Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°C.We aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large cohort.Plasma samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline project.These samples were stored at-80°C for up to 6 years before being used in this study.Our results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage time.However,the level of total tau showed a negative correlation with sample storage time.Notably,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage time.This was not observed in individuals with cognitive impairment.Consequently,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage time.Therefore,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's disease.Furthermore,in cohort studies,it is important to consider the impact of storage time on the overall results.

Unraveling brain aging through the lens of oral microbiota

The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

Cognitive impairment in cerebral small vessel disease induced by hypertension

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

SLC6A14 promotes ulcerative colitis progression by facilitating NLRP3 inflammasome-mediated pyroptosis

BACKGROUND Ulcerative colitis(UC)is an inflammatory condition with frequent relapse and recurrence.Evidence suggests the involvement of SLC6A14 in UC pathogenesis,but the central regulator remains unknown.AIM To explore the role of SLC6A14 in UC-associated pyroptosis.METHODS Quantitative real-time polymerase chain reaction(qRT-PCR),immunoblotting,and immunohistochemical were used to assess SLC6A14 in human UC tissues.Lipopolysaccharide(LPS)was used to induce inflammation in FHC and NCM460 cells and model enteritis,and SLC6A14 levels were assessed.Pyroptosis markers were quantified using enzyme-linked immunosorbent assay,Western blotting,and qRT-PCR,and EdU incubation,CCK-8 assays and flow cytometry were used to examine proliferation and apoptosis.Mouse models of UC were used for verification.RESULTS SLC6A14 was increased and correlated with NLRP3 in UC tissues.LPS-induced FHC and NCM460 cells showed increased SLC6A14 levels.Reducing SLC6A14 increased cell proliferation and suppressed apoptosis.Reducing SLC6A14 decreased pyroptosis-associated proteins(ASC,IL-1β,IL-18,NLRP3).NLRP3 overexpression counteracted the effects of sh-SLC6A14 on LPS-induced FHC and NCM460 cell pyroptosis.SLC6A14 improved the mucosa in mice with dextran sulfate sodium-induced colitis.CONCLUSION SLC6A14 promotes UC pyroptosis by regulating NLRP3,suggesting the therapeutic potential of modulating the SLC6A14/NLRP3 axis.

Network analysis of the relationships between depressive symptoms and social participation activities among Chinese older adults and its implications for nursing

Objective:Network analysis was used to explore the complex inter-relationships between social participation activities and depressive symptoms among the Chinese older population,and the differences in network structures among different genders,age groups,and urban-rural residency would be compared.Methods:Based on the 2018 wave of the Chinese Longitudinal Healthy Longevity Survey(CLHLS),12,043 people aged 65 to 105 were included.The 10-item Center for Epidemiologic Studies Depression(CESD)Scale was used to assess depressive symptoms and 10 types of social participation activities were collected,including housework,tai-chi,square dancing,visiting and interacting with friends,garden work,reading newspapers or books,raising domestic animals,playing cards or mahjong,watching TV or listening to radio,and organized social activities.R 4.2.1 software was used to estimate the network model and calculate strength and bridge strength.Results:21.60%(2,601/12,043)of the participants had depressive symptoms.The total social participation score was negatively associated with depressive symptoms after adjusting for sociodemographic factors.The network of social participation and depressive symptoms showed that“D9(Inability to get going)”and“S9(Watching TV and/or listening to the radio)”had the highest strength within depressive symptoms and social participation communities,respectively,and“S1(Housework)”,“S9(Watching TV and/or listening to the radio)”,and“D5(Hopelessness)”were the most prominent bridging nodes between the two communities.Most edges linking the two communities were negative.“S5(Graden work)-D5(Hopelessness)”and“S6(Reading newspapers/books)-D4(Everything was an effort)”were the top 2 strongest negative edges.Older females had significantly denser network structures than older males.Compared to older people aged 65e80,the age group 81e105 showed higher network global strength.Conclusions:This study provides novel insights into the complex relationships between social participation and depressive symptoms.Except for doing housework,other social participation activities were found to be protective for depression levels.Different nursing strategies should be taken to prevent and alleviate depressive symptoms for different genders and older people of different ages.

Outcomes of surgical correction of Peyronie’s disease with plaque excision and grafting: Comparison of testicular tunica vaginalis graft versus bovine pericardium graft

Objective:Peyronie’s disease(PD)is an abnormal wound healing in the penile tunica albuginea.After fibrotic plaque excision,different graft materials have been used to repair the defects,but the optimal graft remains unknown.This study aimed to compare the functional outcomes of testicular tunica vaginalis grafts and bovine pericardium grafts in patients with severe PD.Methods:A retrospective comparative study was conducted on 33 PD patients undergoing partial plaque excision and grafting from September 2015 to May 2021.The patients were divided into two groups depending on the type of graft used.For 15 patients in Group B,testicular tunica vaginalis grafts were used to repair the defect,while for 18 patients in Group A,bovine pericardium grafts were used.Data of the patient’s age,comorbidities,sexual function,penile curvature,postoperative complications,need for further treatment,change in penile length,and satisfaction were gathered and compared between the groups.Sexual function was evaluated using the 5-item version of the International Index of Erectile Function(IIEF-5),and a functional less than 20-degree penile curvature after surgery was considered a successful intervention.Results:There was no difference in age,comorbidities,degree of curvature,perioperative IIEF-5,operative time,plaque size,or complication rates.After surgery,a statistically significant improvement in curvature degree(p<0.05)and satisfactory penile appearance(p<0.05)were seen in both groups without any superiority between the two groups(p=0.423 and p=0.840,respectively).With a 30-month follow-up,the IIEF-5 was consistent in both groups,with no statistical significance between the groups(p=0.492).The main change in penile length during the operation was increased and still positive in the last follow-up in both groups without statistical significance(p=0.255 and p=0.101,respectively).Conclusion:Partial plaque excision and corporoplasty with both testicular tunica vaginalis or bovine pericardium grafts are equally effective in treating males with clinically significant PD.

Multimodal comparison of plasma proteins associated with blood-brain barrier impairment in Alzheimer’s disease

Background:Vascular impairment is one of the major contributors to dementia.We aimed to identify blood biomarkers suggestive of potential impairment of the blood-brain barrier(BBB)in subjects with Alzheimer’s disease(AD).Methods:We used administrative data from the VA Informatics and Computing Infrastructure Resource Center to study both inpatients and outpatients with AD.Plasma samples from healthy control and AD individuals were analyzed using enzyme-linked immunosorbent assay and proteomics approaches to identify differentially expressed proteins.Bioinformatic analysis was applied to explore significantly enriched pathways.Results:In the same cohort of patients with AD,we found twice number of subjects with cerebral amyloid angiopathy in the two-year period after the onset of AD,compared to the number of subjects with cerebral amyloid angiopathy in the two-year period prior to AD onset.Different pathways related to BBB,like cell adhesion,extracellular matrix organization and Wnt signaling,were activated and differentially expressed proteins such as ADAM22,PDGFR-α,DKK-4,Neucrin and RSOP-1 were identified.Moreover,matrix metalloproteinase-9,which is implicated in causing degradation of basal lamina and BBB disruption,was significantly increased in the plasma of AD patients.Conclusions:Alteration of proteins found in AD subjects could provide new insights into biomarkers regulating permeability and BBB integrity.

Associations of accelerometry-measured and self-reported physical activity and sedentary behavior with skeletal muscle energetics:The Study of Muscle,Mobility and Aging(SOMMA)

Background:Skeletal muscle energetics decline with age,and physical activity(PA)has been shown to offset these declines in older adults.Yet,many studies reporting these effects were based on self-reported PA or structured exercise interventions.Therefore,we examined the associations of accelerometry-measured and self-reported PA and sedentary behavior(SB)with skeletal muscle energetics and explored the extent to which PA and sedentary behavior would attenuate the associations of age with muscle energetics.Methods:As part of the Study of Muscle,Mobility and Aging,enrolled older adults(n=879),810(age=76.4±5.0 years old,mean±SD;58%women)had maximal muscle oxidative capacity measured ex vivo via high-resolution re spirometry of permeabilized myofibers(maximal oxidative phosphorylation(maxOXPHOS))and in vivo by ^(31)phosphorus magnetic resonance spectroscopy(maximal adenosine triphosphate(ATP_(max))).Accelerometry-measured sedentary behavior,light activity,and moderate-to-vigorous PA(MVPA)were assessed using a wrist-worn ActiGraph GT9X over 7 days.Self-reported sedentary behavior,MVPA,and all PA were assessed with the Community Healthy Activities Model Program for Seniors(CHAMPS)questionnaire.Linear regression models with progressive covariate adjustments evaluated the associations of sedentary behavior and PA with muscle energetics,as well as the attenuation of the age/muscle energetics association by MVP A and sedentary behavior.As a sensitivity analysis,we also examined activPAL-measured daily step count and time spent in sedentary behavior and their associations with muscle energetics.Results:Every 30 min/day more of ActiGraph-measured MVPA was associated with 0.65 pmol/(s×mg)higher maxOXPHOS and 0.012 mM/s higher ATP_(max)after adjusting for age,site/technician,and sex(p<0.05).Light activity was not associated with maxOXPHOS or ATP_(max).Meanwhile,every 30 min/day spent in ActiGraph-measured sedentary behavior was associated with 0.39 pmol/s×mg lower maxOXPHOS and0.006 mM/s lower ATP_(max)(p<0.05).Only associations with ATP_(max)held after further adjusting for socioeconomic status,body mass index,lifestyle factors,and multimorbidity.CHAMPS MVPA and all PA yielded similar associations with maxOXPHOS and ATP_(max)(p<0.05),but sedentary behavior did not.Higher activPAL step count was associated with higher maxOXHPOS and AT_(Pmax)(p<0.05),but time spent in sedentary behavior was not.Additionally,age was significantly associated with muscle energetics for men only(p<0.05);adjusting for time spent in ActiGraph-measured MVPA attenuated the age association with ATP_(max)by 58%in men.Conclusion:More time spent in accelerometry-measured or self-reported daily PA,especially MVPA,was associated with higher skeletal muscle energetics.Interventions aimed specifically at increasing higher intensity activity might offer potential therapeutic interventions to slow age-related decline in muscle energetics.Our work also emphasizes the importance of taking PA into consideration when evaluating associations related to skeletal muscle energetics.

The burden and long-term trends of breast cancer by different menopausal status in China

Background: The burden of breast cancer in women of different menopausal status has not been assessed in China previously. We aim to evaluate and project the burden of breast cancer in different menopausal status in China. Methods: The incidence and mortality of breast cancer were estimated using the data of 554 cancer registries in 2017 and the trends of incidence and mortality of 112 cancer registries from 2010 to 2017. Data from 22 continued cancer registries from 2000 to 2017 were applied for long-term trend projection to 2030 using the Bayesian age- period-cohort model. Menopausal status was stratified by age, with premenopause defined as chronological age < 45 years, perimenopause defined as 45-54 years, and postmenopause defined as ≥ 55 years. Results: Approximately 352,300 incident cases and 74,200 deaths of breast cancer occurred in China in 2020, contributing to 2.6 million disability-adjusted life years (DALYs). Perimenopausal women had the highest inci- dence, prevalence, and DALYs rates, with the rates being 100.3 per 100,000, 819.2 per 100,000 and 723.1 per 100,000 persons. While postmenopausal women had the highest mortality rates (25.5 per 100,000 persons). From 2000 to 2017, the largest increase in incidence and mortality for breast cancer was observed in postmenopausal women with an average annual percentage change (AAPC) of 5.6% and 2.94%. The number of breast cancer cases and deaths will increase to 452,000 and 98,800 in 2030, resulting in 3.2 million DALYs. Conclusions: The burden of breast cancer is rapidly increasing in China and varies among different menopausal status. Specific prevention and control strategies for women in different menopausal status will be more helpful in reducing the rapidly growing trends of breast cancer.

Epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China:a hospital-based retrospective study

Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.

Migration and cognitive function:a conceptual framework for Global Health Research

Background:Migration is a fundamental demographic process that has been observed globally.It is suggested that migration is an issue of global health importance that can have an immediate and lasting impact on an individual’s health and well-being.There is now an increasing body of evidence linking migration with cognitive function in older adults.In this paper,we synthesized the current evidence to develop a general conceptual framework to understand the factors contributing to the association between migration and cognitive function.Methods:A comprehensive review of the literature was conducted on the associations between migration and cognition among middle-aged and older adults.Results:Five potential mechanisms were identified from the literature:1)socioeconomic status-including education,occupation,and income;2)psychosocial factors-including social networks,social support,social stressors,and discrimination;3)behavioral factors-including smoking,drinking,and health service utilization;4)physical and psychological health status-including chronic conditions,physical function,and depression;and 5)environmental factors-including both physical and social environment.Several underlying factors were also identified-including early-life conditions,gender,and genetic factors.Conclusions:The factors linking migration and cognitive function are multidimensional and complex.This conceptual framework highlights potential implications for global health policies and planning on healthy aging and migrant health.Additional studies are needed to further examine these mechanisms to extend and refine our general conceptual framework.

WJSC 6^(th) Anniversary Special Issues(2):Mesenchymal stem cells Progress of mesenchymal stem cell therapy for neural and retinal diseases

Complex circuitry and limited regenerative power make central nervous system(CNS)disorders the most challenging and difficult for functional repair.With elusive disease mechanisms,traditional surgical and medical interventions merely slow down the progression of the neurodegenerative diseases.However,the number of neurons still diminishes in many patients.Recently,stem cell therapy has been proposed as a viable option.Mesenchymal stem cells(MSCs),a widely-studied human adult stem cell population,have been discovered for more than 20 years.MSCs have been found all over the body and can be conveniently obtained from different accessible tissues:bone marrow,blood,and adipose and dental tissue.MSCs have high proliferative and differentiation abilities,providing an inexhaustible source of neurons and glia for cell replacement therapy.Moreover,MSCs also show neuroprotective effects without any genetic modification or reprogramming.In addition,the extraordinary immunomodulatory properties of MSCs enable autologous and heterologous transplantation.These qualities heighten the clinical applicability of MSCs when dealing with the pathologies of CNS disorders.Here,we summarize the latest progress of MSC experimental research as well as human clinical trials for neural and retinal diseases.This review article will focus on multiple sclerosis,spinal cord injury,autism,glaucoma,retinitis pigmentosa and age-related macular degeneration.

Saffron (Crocus sativus L.) and major depressive disorder:a meta-analysis of randomized clinical trials

Due to safety concerns and side effects of many antidepressant medications, herbal psychopharmacology research has increased, and herbal remedies are becoming increasingly popular as alternatives to prescribed medications for the treatment of major depressive disorder （MDD）. Of these, accumulating trials reveal positive effects of the spice saffron （Crocus sativus L.） for the treatment of depression. A comprehensive and statistical review of the clinical trials examining the effects of saffron for treatment of MDD is warranted. OBJECTIVE： The purpose of this study was to conduct a meta-analysis of published randomized controlled trials examining the effects of saffron supplementation on symptoms of depression among participants with MDD. SEARCH STRATEGY： We conducted electronic and non-electronic searches to identify all relevant randomized, double-blind controlled trials. Reference lists of all retrieved articles were searched for relevant studies. INCLUSION CRITERIA： The criteria for study selection included the following： （1） adults （aged 18 and older） with symptoms of depression, （2） randomized controlled trial, （3） effects of saffron supplementation on depressive symptoms examined, and （4） study had either a placebo control or antidepressant comparison group. DATA EXTRACTION AND ANALYSIS： Using random effects modeling procedures, we calculated weighted mean effect sizes separately for the saffron supplementation vs placebo control groups, and for the saffron supplementation vs antidepressant groups. The methodological quality of all studies was assessed using the Jadad score. The computer software Comprehensive Meta- analysis 2 was used to analyze the data. RESULTS： Based on our pre-specified criteria, five randomized controlled trials （n = 2 placebo controlled trials, n = 3 antidepressant controlled trials） were included in our review. A large effect size was found for saffron supplementation vs placebo control in treating depressive symptoms （M ES = 1.62, P 〈 0.001）, revealing that saffron supplementation significantly reduced depression symptoms compared to the placebo control. A null effect size was evidenced between saffron supplementation and the antidepressant groups （M ES = -0.15） indicating that both treatments were similarly effective in reducing depression symptoms. The mean Jadad score was 5 indicating high quality of trials. CONCLUSION： Findings from clinical trials conducted to date indicate that saffron supplementation can improve symptoms of depression in adults with MDD. Larger clinical trials, conducted by research teams outside of Iran, with long-term follow-ups are needed before firm conclusions can be made regarding saffron＇s efficacy and safety for treating depressive symptoms.

OTOTOXIC EFFECTS OF CARBOPLATIN IN ORGANOTYPIC CULTURES IN CHINCHILLAS AND RATS

Carboplatin, a second-generation platinum chemotherapeutic drug, is considerably less ototoxic than cisplatin. While common laboratory species such as mice, guinea pigs and rats are highly resistant to carboplatin ototoxicity, the chinchilla stands out as highly susceptible. Moreover, carboplatin causes an unusual gradient of cell death in chinchillas. Moderate doses selectively damage type I spiral ganglion neurons (SGN) and inner hair cells (IHC) and the lesion tends to be relatively uniform along the length of the cochlea. Higher doses eventually damage outer hair cells (OHC), but the lesion follows the traditional gradient in which damage is more severe in the base than the apex. While carboplatin ototoxicity has been well documented in adult animals in vivo, little is known about its in vitro toxicity. To elucidate the ototoxic effects of carboplatin in vitro, we prepared cochlear and vestibular organotypic cultures from postnatal day 3 rats and adult chinchillas. Chinchilla cochlear and vestibular cultures were treated with carboplatin concentrations ranging from 50 μM to 10 mM for 48 h. Consistent with in vivo data, carboplatin selectively damaged IHC at low concentrations (50-100 μM). Surprisingly, IHC loss decreased at higher doses and IHC were intact at doses exceeding 500 μM. The mechanisms underlying this nonlinear response are unclear but could be related to a decrease in carboplatin uptake via active transport mechanisms (e.g., copper). Unlike the cochlea, the carboplatin dose-response function increased with dose with the highest dose destroying all chinchilla vestibular hair cells. Cochlear hair cells and auditory nerve fibers in rat cochlear organotypic cultures were unaffected by carboplatin concentrations <10 μM; however, the damage in OHC were more severe than IHC once the dose reached 100 μM. A dose at 500 μM destroyed all the cochlear hair cells, but hair cell loss decreased at high concentrations and nearly all the cochlear hair cells were present at the highest dose, 5 mM. Unlike the nonlinear dose-response seen with cochlear hair cells, rat auditory nerve fiber and spiral ganglion losses increased with doses above 50 μM with the highest dose destroying virtually all SGN. The remarkable species differences seen in vitro suggest that chinchilla IHC and type I SGN posse some unique biological mechanism that makes them especially vulnerable to carboplatin toxicity.

Ginsenoside Rg1 Attenuates Isoflurane-induced Caspase-3 Activation via Inhibiting Mitochondrial Dysfunction

Objective The inhalation anesthetic isoflurane has been shown to induce mitochondrial dysfunction and caspase activation, which may lead to learning and memory impairment. Ginsenoside Rgl is reported to be neuroprotective. We therefore set out to determine whether ginsenoside Rgl can attenuate isoflurane-induced caspase activation via inhibiting mitochondrial dysfunction. Methods We investigated the effects of ginsenoside Rgl at concentrations of 12.5, 25, and 50 μmol/L and pretreatment times of 12 h and 24 h on isoflurane-induced caspase-3 activation in H4 naive and stably transfected H4 human neuroglioma cells that express full-length human amyloid precursor protein （APP） （H4-APP cells）. For mitochondrial dysfunction, we assessed mitochondrial permeability transition pore （mPTP） and adenosine-5＇-triphosphate （ATP） levels. We employed Western blot analysis, chemiluminescence, and flowcytometry. Results Here we show that pretreatment with 50 μmol/L ginsenoside Rgl for 12 h attenuated isoflurane-induced caspase-3 activation and mitochondrial dysfunction in H4-APP cells, while pretreatment with 25 and 50 μmol/L ginsenoside Rgl for 24 h attenuated isoflurane-induced caspase-3 activation and mitochondrial dysfunction in both H4 naive and H4-APP cells. Conclusion These data suggest that ginsenoside Rgl may ameliorate isoflurane-induced caspase-3 activation by inhibiting mitochondrial dysfunction. Pending further studies, these findings might recommend the use of ginsenoside Rgl in preventing and treating isoflurane-induced neurotoxicity.

Fractal lacunarity of trabecular bone and magnetic resonance imaging:New perspectives for osteoporotic fracture risk assessment

Osteoporosis represents one major health condition for our growing elderly population. It accounts for severe morbidity and increased mortality in postmenopausal women and it is becoming an emerging health concern even in aging men. Screening of the population at risk for bone degeneration and treatment assessment of osteoporotic patients to prevent bone fragility fractures represent useful tools to improve quality of life in the elderly and to lighten the related socio-economic impact. Bone mineral density(BMD) estimate by means of dual-energy X-ray absorptiometry is normally used in clinical practice for osteoporosis diagnosis. Nevertheless, BMD alone does not represent a good predictor of fracture risk. From a clinical point of view, bone microarchitecture seems to be an intriguing aspect to characterize bone alteration patterns in aging and pathology. The widening into clinical practice of medical imaging techniques and the impressive advances in information technologies together with enhanced capacity of power calculation have promoted proliferation of new methods to assess changes of trabecular bone architecture(TBA) during aging and osteoporosis. Magnetic resonance imaging(MRI) has recently arisen as a useful tool to measure bone structure in vivo. In particular, high-resolution MRI techniques have introduced new perspectives for TBA characterization by non-invasive non-ionizing methods. However, texture analysis methods have not found favor with clinicians as they produce quite a few parameters whose interpretation is difficult. The introduction in biomedical field of paradigms, such as theory of complexity, chaos, and fractals, suggests new approaches and provides innovative tools to develop computerized methods that, by producing a limited number of parameters sensitive to pathology onset and progression, would speed up their application into clinical practice. Complexity of living beings and fractality of several physio-anatomic structures suggest fractal analysis as a promising approach to quantify morphofunctional changes in both aging and pathology. In this particular context, fractal lacunarity seems to be the proper tool to characterize TBA texture as it is able to describe both discontinuity of bone network and sizes of bone marrow spaces, whose changes are an index of bone fracture risk. In this paper, an original method of MRI texture analysis, based on TBA fractal lacunarity is described and discussed in the light of new perspectives for early diagnosis of osteoporotic fractures.

Detection of apoptosis by RT-PCR array in mefloquine-induced cochlear damage

Objective To investigate the occurrence and possible mechanisms of apoptosis in cochlear epithelium and spiral ganglion neurons after mefloquine treatment. Methods We used quantitative RT-PCR apoptosis-focused gene arrays （96-well, 84 apoptosis related genes） to assess changes of gene expression in the cochlear basilar membrane （hair cells-supporting cells） and spiral ganglion neurons of rat cochlear organotypic cultures treated with 100 IxM mefloquine for 3 h. Results Significant up-or down-regulation in gene expression was detected in 23 genes in the cochlear basilar membrane, and in 32 genes in the spiral ganglion neurons compared with time-matched controls. The responding genes could be classified as pro-or anti-apoptotic, and were mainly implicated in the Bcl-2, Caspase, Card, IAP, TNF ligand / TNF receptor, Death domain / Death effector domain, DNA damage / p53, and NF-kappa B families. Synthetic analysis suggested that these families could be revised to two major pathways mainly involved in t]he death receptor-mediated signaling pathway and apoptotic mitochondrial pathway. In addition, it was found that numerous anti-apoptotic genes such as Bcl2al, Birclb, Birc3, Birc4, Bnipl, Cflar, II10, Lhx4, Mcll, Nfkbl, Prlr, Prok2, and TNF were greatly up-regulated in the cochlear tissue, which might imply the co-existence of protective response in the ceils at the early stage of mefloquine-induced damage.

5-hydroxymethyl-2-furfural prolongs survival and inhibits oxidative stress in a mouse model of forebrain ischemia

In the present study, we hypothesized that 5-hydroxymethyl-2-furfural could attenuate ischemic brain damage by reducing oxidative injury. Thus, mice were subjected to bilateral common carotid artery occlusion to establish a model of permanent forebrain ischemia. The mice were intraperitoneally injected with 5-hydroxymethyl-2-furfura130 minutes before ischemia or 5 minutes after ischemia. The survival time of mice injected with 5-hydroxymethyl-2-furfural was longer compared with untreated mice. The mice subjected to ischemia for 30 minutes and reperfusion for 5 minutes were intraperitoneally injected with 5-hydroxymethyl-2-furfural 5 minutes prior to reperfusion, which increased superoxide dismutase content and reduced malondialdehyde content, similar to the effects of Edaravone, a hydroxyl radical scavenger used for the treatment of stroke. These findings indicate that intraperitoneal injection of 5-hydroxymethyl-2-furfural can prolong the survival of mice with permanent forebrain ischemia. This outcome may be mediated by its antioxidative effects.

The effect of a urinary incontinence selfmanagement program for older women in South Korea:A pilot study

Background:Although self-management approaches have shown strong evidence of positive outcomes for urinary incontinence prevention and management,few programs have been developed for Korean rural communities.Objectives:This pilot study aimed to develop,implement,and evaluate a urinary incontinence self-management program for community-dwelling women aged 55 and older with urinary incontinence in rural South Korea.Methods:This study used a one-group pre-post-test design to measure the effects of the intervention using standardized urinary incontinence symptom,knowledge,and attitude measures.Seventeen community-dwelling older women completed weekly 90-min group sessions for 5 weeks.Descriptive statistics and paired t-tests and were used to analyze data.Results:The mean of the overall interference on daily life from urine leakage(pre-test:M=5.76±2.68,post-test:M=2.29±1.93,t=4.609,p<0.001)and the sum of International Consultation on Incontinence Questionnaire scores(pre-test:M=11.59±3.00,post-test:M=5.29±3.02,t=-5.881,p<0.001)indicated significant improvement after the intervention.Improvement was also noted on the mean knowledge(pre-test:M=19.07±3.34,post-test:M=23.15±2.60,t=7.550,p<0.001)and attitude scores(pre-test:M=2.64±0.19,post-test:M=3.08±0.41,t=5.150,p<0.001).Weekly assignments were completed 82.4%of the time.Participants showed a high satisfaction level(M=26.82±1.74,range 22e28)with the group program.Conclusions:Implementation of a urinary incontinence self-management program was accompanied by improved outcomes for Korean older women living in rural communities who have scarce resources for urinary incontinence management and treatment.Urinary incontinence self-management education approaches have potential for widespread implementation in nursing practice.

“双盲、安慰剂对照交叉设计研究植物药对于进食量、饱腹感、体重减轻及氧化应激的影响”的研究方案(英文)

背景:植物性治疗药物作为一种重要且尚未被完全开发的药用资源,可能有助于热量控制从而产生长期的减重功效。从藤黄果(Garcinia combogia Desr.)中提取的羟基柠檬酸可能通过影响与饱腹有关的神经通路而减少摄食量和减轻体重。方法与设计:本研究为双盲、安慰剂对照、交叉设计试验,共计划纳入48名超重或肥胖的健康受试者(体重指数25.0～39.9 kg/m^2,年龄50～70岁),研究两种剂量藤黄果来源的羟基柠檬酸对摄食量、饱腹感、体重减轻及氧化应激水平的影响。摄食量作为主要结局指标,根据受试者在测量日的早餐、午餐和晚餐的摄食量计算。与平行设计的研究相比,本研究所使用的受试者数量将大大减少。讨论:本研究选择藤黄果来源的羟基柠檬酸为研究对象是因为该药物能够安全地减少摄食量、减轻体重和降低氧化应激水平。我们将会在研究过程中探讨其可能的作用机制和安全指标。