Severe Neurological Problems Research Articles

The complete genomic sequencing of a Klebsiella pneumoniae isolate derived from the blood of a patient suffering from severe neurological problems in Zhengzhou, China.

This study presents the comprehensive analysis of the genomic sequence of Klebsiella pneumoniae strain FAHZZU7042hy, having a 5,690,191 bp chromosome size. This strain was obtained from a blood sample of a patient suffering from severe neurological problems in Zhengzhou, China, 2023.

Neurologic Symptoms After 177Lu-Prostate-Specific-Membrane Antigen-617 Therapy: A Single-Center Experience.

Treatment with 177Lu-prostate-specific membrane antigen (PSMA)-617 (177Lu-vipivotide tetraxetan [Pluvicto]) prolongs both progression-free and overall survival in advanced PSMA-positive metastatic castration-resistant prostate cancer. Data examining specifically neurologic symptoms after 177Lu-PSMA-617 treatment are scarce. In this study, we aimed to review the neurologic findings in a large cohort of metastatic castration-resistant prostate cancer patients undergoing 177Lu-PSMA-617 therapy. Methods: The clinical records and imaging data of patients who received their initial dose of 177Lu-PSMA-617 between March 2022 and November 2022 were retrospectively reviewed. All patients presenting for medical evaluation, regardless of specific specialty appointments, with new or worsening neurologic symptoms were included in the study. Results: A total of 185 patients underwent 177Lu-PSMA-617 therapy. The median age was 70 y (range, 58-90 y). The mean follow-up time was 12.04 ± 2.87 mo. Fifty-five new or worsening neurologic symptoms were observed in 50 patients (27%, 50/185). Of these, 27 (11.9%, 27/185) reported altered taste. Eleven patients (6%, 11/185) experienced dizziness with no other clear etiology; 2 of these patients were admitted to the emergency department (ED). Paresthesia symptoms were reported in 6 patients (3.2%, 6/185). Five patients (2.7%, 5/185) reported headaches, 3 of these patients were admitted to the ED because of the severity of the symptoms. Two patients (1.08%, 2/185) presented with extremity weakness. Two patients (1.08%, 2/185) had an ischemic stroke and were admitted to the ED. One patient (0.05%, 1/185) exhibited gait disturbances. In total, 7 patients (3.78%, 7/185) were admitted to the ED because of neurologic symptoms. None of the patients discontinued or failed to complete the 177Lu-PSMA-617 therapy because of neurologic symptoms. Conclusion: After 177Lu-PSMA-617 treatment, the most common neurologic symptoms were dysgeusia and dizziness. In this study, our follow-up period and population size might not have been sufficient to detect delayed or uncommon neurologic symptoms. In patients without neurologic symptoms or central nervous system metastases before treatment, we found the development of severe neurologic problems to be rare and unlikely to require discontinuation of treatment.

Traumatic brain injury unmasking Vitamin B12 deficiency in an infant with long-term follow-up

Falls are very common in infancy and toddler age group. We are presenting a case of insignificant fall from the cot causing severe neurological problems in an infant due to previous underlying relatively asymptomatic vitamin B12 deficiency. A six-month-old female infant presented with a fall from a cot followed by altered sensorium, vomiting, right focal seizures, and right sided weakness. On examination, a low Glasgow coma scale (8/15), right sided weakness (MRC power of 3/5 in the right upper and lower limbs), with anaemia were noted. Investigations revealed left frontal contusion with haemorrhage, megaloblastic anaemia, and thrombocytopenia with low vitamin B12 level. The child improved with symptomatic management of raised intracranial pressure and injectable vitamin B12 supplements. Prompt intervention and appropriate treatment led to favourable outcomes in the infant, highlighting the importance of recognizing and addressing concomitant deficiencies in infants with TBI.

Exploring Zika Virus Impact on Endothelial Permeability: Insights into Transcytosis Mechanisms and Vascular Leakage.

Treating brain disease is challenging, and the Zika virus (ZIKV) presents a unique obstacle due to its neuroinvasive nature. In this review, we discuss the immunopathogenesis of ZIKV and explore how the virus interacts with the body's immune responses and the role of the protein Mfsd2a in maintaining the integrity of the blood-brain barrier (BBB) during ZIKV neuroinvasion. ZIKV has emerged as a significant public health concern due to its association with severe neurological problems, including microcephaly and Gillain-Barré Syndrome (GBS). Understanding its journey through the brain-particularly its interaction with the placenta and BBB-is crucial. The placenta, which is designed to protect the fetus, becomes a pathway for ZIKV when infected. The BBB is composed of brain endothelial cells, acts as a second barrier, and protects the fetal brain. However, ZIKV finds ways to disrupt these barriers, leading to potential damage. This study explores the mechanisms by which ZIKV enters the CNS and highlights the role of transcytosis, which allows the virus to move through the cells without significantly disrupting the BBB. Although the exact mechanisms of transcytosis are unclear, research suggests that ZIKV may utilize this pathway.

Mechanistic complexities of sulfite oxidase: An enzyme with multiple domains, subunits, and cofactors

Sulfite oxidase (SO) deficiency, an inherited disease that causes severe neonatal neurological problems and early death, arises from defects in the biosynthesis of the molybdenum cofactor (Moco) (general sulfite oxidase deficiency) or from inborn errors in the SUOX gene for SO (isolated sulfite oxidase deficiency, ISOD). The X-ray structure of the highly homologous homonuclear dimeric chicken sulfite oxidase (cSO) provides a template for locating ISOD mutation sites in human sulfite oxidase (hSO). Catalysis occurs within an individual subunit of hSO, but mutations that disrupt the hSO dimer are pathological. The catalytic cycle of SO involves five metal oxidation states (MoVI, MoV, MoIV, FeIII, FeII), two intramolecular electron transfer (IET) steps, and couples a two-electron oxygen atom transfer reaction at the Mo center with two one-electron transfers from the integral b-type heme to exogenous cytochrome c, the physiological oxidant. Several ISOD examples are analyzed using steady-state, stopped-flow, and laser flash photolysis kinetics and physical measurements of recombinant variants of hSO and native cSO. In the structure of cSO, Mo…Fe = 32 Å, much too long for efficient IET through the protein. Interdomain motion that brings the Mo and heme centers closer together to facilitate IET is supported indirectly by decreasing the length of the interdomain tether, by changes in the charges of surface residues of the Mo and heme domains, as well as by preliminary molecular dynamics calculations. However, direct dynamic measurements of interdomain motion are in their infancy.

Direct and indirect impact of SARS-CoV-2 on the brain.

Although COVID-19 is mostly a pulmonary disease, it is now well accepted that it can cause a much broader spectrum of signs and symptoms and affect many other organs and tissue. From mild anosmia to severe ischemic stroke, the impact of SARS-CoV-2 on the central nervous system is still a great challenge to scientists and health care practitioners. Besides the acute and severe neurological problems described, as encephalopathies, leptomeningitis, and stroke, after 2years of pandemic, the chronic impact observed during long-COVID or the post-acute sequelae of COVID-19 (PASC) greatly intrigues scientists worldwide. Strikingly, even asymptomatic, and mild diseased patients may evolve with important neurological and psychiatric symptoms, as confusion, memory loss, cognitive decline, chronic fatigue, associated or not with anxiety and depression. Thus, the knowledge on the correlation between COVID-19 and the central nervous system is of great relevance. In this sense, here we discuss some important mechanisms obtained from in vitro and in vivo investigation regarding how SARS-CoV-2 impacts the brain and its cells and function.

Effectiveness of robotic assisted laparoscopic nissen fundoplication in neurologically impaired children with severe gastroesophageal reflux disease

Laparoscopic Nissen Fundoplication is still the most widely used surgical technique in the treatment of gastroesophageal reflux disease (GERD) in children. However, there are some technical and anatomical difficulties in the treatment of reflux in NIC with GERD. All these difficulties lead to the high rate of surgical failure observed in neurological impaired children (NIC). Robotic surgery provides several advantages in overcoming these difficulties. This study is the first study to evaluate the effectiveness of robotic surgery in the treatment of GERD in children with severe or moderate neurological impairments reported in Turkey. This study took place between January 2018 and February 2020. We retrospectively evaluated the records of eleven children with severe or moderate neurological problems who were treated using the robotically assisted laparoscopic Nissen fundoplication (RALNF) technique for demographic data, anesthesia time, pre-console time, console time, and postoperative complications. Nine of the patients (81.8%) had serious and two had moderate neurological problems. All of the patients applied to the emergency department at different times due to recurrent lung infections. While the first RALNF console time was 240 minutes, this study revealed that this time decreased to 45 minutes. None of the patients had complications related to the surgical procedure, but four patients required postoperative intensive care unit up to two months due to several problems related to NIC. RALNF can be safely applied to pediatric patients with GERD with severe and moderate NIC.

Exposure of metal toxicity in Alzheimer’s disease: An extensive review

Metals serve important roles in the human body, including the maintenance of cell structure and the regulation of gene expression, the antioxidant response, and neurotransmission. High metal uptake in the nervous system is harmful because it can cause oxidative stress, disrupt mitochondrial function, and impair the activity of various enzymes. Metal accumulation can cause lifelong deterioration, including severe neurological problems. There is a strong association between accidental metal exposure and various neurodegenerative disorders, including Alzheimer’s disease (AD), the most common form of dementia that causes degeneration in the aged. Chronic exposure to various metals is a well-known environmental risk factor that has become more widespread due to the rapid pace at which human activities are releasing large amounts of metals into the environment. Consequently, humans are exposed to both biometals and heavy metals, affecting metal homeostasis at molecular and biological levels. This review highlights how these metals affect brain physiology and immunity and their roles in creating harmful proteins such as β-amyloid and tau in AD. In addition, we address findings that confirm the disruption of immune-related pathways as a significant toxicity mechanism through which metals may contribute to AD.

Specific Recognition of the 5'-Untranslated Region of West Nile Virus Genome by Human Innate Immune System.

In the last few years, the sudden outbreak of COVID-19 caused by SARS-CoV-2 proved the crucial importance of understanding how emerging viruses work and proliferate, in order to avoid the repetition of such a dramatic sanitary situation with unprecedented social and economic costs. West Nile Virus is a mosquito-borne pathogen that can spread to humans and induce severe neurological problems. This RNA virus caused recent remarkable outbreaks, notably in Europe, highlighting the need to investigate the molecular mechanisms of its infection process in order to design and propose efficient antivirals. Here, we resort to all-atom Molecular Dynamics simulations to characterize the structure of the 5-untranslated region of the West Nile Virus genome and its specific recognition by the human innate immune system via oligoadenylate synthetase. Our simulations allowed us to map the interaction network between the viral RNA and the host protein, which drives its specific recognition and triggers the host immune response. These results may provide fundamental knowledge that can assist further antivirals’ design, including therapeutic RNA strategies.

Applications of Nanomaterials for Adsorptive and Catalytic Removal of Chemical Pesticides: An Overview

Chemical pesticides are one of the most frequently encountered pollutants in multiple water sources and made their way into biomagnification. Short-term exposure to pesticides causes headache, vomiting, nausea, blurred vision, pupil constriction, muscle tremors, excessive sweating, etc. whereas prolonged exposure can lead to severe neurological problems, coma and even death. However, conventional methods have been proved to be inefficient in complete removal of pesticides. Over the past few years, nanotechnology is considered to play a significant role in influencing the current environmental engineering and science owing to their excellent physico-chemical properties and tuneable functionalities. Nanomaterials are massively enrolled as adsorbents and photocatalysts for the removal of various chemical pesticides from different sources. In present article, the applicability of different nanomaterials for the removal of various pesticides via adsorption and photocatalytic degradation from aqueous environment was discussed. Furthermore, the influence of surface treatment to their functionalities and efficiencies was reviewed and highlighted.

Delineation of altered brain proteins associated with furious rabies virus infection in dogs by quantitative proteomics

Rabies is a fatal zoonotic disease caused by rabies virus (RABV). Despite the existence of control measures, dog-transmitted human rabies accounts for ˃95% reported cases due to unavailability of sensitive diagnostic methods, inadequate understanding of disease progression and absence of therapeutics. In addition, host factors and their role in RABV infection are poorly understood. In this study, we used 8-plex iTRAQ coupled with HRMS approach to identify differentially abundant proteins (DAPs) of dog brain associated with furious rabies virus infection. Total 40 DAPs including 26 down-regulated and 14 up-regulated proteins were statistically significant in infected samples. GO annotation and IPA showed that calcium signaling and calcium transport, efficient neuronal function, metabolic pathway associated proteins were mostly altered during this infection. Total 34 proteins including 10 down-regulated proteins pertaining to calcium signaling and calcium transport pathways were successfully verified by qRT-PCR and two proteins were verified by western blot, thereby suggesting these pathways may play an important role in this infection. This study provides the map of altered brain proteins and some insights into the molecular pathophysiology associated with furious rabies virus infection. However, further investigations are required to understand their role in disease mechanism. SignificanceTransmission of rabies by dogs poses the greatest hazard world-wide and the rare survival of post-symptomatic patients as well as severe neurological and immunological problems pose a question to understand the molecular mechanism involved in rabies pathogenesis. However, information regarding host factors and their function in RABV infection is still inadequate. Our study has used an advanced quantitative proteomics approach i.e. 8-plex iTRAQ coupled with HRMS and identified 40 DAPs in furious rabies infected dog brain tissues compared to the controls. Further analysis showed that calcium signaling and transport pathway, efficient neuronal functions and metabolic pathway associated brain proteins were most altered during furious rabies virus infection. This data provides a map of altered brain proteins which may have role in furious rabies virus infection. Hence, this will improve our understanding of the molecular pathogenesis of RABV infection.

Chromatin remodeller CHD7 is required for GABAergic neuron development by promoting PAQR3 expression

Mutations in the chromatin remodeller-coding gene CHD7 cause CHARGE syndrome (CS). CS features include moderate to severe neurological and behavioural problems, clinically characterized by intellectual disability, attention-deficit/hyperactivity disorder and autism spectrum disorder. To investigate the poorly characterized neurobiological role of CHD7, we here generate a zebrafish chd7−/− model. chd7−/− mutants have less GABAergic neurons and exhibit a hyperactivity behavioural phenotype. The GABAergic neuron defect is at least in part due to downregulation of the CHD7 direct target gene paqr3b, and subsequent upregulation of MAPK/ERK signalling, which is also dysregulated in CHD7 mutant human cells. Through a phenotype-based screen in chd7−/− zebrafish and Caenorhabditis elegans, we show that the small molecule ephedrine restores normal levels of MAPK/ERK signalling and improves both GABAergic defects and behavioural anomalies. We conclude that chd7 promotes paqr3b expression and that this is required for normal GABAergic network development. This work provides insight into the neuropathogenesis associated with CHD7 deficiency and identifies a promising compound for further preclinical studies.

Can You Identify Autoimmune Psychosis?

Can You Identify Autoimmune Psychosis?

A review on zika virus: clinical aspects and therapeutic responses

The Zika Virus (ZIKV) happens to be one of the recent infections investigated after the Ebola pandemic. It is an arthropod-borne virus (arbovirus) within the family Flaviviridae class. ZIKV is an RNA virus with a single strand, enveloped, icosahedral, non-sectioned, positive sense. It is 40 nm wide and has an outer (E) envelope and a dense inner core. The ZIKV can be transmitted by two methods: human and human-to-human vectors. The vector transmission is by Aedes spp. Mosquitoes and diseases outside Africa are transmitted by Aedes aegypti. Originating in Nigeria in 1947 it was reported as a mild illness and from a rhesus monkey. With a certain passage of time earned significant attention from healthcare organisations for the human population. Many clinical symptoms in adults in French Polynesia have been recorded, ranging from mild illness to severe neurological problems such as Guillain-Barré syndrome. Other symptoms include encephalitis microencephaly, meningoencephalitis, myelitis, paraesthesia, vertigo, facial and ophthalmological paralysis (photophobia and hypertensive iridocyclitis) and auditory manifestations. In this review, the clinical aspects and other therapeutic responses are studied here to understand the approach more treating symptoms arising with the infection of the Zika virus. Various complications have been studied in this review and diagnosis have been performed to identify the presence in the human body and also take clinical measures on alleviating the symptoms of the infected patients.

Cerebral Air Embolism: an Extremely Rare Complication of Tunneled Central Venous Catheter. Case Report

Central venous catheters are commonly used in bone marrow transplantation units and useful for drug administration, supportive treatments, and nutrition. They are used for stem cell infusion and also hemodialysis, hemapheresis, and photopheresis procedures when required during posttransplant period; however, they can sometimes cause severe morbidity and mortality during insertion or removal. While air embolism which may lead to severe neurologic problems is among the rare but severe complications, a meticulous and experienced approach during insertion and removal could significantly decrease this risk. In this case report, we wanted to pull attention to cerebral air embolism which is a rare mechanic complication of central venous catheters.

A basic understanding of mucopolysaccharidosis: Incidence, clinical features, diagnosis, and management.

Mucopolysaccharidoses (MPS) are a group of rare lysosomal storage diseases (LSD) with multi-organic and severe symptoms. MPS occur worldwide in various forms though have relative a low incidence. The prevalent type of MPS varies among different continents, indicating that it may be associated with region and ethnic background. Undegraded glycosaminoglycans (GAGs) induced by deficiency of enzymes are the primary cause of MPS. Clinical features differ depending on the specific enzyme deficiency including coarse facial features, cognitive retardation, hepatosplenomegaly, hernias, kyphoscoliosis, corneal clouding, etc. Symptoms of different types are usually similar especially MPS I and II, but may have distinguishable features such as severe neurological problems in MPS III and hydrops fetails in MPS VII. These clinical features contribute to diagnosis, but early and precisely diagnosis in the asymptomatic stage is imperative for better outcomes. Novel approaches including urinary and blood GAG test, enzyme assay and gene test help to diagnose MPS and to determine its subtype. Hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) are conventional treatment for MPS, but are not effective at treating all MPS. Newer threatments, such as advanced ERT, gene therapy and substrate reduction therapy (SRT), improve therpeutic efficacy. In this review, we update information on the clinical manifestations, diagnosis, and treatment of the different forms of this disease in the hopes of stimulating further interest in MPS.

Defective transcription of ATF3 responsive genes, a marker for Cockayne Syndrome

Cockayne syndrome (CS) is a rare genetic disorder caused by mutations (dysfunction) in CSA and CSB. CS patients exhibit mild photosensitivity and severe neurological problems. Currently, CS diagnosis is based on the inefficiency of CS cells to recover RNA synthesis upon genotoxic (UV) stress. Indeed, upon genotoxic stress, ATF3, an immediate early gene is activated to repress up to 5000 genes encompassing its responsive element for a short period of time. On the contrary in CS cells, CSA and CSB dysfunction impairs the degradation of the chromatin-bound ATF3, leading to a permanent transcriptional arrest as observed by immunofluorescence and ChIP followed by RT-PCR. We analysed ChIP-seq of Pol II and ATF3 promoter occupation analysis and RNA sequencing-based gene expression profiling in CS cells, as well as performed immunofluorescence study of ATF3 protein stability and quantitative RT-PCR screening in 64 patient cell lines. We show that the analysis of few amount (as for example CDK5RAP2, NIPBL and NRG1) of ATF3 dependent genes, could serve as prominent molecular markers to discriminate between CS and non-CS patient’s cells. Such assay can significantly simplify the timing and the complexity of the CS diagnostic procedure in comparison to the currently available methods.

24-hour Holter findings in infants with in-utero exposure to the Zika virus: a series of cases.

ABSTRACTSevere neurological problems and other special manifestations such as high prevalence of structural cardiac changes has been described in infants vertically exposed to the Zika virus (ZIKV) and has been called congenital Zika virus syndrome (CZS). Previous studies have shown that the 24-hour Holter heart rate variability (HRV) analysis allows the prediction of worse outcomes in infants with neurological impairment and higher risk of sudden infant death syndrome (SIDS), hypertension, diabetes mellitus and other cardiovascular diseases. This study describes the 24-hour Holter findings of infants with confirmed vertical exposure to the ZIKV by positive polymerase chain reaction (PCR) assays in the mother's blood during pregnancy and/or in the urine or cerebrospinal fluid of the newborn. Data analysis was descriptive and included two subgroups according to the presence of fetal distress, positive PCR to ZIKV in the newborn, CZS and severe microcephaly. Heart rate, pauses, arrhythmias, ST segment and QT interval analyses and HRV evaluation through R-R, SDNN, pNN50 and rMMSD were described. The Mann-Whitney test was performed to assess differences between the two subgroups. The sample consisted of 15 infants with a mean age of 16 months, nine of whom were male. No arrhythmias or QT interval changes were observed. The comparison of HRV through the Mann-Whitney test showed a significant difference between patients with and without CZS, with and without severe microcephaly, with lower HRV in the groups with severe microcephaly and CZS. The study suggests that there is an increased risk of SIDS and cardiovascular diseases in this group of patients.

Effect of perinatal biotin deficiency on auditory pathway of the Wistar-Albino rats

Aim: Severe biotin deficiency associated with biotinidase enzyme deficiency in newborns is seen as severe neurological problems and hearing loss. However, the effect on the infant of deficiencies in the maternal diet during pregnancy are not clear.Material and methods: The study included 16 female Wistar albino rats and 4 male Wistar albino rats, that were mated and then the females were separated into 4 groups. At 40 days after the birth, 3 pups were selected from each group, and these 12 pups were evaluated with DPOAE and ABR electrophysiologically and the cochlea was examined ultrastructurally with electron microscopy.Results: In the DPOAE evaluation, At 8000 and 11,000 Hz, the signal-noise ratios in the B-N and B-B groups were statistically significantly higher (p < .05). In ABR, lengthening of the latency periods was determined in all the waves at both 8 and 16 kHz in the B-B group. When the IPL periods were examined, lengthening in IPL 1–5 was statistically significant in the B-B group only at 8 kHz.Conclusions: Biotin can be said to have an effect on hearing pathways. However, specifically where on the hearing pathways that biotin is involved has not been clarified.

Growth, health, and motor development of 5-year-old children born after preimplantation genetic diagnosis

To evaluate the growth, health, and motor development of children born after preimplantation genetic diagnosis (PGD). Observational cohort study and comparison of 5-year-old children born after PGD to similar aged children born after IVF/intracytoplasmic sperm injection (ICSI) and children from families with a genetic disorder born after natural conception (NC). University hospital. One hundred three children were included in the PGD group. The two control groups consisted of 90 children born after IVF/ICSI and 58 children born after NC. PGD. We measured height, weight, body circumferences, body mass index, and blood pressure and performed a dysmorphological and neurological examination. We also collected data about the children's medical history, health care consultations, and motor milestones. The mean height, weight, and body mass index were comparable for all groups. Six (5.8%) PGD, four (4.4%) IVF/ICSI, and five (8.6%) NC children had a major congenital abnormality. The incidence of acute and chronic illnesses was similar in all groups. Motor milestones were achieved on time, but the IVF/ICSI group had a slightly younger mean sitting age. None of the children had severe neurological problems. Five-year-old children born after PGD show normal growth, health, and motor development when compared with children born after IVF/ICSI and NC children from families with a genetic disorder. NCT02149485.