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
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
BACKGROUND Early diagnosis is key to prevent bowel damage in inflammatory bowel disease(IBD).Risk factor analyses linked with delayed diagnosis in European IBD patients are scarce and no data in German IBD patients ex...BACKGROUND Early diagnosis is key to prevent bowel damage in inflammatory bowel disease(IBD).Risk factor analyses linked with delayed diagnosis in European IBD patients are scarce and no data in German IBD patients exists.AIM To identify risk factors leading to prolonged diagnostic time in a German IBD cohort.METHODS Between 2012 and 2022,430 IBD patients from four Berlin hospitals were enrolled in a prospective study and asked to complete a 16-item questionnaire to determine features of the path leading to IBD diagnosis.Total diagnostic time was defined as the time from symptom onset to consulting a physician(patient waiting time)and from first consultation to IBD diagnosis(physician diagnostic time).Univariate and multivariate analyses were performed to identify risk factors for each time period.RESULTS The total diagnostic time was significantly longer in Crohn’s disease(CD)compared to ulcerative colitis(UC)patients(12.0 vs 4.0 mo;P<0.001),mainly due to increased physician diagnostic time(5.5 vs 1.0 mo;P<0.001).In a multivariate analysis,the predominant symptoms diarrhea(P=0.012)and skin lesions(P=0.028)as well as performed gastroscopy(P=0.042)were associated with longer physician diagnostic time in CD patients.In UC,fever was correlated(P=0.020)with shorter physician diagnostic time,while fatigue(P=0.011)and positive family history(P=0.046)were correlated with longer physician diagnostic time.CONCLUSION We demonstrated that CD patients compared to UC are at risk of long diagnostic delay.Future efforts should focus on shortening the diagnostic delay for a better outcome in these patients.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
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
The advent of the big data era has provided many types of transportation datasets,such as metro smart card data,for studying residents’mobility and understanding how their mobility has been shaped and is shaping the ...The advent of the big data era has provided many types of transportation datasets,such as metro smart card data,for studying residents’mobility and understanding how their mobility has been shaped and is shaping the urban space.In this paper,we use metro smart card data from two Chinese metropolises,Shanghai and Shenzhen.Five metro mobility indicators are introduced,and association rules are established to explore the mobility patterns.The proportion of people entering and exiting the station is used to measure the jobs-housing balance.It is found that the average travel distance and duration of Shanghai passengers are higher than those of Shenzhen,and the proportion of metro commuters in Shanghai is higher than that of Shenzhen.The jobs-housing spatial relationship in Shenzhen based on metro travel is more balanced than that in Shanghai.The fundamental reason for the differences between the two cities is the difference in urban morphology.Compared with the monocentric structure of Shanghai,the polycentric structure of Shenzhen results in more scattered travel hotspots and more diverse travel routes,which helps Shenzhen to have a better jobs-housing balance.This paper fills a gap in comparative research among Chinese cities based on transportation big data analysis.The results provide support for planning metro routes,adjusting urban structure and land use to form a more reasonable metro network,and balancing the jobs-housing spatial relationship.展开更多
Background:Osteosarcoma is the most common malignant primary bone tumor.The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy.Moreover,current treatment reg...Background:Osteosarcoma is the most common malignant primary bone tumor.The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy.Moreover,current treatment regimens bear a significant risk of serious side effects.Thus,there is an unmet clinical need for effective therapies with improved safety profiles.Taurolidine is an antibacterial agent that has been shown to induce cell death in different types of cancer cell lines.Methods:In this study,we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma.K7M2 murine osteosarcoma cells were injected,both intramuscular and intraperitoneal,into 60 BALB/c mice on day zero.Animals were then randomized to receive treatment with taurolidine 2%(800 mg/kg),taurolidine 1%(400 mg/kg),or NaCl 0.9%control for seven days by intravenous or intraperitoneal administration.Results:After 35 days,mice were euthanized,and the tumors were harvested for analysis.Eighteen mice were excluded from the analysis due to complications.Body weight was significantly lower in the 2%taurolidine intraperitoneal treatment group from day 9 to 21,consistent with elevated mortality in this group.Intraperitoneal tumor weight was significantly lower in the 1%(p=0.003)and 2%(p=0.006)intraperitoneal taurolidine treatment groups compared to the control.No antineoplastic effects were observed on intramuscular tumors or for intravenous administration of taurolidine.There were no significant differences in microvessel density or mitotic rate between treatment groups.Reduced body weight and elevated mortality in the 2%taurolidine intraperitoneal group suggest that the lower 1%dose is preferable.Conclusions:In conclusion,there is no evidence of antiangiogenic activity,and the antitumor effects of taurolidine on osteosarcoma observed in this study are limited.Moreover,its toxic profile grants further evaluation.Given these observations,further research is necessary to refine the use of taurolidine in osteosarcoma treatment.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
Among the adult population in St. Vincent and the Grenadines (SVG), there is a marked prevalence of diabetes and hypertension;diseases that pose significant public health, and socio-economic challenges, This awareness...Among the adult population in St. Vincent and the Grenadines (SVG), there is a marked prevalence of diabetes and hypertension;diseases that pose significant public health, and socio-economic challenges, This awareness raised concerns about the prevalence of the diseases among the youth population, and motivated the SVG Retired Nurses Association (SVGRNA) to collaborate with the Mustique Charitable Trust (MCT) to conduct the “Be Healthy: Know Your Numbers” research project among college-age students. The tri-fold purpose of the project was to determine the prevalence of high blood pressure and blood sugar levels among the college-aged population in Savageries, the awareness of the youths about the causal factors of the diseases, and encourage healthy lifestyle among the demographic. For this mixed-method research project, both quantitative and qualitative data were gathered from a sample of 851 students;306 were males and 545 were females. The results revealed that a significantly high number of students were diabetic and hypertensive, or were at high risk of getting the diseases on account of their poor dietary and lifestyle practices. The highest readings for both diseases were seen among the males. At the onset of the research, the students were largely apathetic toward the diseases. However, there was noticeable attitudinal change, and demonstrable willingness to make the needed lifestyle changes. The study concluded that mitigating the risks of hypertension and diabetes within the youth community in St. Vincent and the Grenadines will be achieved through education about the causal factors and implications of the diseases, as well as through targeted interventions delivered by a wide cross-section of stakeholders.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
The gallbladder(GB)is a susceptible organ,prone to various pathologies that can be identified using different imaging techniques.Transabdominal ultrasound(TUS)is typically the initial diagnostic method due to its nume...The gallbladder(GB)is a susceptible organ,prone to various pathologies that can be identified using different imaging techniques.Transabdominal ultrasound(TUS)is typically the initial diagnostic method due to its numerous well-established advantages.However,in cases of uncertainty or when a definitive diagnosis cannot be established,computed tomography(CT)or magnetic resonance imaging may be employed to provide more detailed information.Nevertheless,CT scans may sometimes offer inadequate spatial resolution,which can limit the differentiation of GB lesions,particularly when smaller yet clinically relevant abnormalities are involved.Conversely,endoscopic ultrasound(EUS)provides higher frequency compared to TUS,superior spatial resolution,and the option for contrast-enhanced harmonic imaging,enabling a more comprehensive examination.Thus,EUS can serve as a supplementary tool when conventional imaging methods are insufficient.This review will describe the standard EUS examination of the GB,focusing on its endosonographic characteristics in various GB path-ologies.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
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
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
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
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
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 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BACKGROUND Early diagnosis is key to prevent bowel damage in inflammatory bowel disease(IBD).Risk factor analyses linked with delayed diagnosis in European IBD patients are scarce and no data in German IBD patients exists.AIM To identify risk factors leading to prolonged diagnostic time in a German IBD cohort.METHODS Between 2012 and 2022,430 IBD patients from four Berlin hospitals were enrolled in a prospective study and asked to complete a 16-item questionnaire to determine features of the path leading to IBD diagnosis.Total diagnostic time was defined as the time from symptom onset to consulting a physician(patient waiting time)and from first consultation to IBD diagnosis(physician diagnostic time).Univariate and multivariate analyses were performed to identify risk factors for each time period.RESULTS The total diagnostic time was significantly longer in Crohn’s disease(CD)compared to ulcerative colitis(UC)patients(12.0 vs 4.0 mo;P<0.001),mainly due to increased physician diagnostic time(5.5 vs 1.0 mo;P<0.001).In a multivariate analysis,the predominant symptoms diarrhea(P=0.012)and skin lesions(P=0.028)as well as performed gastroscopy(P=0.042)were associated with longer physician diagnostic time in CD patients.In UC,fever was correlated(P=0.020)with shorter physician diagnostic time,while fatigue(P=0.011)and positive family history(P=0.046)were correlated with longer physician diagnostic time.CONCLUSION We demonstrated that CD patients compared to UC are at risk of long diagnostic delay.Future efforts should focus on shortening the diagnostic delay for a better outcome in these patients.
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.
基金National Key R&D Program of China(No.2019YFB2103102)Hong Kong Polytechnic University(No.CD06,P0042540)。
文摘The advent of the big data era has provided many types of transportation datasets,such as metro smart card data,for studying residents’mobility and understanding how their mobility has been shaped and is shaping the urban space.In this paper,we use metro smart card data from two Chinese metropolises,Shanghai and Shenzhen.Five metro mobility indicators are introduced,and association rules are established to explore the mobility patterns.The proportion of people entering and exiting the station is used to measure the jobs-housing balance.It is found that the average travel distance and duration of Shanghai passengers are higher than those of Shenzhen,and the proportion of metro commuters in Shanghai is higher than that of Shenzhen.The jobs-housing spatial relationship in Shenzhen based on metro travel is more balanced than that in Shanghai.The fundamental reason for the differences between the two cities is the difference in urban morphology.Compared with the monocentric structure of Shanghai,the polycentric structure of Shenzhen results in more scattered travel hotspots and more diverse travel routes,which helps Shenzhen to have a better jobs-housing balance.This paper fills a gap in comparative research among Chinese cities based on transportation big data analysis.The results provide support for planning metro routes,adjusting urban structure and land use to form a more reasonable metro network,and balancing the jobs-housing spatial relationship.
文摘Background:Osteosarcoma is the most common malignant primary bone tumor.The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy.Moreover,current treatment regimens bear a significant risk of serious side effects.Thus,there is an unmet clinical need for effective therapies with improved safety profiles.Taurolidine is an antibacterial agent that has been shown to induce cell death in different types of cancer cell lines.Methods:In this study,we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma.K7M2 murine osteosarcoma cells were injected,both intramuscular and intraperitoneal,into 60 BALB/c mice on day zero.Animals were then randomized to receive treatment with taurolidine 2%(800 mg/kg),taurolidine 1%(400 mg/kg),or NaCl 0.9%control for seven days by intravenous or intraperitoneal administration.Results:After 35 days,mice were euthanized,and the tumors were harvested for analysis.Eighteen mice were excluded from the analysis due to complications.Body weight was significantly lower in the 2%taurolidine intraperitoneal treatment group from day 9 to 21,consistent with elevated mortality in this group.Intraperitoneal tumor weight was significantly lower in the 1%(p=0.003)and 2%(p=0.006)intraperitoneal taurolidine treatment groups compared to the control.No antineoplastic effects were observed on intramuscular tumors or for intravenous administration of taurolidine.There were no significant differences in microvessel density or mitotic rate between treatment groups.Reduced body weight and elevated mortality in the 2%taurolidine intraperitoneal group suggest that the lower 1%dose is preferable.Conclusions:In conclusion,there is no evidence of antiangiogenic activity,and the antitumor effects of taurolidine on osteosarcoma observed in this study are limited.Moreover,its toxic profile grants further evaluation.Given these observations,further research is necessary to refine the use of taurolidine in osteosarcoma treatment.
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Among the adult population in St. Vincent and the Grenadines (SVG), there is a marked prevalence of diabetes and hypertension;diseases that pose significant public health, and socio-economic challenges, This awareness raised concerns about the prevalence of the diseases among the youth population, and motivated the SVG Retired Nurses Association (SVGRNA) to collaborate with the Mustique Charitable Trust (MCT) to conduct the “Be Healthy: Know Your Numbers” research project among college-age students. The tri-fold purpose of the project was to determine the prevalence of high blood pressure and blood sugar levels among the college-aged population in Savageries, the awareness of the youths about the causal factors of the diseases, and encourage healthy lifestyle among the demographic. For this mixed-method research project, both quantitative and qualitative data were gathered from a sample of 851 students;306 were males and 545 were females. The results revealed that a significantly high number of students were diabetic and hypertensive, or were at high risk of getting the diseases on account of their poor dietary and lifestyle practices. The highest readings for both diseases were seen among the males. At the onset of the research, the students were largely apathetic toward the diseases. However, there was noticeable attitudinal change, and demonstrable willingness to make the needed lifestyle changes. The study concluded that mitigating the risks of hypertension and diabetes within the youth community in St. Vincent and the Grenadines will be achieved through education about the causal factors and implications of the diseases, as well as through targeted interventions delivered by a wide cross-section of stakeholders.
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The gallbladder(GB)is a susceptible organ,prone to various pathologies that can be identified using different imaging techniques.Transabdominal ultrasound(TUS)is typically the initial diagnostic method due to its numerous well-established advantages.However,in cases of uncertainty or when a definitive diagnosis cannot be established,computed tomography(CT)or magnetic resonance imaging may be employed to provide more detailed information.Nevertheless,CT scans may sometimes offer inadequate spatial resolution,which can limit the differentiation of GB lesions,particularly when smaller yet clinically relevant abnormalities are involved.Conversely,endoscopic ultrasound(EUS)provides higher frequency compared to TUS,superior spatial resolution,and the option for contrast-enhanced harmonic imaging,enabling a more comprehensive examination.Thus,EUS can serve as a supplementary tool when conventional imaging methods are insufficient.This review will describe the standard EUS examination of the GB,focusing on its endosonographic characteristics in various GB path-ologies.
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.
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.
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.
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.
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.
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.