Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause CMT2.Mutations located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)model.In addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive control.Of these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut allele.We found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila.Flies heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal morphology.These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

Mental retardation,seizures and language delay caused by new SETD1B mutations:Three case reports

BACKGROUND The SETD1B gene is instrumental in human intelligence and nerve development.Mutations in the SETD1B gene have been linked in recent studies to neurodevelopmental disorders,seizures,and language delay.CASE SUMMARY This study aimed to analyze the clinical manifestations and treatment of three patients suffering from mental retardation,epilepsy,and language delay resulting from a new mutation in the SETD1B gene.Three individuals with these symptoms were selected,and their clinical symptoms,gene test results,and treatment were analyzed.This article discusses the impact of the SETD1B gene mutation on patients and outlines the treatment approach.Among the three patients(two females and one male,aged 8,4,and 1,respectively),all exhibited psychomotor retardation,attention deficit,and hyperactivity disorder,and two had epilepsy.Antiepileptic treatment with sodium tripolyvalproate halted the seizures in the affected child,although mental development remained somewhat delayed.Whole exome sequencing revealed new mutations in the SETD1B gene for all patients,specifically with c.5473C>T(p.Arg1825trp),c.4120C>T(p.Gln1374*,593),c.14_15insC(p.His5Hisfs*33).CONCLUSION Possessing the SETD1B gene mutation may cause mental retardation accompanied by seizures and language delay.Although the exact mechanism is not fully understood,interventions such as drug therapy,rehabilitation training,and family support can assist patients in managing their symptoms and enhancing their quality of life.Furthermore,genetic testing supplies healthcare providers with more precise diagnostic and therapeutic guidance,informs families about genetic disease risks,and contributes to understanding disease pathogenesis and drug research and development.

Analysis of the optimal target node to reduce seizure-like discharge in networks

Network approaches have been widely accepted to guide surgical strategy and predict outcome for epilepsy treatment.This study starts with a single oscillator to explore brain activity,using a phenomenological model capable of describing healthy and epileptic states.The ictal number of seizures decreases or remains unchanged with increasing the speed of oscillator excitability and in each seizure,there is an increasing tendency for ictal duration with respect to the speed.The underlying reason is that the strong excitability speed is conducive to reduce transition behaviors between two attractor basins.Moreover,the selection of the optimal removal node is estimated by an indicator proposed in this study.Results show that when the indicator is less than the threshold,removing the driving node is more possible to reduce seizures significantly,while the indicator exceeds the threshold,the epileptic node could be the removal one.Furthermore,the driving node is such a potential target that stimulating it is obviously effective in suppressing seizure-like activity compared to other nodes,and the propensity of seizures can be reduced 60%with the increased stimulus strength.Our results could provide new therapeutic ideas for epilepsy surgery and neuromodulation.

Current trends and hotspots of etiology of auditory neuropathy in the past 30 years: A bibliometric analysis

Objective:To make an overview of global research trends in the etiology of auditory neuropathy(AN)over the past 30 years using a bibliometric approach.Methods:Bibliometric analyses were conducted by GraphPad Prism 9.0,Citespace 6.2.R2,and an online analysis platform to analyze and visualize publications related to etiology of AN from the Web of Science Core Collection(WoSCC)database from 1996 to 2022.Additionally,genetic factors in human AN were analyzed.Results:In total,604 original articles and reviews related to the etiology of AN from the WoSCC were included for bibliometric analysis.The results showed that annual publications and trend on etiology of AN increased linearly from 2000.Among them,the United States and China published nearly 400 records(40.32%).From the 604 records,a total of 752 keywords and 10 clustered network maps were extracted by Citespace,and‘mutations’was among the top 10 keywords.Analysis of genetic factors found that more than 30 genes were related to AN,and the latest burst occurred in 2022.Conclusion:The bibliometric analysis mapped the global research trends and analyzed hotspots for future.The results indicated that the annual publications increased linearly from 2000.Notably,there was a burst in genetic factors in 2022,which identified that genetic factor would remain a focus of future research.

Recent Advances for Global Perspectives on Etiology, Pathophysiology, Clinical Presentations, and Management of Moyamoya Disease

Moyamoya disease (MMD) is a condition characterized by the gradual narrowing and blockage of blood vessels in the brain, specifically those in the circle of Willis and the arteries that supply it. This results in reduced blood flow and oxygen to the brain, leading to progressive symptoms and potential complications. The underlying pathophysiological mechanism remains elucidated. However, recent studies have highlighted numerous etiologic factors: abnormal immune complex responses, susceptibility genes, branched-chain amino acids, antibodies, heritable diseases, and acquired diseases, which may be the great potential triggers for the development of moyamoya disease. Its clinical presentation has varying degrees from transient asymptomatic events to significant neurological deficits. Moyamoya disease (MMD) shows different patterns in children and adults. Children with MMD are more susceptible to ischemic events due to decreased blood flow to the brain. Conversely, adults with MMD are more prone to hemorrhagic events involving brain bleeding. Children with MMD may experience a range of symptoms including motor impairments, sensory issues, seizures, headaches, dizziness, cognitive delays, or ongoing neurological problems. Although adults may present with similar clinical symptoms as children, they are more prone to experiencing sudden onset intraventricular, subarachnoid, or intracerebral hemorrhages. One of the challenges in moyamoya disease is the potential for misdiagnosis or delayed diagnosis, particularly when physicians fail to consider MMD as a possible cause in stroke patients. This review aims to provide a comprehensive overview of recent global studies on the pathophysiology of MMD, along with advancements in its management. Additionally, the review will delve into various surgical treatment options for MMD, as well as its rare occurrence alongside atrioventricular malformations. Exciting prospects include the use of autologous bone marrow transplant and the potential role of Connexin 43 protein treatment in the development of moyamoya disease.

Epidemiological, Diagnostic and Evolutionary Profile of Seizures in Young Infants at Albert Royer (Dakar/Senegal)

Introduction: Seizures are one of the most common neurological complications in the infant period. The aim of our study was to describe the epidemiological, clinical, therapeutic and prognostic features of seizures in infants at the Albert Royer Children’s Hospital (Senegal). Materials and Methods: This was a retrospective, descriptive study from 1 January 2012 to 30 September 2018 of infants aged 0 days to 2 months who presented with seizures. Results: The hospital rate was 8.5%. Almost all the mothers (99.1%) had undergone at least 3 antenatal visits. Urogenital infection, gestational arterial hypertension and funicular anomalies were the main pregnancy-related pathologies. Delivery was vaginal in the majority of cases (80.9%). Most infants (43.6%) had not cried at birth. The majority of infants (63%) were born at term. Trophicity was normal in 68% of cases. The average age of the infants was 6.7 days. The main causes of seizures were hypoxic-ischemic encephalopathy (48.7%), metabolic disturbances (48.1%) and central ոеrvοսѕ system infections (15.6%). Phenobarbital was the 1st-line anticonvulsant. The case fatality rate was 39.5%. The main sequela observed were delayed psychomotor development (20.6%). Conclusion: Optimal management of infant seizures requires early diagnosis and etiological treatment by improving the quality of perinatal care to ensure better management of risk factors, as well as increasing the availability of neuroimaging equipment.

Possible Cortical Spreading Depression Recorded Intraoperatively Following a Generalized Seizure: Illustrative Case

Background: We present a compelling case fitting the phenomenon of cortical spreading depression detected by intraoperative neurophysiological monitoring (IONM) following an intraoperative seizure during a craniotomy for revascularization. Cortical spreading depression (CSD, also called cortical spreading depolarization) is a pathophysiological phenomenon whereby a wave of depolarization is thought to propagate across the cerebral cortex, creating a brief period of relative neuronal inactivity. The relationship between CSD and seizures is unclear, although some literature has made a correlation between seizures and a cortical environment conducive to CSD. Methods: Intraoperative somatosensory evoked potentials (SSEPs) and electroencephalography (EEG) were monitored continuously during the craniotomy procedure utilizing standard montages. Electrophysiological data from pre-ictal, ictal, and post-ictal periods were recorded. Results: During the procedure, intraoperative EEG captured a generalized seizure followed by a stepwise decrease in somatosensory evoked potential cortical amplitudes, compelling for the phenomenon of CSD. The subsequent partial recovery of neuronal function was also captured electrophysiologically. Discussion: While CSD is considered controversial in some aspects, intraoperative neurophysiological monitoring allowed for the unique analysis of a case demonstrating a CSD-like phenomenon. To our knowledge, this is the first published example of this phenomenon in which intraoperative neurophysiological monitoring captured a seizure, along with a stepwise subsequent reduction in SSEP cortical amplitudes not explained by other variables.

Optimizing anesthesia depth to enhance seizure quality during electroconvulsive therapy in major depressive disorder

This editorial evaluated the findings of a comprehensive study focused on the effects of anesthesia depth on seizure parameters during electroconvulsive therapy(ECT)in patients with major depressive disorder.The study utilized quantitative consciousness and quantitative nociceptive indices for monitoring sedation,hypnosis,and nociceptive responses.The analysis included 193 ECT sessions across 24 patients,revealing significant impacts of anesthesia depth on electroencephalography(EEG)seizure parameters.Key findings include that lighter anesthesia resulted in longer EEG seizure duration and higher post-ictal suppression index,without increasing complications.These insights emphasize the importance of optimal anesthesia management to improve therapeutic outcomes in ECT.

Etiology and Treatment Advances of Hematochezia in Infants Aged ≤3 Months

The incidence of hematochezia in infants aged three months or younger has shown an upward trend in recent years. This condition is characterized by visible bloody stools, which may appear bright red, dark red, jam-like, or mucus-purulent bloody stools, and is often accompanied by positive fecal occult blood tests, with or without additional systemic clinical symptoms. The etiology is multifactorial, potentially influenced by the maternal health status during pregnancy, neonatal diseases or treatments received in the NICU, and the methods used for establishing enteral and parenteral nutrition. Notably, allergic factors have gained prominence in recent years. This paper reviews recent studies to elucidate the incidence, primary causes, and current treatment approaches for early infant hematochezia, providing a reference for clinical practice.

Transient Analysis of a Reactor Coolant Pump Rotor Seizure Nuclear Accident

The reactor coolant pump(RCP)rotor seizure accident is defined as a short-time seizure of the RCP rotor.This event typically leads to an abrupt flow decrease in the corresponding loop and an ensuing reactor and turbine trip.The significant reduction of core coolant flow while the reactor is being operated at full load can have very negative consequences.This potentially dangerous event is typically characterized by a complex transient behavior in terms of flow conditions and energy transformation,which need to be analyzed and understood.This study constructed transient flow and rotational speed mathematical models under various degrees of rotor seizure using the test data collected from a dedicated transient rotor seizure test system.Then,bidirectional fluid-solid coupling simulations were conducted to investigate the flow evolution mechanism.It is found that the influence of the impeller structure size and transient braking acceleration on the unsteady head(Hu)is dominant in rotor seizure accident events.Moreover,the present results also show that the rotational acceleration additional head(Hu1)is much higher than the instantaneous head(Hu2).

A Novel Optimized Deep Convolutional Neural Network for Efficient Seizure Stage Classification

Brain signal analysis from electroencephalogram(EEG)recordings is the gold standard for diagnosing various neural disorders especially epileptic seizure.Seizure signals are highly chaotic compared to normal brain signals and thus can be identified from EEG recordings.In the current seizure detection and classification landscape,most models primarily focus on binary classification—distinguishing between seizure and non-seizure states.While effective for basic detection,these models fail to address the nuanced stages of seizures and the intervals between them.Accurate identification of per-seizure or interictal stages and the timing between seizures is crucial for an effective seizure alert system.This granularity is essential for improving patient-specific interventions and developing proactive seizure management strategies.This study addresses this gap by proposing a novel AI-based approach for seizure stage classification using a Deep Convolutional Neural Network(DCNN).The developed model goes beyond traditional binary classification by categorizing EEG recordings into three distinct classes,thus providing a more detailed analysis of seizure stages.To enhance the model’s performance,we have optimized the DCNN using two advanced techniques:the Stochastic Gradient Algorithm(SGA)and the evolutionary Genetic Algorithm(GA).These optimization strategies are designed to fine-tune the model’s accuracy and robustness.Moreover,k-fold cross-validation ensures the model’s reliability and generalizability across different data sets.Trained and validated on the Bonn EEG data sets,the proposed optimized DCNN model achieved a test accuracy of 93.2%,demonstrating its ability to accurately classify EEG signals.In summary,the key advancement of the present research lies in addressing the limitations of existing models by providing a more detailed seizure classification system,thus potentially enhancing the effectiveness of real-time seizure prediction and management systems in clinical settings.With its inherent classification performance,the proposed approach represents a significant step forward in improving patient outcomes through advanced AI techniques.

Temporal lobe malacia as a rare cause of gelastic seizure:A case report

BACKGROUND Gelastic seizure(GS)is a rare type of epilepsy that most commonly appears in patients with hypothalamic hamartoma.It is rarely associated with other types of brain damage.This particular type of epilepsy is relatively rare and has few links to other brain lesions.Temporal lobe malacia is mostly caused by cerebral infarction or cerebral hemorrhage,which can lead to seizures.We report a case of GS in a woman with temporal lobe malacia which was reported for the first time in the literature.CASE SUMMARY A 73-year-old female,diagnosed case of GS,presented with repetitive stereotyped laughter a month prior to presentation,happening multiple times daily and with each time lasting for 5-15s.Electroencephalogram displayed a focal seizure seen in the right temporal region.Magnetic resonance imaging head with contrast showed a right temporal lobe malacia.The patient was started on levetiracetam daily.The patient indicated that they had fully recovered and were not experiencing any recurrent or stereotyped laughter during their daily routines.These results remained consistent even after a one-year follow-up period.CONCLUSION GS can be caused by temporal lobe malacia,which is an uncommon but potentially grave condition.The outcome of this present case exhibited the importance of the temporal lobe in the genesis of GS.

Neuroimaging features in a patient with non-ketotic hyperglycaemic seizures: A case report

BACKGROUND Non-ketotic hyperglycaemic(NKH)seizures are a rare neurological complication of diabetes caused by hyperglycaemia in non-ketotic and non-hyperosmotic states.The clinical characteristics of NKH seizures are atypical and lack unified diagnostic criteria,leading to potential misdiagnoses in the early stages of the disease.CASE SUMMARY This report presents a rare case of NKH seizures in a 52-year-old male patient with a history of type 2 diabetes mellitus.We performed comprehensive magnetic resonance imaging(MRI)studies at admission,12 d post-admission,and 20 d post-discharge.The imaging techniques included contrast-enhanced head MRI,T2-weighted imaging(T2WI),fluid-attenuated inversion recovery(FLAIR),diffusion-weighted imaging,susceptibility-weighted imaging,magnetic reso-nance spectroscopy(MRS),and magnetic resonance venography.At the time of admission,T2WI and FLAIR of the cranial MRI showed that the left parieto-occipital cortex had gyrus-like swelling and high signal,and subcortical stripes had low signal.MRS showed a reduced N-acetylaspartate peak and increased creatine and choline peaks in the affected areas.A follow-up MRI 20 d later showed that the swelling and high signal of the left parieto-occipital cortex had disappeared,and the low signal of the subcortex had disappeared.CONCLUSION This case study provides valuable insights into the potential pathogenesis,diagnosis,and treatment of NKH seizures.The comprehensive MRI findings highlight the potential utility of various MRI sequences in diagnosing and characterizing NKH seizures.

Clinical efficacy of Baijin pills in the treatment of generalized tonicclonic seizure epilepsy with cognitive impairment

BACKGROUND The generalized tonic-clonic seizure(GTCS)is the most usual variety of epileptic seizure.It is mainly characterized by strong body muscle rigidity,loss of consciousness,a disorder of plant neurofunction,and significant damage to cognitive function.The effect of antiepileptic drugs on cognition should also be considered.At present,there is no effective treatment for patients with epilepsy,but traditional Chinese medicine has shown a significant effect on chronic disease with fewer harmful side effects and should,therefore,be considered for the therapy means of epilepsy with cognitive dysfunction.AIM To investigate the clinical efficacy of Baijin pills for treating GTCS patients with cognitive impairment.METHODS This prospective study enrolled patients diagnosed with GTCS between January 2020 and December 2023 and separate them into two groups(experimental and control)using random number table method.The control group was treated with sodium valproate,and the experimental group was Baijin pills and sodium valproate for three months.The frequency and duration of each seizure,the Montreal Cognitive Assessment Scale(MoCA),and the Quality of Life Rating Scale(QOLIE-31)were recorded before and after treatment.RESULTS There were 85 patients included(42 in the control group and 43 in the experimental group).After treatment,the seizure frequency in the experimental group was significantly reduced(P<0.05),and seizure duration was shortened(P<0.01).The total MoCA score in the experimental group significantly increased compared to before treatment(P<0.01),and the sub-item scores,except naming and abstract generalization ability,significantly increased(P<0.05),whereas the total MoCA score in the control group significantly decreased after treatment(P<0.05).The QOLIE-31 score of the experimental group increased significantly after treatment compared to before treatment(P<0.01).CONCLUSION Baijin pills have a good clinical effect on epilepsy with cognitive dysfunction.

In-hospital new-onset seizures in patients admitted to the medical intensive care unit:An observational study and algorithmic approach

BACKGROUND Seizures are one of the most common neurological complications encountered in the intensive care unit(ICU).They can occur in the background of exacerbation of a known neurological disease or secondary to non-neurological conditions such as sepsis and metabolic disturbances.However,there is a paucity of literature on the incidence and pattern of new-onset seizures in ICUs.AIM To study the incidence and patterns of new-onset seizures in patients admitted to the medical ICU.METHODS This was a prospective,multicenter,observational study performed in two tertiary care centers in Hyderabad,India over a period of 1 year.Patients upon ICU admission,who developed new-onset generalized tonic clonic seizures(GTCS),were enrolled.Those with a pre-existing seizure disorder,acute cerebrovascular accident,head injury,known structural brain lesions,or chronic liver disease were excluded as they have a higher likelihood of developing seizures.All enrolled patients were subjected to biochemical routines,radiological imaging of either computed tomography or magnetic resonance imaging,and other relevant laboratory tests as per clinical suspicion according to the protocol,and their data were recorded.Statistical analyses were conducted using descriptive statistics,χ^(2) tests,and linear regression.RESULTS A total of 61 of 2522 patients developed GTCS.Among all etiologies of seizures,metabolic causes were most frequent(35%)followed by infective causes(27%)and others(new-onset structural,drug withdrawal,druginduced,toxicology-related,and miscellaneous factors).Logistic regression analysis showed that increased sodium and calcium levels were associated with a lower likelihood of developing seizures.CONCLUSION This study identified the etiology of new-onset seizures developing in critically ill patients admitted to the ICU.These findings highlight the need for targeted monitoring of those at risk of developing seizures.

Changes in the etiology of liver cirrhosis and the corresponding management strategies

We read with interest the article by Xing Wang,which was published in the recent issue of the World Journal of Hepatology 2023;15:1294-1306.This article focuses particularly on the prevalence and trends in the etiology of liver cirrhosis(LC),prognosis for patients suffering from cirrhosis-related complications and hepatocellular carcinoma(HCC),and management strategies.The etiology of cirrhosis varies according to geographical,economic,and population factors.Viral hepatitis is the dominant cause in China.Vaccination and effective treatment have reduced the number of people with viral hepatitis,but the overall number is still large.Patients with viral hepatitis who progress over time to LC and HCC remain an important population to manage.The increased incidence of metabolic syndrome and alcohol consumption is likely to lead to a potential exponential increase in metabolic dysfunction-associated steatotic liver disease(MASLD)-associated LC and alcoholic liver disease in the future.Investigating the evolution of the etiology of LC is important for guiding the direction of future research and policy development.These changing trends indicate a need for greater emphasis on tackling obesity and diabetes,and implementing more effective measures to regulate alcohol consumption in order to reduce the occurrence of MASLD.In an effort to help cope with these changing trends,the authors further proposed countermeasures for healthcare authorities doctors,and patients.

Etiology and pathogenesis of corona virus disease 2019 on the view of Chinese medicine

Traditional Chinese Medicine has played an important role in the prevention and treatment of the Corona Virus Disease 2019 epidemic.But in views of different TCM scholars there are different opinions about disease name,characteristic of etiology,law of pathogenesis about this epidemic.Based on related literatures,this article overviews of the characteristics of TCM etiology,law of pathogenesis and methods of syndrome differentiation,hoping to find research method that fit in with TCM clinical practice.Prerequisite of treatment is identifying the cause.The clinical manifestations of patients are important to TCM,and the etiological attributes can be inferred from the clinical manifestations.SARS-CoV-2 belongs to exogenous etiological factors,but there are different opinions about its characteristics of six pathogenic factors.Cold,Dampness,Warm,Dry,Toxin,Summer-heat,Wind,are all involved.Thus,different understanding of the pathogenesis and the law of transmission is caused.Such as cold and dampness hurt Yang,furthermore,consumed of Qi;dampness and toxin infected from external environment,turbid dampness produced inside the body;dryness affecting lungs and consume of Yin;warm-heat-turbid-toxin affected lungs,stomach and intestine;and then produced phlegm stagnation or blood stasis,furthermore consumed Qi and Yin.Based on those differences,methods of syndrome differentiation in treatment of COVID-19 are diverse,which contain pattern differentiation of zang-fu organs,pattern differentiation of Wei-defence,Qi,Ying nutrients and blood;pattern differentiation by the eight principles,and pattern differentiation of six meridians.Because of SARS-CoV-2 can spread to the whole country or even the whole world in a short period of time,its pathogenic nature should be roughly the same.So studying the treatment of COVID-19 based on clinical cases,refining the similarities and differences in the clinical presentation of patients with different subtypes during the epidemic,clarification of the etiologic attribution and evolutionary patterns of disease mechanisms,developing a comprehensive understanding of COVID-19 in Chinese medicine is needed.Furthermore,getting a full understanding of COVID-19,and providing reference for the prevention and treatment of unknown infectious diseases.

Primary Multiple Cerebral Hydatid Cyst in 8 Year-Old Girl: A Rare Cause of Childhood Seizure

Background: Cystic echinococcosis is a zoonotic infection that occurs worldwide. Humans are infected through ingestion of parasite eggs in contaminated food, water or through direct contact with infected dogs, which are the definite host. Humans serve accidentally as intermediate host, and occurrences are common in children and young adults. Cystic echinococcosis is endemic in Mediterranean, South American, Middle Eastern, Central Asia, East Africa countries and Australia. Multiple cerebral hydatid cysts are very rare with only a few reports in the literature. Case Description: We present the case of an 8-year-old girl who presented with focal seizures, hemiparesis, headache, vomiting and bilateral optic atrophy. Diagnostic workup was performed, and magnetic resonance imaging revealed multiple intracranial cysts predominantly in the right frontal region with significant mass effect. A total of 11 intracranial cysts were removed surgically, and the child recovered uneventfully. Conclusion: Neurosurgeons should keep hydatidosis in the list of differentials when evaluating patients with cystic diseases of the brain. Although the removal of such cysts is challenging, outcomes are excellent when cysts are evacuated without rupture and patients show complete resolution of symptoms.

Genetic regulation of cell type-specific chromatin accessibility shapes brain disease etiology

Nucleotide variants in cell type-specific gene regulatory elements in the human brain are risk factors for human disease.We measured chromatin accessibility in 1932 aliquots of sorted neurons and non-neurons from 616 human postmortem brains and identified 34,539 open chromatin regions with chromatin accessibility quantitative trait loci(caQTLs).Only 10.4%of caQTLs are shared between neurons and non-neurons,which supports cell type-specific genetic regulation of the brain regulome.Incorporating allele-specific chromatin accessibility improves statistical fine-mapping and refines molecular mechanisms that underlie disease risk.Using massively parallel reporter assays in induced excitatory neurons,we screened 19,893 brain QTLs and identified the functional impact of 476 regulatory variants.Combined,this comprehensive resource captures variation in the human brain regulome and provides insights into disease etiology.

Importance of etiologies of secondary diabetes:How often do we think off in clinical practice?

The article"Secondary diabetes due to different etiologies:Four case reports"by Song et al,published in the World Journal of Clinical Cases,delves into the identi-fication of rare causes of secondary diabetes and emphasizes the necessity for healthcare professionals to recognize these conditions.Failure to do so can result in treatment delays and compromised patient outcomes.The article discusses spe-cific types of diabetes,including maturity onset of diabetes in young,pancreas-related diseases,endocrinopathies,drug-induced diabetes,infections,and con-genital genetic syndromes associated with diabetes mellitus.Case summaries highlight how patients with secondary diabetes,stemming from conditions such as Williams-Beuren syndrome and pituitary adenoma,often exhibit distinct characteristics overlooked in clinical practice.The authors stress the importance of a holistic diagnostic approach and advocate for proactive management through early intervention,including genetic tests and antibody detection.Increased awa-reness and education are crucial for timely identification and proper management,ultimately improving patient well-being.These findings prompt a call to action for healthcare professionals to consider rare causes of secondary diabetes,facili-tating better glycemic control and overall patient care.