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Aim of this work is to verify the effect of some neurotoxins, physical factors and geography in presentation of some Relevant Neurological disorder like some form of ASL, PD, AD. The geographic diffusion of the ASL/PD in west pacific (GUAM foci), and mutation of SOD 1 and other mutations are interesting facts to verify the recent literature about the neurotoxic process. Related to the references presented a global conclusion about the pathogenetic progression of some neurological disease will be produced as instrument for new hypothesis and for the introduction of new innovative therapeutic strategies.

Lesions that spontaneously come and go in central nervous system without any treatment at different time points and at different locations (CNS) usually lead ones to think of the possibilities of multiple sclerosis. However, sometimes there are exceptions. Surgical biopsy remains an important tool for definitive diagnosis in difficult cases. We report a case of intracranial diffuse large B cell lymphoma that spontaneously disappeared without any treatment and then reappeared at different time points and different locations.

Aim:The work was to perform a comparative study of the neuroprotective and nootropic activities of two pharmaceutical substances, the HLDF-6 peptide and its amide form (HLDF-6-NH2). Materials and Methods: We used in the study healthy adult male Wistar rats aged 180–200 days weighing 280–300 g. We modelled ischemic stroke in rats by chronical occlusion of carotid arteries. Solutions of the HLDF-6-NH2 and HLDF-6 peptides were administered intranasally. Cognitive functions we assessed with Novel object recognition test and Morris maze. Results: The amide form of HLDF-6 peptide is more efficient: the neuroprotective activity of HLDF-6-NH2, evaluated by improvement of cognitive functions in animals, surpassed that of the native HLDF-6 peptide. A dose of 250 µg/kg of HLDF-6-NH2 peptide resulted in practically complete restoration of the disturbed functions. In the model of ischemic stroke, the amide form of the peptide significantly excelled the reference substance mexidol both in the effective dose and biological activity. Conclusion: The results of study of the agent allow hoping for its success in further clinical investigation. In view of high demand for the agent and in case of successful clinical trials, it will surely become widely used in clinical practice in treatment of IS.

Background: A Grey 12-year-old Arabian endurance horse gelding was referred to the SHS Veterinary Center for anorexia, mild colic of 5 days duration, and melena of 1 day duration. The owner reported recurring colic, 12 episodes of mild colic in the previous year. Methods: On admission, vital signs were within normal limits and body condition score was estimated to be 3/9. Results: Packed cell volume (PCV) was 28% [reference range (RR): 31% to 47%] and plasma total protein was 58 g/L (RR: 60 to 80 g/L). Hematochezia was observed. Abdominal ultrasound examination detected no abnormalities. Over the next 12 h, the horse experienced hematochezia and several mild episodes of colic and death. A necropsy was performed. A mass arising from the right dorsal ascending colon near the base of the cecum and extending transmurally from the colonic mucosa into the mesocolon was a 8 cm × 5 cm × 8 cm firm, homogenous, tan mass. The portion of the mass that extended into the colonic lumen was pedunculated, with an ulcerated surface. The adjacent segments of colon were markedly reddened and edematous. Histologically, the mass was comprised of large interweaving sheets of small, spindle cells with ill-defined cell borders embedded in abundant myxomatous matrix. Tumor cells contained scant eosinophilic cytoplasm and oval to elongate nuclei with finely stippled chromatin and inconspicuous nucleoli. Mitotic figures were rare (1/10) high power fields. Tumor infiltrated between the muscularis interna and the muscularis externa at the myenteric plexi. Conclusion: Gross and histologic appearance, were consistent with a diagnosis of gastrointestinal stromal tumor.

Background: Drosophila models of amyotrophic lateral sclerosis (ALS) have been widely used in understanding molecular mechanisms of ALS pathogenesis as well as discovering potential targets for therapeutic drugs. Mutations in the copper/zinc superoxide dismutase (SOD1) cause ALS by gain of toxic functions and induce toxicity in fly motor neurons. Results: In this study, we have determined that human carbonic anhydrase I (CA1) can alleviate mutant SOD1-induced motor neuron toxicity in the transgenic fly model of ALS. Interestingly, we found that motor neuron expression of CA1 could independently induce locomotion defect as well as decreasing the survival rate. In addition, CA1-induced toxicity in motor neurons is anhydrase activity-dependent. Mechanistically, we identified that both SOD1- and CA1-induced toxicity involve the activation of eIF2α in the ER stress response pathway. Downstream activation of the JNK pathway has also been implicated in the induced toxicity. Conclusion: Our results have confirmed that SOD1-induced toxicity in fly motor neuron also involves endoplasmic reticulum (ER) stress pathway. More importantly, we have discovered a new cellular role that CA1 plays by antagonizing mutant SOD1-induced toxicity in motor neurons involving the ER stress pathway. Such information can be potentially useful for further understanding disease mechanisms and developing therapeutic targets for ALS. 

The biological changes caused by oxidative stress (OS) are known to be involved in the etiology of neurodegenerative disorders, including Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and Parkinson’s disease. The brain is particularly vulnerable to OS due to its high lipid content and extensive consumption of oxygen. OS processes, particularly the excessive production of reactive oxygen species (ROS), play a critical role in how neurodegenerative disorders develop. This is evidenced by in vivo studies investigating various biomolecules related to OS, such as products of lipid and DNA oxidation. Accordingly, ROS can also cause oxidative-related damage in neurodegenerative disorders, including dopamine auto-oxidation, mitochondrial dysfunction, glial cell activation, α-synuclein aggregation, excessive free iron, and changes in calcium signaling. Furthermore, excessive levels of cellular oxidants reduce antioxidant defenses, which in turn propagate the cycle of OS. As such, it is increasingly important to determine the linkage between a high intake of antioxidants through dietary interventions and a lower risk of developing neurodegenerative diseases. Indeed, in addition to modulating the immune system, optimal nutritional status is capable of changing various processes of neuroinflammation known to be involved in the pathogenesis of neurodegeneration. Accordingly, a better understanding of the role ROS plays in the etiology of neurodegeneration is needed, along with the identification of dietary interventions that may lead to improved therapeutic strategies for both the treatment and prevention of neurodegenerative disorders. Therefore, this review presents a comprehensive summary of the role of ROS in the pathogenesis of neurodegenerative disorders. In addition, nutrients believed to be useful for mitigating and counteracting ROS are discussed. 

Background: Gliomas represent the most frequent primary tumors of central nervous system (CNS), contributing to more than half of the incidence of brain tumors. Cancer stem cell markers (CSC) identify a group of patients at high risk for progression. Nestin is an intermediate filament (IF) protein was first described as a neural stem cell/progenitor cell marker. Nestin-positive neuroepithelial stem cells are detected in the subventricular zone of the human adult brain and they remain mitotically active throughout adulthood. The expression of Nestin in gliomas has been suggested to be related to dedifferentiation, improved cell motility, invasive potential and increased malignancy. This study aims to investigate Nestin immunohistochemical expression in different types of glioma and its correlation with different clinicopathological parameters. Materials and Methods: Nestin immunostaining was studied in 60 specimens of glioma using avidin-biotin peroxidase method. Results: Nestin was strongly expressed in 11/60 (18.33%), moderately expressed in 29/60 (48.33%) and weekly expressed in 15/60 (25%) of studied gliomas. A significant positive correlation was found between Nestin expression and histologic type (p < 0.001) and increasing grade of gliomas (p < 0.001). Conclusion: Increased Nestin expression is correlated with tumor progression, increasing grade and poor prognostic parameter of glioma. Nestin is a useful marker for detection of CSC in high-grade glioma which is responsible for resistance to chemo-radiotherapy and may serve as a predictor for patient outcomes.

Blood vessels that supply and feed the central nervous system (CNS) possess unique and exclusive properties, named as blood–brain barrier (BBB). It is responsible for tight regulation of the movement of ions, molecules, and cells between the blood and the brain thereby maintaining controlled chemical composition of the neuronal milieu required for appropriate functioning. It also protects the neural tissue from toxic plasma components, blood cells and pathogens from entering the brain. In this review the importance of BBB and its disruption causing brain pathology and progression to different neurological diseases like Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD) etc. will be discussed.

We report a case of 30-year-old immunocompetent man, with a previous history of cranial-facial trauma, who presented with progressive left exophthalmos due to an intracranial left frontal-ethmoidal-orbital mass. Histology of the resected tumor revealed a classical Hodgkin’s Lymphoma (HL). Epstein-Barr virus encoded RNA/EBER was detected in typical Hodgkin and Reed-Sternberg cells. After postoperative radiotherapy and chemotherapy administration, the patient remains free of systemic disease or recurrence on 4 years of follow-up. Intracranial involvement by HL has rarely been described, mostly as a late localization or as a recurrence of a disseminated disease, in a setting of immunosuppression. Primary HL of the central nervous system occurring as an isolated disease is even more uncommon, with only 16 reported cases documented to date. The prognosis of these rare cases appears comforting with appropriate treatment. Tumor resection and, in appropriate cases, treatment with radiation and/or chemotherapy seem to warrant a durable response. For this reason a systemic disease should be excluded in all cases intracranial HL by a comprehensive work-up. To the best of our knowledge, this case represents the first report that documents the association of intracranial HL and local trauma with subsequent intracranial infection.

Sleep related breathing disorders (SRBD) are among seven well-established major categories of sleep disorders defined in the third edition of The International Classification of Sleep Disorders (ICSD-3), and Obstructive Sleep Apnea (OSA) is the most common SRBD [1,2]. Several studies have demonstrated that obstructive sleep apnea treatment increases the quality of life in OSA patients [3-8]. Indeed, excessive daytime sleepiness (EDS), cognitive impairment (e.g., deficits in attention-concentration, memory, dexterity, and creativity), traffic accidents, and deterioration of social activities are frequently reported in untreated patients [9-11]. Furthermore, an increase in cardiovascular morbidities and mortality (systemic hypertension, stroke, cardiac arrhythmias, pulmonary arterial hypertension, heart failure) [12], metabolic dysfunction, cerebrovascular ischemic events and chemical/structural central nervous system cellular injuries (gray/white matter) has been reported in OSA patients [13-17].  Continuous positive airway pressure (CPAP) therapy is considered the gold standard for treatment of moderate-severe OSA, nevertheless there is an increasing body of evidence supporting the usefulness of mandibular advancement devices (MADs) for improving quality of life and respiratory parameters even among patients with a high severity of OSA burden [5,10,18,19]. According to the standard of care of the American Academy of Sleep Medicine (AASM), MADs are indicated for mild to moderate OSA particularly in the context of CPAP intolerance or refusal, surgical contraindication, or the need for a short-term substitute therapy [9,15,20-22]. In Cuba, CPAP machines are not readily available; they are expensive and the majority of OSA patients cannot obtain this mode of therapy. Taking into account this problem, our hypothesis was based in the scientific evidences of MAD effectiveness, considering that low cost MADs could offer a reasonable alternative treatment for patients with OSA where CPAP technology are not handy. In this way our purpose was to assess the efficacy of one of the most simple, low cost, manufactured monoblock MAD models (SAS de Zúrich) in terms of improvements in cerebral function, sleep quality and drowsiness reports in a group of Cuban OSA patients with mild to severe disease. Outcome measures included changes in the brain electrical activity, sleep quality, and respiratory parameters, measured by EEG recording with qEEG analysis and polysomnographic studies correspondingly, which were recorded before and during treatment with an MAD, as well as subjective/objective improvements in daytime alertness. 

A mass arising from the pituitary gland commonly damages cells of the anterior pituitary gland and affects the secretion of gonadotropins and growth hormone. However, central hypothyroidism and secondary adrenal insufficiency from such damage is a rare phenomenon. Acute urinary retention as the main symptom of central hypothyroidism is also an unusual initial presentation. We report a male patient who comes with frequent urinary retention and hyponatremia at our hospital.

Delayed cerebral ischemia (DCI) is one of the main complications of spontaneous subarachnoid haemorrhage and one of its causes is the cortical spreading depolarizations (CSDs). Cortical spreading depolarizations are waves of neuronal and glial depolarizations in which there is loss of neuronal ionic homeostasis with potassium efflux and sodium and calcium influx. In damaged brain areas and brain areas at risk, such as those adjacent to subarachnoid haemorrhage (SAH), CSDs induce microvascular vasoconstriction and, therefore, hypoperfusion and spread of ischemia. Several studies have been devoted to minimize secondary injuries that occur hours to days after an acute insult. Ketamine, a drug until recently contraindicated in the neurosurgical population for potentially causing intracranial hypertension, has re-emerged as a potential neuroprotective agent due to its pharmacodynamic effects at the cellular level. These effects include anti-inflammatory mechanisms, and those of microthrombosis and cell apoptosis controls, and of modulation of brain excitotoxicity and CSDs. A literature review was performed at PubMed covering the period from 2002 to 2019. Retrospective studies confirmed the effects of ketamine on the control of CSDs and, consequently, of DCI in patients with SAH, but did not show improvement in clinical outcome. The influence of ketamine on the occurrence/development of DCI needs to be further confirmed in prospective randomized studies

Background: A misguided auto-reactive injury is responsible for several types of central nervous system (CNS) conditions in pediatrics. We propose that, in some of these conditions, the adaptive immune system has a common cellular immune pathogenesis, driven predominantly by T cells, despite variability on the phenotypical clinical presentation. Methods: We have characterized the CD4+/CD8+ adaptive immune response (AIR) on pediatric patients presenting with clinical symptoms compatible with Neuroimmune Disorders (NID). Flow cytometry with deep immunophenotyping of T cells was performed on peripheral blood obtained during the acute clinical phase and compared to an age-matched cohort group (Co). Results: We found that pediatric patients with confirmed NID, exhibit a pattern of dysregulation of CD4+ lineages associated with autoimmune processes. Discussion: The autoimmune associated CD4+ dysregulation was associated with patients with NID, as compared to healthy controls and patients with non-autoimmune diagnoses. If we can improve our capacity for early accurate diagnosis and meaningful disease monitoring of pathogenic T cell subsets, we can both expedite disease detection and may serve as a guide to the administration of effective immunotherapeutic agents.

Parkinson’s disease (PD) is thought to be the most common neurodegenerative disease with movement disorder. The key motor symptoms are rigidity, tremor, akinesis/hypokinesia/bradykinesia, and postural instability. However, in our day-to-day clinical practice we tend to see several other symptoms which may be motor or non-motor. Non-motor symptoms (NMS) are quite common and debilitating. The pathological hallmarks of PD are loss of dopaminergic neurons in the substantia nigra pars compacta (SNPc) and accumulation of unfolded or misfolded alpha-synuclein. Diagnosis of PD is difficult in the pre-motor stage. Late diagnosis renders a substantial loss of dopaminergic neurons in SNPc and spread of disease in other parts of the brain. This may manifest as either full blown symptoms requiring multiple medications or may even lead to life threatening condition due to lack of early diagnostic tools and techniques. Biomarkers are required to diagnose PD at a very early stage when prevention is possible. Hence, we see a lot of interest among researchers involved in finding a biomarker specific to the disease. Biomarkers may be clinical, image based, genetic, and biochemical. Cerebrospinal fluid (CSF) and serum markers which may correlate with disease pathophysiology are of great significance. One such molecule which recently gained a lot of attention is neuron-specific enolase (NSE). The main aim of this paper is to highlight the role of NSE in predicting neurodegeneration and neuroinflammation ultimately reflecting damage of brain cells in PD.

Repressive regulation of potassium channel genes by Polycomb group (PcG) proteins contributes to PcG protein-mediated neuroprotection against neuronal ischemic injury, as seen in an ischemic stroke. Here we asked the question whether Trithorax group (TrxG) proteins, the antagonistic partners of PcG proteins (i.e, epigenetic activators targeting the same genes) may also regulate potassium channels. Results of patch-clamp studies on cultured neuronal cells showed that inhibition of TrxG protein MLL-1 led to an increase in potassium channel activity, an unexpected effect for a presumed gene activator. In contrast, decreased sodium currents were observed with MLL-1 inhibition. Increased or decreased levels of potassium channel protein Kv2.1 or sodium channel protein Nav1.2, respectively, were seen with MLL-1 inhibition, as determined by immunocytochemistry. These results, for the first time, demonstrate an involvement of TrxG protein MLL-1 in regulating neuronal ion channels, potentially repressing potassium channel genes.

Familial dysautonomia is a rare autosomal recessive neurodegenerative disease affecting cells of the autonomic nervous system. Patients with this disease are insensitive to pain but their autonomic nervous system is still activated with noxious stimuli. This report details a case of a patient with familial dysautonomia who underwent right ankle open reduction and internal fixation for a bimalleolar right ankle fracture. The patients preoperative and intraoperative course were uneventful but shortly after handoff to the intensive care unit, the patient experienced an autonomic crisis. Management of these patients is complex, requiring maintenance of physiologic homeostasis as well as preventing hemodynamic instability caused by noxious stimuli. Any deviations from baseline may cause an autonomic crisis, as happened in our patient. Herein, we detail the perioperative management of a patient with familial dysautonomia in further detail.

Flow cytometry (FCM) is a unique technique that allows rapid quantitative measurement of multiple parameters on a large number of cells at the individual level. FCM is based on immunolabelling with fluorochrome-conjugated antibodies, leading to high sensitivity and precision while time effective sample preparation. FCM can be performed on tissue following enzymatic or mechanical dissociation. The expression of epithelial antigens and cytokeratin isoforms help in distinguishing tumor cells from adjacent epithelial cells and from tumor infiltrating leukocytes. Tumor phenotypes can be characterized on expression intensity, aberrancies and presence of tumor-associated antigens as well as their cell proliferation rate and eventual heteroploidy. FCM can measure quantitative expression of hormone or growth factor receptors, immunoregulatory proteins to guide adjuvant therapy. Expression of adhesion molecules tells on tumor’s capacity for tissue invasion and metastasis seeding. Tumor heterogeneity can be explored quantitatively and rare, potentially emerging, clones with poor prognosis can be detected. FCM is easily applicable on fine needle aspiration and in any tumor related biological fluids. FCM can also be used to detect circulating tumor cells (CTC) to assess metastatic potential at diagnosis or during treatment. Detecting CTC could allow early detection of tumors before they are clinically expressed although some difficulties still need to be solved. It thus appears that FCM should be in the pathologist tool box to improve cancer diagnosis, classification and prognosis evaluation as well as in orientating personalized adjuvant therapy and immunotherapy. More developments are still required to better known tumor phenotypes and their potential invasiveness

We report a case of a right gluteal mass from the sacroiliac joint to the knee of an infant girl. Biopsy showed histopathological features similar to infantile fibrosarcoma (IFS). However, unlike most IFS, no ETV6-NTRK3 fusion gene abnormality was detected. Molecular analysis with TruSight RNA Pan-Cancer Panel detected the presence of KIAA1549-BRAF translocation and an oncogenic NF2p.Q459* SNV with potential clinical significance. A review revealed that the combination of this patient’s tumor site with the presence of a KIAA1549-BRAF translocation abnormality and an accompanying single nucleotide variant has not been previously described. The detection of this translocation abnormality raises the possibility that the spindle cell tumors in infants with an absence of the ETV6-NTRK3 fusion gene abnormality might have a distinct pathogenetic mechanism different from the previously known IFS and congenital mesoblastic nephroma. Furthermore, the discovery of BRAF translocation and its aberrant signaling of the mitogen-activated protein kinase (MAPK) pathway in this tumor contributes to the promise of clinical benefit of using the MEKi trametinib for the treatment of progressive disease that is refractory to conventional chemotherapy. 

Development of genetic profiles from the biological mixtures has remained challenging, although modern-day technologies may help forensic scientists to attain a reliable genetic profile in the identification of the accused. In the case of rape, vaginal swab exhibits usually contain epithelial cells of victims and sperm cells of accused, such samples are more challenging when there is more than one contributor. In such cases, separation of distinct cells from a mixture that includes blood cells, epithelial cells and sperm cells for their single genetic profile is important. In the last ten decades several new techniques were developed and invented for the separation of single cell from the biological mixture that includes differential lysis, laser micro-dissection, cell sorting (FACS), sieve-based filtration, (vi) micro-fluidic devices or immunomagnetic beads cell separation of fresh samples, and the magnetic activated cell sorting (MACS). Out of them, some techniques have been commonly applied for cell separation in forensic biology. Each technique has its own limitation. Some recent studies showed, magnetic activated cell sorting (MACS), laser capture microdissection (LCM), DEPArray technology and fluorescence activated cell sorting (FACS) has proved to be effective in separation of single cell from cell mixtures. Therefore, in this review we have evaluated these four alternative methods and their potential application in the modern-day over the others for the separation of a single cell from the mixture. In this review we also discuss the advantage of these methods and their modern–day applicability and acceptance in the forensic world.

Introduction: Cancer treatment and prognosis depend heavily on early detection. Survival in the early stages is excellent for almost all types of cancer. Unfortunately, in Saudi Arabia, a large number of cancer patients present with advanced disease, resulting in a poor prognosis. There are three levels of delay in the management of cancer patients. The first level is the time between the first cancer-related symptoms and the presentation to the health facility, the second level is from the presentation to the diagnosis, and the third level is between the diagnosis and the treatment. This study aims to determine if there is a delay, at what level and to study the factors causing such delays.Materials and methods: Two hundred cancer patients who presented to the Armed Forces Hospital Southern Region, Oncology Department, were interviewed from January 1st to June 30th, 2018. The interviews were conducted by trained physicians familiar with the questionnaire’s contents. The questionnaire consisted of four sections: a demographic section and three more sections to identify factors causing the delay at the three levels from the patients’ perspectives. All data were analyzed using the SPSS version 20.0.Results: The mean patient age was 63 years. A total of 112 patients were female and 88 were male. The most common cancer type was breast cancer (27.5%). Among the patients, 61% were illiterate and 25.5% had elementary school degrees, 86% expressed little or no general medical knowledge about cancer. More women than men paid attention to cancer symptoms (70% vs. 54%). 75% of the patients presented to the first health facility after 2 months from the first appearance of symptoms (level 1 delay). Only 2% of the patients presented within one week. 50% of the patients received a diagnosis after visiting two health facilities. All patients were diagnosed at hospitals. 40% of patients used alternative medicines, 70% of whom thought this was the cause of their delayed presentations. 67% had their diagnosis confirmed within one month (level 2 delay), and 66% started their definitive treatment within one month (level 3 delay). 75% of the patients blame themselves for the delay. Educational level (p = 0.03), knowledge about cancer (p < 0.01), and the use of complementary and alternative medicines (CAM) (p = 0.01) were significantly associated with delayed presentation of patients to the health facility. Conclusion: There is a delay in the presentation of cancer patients (level 1) in the southern part of Saudi Arabia. Educational level, knowledge of cancer symptoms, and use of complementary and alternative medicines are the main causes. There were no delays in diagnosis and start of treatment (level 2,3).