Central Nervous Research Articles

Pathogenesis of PM2.5-Related Disorders in Different Age Groups: Children, Adults, and the Elderly.

The effects of PM2.5 on human health fluctuate greatly among various age groups, influenced by a range of physiological and immunological reactions. This paper compares the pathogenesis of the disease caused by PM2.5 in people of different ages, focusing on how children, adults, and the elderly are each susceptible to it because of differences in their bodies. Regarding children, exposure to PM2.5 is linked to many negative consequences. These factors consist of inflammation, oxidative stress, and respiratory problems, which might worsen pre-existing conditions and potentially cause neurotoxicity and developmental issues. Epigenetic changes can affect the immune system and make people more likely to get respiratory diseases. On the other hand, exposures during pregnancy can change how the cardiovascular and central nervous systems develop. In adults, the inhalation of PM2.5 is associated with a wide range of health problems. These include respiratory difficulties, reduced pulmonary function, and an increased susceptibility to illnesses such as asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. In addition, exposure to PM2.5 induces systemic inflammation, cardiovascular diseases, insulin resistance, and neurotoxic consequences. Evident disturbances in the immune system and cognitive function demonstrate the broad impact of PM2.5. The elderly population is prone to developing respiratory and cardiovascular difficulties, which worsen their pre-existing health issues and raise the risk of cognitive decline and neurological illnesses. Having additional medical conditions, such as peptic ulcer disease, significantly increases the likelihood of being admitted to hospital.

CARCINOGENIC EFFECT OF VARIOUS TYPES OF SMOKE

All types of smoke are carcinogenic. Increasing air smoke is a serious global problem. Knowledge on carcinogenic effects of various types of smoke is necessary to work out effective preventive measures.
 The purpose of the review is to characterize the general characteristics and peculiarities of the carcinogenic effects of various types of smoke. The most significant carcinogens of all types of smoke are polycyclic aromatic hydrocarbons, heavy metals and carbon microparticles. Any smoke is an etiological factor for respiratory tract cancer, and systemic neoplasms (tumors of hematopoietic and lymphoid tissues, central and peripheral nervous systems, soft tissues and skeleton). Tobacco smoke may be involved in the pathogenesis of cervical cancer due to the induction of local immunosuppression and specific tropic nitrosamines. Exhaust fumes due to high benzene content may cause hematological malignancies, especially leukemia in children. Wildfire smoke, due to significant amounts of ultra-fine carbon particles PM0.1, contributes to the development of central nervous system tumors. Severe contamination with natural and artificial radionuclides makes wildfire smoke a factor of high carcinogenic danger for the human population globally. Prevention of malignant neoplasms caused by smoke requires government measures to promote smoking cessation, hybrid and electric engines in automobiles, as well as wildfire prevention, early detection and extinction. Effective respirators and indoor air filters should be used for personal protection. To relieve environmentally caused oxidative stress, herbal medicines and food products that stimulate autophagy, as well as transfer factors for immunodeficiency correction, are recommended.

Disposable paper electrodes for detection of changes in dopamine concentrations in rat brain homogenates

Dopamine, the main catecholamine neurotransmitter plays an important role in renal, cardiovascular, central nervous systems, and pathophysiological processes. The abnormal dopamine levels can result in neurological disorders such as Parkinson's, Alzheimer's, schizophrenia, acute anxiety, neuroblastoma and also contribute to cognitive dysfunctions. Given the widespread importance of dopamine concentration levels, it is imperative to develop sensors that are able to monitor dopamine. Herein, we have developed pre-anodized disposable paper electrode modified with 1-pyrenebutyric acid, for the selective and sensitive determination of dopamine. The sensor was characterized with Fourier transform infrared spectroscopy, Energy dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and electrochemical techniques for addressing the robust formation and electrochemical activity. The modified electrode exhibited excellent electrocatalytic activity towards dopamine without the common interference from ascorbic acid. The calibration plot for the dopamine sensor resulted linear range from 0.003 μM to 0.5 μM with a detection limit of 0.11 nM. The sensor's potential utility was tested by monitoring dopamine concentration changes in rat brain homogenates when subjected to neurotoxicity. The developed sensor was validated with gold-standard UV–Vis spectroscopy studies and computational studies were performed to understand the interaction between 1-pyrenebutyric acid and dopamine.

To the anniversary of Evgeny Ivanovich Chumasov

On March 19, 2024, Evgeniy Ivanovich Chumasov, a well-known neuromorphologist, Doctor of Biological Sciences, and Professor, celebrated his 85th birthday. Here we describe the stages of E.I. Chumasov’s scientific way in the field of normal and pathological neurohistology. Evgeniy Ivanovich is a highly qualified professional in cell biology, cytology, zoology, and histology. Throughout his life, he studied the histogenesis and regeneration of tissues of the central and peripheral nervous systems. He is a great specialist in the cultivation of the nervous tissue; his works on the development of embryonic anlages of the central nervous system and PNS in vitro and after transplantation are still highly relevant and being cited. He authored multiple books and textbooks, several patents, and inventions.

Hungry brain: about the possible contribution of neurotrophic factors to anorexia nervosa

Introduction: Anorexia nervosa (AN) is an eating disorder characterized by restricted energy intake leading to weight loss below the healthy range. It is accompanied by anxiety and distorted body perception. While the disorder often manifests during adolescence, there is a noted decrease in the average age of onset, with an increasing number of cases in childhood. Successful treatment and maintenance of healthy body weight require an understanding of the complex etiology of AN, encompassing both psychosocial and specific biological factors. Material and methods: For the review, databases PubMed, Cochrane, and Google Scholar were utilized, searching for the following keywords: anorexia nervosa, neurotrophins, neurotrophin 3, neurotrophin 4, BDNF, nerve growth factor, from the inception of the databases until September 2023. Discussion: In the biological context, neurotrophic growth factors such as neurotrophin 3 (NT-3), neurotrophin 4 (NT-4), brainderived neurotrophic factor (BDNF), and nerve growth factor (NGF) may play a significant role in the etiopathogenesis of AN. These substances are involved in processes such as neuroprotection, proliferation, maturation, and survival of neurons in both the central and peripheral nervous systems. They regulate neuronal plasticity, impact the production of neurotransmitters, and control synaptic activity. BDNF and neurotrophin 3 influence the serotoninergic and noradrenergic systems, which may be associated with neurobiological processes responsible for anxiety and mood disorders. Conclusions: Understanding the role of neurotrophins in AN has the potential to lead to more effective and personalized therapies, enabling a better comprehension of the biological mechanisms of this disorder and the development of targeted pharmacological interventions. Keywords: anorexia nervosa, bdnf, neurotrophin 3, neurotrophin 4, nerve growth factor

Abstract 1963: BB102, a highly selective and potent reversible-covalent FGFR4 inhibitor effective in multiple xenograft tumor models

Abstract Introduction: Fibroblast growth factor receptor 4 (FGFR4) belongs to the FGFR family which interact with fibroblast growth factors (FGFs) to regulate cell proliferation, differentiation and apoptosis. Due to unique structural domain, FGFR4 is specifically bound by FGF19 with high affinity in the presence of co-receptor β-Klotho. Hyperactivated FGF19/FGFR4 signaling, induced by FGF19/FGFR4 overexpression and FGFR4 mutation, was reported to be associated with the growth, metastasis and invasion of various cancer. Thus, FGFR4 is considered as a novel target to treat cancer with hyperactivated FGF19/FGFR4 signaling. Here we report BB102 as a highly selective and potent reversible-covalent FGFR4 inhibitor. Methods: BB102 was developed through structure-based drug design, and optimized by SAR analysis and medicinal chemistry iteration. Biochemical and cell assays were applied in evaluation of BB102 inhibitory activity. Preclinical studies including pharmacokinetic (PK) and toxicity were performed in rats and dogs. Xenograft tumor models in mice were conducted to demonstrate the in vivo efficacy of BB102. Results: As a reversible-covalent FGFR4 inhibitor, about half compound of BB102 dissociated from FGFR4 kinase within 24 h, which was conducive to overcome the fast re-synthesis rate of FGFR4 (< 2 h) in hepatocellular carcinoma cells. BB102 only inhibited kinase activity of FGFR4WT, FGFR4N535K and FGFR4V550L at nanomolar levels in 207 kinase panel screening. BB102 completely blocked the phosphorylation of the downstream protein ERK at 16.7 nM. BB102 exhibited strong inhibitory effects on the cell proliferation in vitro and tumor growth in mouse models inoculated with the high expression of both FGF19 and FGFR4, or FGFR4 mutated tumor cells. PK profile of BB102 showed good oral bioavailability (F>70%) with a nearly linear dose-dependent exposure. The compound had no effects on the respiratory and central nervous systems in rats, cardiovascular system in Beagle dogs or hERG liability in vitro. In comprehensive safety evaluation, the Severely Toxic Dose in 10% (STD10) in rats was 300 mg/kg/day and the Highest Non-Severely Toxic Dose (HNSTD) in dogs were 100 mg/kg/day. Conclusion: BB102 is a highly selective and potent reversible-covalent FGFR4 inhibitor with promising efficacy in high expression of both FGF19 and FGFR4, and/or FGFR4 mutated tumor models and good safety in preclinical studies. The phase I study of BB102 is in progress. Citation Format: Qi Wang, Gongping Duan, Wei Hua, Xianglong Wei, Min Li, Junheng Wang, Xingmin Zhang. BB102, a highly selective and potent reversible-covalent FGFR4 inhibitor effective in multiple xenograft tumor models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1963.

Abstract 4649: BLX-3030, a potent, selective, orally available small molecule CDK9 inhibitor for aggressive variant prostate cancers

Abstract Background: The use of novel, potent targeted therapies in prostate cancers has led to the development of highly aggressive variant cancers, including neuroendocrine prostate cancer (NEPC). Gene amplification of N-MYC and C-MYC oncogenes leads to its overexpression in NEPC and mCRPC patients, highly prevalent in these lethal subtypes of cancers detected in 2% of all Prostate Cancers (PCa) and over 10-17% of mCRPC patients. N-MYC is a transcriptional target of CDK9, which acts as an oncogenic driver sufficient to transform human-derived prostate cancer to take on NEPC phenotypic changes resulting in a more aggressive disease identified in late-stage human PCa patients. Additionally, N-MYC and C-MYC are required for tumor drug resistance, and their downregulation through CDK9 inhibition lowers tumor growth. Our efforts have demonstrated that targeting both N-MYC and C-MYC as a driver of NEPC and mCRPC with highly selective CDK9 inhibitor BLX-3030 is a viable approach for therapeutic intervention of mCRPC and NEPC. Materials and Methods: Our empirical data-driven AI/ML MolecuLernTM fragment library, workflows, LigEdit design strategies, and hit2-lead optimization methods are employed. In vitro experiments include kinase glo, cell titer glo, selectivity profiler, ADME-Tox, FACS/apoptosis, cell migration, live cell imaging, immunofluorescent, western blot, combination studies and in vivo experiments including PK, prostate tumor models, 7-day tox, BLX-3030 non (GMP) scaleup and safety pharmacology experiments conducted. Results: We synthesized a series of novel small molecule CDK9 inhibitors that reversibly bind to CDK9, competitively block the ATP site with an IC50 of 1.06 nM, and elicit pharmacological responses in N-MYC, C-MYC, and other prostate cancer cells in vitro and in vivo. We studied the CDK9 N-MYC expression detected in PC-3, DU-145, LNCaP, and in LASCPC-01, NCI-H660, and 22RV1 cell lines. BLX-3030 exhibited potent cellular efficacy with an IC50 of 22 to 590 nM in PC cell lines and in N-MYC expressed cells had an activity of 76, 470, and 132 nM respectively, and reduced pCDK9, C-MYC, Mcl-1, N-MYC and its downstream RNA Pol II (Ser-2) and pAR (Ser-81) dose-dependently. BLX-3030 exhibits in vivo antitumor activity in LASCPC-01, 22RV1, and C4-2 prostate cancer mouse models. Several ADME-Tox, MTD, dose range finding, hERG and other in vivo safety pharmacology experiments have advanced BLX-3030 to the IND enabling studies. Conclusions: BLX-3030 is currently being investigated in non-clinical toxicology, toxicokinetic, and core battery of safety pharmacology studies including the assessment of effects on cardiovascular, central nervous, and respiratory systems. Citation Format: Zhaoang li, Chenyu Lin, Kyle Medley, Hariprasad Vankayalapati, David J. Bearss. BLX-3030, a potent, selective, orally available small molecule CDK9 inhibitor for aggressive variant prostate cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4649.

Roles of KCNA2 in Neurological Diseases: from Physiology to Pathology.

Potassium voltage-gated channel subfamily a member 2 (Kv1.2, encoded by KCNA2) is highly expressed in the central and peripheral nervous systems. Based on the patch clamp studies, gain-of function (GOF), loss-of-function (LOF), and a mixed type (GOF/LOF) variants can cause different conditions/disorders. KCNA2-related neurological diseases include epilepsy, intellectual disability (ID), attention deficit/hyperactive disorder (ADHD), autism spectrum disorder (ASD), pain as well as autoimmune and movement disorders. Currently, the molecular mechanisms for the reported variants in causing diverse disorders are unknown. Consequently, this review brings up to date the related information regarding the structure and function of Kv1.2 channel, expression patterns, neuronal localizations, and tetramerization as well as important cell and animal models. In addition, it provides updates on human genetic variants, genotype-phenotype correlations especially highlighting the deep insight into clinical prognosis of KCNA2-related developmental and epileptic encephalopathy, mechanisms, and the potential treatment targets for all KCNA2-related neurological disorders.

Neuropeptides as Potential Biomarkers in Vascular Dementia.

Neuropeptides are endogenous active substances within the central and peripheral nervous systems that play important roles in a wide range of brain functions, including metabolism, food intake, social behavior, reproduction, learning, sleep, and wakefulness. This article reviews recent advances in the involvement of neuropeptides in vascular dementia. Neuropeptides are present in the brain as chemical signals and last for nearly 50 years. Peptide hormones are chemical signals of the endocrine system. Thus, neuropeptides are the most diverse class of signaling molecules in the brain, involving the genomes of many mammals, encoding neuropeptide precursors and many bioactive neuropeptides. Here the aim is to describe the recent advances in classical neuropeptides, as well as putative neuropeptides from other families, in the control of or as diagnostic tools for vascular dementia. Additionally, its molecular mechanisms are described to explore new avenues of treatment and early diagnosis, as there is increasing evidence that dysregulation of vascular processes is associated with different pathological conditions.

Functional connections between the temporomandibular joint and the hip joint

Introduction. Some of the factors in the formation of temporomandibular joint disorders are changes in the central and peripheral nervous systems. In the context of creating connections between two joints, fascia and the concept of biotensegration are important. The tension created in the tissue is linearly distributed along the entire body. The creation of excessive tension within one structure can lead to the creation of identical tension in a distant structure. Aim of the study. The research hypothesis was that soft tissue manual treatments of the temporomandibular joint, with a duration of 7 minutes per side would affect increased mobility in the hip joint for the motion of the abduction. Results. The obtained value for the right and left hip joint shows a strong and positive correlation. This proves that the therapy performed had an effect on increasing the range of motion. Conclusions. Myofascial release of the tissues of the temporomandibular joint had a positive effect on the increase in the range of motion for hip abduction.

The role of clinical characteristics of Lyme borreliosis in predicting cognitive impairment

Background. Lyme disease is characterized by a wide polymorphism of clinical manifestations, including various lesions of the central and peripheral nervous systems. Along with neurological disorders, diverse manifestations and signs of cognitive impairments are often found. Despite the high prevalence of cognitive disorders in Lyme borreliosis, data on their frequency and risk factors are contradictory. The examination of cognitive status is still not included in the standard clinical examination of this category of patients. The aim of the study is to identify predictors that may independently influence the development of cognitive dysfunction in patients with Lyme borreliosis. Materials and methods. A prospective cohort study of 69 patients (47 females, 22 males) diagnosed with Lyme borreliosis, aged between 23 and 77 (average of 49.90 ± 16.26) years, was carried out. The Montreal Cognitive Assessment was used to evaluate cognitive function. To determine the relationship between cognitive dysfunction and its potential predictors, the participants were divided into two groups: patients without cognitive impairment (n = 30) and those with cognitive dysfunction (n = 39) based on the Montreal Cognitive Assessment score. Results. It was found that risk factors for the development of cognitive impairment include: diagnosis of Lyme borreliosis at the age of 45.5 years and older (hazard ratio (HR) 5.09; 95% confidence interval (CI) [1.82–14.27]; p = 0.001), presence of neuroborreliosis (HR 5.98; 95% CI [2.0–17.8]; р < 0.001), Lyme carditis (HR 8.7; 95% CI [1.04–73.06]; р = 0.021), hypertension (HR 7.19; 95% CI [2.32–22.28]; р < 0.001), anxiety disorders. Conclusions. The prospect for further research is to study and analyze the features of the correlation between cognitive and psycho-emotional disorders and the quality of life of patients with different forms and duration of Lyme borreliosis.

Suppression of Borna Disease Virus Replication during Its Persistent Infection Using the CRISPR/Cas13b System.

Borna disease virus (BoDV-1) is a bornavirus that infects the central nervous systems of various animal species, including humans, and causes fatal encephalitis. BoDV-1 also establishes persistent infection in neuronal cells and causes neurobehavioral abnormalities. Once neuronal cells or normal neural networks are lost by BoDV-1 infection, it is difficult to regenerate damaged neural networks. Therefore, the development of efficient anti-BoDV-1 treatments is important to improve the outcomes of the infection. Recently, one of the clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) systems, CRISPR/Cas13, has been utilized as antiviral tools. However, it is still unrevealed whether the CRISPR/Cas13 system can suppress RNA viruses in persistently infected cells. In this study, we addressed this question using persistently BoDV-1-infected cells. The CRISPR/Cas13 system targeting viral mRNAs efficiently decreased the levels of target viral mRNAs and genomic RNA (gRNA) in persistently infected cells. Furthermore, the CRISPR/Cas13 system targeting viral mRNAs also suppressed BoDV-1 infection if the system was introduced prior to the infection. Collectively, we demonstrated that the CRISPR/Cas13 system can suppress BoDV-1 in both acute and persistent infections. Our findings will open the avenue to treat prolonged infection with RNA viruses using the CRISPR/Cas13 system.

Update on Neuro-ophthalmic Manifestations of Immune Checkpoint Inhibitors.

Immune checkpoint inhibitor (ICI) use has been on the rise for treatment of many different malignancies. Subsequently, more has been learned about immune-related adverse events (irAEs) that occur up to 12months after treatment. This review summarizes the latest findings and management of neuro-ophthalmic associated irAEs. irAEs can affect the afferent and efferent neuro-ophthalmic pathways, thereby targeting central and peripheral nervous systems. As more cases are being reported, it is becoming apparent that neuro-ophthalmic irAEs often present with atypical features when compared to their spontaneous autoimmune counterparts. These neuro-ophthalmic presentations can also be signs of a more extensive inflammatory process that spans other organ systems, such as myopathies, endocrinopathies, and paraneoplastic syndromes. Awareness of neuro-ophthalmic irAEs and their atypical presentations can lead to early detection, termination of ICI treatment, and immunosuppressant therapy initiation.

Mind, Mood and Microbiota-Gut-Brain Axis in Psychiatric Disorders.

Psychiatric disorders represent a primary source of disability worldwide, manifesting as disturbances in individuals' cognitive processes, emotional regulation, and behavioral patterns. In the quest to discover novel therapies and expand the boundaries of neuropharmacology, studies from the field have highlighted the gut microbiota's role in modulating these disorders. These alterations may influence the brain's processes through the brain-gut axis, a multifaceted bidirectional system that establishes a connection between the enteric and central nervous systems. Thus, probiotic and prebiotic supplements that are meant to influence overall gut health may play an insightful role in alleviating psychiatric symptoms, such as the cognitive templates of major depressive disorder, anxiety, or schizophrenia. Moreover, the administration of psychotropic drugs has been revealed to induce specific changes in a microbiome's diversity, suggesting their potential utility in combating bacterial infections. This review emphasizes the intricate correlations between psychiatric disorders and the gut microbiota, mentioning the promising approaches in regard to the modulation of probiotic and prebiotic treatments, as well as the antimicrobial effects of psychotropic medication.

Dengue encephalopathy in an adult due to dengue virus type 1 infection

BackgroundDengue is an important public health problem, which caused by the dengue virus (DENV), a single-stranded RNA virus consisted of four serotypes. Central nervus system (CNS) impairment in dengue usually results from DENV-2 or DENV-3 infection, which lead to life-threatening outcomes. Furthermore, neurological complications due to DENV-1 was rare especially in adult patients.Case presentationA 44-year-old man without comorbidities had lethargy after hyperpyrexia and a positive DENV NS1 antigen was detected for confirming the diagnosis of dengue on day 8 of onset. Then logagnosia, decreased muscle strength, delirium and irritability were occurred even radiographic examination were normal. He was treated with low-dose hormone, sedatives and gamma goblin with a short duration of 6 days. The cerebrospinal fluid (CSF) tests were persistent normal. However, presence of DENV-1 RNA was confirmed both in CSF and serum. Furthermore, the complete sequence of the DENV isolated from the patient’s serum was performed (GenBank No.: MW261838). The cytokines as IL-6, IL-10 and sVCAM-1 were increased in critical phase of disease. Finally, the patient was discharged on day 24 of onset without any neurological sequelae.ConclusionEncephalopathy caused by a direct CNS invasion due to DENV-1 during viremia was described in an adult patient. Treatment with low-dose hormone and gamma goblin was helpful for admission.

Unveiling the negative correlation of formaldehyde and hydrogen sulfide in Parkinson’s disease models using a dual-responsive ruthenium(II) complex probe

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases caused by various complicated pathological processes. Recent studies have revealed that formaldehyde (FA) and hydrogen sulfide (H2S) are essential signal molecules closely linked to central nervous systems. Therefore, understanding the physiological functions and relationship of FA and H2S in PD is beneficial for the early diagnosis and treatment of PD. However, an effective tool that could detect and visualize FA and H2S simultaneously in PD is still lacking. Herein we report the design and synthesis of a novel dual-responsive ruthenium(II) complex-based luminescent probe, Ru-aza-NBD, for the discriminatory detection of FA and H2S in aqueous media and PD models of living cells and mouse brains. Notably, using Ru-aza-NBD as a probe, the increased level of FA and the decreased level of H2S in PD models were discovered, which revealed the negative correlation of FA and H2S in PD for the first time. Collectively, Ru-aza-NBD could be an excellent tool for further investigating the biological functions of FA and H2S in pathological processes of PD, which offers a promising approach for the exploration of the pathogenic mechanism, diagnosis and treatment of this disease.

Evaluation and Management of Diabetic Neuropathy from the Perspective of People with Diabetes

Diabetic foot ulcers (DFU) and infections are the most common complications of diabetic foot disease. Mortality and financial burdens for both patients and society on the whole are caused by the prevalence of complications. Peripheral neuropathy, peripheral arterial disease, and immune response dysfunction are just a few of the main contributing factors that must be understood in order to effectively treat the condition. In order to treat diabetic foot disease, you must first get a comprehensive physical examination and a detailed history of your condition. Diabetic neuropathy and peripheral vascular disease, as well as any evidence of diabetic foot ulcers or infection, should be examined during this procedure. Patients with diabetes mellitus were studied to see if there was a link between cognitive impairment and the condition of their feet and whether or not they followed their doctor's recommendations for glycemic control. Using a random sample of diabetes patients, researchers conducted a prospective study to see how many people had the condition. The Mini-Mental State Valuation, the Trail Making Judgments, and the Michigan Screening Instrument were used to assess cognitive abilities. In the one-month follow-up, glycated hemoglobin (HB1Ac >7 %) was linked to the MMSE and medication adherence, but no link was seen between cognitive function and neuropathy. According to the results of a ROC curve investigation, HB1Ac and the MNSI score both significantly (p< 0,05) mitigate towards eventual adherence to medicine for foot problems. For the purpose of determining if DFU was associated with cognitive impairment, the Chi square valuation was used in the statistical examination. As a determinant of MMSE and MoCA scores, the researchers used linear regression to come to their conclusion. Diabetic foot issues should be managed with good blood sugar control and less acute neuropathy, and this does not seem to be linked to cognitive dysfunction. More study is required in order to personalize treatments for diseases of the central and peripheral nervous systems appropriately. Cognitive dysfunction should be taken into account by doctors and podiatrists while treating diabetic foot problems

Neuromodulation: What the neurointerventionalist needs to know.

Neuromodulation is the alteration of neural activity in the central, peripheral, or autonomic nervous systems. Consequently, this term lends itself to a variety of organ systems including but not limited to the cardiac, nervous, and even gastrointestinal systems. In this review, we provide a primer on neuromodulation, examining the various technological systems employed and neurological disorders targeted with this technology. Ultimately, we undergo a historical analysis of the field's development, pivotal discoveries and inventions gearing this review to neuro-adjacent subspecialties with a specific focus on neurointerventionalists.

Gastroschisis and omphalocele: Incidence and outcome

Gastroschisis and omphalocele are the most common congenital abdominal wall defects. The main purpose of this study was to investigate the incidence, other associated anomalies and the course of these diseases in Iceland. The study was retrospective. The population was all newborns who were admitted to the NICU of Children's Hospital Iceland due to gastroschisis or omphalocele in 1991-2020. Furthermore, all fetuses diagnosed prenatally or post mortem where the pregnancy ended in spontaneous or induced abortion, were included. During the study period, 54 infants were born with gastroschisis and five with omphalocele. The incidence of gastroschisis was 4.11 and omphalocele 0,38/10,000 births. There was no significant change in the incidence of the diseases during the study period. In addition, five fetuses were diagnosed with gastroschisis and 31 with omphalocele where the pregnancy was terminated. In addition to gastroschisis in the live born infants and fetuses the most common associated anomalies were in the gastrointestinal or urinary tract but in infants and fetuses with omphalocele anomalies of the cardiac, central nervous or skeletal systems were the most common. Sixteen fetuses diagnosed with omphalocele had trisomy 18. Mothers aged 16-20 were more likely to give birth to an infant with gastroschisis than older mothers (p< 0.001). Primary closure was successful in 86% of the infants. Those reached full feedings significantly earlier and were discharged earlier. Overall survival rate was 95%. Three children were still receiving parenteral nutrition at discharge due to short bowel syndrome. The incidence of gastroschisis in Iceland is in accordance with studies in other countries but but the incidence of omphalocele is lower, which can be partly explained by spontaneous or induced abortions. Other anomalies associated with omphalocele are more severe than those associated with gastroschisis. Primary closure was associated with more benign course. Children with gastroschisis may need prolonged parenteral nutrition due to shortening of their intestines.

Challenges in the Therapeutic Targeting of KCa Channels: From Basic Physiology to Clinical Applications.

Calcium-activated potassium (KCa) channels are ubiquitously expressed throughout the body and are able to regulate membrane potential and intracellular calcium concentrations, thereby playing key roles in cellular physiology and signal transmission. Consequently, it is unsurprising that KCa channels have been implicated in various diseases, making them potential targets for pharmaceutical interventions. Over the past two decades, numerous studies have been conducted to develop KCa channel-targeting drugs, including those for disorders of the central and peripheral nervous, cardiovascular, and urinary systems and for cancer. In this review, we synthesize recent findings regarding the structure and activating mechanisms of KCa channels. We also discuss the role of KCa channel modulators in therapeutic medicine. Finally, we identify the major reasons behind the delay in bringing these modulators to the pharmaceutical market and propose new strategies to promote their application.