Hepatitis C virus(HCV)infection is considered a systemic disease because of involvement of other organs and tissues concomitantly with liver disease.Among the extrahepatic manifestations,neuropsychiatric disorders hav...Hepatitis C virus(HCV)infection is considered a systemic disease because of involvement of other organs and tissues concomitantly with liver disease.Among the extrahepatic manifestations,neuropsychiatric disorders have been reported in up to 50%of chronic HCV infected patients.Both the central and peripheral nervous system may be involved with a wide variety of clinical manifestations.Main HCV-associated neurological conditions include cerebrovascular events,encephalopathy,myelitis,encephalomyelitis,and cognitive impairment,whereas"brain fog",depression,anxiety,and fatigue are at the top of the list of psychiatric disorders.Moreover,HCV infection is known to cause both motor and sensory peripheral neuropathy in the context of mixed cryoglobulinemia,and has also been recently recognized as an independent risk factor for stroke.These extrahepatic manifestations are independent of severity of the underlying chronic liver disease and hepatic encephalopathy.The brain is a suitable site for HCV replication,where the virus may directly exert neurotoxicity;other mechanisms proposed to explain the pathogenesis of neuropsychiatric disorders in chronic HCV infection include derangement of metabolic pathways of infected cells,alterations in neurotransmitter circuits,autoimmune disorders,and cerebral or systemic inflammation.A pathogenic role for HCV is also suggested by improvement of neurological and psychiatric symptoms in patients achieving a sustained virologic response following interferon treatment;however,further ad hoc trials are needed to fully assess the impact of HCV infection and specific antiviral treatments on associated neuropsychiatric disorders.展开更多
As drivers age, roadway conditions may become more challenging, particularly when normal aging is coupled with cognitive decline. Driving during lower visibility conditions, such as inclement weather, is especially ch...As drivers age, roadway conditions may become more challenging, particularly when normal aging is coupled with cognitive decline. Driving during lower visibility conditions, such as inclement weather, is especially challenging for older drivers due to their sensitivity to glare and reduced visibility. As a result, older drivers may adjust their behavior during adverse weather. This paper explores the differential impacts of weather on older drivers with cognitive decline compared to older drivers with normal cognitive function. Data were from a naturalistic driving study of older drivers in Omaha, Nebraska. Driver speed and weather data were extracted and the correlation between speed compliance, road weather conditions, and the cognitive/neurological status of the drivers was examined. Speed compliance was used as the surrogate safety measure since driving at lower speeds can indicate that the driver is challenged by roadway or environmental conditions and can therefore indicate a risk. The percentage of time during a trip when drivers were 16.1 kph under the speed limit was modeled as the dependent variable using beta regression. The variables that resulted in the best fit model were mild cognitive impairment (MCI), age group, traffic density, and weather. Results indicated that the youngest group of older drivers (young-old) spent less time driving at impeding speeds and had the least variability compared to the other two age groups. The middle group of older drivers (middle-old) had the highest amount of time driving at impeding speeds and had more variability than young-old drivers. The oldest group of older drivers (old-old) were the most likely to drive at impeding speeds and had the most variability. In general, older drivers were more likely to drive at impeding speeds during peak hours than during non-peak hours. Additionally, in most cases, older drivers spent less time below the speed limit when the weather was clear than in adverse conditions. Results indicate that older drivers are impacted by weather conditions, and distinct patterns were noted between older drivers who were cognitively impaired compared to drivers with normal cognition.展开更多
Background and Objective:Idiopathic intracranial hypertension(IIH)is a disorder of raised intracranial pressure(ICP)associated with overweight and obesity,with weight loss being the mainstay of management.Diet and lif...Background and Objective:Idiopathic intracranial hypertension(IIH)is a disorder of raised intracranial pressure(ICP)associated with overweight and obesity,with weight loss being the mainstay of management.Diet and lifestyle changes alone are often unsuccessful at achieving meaningful or sustained weight loss.Glucagon-like peptide-1 receptor agonists(GLP-1RA)are a class of medications developed for the treatment of diabetes but are also highly effective for weight reduction.The objective of this narrative review is to present the current evidence for GLP-1RAs in the management of IIH.Methods:Articles were searched for inclusion through OVID using the following terms:[papilledema OR intracranial hypertension OR idiopathic intracranial hypertension OR brain pseudotumor]and[glucagon like peptide 1 OR glucagon like peptide 1 receptor agonist OR semaglutide OR exendin 4 OR liraglutide OR tirzepatide].Titles and abstracts were screened manually for relevance.There were no exclusion criteria for time frame,language,population or article type,although conference abstracts were not included.An illustrative case of a patient with IIH treated with tirzepatide and semaglutide is also presented.Key Content and Findings:GLP-1RAs have demonstrated the potential for significantly greater weight loss in patients with IIH,with a reduced requirement for IIH medications and improved symptoms,compared to conventional weight management.Treatment with GLP-1RAs has also been shown to result in a rapid and persistent reduction in ICP in both rat and human studies.The side effects of GLP-1RAs are generally well-tolerated,with low rates of discontinuation in clinical trials.However,continuous treatment is likely required to avoid weight rebound and symptom recurrence after cessation.Conclusions:Despite highly promising preliminary evidence,further clinical trials are needed to determine the most effective GLP-1RA medications within this class,appropriate dosing regimens and treatment duration.展开更多
It is believed that overproduction and deposition of amyloid-β (Aβ) plaques in the hippocampus and cortex region of the brain cause neuronal dysfunction leading to cognitive impairments in Alzheimer’s disease (AD)....It is believed that overproduction and deposition of amyloid-β (Aβ) plaques in the hippocampus and cortex region of the brain cause neuronal dysfunction leading to cognitive impairments in Alzheimer’s disease (AD).Until now,there has been no effective treatment to reduce plaque load from the brain.Recent studies have shown that regular treadmill exercise lowers plaques from the brain of a mouse model of AD.展开更多
BACKGROUND The World Health Organization defined long coronavirus disease 2019(COVID-19)as the continuation or development of new symptoms 3 months after the initial severe acute respiratory syndrome coronavirus 2 inf...BACKGROUND The World Health Organization defined long coronavirus disease 2019(COVID-19)as the continuation or development of new symptoms 3 months after the initial severe acute respiratory syndrome coronavirus 2 infection,with these symptoms lasting for at least 2 months with no other explanation.AIM To evaluate the potential laboratory and instrumental findings(short-term and long-term)resulting from COVID-19.METHODS This longitudinal observational COVID-19 cohort study(March 1,2020-March 1,2021)was carried out on patients≥18 years old who were admitted to the University Hospitals of Pisa,Siena and Careggi and the Azienda USL Toscana Nord Ovest,Sud Est and USL Centro Toscana and were subjected to follow-up.Follow-up was conducted between 0 day and 89 days,90 days and 179 days,180 days and 269 days,270 days and 359 days,and more than 360 days after hospitalization.RESULTS Of 2887 patients(58.5%males,average age 66.2 years)hospitalized in the study period(March 1,2020-March 1,2021)carrying out at least one follow-up examination within 12 months of discharge,a total of 1739 patients(705 males,average age 66 years)underwent laboratory tests,of whom 714 patients(470 males,average age 63 years)underwent spirometry.Some laboratory test results remained above the threshold even at follow-up beyond 360 days(C-reactive protein:36%,fibrin degradation fragment:48.8%,gamma-glutamyl transferase:16.8%),while others showed a return to normal range more quickly in almost all patients.Alterations in liver enzymes,hematocrit,hemoglobin,lymphocytes and neutrophils were associated with the risk of requiring oxygen therapy or forced expiratory volume in one second/forced vital capacity alterations at follow-up.CONCLUSION Alterations in liver enzymes,hematocrit or hemoglobin,lymphocytes and neutrophils were associated with risk outcomes(need for oxygen therapy or spirometry alterations).These imbalanced conditions may contribute to pulmonary dysfunction.展开更多
<strong>Background:</strong> Genetics research of humans has established that a genetic basis contributes to the susceptibility to epilepsy for a majority of the cases. Although many epilepsies are seconda...<strong>Background:</strong> Genetics research of humans has established that a genetic basis contributes to the susceptibility to epilepsy for a majority of the cases. Although many epilepsies are secondary to injury or another illness, approximately 40% are idiopathic, meaning that the original cause is unknown. It is presumed that most idiopathic epilepsies result from genetic abnormalities, with the majority likely caused by mutations in multiple currently unidentified genes. However, research has revealed a growing number of single-gene mutations that cause epilepsy. <strong>Objective:</strong> To detect some of the genetic mutations which may cause idiopathic epilepsy. <strong>Methods:</strong> The current study is a cross-sectional study that had been performed at Sheikh Mohamed Khair center, Banat, Omdurman, and National Centre for Neurological Sciences (NCNS) Khartoum state, during the period 2016 to 2019. Ninety-nine participants were enrolled in this study. Demographic data were collected in a predesigned questionnaire blood samples were analyzed for biochemical and molecular tests. <strong>Results:</strong> Ninety-nine patients diagnosed with idiopathic epilepsy were recruited in this study. The most affected age group was 18 - 40 years accounted for 55% of patients. Females were the majority with 53%. Fifty percent of the patients had the first seizure at age less than 5 years. Ninety percent of the patients have no Family history with epilepsy. All sequenced samples showed genetic mutations, deletion mutation was detected in 71% of the samples. Bioinformatics tools detected a frameshift mutation in the chain of the amino acids. <strong>Conclusion:</strong> The current study detected deletion mutations in SCN1A gene (frameshift) can cause epilepsy by changing some amino acids with residues that can affect neuronal stability indirectly.展开更多
The aryl hydrocarbon receptor （AhR） was discovered almost 30 years ago as a specific binding site for the halogenated polycyclic aromatic hydrocarbon, 2,3,7,8-tetrachlorodibenzo-p-dioxin （TCDD）, an environmental t...The aryl hydrocarbon receptor （AhR） was discovered almost 30 years ago as a specific binding site for the halogenated polycyclic aromatic hydrocarbon, 2,3,7,8-tetrachlorodibenzo-p-dioxin （TCDD）, an environmental toxin （as reviewed in [1]）. Within the last decade, AhR was found to have a basic helixloop-helix and function as a ligand-activated transcription factor.展开更多
Long-term epilepsy associated tumors(LEAT) represent a well known cause of focal epilepsies. Glioneuronaltumors are the most frequent histological type consisting of a mixture of glial and neuronal elements and most c...Long-term epilepsy associated tumors(LEAT) represent a well known cause of focal epilepsies. Glioneuronaltumors are the most frequent histological type consisting of a mixture of glial and neuronal elements and most commonly ariseing in the temporal lobe. Cortical dysplasia or other neuronal migration abnormalities often coexist. Epilepsy associated with LEAT is generally poorly controlled by antiepileptic drugs while, on the other hand, it is high responsive to surgical treatment. However the best management strategy of tumor-related focal epilepsies remains controversial representing a contemporary issues in epilepsy surgery. Temporo-mesial LEAT have a widespread epileptic networkwith complex epileptogenic mechanisms. By using an epilepsy surgery oriented strategy LEAT may have an excellent seizure outcome therefore surgical treatment should be offered early, irrespective of pharmacoresistance, avoiding both the consequences of uncontrolled seizures as well as the side effects of prolonged pharmacological therapy and the rare risk of malignant transformation.展开更多
Gastric carcinoma(GC) develops in only 1%-3% of Helicobacter pylori(H. pylori) infected people. The role in GC formation of the bacterial genotypes, gene polymorphisms and host's factors may therefore be important...Gastric carcinoma(GC) develops in only 1%-3% of Helicobacter pylori(H. pylori) infected people. The role in GC formation of the bacterial genotypes, gene polymorphisms and host's factors may therefore be important. The risk of GC is enhanced when individuals are infected by strains expressing the oncoprotein CagA, in particular if CagA has a high number of repeats containing the EPIYA sequence in its C'-terminal variable region or particular amino acid sequences flank the EPIYA motifs. H. pylori infection triggers an inflammatory response characterised by an increased secretion of some chemokines by immunocytes and colonised gastric epithelial cells; these molecules are especially constituted by proteins composing the interleukin-1beta(IL-1β) group and tumour necrosis factor-alpha(TNF-α). Polymorphisms in the promoter regions of genes encoding these molecules, could account for high concentrations of IL-1β and TNF-α in the gastric mucosa, which may cause hypochlorhydria and eventually GC. Inconsistent results have been attained with other haplotypes of inflammatory and anti-inflammatory cytokines. Genomic mechanisms of GC development are mainly based on chromosomal or microsatellite instability(MSI) and deregulation of signalling transduction pathways. H. pylori infection may induce DNA instability and breaks of double-strand DNA in gastric mucocytes. Different H. pylori strains seem to differently increase the risk of cancer development run by the host. Certain H. pylori genotypes(such as the cagA positive) induce high degrees of chronic inflammation and determine an increase of mutagenesis rate, oxidative-stress, mismatch repair mechanisms, down-regulation of base excision and genetic instability, as well as generation of reactive oxygen species that modulate apoptosis; these phenomena may end to trigger or concur to GC development.展开更多
Helicobacter pylori (H. pylori) infection could be associated with extra-digestive diseases. Here, we report the evidences concerning the decrease in reproductive potential occurring in individuals infected by H. pylo...Helicobacter pylori (H. pylori) infection could be associated with extra-digestive diseases. Here, we report the evidences concerning the decrease in reproductive potential occurring in individuals infected by H. pylori, especially by strains expressing CagA. This infection is more prevalent in individuals with fertility disorders. Infected women have anti-H. pylori antibodies in cervical mucus and follicular fluid that may decrease sperm motility and cross react immunologically with spermatozoa, conceivably hampering the oocyte/sperm fusion. Infection by CagA positive organisms enhances the risk of preeclampsia, which is a main cause of foetus death. These findings are supported by the results of experimental infections of pregnant mice, which may cause reabsorption of a high number of foetuses and alter the balance between Th1 and Th2 cell response. Infected men have decreased sperm motility, viability and numbers of normally shaped sperm and augmented systemic levels of inflammatory cytokines, such as tumor necrosis factor-α, which may damage spermatozoa. In countries where parasitic infestation is endemic, detrimental effects of infection upon spermatozoa may not occur, because the immune response to parasites could determine a switch from a predominant Th1 type to Th2 type lymphocytes, with production of anti-inflammatory cytokines. In conclusion, the evidences gathered until now should be taken into consideration for future studies aiming to explore the possible role of H. pylori infection on human reproduction.展开更多
AIM: To evaluate the effect of systemic ozonated major autohaemotherapy (O3-AHT) in patients affected by dry age related macular degeneration (AMD). METHODS: This study was a randomized, controlled clinical study. One...AIM: To evaluate the effect of systemic ozonated major autohaemotherapy (O3-AHT) in patients affected by dry age related macular degeneration (AMD). METHODS: This study was a randomized, controlled clinical study. One hundred and forty patients with the diagnosis of AMD in both eyes, with the study eye presenting dry AMD and soft drusen, were randomly assigned in a 1:1 ratio to either receive 27 major ozonated autohemotherapy treatments during 12-month period, or a standardized multi-vitamin therapy. Primary outcome was the change in best corrected visual acuity (mean logMar change) between the baseline and 6 and 12 months, end point of the study. In addition, to investigate the safety of prolonged ozonated autohaemotherapy, we measured the routine haemato- chemical parameters and biochemical oxidative stress values at baseline and after 12 months treatment time. RESULTS: The mean baseline best corrected visual acuity in study eyes was 0.36 in the treatment group and 0.38 in the control group (difference not statistically significant). At the primary endpoint, 6 months post-baseline, the mean logMAR change in the treated group improved by 0.1 and the values of the control group at the same time impaired by 0.2 respect to the baseline. Four percent and twenty-five percent of eyes in the group treated with O3-AHT gained 1 or more lines after 6 and 12 months respectively compared to 0% in the eyes which received no treatment (P <0.05 at 12 months). None of the treated patients experienced a loss in visual acuity in their study eye at 6 and 12 months, compared to 16% and 40 % of patients in the control group who lost 2 lines or more at 6 months and 12 months respectively (P <0.05 treated vs control group)). Major ozonated autohemotherapy was shown to be safe and well- tolerated by the patients. Moreover, the haematochemical parameters showed a decrease in the Reactive Oxygen Metabolites (300±10.1 UCARR at 12 months compared to a baseline value of 380±10.4 UCARR, P <0.05) and an increase in Biological Antioxidant Potential plasma values (2100±34.8 micromoles/ C vitamin after 12 months compared to the baseline value of 1610±36.2, P <0.05) in the treated patients when compared to the control group. This data suggests that major ozonated autohaemotherapy may exert a role in reducing oxidative stress by endogenously stimulating the production of antioxidant molecules. CONCLUSION: The results of this study suggests that major ozonated autohaemotherapy could be a safe and effective therapeutic option for high-risk patients with dry AMD, and that a series of such treatments could improve the natural course of AMD.展开更多
Biliary tract carcinomas are relatively rare,representing less than 1%of cancers.However,their incidence has increased in Japan and in industrialized countries like the USA.Biliary tract tumors have a poor prognosis a...Biliary tract carcinomas are relatively rare,representing less than 1%of cancers.However,their incidence has increased in Japan and in industrialized countries like the USA.Biliary tract tumors have a poor prognosis and a high mortality rate because they are usually detected late in the course of the disease;therapeutic treatment options are often limited and of minimal utility.Recent studies have shown the importance of serum and molecularmarkers in the diagnosis and follow up of biliary tract tumors.This review aims to introduce the main features of the most important serum and molecular markers of biliary tree tumors.Some considerable tumor markers are cancer antigen 125,carbohydrate antigen 19-9,carcinoembryonic antigen,chromogranin A,mucin 1,mucin 5,alpha-fetoprotein,claudins and cytokeratins.展开更多
In acute ischemic stroke,collateral circulation plays an important role in maintaining blood flow to the tissue that is at risk of progressing into ischemia,and in increasing the successful recanalization rate without...In acute ischemic stroke,collateral circulation plays an important role in maintaining blood flow to the tissue that is at risk of progressing into ischemia,and in increasing the successful recanalization rate without hemorrhagic transformation.We have reported that well-developed collateral circulation is associated with smaller infarct volume and better long-term neurological outcome,and it disappears promptly once the effective recanalization is achieved.Contrary to the belief that collateral vessels develop over time in chronic stenotic condition,there exists a phenomenon that collateral circulation develops immediately in acute stenosis or occlusion of the arteries and it seems to be triggered by fluid shear stress,which occurs between the territories of stenotic/occluded arteries and those fed by surrounding intact arteries.We believe that this acute development of collateral circulation is a target of novel therapeutics in ischemic stroke and refer our recent attempt in enhancing collateral circulation by modulating sphingosine-1-phosphate receptor 1,which is a known shear-stress mechanosensing protein.展开更多
AIM： To evaluate the levels of serum carnitine in patients with cancer in digestive organs and to compare them with other cancers in order to provide new insights into the mechanisms of cachexia. METHODS： Fifthy-fiv...AIM： To evaluate the levels of serum carnitine in patients with cancer in digestive organs and to compare them with other cancers in order to provide new insights into the mechanisms of cachexia. METHODS： Fifthy-five cachectic patients with or without gastrointestinal cancer were enrolled in the present study. They underwent routine laboratory investigations, including examination of the levels of various forms of carnitine present in serum （i.e., long-chain acylcarnitine, short-chain acylcarnitine, free carnitine, and total carnitine）. These values were compared with those found in 60 cancer patients in good nutritional status as well as with those of 30 healthy control subjects. RESULTS： When the cachectic patients with gastrointestinal cancer were compared with the cachectic patients without gastrointestinal cancer, the difference was -6.8 μmol/L in free carnitine （P 〈 0.005）, 0.04 μmol/ L in long chain acylcarnitine （P 〈 0.05）, 8.7 μmol/L in total carnitine （P 〈 0.001）. In the cachectic patients with or without gastrointestinal cancer, the difference was 12.2 μmol/L in free carnitine （P 〈 0.001）, 4.60 μmol/L in short chain acylcarnitine （P 〈 0.001）, and 0.60 μmol/L in long-chain acylcarnitine （P 〈 0.005） and 17.4 μmol/L in total carnitine （P 〈 0.001）. In the cachectic patients with gastrointestinal cancer and the healthy control subjects, the difference was 15.5 μmol/L in free carnitine （P 〈 0.001）, 5.2 μmol /L in short-chain acylcarnitine （P 〈 0.001）, 1.0 μmol/L in long chain acylcarnitine （P 〈 0.001）, and 21.8 μmol/L in total carnitine （P 〈 0.001）. CONCLUSION： Low serum levels of carnitine in terminal neoplastic patients are decreased greatly due to the decreased dietary intake and impaired endogenous synthesis of this substance. These low serum carnitine levels also contribute to the progression of cachexia in cancer patients.展开更多
The cervical spine injury represents a potential devastating disease with 6% associated in-hospital mortality （lain et al., 2015）. Neurological deterioration ranging from complete spinal cord injury （SCI） to incom...The cervical spine injury represents a potential devastating disease with 6% associated in-hospital mortality （lain et al., 2015）. Neurological deterioration ranging from complete spinal cord injury （SCI） to incomplete SCI or single radiculopathy are potential consequences of the blunt trauma over this region. The subaxial cervical spine accounts the vast majority of cervical injuries, making up two thirds of all cervical fractures （Alday, 1996）. Few classifications （Holdsworth, 1970; White et al., 1975; Mien et al., 1982; Denis, 1984; Vaccaro et al., 2007） have been proposed to describe injuries of the cervical spine for several reasons. First, to delineate the best treatment in each case; second, to determinate an accurate neurological prognosis, and third, to establish a standard way to communicate and describe specific characteristics of cervical injuries patterns. Classical systems are primarily descriptive and no single system has gained widespread use, largely because of restrictions in clinical relevance and its complexity.展开更多
While in one hand, due to genetic alterations, lifestyle changes, infections or injuries, or sudden turn of life events, we get health problems, on the other, we have been endowed with enormous natural remedies to tak...While in one hand, due to genetic alterations, lifestyle changes, infections or injuries, or sudden turn of life events, we get health problems, on the other, we have been endowed with enormous natural remedies to take care our health. Cinnamon, the brown bark of cinna- mon tree, is one such natural product that has already been being used for centuries throughout the world as spice or flavoring agent. In addition, medieval physicians used cinnamon for medical purposes to treat a variety of disorders including arthritis, coughing, hoarseness, sore throats, etc. It was once so highly-prized that several wars were fought over it.展开更多
Injuries to the nervous system manifest in various forms ranging from stroke to trauma（i.e.,motor vehicle accidents,combats）to diabetic neuropathy as well as many other neurological diseases.Nerve regeneration remai...Injuries to the nervous system manifest in various forms ranging from stroke to trauma（i.e.,motor vehicle accidents,combats）to diabetic neuropathy as well as many other neurological diseases.Nerve regeneration remains a complex biological process that is challenging to address clinically.There is no effective medical treatment for central nervous system repair.展开更多
Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial ac...Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial activation and neuroinflammation, edema, ischemia, vascular injury, energy failure, and peripheral immune cell infiltration. The timing of these events post injury has been linked to injury severity and functional outcome. Extracellular vesicles are membrane bound secretory vesicles that contain markers and cargo pertaining to their cell of origin and can cross the blood-brain barrier. These qualities make extracellular vesicles intriguing candidates for a liquid biopsy into the pathophysiologic changes occurring at the cellular level post traumatic brain injury. Herein, we review the most commonly reported cargo changes in extracellular vesicles from clinical traumatic brain injury samples. We then use knowledge from animal and in vitro models to help infer what these changes may indicate regrading cellular responses post traumatic brain injury. Future research should prioritize labeling extracellular vesicles with markers for distinct cell types across a range of timepoints post traumatic brain injury.展开更多
基金Supported by Research grant from Regione Campania,Italy
文摘Hepatitis C virus(HCV)infection is considered a systemic disease because of involvement of other organs and tissues concomitantly with liver disease.Among the extrahepatic manifestations,neuropsychiatric disorders have been reported in up to 50%of chronic HCV infected patients.Both the central and peripheral nervous system may be involved with a wide variety of clinical manifestations.Main HCV-associated neurological conditions include cerebrovascular events,encephalopathy,myelitis,encephalomyelitis,and cognitive impairment,whereas"brain fog",depression,anxiety,and fatigue are at the top of the list of psychiatric disorders.Moreover,HCV infection is known to cause both motor and sensory peripheral neuropathy in the context of mixed cryoglobulinemia,and has also been recently recognized as an independent risk factor for stroke.These extrahepatic manifestations are independent of severity of the underlying chronic liver disease and hepatic encephalopathy.The brain is a suitable site for HCV replication,where the virus may directly exert neurotoxicity;other mechanisms proposed to explain the pathogenesis of neuropsychiatric disorders in chronic HCV infection include derangement of metabolic pathways of infected cells,alterations in neurotransmitter circuits,autoimmune disorders,and cerebral or systemic inflammation.A pathogenic role for HCV is also suggested by improvement of neurological and psychiatric symptoms in patients achieving a sustained virologic response following interferon treatment;however,further ad hoc trials are needed to fully assess the impact of HCV infection and specific antiviral treatments on associated neuropsychiatric disorders.
文摘As drivers age, roadway conditions may become more challenging, particularly when normal aging is coupled with cognitive decline. Driving during lower visibility conditions, such as inclement weather, is especially challenging for older drivers due to their sensitivity to glare and reduced visibility. As a result, older drivers may adjust their behavior during adverse weather. This paper explores the differential impacts of weather on older drivers with cognitive decline compared to older drivers with normal cognitive function. Data were from a naturalistic driving study of older drivers in Omaha, Nebraska. Driver speed and weather data were extracted and the correlation between speed compliance, road weather conditions, and the cognitive/neurological status of the drivers was examined. Speed compliance was used as the surrogate safety measure since driving at lower speeds can indicate that the driver is challenged by roadway or environmental conditions and can therefore indicate a risk. The percentage of time during a trip when drivers were 16.1 kph under the speed limit was modeled as the dependent variable using beta regression. The variables that resulted in the best fit model were mild cognitive impairment (MCI), age group, traffic density, and weather. Results indicated that the youngest group of older drivers (young-old) spent less time driving at impeding speeds and had the least variability compared to the other two age groups. The middle group of older drivers (middle-old) had the highest amount of time driving at impeding speeds and had more variability than young-old drivers. The oldest group of older drivers (old-old) were the most likely to drive at impeding speeds and had the most variability. In general, older drivers were more likely to drive at impeding speeds during peak hours than during non-peak hours. Additionally, in most cases, older drivers spent less time below the speed limit when the weather was clear than in adverse conditions. Results indicate that older drivers are impacted by weather conditions, and distinct patterns were noted between older drivers who were cognitively impaired compared to drivers with normal cognition.
文摘Background and Objective:Idiopathic intracranial hypertension(IIH)is a disorder of raised intracranial pressure(ICP)associated with overweight and obesity,with weight loss being the mainstay of management.Diet and lifestyle changes alone are often unsuccessful at achieving meaningful or sustained weight loss.Glucagon-like peptide-1 receptor agonists(GLP-1RA)are a class of medications developed for the treatment of diabetes but are also highly effective for weight reduction.The objective of this narrative review is to present the current evidence for GLP-1RAs in the management of IIH.Methods:Articles were searched for inclusion through OVID using the following terms:[papilledema OR intracranial hypertension OR idiopathic intracranial hypertension OR brain pseudotumor]and[glucagon like peptide 1 OR glucagon like peptide 1 receptor agonist OR semaglutide OR exendin 4 OR liraglutide OR tirzepatide].Titles and abstracts were screened manually for relevance.There were no exclusion criteria for time frame,language,population or article type,although conference abstracts were not included.An illustrative case of a patient with IIH treated with tirzepatide and semaglutide is also presented.Key Content and Findings:GLP-1RAs have demonstrated the potential for significantly greater weight loss in patients with IIH,with a reduced requirement for IIH medications and improved symptoms,compared to conventional weight management.Treatment with GLP-1RAs has also been shown to result in a rapid and persistent reduction in ICP in both rat and human studies.The side effects of GLP-1RAs are generally well-tolerated,with low rates of discontinuation in clinical trials.However,continuous treatment is likely required to avoid weight rebound and symptom recurrence after cessation.Conclusions:Despite highly promising preliminary evidence,further clinical trials are needed to determine the most effective GLP-1RA medications within this class,appropriate dosing regimens and treatment duration.
基金supported by merit awards (1I01BX005002 and I01BX005613) from US Department of Veterans Affairsa grant (AT10980) from NIH (to KP)。
文摘It is believed that overproduction and deposition of amyloid-β (Aβ) plaques in the hippocampus and cortex region of the brain cause neuronal dysfunction leading to cognitive impairments in Alzheimer’s disease (AD).Until now,there has been no effective treatment to reduce plaque load from the brain.Recent studies have shown that regular treadmill exercise lowers plaques from the brain of a mouse model of AD.
基金Supported by Regione Toscana,No.D55H20000210002.
文摘BACKGROUND The World Health Organization defined long coronavirus disease 2019(COVID-19)as the continuation or development of new symptoms 3 months after the initial severe acute respiratory syndrome coronavirus 2 infection,with these symptoms lasting for at least 2 months with no other explanation.AIM To evaluate the potential laboratory and instrumental findings(short-term and long-term)resulting from COVID-19.METHODS This longitudinal observational COVID-19 cohort study(March 1,2020-March 1,2021)was carried out on patients≥18 years old who were admitted to the University Hospitals of Pisa,Siena and Careggi and the Azienda USL Toscana Nord Ovest,Sud Est and USL Centro Toscana and were subjected to follow-up.Follow-up was conducted between 0 day and 89 days,90 days and 179 days,180 days and 269 days,270 days and 359 days,and more than 360 days after hospitalization.RESULTS Of 2887 patients(58.5%males,average age 66.2 years)hospitalized in the study period(March 1,2020-March 1,2021)carrying out at least one follow-up examination within 12 months of discharge,a total of 1739 patients(705 males,average age 66 years)underwent laboratory tests,of whom 714 patients(470 males,average age 63 years)underwent spirometry.Some laboratory test results remained above the threshold even at follow-up beyond 360 days(C-reactive protein:36%,fibrin degradation fragment:48.8%,gamma-glutamyl transferase:16.8%),while others showed a return to normal range more quickly in almost all patients.Alterations in liver enzymes,hematocrit,hemoglobin,lymphocytes and neutrophils were associated with the risk of requiring oxygen therapy or forced expiratory volume in one second/forced vital capacity alterations at follow-up.CONCLUSION Alterations in liver enzymes,hematocrit or hemoglobin,lymphocytes and neutrophils were associated with risk outcomes(need for oxygen therapy or spirometry alterations).These imbalanced conditions may contribute to pulmonary dysfunction.
文摘<strong>Background:</strong> Genetics research of humans has established that a genetic basis contributes to the susceptibility to epilepsy for a majority of the cases. Although many epilepsies are secondary to injury or another illness, approximately 40% are idiopathic, meaning that the original cause is unknown. It is presumed that most idiopathic epilepsies result from genetic abnormalities, with the majority likely caused by mutations in multiple currently unidentified genes. However, research has revealed a growing number of single-gene mutations that cause epilepsy. <strong>Objective:</strong> To detect some of the genetic mutations which may cause idiopathic epilepsy. <strong>Methods:</strong> The current study is a cross-sectional study that had been performed at Sheikh Mohamed Khair center, Banat, Omdurman, and National Centre for Neurological Sciences (NCNS) Khartoum state, during the period 2016 to 2019. Ninety-nine participants were enrolled in this study. Demographic data were collected in a predesigned questionnaire blood samples were analyzed for biochemical and molecular tests. <strong>Results:</strong> Ninety-nine patients diagnosed with idiopathic epilepsy were recruited in this study. The most affected age group was 18 - 40 years accounted for 55% of patients. Females were the majority with 53%. Fifty percent of the patients had the first seizure at age less than 5 years. Ninety percent of the patients have no Family history with epilepsy. All sequenced samples showed genetic mutations, deletion mutation was detected in 71% of the samples. Bioinformatics tools detected a frameshift mutation in the chain of the amino acids. <strong>Conclusion:</strong> The current study detected deletion mutations in SCN1A gene (frameshift) can cause epilepsy by changing some amino acids with residues that can affect neuronal stability indirectly.
文摘The aryl hydrocarbon receptor （AhR） was discovered almost 30 years ago as a specific binding site for the halogenated polycyclic aromatic hydrocarbon, 2,3,7,8-tetrachlorodibenzo-p-dioxin （TCDD）, an environmental toxin （as reviewed in [1]）. Within the last decade, AhR was found to have a basic helixloop-helix and function as a ligand-activated transcription factor.
文摘Long-term epilepsy associated tumors(LEAT) represent a well known cause of focal epilepsies. Glioneuronaltumors are the most frequent histological type consisting of a mixture of glial and neuronal elements and most commonly ariseing in the temporal lobe. Cortical dysplasia or other neuronal migration abnormalities often coexist. Epilepsy associated with LEAT is generally poorly controlled by antiepileptic drugs while, on the other hand, it is high responsive to surgical treatment. However the best management strategy of tumor-related focal epilepsies remains controversial representing a contemporary issues in epilepsy surgery. Temporo-mesial LEAT have a widespread epileptic networkwith complex epileptogenic mechanisms. By using an epilepsy surgery oriented strategy LEAT may have an excellent seizure outcome therefore surgical treatment should be offered early, irrespective of pharmacoresistance, avoiding both the consequences of uncontrolled seizures as well as the side effects of prolonged pharmacological therapy and the rare risk of malignant transformation.
文摘Gastric carcinoma(GC) develops in only 1%-3% of Helicobacter pylori(H. pylori) infected people. The role in GC formation of the bacterial genotypes, gene polymorphisms and host's factors may therefore be important. The risk of GC is enhanced when individuals are infected by strains expressing the oncoprotein CagA, in particular if CagA has a high number of repeats containing the EPIYA sequence in its C'-terminal variable region or particular amino acid sequences flank the EPIYA motifs. H. pylori infection triggers an inflammatory response characterised by an increased secretion of some chemokines by immunocytes and colonised gastric epithelial cells; these molecules are especially constituted by proteins composing the interleukin-1beta(IL-1β) group and tumour necrosis factor-alpha(TNF-α). Polymorphisms in the promoter regions of genes encoding these molecules, could account for high concentrations of IL-1β and TNF-α in the gastric mucosa, which may cause hypochlorhydria and eventually GC. Inconsistent results have been attained with other haplotypes of inflammatory and anti-inflammatory cytokines. Genomic mechanisms of GC development are mainly based on chromosomal or microsatellite instability(MSI) and deregulation of signalling transduction pathways. H. pylori infection may induce DNA instability and breaks of double-strand DNA in gastric mucocytes. Different H. pylori strains seem to differently increase the risk of cancer development run by the host. Certain H. pylori genotypes(such as the cagA positive) induce high degrees of chronic inflammation and determine an increase of mutagenesis rate, oxidative-stress, mismatch repair mechanisms, down-regulation of base excision and genetic instability, as well as generation of reactive oxygen species that modulate apoptosis; these phenomena may end to trigger or concur to GC development.
文摘Helicobacter pylori (H. pylori) infection could be associated with extra-digestive diseases. Here, we report the evidences concerning the decrease in reproductive potential occurring in individuals infected by H. pylori, especially by strains expressing CagA. This infection is more prevalent in individuals with fertility disorders. Infected women have anti-H. pylori antibodies in cervical mucus and follicular fluid that may decrease sperm motility and cross react immunologically with spermatozoa, conceivably hampering the oocyte/sperm fusion. Infection by CagA positive organisms enhances the risk of preeclampsia, which is a main cause of foetus death. These findings are supported by the results of experimental infections of pregnant mice, which may cause reabsorption of a high number of foetuses and alter the balance between Th1 and Th2 cell response. Infected men have decreased sperm motility, viability and numbers of normally shaped sperm and augmented systemic levels of inflammatory cytokines, such as tumor necrosis factor-α, which may damage spermatozoa. In countries where parasitic infestation is endemic, detrimental effects of infection upon spermatozoa may not occur, because the immune response to parasites could determine a switch from a predominant Th1 type to Th2 type lymphocytes, with production of anti-inflammatory cytokines. In conclusion, the evidences gathered until now should be taken into consideration for future studies aiming to explore the possible role of H. pylori infection on human reproduction.
文摘AIM: To evaluate the effect of systemic ozonated major autohaemotherapy (O3-AHT) in patients affected by dry age related macular degeneration (AMD). METHODS: This study was a randomized, controlled clinical study. One hundred and forty patients with the diagnosis of AMD in both eyes, with the study eye presenting dry AMD and soft drusen, were randomly assigned in a 1:1 ratio to either receive 27 major ozonated autohemotherapy treatments during 12-month period, or a standardized multi-vitamin therapy. Primary outcome was the change in best corrected visual acuity (mean logMar change) between the baseline and 6 and 12 months, end point of the study. In addition, to investigate the safety of prolonged ozonated autohaemotherapy, we measured the routine haemato- chemical parameters and biochemical oxidative stress values at baseline and after 12 months treatment time. RESULTS: The mean baseline best corrected visual acuity in study eyes was 0.36 in the treatment group and 0.38 in the control group (difference not statistically significant). At the primary endpoint, 6 months post-baseline, the mean logMAR change in the treated group improved by 0.1 and the values of the control group at the same time impaired by 0.2 respect to the baseline. Four percent and twenty-five percent of eyes in the group treated with O3-AHT gained 1 or more lines after 6 and 12 months respectively compared to 0% in the eyes which received no treatment (P <0.05 at 12 months). None of the treated patients experienced a loss in visual acuity in their study eye at 6 and 12 months, compared to 16% and 40 % of patients in the control group who lost 2 lines or more at 6 months and 12 months respectively (P <0.05 treated vs control group)). Major ozonated autohemotherapy was shown to be safe and well- tolerated by the patients. Moreover, the haematochemical parameters showed a decrease in the Reactive Oxygen Metabolites (300±10.1 UCARR at 12 months compared to a baseline value of 380±10.4 UCARR, P <0.05) and an increase in Biological Antioxidant Potential plasma values (2100±34.8 micromoles/ C vitamin after 12 months compared to the baseline value of 1610±36.2, P <0.05) in the treated patients when compared to the control group. This data suggests that major ozonated autohaemotherapy may exert a role in reducing oxidative stress by endogenously stimulating the production of antioxidant molecules. CONCLUSION: The results of this study suggests that major ozonated autohaemotherapy could be a safe and effective therapeutic option for high-risk patients with dry AMD, and that a series of such treatments could improve the natural course of AMD.
文摘Biliary tract carcinomas are relatively rare,representing less than 1%of cancers.However,their incidence has increased in Japan and in industrialized countries like the USA.Biliary tract tumors have a poor prognosis and a high mortality rate because they are usually detected late in the course of the disease;therapeutic treatment options are often limited and of minimal utility.Recent studies have shown the importance of serum and molecularmarkers in the diagnosis and follow up of biliary tract tumors.This review aims to introduce the main features of the most important serum and molecular markers of biliary tree tumors.Some considerable tumor markers are cancer antigen 125,carbohydrate antigen 19-9,carcinoembryonic antigen,chromogranin A,mucin 1,mucin 5,alpha-fetoprotein,claudins and cytokeratins.
文摘In acute ischemic stroke,collateral circulation plays an important role in maintaining blood flow to the tissue that is at risk of progressing into ischemia,and in increasing the successful recanalization rate without hemorrhagic transformation.We have reported that well-developed collateral circulation is associated with smaller infarct volume and better long-term neurological outcome,and it disappears promptly once the effective recanalization is achieved.Contrary to the belief that collateral vessels develop over time in chronic stenotic condition,there exists a phenomenon that collateral circulation develops immediately in acute stenosis or occlusion of the arteries and it seems to be triggered by fluid shear stress,which occurs between the territories of stenotic/occluded arteries and those fed by surrounding intact arteries.We believe that this acute development of collateral circulation is a target of novel therapeutics in ischemic stroke and refer our recent attempt in enhancing collateral circulation by modulating sphingosine-1-phosphate receptor 1,which is a known shear-stress mechanosensing protein.
文摘AIM： To evaluate the levels of serum carnitine in patients with cancer in digestive organs and to compare them with other cancers in order to provide new insights into the mechanisms of cachexia. METHODS： Fifthy-five cachectic patients with or without gastrointestinal cancer were enrolled in the present study. They underwent routine laboratory investigations, including examination of the levels of various forms of carnitine present in serum （i.e., long-chain acylcarnitine, short-chain acylcarnitine, free carnitine, and total carnitine）. These values were compared with those found in 60 cancer patients in good nutritional status as well as with those of 30 healthy control subjects. RESULTS： When the cachectic patients with gastrointestinal cancer were compared with the cachectic patients without gastrointestinal cancer, the difference was -6.8 μmol/L in free carnitine （P 〈 0.005）, 0.04 μmol/ L in long chain acylcarnitine （P 〈 0.05）, 8.7 μmol/L in total carnitine （P 〈 0.001）. In the cachectic patients with or without gastrointestinal cancer, the difference was 12.2 μmol/L in free carnitine （P 〈 0.001）, 4.60 μmol/L in short chain acylcarnitine （P 〈 0.001）, and 0.60 μmol/L in long-chain acylcarnitine （P 〈 0.005） and 17.4 μmol/L in total carnitine （P 〈 0.001）. In the cachectic patients with gastrointestinal cancer and the healthy control subjects, the difference was 15.5 μmol/L in free carnitine （P 〈 0.001）, 5.2 μmol /L in short-chain acylcarnitine （P 〈 0.001）, 1.0 μmol/L in long chain acylcarnitine （P 〈 0.001）, and 21.8 μmol/L in total carnitine （P 〈 0.001）. CONCLUSION： Low serum levels of carnitine in terminal neoplastic patients are decreased greatly due to the decreased dietary intake and impaired endogenous synthesis of this substance. These low serum carnitine levels also contribute to the progression of cachexia in cancer patients.
文摘The cervical spine injury represents a potential devastating disease with 6% associated in-hospital mortality （lain et al., 2015）. Neurological deterioration ranging from complete spinal cord injury （SCI） to incomplete SCI or single radiculopathy are potential consequences of the blunt trauma over this region. The subaxial cervical spine accounts the vast majority of cervical injuries, making up two thirds of all cervical fractures （Alday, 1996）. Few classifications （Holdsworth, 1970; White et al., 1975; Mien et al., 1982; Denis, 1984; Vaccaro et al., 2007） have been proposed to describe injuries of the cervical spine for several reasons. First, to delineate the best treatment in each case; second, to determinate an accurate neurological prognosis, and third, to establish a standard way to communicate and describe specific characteristics of cervical injuries patterns. Classical systems are primarily descriptive and no single system has gained widespread use, largely because of restrictions in clinical relevance and its complexity.
基金supported by grants from National Institutes of Health(AT6681 and NS83054)
文摘While in one hand, due to genetic alterations, lifestyle changes, infections or injuries, or sudden turn of life events, we get health problems, on the other, we have been endowed with enormous natural remedies to take care our health. Cinnamon, the brown bark of cinna- mon tree, is one such natural product that has already been being used for centuries throughout the world as spice or flavoring agent. In addition, medieval physicians used cinnamon for medical purposes to treat a variety of disorders including arthritis, coughing, hoarseness, sore throats, etc. It was once so highly-prized that several wars were fought over it.
基金supported in part by the American Brain Foundation/Academy of Neurology and NIH grant K08NS089976
文摘Injuries to the nervous system manifest in various forms ranging from stroke to trauma（i.e.,motor vehicle accidents,combats）to diabetic neuropathy as well as many other neurological diseases.Nerve regeneration remains a complex biological process that is challenging to address clinically.There is no effective medical treatment for central nervous system repair.
基金supported by Canadian Institutes for Health Research (CIHR)(to ADR and WW)Ontario Graduate Scholarship (to NOB)+2 种基金Alzheimer's Society of CanadaHeart and Stroke Foundation of Canada,CIHRthe Canadian Consortium for Neurodegeneration and Aging (CCNA)(to SNW)。
文摘Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial activation and neuroinflammation, edema, ischemia, vascular injury, energy failure, and peripheral immune cell infiltration. The timing of these events post injury has been linked to injury severity and functional outcome. Extracellular vesicles are membrane bound secretory vesicles that contain markers and cargo pertaining to their cell of origin and can cross the blood-brain barrier. These qualities make extracellular vesicles intriguing candidates for a liquid biopsy into the pathophysiologic changes occurring at the cellular level post traumatic brain injury. Herein, we review the most commonly reported cargo changes in extracellular vesicles from clinical traumatic brain injury samples. We then use knowledge from animal and in vitro models to help infer what these changes may indicate regrading cellular responses post traumatic brain injury. Future research should prioritize labeling extracellular vesicles with markers for distinct cell types across a range of timepoints post traumatic brain injury.
