Tauopathies are a group of neurodegenerative diseases characterized by abnormal metabolism of the misfolded tau protein. Tau is encoded by the microtubule-associated protein tau gene(MAPT) and can be classified as eit...Tauopathies are a group of neurodegenerative diseases characterized by abnormal metabolism of the misfolded tau protein. Tau is encoded by the microtubule-associated protein tau gene(MAPT) and can be classified as either 3-repeat(3R) or 4-repeat(4R) based on the number of repeat domains from alternative splicing of exon 10 of the MAPT gene.展开更多
Peanut allergy is majorly related to severe food induced allergic reactions.Several food including cow's milk,hen's eggs,soy,wheat,peanuts,tree nuts(walnuts,hazelnuts,almonds,cashews,pecans and pistachios),fis...Peanut allergy is majorly related to severe food induced allergic reactions.Several food including cow's milk,hen's eggs,soy,wheat,peanuts,tree nuts(walnuts,hazelnuts,almonds,cashews,pecans and pistachios),fish and shellfish are responsible for more than 90%of food allergies.Here,we provide promising insights using a large-scale data-driven analysis,comparing the mechanistic feature and biological relevance of different ingredients presents in peanuts,tree nuts(walnuts,almonds,cashews,pecans and pistachios)and soybean.Additionally,we have analysed the chemical compositions of peanuts in different processed form raw,boiled and dry-roasted.Using the data-driven approach we are able to generate new hypotheses to explain why nuclear receptors like the peroxisome proliferator-activated receptors(PPARs)and its isoform and their interaction with dietary lipids may have significant effect on allergic response.The results obtained from this study will direct future experimeantal and clinical studies to understand the role of dietary lipids and PPARisoforms to exert pro-inflammatory or anti-inflammatory functions on cells of the innate immunity and influence antigen presentation to the cells of the adaptive immunity.展开更多
Fracture of the lateral process of the talus(FLPT)is uncommon in clinical practice and can be easily missed or misdiagnosed.In recent years,as researchers from all over the world have further deepened their research o...Fracture of the lateral process of the talus(FLPT)is uncommon in clinical practice and can be easily missed or misdiagnosed.In recent years,as researchers from all over the world have further deepened their research on FLPT,there has been a breakthrough in the classification,and the methods and principles of clinical management have changed accordingly;however,there is still no standardized guideline for the diagnosis and management of FLPT,and there have been few relevant literature review articles related to this kind of fracture in the past at least 5 years.In this article,we review the clinical classification,classification-based therapeutic recommendations,and prognosis of FLPT,with the aim of providing a reference for the clinical diagnosis and management of this infrequent fracture.展开更多
Theword“cancer”is associated with terrifying situations,and there is often an aggressive intent to cure.Uncertainty about survival and fear of disfigurement cause major turmoil in the minds of patients and relatives...Theword“cancer”is associated with terrifying situations,and there is often an aggressive intent to cure.Uncertainty about survival and fear of disfigurement cause major turmoil in the minds of patients and relatives.Teamwork with multimodal care is the key to achieving satisfactory outcomes.Advanced imaging modalities have aided in early detection and derivation of optimal treatment plans.Although radical excision of tumors with neoadjuvant or concurrent chemotherapy/radiotherapy has long been the best management option,we have moved froma radical to a conservative approach.In advanced disease,the plan should be to provide supportive care and improve quality of life.Compassion and counseling play important roles.Nutritional support for correcting cancer cachexia is equally important during tumor excision.Newer therapies such as targeted therapy,stem cell therapy,and chemodynamic therapy are all focused on ensuring safe and efficient outcomes;however,the war against cancer continues to oscillate between hope and despair.展开更多
Objective:To assess the epidemiology of urinary schistosomiasis and soil-transmitted helminthiasis among women of reproductive age in Mwaluphamba,Kwale County,Kenya.Methods:A community-based cross-sectional study desi...Objective:To assess the epidemiology of urinary schistosomiasis and soil-transmitted helminthiasis among women of reproductive age in Mwaluphamba,Kwale County,Kenya.Methods:A community-based cross-sectional study design was employed to randomly sample 422 women of reproductive age(15-<50 years)from four villages in Mwaluphamba location.Stool specimens were collected and examined using the Kato-Katz method,while filtration technique was used to analyze urine specimens.Participants’sociodemographic details were obtained using a standardized questionnaire.Results:Urinary schistosomiasis prevalence was at 4.7%(20/422,95%CI 2.8%-6.9%)while the prevalence of soil-transmitted helminthiasis infection was 4.5%(19/422,95%CI 2.6%-6.7%).The infection intensities of urinary schistosomiasis among the study participants ranged from 1 to 120 eggs/10 mL of urine with median egg count of 18.45 eggs/10 mL.The patients were diagnosed with light infection,of 56.16 egg/gram and 48.48 egg/gram for Trichuris trichiura and hookworms,respectively.Women without latrines had 15.7 times higher risk of having urinary schistosomiasis compared to those with a latrine.Similarly,use of surface water(aOR=1.0,95%CI 0.2-1.4,P=0.010)and crossing the river to go to a place(aOR=1.1,95%CI 0.3-1.6,P=0.009)were statistically significant risk factors for getting urinary schistosomiasis.In bivariable regression analysis,defecating around the water source(OR=4.3,95%CI 1.5-12.9)had a statistically significant association with the prevalence of soil-transmitted helminthiasis(P=0.008).Conclusions:This study has given an insight on the prevalence and intensity of urinary schistosomiasis and soil-transmitted helminthiasis in Mwaluphamba location that form a basis for strengthening the control and elimination programmes for these neglected tropical diseases.展开更多
Biodegradable implants are critical for regenerative orthopaedic procedures,but they may suffer from too fast corrosion in human-body environment.This necessitates the synthesis of a suitable coating that may improve ...Biodegradable implants are critical for regenerative orthopaedic procedures,but they may suffer from too fast corrosion in human-body environment.This necessitates the synthesis of a suitable coating that may improve the corrosion resistance of these implants without compromising their mechanical integrity.In this study,an AZ91 magnesium alloy,as a representative for a biodegradable Mg implant material,was modified with a thin reduced graphene oxide(RGO)-calcium carbonate(CaCO_(3))composite coating.Detailed analytical and in-vitro electrochemical characterization reveals that this coating significantly improves the corrosion resistance and mechanical integrity,and thus has the potential to greatly extend the related application field.展开更多
BACKGROUND Diabetic peripheral neuropathy(DPN)is a common complication of diabetes mellitus and can lead to serious complications.Therapeutic strategies for pain control are available but there are few approaches that...BACKGROUND Diabetic peripheral neuropathy(DPN)is a common complication of diabetes mellitus and can lead to serious complications.Therapeutic strategies for pain control are available but there are few approaches that influence neurological deficits such as numbness.AIM To investigate the effectiveness of acupuncture on improving neurological deficits in patients suffering from type 2 DPN.METHODS The acupuncture in DPN(ACUDPN)study was a two-armed,randomized,controlled,parallel group,open,multicenter clinical trial.Patients were randomized in a 1:1 ratio into two groups:The acupuncture group received 12 acupuncture treatments over 8 wk,and the control group was on a waiting list during the first 16 wk,before it received the same treatment as the other group.Both groups received routine care.Outcome parameters were evaluated after 8,16 and 24 wk and included neurological scores,such as an 11-point numeric rating scale(NRS)11 for hypesthesia,neuropathic pain symptom inventory(NPSI),neuropathy deficit score(NDS),neuropathy symptom score(NSS);nerve conduction studies(NCS)were assessed with a handheld point-of-care device.RESULTSSixty-two participants were included.The NRS for numbness showed a difference of 2.3(P<0.001)in favor of theacupuncture group,the effect persisted until week 16 with a difference of 2.2(P<0.001)between groups and 1.8points at week 24 compared to baseline.The NPSI was improved in the acupuncture group by 12.6 points(P<0.001)at week 8,the NSS score at week 8 with a difference of 1.3(P<0.001);the NDS and the TNSc score improvedfor the acupuncture group in week 8,with a difference of 2.0 points(P<0.001)compared to the control group.Effects were persistent in week 16 with a difference of 1.8 points(P<0.05).The NCS showed no meaningfulchanges.In both groups only minor side effects were reported.CONCLUSION Study results suggest that acupuncture may be beneficial in type 2 diabetic DPN and seems to lead to a reductionin neurological deficits.No serious adverse events were recorded and the adherence to treatment was high.Confirmatory randomized sham-controlled clinical studies with adequate patient numbers are needed to confirmthe results.展开更多
Objectives: The study aimed to determine the most appropriate hearing screening test to identify disabling hearing loss for adults aged 65 years or older.Methods: This study included 577 older adults. Four hearing scr...Objectives: The study aimed to determine the most appropriate hearing screening test to identify disabling hearing loss for adults aged 65 years or older.Methods: This study included 577 older adults. Four hearing screening tests were considered in the study, including the Hearing Handicap Inventory for Elderly Screening(HHIE-s), three single question tests, the whisper test, and the finger rub test. The sensitivity and specificity of these tests referenced to the hearing threshold of disabling hearing loss were estimated.Results: Among all tests, only the single self-perception question(0.7064 for sensitivity;0.7225 for specificity) and whisper test(0.7833 for sensitivity;0.7708 for specificity) could obtain both sensitivity and specificity higher than 70% for adults aged ≥65 years.Conclusion: Overall, we suggest using the whisper test to identify disabling hearing loss(>40 dB HL at the better ear) for adults aged 65 years or older. However, if the conditions do not permit, the single selfperception question is also acceptable. Moreover, HHIE-s might not be a good test to detect disabling hearing loss for adults aged 80 years or older.展开更多
Defects in the endothelial cell barrier accompany diverse malfunctions of the central nervous system such as neurodegenerative diseases,stroke,traumatic brain injury,and systemic diseases such as sepsis,viral and bact...Defects in the endothelial cell barrier accompany diverse malfunctions of the central nervous system such as neurodegenerative diseases,stroke,traumatic brain injury,and systemic diseases such as sepsis,viral and bacterial infections,and cancer.Compromised endothelial sealing leads to leaking blood vessels,followed by vasogenic edema.Brain edema as the most common complication caused by stroke and traumatic brain injury is the leading cause of death.Brain microvascular endothelial cells,together with astrocytes,pericytes,microglia,and neurons form a selective barrier,the so-called blood-brain barrier,which regulates the movement of molecules inside and outside of the brain.Mechanisms that regulate blood-brain barrier permeability in health and disease are complex and not fully understood.Several newly discovered molecules that are involved in the regulation of cellular processes in brain microvascular endothelial cells have been described in the literature in recent years.One of these molecules that are highly expressed in brain microvascular endothelial cells is protocadherin gamma C3.In this review,we discuss recent evidence that protocadherin gamma C3 is a newly identified key player involved in the regulation of vascular barrier function.展开更多
Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse eff...Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse effects of treatment regimens that cause significant morbidity. Pyridoxine is often added to treatment regimens for the prevention and/or treatment of these side effects. The basis and effectiveness of this practice are unclear. We conducted a systematic review to evaluate the effectiveness of pyridoxine in preventing and/or treating neuropathy and neurotoxicity associated with RR-TB treatment. We included studies with patients with RR-TB who experienced neuropathy or neurotoxicity attributed to RR-TB regimens and were given pyridoxine. Our findings showed contradicting evidence on the use of pyridoxine for preventing or treating neurotoxicity due to cycloserine in the treatment of RR-TB. Moreover, pyridoxine did not have a protective effect against neuropathy and/or neurotoxicity caused by other RR-TB regimens that do not contain isoniazid. In conclusion, we found that withdrawing or withholding medications such as linezolid, cycloserine, thioamides, fluoroquinolones, and ethambutol, implicated in causing neuropathy or neurotoxicity was more effective than using pyridoxine to stop the progression of symptoms, and in some instances, led to their reversal over time.展开更多
Background: Pressure measurement in total cavopulmonary connection (TCPC) patients is a domain of cardiaccatheterization. 4D velocity encoded cardiovascular magnetic resonance (4D–flow MRI) offers an alternative fora...Background: Pressure measurement in total cavopulmonary connection (TCPC) patients is a domain of cardiaccatheterization. 4D velocity encoded cardiovascular magnetic resonance (4D–flow MRI) offers an alternative forassessment of even minor pressure differences. The scope of this study was to measure even minor pressure differencesin the anastomosis of TCPC patients, who are clinically uncompromised. Methods: Twenty-four patients(median 15 years [8;34]) with TCPC were studied prospectively by 4D-flow MRI. Pressure differences betweensuperior vena cava (SVC) and extracardiac conduit (C) to both right pulmonary artery (RPA) and left pulmonaryartery (LPA) were assessed. Small fluid obstructions as vortices within the anastomosis were detected by flowpathlines from 4D-flow MRI. In two patients pressure differences were calculated also by computational flowdynamics (CFD) as a plausibility check for the order of magnitude. Results: Median values of pressure differencesin the anastomosis between SVC and RPA were 0.63 (0.21–2.1) mmHg, between C and RPA 0.67 (0.3–2.2)mmHg, between SVC and LPA 0.8 (0.3–2.4) mmHg and between C and LPA 0.7 (0.2–1.9) mmHg. Patients withpotential flow obstruction (stents, occluder, vortices) had significantly higher gradients at the anastomosis (p <0.05) than patients without potential obstructions, although the absolute values were small. CFD- and measurement-based pressure difference showed good agreement. Conclusion: 4D-flow MRI is able to detect minor pressuredifferences within the Fontan circuit even in patients with apparently satisfactory TCPC. Slightly higherpressure differences are due to the presence of small flow obstruction.展开更多
Background:Examine the degree of disability in adult ADHD patients in relation to the core symptoms attention deficits and hyperactivity and concomitant minimal cerebral dysfunctions.Methods:Patients from a psychosoma...Background:Examine the degree of disability in adult ADHD patients in relation to the core symptoms attention deficits and hyperactivity and concomitant minimal cerebral dysfunctions.Methods:Patients from a psychosomatic rehabilitation hospital(N=1,453)had answered the“ADHS-SB(attention deficit hyperactivity scale)”,the“MCD-scale(minimal cerebral dysfunction self rating scale)”,the“SCL-90R(Symptom Checklist)”,and reported about impairment at work.Results:Psychological distress and the ability to work are primarily related to problems of orientation,cognitive impairment,vegetative lability,emotional problems,disorders of motor function,but only to a lesser degree to hyperactivity and attention deficit.Conclusion:When dealing with ADHD patients,clinicians should take into account the full variety of MCD symptoms as these are decisive in regard to participation and problems in life.展开更多
Mineral and bone disorder(MBD)in chronic kidney disease(CKD)is tightly linked to cardiovascular disease(CVD).In this study,we aimed to compare the prognostic value of nine MBD biomarkers to determine those associated ...Mineral and bone disorder(MBD)in chronic kidney disease(CKD)is tightly linked to cardiovascular disease(CVD).In this study,we aimed to compare the prognostic value of nine MBD biomarkers to determine those associated best with adverse cardiovascular(CV)outcomes and mortality.In 5217 participants of the German CKD(GCKD)study enrolled with an estimated glomerular filtration rate(eG FR)between 30–60 mL·min-1 per 1.73 m2 or overt proteinuria,serum osteoprotegerin(OPG),C-terminal fibroblast growth factor-23(FGF23),intact parathyroid hormone(iP TH),bone alkaline phosphatase(BAP),cross-linked C-telopeptide of type 1 collagen(CTX1),procollagen 1intact N-terminal propeptide(P1NP),phosphate,calcium,and 25-OH vitamin D were measured at baseline.Participants with missing values among these parameters(n=971)were excluded,leaving a total of 4246 participants for analysis.During a median follow-up of6.5 years,387 non-CV deaths,173 CV deaths,645 nonfatal major adverse CV events(MACEs)and 368 hospitalizations for congestive heart failure(CHF)were observed.OPG and FGF23 were associated with all outcomes,with the highest hazard ratios(HRs)for OPG.In the final Cox regression model,adjusted for CV risk factors,including kidney function and all other investigated biomarkers,each standard deviation increase in OPG was associated with non-CV death(HR 1.76,95%CI:1.35–2.30),CV death(HR 2.18,95%CI:1.50–3.16),MACE(HR 1.38,95%CI:1.12–1.71)and hospitalization for CHF(HR 2.05,95%CI:1.56–2.69).Out of the nine biomarkers examined,stratification based on serum OPG best identified the CKD patients who were at the highest risk for any adverse CV outcome and mortality.展开更多
Background: The apolipoprotein E (APOE, gene;apoE, protein) ε4 allele is the most commonly identified genetic risk factor for typical late-onset sporadic Alzheimer’s disease (AD). Each APOE ε4 allele roughly triple...Background: The apolipoprotein E (APOE, gene;apoE, protein) ε4 allele is the most commonly identified genetic risk factor for typical late-onset sporadic Alzheimer’s disease (AD). Each APOE ε4 allele roughly triples the relative risk for AD compared to that of the reference allele, APOE ε3. Methods: We have employed hyperspectral fluorescence imaging with an amyloid-specific, conformation-sensing probe, p-FTAA, to elucidate protein aggregate structure and morphology in fresh frozen prefrontal cortex samples from human postmortem AD brain tissue samples from patients homozygous for either APOE ε3 or APOE ε4. Results: As expected APOE ε4/ε4 tissues had a significantly larger load of CAA than APOE ε3/ε3. APOE isoform-dependent morphological differences in amyloid plaques were also observed. Amyloid plaques in APOE ε3/ε3 tissue had small spherical cores and large coronas while amyloid plaques in APOE ε4/ε4 tissues had large irregular and multi-lobulated plaques with relatively smaller coronas. Despite the different morphologies of their cores, the p-FTAA stained APOE ε3/ε3 amyloid plaque cores had spectral properties identical to those of APOE ε4/ε4 plaque cores. Conclusions: These data support the hypothesis that one mechanism by which the APOE ε4 allele affects AD is by modulating the macrostructure of pathological protein deposits in the brain. APOE ε4 is associated with a higher density of amyloid plaques (as compared to APOE ε3). We speculate that multilobulated APOE ε4-associated plaques arise from multiple initiation foci that coalesce as the plaques grow.展开更多
基金supported by the Rainwater Charitable Foundation。
文摘Tauopathies are a group of neurodegenerative diseases characterized by abnormal metabolism of the misfolded tau protein. Tau is encoded by the microtubule-associated protein tau gene(MAPT) and can be classified as either 3-repeat(3R) or 4-repeat(4R) based on the number of repeat domains from alternative splicing of exon 10 of the MAPT gene.
文摘Peanut allergy is majorly related to severe food induced allergic reactions.Several food including cow's milk,hen's eggs,soy,wheat,peanuts,tree nuts(walnuts,hazelnuts,almonds,cashews,pecans and pistachios),fish and shellfish are responsible for more than 90%of food allergies.Here,we provide promising insights using a large-scale data-driven analysis,comparing the mechanistic feature and biological relevance of different ingredients presents in peanuts,tree nuts(walnuts,almonds,cashews,pecans and pistachios)and soybean.Additionally,we have analysed the chemical compositions of peanuts in different processed form raw,boiled and dry-roasted.Using the data-driven approach we are able to generate new hypotheses to explain why nuclear receptors like the peroxisome proliferator-activated receptors(PPARs)and its isoform and their interaction with dietary lipids may have significant effect on allergic response.The results obtained from this study will direct future experimeantal and clinical studies to understand the role of dietary lipids and PPARisoforms to exert pro-inflammatory or anti-inflammatory functions on cells of the innate immunity and influence antigen presentation to the cells of the adaptive immunity.
基金Supported by The China Scholarship Council,No.202308420035.
文摘Fracture of the lateral process of the talus(FLPT)is uncommon in clinical practice and can be easily missed or misdiagnosed.In recent years,as researchers from all over the world have further deepened their research on FLPT,there has been a breakthrough in the classification,and the methods and principles of clinical management have changed accordingly;however,there is still no standardized guideline for the diagnosis and management of FLPT,and there have been few relevant literature review articles related to this kind of fracture in the past at least 5 years.In this article,we review the clinical classification,classification-based therapeutic recommendations,and prognosis of FLPT,with the aim of providing a reference for the clinical diagnosis and management of this infrequent fracture.
文摘Theword“cancer”is associated with terrifying situations,and there is often an aggressive intent to cure.Uncertainty about survival and fear of disfigurement cause major turmoil in the minds of patients and relatives.Teamwork with multimodal care is the key to achieving satisfactory outcomes.Advanced imaging modalities have aided in early detection and derivation of optimal treatment plans.Although radical excision of tumors with neoadjuvant or concurrent chemotherapy/radiotherapy has long been the best management option,we have moved froma radical to a conservative approach.In advanced disease,the plan should be to provide supportive care and improve quality of life.Compassion and counseling play important roles.Nutritional support for correcting cancer cachexia is equally important during tumor excision.Newer therapies such as targeted therapy,stem cell therapy,and chemodynamic therapy are all focused on ensuring safe and efficient outcomes;however,the war against cancer continues to oscillate between hope and despair.
文摘Objective:To assess the epidemiology of urinary schistosomiasis and soil-transmitted helminthiasis among women of reproductive age in Mwaluphamba,Kwale County,Kenya.Methods:A community-based cross-sectional study design was employed to randomly sample 422 women of reproductive age(15-<50 years)from four villages in Mwaluphamba location.Stool specimens were collected and examined using the Kato-Katz method,while filtration technique was used to analyze urine specimens.Participants’sociodemographic details were obtained using a standardized questionnaire.Results:Urinary schistosomiasis prevalence was at 4.7%(20/422,95%CI 2.8%-6.9%)while the prevalence of soil-transmitted helminthiasis infection was 4.5%(19/422,95%CI 2.6%-6.7%).The infection intensities of urinary schistosomiasis among the study participants ranged from 1 to 120 eggs/10 mL of urine with median egg count of 18.45 eggs/10 mL.The patients were diagnosed with light infection,of 56.16 egg/gram and 48.48 egg/gram for Trichuris trichiura and hookworms,respectively.Women without latrines had 15.7 times higher risk of having urinary schistosomiasis compared to those with a latrine.Similarly,use of surface water(aOR=1.0,95%CI 0.2-1.4,P=0.010)and crossing the river to go to a place(aOR=1.1,95%CI 0.3-1.6,P=0.009)were statistically significant risk factors for getting urinary schistosomiasis.In bivariable regression analysis,defecating around the water source(OR=4.3,95%CI 1.5-12.9)had a statistically significant association with the prevalence of soil-transmitted helminthiasis(P=0.008).Conclusions:This study has given an insight on the prevalence and intensity of urinary schistosomiasis and soil-transmitted helminthiasis in Mwaluphamba location that form a basis for strengthening the control and elimination programmes for these neglected tropical diseases.
文摘Biodegradable implants are critical for regenerative orthopaedic procedures,but they may suffer from too fast corrosion in human-body environment.This necessitates the synthesis of a suitable coating that may improve the corrosion resistance of these implants without compromising their mechanical integrity.In this study,an AZ91 magnesium alloy,as a representative for a biodegradable Mg implant material,was modified with a thin reduced graphene oxide(RGO)-calcium carbonate(CaCO_(3))composite coating.Detailed analytical and in-vitro electrochemical characterization reveals that this coating significantly improves the corrosion resistance and mechanical integrity,and thus has the potential to greatly extend the related application field.
文摘BACKGROUND Diabetic peripheral neuropathy(DPN)is a common complication of diabetes mellitus and can lead to serious complications.Therapeutic strategies for pain control are available but there are few approaches that influence neurological deficits such as numbness.AIM To investigate the effectiveness of acupuncture on improving neurological deficits in patients suffering from type 2 DPN.METHODS The acupuncture in DPN(ACUDPN)study was a two-armed,randomized,controlled,parallel group,open,multicenter clinical trial.Patients were randomized in a 1:1 ratio into two groups:The acupuncture group received 12 acupuncture treatments over 8 wk,and the control group was on a waiting list during the first 16 wk,before it received the same treatment as the other group.Both groups received routine care.Outcome parameters were evaluated after 8,16 and 24 wk and included neurological scores,such as an 11-point numeric rating scale(NRS)11 for hypesthesia,neuropathic pain symptom inventory(NPSI),neuropathy deficit score(NDS),neuropathy symptom score(NSS);nerve conduction studies(NCS)were assessed with a handheld point-of-care device.RESULTSSixty-two participants were included.The NRS for numbness showed a difference of 2.3(P<0.001)in favor of theacupuncture group,the effect persisted until week 16 with a difference of 2.2(P<0.001)between groups and 1.8points at week 24 compared to baseline.The NPSI was improved in the acupuncture group by 12.6 points(P<0.001)at week 8,the NSS score at week 8 with a difference of 1.3(P<0.001);the NDS and the TNSc score improvedfor the acupuncture group in week 8,with a difference of 2.0 points(P<0.001)compared to the control group.Effects were persistent in week 16 with a difference of 1.8 points(P<0.05).The NCS showed no meaningfulchanges.In both groups only minor side effects were reported.CONCLUSION Study results suggest that acupuncture may be beneficial in type 2 diabetic DPN and seems to lead to a reductionin neurological deficits.No serious adverse events were recorded and the adherence to treatment was high.Confirmatory randomized sham-controlled clinical studies with adequate patient numbers are needed to confirmthe results.
文摘Objectives: The study aimed to determine the most appropriate hearing screening test to identify disabling hearing loss for adults aged 65 years or older.Methods: This study included 577 older adults. Four hearing screening tests were considered in the study, including the Hearing Handicap Inventory for Elderly Screening(HHIE-s), three single question tests, the whisper test, and the finger rub test. The sensitivity and specificity of these tests referenced to the hearing threshold of disabling hearing loss were estimated.Results: Among all tests, only the single self-perception question(0.7064 for sensitivity;0.7225 for specificity) and whisper test(0.7833 for sensitivity;0.7708 for specificity) could obtain both sensitivity and specificity higher than 70% for adults aged ≥65 years.Conclusion: Overall, we suggest using the whisper test to identify disabling hearing loss(>40 dB HL at the better ear) for adults aged 65 years or older. However, if the conditions do not permit, the single selfperception question is also acceptable. Moreover, HHIE-s might not be a good test to detect disabling hearing loss for adults aged 80 years or older.
文摘Defects in the endothelial cell barrier accompany diverse malfunctions of the central nervous system such as neurodegenerative diseases,stroke,traumatic brain injury,and systemic diseases such as sepsis,viral and bacterial infections,and cancer.Compromised endothelial sealing leads to leaking blood vessels,followed by vasogenic edema.Brain edema as the most common complication caused by stroke and traumatic brain injury is the leading cause of death.Brain microvascular endothelial cells,together with astrocytes,pericytes,microglia,and neurons form a selective barrier,the so-called blood-brain barrier,which regulates the movement of molecules inside and outside of the brain.Mechanisms that regulate blood-brain barrier permeability in health and disease are complex and not fully understood.Several newly discovered molecules that are involved in the regulation of cellular processes in brain microvascular endothelial cells have been described in the literature in recent years.One of these molecules that are highly expressed in brain microvascular endothelial cells is protocadherin gamma C3.In this review,we discuss recent evidence that protocadherin gamma C3 is a newly identified key player involved in the regulation of vascular barrier function.
文摘Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse effects of treatment regimens that cause significant morbidity. Pyridoxine is often added to treatment regimens for the prevention and/or treatment of these side effects. The basis and effectiveness of this practice are unclear. We conducted a systematic review to evaluate the effectiveness of pyridoxine in preventing and/or treating neuropathy and neurotoxicity associated with RR-TB treatment. We included studies with patients with RR-TB who experienced neuropathy or neurotoxicity attributed to RR-TB regimens and were given pyridoxine. Our findings showed contradicting evidence on the use of pyridoxine for preventing or treating neurotoxicity due to cycloserine in the treatment of RR-TB. Moreover, pyridoxine did not have a protective effect against neuropathy and/or neurotoxicity caused by other RR-TB regimens that do not contain isoniazid. In conclusion, we found that withdrawing or withholding medications such as linezolid, cycloserine, thioamides, fluoroquinolones, and ethambutol, implicated in causing neuropathy or neurotoxicity was more effective than using pyridoxine to stop the progression of symptoms, and in some instances, led to their reversal over time.
基金This work was supported by Deutsche Herzstiftung e.V.
文摘Background: Pressure measurement in total cavopulmonary connection (TCPC) patients is a domain of cardiaccatheterization. 4D velocity encoded cardiovascular magnetic resonance (4D–flow MRI) offers an alternative forassessment of even minor pressure differences. The scope of this study was to measure even minor pressure differencesin the anastomosis of TCPC patients, who are clinically uncompromised. Methods: Twenty-four patients(median 15 years [8;34]) with TCPC were studied prospectively by 4D-flow MRI. Pressure differences betweensuperior vena cava (SVC) and extracardiac conduit (C) to both right pulmonary artery (RPA) and left pulmonaryartery (LPA) were assessed. Small fluid obstructions as vortices within the anastomosis were detected by flowpathlines from 4D-flow MRI. In two patients pressure differences were calculated also by computational flowdynamics (CFD) as a plausibility check for the order of magnitude. Results: Median values of pressure differencesin the anastomosis between SVC and RPA were 0.63 (0.21–2.1) mmHg, between C and RPA 0.67 (0.3–2.2)mmHg, between SVC and LPA 0.8 (0.3–2.4) mmHg and between C and LPA 0.7 (0.2–1.9) mmHg. Patients withpotential flow obstruction (stents, occluder, vortices) had significantly higher gradients at the anastomosis (p <0.05) than patients without potential obstructions, although the absolute values were small. CFD- and measurement-based pressure difference showed good agreement. Conclusion: 4D-flow MRI is able to detect minor pressuredifferences within the Fontan circuit even in patients with apparently satisfactory TCPC. Slightly higherpressure differences are due to the presence of small flow obstruction.
文摘Background:Examine the degree of disability in adult ADHD patients in relation to the core symptoms attention deficits and hyperactivity and concomitant minimal cerebral dysfunctions.Methods:Patients from a psychosomatic rehabilitation hospital(N=1,453)had answered the“ADHS-SB(attention deficit hyperactivity scale)”,the“MCD-scale(minimal cerebral dysfunction self rating scale)”,the“SCL-90R(Symptom Checklist)”,and reported about impairment at work.Results:Psychological distress and the ability to work are primarily related to problems of orientation,cognitive impairment,vegetative lability,emotional problems,disorders of motor function,but only to a lesser degree to hyperactivity and attention deficit.Conclusion:When dealing with ADHD patients,clinicians should take into account the full variety of MCD symptoms as these are decisive in regard to participation and problems in life.
基金supported by grants from the Federal Ministry of Education and Research(Bundesministerium für Bildung und ForschungBMBF+7 种基金www.bmbf.deFKZ 01ER 0804,01ER 0818,01ER 0819,01ER 0820,and 01ER 0821)the Foundation for Preventive Medicine of the KfH(Kuratorium für Heimdialyze und Nierentransplantation e.V.-Stiftung Praventivmedizin),and corporate sponsorsfurther supported by the German Research Foundation(SFB/TRR219 project C1—Project-ID 322900939)supported by the clinician scientist program of the German Society of Internal Medicine(DGIM)the Else Kr?ner-FreseniusStiftung Excellence Fellowship(2022_EKES.03)supported by a clinician scientist position funded by the German Research Council(DFG)within the clinical research unit 344(CRU344)supported by BMBF within the framework of the e:Med research and funding concept(grant 01ZX1912B)。
文摘Mineral and bone disorder(MBD)in chronic kidney disease(CKD)is tightly linked to cardiovascular disease(CVD).In this study,we aimed to compare the prognostic value of nine MBD biomarkers to determine those associated best with adverse cardiovascular(CV)outcomes and mortality.In 5217 participants of the German CKD(GCKD)study enrolled with an estimated glomerular filtration rate(eG FR)between 30–60 mL·min-1 per 1.73 m2 or overt proteinuria,serum osteoprotegerin(OPG),C-terminal fibroblast growth factor-23(FGF23),intact parathyroid hormone(iP TH),bone alkaline phosphatase(BAP),cross-linked C-telopeptide of type 1 collagen(CTX1),procollagen 1intact N-terminal propeptide(P1NP),phosphate,calcium,and 25-OH vitamin D were measured at baseline.Participants with missing values among these parameters(n=971)were excluded,leaving a total of 4246 participants for analysis.During a median follow-up of6.5 years,387 non-CV deaths,173 CV deaths,645 nonfatal major adverse CV events(MACEs)and 368 hospitalizations for congestive heart failure(CHF)were observed.OPG and FGF23 were associated with all outcomes,with the highest hazard ratios(HRs)for OPG.In the final Cox regression model,adjusted for CV risk factors,including kidney function and all other investigated biomarkers,each standard deviation increase in OPG was associated with non-CV death(HR 1.76,95%CI:1.35–2.30),CV death(HR 2.18,95%CI:1.50–3.16),MACE(HR 1.38,95%CI:1.12–1.71)and hospitalization for CHF(HR 2.05,95%CI:1.56–2.69).Out of the nine biomarkers examined,stratification based on serum OPG best identified the CKD patients who were at the highest risk for any adverse CV outcome and mortality.
文摘Background: The apolipoprotein E (APOE, gene;apoE, protein) ε4 allele is the most commonly identified genetic risk factor for typical late-onset sporadic Alzheimer’s disease (AD). Each APOE ε4 allele roughly triples the relative risk for AD compared to that of the reference allele, APOE ε3. Methods: We have employed hyperspectral fluorescence imaging with an amyloid-specific, conformation-sensing probe, p-FTAA, to elucidate protein aggregate structure and morphology in fresh frozen prefrontal cortex samples from human postmortem AD brain tissue samples from patients homozygous for either APOE ε3 or APOE ε4. Results: As expected APOE ε4/ε4 tissues had a significantly larger load of CAA than APOE ε3/ε3. APOE isoform-dependent morphological differences in amyloid plaques were also observed. Amyloid plaques in APOE ε3/ε3 tissue had small spherical cores and large coronas while amyloid plaques in APOE ε4/ε4 tissues had large irregular and multi-lobulated plaques with relatively smaller coronas. Despite the different morphologies of their cores, the p-FTAA stained APOE ε3/ε3 amyloid plaque cores had spectral properties identical to those of APOE ε4/ε4 plaque cores. Conclusions: These data support the hypothesis that one mechanism by which the APOE ε4 allele affects AD is by modulating the macrostructure of pathological protein deposits in the brain. APOE ε4 is associated with a higher density of amyloid plaques (as compared to APOE ε3). We speculate that multilobulated APOE ε4-associated plaques arise from multiple initiation foci that coalesce as the plaques grow.
基金supported by the National key Research and Development Program of China (2019YFC1709500)the National Collaboration Project of Critical Illness by Integrating Chinese Medicine and Western Medicine+8 种基金the Project of Heilongjiang Province Innovation Team “Tou Yan”the Yi-Xun Liu and Xiao-Ke Wu Academician Workstationthe Innovation Team of Reproductive Technique with Integrative Chinese Medicine and Western Medicine in Xuzhou City, ChinaHeilongjiang University of Chinese Medicine from the National Clinical Trial BaseHeilongjiang Provincial Clinical Research Center for Ovary Diseasesthe Research Grant Council (T13-602/21-N, C5045-20EF, and 14122021)Food and Health Bureau in Hong Kong, China (06171026)supported by a National Health and Medical Research Council (NHMRC) Investigator grant (GNT1176437)travel support from Merck.