Early Abnormalities Research Articles

Correlation between mri findings and cebrebrospinal pressures in patients with idiopathic intracranial hypertension

Background: Idiopathic Intracranial Hypertension (IIH) is characterized by elevated intracranial pressure (ICP) without identifiable etiology. While Magnetic Resonance Imaging (MRI) often reveals findings such as empty sella turcica, optic nerve abnormalities, and transverse sinus stenosis, their correlation with cerebrospinal fluid (CSF) pressure remains unclear. Objective: To investigate the correlation between MRI abnormalities and lumbar opening and closing pressures in patients with IIH. Methods: A cross-sectional study was conducted with 21 IIH patients diagnosed using the Modified Dandy Criteria over five years. MRI findings were categorized as normal or abnormal (empty sella, optic nerve abnormalities, and transverse sinus stenosis), and their association with lumbar opening and closing pressures, measured during the initial lumbar puncture, was analyzed using Student's T-test. Results: No statistically significant differences in lumbar opening or closing pressures were observed between patients with normal and abnormal MRI findings (P = 0.605 and P = 0.778, respectively). Similarly, no significant associations were identified for optic nerve abnormalities (P = 0.494 and P = 0.522), venous sinus abnormalities (P = 0.356 and P = 0.370), or empty sella turcica (P = 0.685 and P = 0.591). Conclusion: The study found no significant correlation between MRI findings and CSF pressures in IIH patients. These results align with existing literature, suggesting that MRI findings alone may not adequately predict CSF pressure levels. Alternative diagnostic methods, such as optical coherence tomography, may be more sensitive in detecting early optic nerve abnormalities.

Relationship between BDNF content in cord blood and early neurobehavior in newborns with subclinical hypothyroidism during pregnancy: a preliminary study

ObjectivesResearch on neurobehavioral abnormalities in neonates of mothers with subclinical hypothyroidism (SCH) is limited. The link between umbilical cord blood brain-derived neurotrophic factor (BDNF) levels and neurobehavioral outcomes in neonates has not been explored. This study investigates the correlation between alterations in umbilical cord blood BDNF levels and early neurobehavioral abnormalities in neonates born to pregnant women with SCH.MethodsThis study recruited 72 pregnant women with SCH and 76 healthy controls (HC). The study collected general information for all subjects, including body mass index, parity, thyroid function assessed during early to late pregnancy, and neonatal birth weight. Neonatal behavioral and neural abilities were evaluated using the Neonatal Behavioral Neurological Assessment (NBNA). BDNF levels in umbilical cord blood were measured using the Enzyme-Linked Immunosorbent Assay method.ResultsThe results indicated that neonates with SCH during pregnancy had lower total NBNA scores, behavioral ability, passive muscle tone, active muscle tone, primitive reflexes, general assessment, and lower levels of cord blood BDNF compared to healthy controls. The cord blood BDNF of newborns with SCH during pregnancy was positively correlated with total NBNA score, behavioral ability, active muscle tone, and general assessment. Moreover, multiple linear regression analysis demonstrated an association between cord blood BDNF levels in pregnant patients with SCH and multiple measures of newborn health, including total NBNA score, behavioral ability, active muscle tone, and general assessment.ConclusionInfants born to pregnant women with SCH exhibit reduced behavioral and neural abilities linked to BDNF levels in umbilical cord blood.

Is Any ABCDE Stress Echocardiography Score Equivalent to Stress-Induced Ischaemia? Reply With a Modified 2-Stage Approach.

Stress echocardiography has evolved from the sole assessment of regional wall motion abnormalities (RWMAs) to the ABCDE protocol, as recommended by the recent clinical consensus statement from the European Association of Cardiovascular Imaging, reflecting the need for a more systematic patient assessment. Steps A, B, C, D, and E assess RWMAs, lung B-lines, left ventricular contractile reserve, coronary flow velocity reserve (CFVR) in mid-distal left anterior descending artery, and heart rate reserve, respectively. Impairment of CFVR is considered as the earliest abnormality in the ischaemic cascade. While mostly steps A and D have been studied for their relation to obstructive and non-obstructive coronary artery disease, the diagnostic accuracy of steps B, C, and E for chronic coronary syndromes (CCSs) remains unknown, particularly in the context of negative steps A and D. Additionally, while ABCDE steps have been studied for their prognostic significance, there is no evidence of patients management based on this protocol in order to change the estimated risk. These concepts could be depicted in a 2-stage approach. A negative stage 1 (no stress-induced RWMAs as assessed in step A and normal CFVR as assessed in step D) imply good prognosis and non-coronary causes of symptoms should be considered, whereas guidelines for CCSs should be followed in a positive stage 1. Stage 2 includes steps B, C, and E, for further risk stratification or symptoms assessment, but it lacks evidence-based risk-modifying management and is mainly useful when stage 1 is negative and a cardiac origin of symptoms is still suspected.

Corticostriatal maldevelopment in the R6/2 mouse model of juvenile Huntington's disease.

There is a growing consensus that brain development in Huntington's disease (HD) is abnormal, leading to the idea that HD is not only a neurodegenerative but also a neurodevelopmental disorder. Indeed, structural and functional abnormalities have been observed during brain development in both humans and animal models of HD. However, a concurrent study of cortical and striatal development in a genetic model of HD is still lacking. Here we report significant alterations of corticostriatal development in the R6/2 mouse model of juvenile HD. We examined wildtype (WT) and R6/2 mice at postnatal (P) days 7, 14, and 21. Morphological examination demonstrated early structural and cellular alterations reminiscent of malformations of cortical development, and ex vivo electrophysiological recordings of cortical pyramidal neurons (CPNs) demonstrated significant age- and genotype-dependent changes of intrinsic membrane and synaptic properties. In general, R6/2 CPNs had reduced cell membrane capacitance and increased input resistance (P7 and P14), along with reduced frequency of spontaneous excitatory and inhibitory synaptic events during early development (P7), suggesting delayed cortical maturation. This was confirmed by increased occurrence of GABAA receptor-mediated giant depolarizing potentials at P7. At P14, the rheobase of CPNs was significantly reduced, along with increased excitability. Altered membrane and synaptic properties of R6/2 CPNs recovered progressively, and by P21 they were similar to WT CPNs. In striatal medium-sized spiny neurons (MSNs), a different picture emerged. Intrinsic membrane properties were relatively normal throughout development, except for a transient increase in membrane capacitance at P14. The first alterations in MSNs synaptic activity were observed at P14 and consisted of significant deficits in GABAergic inputs, however, these also were normalized by P21. In contrast, excitatory inputs began to decrease at this age. We conclude that the developing HD brain is capable of compensating for early developmental abnormalities and that cortical alterations precede and are a main contributor of striatal changes. Addressing cortical maldevelopment could help prevent or delay disease manifestations.

Differential impact of glucose abnormalities and iron overload in TM (TM) and TI(TI): A comparative analysis of diagnostic approaches and management strategies for optimized care

Introduction: Thalassemia syndromes, specifically TM (TM) and TI(TI), are inherited blood disorders characterized by impaired hemoglobin synthesis, leading to chronic anemia. TM requires frequent blood transfusions, causing iron overload and elevating the risk for glucose metabolism issues, while TI, with fewer transfusions, experiences a lower incidence of these metabolic complications. Objectives: The review aims to compare glucose abnormalities, iron overload patterns, diagnostic approaches, iron chelation efficacy, and metabolic complications between TM and TI, offering insights into optimizing clinical management for each condition. Methods: A comprehensive literature review was conducted on studies from the past two decades, focusing on glucose metabolism, iron overload, and related complications in TM and TI patients. Data sources included PubMed, ScienceDirect, and Google Scholar, emphasizing studies that examined glucose abnormalities, iron accumulation, and treatment efficacy. Results: The findings indicate that TM patients have a higher prevalence of glucose abnormalities due to more severe iron overload, predominantly affecting pancreatic beta-cell function and insulin sensitivity. In contrast, TI patients generally exhibit milder metabolic complications due to less frequent transfusions and lower iron loads. Diagnostic tools like the Oral Glucose Tolerance Test (OGTT) and Continuous Glucose Monitoring (CGM) have been shown to detect early glucose abnormalities. Iron chelation therapy, critical for TM, is often more intensive, while TI patients benefit from intermittent chelation, effectively controlling iron without extensive intervention. Additionally, TM patients frequently require pharmacologic glycemic therapy, such as insulin or oral hypoglycemics, to manage more severe glucose dysregulation, whereas TI patients typically maintain stable glucose levels with lifestyle modifications. Discussion: TM and TI patients show distinct profiles in glucose dysregulation and iron overload. TM's high transfusion dependency results in rapid iron accumulation, necessitating aggressive iron chelation and regular glucose monitoring to mitigate the risk of diabetes. OGTT remains a viable option both for TM and TI. Individualized chelation strategies based on transfusion needs and iron levels are essential to minimize glucose-related complications, particularly in TM patients. Conclusions: TM patients experience higher and earlier glucose abnormalities compared to TI, primarily due to transfusion-induced iron overload. Personalized management involving intensive chelation, glucose monitoring, and lifestyle modifications can improve outcomes, especially in TM. For TI patients, milder chelation and lifestyle interventions suffice to maintain stable glucose levels. This review highlights the need for tailored approaches to address the unique challenges in glucose and iron management in TM and TI.

Progressive Early Interstitial Lung Abnormalities in Persons at Risk for Familial Pulmonary Fibrosis: A Prospective Cohort Study.

Rationale: Relatives of patients with familial pulmonary fibrosis (FPF) are at increased risk to develop FPF. Interstitial lung abnormalities (ILAs) are a radiologic biomarker of subclinical disease, but the implications of very mild abnormalities remain unclear. Objectives: To quantify the progression risk among FPF relatives with abnormalities below the threshold for ILAs as described by the Fleischner Society and to describe the characteristics of participants with new or progressive ILAs during observation. Methods: Asymptomatic FPF relatives undergo serial screening high-resolution chest computed tomography. For this analysis, early ILAs (no minimum threshold of lung involvement) were subclassified as mild (all interstitial abnormalities involve <5% of a lung zone) or moderate (any abnormality involves >5%). Identification of new or progressive ILAs on high-resolution chest computed tomography and the development of pulmonologist-diagnosed clinical FPF were defined as progression. Covariate-adjusted logistic regression identified progression-associated characteristics. Measurements and Main Results: From 2008 to 2023, 273 participants in follow-up procedures were 53.2 ± 9.4 years of age at enrollment, 95 (35%) were men, and 73 of 268 (27%) were ever-smokers. During a mean follow-up period of 6.2 ± 3.0 years, progression occurred among 31 of 211 (15%) of those with absence of ILAs at enrollment, 32 of 49 (65%) of those with mild ILAs, and 10 of 13 (77%) of those with moderate ILAs. Subjects with mild ILAs had 9.15 (95% confidence interval, 4.40-19.00; P < 0.0001) times and those with moderate ILAs had 17.14 (95% confidence interval, 4.42-66.49; P < 0.0001) times the odds of progression as subjects without ILAs. Conclusions: In persons at risk for FPF, minor interstitial abnormalities, including reticulation that is unilateral or involves <5% of a lung zone, frequently represent subclinical disease.

Diagnostic accuracy of neonatal structural MRI scores to predict 6-year motor outcomes of children born very preterm.

This study aimed to (1) evaluate associations between Early and Term structural MRI (sMRI) brain abnormality scores and adverse motor outcomes at 6-years corrected age (CA), (2) determine their diagnostic accuracy in predicting adverse motor outcomes and cerebral palsy (CP) at 6-years CA. Infants born<31-weeks gestational age (GA) returning for 6-year follow-up were included. Early and Term sMRI were scored using a validated method, deriving white matter, cortical grey matter, deep grey matter, cerebellar and global brain abnormality scores (GBAS). At 6-years CA, Movement Assessment Battery for Children-2nd Edition (MABC-2) was administered. Linear regression assessed associations between Early and Term GBAS/subscale scores and 6-year MABC-2 total score. For diagnostic accuracy, sMRI scores were categorised as none/mild vs moderate/severe, MABC-2 cut-off≤5th percentile, and CP as present/absent. Infants had Early MRI (n=123) at mean PMA 32.5-weeks (median GA 28.4-weeks; mean birthweight 1101g) and n=114 had Term MRI (Mean PMA 40.8-weeks). Nine had CP and n=116 had MABC-2 scores. Early (B: -1.92; p≤0.001) and Term (B: -1.67; p≤0.01) GBAS were negatively associated with MABC-2 scores. Both Early and Term GBAS had high specificity (Sp) and low sensitivity (Se) in predicting MABC-2≤5th percentile (Early: Se 36%, Sp 82%; Term: Se 28%, Sp 93%) and predicted CP with high Se and Sp (Early: Se 78%, Sp 78%; Term: Se 75%, Sp 89%). High Sp of Early and Term MRI predicting an outcome on MABC-2 may help accurately identify infants unlikely to develop motor impairments at 6-years CA.

Gross anatomical features of the insular cortex in affective disorders

IntroductionThe number of insular gyri is elevated in patients with schizophrenia. Thus, it has potential as a marker of early neurodevelopmental abnormalities. However, currently it remains unclear whether patients with other neuropsychiatric disorders, such as affective disorders, also have this gross brain anatomical feature.Materials and methodsThe macroscopic features of the insular cortex in 26 patients with bipolar disorder (BD), 56 with major depressive disorder (MDD), and control subjects for each clinical group (24 for BD and 33 for MDD) were assessed using magnetic resonance imaging.ResultsThe number of short insular gyri was higher in BD patients than in matched controls bilaterally with well-developed accessory and middle short gyri. Furthermore, the left middle short gyrus was more developed in MDD patients than in matched controls, and was weakly associated with the severity of depressive symptoms.DiscussionThe present results indicate that changes in the gross morphology of the insular cortex in BD and MDD is a potential vulnerability factor associated with their neurodevelopmental pathologies, and may also contribute to the severity of symptoms in MDD.

Prevalence and factors linked to renal involvement in prediabetes patients across Europe in the ePREDICE trial

This sub-analysis of the ePREDICE trial, investigated the prevalence and determinants of renal complications, specifically glomerular hyperfiltration, albuminuria, and reduced kidney function, in individuals with prediabetes (PD). The cohort consisted of 967 participants from diverse backgrounds across seven countries. The kidney function was evaluated using the MDRD-4 equation, and the influence of various clinical and demographic factors on renal involvement was assessed by multivariable regression models. Additionally, insulinogenic and disposition indices were examined. Overall, the prevalence of renal abnormalities in this PD cohort was 9.2% (n = 89). Key findings included the detection of hyperfiltration in 20 (2%) individuals, albuminuria in 45 (4.7%), and CKD stage G3a in 29 (3%). Hyperfiltration was inversely correlated with age and height, while albuminuria showed a significant direct association with the disposition index (DI). Age and waist circumference were significantly and directly associated with estimated glomerular filtration rate (eGFR). The ePREDICE study highlights critical factors that affect renal involvement in PD individuals, revealing complex interactions among various parameters. These findings further emphasize the necessity for the search of early kidney abnormalities in people with PD especially in those in older age groups and with a large waist circumference.

Early basal ganglia imaging abnormalities in pre‐symptomatic and early symptomatic novel APP duplication carriers

Early basal ganglia imaging abnormalities in pre‐symptomatic and early symptomatic novel APP duplication carriers

The Importance of Prenatal Diagnosis for the Early Detection of Fetal Abnormalities in Rural Areas, Indonesia: A Mixed-Method Study

Background: Prenatal diagnosis in rural areas is a global challenge especially for maternal reproductive health. The challenges of implementing prenatal diagnosis in rural areas include: low public awareness and knowledge, minimal access to health care facilities, low economic factors. Yogyakarta represents Indonesia as a province with the same proportion of urban and rural areas. Apart from that, there is still a culture that influences the knowledge and behavior the health care community. The incidence of congenital abnormalities is increasing in rural areas due to delays in early detection during pregnancy. By using a mixed-method approach, this study aims to provide insight into the importance of prenatal diagnosis for pregnant women in rural areas. Methods: This research is a mixed-method study with 100 webinar participants of community service, 6 health care workers, and 6 pregnant women. Demographic data and knowledge about prenatal diagnosis are presented through quantitative methods. The qualitative data presented through in-depth interviews explored the perspectives of health care workers and pregnant women regarding experiences, obstacles, and support in carrying out prenatal diagnosis. Thematic analysis was used in this study. Results: The importance of knowledge in the early detection of fetal abnormalities and children’s growth development has a significance value of 0.000 each (p-value &lt; 0.05). In contrast, the hospital services expectation has 0.243. Qualitative reports indicated that the achievement of prenatal diagnosis services requires awareness of pregnant women and support from health care workers as direct providers of counseling and services. Pregnant women in this study realized the importance of prenatal diagnosis to detect early pregnancy abnormalities. Conclusions: Prenatal diagnosis in rural areas is an effort to increase early detection of fetal abnormalities and improve child development. The implementation of prenatal diagnosis in rural areas is supported by the active role of health workers and non-health workers. Several obstacles to the implementation of prenatal diagnosis in rural areas are the lack of knowledge of pregnant women, fear of poor examination results, distance from the pregnant woman’s house to the health care facilities, uneven availability of ultrasound equipment, and high costs of ultrasound examinations. The government can increase access of prenatal diagnosis in rural areas, through free ultrasound subsidies and the implementation of pregnant women’s classes in each village.

Serous Tubal Intraepithelial Carcinoma (STIC): A Review of the Literature on the Incidence at the Time of Prophylactic Surgery.

Serous tubal intraepithelial carcinoma (STIC) is an early-stage cancerous lesion found in the fallopian tubes, often at the fimbrial end. It is strongly associated with high-grade serous carcinoma (HGSC), a highly aggressive type of ovarian cancer. STIC is considered a precursor to many HGSC cases, originating in the fallopian tubes. Its development is frequently linked to mutations in the TP53 gene, leading to the formation of a p53 signature, an early abnormality that may progress to HGSC. This signature is more common in BRCA mutation carriers, explaining the higher incidence of STIC in this group. The aim of this review is to evaluate the literature on the incidence of serous tubal intraepithelial carcinoma in patients (both BRCA-positive and BRCA-negative) undergoing preventive salpingo-oophorectomy, analysing the available data and identifying associations between specific characteristics and the onset of STIC. A comprehensive review of the literature from 2016 to 2023 was conducted using PubMed, focusing on studies analysing the incidence of STIC in BRCA-positive patients undergoing preventive salpingo-oophorectomy. Data on patient characteristics, interventions, outcomes, and incidence of STIC were extracted and analysed. Nine international studies were included in the review, reporting varying incidences of STIC among patients undergoing salpingo-oophorectomy. The overall incidence of STIC in all the women included in the studies was 7.31%, while that in the BRCA-mutated women was approximately 6.08%. Notably, the presence of the TP53 signature was significantly associated with the occurrence of STIC. The etiopathogenesis of STIC involves complex interactions between genetic, environmental, and molecular factors. Further research is needed to fully understand its mechanisms and identify additional risk factors beyond BRCA mutations. Establishing a national database of STIC cases could facilitate future research and improve patient outcomes.

Exploring the effects of mavacamten through hemodynamic force analysis in patients with obstructive hypertrophic cardiomyopathy

Abstract Introduction Mavacamten is a first-in-class allosteric myosin inhibitor effective in relieving left ventricular (LV) outflow tract obstruction in patients with obstructive hypertrophic cardiomyopathy (oHCM). To date, however, its effect on cardiac mechanics is still unclear. Hemodynamic force (HDF) analysis represents the fluid dynamics correlate of deformation imaging, showing a greater sensitivity in detecting early mechanical abnormalities or response to treatment [1]. Purpose To explore the in vivo effect of mavacamten on cardiac mechanics in patients with HCM after a 3 year-treatment, using HDF analysis. Methods LV HDF analysis was performed in 6 patients with oHCM (representing a cohort of the MAVA-LTE study) at baseline and after 3 years of treatment. Apical 4-, 2-, and 3-chamber echocardiographic views were analysed using a dedicated and sofisticated software. Base-apex forces (where positive deflections represent a force directed from the apex to the base of LV, whilst negative ones are directed toward the LV apex) were assessed in terms of timing indexed to cardiac cycle duration. HDF curves from the 6 patients treated with macavamten were compared to those obtained from oHCM patients (n=20), non-obstructive HCM (noHCM) patients (n=20), and healthy controls (n=22). Results Figure 1 shows a different pattern of transition between diastole and systole in HCM patients compared to controls. Specifically, HCM patients exhibited an earlier onset of the systolic phase, expressed as a fusion of late diastolic deceleration and systolic thrust. This was numerically represented as a decrease in diastolic-systolic transition time, which is 0.22 [0.20-0.24] for oHCM, 0.23 [0.21-0.25] for noHCM and 0.26 [0.26-0.30] for controls (p ≤0.001 for control vs oHCM, p ≤0.01 for control vs noHCM). Additionally, HCM patients showed an increased rate of force generation. The time to systolic peak (i.e., time interval from the onset of systole to the maximum force) was reduced in HCM patients compared to controls, and was shorter in oHCM than in noHCM patients (0.13 [0.11-0.15] vs 0.16 [0.14-0.17], p ≤0.01), thus reflecting an increased clinotropism in HCM. After 3 years of mavacamten treatment, the diastolic-systolic transition time and the time to systolic peak returned to a level similar to that of healthy controls (0.30 [0.27-0.30] in mavacamten group vs 0.26 [0.26-0.30], p &amp;gt;0.05, and 0.21 [0.20-0.22] vs 0.19[0.17-0.20], p=0.04, respectively) (Figure 2). Conclusion HDF analysis reveals that mavacamten affects the duration of transition from diastole to systole and prolongs time from the onset to the peak in systole. These findings may explain the removal of the mechanical coupling substrate responsible for the systolic anterior movement of mitralic leaflets and the subsequent resolution of LV outflow tract obstruction by mavacamten.Distribution of time parameters

Approaches to a crisis in early pregnancy: an explorative qualitative study of medical students and doctors in training in Ireland, using a story completion model

A crisis in early pregnancy can be due to an unplanned pregnancy or a suspected abnormality. Pregnant people have the right to unbiased and comprehensive advice of all options from healthcare providers. Using story completion models (SCM), the aim of this qualitative study was to explore the attitudes of medical students and doctors in training towards crisis pregnancy, specifically two scenarios: early unplanned pregnancy and fatal fetal abnormality (anencephaly). Participants were invited from medical students attending University College Dublin (UCD) and trainees in Obstetrics and Gynaecology in the Royal College of Physicians of Ireland (RCPI) from July to December 2022. SCM involve giving the consenting participant an introduction to a hypothetical situation that acts as the beginning of a story and asking them to complete it. Stories were compiled and analysed using thematic analysis. Research Ethics Committee approval was given by both UCD and the RCPI. The standards for reporting of qualitative research guidelines were followed. Eight doctors in training and six medical students consented to participate in the study; all but two medical students completed both stories to the required word count, giving 25 stories for analysis. For both situations, stories described a variety of approaches, all of which were based on the person, or couples wishes, from continuing in pregnancy to deciding to end the pregnancy. SCM allowed detailed analysis of potentially sensitive subjects such as pregnancy options. This study showed that participating medical students and doctors in training recognise that pregnant people have the right to all choices in crisis pregnancy.

Corticostriatal Maldevelopment in the R6/2 Mouse Model of Juvenile Huntington's Disease.

There is a growing consensus that brain development in Huntington's disease (HD) is abnormal, leading to the idea that HD is not only a neurodegenerative but also a neurodevelopmental disorder. Indeed, structural and functional abnormalities have been observed during brain development in both humans and animal models of HD. However, a concurrent study of cortical and striatal development in a genetic model of HD is still lacking. Here we report significant alterations of corticostriatal development in the R6/2 mouse model of juvenile HD. We examined wildtype (WT) and R6/2 mice at postnatal (P) days 7, 14, and 21. Morphological examination demonstrated early structural and cellular alterations reminiscent of malformations of cortical development, and ex vivo electrophysiological recordings of cortical pyramidal neurons (CPNs) demonstrated significant age- and genotype-dependent changes of intrinsic membrane and synaptic properties. In general, R6/2 CPNs had reduced cell membrane capacitance and increased input resistance (P7 and P14), along with reduced frequency of spontaneous excitatory and inhibitory synaptic events during early development (P7), suggesting delayed cortical maturation. This was confirmed by increased occurrence of GABA A receptor-mediated giant depolarizing potentials at P7. At P14, the rheobase of CPNs was significantly reduced, along with increased excitability. Altered membrane and synaptic properties of R6/2 CPNs recovered progressively, and by P21 they were similar to WT CPNs. In striatal medium-sized spiny neurons (MSNs), a different picture emerged. Intrinsic membrane properties were relatively normal throughout development, except for a transient increase in membrane capacitance at P14. The first alterations in MSNs synaptic activity were observed at P14 and consisted of significant deficits in GABAergic inputs, however, these also were normalized by P21. In contrast, excitatory inputs began to decrease at this age. We conclude that the developing HD brain is capable of compensating for early developmental abnormalities and that cortical alterations precede and are a main contributor of striatal changes. Addressing cortical maldevelopment could help prevent or delay disease manifestations.

Insights into the Novel Biomarkers Expressed in Diabetic Nephropathy: Potential Clinical Applications.

Diabetic nephropathy (DN) is increasing worldwide in parallel with type 2 diabetes mellitus. Identifying diagnostic biomarkers for DN at an early stage is crucial due to the considerable societal and economic burden associated with diabetes mellitus (DM) and its risk factors. In the past, early indicators of microvascular problems, such as microalbuminuria (MA), have been used to predict the possibility of developing advanced chronic kidney disease (CKD). However, because of the incapacity of MA to appropriately estimate DN, particularly, non-albuminuric DN, additional markers have been suggested for recognizing the early renal abnormalities and structural lesions, even before MA. This study aims to assess the existing and future biomarkers used to diagnose or predict early DN. This review provides comprehensive insight into diagnostic approaches for early detection of CKD, addressing the following areas: (i) markers of glomerular damage, (ii) markers of tubular damage, (iii) oxidative stress biomarkers, (iv) inflammatory biomarkers and (v) futuristic biomarkers such as micro-ribonucleic acids (miRNAs), proteomics, metabolomics and genomics and gut microbiota. Early detection of DN may lead to improvement in clinical management and quality of life, emphasizing the importance of identifying a specific and reliable predictive biomarker. Emerging serum and urinary biomarkers offer promise for early DN diagnosis, potentially reducing prevalence and preventing progression to end-stage renal disease (ESRD). Further advancements in miRNAs, proteomics, metabolomics genomics and gut microbiota offer prospects for even earlier and more precise DN diagnosis.

Impacts of Maternal Preeclampsia Exposure on Offspring Neuronal Development: Recent Insights and Interventional Approaches.

Preeclampsia, a hypertensive disorder during pregnancy, frequently correlates with adverse neurological outcomes in offspring, including cognitive impairments, autism spectrum disorder, depressive disorder, attention deficit hyperactivity disorder, and cerebral palsy. Despite these known consequences, the understanding of neuronal damage in the offspring of preeclamptic mothers remains insufficient. Here, we review the neuronal abnormalities resulting from maternal preeclampsia exposure, which include disrupted neurogenesis, loss of neuronal cell integrity, accumulation of cellular debris, decreased synaptogenesis and myelination, and increased neurite growth stimulated by maternal preeclampsia serum. The underlying mechanisms potentially driving these effects involve microglial activation, inflammatory responses, and reduced angiogenesis. Intervention strategies aimed at improving fetal neuronal outcomes are also discussed, encompassing pharmacological treatments such as pravastatin, tadalafil, and melatonin, as well as non-pharmacological approaches like dietary modifications, maternal exercise, and standard care for children. These interventions hold promise for clinical application, offering avenues to address early neuronal abnormalities and prevent the onset of long-term neurological disorders.

Progress in impulse oscillometry on chronic obstructive pulmonary disease

Impulse oscillometry (IOS) is a force-free, easy-to-use tool for the detection of airway resistance. Compared with spirometry, IOS is more sensitive in detecting early abnormalities in chronic obstructive pulmonary disease (COPD), and IOS parameters have potential research value in identifying the progression of COPD and monitoring the effect of treatment. This review aimed to highlight the significant research findings of IOS in chronic obstructive pulmonary disease and to address the urgent issue that need to be resolved.

Lentiviral Gene Therapy for Cerebral Adrenoleukodystrophy

BackgroundCerebral adrenoleukodystrophy is a severe form of X-linked adrenoleukodystrophy characterized by white-matter disease, loss of neurologic function, and early death. Elivaldogene autotemcel (eli-cel) gene therapy, which consists of autologous CD34+ cells transduced with Lenti-D lentiviral vector containing ABCD1 complementary DNA, is being tested in persons with cerebral adrenoleukodystrophy.MethodsIn a phase 2–3 study, we evaluated the efficacy and safety of eli-cel therapy in boys with early-stage cerebral adrenoleukodystrophy and evidence of active inflammation on magnetic resonance imaging (MRI). The primary efficacy end point was survival without any of six major functional disabilities at month 24. The secondary end points included overall survival at month 24 and the change from baseline to month 24 in the total neurologic function score.ResultsA total of 32 patients received eli-cel; 29 patients (91%) completed the 24-month study and are being monitored in the long-term follow-up study. At month 24, none of these 29 patients had major functional disabilities; overall survival was 94%. At the most recent assessment (median follow-up, 6 years), the neurologic function score was stable as compared with the baseline score in 30 of 32 patients (94%); 26 patients (81%) had no major functional disabilities. Four patients had adverse events that were directly related to eli-cel. Myelodysplastic syndrome (MDS) with excess blasts developed in 1 patient at month 92; the patient underwent allogeneic hematopoietic stem-cell transplantation and did not have MDS at the most recent follow-up.ConclusionsAt a median follow-up of 6 years after lentiviral gene therapy, most patients with early cerebral adrenoleukodystrophy and MRI abnormalities had no major functional disabilities. However, insertional oncogenesis is an ongoing risk associated with the integration of viral vectors. (Funded by Bluebird Bio; ALD-102 and LTF-304 ClinicalTrials.gov numbers NCT01896102 and NCT02698579, respectively.)

Neurodevelopmental predictors of treatment response in schizophrenia and bipolar disorder.

Treatment resistance is a major challenge in psychiatric disorders. Early detection of potential future resistance would improve prognosis by reducing the delay to appropriate treatment adjustment and recovery. Here, we sought to determine whether neurodevelopmental markers can predict therapeutic response. Healthy controls (N = 236), patients with schizophrenia (N = 280) or bipolar disorder (N = 78) with a known therapeutic outcome, were retrospectively included. Age, sex, education, early developmental abnormalities (obstetric complications, height, weight, and head circumference at birth, hyperactivity, dyslexia, epilepsy, enuresis, encopresis), neurological soft signs (NSS), and ages at first subjective impairment, clinical symptoms, treatment, and hospitalization, were recorded. A supervised algorithm leveraged NSS and age at first clinical signs to classify between resistance and response in schizophrenia. Developmental abnormalities were more frequent in schizophrenia and bipolar disorder than in controls. NSS significantly differed between controls, responsive, and resistant participants with schizophrenia (5.5 ± 3.0, 7.0 ± 4.0, 15.0 ± 6.0 respectively, p = 3 × 10-10) and bipolar disorder (5.5 ± 3.0, 8.3 ± 3.0, 12.5 ± 6.0 respectively, p < 1 × 10-10). In schizophrenia, but not in bipolar disorder, age at first subjective impairment was three years lower, and age at first clinical signs two years lower, in resistant than responsive subjects (p = 2 × 10-4 and p = 9 × 10-3, respectively). Age at first clinical signs and NSS accurately predicted treatment response in schizophrenia (area-under-curve: 77 ± 8%, p = 1 × 10-14). Neurodevelopmental features such as NSS and age of clinical onset provide a means to identify patients who may require rapid treatment adaptation.