Ailment repairing regiments has turn out to be arduous, despite a plenty of understanding and knowledge acquired in the past relating to the molecular underpinnings of Alzheimer’s disease (AD. Umpteen clinical experiments targeting the fabrication and accumulation have been turned fruitless to fit potency standards. The tests aiming beta-amyloid hypothesis also turned futile making it exigent for further handling tactics. The new emanation of a comparably candid, economical, and punctilious system known as gene editing have showed light in path of cure for AD by CRISPR/Cas9 gene editing. Being a straight approach this procedure has already shown assurance in other neurological disorders too such as Huntington’s disease. This review standpoint the immanent service of CRISPR/Cas9 as a remedial option for AD by aiming on specific genes inclusive of those that induce early-onset AD, as well as those that are substantial risk components for late-onset AD such as the apolipoprotein E4 (APOE4) gene.
Yvonne A Efebera*, Amy S Ruppert, Apollinaire Ngankeu, Sabrina Garman, Prasanthi Kumchala, Alan Howard, Steven M Devine, Parvathi Ranganathan and Ramiro Garzon
Allogeneic hematopoietic stem cell transplant (alloHSCT) is a curative treatment for many hematologic malignancies. Unfortunately, about 30-50% of all recipients undergoing alloHSCT develop acute graft-versus-host-disease (aGVHD), which is associated with high morbidity and mortality [1,2]. Treatment of aGVHD involves the use of immune suppressive drugs such as high dose of steroids that leads to further immunosuppression and risk for opportunistic infections. Often patients are refractory to steroids therapy making the prognosis dismal. Thus, it is critical to identify robust biomarkers to detect aGVHD before onset of clinical symptoms so that therapeutic strategies can be implemented that may result in better treatment responses and less toxicity.
The growth of Rehabilitation, in all of its field and mainly in neuro-rehabilitation applications and settings, is showing increasingly strong interaction with the growth of technology and its innovative applications.
Nevertheless, is should be stressed that the use of machinery has always been a fundamental mainstay of Rehabilitation practices facing the whole person’s aspects and involving the whole physical world around the disabled people as it is: as it was in the past with physical exercises, physical modalities, and in many other trainings and activities that employed physical and technological means as Aids, Prostheses and Orthotics.
Nathanielly de Lima Silva*, Josiel Nascimento dos Santos, Márcia Santos Rezende, Lúcio Henrique Sousa Pinheiro, Carlos Arthur Cardoso Almeida, Dulce Marta Schimieguel and Danilo Nobre
Summary: Myelodysplastic Syndrome (MDS) is a heterogeneous group of clonal hematopoietic malignancies characterized by progressive cytopenias, ineffective hematopoiesis, bone marrow hypercellularity and transformation to acute myeloid leukemia (AML).
Objectives: Identify plasma proteins from MDS patients and from two healthy controls groups (young and elderly) by SDS-Page.
Methods: Plasma from 08 healthy young, 08 healthy elderly and 08 MDS patients were used for this study. Proteins were fractionated, precipitated, used for SDS-PAGE gel analysis, stained with comassie brilliant blue, scanned and bands were analyzed.
Results: It was possible to identify in both, 20% fraction and supernatant, proteins that were differentially expressed in each group. The ones that have showed some clinical relevance. Fibronectin was highly expressed only in the young control group. α2-Macroglobulin was also expressed in both control groups, but it was not expressed in the MDS group. Haptoglobin was highly expressed only in the elderly control and SMD groups.
Conclusion: Protein expression in plasma can be a biomarker for MDS, and may play a key role in the process of aging and hematologic malignancies development.
Cranioplasty is a reconstructive procedure for the repair of skull defects or deformities. Polymethyl-methacrylate (PMMA) is a commonly used alloplastic material when autologous bone is unavailable. However, manual shaping of bone cement for frontal and orbital bone defects is challenging and may not lead to cosmetically satisfactory results. Advances in computer-aided 3-dimensional (3D) design and printing technology allow the production of patient-customized implants with improved cosmetic and functional results. A 39-year-old female patient presented with right-sided frontal swelling and headache. Computerized tomography (CT) demonstrated a right frontal calvarial mass extending to the orbital wall. The boundaries of the lesion were marked using a 3D design software. A polyethylene terephthalate glycol (PETG) mold was manufactured with help of a 3D printer. Artificial bone flap was formed by pouring PMMA into the mold. After surgical resection of the calvarial mass, customized PMMA implant was applied with titanium mini plate and screws. The defect was closed properly with good aesthetic results. Production of customized PMMA cranioplasty implants with 3D printed molds is a useful technique and can be preferred for calvarial defects due to skull tumors, bone resorption and traumatic bone loss.
Background: With the advancement of cell therapy research, there is an increasing need for healthy volunteers (HV) to donate small volumes (30 ml) of human bone marrow (BM). The BM procedure required to procure small volumes is invasive, although short-lived (25 seconds), is not without risk. To ensure a sustainable supply of BM for research and cell therapy, greater information of the risks and factors that motivate HV to donate small volumes of BM will help optimize the procedure and HV enrolment, ensuring donors are fully informed of the potential risks.
Objective: To identify the adverse events (AE) experienced by HV during and after small volume BM procedure and understand the motivating factors that influence HV to donate BM for research.
Method: HV (n = 55) who donated BM (30 ml) for scientific research and provided informed consent were administered a questionnaire to identify the type, duration and severity of AE experienced during and post-BM aspiration; and to determine the motivating factors that influenced their willingness to donate BM.
Results: Pain was experienced by 89% of participants during the BM procedure with moderate grade reported by 40%. One/more of the following AE were experienced by 73% of the volunteers post-BM procedure: pain, fatigue, site reaction, nausea and transient hypotension. AE resolved within an average of three days. The reported motivational factors ranked in the following order: first, to advance research for the benefit of future patients; compensation for participation; free medical check-up; lastly, the research question was interesting.
Conclusion: Young HV, motivated primarily by altruism and financial compensation, risk the occurrence of transient AE following donation of small-volume BM for research.
Mauro Luisetto*, Naseer Almukhtar, Ahmed Yesvi Rafa, Behzad Nili Ahmadabadi, Ghulam Rasool Mashori, Farhan Ahmad Khan, Ram Kumar Sahu, Gamal Abdul Hamid and Khaled Edbey
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.
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.
Farmanullah*, Khalid Javed, Mohammad Salim, Momen Khan, Sajid Ali, Talpur Hira Sajjad, Muhammad Altaf Hussain, Ihsanullah Kakar, Inayat Ur Rehman, Asma Babar, Sajjad Ahmad, Bhunesh and Sami Ullah Khan
The liaison of birth weight to neonatal and mature vigor is especially given important if have the acquaintance of factors distressing in birth weight. Unbiased Best linear prediction of breeding values was estimated from pedigree birth weight records of 13715 Kajli sheep of livestock Experiment Station Khizerabad born 1994 to 2010, and Livestock Experimental Station, Khushab. Data records were statistically analyzed by means of using computer programmed Mixed Model Harvey’s Least Squares and Maximum Likelihood. An animal model was used for heritability estimation following Maximum Likelihood procedure. Estimates of birth weight heritability in Kajli sheep were 0.05 ± 0.019. The estimated breeding values of both forms for males, females, and sire were calculated with significant variation. Both farms data were analyzed by using an animal model program. The squares mean slightest for weight at birth (kg), remained 4.13 ± 0.01 kg. In addition, birth of the year, the birth of type, flock and sex significantly affects the (p < 0.001) trait of birth weight. The domino effect of the current study has rational implications not only for sheep husbandry nevertheless as well as for amplified acquaintance of parameters which drastically persuade deviation of weight in birth as weight in birth has become itself noteworthy forecaster of anon fitness outcomes. These results showed the decreasing genetic and static phenotypic at birth weight. It is likely that there are complex interactions between genetics and environmental factors of parental, placental and fetal origin. Birth weight is highly influenced trait by maternal nutrition, genes, care, management, climate, seasonal variation and type of birth.
Aim of this work is to produce a general theory related an new depurative strategy to be devalued for reduce or delay some spinal cord and brain degenerative and inflammatory chronic disease or acute traumatic condition. It is used and informatics approach in order to set correct the problem and the process. Scope of this project is to submit to the researcher a new therapeutic strategy (under a depurative- toxicological-pharmacological) in this complex kind of disease. A Turing machine theory say us a method to TRASLATE the need of a strategy in a practical hypotesys of work. A global conceptual map can help in this field.
In 2013, the World Health Organization (WHO) reported that small, pet turtles had caused multistate Salmonella outbreaks in the United States, from where small turtles were subsequently exported into the Republic of Korea. We investigated cases of salmonellosis in South Korea associated with domestic small turtles and analysed genetic characteristics of Salmonella isolates in commercially-available small turtles. We traced six Salmonella serovars, known to have caused human infection in the United States (S. Sandiego, S. Pomona, S. Poona, S. Newport, I 4,(5),12:i:-, and S. Typhimurium), in isolates from suspected Salmonella infection cases in Korea from 2006 to 2015. Additionally, we conducted a pilot study of isolates from small turtles being sold in Korean markets, and performed molecular genetic analysis on the identified strains. S. Pomona was identified in one Salmonella infection case, while all strains isolated from small turtles belonged to either subspecies I (enterica, n = 10, 71.4%) or subspecies IIIb (diarizonae, n = 4, 28.6%). Two serovars (S. Pomona and S. Sandiego) that were highly associated with turtle-to-human transmission were identified with 100% homology to human isolates. Previous to this study, turtle-associated human S. Pomona infections were not well reported in Korea. We report Salmonella infection in small turtles in Korea, and confirm that small turtles should be considered the first infectious agent in S. Pomona infection. We therefore suggest quarantine measures for importing small turtles be enhanced in Korea.
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.
Ausraful Islam*, Ashika Akbar Trisha, Md. Safiul Ahad Sardar, Mohammady Akbor, Abdulla Al Mamun Bhuyan, Md. Sazzad Hossain, Md. Ashraf Zaman Faruk, Sheikh Muhammad Khaled Sharif, Zannatun Nahar and Anisuzzaman
We interviewed 207 pig raisers from seven different districts of Bangladesh to explore their practices related to their pig farming. We used structured questionnaires to interview the pig raisers and used descriptive statistics for analysis. Most of the pig raisers (54%) were illiterate. 50% (104) of them had a monthly income of less than 10000 BDT and 60% (124) were landless. Most of the pig raisers (92%, 191) were rearing local breed and 67% of them were practicing semi-scavenging system. As feed source 55% (114) pig owners used kitchen waste and 54% (111) used rice husk. The pig raisers mentioned different types of challenges such as social problem (16%), disease (50%), less profitable (20%) and unavailability of feed (19%). In our study, we found that 31% respondents visited veterinarians, 28% visited quack and 21% do not take any action when their pigs were sick. Only 16% pig raisers used vaccines against different infectious diseases and 36% used anthelmintics against parasitic diseases. Awareness buildup of the pig raisers may help them raising pigs in a better way which will improve the farming system and reduce the probability of disease transmission.
Tamsulosin is used to treat Benign Prostatic Hyperplasia (BPH), prescribed annually to about 12.6 million patients worldwide. It is an alpha-adrenergic antagonist that reduces the tone of the prostate smooth muscle involved in the pathophysiology of BPH. By acting on alpha 1A receptors, predominant in the prostate, tamsulosin also acts on receptors present in the brain. This study consisted of a literature review aimed at disseminating scientific knowledge about the relationship between the use of tamsulosin and the onset of dementia. PubMed, Scopus, Scielo, Embase, and Web of Science studies involving dementia in patients using tamsulosin in the last five years were selected. The review showed a risk correlation and a higher incidence of dementia in treated patients. The risk ratio, when compared to other medicines, approached 1.20. In conclusion, it was identified the need for clinical trials with higher sampling power to increase relational significance due to the high prevalence of BPH and the extensive use of tamsulosin in elderly patients with the disease.
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.
Background: The acaricidal action of Ozonized sunflower oil (OSO) has demonstrated in different clinical cases of different animal species, such as psoroptic rabbits and pig sarcoptic scabies and recently in demodesic goat.
Objectives: This study evaluated the effectiveness of OSO as treatment for generalized demodicosis mange in dogs.
Animals: Twenty dogs of different breeds, between six months and one year of age with generalized demodicosic mange that attended to Veterinary Clinic “José Luis Callejas” Havana, Cuba, during the year 2015, were included in the study.
Methods: The demodicosis diagnostic was based on its clinical history, the mite’s presence by deep scraping and clinical signs. All cases had a history of receiving before conventional treatments without solution. OSO treatment was topically applied daily, every 12 hours, after shaving all affected areas. Monitoring of clinical signs, mite counting on scaling, pruritus and capillary regrowth (7, 14, 28, 56 and 84 days) were performed.
Results: The results showed a significant reduction of mite counts, clinical signs and pruritus since the 7th day of application. The animals recovered the fur on more than 90% of the body surface. All the animals (100%) recovered from generalized demodesic mange in 84 days of treatment.
Conclusion: The effectiveness and safety of OSO as election treatment of generalized demodicosis mange in dogs was demonstrated.
Observing the epidemiology of some neurodegenerative disease is interesting to verify some similarity and also related advanced or non-advanced countries and related diet habits. There are relationship between this conditions and diet habits? Some neurological condition related neuro-degeneration can be related to a complex dynamic system like the glymphatic system and the brain vascular clearance. Failure in this system seem related to aggravates of some condition like PD or vascular or diabetic dementia. (Animal model). But what happen if this dynamic system is saturated? A deep investigation related the specific role in CNS make possible to search new innovative strategies. The social economic cost for the neurodegenerative disease is the right tool to new research.
Sleep is considered as a complex process in human beings and is least understood mechanism. Role of sleep in synaptic plasticity remains a debatable topic till date. Sleep is influenced by genetic background of the individual. EEG done in human sleep showed strong influence of genetic factors. A handful of familial analyses involving specific gene loci and twin studies has been done in this regard. In this review article focused discussion on genetic contribution to sleep phenotypes, twin and familial linkage studies and effect of genetic variation on sleep will be covered
Objective: Currently, Parkinson’s disease (PD) is becoming more common among younger people of ages from 30 – 40 years. The incidence is higher among patients with higher body mass index (BMI), and some reports had it that Obesity is a risk factor for PD while some reported that there is no relationship between obesity and PD. PD patient at the time of diagnosis has an above-normal BMI but which goes below normal as the disease progresses. Therefore, it is essential to explore the relationship between PD and Obesity.
Methods: 349 outpatients and inpatients with PD were selected from Jiangsu University Affiliated People’s Hospital from January 2014 to December 2018, while 74 inpatients with non-cerebrovascular illness in the same period were selected as the control group. According to Hoehn-Yahr grade, Parkinson’s patients were divided into three groups. The height, weight, waist and hip circumference, total cholesterol (TC), Total Glycerol (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured and recorded. The relationship between the severity of Parkinson’s disease and blood lipids was evaluated.
Results: The BMI of patients with PD in the early stage was higher than that of the control group, but lower than that of the control group in the late stage, and the level of blood lipid in the patients with early PD was significantly higher than that in the control group and patients with advanced PD, especially in TG. The waist circumference and hip circumference of the patients with early PD were higher than those in the control group, but there was no statistical difference.
Conclusion: i) Obesity may increase the prevalence of PD. ii) The BMI of patients with PD shows two-way changes in different periods. iii) The BMI is higher and cholesterol is more elevated in the early stage of patients with PD, while at the advanced stage of the disease, the BMI and lipid levels of the patients showed a downward trend, which may be associated with a metabolic syndrome associated with dopamine depletion.
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