a higher risk for incident AF. Total cholesterol and daily smoking were significantly related to incident MI but not AF. Combined population attributable fraction of cardiovascular risk factors was >70% for incident MI, whereas it was only 27% for AF. Subsequent MI after AF (hazard ratio [HR], 1.68; 95% CI, 1.03–2.74) and subsequent AF after MI (HR, 1.75; 95% CI, 1.31–2.34) both significantly increased overall mortality risk.ConclusionsWe observed different associations of cardiovascular risk factors with both diseases indicating distinct pathophysiological pathways. Subsequent diagnoses of MI and AF significantly increased mortality risk.

Calystegines Improve the Metabolic Activity of Human Adipose Derived Stromal Stem Cells (ASCs) under Hyperglycaemic Condition through the Reduction of Oxidative/ER Stress, Inflammation, and the Promotion of the AKT/PI3K/mTOR Pathway.

Hyperglycaemia and its resulting glucotoxicity are among the most prominent hallmarks of diabetes mellitus (DM) development. Persistent hyperglycaemia further leads to oxidative stress via mitochondrial dysfunction and subsequent ER stress onset, while associated hyperlipidaemia triggers the adipose tissue to secrete pro-inflammatory cytokines. In this study, the effect of calystegines has been investigated in an experimental model of hyperglycaemia induced on human ASCs cells. Different cellular pathways including apoptosis, oxidative and ER stress, inflammation as well as Pi3K/AKT/mTOR metabolic-associated axis have been evaluated by means on RT-qPCR, western blot, and flow cytometry techniques. Treatment of HuASCs cells with calystegines strongly promoted the hyperglycaemic cells survival and significantly diminished oxidative stress, mitochondrial dynamics failure and ER stress, while improving the endogenous cellular antioxidant defenses. Interestingly, nortropane alkaloids efficiently prevented the hyperglycaemia-mediated inflammatory response, as evidenced by the regulation of the pro- and anti-inflammatory response in HuASCs cells. Finally, we evidenced that calystegines may exert their protective effect on HuASCs cells metabolic functions through the restoration of the defective PI3K/AKT/mTOR pathway. Overall, the present investigation demonstrated that calystegines possess important abilities to protect HuASCs against hyperglycaemia-induced cellular dysfunction, and it evidenced that the observed effects are associated to the promotion of PI3K/AKT/mTOR pathway.

THE PROSECUTORIAL MONOPOLY OF THE SLOVAK PUBLIC PROSECUTION SERVICE: NO ACCESS TO JUSTICE FOR THE INJURED PARTY?

The recodification of criminal law realised in the Slovak Republic in 2005 brought several new elements to criminal proceedings. One of them was the expansion and significant strengthening of the discretion of the public prosecutor in criminal proceedings. However, this authority of the public prosecutor’s office is, in many cases, perceived sensitively and controversially in Slovak society, especially in connection with many cases and scandals, when the prosecutor simply stated that ‘the act did not occur’. One of the related problems is the fact that the injured party in the Slovak Republic has essentially no powers that would, independently of the prosecutor’s office, ensure the control of the prosecutor’s discretionary powers directly through an independent and impartial court. This situation also stems from the fact that the public prosecutor’s office has a prosecution monopoly in Slovak criminal proceedings. However, the current prosecution monopoly of the prosecutor’s office is not a rational consequence of its historical development in our territory but a consequence of the coup d’état in 1948 and the subsequent onset of the communist regime. The possibility for other entities (e.g., the injured party) to exercise their rights through criminal law institutions has thus been minimised. Based on the above, the aim of this paper is to examine the existing scope of the discretion of public prosecutors in Slovakia, analyse the possibilities of controlling the exercise of these powers, and answer the question of how to improve the current possibilities of the control.

A Bidirectional Relationship Between Hyperuricemia and Metabolic Dysfunction-Associated Fatty Liver Disease.

Background and aimsMetabolic dysfunction-associated fatty liver disease (MAFLD) is a newly emerged term that is suggested to better reflect the pathogenesis of nonalcoholic fatty liver disease (NAFLD); however, the association between hyperuricemia and MAFLD has not been explored in the Chinese population. Meantime, this study also examined the temporal relationship between the two entities in a longitudinal cohort.MethodsWe conducted a retrospective cross-sectional study including 1,587,962 individuals from 19 health check-up centers in China from 2009-2017 and a longitudinal study with 16,112 individuals. A logistic regression model was applied to determine the association between hyperuricemia and MAFLD in a cross-sectional study. The Cox regression model was used to explore the association between hyperuricemia at baseline and subsequent onset of MAFLD or the association between the presence of MAFLD at baseline and the subsequent incidence of hyperuricemia. The cross-lagged analysis was applied to exam the temporal relationship between hyperuricemia and MAFLD.ResultsIn the cross-sectional study, hyperuricemia showed a strong positive association with MAFLD after controlled potential confounders. In the longitudinal cohorts, hyperuricemia at baseline was associated with the new-onset of MAFLD, with a hazard ratio (HR) of 1.765 (95% CI: 1.512, 2.060). Interestingly, baseline MAFLD was also associated with the subsequent incidence of hyperuricemia, with an HR of 1.245 (95% CI: 1.106, 1.400). The cross-lagged path analysis revealed a bidirectional relationship between hyperuricemia and MAFLD.ConclusionsThe results suggested that hyperuricemia and MAFLD form a vicious cycle, resulting in more deterioration of metabolic status.

Temporal specificity of abnormal neural oscillations during phonatory events in laryngeal dystonia.

Laryngeal dystonia is a debilitating disorder of voicing in which the laryngeal muscles are intermittently in spasm resulting in involuntary interruptions during speech. The central pathophysiology of laryngeal dystonia, underlying computational impairments in vocal motor control, remains poorly understood. Although prior imaging studies have found aberrant activity in the CNS during phonation in patients with laryngeal dystonia, it is not known at what timepoints during phonation these abnormalities emerge and what function may be impaired. To investigate this question, we recruited 22 adductor laryngeal dystonia patients (15 female, age range = 28.83–72.46 years) and 18 controls (eight female, age range = 27.40–71.34 years). We leveraged the fine temporal resolution of magnetoencephalography to monitor neural activity around glottal movement onset, subsequent voice onset and after the onset of pitch feedback perturbations. We examined event-related beta-band (12–30 Hz) and high-gamma-band (65–150 Hz) neural oscillations. Prior to glottal movement onset, we observed abnormal frontoparietal motor preparatory activity. After glottal movement onset, we observed abnormal activity in the somatosensory cortex persisting through voice onset. Prior to voice onset and continuing after, we also observed abnormal activity in the auditory cortex and the cerebellum. After pitch feedback perturbation onset, we observed no differences between controls and patients in their behavioural responses to the perturbation. But in patients, we did find abnormal activity in brain regions thought to be involved in the auditory feedback control of vocal pitch (premotor, motor, somatosensory and auditory cortices). Our study results confirm the abnormal processing of somatosensory feedback that has been seen in other studies. However, there were several remarkable findings in our study. First, patients have impaired vocal motor activity even before glottal movement onset, suggesting abnormal movement preparation. These results are significant because (i) they occur before movement onset, abnormalities in patients cannot be ascribed to deficits in vocal performance and (ii) they show that neural abnormalities in laryngeal dystonia are more than just abnormal responses to sensory feedback during phonation as has been hypothesized in some previous studies. Second, abnormal auditory cortical activity in patients begins even before voice onset, suggesting abnormalities in setting up auditory predictions before the arrival of auditory feedback at voice onset. Generally, activation abnormalities identified in key brain regions within the speech motor network around various phonation events not only provide temporal specificity to neuroimaging phenotypes in laryngeal dystonia but also may serve as potential therapeutic targets for neuromodulation.

Cardiovascular Disease-Associated MicroRNA Dysregulation during the First Trimester of Gestation in Women with Chronic Hypertension and Normotensive Women Subsequently Developing Gestational Hypertension or Preeclampsia with or without Fetal Growth Restriction.

The aim of the study was to assess if cardiovascular disease-associated microRNAs would be able to predict during the early stages of gestation (within 10 to 13 weeks) subsequent onset of hypertensive pregnancy-related complications: gestational hypertension (GH) or preeclampsia (PE). Secondly, the goal of the study was to assess if cardiovascular disease-associated microRNAs would be able to detect the presence of chronic hypertension in early pregnancies. The retrospective study was performed on whole peripheral blood samples collected from singleton Caucasian pregnancies within the period November 2012 to March 2020. The case control study, nested in a cohort, involved all women with chronic hypertension (n = 29), all normotensive women that later developed GH (n = 83) or PE with or without fetal growth restriction (FGR) (n = 66), and 80 controls selected on the base of equal sample storage time. Whole peripheral blood profiling was performed with the selection of 29 cardiovascular disease-associated microRNAs using real-time RT-PCR. Upregulation of miR-1-3p (51.72% at 10.0% FPR) was observed in patients with chronic hypertension only. Upregulation of miR-20a-5p (44.83% and 33.33% at 10.0% FPR) and miR-146a-5p (65.52% and 42.42% at 10.0% FPR) was observed in patients with chronic hypertension and normotensive women with later occurrence of PE. Upregulation of miR-181a-5p was detected in normotensive women subsequently developing GH (22.89% at 10.0% FPR) or PE (40.91% at 10.0% FPR). In a part of women with subsequent onset of PE, upregulation of miR-143-3p (24.24% at 10.0% FPR), miR-145-5p (21.21% at 10.0% FPR), and miR-574-3p (27.27% at 10.0% FPR) was also present. The combination of microRNA biomarkers (miR-20a-5p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, and miR-574-3p) can predict the later occurrence of PE in 48.48% of pregnancies at 10.0% FPR in early stages of gestation. The combination of upregulated microRNA biomarkers (miR-1-3p, miR-20a-5p, and miR-146a-5p) is able to identify 72.41% of pregnancies with chronic hypertension at 10.0% FPR in early stages of gestation. Cardiovascular disease-associated microRNAs represent promising biomarkers with very good diagnostical potential to be implemented into the current first trimester screening program to predict later occurrence of PE with or without FGR. The comparison of the predictive results of the routine first trimester screening for PE and/or FGR based on the criteria of the Fetal Medicine Foundation and the first trimester screening for PE wo/w FGR using a panel of six cardiovascular disease-associated microRNAs only revealed that the detection rate of PE increased 1.45-fold (48.48% vs. 33.33%).

CHANGE IN URGENCY STATUS AMONG ULCERATIVE COLITIS PATIENTS: UNDERSTANDING THE IMPACT OF TREATMENT CHANGES FROM THE COREVITAS INFLAMMATORY BOWEL DISEASE REGISTRY

Abstract BACKGROUND Stooling urgency (also known as urgency to defecate) is one of the most common symptoms among Ulcerative Colitis (UC) patients (pts). Understanding factors associated with changes in urgency status, such as the association between timing of treatment changes and subsequent onset or resolution of urgency symptoms, are essential in addressing unmet pts needs. Our aim was to explore treatment frequency and persistence among UC pts stratified by a change in urgency status from enrollment to the 6-month follow-up (6M) visit. METHODS Participants included UC pts in the CorEvitas Inflammatory Bowel Disease Registry between 5/3/17-9/1/20. Stooling urgency was defined as no urgency or urgency using the categories, none and hurry/immediate, from the Simple Clinical Colitis Activity Index (SCCAI). Urgency status groups were formed by urgency at enrollment and the 6M visit: no persistent urgency (NPU), i.e., no urgency at both visits; change from urgency to no urgency (UN); change from no urgency to urgency (NU); and persistent urgency at both visits (PU). Chi-square tests were conducted to compare treatment use and change between urgency status groups (NPU=reference group). Kaplan Meier curves and log-rank tests were used to assess time to first treatment change between urgency status groups. RESULTS The urgency status groups (n=400) included: 44% NPU (n=175), 21% UN (n=86), 14% NU (n=56), and 21% PU (n=83). A higher proportion of UN (47%, p=0.03) and PU (51%, p=0.01) pts received two or more treatments compared to NPU (33%) pts. Compared to NPU pts, pts in all three groups, UN (52% vs. 27%, p&amp;lt; 0.001), NU (45% vs. 27%, p=0.02), and PU (53% vs. 27%, p&amp;lt; 0.001) were more likely to change treatment between enrollment and the 6M visit. Similarly, a higher proportion of pts on a biologic at enrollment, UN (24% vs. 11%, p=0.01), NU (23% vs. 11%, p=0.03), and PU (35% vs 11%, p&amp;lt; 0.001), changed treatment between enrollment and the 6M visit vs. NPU pts. The time to first treatment change was shorter for all other urgency status groups when compared to NPU pts (log-rank tests, all p&amp;lt;0.02) (Figure 1). Among pts without urgency at enrollment, the time to first treatment change was shorter for NU vs. NPU pts (p=0.01) whereas it was similar for pts with urgency at enrollment, UN vs. PU pts (p=0.93) (Figure 1). CONCLUSION Among UC pts in a real-world setting, there were significant differences in change of treatment and time to treatment change between pts who experienced urgency either at their enrollment visit, 6M, or both, compared to those without urgency. Urgency at any time point is a symptom of great concern to UC pts, is a sign of inadequate therapy, and often is an indication to switch treatment therapy.

CHANGE IN URGENCY STATUS AMONG ULCERATIVE COLITIS PATIENTS: UNDERSTANDING THE IMPACT OF TREATMENT CHANGES FROM THE COREVITAS INFLAMMATORY BOWEL DISEASE REGISTRY

Stooling urgency (also known as urgency to defecate) is one of the most common symptoms among Ulcerative Colitis (UC) patients (pts). Understanding factors associated with changes in urgency status, such as the association between timing of treatment changes and subsequent onset or resolution of urgency symptoms, are essential in addressing unmet pts needs. Our aim was to explore treatment frequency and persistence among UC pts stratified by a change in urgency status from enrollment to the 6-month follow-up (6M) visit.

Structural development and tectonostratigraphic evolution of the Sylhet Trough (northeastern Bengal Basin) in the context of Cenozoic Himalayan Orogeny: Insights from geophysical data interpretation

The Sylhet Trough of the Bengal Basin in the northeastern Indian Plate had started to develop since the Late Mesozoic Gondwana break-up and subsequent onset of the Cenozoic Himalayan Orogeny. However, very little is known about evolution of the Cenozoic Sylhet Trough in response to the latter tectonic event. Therefore, we aim at providing insights into the nature of basement, variations in structural style, kinematics and possible timing of structural activation(s) and tectonostratigraphic evolution of the Sylhet Trough based on geophysical data interpretation. Results show that the Sylhet Trough is mostly underlain by an attenuated continental or oceanic crust, bounded by a NE-SW-trending geophysical feature in the northwest that corresponds to the boundary with the Precambrian continental crust. The overlying Cenozoic sediments show variations in style of deformations and can be divided into three structural domains. Domains 1 and 2 in the southeastern and northeastern parts of the Sylhet Trough, respectively, are characterized by anticlines that are highly deformed to the east and are mostly associated with west- or northwest-dipping reverse faults. However, the anticlinal trends are deviated from a generalized NS-orientation in the Domain 1 to a dominant NE-SW-orientation in the Domain 2. Many of these anticlines resemble positive flower structures, indicating possible impacts of regional transpression associated with the Dauki and Kaladan faults to the north and east; respectively. In contrast, the Domain 3 to the west shows NE-SW-trending extensional structures. A southward thickening of the Oligocene to Miocene pre-kinematic packages indicates an early episode of foreland basin subsidence, although there is no evidence of a major structural activation. Rather, the presence of the Pliocene syn-kinematic packages indicates a major structural reactivation in response to the E-W and N-S crustal shortening since the Pliocene. This younger episode of structural activation can be directly linked with the late Cenozoic subduction related processes of the Indian Plate to the north and to the east, which is also responsible for the transformation of the Sylhet Trough into a remnant ocean basin. This latter (i.e., Pliocene and onward) episode of crustal shortening played a significant role in structural trap formation and preservation of hydrocarbons in the Sylhet Trough.

Brca2-mutant zebrafish exhibit context- and tissue-dependent alterations in cell phenotypes and response to injury

Cancer cells frequently co-opt molecular programs that are normally activated in specific contexts, such as embryonic development and the response to injury. Determining the impact of cancer-associated mutations on cellular phenotypes within these discrete contexts can provide new insight into how such mutations lead to dysregulated cell behaviors and subsequent cancer onset. Here we assess the impact of heritable BRCA2 mutation on embryonic development and the injury response using a zebrafish model (Danio rerio). Unlike most mouse models for BRCA2 mutation, brca2-mutant zebrafish are fully viable and thus provide a unique tool for assessing both embryonic and adult phenotypes. We find that maternally provided brca2 is critical for normal oocyte development and embryonic survival in zebrafish, suggesting that embryonic lethality associated with BRCA2 mutation is likely to reflect defects in both meiotic and embryonic developmental programs. On the other hand, we find that adult brca2-mutant zebrafish exhibit aberrant proliferation of several cell types under basal conditions and in response to injury in tissues at high risk for cancer development. These divergent effects exemplify the often-paradoxical outcomes that occur in embryos (embryonic lethality) versus adult animals (cancer predisposition) with mutations in cancer susceptibility genes such as BRCA2. The altered cell behaviors identified in brca2-mutant embryonic and adult tissues, particularly in adult tissues at high risk for cancer, indicate that the effects of BRCA2 mutation on cellular phenotypes are both context- and tissue-dependent.

Medication-Induced Oculomotor Dysfunction: a report of two cases

Background: Consideration of current medications and their interactions as a source of new onset oculomotor dysfunction is imperative for providing good eye care. Medication etiology should be particularly suspected when the symptoms begin with the initiation of a new medication and resolved with discontinuation of the same medication. Case Reports: Presented are two cases demonstrating that it is prudent to be aware of medications capable of inducing oculomotor dysfunction. Each case reveals instances of acute oculomotor dysfunction after the initiation of a central nervous system affecting medication. Case 1 details a partial pupil sparing third nerve palsy after initiating the anti-anxiety drug, buspirone. Case 2 accounts the addition of zolpidem (Ambien), a sedative, and the subsequent new onset nystagmus and hypertropia. Conclusion: In each case, no organic etiology was found, and the oculomotor dysfunction resolved following discontinuation of the recently added CNS affecting medication. Specific drug interactions are also considered as contributing factors to the oculomotor dysfunction in both cases.

Interhemispheric asymmetry of EEG rhythm connections during spontaneous awakenings after short sleep episodes during a monotonous psychomotor test

To study interhemispheric asymmetry (IHA) according to electroencephalography (EEG) data of a healthy person during cognitive awakening from the second stage of daytime sleep before restoring the performance of the psychomotor test. In 23 healthy adult subjects, we studied IHA in the amplitude-amplitude interaction of EEG rhythms for 20 sec segments before spontaneous awakening determined by the moment the alpha-rhythm appearance on the EEG and the subsequent onset of psychomotor activity. The state of the subject during this period (in the initial stage of the so-called cognitive awakening preceding the behavioral awakening), when the person is unable to move, but is able to perceive external stimuli, is an experimental model for highlighting signs of conscious activity of patients when coming out of a coma. Wavelet transform was used to calculate the rhythmic characteristics of bioelectrical activity. The Kendall correlation coefficient served as a measure of rhythm interaction. IHA in the interaction of EEG rhythms is dynamic nature and formed by theta rhythm connections with alpha2- and beta-rhythms in the left brain hemisphere and delta-type connections in the right. Possibly, the greater activation of the left hemisphere is related to the retrieval of an instruction from memory, which subsequently allows to return to the activity interrupted by sleep.