Hepatitis B virus(HBV) infection has shown an intermediate or high endemicity level in low-income countries over the last five decades. In recent years, however, the incidence of acute hepatitis B and the prevalence o...Hepatitis B virus(HBV) infection has shown an intermediate or high endemicity level in low-income countries over the last five decades. In recent years, however, the incidence of acute hepatitis B and the prevalence of hepatitis B surface antigen chronic carriers have decreased in several countries because of the HBV universal vaccination programs started in the nineties. Some countries, however, are still unable to implement these programs, particularly in their hyperendemic rural areas. The diffusion of HBV infection is still wide in several low-income countries where the prevention, management and treatment of HBV infection are a heavy burden for the governments and healthcare authorities. Of note, the information on the HBV epidemiology is scanty in numerous eastern European and Latin-American countries. The studies on molecular epidemiology performed in some countries provide an important contribution for a more comprehensive knowledge of HBV epidemiology, and phylogenetic studies provide information on the impact of recent and older migratory flows.展开更多
A severe spinal cord involvement may rarely occur in patients with cirrhosis and other chronic liver diseases;this complication is usually associated with overt liver failure and surgical or spontaneous porto-systemic...A severe spinal cord involvement may rarely occur in patients with cirrhosis and other chronic liver diseases;this complication is usually associated with overt liver failure and surgical or spontaneous porto-systemic shunt.Hepatic myelopathy(HM)is characterized by progressive weakness and spasticity of the lower extremities,while sensory and sphincter disturbances have rarely been described and are usually less important.The diagnosis is assigned in the appropriate clinical setting on clinical grounds after the exclusion of other clinical entities leading to spastic paraparesis.Magnetic resonance imaging is often unremarkable;however,also intracerebral corticospinal tract abnor-malities have been reported recently.The study of motor evoked potentials may disclose central conduction abnormalities even before HM is clinically manifest.HM responds poorly to blood ammonia-lowering and other conservative medical therapy.Liver transplantation represents a potentially definitive treatment for HM in patients with decompensated cirrhosis of Child-Pugh B and C grades.Other surgical treatment options in HM include surgical ligation,shunt reduction,or occlusion by interventional procedures.展开更多
Spontaneous intracerebral hemorrhage is a type of stroke associated with poor outcomes. Mortality is elevated, especially in the acute phase. From a pathophysiological point of view the bleeding must traverse differen...Spontaneous intracerebral hemorrhage is a type of stroke associated with poor outcomes. Mortality is elevated, especially in the acute phase. From a pathophysiological point of view the bleeding must traverse different stages dominated by the possibility of re-bleeding, edema, intracranial hypertension, inflammation and neurotoxicity due to blood degradation products, mainly hemoglobin and thrombin. Neurological deterioration and death are common in early hours, so it is a true neurologicalneurosurgical emergency. Time is brain so that action should be taken fast and accurately. The most significant prognostic factors are level of consciousness, location, volume and ventricular extension of the bleeding. Nihilism and early withdrawal of active therapy undoubtedly influence the final result. Although there are no proven therapeutic measures, treatment should be individualized and guided preferably by pathophysiology. The multidisciplinary teamwork is essential. Results of recently completed studies have birth to promising new strategies. For correct management it's important to establish an orderly and systematic strategy based on clinical stabilization, evaluation and establishment of prognosis, avoiding secondary insults and adoption of specific individualized therapies, including hemostatic therapy and intensive control of elevated blood pressure. Uncertainty continues regarding the role of surgery.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
Alzheimer’s disease(AD)is a progressive neurodegenerative disorder that affects both cognition and non-cognition functions.The disease follows a continuum,starting with preclinical stages,progressing to mild cognitiv...Alzheimer’s disease(AD)is a progressive neurodegenerative disorder that affects both cognition and non-cognition functions.The disease follows a continuum,starting with preclinical stages,progressing to mild cognitive and behavioral impairment,ultimately leading to dementia.Early detection of AD is crucial for better diagnosis and more effective treatment.However,the current AD diagnostic tests of biomarkers using cerebrospinal fluid and/or brain imaging are invasive or expensive,and mostly are still not able to detect early disease state.Consequently,there is an urgent need to develop new diagnostic techniques with higher sensitivity and specificity during the preclinical stages of AD.Various non-cognitive manifestations,including behavioral abnormalities,sleep disturbances,sensory dysfunctions,and physical changes,have been observed in the preclinical AD stage before occurrence of notable cognitive decline.Recent research advances have identified several biofluid biomarkers as early indicators of AD.This review focuses on these non-cognitive changes and newly discovered biomarkers in AD,specifically addressing the preclinical stages of the disease.Furthermore,it is of importance to explore the potential for developing a predictive system or network to forecast disease onset and progression at the early stage of AD.展开更多
Hyperglycemia reduces the number of circulating endothelial progenitor cells, accelerates their senescence and impairs their function.However, the relationship between blood glucose levels and endothelial progenitor c...Hyperglycemia reduces the number of circulating endothelial progenitor cells, accelerates their senescence and impairs their function.However, the relationship between blood glucose levels and endothelial progenitor cells in peripheral blood of patients with traumatic brain injury is unclear. In this study, 101 traumatic brain injury patients admitted to the Department of Neurosurgery, Tianjin Medical University General Hospital or the Department of Neurosurgery, Tianjin Huanhu Hospital, China, were enrolled from April 2005 to March 2007. The number of circulating endothelial progenitor cells and blood glucose levels were measured at 1, 4, 7, 14 and 21 days after traumatic brain injury by flow cytometry and automatic biochemical analysis, respectively. The number of circulating endothelial progenitor cells and blood sugar levels in 37 healthy control subjects were also examined. Compared with controls, the number of circulating endothelial progenitor cells in traumatic brain injury patients was decreased at 1 day after injury, and then increased at 4 days after injury,and reached a peak at 7 days after injury. Compared with controls, blood glucose levels in traumatic brain injury patients peaked at 1 day and then decreased until 7 days and then remained stable. At 1, 4, and 7 days after injury, the number of circulating endothelial progenitor cells was negatively correlated with blood sugar levels(r =-0.147, P < 0.05). Our results verify that hyperglycemia in patients with traumatic brain injury is associated with decreased numbers of circulating endothelial progenitor cells. This study was approved by the Ethical Committee of Tianjin Medical University General Hospital, China(approval No. 200501) in January 2015.展开更多
The aging population is growing rapidly all over the world due to the increase in average life.One of the major challenges associated with an aging population is dementia.Worldwide,it is estimated that by 2050 the num...The aging population is growing rapidly all over the world due to the increase in average life.One of the major challenges associated with an aging population is dementia.Worldwide,it is estimated that by 2050 the number of people with dementia could triple,and dementia not only dramatically changes the lives of those who suffer from it,but it also results in a serious burden for health care systems and caregivers.展开更多
The studies on hepatitis C virus(HCV) infection in prison populations are few and mostly cross-sectional. We analyzed prevalently the articles appearing on Pub Med in the last ten years. HCV infection is frequent in p...The studies on hepatitis C virus(HCV) infection in prison populations are few and mostly cross-sectional. We analyzed prevalently the articles appearing on Pub Med in the last ten years. HCV infection is frequent in prisoners, prevalences ranging from 3.1% to 38% according to the HCV endemicity in the geographical location of the prison and in the countries of origin of the foreign prisoners and to the prevalence of intravenous drug use, which is the most important risk factor for HCV infection, followed by an older age of prisoners and previous prison terms. HCV replication in anti-HCVpositive cases varies from 45% to 90% in different studies, and the most common HCV genotypes are generally 1 and 3. The response to antiviral treatment is similar in prisoners to that of the general population. Unfortunately, treatment is administered less frequently to prisoners because of the difficulties in management and follow-up. The new directly acting antivirals offer a good therapy option for inmates because of their good efficacy, short duration of treatment and low incidence of side effects. The efforts of the prison authorities and medical staff should be focused on reducing the spread of HCV infection in prisons by extending the possibility of follow-up and treatment to more prisoners with chronic hepatitis C.展开更多
AIM:To evaluate steatosis,insulin resistance(IR)and patatin-like phospholipase domain-containing 3(PNPLA3) and their relation to disease progression in hepatitis B and C viruses(HCV-HBV) coinfected patients.METHODS:Th...AIM:To evaluate steatosis,insulin resistance(IR)and patatin-like phospholipase domain-containing 3(PNPLA3) and their relation to disease progression in hepatitis B and C viruses(HCV-HBV) coinfected patients.METHODS:Three hundred and thirty patients with biopsy proven chronic hepatitis were enrolled:66 had HBV-HCV,66 HBV and 198 HCV infection.Prevalence of steatosis,IR and PNPLA3 polymorphisms and their relation to anthropometric,biochemical,virological and histological parameters were evaluated.RESULTS:Prevalence of steatosis in group HBV-HCV was similar to that in HCV(47.0% vs 49.5%,respec-tively);group HBV showed the lowest steatosis(33.3%).Group HBV-HCV had a lesser degree of steatosis than HCV(P = 0.016),lower HCV RNA levels(P = 0.025) and lower prevalence and degree of IR(P = 0.01).PNPLA3 polymorphisms were associated with steatosis.Group HBV-HCV showed higher levels of liver fibrosis than group HCV(P = 0.001),but similar to that ob-served in HBV group.In HBV-HCV group,liver fibrosis was not associated with steatosis,IR or PNPLA3.HBV infection was the independent predictor of advanced liver fibrosis.CONCLUSION:HBV-HCV co-infected patients have lower degree of hepatic steatosis,IR and HCV RNA than HCV mono-infected;co-infected patients showed a more rapid liver fibrosis progression that seems to be due to the double infection and/or HBV dominance.展开更多
BACKGROUND Research on physiopathology of obesity may receive new hints from studies on skinny people(SP). These are individuals who show a poor or null gaining of body weight, in spite of high-calorie intake, by far ...BACKGROUND Research on physiopathology of obesity may receive new hints from studies on skinny people(SP). These are individuals who show a poor or null gaining of body weight, in spite of high-calorie intake, by far exceeding the body requirements.AIM To evaluate how circulating factors present in the SP sera may affect adipogenesis of mesenchymal stromal cells(MSCs).METHODS We isolated MSCs from bone marrow of healthy donors with both normal body mass index(BMI) and caloric consumption. MSC cultures were primed with sera collected from SP or normal people(NP). Then biomolecular assays were performed to evaluate effect on proliferation, apoptosis, senescence, cell commitment, and differentiation.RESULTS SP priming affected adipocyte cell commitment and reduced spontaneous adipogenesis. Moreover, an in-depth analysis of exogenous-induced adipocyte differentiation showed striking differences between differentiation in SP-primed samples compared with NP ones. In adipocytes from SP cultures we observed a reduced size of lipid droplets, an increased expression of adipose triglyceride lipase, along with high mitochondria content and ability to produce ATP in starvation condition. These data and the expression of UCP1 protein, indicated that SP pretreatment produced a bias toward brown adipocyte differentiation.CONCLUSION Our data suggest that sera from SP may promote brown adipogenesis rather that white adipocyte differentiation. This finding could explain why SP present normal body composition in spite of an excess of caloric intake. We hypothesize that some circulating components present in the blood of these individuals may favor brown adipogenesis at expense of white adipocyte production.展开更多
We investigated the relationship between health-related quality of life (HRQOL) and psychological distress in intensive care unit (ICU) survivors 12 months after ICU discharge. The purpose of this study, conducted and...We investigated the relationship between health-related quality of life (HRQOL) and psychological distress in intensive care unit (ICU) survivors 12 months after ICU discharge. The purpose of this study, conducted and completed before the onset of the COVID-19 pandemic, was to find correlations among psychiatric symptoms detected by a screening tool as the General Health Questionnaire-28 (GHQ-28) and the different domains of HRQOL measured with the SF-36 health survey (SF-36), in order to identify ICU survivors with Post-Intensive Care Syndrome (PICS) who need a specific psychiatric intervention to improve their HRQOL. Among 298 ICU survivors who stayed in the ICU for at least 72 hours, 48 patients were enrolled one year after discharge undergoing a clinical interview to assess their functional impairment (Barthel index), mental health (GHQ-28), and health-related quality of life (SF-36). 19% of those subjects had a GHQ-28 ≥ 5 and were identified as “psychiatric cases”, and they were older and experienced a greater impairment in HRQOL. Anxiety, insomnia, and depressive symptoms seemed to be particularly involved in the impairment of HRQOL. A negative correlation between GHQ-28 total scores and subscales and SF-36 subscales was found. Our findings highlighted that psychological distress in ICU survivors may negatively impact physical health recovery and quality of life;conversely, physical impairment and functional disability may trigger the onset of psychiatric symptoms after discharge. The present study is firstly to investigate the correlations between HRQOL and psychological distress in ICU survivors through the GHQ-28, and then affirms the need to carry out follow-up checks for psychiatric symptoms in ICU survivors.展开更多
Three recent articles published in Cell1,2 and Cell Research3 have reported multiple cryo-electron microscopy(cryo-EM)structures of the D1 dopamine receptor(DRD1)bound to either dopamine,various DRD1 agonists,or a pos...Three recent articles published in Cell1,2 and Cell Research3 have reported multiple cryo-electron microscopy(cryo-EM)structures of the D1 dopamine receptor(DRD1)bound to either dopamine,various DRD1 agonists,or a positive allosteric modulator(PAM),while in complex with the active heterotrimeric Gs protein.These studies describe for the first time active-state structures of the DRD1,an exciting advancement in the field that will allow for a better understanding of selective agonist binding,DRD1 activation,G protein selectivity,and the provision of multiple templates to facilitate future drug design and discovery for this important therapeutic target.展开更多
Studies in animal models of epilepsy and pre-surgical patients have unanimously found a strong correlation between high-frequency oscillations(HFOs,>80 Hz)and the epileptogenic zone,suggesting that HFOs can be a po...Studies in animal models of epilepsy and pre-surgical patients have unanimously found a strong correlation between high-frequency oscillations(HFOs,>80 Hz)and the epileptogenic zone,suggesting that HFOs can be a potential biomarker of epileptogenicity and epileptogenesis.This consensus includes the definition and standard detection techniques of HFOs,the localizing value of pathological HFOs for epileptic foci,and different ways to distinguish physiological from epileptic HFOs.The latest clinical applications of HFOs in epilepsy and the related findings are also discussed.HFOs will advance our understanding of the pathophysiology of epilepsy.展开更多
Autophagy in eukaryotic cells is a constitutive process and functions as a homeostatic mechanism; it is up-regulated in response to specific stress stimuli such as starvation, hypoxia and as oxidative stress. In addit...Autophagy in eukaryotic cells is a constitutive process and functions as a homeostatic mechanism; it is up-regulated in response to specific stress stimuli such as starvation, hypoxia and as oxidative stress. In addition to playing a crucial role in adaptive responses to different stimuli, autophagy is also required for intracellular quality control. This second aspect is important to prevent the activation of pathological processes. Autophagy also plays a central role in cellular development and differentiation because it is involved in the regulation of energetic balance. This final aspect is critical for maintaining proper bone and muscle function as well as to prevent any pathological changes. Therefore, identifying new molecular targets involved in autophagy is critical to assure a good quality of life.展开更多
Meta-analyses are often misused and underused in neurology. This editorial provides some comments on the role of meta-analyses in neurological research.Recently, a huge increase in the number of metaanalyses and syste...Meta-analyses are often misused and underused in neurology. This editorial provides some comments on the role of meta-analyses in neurological research.Recently, a huge increase in the number of metaanalyses and systematic reviews has been observed in neurological journals. The major strengths of metaanalyses are the increase of statistical power. However, as for any other investigative tool, meta-analytic research is a research method itself which can produce severe shortcomings. Specifically, the issues of search terms, time periods of published studies, databases used for searching, the definitions of inclusion and exclusion criteria for papers(which greatly affect clinical heterogeneity), publication bias; and the statistical methods used, dramatically influence the results of metaanalyses. The main problem of meta-analyses is that they cannot be expected to overcome the limitations of the studies they include(the so-called "garbage in,garbage out" phenomenon). Furthermore, most systematic reviews in the neurological literature lead to the unsatisfying and clinically frustrating statement "further studies are needed". However it is much more frustrating to see how the gaps in scientific knowledge identified by meta-analyses have not been translated into serious efforts to fill them. Besides their role in evaluating efficacy and tolerability of drugs, meta-analyses may be used to assess diagnostic values of debatable clinical findings, as they represent powerful tools to try to answer questions not posed by individual studies and to settle controversies arising from conflicting claims.展开更多
The anatomical plan of adult muscle innervation is relatively simple： a given muscle comprises several motor units, each constituted by one motor neuron and the muscle fibers that it innervates; moreover, every muscl...The anatomical plan of adult muscle innervation is relatively simple： a given muscle comprises several motor units, each constituted by one motor neuron and the muscle fibers that it innervates; moreover, every muscle fiber is innervated by only one axonal terminal. In other words, motor units have separate, although intermingled, territories of inner- vation （Figure 1D）. In striking contrast, the anatomical organization is different at birth, when every muscle fiber is innervated by several nerve terminals belonging to different motor neurons, a condition known as ＂polyneuronal inner- vation＂, with the consequence that motor units have larger and overlapped territories of innervation （Figure 1A） （Tapia and Lichtman, 2012）. Soon after birth, redundant nerve ter- minals are progressively eliminated in a couple of weeks in rodents, and muscle fibers acquire their mature mononeu- ronal innervation. The same process occurs again in the adult muscle during reinnervation after nerve damage, when a transient period of polyneuronal innervation involves a good fraction of the fibers （Rich and Lichtman, 1989;展开更多
Among multiple sclerosis(MS)susceptibility genes,the strongest non-human leukocyte antigen(HLA)signal in the Italian population maps to the TNFSF14 gene encoding LIGHT,a glycoprotein involved in dendritic cell(DC)matu...Among multiple sclerosis(MS)susceptibility genes,the strongest non-human leukocyte antigen(HLA)signal in the Italian population maps to the TNFSF14 gene encoding LIGHT,a glycoprotein involved in dendritic cell(DC)maturation.Through fine-mapping in a large Italian dataset(4,198 patients with MS and3,903 controls),we show that the TNFSF14 intronic SNP rs1077667 is the primarily MS-associated variant in the region.Expression quantitative trait locus(e QTL)analysis indicates that the MS risk allele is significantly associated with reduced TNFSF14 messenger RNA levels in blood cells,which is consistent with the allelic imbalance in RNA-Seq reads(P<0.0001).The MS risk allele is associated with reduced levels of TNFSF14 gene expression(P<0.01)in blood cells from 84 Italian patients with MS and 80 healthy controls(HCs).Interestingly,patients with MS are lower expressors of TNFSF14 compared to HC(P<0.007).Individuals homozygous for the MS risk allele display an increased percentage of LIGHT-positive peripheral blood myeloid DCs(CD11 c+,P=0.035)in 37 HCs,as well as in in vitro monocyte-derived DCs from 22 HCs(P=0.04).Our findings suggest that the intronic variant rs1077667 alters the expression of TNFSF14 in immune cells,which may play a role in MS pathogenesis.展开更多
Spontaneous light emission from living animals can overcome the investigated light signals in small animal luminescence imaging. Despite autofluorescence emission is well studied the spontaneous luminescence backgroun...Spontaneous light emission from living animals can overcome the investigated light signals in small animal luminescence imaging. Despite autofluorescence emission is well studied the spontaneous luminescence background is less known and its importance is growing due to the new born imaging techniques like Cerenkov Luminescence Imaging and Radionuclide Luminescence Imaging in which faint sources are often involved. In order to investigate the spontaneous emission we studied the background luminescence in vivo from health Nu/Nu mice in optical imaging acquisitions and we related it with the optical properties of the diet of the animals. In particular luminescence images of mice feed with normal diet used in animal facilities were acquired using a commercial optical imager. The intensity and the spectral features of the luminescence emission from the animal surface after sunshine exposition and after normal lighting laboratory conditions were measured. The same was done with the pellets of food used to feed the animals. We found a background emission from the entire animal surface and localized light sources in the abdominal/lumbar region. Their intensity can be modulated by the light exposition of the animals before the imaging session and decreases along the time when they are put in darkness. The comparison of the luminescence time decay of animals and pellets suggests that the light sources are related to the persistent luminescence of the molecules contained in the food. So ambient exposure before imaging is important for luminescence imaging in order to keep down the background. The optical properties of food are also important and it necessary to check them before to feed the animals not only in fluorescence imaging but also in luminescence imaging.展开更多
文摘Hepatitis B virus(HBV) infection has shown an intermediate or high endemicity level in low-income countries over the last five decades. In recent years, however, the incidence of acute hepatitis B and the prevalence of hepatitis B surface antigen chronic carriers have decreased in several countries because of the HBV universal vaccination programs started in the nineties. Some countries, however, are still unable to implement these programs, particularly in their hyperendemic rural areas. The diffusion of HBV infection is still wide in several low-income countries where the prevention, management and treatment of HBV infection are a heavy burden for the governments and healthcare authorities. Of note, the information on the HBV epidemiology is scanty in numerous eastern European and Latin-American countries. The studies on molecular epidemiology performed in some countries provide an important contribution for a more comprehensive knowledge of HBV epidemiology, and phylogenetic studies provide information on the impact of recent and older migratory flows.
文摘A severe spinal cord involvement may rarely occur in patients with cirrhosis and other chronic liver diseases;this complication is usually associated with overt liver failure and surgical or spontaneous porto-systemic shunt.Hepatic myelopathy(HM)is characterized by progressive weakness and spasticity of the lower extremities,while sensory and sphincter disturbances have rarely been described and are usually less important.The diagnosis is assigned in the appropriate clinical setting on clinical grounds after the exclusion of other clinical entities leading to spastic paraparesis.Magnetic resonance imaging is often unremarkable;however,also intracerebral corticospinal tract abnor-malities have been reported recently.The study of motor evoked potentials may disclose central conduction abnormalities even before HM is clinically manifest.HM responds poorly to blood ammonia-lowering and other conservative medical therapy.Liver transplantation represents a potentially definitive treatment for HM in patients with decompensated cirrhosis of Child-Pugh B and C grades.Other surgical treatment options in HM include surgical ligation,shunt reduction,or occlusion by interventional procedures.
文摘Spontaneous intracerebral hemorrhage is a type of stroke associated with poor outcomes. Mortality is elevated, especially in the acute phase. From a pathophysiological point of view the bleeding must traverse different stages dominated by the possibility of re-bleeding, edema, intracranial hypertension, inflammation and neurotoxicity due to blood degradation products, mainly hemoglobin and thrombin. Neurological deterioration and death are common in early hours, so it is a true neurologicalneurosurgical emergency. Time is brain so that action should be taken fast and accurately. The most significant prognostic factors are level of consciousness, location, volume and ventricular extension of the bleeding. Nihilism and early withdrawal of active therapy undoubtedly influence the final result. Although there are no proven therapeutic measures, treatment should be individualized and guided preferably by pathophysiology. The multidisciplinary teamwork is essential. Results of recently completed studies have birth to promising new strategies. For correct management it's important to establish an orderly and systematic strategy based on clinical stabilization, evaluation and establishment of prognosis, avoiding secondary insults and adoption of specific individualized therapies, including hemostatic therapy and intensive control of elevated blood pressure. Uncertainty continues regarding the role of surgery.
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.
基金supported by funding from the National Natural Science Foundation of China(Nos.32220103006 and 82271524)the Intramural Research Program of NIH,National Institute on Aging(Nos.ZIA AG000944 and AG000928).
文摘Alzheimer’s disease(AD)is a progressive neurodegenerative disorder that affects both cognition and non-cognition functions.The disease follows a continuum,starting with preclinical stages,progressing to mild cognitive and behavioral impairment,ultimately leading to dementia.Early detection of AD is crucial for better diagnosis and more effective treatment.However,the current AD diagnostic tests of biomarkers using cerebrospinal fluid and/or brain imaging are invasive or expensive,and mostly are still not able to detect early disease state.Consequently,there is an urgent need to develop new diagnostic techniques with higher sensitivity and specificity during the preclinical stages of AD.Various non-cognitive manifestations,including behavioral abnormalities,sleep disturbances,sensory dysfunctions,and physical changes,have been observed in the preclinical AD stage before occurrence of notable cognitive decline.Recent research advances have identified several biofluid biomarkers as early indicators of AD.This review focuses on these non-cognitive changes and newly discovered biomarkers in AD,specifically addressing the preclinical stages of the disease.Furthermore,it is of importance to explore the potential for developing a predictive system or network to forecast disease onset and progression at the early stage of AD.
基金supported by the National Natural Science Foundation of China,No.30772229(to JNZ),No.81200907(to HJW)the Natural Science Foundation of Tianjin of China,No.12JCQNJC06800(to HJW)+1 种基金the Science and Technology Projects in Key Areas of Traditional Chinese Medicine of Tianjin of China,No.2018001(to ZGW)the Scientific Research Program Project of Tianjin Education Commission of China,No.2018ZD03(to ZGW)
文摘Hyperglycemia reduces the number of circulating endothelial progenitor cells, accelerates their senescence and impairs their function.However, the relationship between blood glucose levels and endothelial progenitor cells in peripheral blood of patients with traumatic brain injury is unclear. In this study, 101 traumatic brain injury patients admitted to the Department of Neurosurgery, Tianjin Medical University General Hospital or the Department of Neurosurgery, Tianjin Huanhu Hospital, China, were enrolled from April 2005 to March 2007. The number of circulating endothelial progenitor cells and blood glucose levels were measured at 1, 4, 7, 14 and 21 days after traumatic brain injury by flow cytometry and automatic biochemical analysis, respectively. The number of circulating endothelial progenitor cells and blood sugar levels in 37 healthy control subjects were also examined. Compared with controls, the number of circulating endothelial progenitor cells in traumatic brain injury patients was decreased at 1 day after injury, and then increased at 4 days after injury,and reached a peak at 7 days after injury. Compared with controls, blood glucose levels in traumatic brain injury patients peaked at 1 day and then decreased until 7 days and then remained stable. At 1, 4, and 7 days after injury, the number of circulating endothelial progenitor cells was negatively correlated with blood sugar levels(r =-0.147, P < 0.05). Our results verify that hyperglycemia in patients with traumatic brain injury is associated with decreased numbers of circulating endothelial progenitor cells. This study was approved by the Ethical Committee of Tianjin Medical University General Hospital, China(approval No. 200501) in January 2015.
文摘The aging population is growing rapidly all over the world due to the increase in average life.One of the major challenges associated with an aging population is dementia.Worldwide,it is estimated that by 2050 the number of people with dementia could triple,and dementia not only dramatically changes the lives of those who suffer from it,but it also results in a serious burden for health care systems and caregivers.
文摘The studies on hepatitis C virus(HCV) infection in prison populations are few and mostly cross-sectional. We analyzed prevalently the articles appearing on Pub Med in the last ten years. HCV infection is frequent in prisoners, prevalences ranging from 3.1% to 38% according to the HCV endemicity in the geographical location of the prison and in the countries of origin of the foreign prisoners and to the prevalence of intravenous drug use, which is the most important risk factor for HCV infection, followed by an older age of prisoners and previous prison terms. HCV replication in anti-HCVpositive cases varies from 45% to 90% in different studies, and the most common HCV genotypes are generally 1 and 3. The response to antiviral treatment is similar in prisoners to that of the general population. Unfortunately, treatment is administered less frequently to prisoners because of the difficulties in management and follow-up. The new directly acting antivirals offer a good therapy option for inmates because of their good efficacy, short duration of treatment and low incidence of side effects. The efforts of the prison authorities and medical staff should be focused on reducing the spread of HCV infection in prisons by extending the possibility of follow-up and treatment to more prisoners with chronic hepatitis C.
基金The Expert Workshop(Liverpool,UK,October 2012),upon which the present manuscript was based,was supported by The Pain Relief Foundation,Liverpool The Great-Britain Sasakawa Foundation Awards ProgrammeBaxter+3 种基金BPLBiotestCSLBehringand Grifols
文摘AIM:To evaluate steatosis,insulin resistance(IR)and patatin-like phospholipase domain-containing 3(PNPLA3) and their relation to disease progression in hepatitis B and C viruses(HCV-HBV) coinfected patients.METHODS:Three hundred and thirty patients with biopsy proven chronic hepatitis were enrolled:66 had HBV-HCV,66 HBV and 198 HCV infection.Prevalence of steatosis,IR and PNPLA3 polymorphisms and their relation to anthropometric,biochemical,virological and histological parameters were evaluated.RESULTS:Prevalence of steatosis in group HBV-HCV was similar to that in HCV(47.0% vs 49.5%,respec-tively);group HBV showed the lowest steatosis(33.3%).Group HBV-HCV had a lesser degree of steatosis than HCV(P = 0.016),lower HCV RNA levels(P = 0.025) and lower prevalence and degree of IR(P = 0.01).PNPLA3 polymorphisms were associated with steatosis.Group HBV-HCV showed higher levels of liver fibrosis than group HCV(P = 0.001),but similar to that ob-served in HBV group.In HBV-HCV group,liver fibrosis was not associated with steatosis,IR or PNPLA3.HBV infection was the independent predictor of advanced liver fibrosis.CONCLUSION:HBV-HCV co-infected patients have lower degree of hepatic steatosis,IR and HCV RNA than HCV mono-infected;co-infected patients showed a more rapid liver fibrosis progression that seems to be due to the double infection and/or HBV dominance.
基金a 2018 Grant of Experimental Medicine Department(Luigi Vanvitelli Campania University)to Umberto Galderisi and Marcellino Monda(partially)
文摘BACKGROUND Research on physiopathology of obesity may receive new hints from studies on skinny people(SP). These are individuals who show a poor or null gaining of body weight, in spite of high-calorie intake, by far exceeding the body requirements.AIM To evaluate how circulating factors present in the SP sera may affect adipogenesis of mesenchymal stromal cells(MSCs).METHODS We isolated MSCs from bone marrow of healthy donors with both normal body mass index(BMI) and caloric consumption. MSC cultures were primed with sera collected from SP or normal people(NP). Then biomolecular assays were performed to evaluate effect on proliferation, apoptosis, senescence, cell commitment, and differentiation.RESULTS SP priming affected adipocyte cell commitment and reduced spontaneous adipogenesis. Moreover, an in-depth analysis of exogenous-induced adipocyte differentiation showed striking differences between differentiation in SP-primed samples compared with NP ones. In adipocytes from SP cultures we observed a reduced size of lipid droplets, an increased expression of adipose triglyceride lipase, along with high mitochondria content and ability to produce ATP in starvation condition. These data and the expression of UCP1 protein, indicated that SP pretreatment produced a bias toward brown adipocyte differentiation.CONCLUSION Our data suggest that sera from SP may promote brown adipogenesis rather that white adipocyte differentiation. This finding could explain why SP present normal body composition in spite of an excess of caloric intake. We hypothesize that some circulating components present in the blood of these individuals may favor brown adipogenesis at expense of white adipocyte production.
文摘We investigated the relationship between health-related quality of life (HRQOL) and psychological distress in intensive care unit (ICU) survivors 12 months after ICU discharge. The purpose of this study, conducted and completed before the onset of the COVID-19 pandemic, was to find correlations among psychiatric symptoms detected by a screening tool as the General Health Questionnaire-28 (GHQ-28) and the different domains of HRQOL measured with the SF-36 health survey (SF-36), in order to identify ICU survivors with Post-Intensive Care Syndrome (PICS) who need a specific psychiatric intervention to improve their HRQOL. Among 298 ICU survivors who stayed in the ICU for at least 72 hours, 48 patients were enrolled one year after discharge undergoing a clinical interview to assess their functional impairment (Barthel index), mental health (GHQ-28), and health-related quality of life (SF-36). 19% of those subjects had a GHQ-28 ≥ 5 and were identified as “psychiatric cases”, and they were older and experienced a greater impairment in HRQOL. Anxiety, insomnia, and depressive symptoms seemed to be particularly involved in the impairment of HRQOL. A negative correlation between GHQ-28 total scores and subscales and SF-36 subscales was found. Our findings highlighted that psychological distress in ICU survivors may negatively impact physical health recovery and quality of life;conversely, physical impairment and functional disability may trigger the onset of psychiatric symptoms after discharge. The present study is firstly to investigate the correlations between HRQOL and psychological distress in ICU survivors through the GHQ-28, and then affirms the need to carry out follow-up checks for psychiatric symptoms in ICU survivors.
基金the Intramural Research Programs of the National Institute of Neurological Disorders(ZIA-NS002263)Stroke and the National Institute on Drug Abuse(Z1A DA000609).
文摘Three recent articles published in Cell1,2 and Cell Research3 have reported multiple cryo-electron microscopy(cryo-EM)structures of the D1 dopamine receptor(DRD1)bound to either dopamine,various DRD1 agonists,or a positive allosteric modulator(PAM),while in complex with the active heterotrimeric Gs protein.These studies describe for the first time active-state structures of the DRD1,an exciting advancement in the field that will allow for a better understanding of selective agonist binding,DRD1 activation,G protein selectivity,and the provision of multiple templates to facilitate future drug design and discovery for this important therapeutic target.
基金the National Key R&D Program(No.2018YFC1314500)the National Natural Science Foundation of China(No.81701297,81801124).
文摘Studies in animal models of epilepsy and pre-surgical patients have unanimously found a strong correlation between high-frequency oscillations(HFOs,>80 Hz)and the epileptogenic zone,suggesting that HFOs can be a potential biomarker of epileptogenicity and epileptogenesis.This consensus includes the definition and standard detection techniques of HFOs,the localizing value of pathological HFOs for epileptic foci,and different ways to distinguish physiological from epileptic HFOs.The latest clinical applications of HFOs in epilepsy and the related findings are also discussed.HFOs will advance our understanding of the pathophysiology of epilepsy.
文摘Autophagy in eukaryotic cells is a constitutive process and functions as a homeostatic mechanism; it is up-regulated in response to specific stress stimuli such as starvation, hypoxia and as oxidative stress. In addition to playing a crucial role in adaptive responses to different stimuli, autophagy is also required for intracellular quality control. This second aspect is important to prevent the activation of pathological processes. Autophagy also plays a central role in cellular development and differentiation because it is involved in the regulation of energetic balance. This final aspect is critical for maintaining proper bone and muscle function as well as to prevent any pathological changes. Therefore, identifying new molecular targets involved in autophagy is critical to assure a good quality of life.
文摘Meta-analyses are often misused and underused in neurology. This editorial provides some comments on the role of meta-analyses in neurological research.Recently, a huge increase in the number of metaanalyses and systematic reviews has been observed in neurological journals. The major strengths of metaanalyses are the increase of statistical power. However, as for any other investigative tool, meta-analytic research is a research method itself which can produce severe shortcomings. Specifically, the issues of search terms, time periods of published studies, databases used for searching, the definitions of inclusion and exclusion criteria for papers(which greatly affect clinical heterogeneity), publication bias; and the statistical methods used, dramatically influence the results of metaanalyses. The main problem of meta-analyses is that they cannot be expected to overcome the limitations of the studies they include(the so-called "garbage in,garbage out" phenomenon). Furthermore, most systematic reviews in the neurological literature lead to the unsatisfying and clinically frustrating statement "further studies are needed". However it is much more frustrating to see how the gaps in scientific knowledge identified by meta-analyses have not been translated into serious efforts to fill them. Besides their role in evaluating efficacy and tolerability of drugs, meta-analyses may be used to assess diagnostic values of debatable clinical findings, as they represent powerful tools to try to answer questions not posed by individual studies and to settle controversies arising from conflicting claims.
文摘The anatomical plan of adult muscle innervation is relatively simple： a given muscle comprises several motor units, each constituted by one motor neuron and the muscle fibers that it innervates; moreover, every muscle fiber is innervated by only one axonal terminal. In other words, motor units have separate, although intermingled, territories of inner- vation （Figure 1D）. In striking contrast, the anatomical organization is different at birth, when every muscle fiber is innervated by several nerve terminals belonging to different motor neurons, a condition known as ＂polyneuronal inner- vation＂, with the consequence that motor units have larger and overlapped territories of innervation （Figure 1A） （Tapia and Lichtman, 2012）. Soon after birth, redundant nerve ter- minals are progressively eliminated in a couple of weeks in rodents, and muscle fibers acquire their mature mononeu- ronal innervation. The same process occurs again in the adult muscle during reinnervation after nerve damage, when a transient period of polyneuronal innervation involves a good fraction of the fibers （Rich and Lichtman, 1989;
基金supported by the Italian Foundation of Multiple Sclerosis(FISM,2011/R/142015/R/10,2019/R-Multi/033)by the Italian Ministry of Health(RF-2016-02361294)the AGING Project for Department of Excellence at the Department of Translational Medicine(DIMET),Universitàdel Piemonte Orientale,Novara,Italy+1 种基金supported by Consorzio Interuniversitario di Biotecnologie(CIB)partially supported by Multiple MS project(Horizon 2020 European Grant 733161),Stockholm。
文摘Among multiple sclerosis(MS)susceptibility genes,the strongest non-human leukocyte antigen(HLA)signal in the Italian population maps to the TNFSF14 gene encoding LIGHT,a glycoprotein involved in dendritic cell(DC)maturation.Through fine-mapping in a large Italian dataset(4,198 patients with MS and3,903 controls),we show that the TNFSF14 intronic SNP rs1077667 is the primarily MS-associated variant in the region.Expression quantitative trait locus(e QTL)analysis indicates that the MS risk allele is significantly associated with reduced TNFSF14 messenger RNA levels in blood cells,which is consistent with the allelic imbalance in RNA-Seq reads(P<0.0001).The MS risk allele is associated with reduced levels of TNFSF14 gene expression(P<0.01)in blood cells from 84 Italian patients with MS and 80 healthy controls(HCs).Interestingly,patients with MS are lower expressors of TNFSF14 compared to HC(P<0.007).Individuals homozygous for the MS risk allele display an increased percentage of LIGHT-positive peripheral blood myeloid DCs(CD11 c+,P=0.035)in 37 HCs,as well as in in vitro monocyte-derived DCs from 22 HCs(P=0.04).Our findings suggest that the intronic variant rs1077667 alters the expression of TNFSF14 in immune cells,which may play a role in MS pathogenesis.
文摘Spontaneous light emission from living animals can overcome the investigated light signals in small animal luminescence imaging. Despite autofluorescence emission is well studied the spontaneous luminescence background is less known and its importance is growing due to the new born imaging techniques like Cerenkov Luminescence Imaging and Radionuclide Luminescence Imaging in which faint sources are often involved. In order to investigate the spontaneous emission we studied the background luminescence in vivo from health Nu/Nu mice in optical imaging acquisitions and we related it with the optical properties of the diet of the animals. In particular luminescence images of mice feed with normal diet used in animal facilities were acquired using a commercial optical imager. The intensity and the spectral features of the luminescence emission from the animal surface after sunshine exposition and after normal lighting laboratory conditions were measured. The same was done with the pellets of food used to feed the animals. We found a background emission from the entire animal surface and localized light sources in the abdominal/lumbar region. Their intensity can be modulated by the light exposition of the animals before the imaging session and decreases along the time when they are put in darkness. The comparison of the luminescence time decay of animals and pellets suggests that the light sources are related to the persistent luminescence of the molecules contained in the food. So ambient exposure before imaging is important for luminescence imaging in order to keep down the background. The optical properties of food are also important and it necessary to check them before to feed the animals not only in fluorescence imaging but also in luminescence imaging.
