Early Onset Research Articles

Immunological Evaluation of Pediatric Patients with Polyautoimmunity.

Autoimmunity can be the first or predominant manifestation in patients with primary immunodeficiency disorder, also referred to as inborn errors of immunity (IEI). This study aims to evaluate the immune status of pediatric patients with polyautoimmunity to identify those with underlying immune defects. In this cross-sectional study, pediatric patients with polyautoimmunity including at least one confirmed autoimmune endocrine disease were enrolled. Demographic and clinical data were collected using a questionnaire based on medical records and direct family interviews. For each patient, a basic immunologic evaluation was performed. The clinical diagnosis was established according to the criteria of the European Society for Immunodeficiencies (ESID). Based on the presence or absence of a history of severe and/or recurrent infections, patients were divided into two groups for comparison. Thirty-nine patients, 18 males (46.2%) and 21 females (53.8%), were included. Fourteen patients (35.9%) had consanguineous parents. Fifteen patients (38.5%) had a history of severe and/or recurrent infections. The median (interquartile range: IQR) age of our patients at the time of evaluation was 11.1 (9-16) years. The median (IQR) age at the onset of infections and autoimmunities were 3 (1-10.8) and 5 (2.6-8) years, respectively. The most common infectious complications reported were pneumonia and candidiasis, each in 12.8% of the patients. The most prevalent autoimmune disorders were type 1 diabetes (74.3%) and autoimmune thyroiditis (58.9%). IEI was diagnosed in six patients (15.38%), five of which were from the group with severe or recurrent infections: three with selective IgA deficiency, two with common variable immunodeficiency (CVID), and one with immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX), but without a history of infections. The occurrence of early onset polyautoimmunity in association with severe and/or recurrent infections or in patients with a positive family history should be a warning sign for physicians to initiate an evaluation for possible immunodeficiency disorders to prevent complications through early treatment.

A service evaluation study of the impact of ageless policy in a London inner-city early intervention in psychosis service.

Schizophreniform disorders tend to have an early onset. Early intervention in psychosis (EIP) services aim to provide early treatment, reduce long-term morbidity and improve social functioning. In 2016, changes to mental health policy in England mandated that the primarily youth-focused model should be extended to an ageless one, to prevent ageism; however, this was without strong research evidence. An inner-city London EIP service compared sociodemographic and clinical factors between the under-35 years and over-35 years caseload cohorts utilising the EIP package following the implementation of the ageless policy. Both groups received similar care, despite the younger group having significantly more clinical morbidity and needs. Our results may indicate that service provisions are being driven by policy rather than clinical needs, potentially diverting resources from younger patients. These findings have important implications for future provision of EIP services and would benefit from further exploration.

Recent Advances in Photodynamic Therapy for Vascular Abnormalities.

Abstract Background: Photodynamic therapy (PDT) is a minimally invasive therapy that was gradually established as a first-line treatment for vascular abnormalities. Its action depends on the appropriate wavelength of light and photosensitizer to produce toxic oxygen species and cause cell death. Objective: Several new clinical improvements and trends in PDT have been described in recent years. The aim of this review is to provide an overview of the current data from clinical trials. Methods: In this review, we introduce and generalize the wavelength, duration, dose, strength, and photosensitizer of PDT for the treatment of vascular abnormalities, such as circumscribed choroidal hemangiomas (CCH), choroidal neovascularization (CNV) and capillary malformation (CM). Results: The systematic review findings indicate that the application of PDT is a safe effective method to treat CCH, CNV and CM. However, PDT also has early onset side effects and late onset side effects. Conclusions: Based on the discussion of the effectiveness of PDT, we conclude that PDT has great potential for clinical use, although PDT has possible side effects.

The myosin chaperone UNC-45 has an important role in maintaining the structure and function of muscle sarcomeres during adult aging.

C. elegans undergo age-dependent declines in muscle organization and function, similar to human sarcopenia. The chaperone UNC-45 is required to fold myosin heads after translation and is likely used for re-folding after thermally- or chemically-induced unfolding. UNC-45's TPR region binds Hsp90 and its UCS domain binds myosin heads. We observe early onset sarcopenia when UNC-45 is reduced at the beginning of adulthood. There is sequential decline of HSP-90, UNC-45, and MHC B myosin. A mutation in age-1 delays sarcopenia and loss of HSP-90, UNC-45 and myosin. UNC-45 undergoes age-dependent phosphorylation, and mass spectrometry reveals phosphorylation of 6 serines and 2 threonines, 7 of which occur in the UCS domain. Additional expression of UNC-45 results in maintenance of MHC B myosin and suppression of A-band disorganization in old animals. Our results suggest that increased expression or activity of UNC-45 might be a strategy for prevention or treatment of sarcopenia.

Somatic burden of attention-deficit/hyperactivity disorder across the lifecourse.

A thorough and comprehensive knowledge base on the extent of comorbidity of attention-deficit/hyperactivity disorder (ADHD) and somatic conditions is needed. We compared the prevalence of a wide range of somatic conditions in individuals with and without ADHD and described sex and lifecourse differences. Individuals with an ADHD diagnosis (N = 87,394) and age and sex-matched individuals without an ADHD diagnosis were identified from a large health claims dataset representative of the general German population, including both primary and specialized care (N = 4.874,754). Results were provided for the full sample as well as stratified for sex and age (<12 years, 13-17 years, 18-29 years, 30-59 years, ≥60 years). The results showed that ADHD is associated with a wide variety of somatic conditions across the entire lifecourse. Specifically neurological disorders such as Parkison's disease (odds ratio [OR]: 5.21) and dementia (OR: 2.23), sleep-related disorders (OR: 2.38) and autoimmune disorders affecting the musculoskeletal, digestive, and endocrine system (fibromyalgia OR: 3.33; lupus OR: 2.17) are strongly and significantly associated with ADHD. Additionally, ADHD is associated with higher occurrence of common acute diseases typically treated by the general practitioner, hinting at an overall general lower health status. Sex differences in somatic comorbidity were not prominent. Age differences, in contrast, stood out: in particular endocrine, cardiovascular, and neurological disorders had an early onset in individuals with compared to individuals without ADHD. This research underlines the high burden of disease due to somatic conditions among individuals with ADHD. The findings indicate the need for preventive measures to reduce comorbidity.

Is there an increased risk of genetic abnormalities in fetuses with congenital heart disease in the setting of growth restriction?

To determine if the presence of fetal growth restriction (FGR) is associated with an increased risk of genetic abnormalities in the setting of congenital heart disease (CHD). This was a retrospective cohort study involving pregnancies that met the following criteria: (i) prenatal diagnosis of CHD, (ii) singleton live-birth, and (iii) genetic testing was performed either pre- or postnatally. Genetic results were reviewed by a clinical geneticist for updated variant classification. Fetal growth was stratified as appropriate for gestational age (AGA) or FGR. Of the total of 445 fetuses that met the study criteria, 325 (73.0%) were AGA and 120 (27.0%) were FGR. Genetic abnormalities were detected in 131 (29.4%) pregnancies. There was a higher rate of genetic abnormalities (36.7% vs. 26.8%, p=0.04), which was driven by aneuploidies (20.8% vs. 8.9%, p=0.0006) in the FGR population. Early onset growth restriction was associated with a higher rate of genetic abnormalities (44.5% vs. 25.9%, p=0.03). The rate of genetic abnormalities was significantly higher in the shunt category as compared to remainder of the cardiac anomalies (62.5% in shunt lesions vs. 24.7%, p<0.00001). The rates of FGR (40.9% vs. 21.4%, p<0.0001) and genetic abnormalities (52% vs. 20.4%, p<0.0001) were significantly higher in the presence of extra-cardiac anomalies (ECA). The presence of FGR in fetal CHD population was associated with underlying genetic abnormalities, specifically aneuploidies. Patients should be appropriately counseled regarding the higher likelihood of a genetic condition in the presence of FGR, early onset FGR, shunt lesions and ECA.

Reduction of DUP in early intervention programmes: No pain… almost no gain.

Considering the negative impact of long duration of untreated psychosis (DUP) on outcome, its reduction has become one of the aims of early intervention programmes. The TIPP programme (Treatment and early Intervention in Psychosis Program) was implemented in 2004 in Lausanne and hoped to reduce DUP, without any specific campaign in this regard, through the provision of accessible and specialized treatment. The aim of this study was to evaluate the evolution of patients' DUP over time and the characteristics of patients with extreme DUP. Clinical follow-up data of 380 patients aged 18-35 years with a first psychotic episode who entered the TIPP programme between 2004 and 2017 were analysed. The evolution of DUP over time as well as referring entities and destination after the programme were assessed. The characteristics of patients with extreme DUPs (>percentile 90) were compared with that of other patients. The mean value of the DUP was 452.11 days with a median of 88 days. DUP decreased only moderately over time. We also observe a decrease in discharges to specialized outpatient care at our university hospital. The main characteristics of patients with extreme DUP were early age of onset of psychosis, diagnosis of schizophrenia and presence of history of psychiatric treatment for other conditions before onset of psychosis. These figures suggest that the DUP has reduced over time but that without specific interventions at this level, this reduction is only moderate.

Evaluation of crankshaft phenomenon after posterior fusion for early onset scoliosis using an inverse trigonometric function: a multicenter retrospective cohort study.

The crankshaft phenomenon (CSP) is a corrective loss after posterior surgery for early onset scoliosis (EOS). However, an accurate method for CSP evaluation has yet to be developed. In this study, we evaluated pedicle screw (PS) length and rotation angle using an inverse trigonometric function and investigated the prevalence of the CSP. Fifty patients from nine institutions (mean age 10.6years, male/female ratio 4:46) who underwent early definitive fusion surgery at ≤ 11years of age were included. The rotation angle was calculated as arctan (lateral/frontal PS length) using radiography. Measurements were taken at the apex and lower instrumented vertebra (LIV) immediate, 2-, and 5-year postoperatively. CSP was defined as a rotation angle progression ≥ 5°. We divided patients into CSP and non-CSP groups and measured the demographic parameters, Risser grade, state of the triradiate cartilage, major coronal Cobb angle, T1-T12 length, T1-S1 length, and presence of distal adding-on (DAO). We compared these variables between groups and investigated the correlation between the measured variables and vertebral rotation. Logistic regression analysis investigated factors associated with CSP. The rotation angle progressed by 2.4 and 1.3° over 5years for the apex and LIV, respectively. CSP occurred in 15 cases (30%), DAO in 11 cases (22%), and CSP and DAO overlapped in 4 cases (8%). In the CSP group, the T1-T12 length was low immediate postoperatively. The rotation angle was negatively correlated with preoperative height (r = -0.33), T1-T12 length (r = -0.35), and T1-S1 length (r = -0.30). A lower preoperative T1-T12 length was associated with CSP (odds ratio: 0.996, p = 0.048). CSP occurred in 30% of patients with EOS who underwent definitive fusion. The presence of CSP was associated with a lower preoperative T1-T12 length. Diagnosis, level IV.

Global modified Delphi consensus on diagnosis, phenotypes, and treatment of SCN8A-related epilepsy and/or neurodevelopmental disorders.

We aimed to develop consensus for diagnosis/management of SCN8A-related disorders. Utilizing a modified Delphi process, a global cohort of experienced clinicians and caregivers provided input on diagnosis, phenotypes, treatment, and management of SCN8A-related disorders. A Core Panel (13 clinicians, one researcher, six caregivers), divided into three subgroups (diagnosis/phenotypes, treatment, comorbidities/prognosis), performed a literature review and developed questions for the modified Delphi process. Twenty-eight expert clinicians, one researcher, and 13 caregivers from 16 countries participated in the subsequent three survey rounds. We defined consensus as follows: strong consensus, ≥80% fully agree; moderate consensus, ≥80% fully/partially agree, <10% disagree; and modest consensus, 67%-79% fully/partially agree, <10% disagree. Early diagnosis is important for long-term clinical outcomes in SCN8A-related disorders. There are five phenotypes: three with early seizure onset (severe developmental and epileptic encephalopathy [DEE], mild/moderate DEE, self-limited (familial) infantile epilepsy [SeL(F)IE]) and two with later/no seizure onset (neurodevelopmental delay with generalized epilepsy [NDDwGE], NDD without epilepsy [NDDwoE]). Caregivers represented six patients with severe DEE, five mild/moderate DEE, one NDDwGE, and one NDDwoE. Phenotypes vary by age at seizures/developmental delay onset, seizure type, electroencephalographic/magnetic resonance imaging findings, and first-line treatment. Gain of function (GOF) versus loss of function (LOF) is valuable for informing treatment. Sodium channel blockers are optimal first-line treatment for GOF, severe DEE, mild/moderate DEE, and SeL(F)IE; levetiracetam is relatively contraindicated in GOF patients. First-line treatment for NDDwGE is valproate, ethosuximide, or lamotrigine; sodium channel blockers are relatively contraindicated in LOF patients. This is the first-ever global consensus for the diagnosis and treatment of SCN8A-related disorders. This consensus will reduce knowledge gaps in disease recognition and inform preferred treatment across this heterogeneous disorder. Consensus of this type allows more clinicians to provide evidence-based care and empowers SCN8A families to advocate for their children.

Congenital LMNA-Related Muscular Dystrophy in Paediatrics: Cardiac Management in Monozygotic Twins

Pathogenic variants in LMNA have been associated with a wide spectrum of muscular conditions: the laminopathies. LMNA-related congenital muscular dystrophy is a laminopathy characterised by the early onset of symptoms and often leads to a fatal outcome at young ages. Children face a heightened risk of malignant arrhythmias. No established paediatric protocols for managing this condition are available. We review published cases and provide insights into disease progression in two twin sisters with LMNA-related muscular dystrophy. Our objective is to propose a cardiac surveillance and management plan tailored specifically for paediatric patients. We present a family of five members, including two twin sisters with LMNA-related muscular dystrophy. A comprehensive neuromuscular and cardiac work-up was performed in all family members. Genetic analysis using massive sequencing technology was performed in both twins. Clinical assessment showed that only the twins showed diagnoses of LMNA-related muscular dystrophy. Follow-up showed an early onset of symptoms and life-threatening arrhythmias, with differing disease progressions despite both twins passing away. Genetic analysis identified a de novo rare missense deleterious variant in the LMNA gene. Other additional rare variants were identified in genes associated with myasthenic syndrome. Early-onset neuromuscular symptoms could be related to a prognosis of worse life-threatening arrhythmias in LMNA related muscular dystrophy. Being a carrier of other rare variants may be a modifying factor in the progression of the phenotype, although further studies are needed. There is a pressing need for specific cardiac recommendations tailored to the paediatric population to mitigate the risk of malignant arrhythmias.

Attention-deficit/hyperactivity disorder in children with epilepsy: A systematic review and meta-analysis of prevalence and risk factors.

To evaluate the prevalence of and risk factors for attention-deficit/hyperactivity disorder (ADHD) in children with epilepsy (CWE). We conducted a systematic search in PubMed and Embase for the meta-analysis. The pooled prevalence of ADHD was calculated using a random-effects model; subgroup analyses were performed to explore heterogeneity. We collected raw data from articles reporting potential risk factors, which were included in the subsequent risk factor analysis. Forty-six articles met the inclusion criteria for the meta-analysis, which showed a pooled ADHD prevalence of 30.7% in CWE, with a predominance of the inattentive subtype of ADHD; the heterogeneity of prevalence was related to population source/study setting (clinic based, community based, or database based) and method of ADHD diagnosis (with or without clinical review). Risk factors for ADHD in epilepsy included younger age, intellectual/developmental disabilities, a family history of epilepsy, earlier epilepsy onset, absence epilepsy, more frequent seizures, and polytherapy; In contrast, risk factors such as sex, generalized epilepsy or seizures, epilepsy etiology, and electroencephalogram abnormalities were not significantly associated with the occurrence of ADHD. The prevalence of ADHD in CWE is high and several potential risk factors are associated with it. This study contributes to a better understanding of ADHD in epilepsy for screening and treatment. This systematic review summarizes the prevalence of attention-deficit/hyperactivity disorder (ADHD) occurring in children with epilepsy and analyses the risk factors for comorbid ADHD in epilepsy. By reviewing 46 articles, we concluded that the overall prevalence of ADHD in children with epilepsy was 30.7% and that intellectual/developmental disabilities were the most significant risk factor for combined ADHD in children with epilepsy. This study provides a wealth of information on comorbid ADHD in epilepsy, which will help clinicians identify and treat potential ADHD in children with epilepsy in a timely manner.

Research progress and future trends of early-onset gastric cancer

Early onset gastric cancer (EOGC), defined as gastric cancer occurring at a younger age. Early-onset gastric cancer tends to be poorly differentiated and highly malignant. Genetic material and environmental exposure factors may be the main causes of early occurrence of gastric cancer. Prolonging the survival and improving the quality of life of patients with early-onset gastric cancer is our main research goal in the future. This article aims to elaborate on the current research status and progress of EOGC in terms of its clinicopathological characteristics, molecular genetics, microecological environment, prediction methods, treatment plans, and prognosis, while also exploring potential avenues for future research.

Trends, challenges, and reflections on early-onset gastric cancer

Early onset gastric cancer (EOGC), as a distinct type of gastric cancer, has seen a gradually increasing incidence in recent years, imposing significant negative impacts on society and families, and has attracted widespread attention. EOGC presents a series of clinical characteristics, such as a higher prevalence among women, pathological types predominantly being poorly differentiated or undifferentiated, and Lauren classification often being diffuse, making it more prone to distant metastasis. However, the causes and mechanisms of its onset are not yet fully understood. Notably, about 10% of EOGC cases exhibit familial clustering and germline mutations in the Cadherin-1 (CDH1) or α-1 catenin (CTNNA1) genes, known as hereditary diffuse gastric cancer (HDGC). These unique clinical features pose significant challenges for the diagnosis and treatment of EOGC. The core of treatment for early onset gastric cancer focuses on strong efficacy, function preservation, rehabilitation, and social reintegration. Clinically, a multidisciplinary approach and comprehensive treatment are essential, with equal emphasis on physiological and psychological aspects, balancing therapeutic effectiveness with functional outcomes, to benefit more patients with EOGC.

Familial aggregation of sinus node dysfunction indicating pacemaker implantation: A nation-wide cohort study

Abstract Background Rare genetically inherited forms of sinus node dysfunction (SND) have been described but the significance of a family history of SND and the associated prognosis remains unknown. Purpose To investigate the risk of SND indicating pacemaker implantation and mortality in first-degree relatives to patients who received a pacemaker because of SND, and to assess the effect of age of onset on disease risk. Methods This was a nationwide retrospective register-based cohort study including all Danish citizens born after 1954. SND was defined to be present when a first pacemaker was implanted on this indication. To establish family structures, we retrieved data from the Danish civil registration registry which contains information on parental links and merged them with the Danish Pacemaker and ICD registry which contains information on all pacemaker implanted because of SND in Denmark. Using Poisson regression, we compared the rates of SND and the risk of all-cause mortality in first-degree relatives of SND patients with the rates in the general population between January 1st 1982 and August 31st 2022. Analyses were adjusted for selected diagnosis- and procedure codes from the Danish National Patient Registry, including hypertension, diabetes mellitus, heart failure, coronary artery disease, atrial fibrillation or flutter, valvular heart disease, stroke, and cardiac surgery. Results We included 6,027,090 individuals among whom 2,477 first pacemakers were implanted due to SND in the time period. The adjusted rate ratio (RR) of SND was 2.9 (95% CI 2.4-3.6), p&amp;lt;0.001, for individuals having any father, mother or sibling with SND compared with the general population. This risk was increased in first-degree relatives across all ages of SND onset in the index person but substantially higher if SND onset in the index person occurred ≤50 years (adjusted RR=7.1 (95% CI 3.5-14.3), p&amp;lt;0.001). Comparable risks of SND were observed for first-degree relatives to mothers, fathers and siblings with SND as well as for men and women. Overall, mortality was similar between individuals having any father, mother or sibling with SND and the general population (adjusted RR=1.02 (0.97-1.08), p=0.45). However, there was a trend towards an increased mortality among first-degree relatives to index persons with an early onset. Conclusions First-degree relatives to SND patients are at increased risk of SND with risk being inversely associated with age of onset in the index person. Overall, mortality in first-degree relatives was comparable to the general population, suggesting a benign prognosis in the vast majority of cases with genetically inherited SND.Table 1Figure 1

Facilitating Culturally Competent Breast Imaging Care in South Asian Patients.

South Asians are a rapidly growing subset of the Asian population in the United States. They comprise people from multiple countries with diverse beliefs, languages, and cultural identities and values. The incidence of breast cancer is rising in South Asian women in the United States, with earlier onset and predilection for HER2-enriched tumors. Despite the rising incidence of breast cancer, participation in screening remains lower than other populations. Health care inequities in South Asian women are multifactorial and may be due to traditional health beliefs and practices, language barriers, cultural differences, and lack of overall awareness. Developing a culturally sensitive environment in breast imaging clinic practice can lead to improved patient care and adherence. Given the scarcity of data specific to the South Asian population in United States, there is a need for health service researchers and practice leaders to obtain more high-quality data to understand the needs of South Asian patient populations.

Decreased but persistent epigenetic age acceleration is associated with changes in T-cell subsets after initiation of highly active antiretroviral therapy in persons living with HIV

IntroductionPersons living with HIV (PLWH) experience the early onset of age-related illnesses, even in the setting of successful human immunodeficiency virus (HIV) suppression with highly active antiretroviral therapy (HAART). HIV infection is associated with accelerated epigenetic aging as measured using DNA methylation (DNAm)-based estimates of biological age and of telomere length (TL).MethodsDNAm levels (Infinium MethylationEPIC BeadChip) from peripheral blood mononuclear cells from 200 PLWH and 199 HIV-seronegative (SN) participants matched on chronologic age, hepatitis C virus, and time intervals were used to calculate epigenetic age acceleration, expressed as age-adjusted acceleration residuals from 4 epigenetic clocks [Horvath’s pan-tissue age acceleration residual (AAR), extrinsic epigenetic age acceleration (EEAA), phenotypic epigenetic age acceleration (PEAA), and grim epigenetic age acceleration (GEAA)] plus age-adjusted DNAm-based TL (aaDNAmTL). Epigenetic age acceleration was compared for PLWH and SN participants at two visits: up to 1.5 years prior and 2–3 years after HAART (or equivalent visits). Flow cytometry was performed in PLWH and SN participants at both visits to evaluate T-cell subsets.ResultsEpigenetic age acceleration in PLWH decreased after the initiation of HAART but remained greater post-HAART than that in age-matched SN participants, with differences in medians of 6.6, 9.1, and 7.7 years for AAR, EEAA, and PEAA, respectively, and 0.39 units of aaDNAmTL shortening (all p &amp;lt; 0.001). Cumulative HIV viral load after HAART initiation was associated with some epigenetic acceleration (EEAA, PEAA, and aaDNAmTL), but even PLWH with undetectable HIV post-HAART showed persistent epigenetic age acceleration compared to SN participants (p &amp;lt; 0.001). AAR, EEAA, and aaDNAmTL showed significant associations with total, naïve, and senescent CD8 T-cell counts; the total CD4 T-cell counts were associated with AAR, EEAA, and PEAA (p = 0.04 to &amp;lt;0.001). In an epigenome-wide analysis using weighted gene co-methylation network analyses, 11 modules demonstrated significant DNAm differences pre- to post-HAART initiation. Of these, nine were previously identified as significantly different from pre- to post-HIV infection but in the opposite direction.DiscussionIn this large longitudinal study, we demonstrated that, although the magnitude of the difference decreases with HAART is associated with the cumulative viral load, PLWH are persistently epigenetically older than age-matched SN participants even after the successful initiation of HAART, and these changes are associated with changes in T-cell subsets.

Knockdown of NeuroD2 leads to seizure-like behaviour, brain neuronal hyperactivity and a leaky blood-brain barrier in a Xenopus laevis tadpole model of DEE75.

Developmental and Epileptic Encephalopathies (DEE) are a genetically diverse group of severe, early onset seizure disorders. DEE are normally identified clinically in the first six months of life by the presence of frequent, difficult to control seizures and accompanying stalling or regression of development. DEE75 results from de novo mutations of the NEUROD2 gene that result in loss of activity of the encoded transcription factor, and the seizure phenotype was shown to be recapitulated in Xenopus tropicalis tadpoles. We used CRISPR/Cas9 to make a DEE75 model in Xenopus laevis, to further investigate the developmental aetiology. NeuroD2.S CRISPR/Cas9 edited tadpoles were more active, swam faster on average, and had more seizures (C-shaped contractions resembling unprovoked C-start escape responses) than their sibling controls. Live imaging of Ca2+ signalling revealed prolongued, strong signals sweeping through the brain, indicative of neuronal hyperactivity. While the resulting tadpole brain appeared grossly normal, the blood-brain barrier was found to be leakier than that of controls. Additionally, the TGFβ antagonist Losartan was shown to have a short-term protective effect, reducing neuronal hyperactivity and reducing permeability of the blood-brain barrier. Treatment of NeuroD2 CRISPant tadpoles with 5 mM Losartan decreased seizure events by more than fourfold compared to the baseline. Our results support a model of DEE75 resulting from reduced NeuroD2 activity during vertebrate brain development, and indicate that a leaky blood-brain barrier contributes to epileptogenesis.

Structural and Functional Characteristics of the Dorsolateral Prefrontal Cortex in Schizophrenia Spectrum Disorders and Their Associations with Onset Age

Background: the dorsolateral prefrontal cortex (DLPFC) is one of the latest brain structures to mature during the ontogeny, and its structural and functional abnormalities play an important role in the pathogenesis of schizophrenia. As schizophrenia spectrum disorders usually start before the complete brain maturation and their earlier onset is coupled with worse prognosis, we suggested that earlier illness onset is related to more pronounced aberrations of the DLPFC. The aim of study was to analyze the associations of the onset age of schizophrenia spectrum disorders with structural and functional characteristics of the DLPFC that differentiated patients with schizophrenia spectrum disorders from healthy controls. Patients and methods: male patients with a diagnosis of schizophrenia spectrum disorders (n = 82) and healthy controls (n = 86) underwent structural MRI and functional resting-state fMRI. Cortical thickness and whole-brain functional connectivity of the DLPFC as well as local coherence and amplitude of low-frequency fluctuations of haemodynamic signal in the DLPFC were analyzed. Results: patients demonstrated a decreased gray matter thickness in the DLPFC bilaterally along with aberrant (predominantly decreased) functional connectivity of the DLPFC with other brain structures in each hemisphere. These measures were not associated with the age of illness onset. Conclusions: structural and functional abnormalities revealed in this study coincide with conventional view on the DLPFC as one of the key regions in schizophrenia spectrum disorders pathogenesis, however, these aberrations were not related to the age of psychosis onset. Possible interpretations of our results and limitations of the study are discussed in the article.

Trichoscopy of Frontal Fibrosing Alopecia Affecting Black Scalp: A Literature Review

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Frontal fibrosing alopecia (FFA) is a primary lymphocytic scarring alopecia characterized by progressive recession of the frontotemporal hairline, affecting mainly postmenopausal and, lately, premenopausal women of African descent. Considering the importance of trichoscopy on FFA diagnosis and the peculiarities found in patients with higher skin phototypes, this study aimed to review the FFA trichoscopy in the black scalp (Fitzpatrick IV–VI), a topic that remains sparsely described in the existing literature. &lt;b&gt;&lt;i&gt;Summary:&lt;/i&gt;&lt;/b&gt; In black patients, FFA may manifest singular features on presentation posing diagnostic clinical and trichoscopic challenges. This group has lower prevalence of the FFA compared to other alopecias. It may have an earlier age of onset and often exhibits more severe manifestations due to the coexistence of other types of alopecia and delay in diagnosis. The early signs of the disease in black patients may manifest in the eyebrows before scalp hair loss and lichen planus pigmentosus may be a herald sign. &lt;b&gt;&lt;i&gt;Key Messages:&lt;/i&gt;&lt;/b&gt; Our research analyzes FFA trichoscopy findings in black patients to help precise diagnosis and treatment. Raising awareness of the disease characteristics on trichoscopy contributes to improving hair care in this population.

#1731 Clinico-epidemiological characteristics of early versus late onset cytomegalovirus disease among renal transplant recipients: two decade experience

Abstract Background and Aims The epidemiology of the Cytomegalo virus (CMV) disease among renal transplant recipients has changed with the advent of effective antiviral prophylaxis usually occurs in the later part of the post transplant period. To study the difference between CMV infections occurring in early versus late post renal transplant period with respect to nature of immunosuppressive medications (induction agents, maintenance agents and heightening of immunosuppression), type of CMV infection and occurrence of biopsy proven rejection post CMV infection. Method A single centre retrospective observational study was conducted among renal transplant recipients who underwent kidney transplant between 1st January, 2002 and 31st December, 2021. CMV disease was classified as early or late depending on detection before or after 90 days post transplant. The differences in clinical presentation between early and late onset CMV disease, use of immunosuppression, and the impact on graft outcomes were studied. Results Total number of recipients with CMV disease was 156 (7.2%) out of total 2164 renal transplant recipients. Twenty-five (16%) patients had early CMV while one hundred and thirty one (84%) had late CMV. The two groups did not differ with respect to induction or use of maintenance immunosuppressive agents. Proportion of CMV syndrome was more among early CMV group (56.0% vs 26.7%, p = 0.01) while tissue invasive disease was more frequent among late CMV group (44.0% vs. 73.3%, p = 0.01). Diarrhoea was more frequent in late (63.4%) versus early CMV (36%) (p = 0.01). Graft loss occurred in 4.0% of early and 25.2% of late CMV cases (p = 0.03). However, both groups did not differ with respect to occurrence of biopsy proven rejection post infection. Conclusion Early CMV presents more frequently as CMV syndrome while late CMV usually manifests as tissue invasive disease. Graft loss is more common in patients with late onset disease.