Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease

Stroke and Alzheimer's disease are common neurological disorders and often occur in the same individuals.The comorbidity of the two neurological disorders represents a grave health threat to older populations.This review presents a brief background of the development of novel concepts and their clinical potentials.The activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal function.An ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic site.This Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute excitotoxicity.Furthermore,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death pathways.Based on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic neuropathogenesis.The N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic excitotoxicity.Ischemic stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time courses.It is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related dementia.This early treatment simultaneously serves as a preconditioning therapy against ischemic stroke that often attacks the same individuals during abnormal aging.

Sorl1 knockout inhibits expression of brain-derived neurotrophic factor:involvement in the development of late-onset Alzheimer's disease

Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.

Salivary C-reactive protein and mean platelet volume as possible diagnostic markers for late-onset neonatal pneumonia

BACKGROUND Neonatal sepsis,a formidable threat to newborns,is a leading cause of neonatal mortality,with late-onset sepsis manifesting after 72 hours post-birth being particularly concerning.Pneumonia,a prevalent sepsis presentation,poses a significant risk,especially during the neonatal phase when lung defenses are compromised.Accurate diagnosis of pneumonia is imperative for timely and effective interventions.Saliva,a minimally invasive diagnostic medium,holds great promise for evaluating infections,especially in infants.AIM To investigate the potential of serum C-reactive protein(CRP),salivary CRP(sCRP),and mean platelet volume(MPV)as diagnostic markers for late-onset neonatal pneumonia(LONP).METHODS Eighty full-term neonates were systematically examined,considering anthropometric measurements,clinical manifestations,radiology findings,and essential biomarkers,including serum CRP,sCRP,and MPV.RESULTS The study reveals noteworthy distinctions in serum CRP levels,MPV,and the serum CRP/MPV ratio between neonates with LONP and healthy controls.MPV exhibited a robust discriminatory ability[area under the curve(AUC)=0.87]with high sensitivity and specificity at a cutoff value of>8.8.Correlations between serum CRP,sCRP,and MPV were also identified.Notably,sCRP demonstrated excellent predictive value for serum CRP levels(AUC=0.89),underscoring its potential as a diagnostic tool.CONCLUSION This study underscores the diagnostic promise of salivary and serum biomarkers,specifically MPV and CRP,in identifying and predicting LONP among neonates.These findings advocate for further research to validate their clinical utility in larger neonatal cohorts.

Survey for late-onset hypogonadism among old anti middle-aged males in Shanghai communities

This study sought to investigate late-onset hypogonadism （LOH） in old and middle-aged males in Shanghai communities, using symptom score evaluation systems and measurements of sex hormone levels. One thousand cases of males aged 40-70 years were investigated. The aging male symptoms （AMS） scale and androgen deficiency in aging males （ADAM） questionnaire were used at the beginning of the investigation, followed by measurement of the sex hormone-related factors （total testosterone （TT）, free testosterone （fT）, sex hormone-binding globulin （SHBG） and bioavailability of testosterone （Bio-T））. There were 977 valid questionnaires. The LOH-positive rates shown by AMS and ADAM were 59.88% and 84.65%, respectively; values increased with the age of the patients. There were 946 results related to sex hormone measurements, which showed the following results： TT was not related to aging （P〉O.05）; levels of SHBG increased with age; and fT and Bio-T decreased with age. There was a significant difference in fT between LOH-positive and LOH-negative patients, as shown by the ADAM. In summary, TT levels were not related to aging, even though SHBG did increase while fT and Bio-T decreased with aging. Clinically, the diagnosis of LOH cannot be based on serum TT level.

Erectile function and late-onset hypogonadism symptoms related to lower urinary tract symptom severity in elderly men

The aim of this study was to evaluate the relationship between lower urinary tract symptoms （LUTSs）, erectile dysfunction （ED） and symptomatic late-onset hypogonadism （SLOH） in ageing men in the Aegean region of Turkey. Five hundred consecutive patients 〉40 years old who had been in a steady sexual relationship for the past 6 months and were admitted to one of six urology clinics were included in the study. Serum prostate-specific antigen and testosterone levels and urinary flow rates were measured. All patients filled out the International Prostate Symptom Score and Quality of Life （IPSS-QoL）, International Index of Erectile Function （IIEF） and Aging Males＇ Symptoms （AMS） scale forms. Of the patients, 23.9% had mild LUTSs, 53.3% had moderate LUTSs and 22.8% had severe LUTSs. The total testosterone level did not differ between groups. Additionally, 69.6% had ED. The presence of impotence increased with increasing LUTS severity. Symptomatic late-onset hypogonadism （AMS 〉27） was observed in 71.2% of the patients. The prevalence of severe hypogonadism symptoms increased with the IPSS scores. A correlation analysis revealed that all three questionnaire scores were significantly correlated. In conclusion, LUTS severity is an age-independent risk factor for ED and SLOH. LUTS severity and SLOH symptoms appear to have a strong link that requires etiological and biological clarification in future studies.

How to recognize late-onset hypogonadism in men wit sexual dysfunction

Late-onset hypogonadism （LOH） has been considered the most common form of male hypogonadism with a prevalence of approximately 1 in 100 men. Diagnosis of LOH should be made in symptomatic men with unequivocally low serum testosterone （T） levels. However, its clinical presentation is often insidious and difficult to recognize because it is characterized by nonspecific symptoms that make differential diagnosis with physiological ageing problematic. Sexual dysfunction is the most important determinant for medical consultation and the most specific symptom associated with low T. We therefore analysed a consecutive series of 1734 subjects who attended our unit for sexual dysfunction to investigate the associations between low T （different thresholds）, sexual parameters, medical history data （delayed puberty, pituitary disease or cryptorchidism） and their physical exam results. Metabolic parameters, in particular waist circumference, display the greatest accuracy in detecting low T. We found that only the association of several symptoms and signs could significantly raise the clinical suspicion of low T. Structured inventories, which cluster together symptoms and signs of hypogonadism, can help clinicians suspect androgen deficiency. In particular, structured interviews, such as ANDROTEST, have been demonstrated to have a greater accuracy when compared to self reported questionnaires in detecting low T levels.

Late-onset Leigh syndrome without delayed development in China:A case report

BACKGROUND Leigh syndrome(LS)is one of the most common mitochondrial diseases in infants and children.LS often manifests as early-onset with delayed phenotypic development.However,late-onset LS with normal development and white matter lesions in the brain is rarely reported,thereby highlighting the phenotypic variability of LS expression.CASE SUMMARY We report a 12-year-old boy who presented with an unusual late-onset and fulminant form of LS that is maternally inherited without developmental delay.The patient was admitted to the hospital with symptoms of ptosis and somnolence,and died within 2 mo.Analysis of peripheral blood leukocytes showed a homoplasmic m.9176T>C mutation in the patient.Magnetic resonance imaging also revealed lesions in bilateral white matter as well as symmetrical lesions in the basal ganglia and brain stem.The patient was diagnosed with LS.The patient was treated with vitamin C,vitamin D,and adenosine-triphosphate.The patient died within 2 mo of hospital admission.CONCLUSION LS can present in both infants and older children with different phenotypes.

Molecular Genetic Analysis of Autosomal Dominant Late-Onset Cataract in a Chinese Family

Congenital cataract is a highly heterogeneous disorder at both the genetic and the clinical-phenotypic levels.A unique cataract was observed in a 4-generation Chinese family,which was characterized by autosomal dominant inheritance and late-onset.Mutations in the 13 known genes (CRYAA,CRYAB,CRYBB1,CRYBB2,CRYGC,CRYBA1/A3,CRYGD,Connexin50,Connexin46,intrinsic membrane protein LIM2,cytoskeletal protein BFSP2,the major intrinsic protein-MIP and the heat shock factor HSF4) have previously been demonstrated to be the frequent reason for isolated congenital cataracts,but the exact molecular basis and underlying mechanisms of congenital cataract still remain unclear.This study was designed to find whether these 13 genes developed any mutation in the family members and to identify the disease-causing gene.Polymerase chain reaction (PCR) and direct DNA sequence analysis were carried out to detect the 13 genes.The results showed that no mutation causing amino acid alternations was found in these potential candidate genes among all patients in the family,and only several single-nucleotide polymorphisms (SNPs) were identified.A transitional mutation in the fourth intron of CRYBB2 and some silent mutations in the first exon of BFSP2 and CRYGD were found in the cataract family,but further study showed that these mutations could also be found in normal controls.It was concluded that some unidentified genes may underlie the occurrence of late-onset cataract in this family.A genome-wide screening will be carried out in the next study.

Plasma D-dimer level in early and late-onset neonatal sepsis

BACKGROUND Neonatal sepsis is a life-threatening disease.Early diagnosis is essential,but no single marker of infection has been identified.Sepsis activates a coagulation cascade with simultaneous production of the D-dimers due to lysis of fibrin.Ddimer test reflects the activation of the coagulation system.AIM To assess the D-dimer plasma level,elaborating its clinicopathological value in neonates with early-onset and late-onset neonatal sepsis.METHODS The study was a prospective cross-sectional study that included ninety neonates;divided into three groups:Group I:Early-onset sepsis(EOS);Group II:Late-onset sepsis(LOS);and GroupⅢ:Control group.We diagnosed neonatal sepsis according to our protocol.C-reactive protein(CRP)and D-dimer assays were compared between EOS and LOS and correlated to the causative microbiological agents.RESULTS D-dimer was significantly higher in septic groups with a considerably higher number of cases with positive D-dimer.Neonates with LOS had substantially higher levels of D-dimer than EOS,with no significant differences in CRP.Neonates with LOS had a significantly longer hospitalization duration and higher gram-negative bacteriemia and mortality rates than EOS(P<0.01).Gramnegative bacteria have the highest D-dimer levels(Acinetobacter,Klebsiella,and Pseudomonas)and CRP(Serratia,Klebsiella,and Pseudomonas);while gram-positive sepsis was associated with relatively lower levels.D-dimer had a significant negative correlation with hemoglobin level and platelet count;and a significant positive correlation with CRP,hospitalization duration,and mortality rates.The best-suggested cut-off point for D-dimer in neonatal sepsis was 0.75 mg/L,giving a sensitivity of 72.7%and specificity of 86.7%.The D-dimer assay has specificity and sensitivity comparable to CRP in the current study.CONCLUSION The current study revealed a significant diagnostic value for D-dimer in neonatal sepsis.D-dimer can be used as an adjunct to other sepsis markers to increase the sensitivity and specificity of diagnosing neonatal sepsis.

Late-onset multiple acyl-CoA dehydrogenase deficiency with cardiac syncope: A case report

BACKGROUND Multiple acyl-CoA dehydrogenase deficiency(MADD)is an uncommon autosomal recessive disorder of mitochondrial fatty acid beta-oxidation.Syncope is a transient loss of consciousness due to acute global cerebral hypoperfusion.Late-onset MADD with syncope has not been reported previously.CASE SUMMARY We report a 17-year-old girl with exercise intolerance and muscle weakness.She felt palpitation and shortness of breath after short bouts of exercise.She also suffered from a transient loss of consciousness many times.Muscle biopsy showed lipid storage.Genetic mutation analysis indicated a compound heterozygous mutation c.250G>A(p.A84T)and c.872T>G(p.V291G)in the ETFDH gene.The results of Holter electrocardiogram monitoring showed supraventricular tachycardia when the patient experienced a loss of consciousness.After treatment with riboflavin and carnitine,muscle weakness and palpitation symptoms improved rapidly.No loss of consciousness occurred,and the Holter electrocardiogram monitoring was normal.CONCLUSION Late-onset MADD with supraventricular tachycardia can cause cardiac syncope.Carnitine and riboflavin supplement were beneficial for treating the late-onset MADD with cardiac syncope.Attention should be paid to the prevention of cardiac syncope when diagnosing late-onset MADD.

A non-invasive,rapid method to genotype late-onset Alzheimer's disease-related apolipoprotein E gene polymorphisms

The apolipoprotein E gene ε4 allele is considered a negative factor for neural regeneration in late-onset Alzheimer＇s disease cases. The aim of this study was to establish a non-invasive, rapid method to genotype apolipoprotein E gene polymorphisms. Genomic DNA from mouth swab specimens was extracted using magnetic nanoparticles, and genotyping was performed by real-time PCR using TaqMan-BHQ probes. Genotyping accuracy was validated by DNA se- quencing. Our results demonstrate 100% correlation to DNA sequencing, indicating reliability of our protocol. Thus, the method we have developed for apolipoprotein E genotyping is accurate and reliable, and also suitable for genotyping large samples, which may help determine the role of the apolipoprotein E ε4 allele in neural regeneration in late-onset Alzheimer＇s disease cases.

SLC26A4 gene polymorphism and late-onset Alzheimer’s disease in a Han Chinese population from Qingdao,China

In a recent genome-wide association study, the SLC26A4 gene rs2072064 polymorphism was found to be associated with late-onset Alzheimer＇s disease in Caucasians. Here, we investigated this association in a large Northern Han Chinese cohort consisting of 599 sporadic late-onset Alzheimer＇s disease patients and 598 healthy controls matched for sex and age in a Northern Han Chinese population from Qingdao, China. Genotyping by the polymerase chain reaction-ligase detection reaction revealed that there were significant differences in the genotype （P = 0.017） and allele （P = 0.007） frequencies of the rs2072064 polymorphism between late-onset Alzheimer＇s disease patients and controls. The A allele of this polymorphism was significantly associated with a reduced risk of late-onset Alzheimer＇s disease （odds ratio （OR） = 0.792, 95% confidence interval （CI） = 0.670-0.937, P = 0.007）. When the data were stratified by the apolipoprotein E E4 status, there was a significant difference only among apolipoprotein E E4 non-carriers （genotypic P = 0.001, allelic P = 0.001）. Furthermore, the association between rs2072064 and late-onset Alzheimer＇s disease remained significant by logistic regression analysis after adjustment for age, gender, and the apolipoprotein E E4 carrier status （dominant model： OR = 0.787, 95% CI = 0.619-1.000, P = 0.050; recessive model： OR = 0.655, 95% CI = 0.448-0.959, P= 0.030; additive model： OR = 0.792, 95% CI = 0.661-0.950, P = 0.012）. These findings suggest that SLC26A4 is a susceptibility gene for late-onset Alzheimer＇s disease in a Northern Han Chinese population from the Qingdao area.

Study of Tripterygium Associated with Nicotinamide in Treating Late-onset Autoimmune Diabetes Mellitus in Adults

Objective: To explore the effect of Tripterygium polyglycoside (TP) associated with nicotinamide on the islet cell function, immune parameters and lipoperoxide (LPO) in adult patients with late-onset autoimmune diabetes mellitus (LADA). Methods: Thirty-six cases of LADA were randomly divided into three groups: TP group (n=12), treated with TP plus orally taken metformin; combined treatment group (n= 12), treated with TP combined with nicotinamide and metformin, and control group (n=12) treated with metformin alone. They were followed-up for 18 months. Results: (1) Compared with the control group after 9 months of treatment, postprandial plasma glucose and LPO in combined treatment group were decreased (P <0.05), and the postprandial C-peptide was higher (P<0.05). At the 18th month, the value of postprandial C-peptide in the TP and combined treatment group was higher than that in the control group. The slL-2R level of both TP and combined treatment groups were lowered (P<0.01); (2) Islet cell antibody (ICA) positive of 5 cases in the TP group and 6 cases in the combined treatment group got converted to the negative respectively , while only one in the control group at the time (P<0.05); (3) The level of LPO in the combined treatment group was significantly lower than that in the TP group at the 18th month of treatment (P<0. 05). Conclusion: TP combined with nicotinamide played a role in immunity regulation, decreasing the titer of islet cell antibody and slL-2R, which also reduced the production of LPO and had a tendency to improve islet cell function in early LADA patients.

Studying the relationship between clinical features and mental health among late-onset myasthenia gravis patients

BACKGROUND Mental disorders are common comorbidities among individuals with neurological diseases, and the prevalence of depressive and anxiety-related symptoms in newly referred patients at neurology outpatient clinics is high. There have been few studies on the mental health of patients with late-onset myasthenia gravis(MG).AIM To examine the relationship between clinical features and the mental health symptoms within late-onset MG patients.METHODS A total of 105 patients diagnosed with MG were recruited consecutively from a neuromuscular outpatient clinic between December 2020 and February 2021. Patients were classified into two groups: early-onset MG(age at onset < 50 years, n = 63) and late-onset MG(age at onset ≥ 50 years, n = 42). Social demographic data and information about marital status, education level, clinical symptoms, serum antibody levels, and therapies used were collected for all participants. Participants were also evaluated using the Myasthenia Gravis Composite scale, the Myasthenia Gravis Activities of Daily Living scale, the Myasthenia Gravis Quality of Life 15(MG-QOL-15) questionnaire, the 17-item version of the Hamilton Depression Rating Scale(HAM-D) and the Hamilton Anxiety Rating Scale(HAM-A). The relationship between clinical features and mental health in late-onset MG patients was examined using multivariate logistic regression analyses.RESULTS Late-onset MG patients were more prone to dyspnea, had higher levels of serum anti-acetylcholine receptor antibodies, and higher total scores on the MG-QOL-15, HAM-D, and HAM-A questionnaires, than early-onset MG patients had(P < 0.05). Among those with late-onset MG, female patients had higher total HAM-D and HAM-A scores than male patients had(P < 0.05). High scores on the QOL-15 questionnaire were associated with higher incidences of anxiety and depression, and the association was found to be independent after adjusting for confounding risk factors. In the late-onset subgroup, the areas under the receiver operating characteristic curves for the MG-QOL-15 score-based diagnostic accuracy for anxiety and depression state were 0.816(P = 0.001) and 0.983(P < 0.001), respectively.CONCLUSION Higher MG-QOL-15 scores were a risk factor for anxiety and depression in late-onset MG, and women with late-onset MG were more likely to have anxiety and depression than men were.

A Rare Cause of Late-Onset Epilepsy: Linear Scleroderma en Coup de Sabre

Late-Onset Epilepsy (LOE), with onset in adult life, is often attributed to cerebrovascular disease and intracranial tumor. Herein we present a LOE patient with history of Linear Scleroderma en Coup de Sabre (LScs) and abnormal cranial MRI signs. Curiously, his band-like skin lesion, presenting on the forehead, was in line with the surface projection of the intracranial focus shown in MRI. This gave a clue of the link between the skin lesion and the intracranial focus and the epilepsy. To sum up, it exposed a rare cause of LOE. Moreover, it underlined the significance of recognizing the cause to be associated with a substantially increased risk of developing epilepsy.

restosterone replacement therapy for late-onsel lypogonadism： current trends in Korea

Testosterone levels in men older than 40 years can decrease at a rate of 1%-2% per year, and reports show that more than 50% of 80-year-old men have testosterone levels consistent with hypogonadism. Late-onset hypogonadism （LOH） is a clinical and biochemical syndrome associated with advancing age and characterized by typical symptoms of serum testosterone deficiency. In recent decades, the concept of LOH in ageing men has become familiar in European countries and the United States. It is also a topic of interest and debate throughout Korea. However, most of the data regarding advantages or disadvantages of testosterone replacement therapy （TRT） as treatment for LOH have been primarily obtained from studies on Western populations; therefore, studies of the effects of TRT in Asian men, who may have different serum testosterone compared to Western men, are needed. TRT is commonly prescribed in Korea, despite the paucity of studies on the effects of TRT in Asian populations. Data from various TRT studies based on Korean have shown its efficacy in increasing serum testosterone levels and improving subjective symptoms as assessed by questionnaires. Currently, patches and short-acting intramuscular injections are displaced by gels and long-acting formulations. However, to prevent overdiagnosis and overtreatment, indication for TRT should include both low testosterone levels and symptoms and signs of hypogonadism.

Alzheimer’s disease:a tale of two diseases?

Sporadic late-onset Alzheimer’s disease(SLOAD)and familial early-onset Alzheimer’s disease(FEOAD)associated with dominant mutations in APP,PSEN1 and PSEN2,are thought to represent a spectrum of the same disorder based on near identical behavioral and histopathological features.Hence,FEOAD transgenic mouse models have been used in past decades as a surrogate to study SLOAD pathogenic mechanisms and as the gold standard to validate drugs used in clinical trials.Unfortunately,such research has yielded little output in terms of therapeutics targeting the disease’s development and progression.In this short review,we interrogate the widely accepted view of one,dimorphic disease through the prism of the Bmi1+/–mouse model and the distinct chromatin signatures observed between SLOAD and FEOAD brains.

Early-Onset Alzheimer’s Disease and Metabolic Dysfunction, a Comparative Review

Alzheimer’s disease is quickly becoming one of the most known diseases in the country due to its devastating effects and lack of treatment options. Within this lethal disease, there is a smaller group, those individuals that are diagnosed with early-onset Alzheimer’s disease. It is understood that these individuals see faster effects of the disease and die considerably sooner, but it is not understood why. This review compares the early-onset (EOAD) and late-onset (LOAD) types to try and determine some of the most blaring differences between the two. The genetic basis linking EOAD and LOAD has been the apolipoprotein E gene (APOE) to indicate metabolic alteration with the &#949;4 allele specifically. The topographical atrophy disparities between EOAD and LOAD supported the more noticeable cognitive differences between the two Alzheimer’s disease categories. The faster and wider spread atrophy of EOAD patients correlates with the difficulty they experience with attention, language, visuo-spatial, and executive functions. Finally, brain metabolism differs between both AD subtypes as well, where EOAD indicates the wide spread damage and metabolic breakdown across more diverse regions of the brain.

Elabela is a reliable biomarker for predicting early onset preeclampsia:A comparative study

BACKGROUND Preeclampsia(PE)is a multisystemic metabolic disease with an undetermined etiology.PE is a worldwide cause of maternal and perinatal morbidity,subdivided into early(EoPE)and late-onset(LoPE)according to 34 wk of gestation as a divider.Many researchers investigated biomarkers for predicting PE to halt its consequences on the feto-maternal outcome.Elabela(Ela)is a newly discovered peptide hormone that was implicated in PE pathogenesis.Earlier rodent studies discussed Ela’s role in controlling blood pressure.Moreover,Ela deficiency was associated with PE development.AIM To test whether plasma Ela could serve as a reliable marker for predicting PE based on the time of onset(EoPE vs LoPE)compared to age and body mass matched healthy controls since no definitive treatment exists for PE but to terminate a pregnancy.METHODS This case-control study recruited(n=90)pregnant who fulfilled inclusion criteria;they were allocated into three groups:EoPE(30/90)(<34 wk of gestation);LoPE(30/90)(≥34 wk of gestation);and healthy pregnant(30/90).Demographic criteria;biochemical,hematological,and maternal plasma Ela levels were recorded for comparison.RESULTS Serum Ela was significantly reduced in EoPE compared to LoPE and healthy controls(P=0.0023).The correlation confirmed a strong inverse relationship with mean atrial blood pressure(r=-0.7,P<0.001),while gestational age and platelets count showed a moderate correlation with(r=0.4 with P<0.0001).No correlation was confirmed between the body mass index(BMI)and urine albumin.The predictive ability of 25 centile serum Ela had an Odds ratio of 5.21,95%confidence interval(1.28,21.24),P=0.02 for predicting EoPE.The receiver operator characteristic curve defined the Ela cutoff value at>9.156 with 96.7%and 93.3%sensitivity and specificity,P<0.0001 in predicting EoPE.CONCLUSION A strong correlation of serum Ela with PE parameters with excellent sensitivity and specificity in distinguishing EoPE independent of the BMI,age,and blood pressure which makes Ela a recommendable marker in screening.Further research is warranted to explore prognostic and therapeutic applications for Ela in PE.

Clinical Significance of Pulmonary Function Tests in Long-Term Survivors after Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation

We retrospectively assessed long-term pulmonary function in adults surviving for ≥5 years after myeloablative allogeneic hematopoietic stem cell transplantation and identified risk factors for late-onset noninfectious pulmonary complications. Among 174 patients undergoing transplantation for hematologic malignancies between May 1994 and December 2004, 81 long-term survivors were evaluated. Pulmonary function tests (PFTs) were performed before conditioning, 3 months and 1 year after transplantation, and then annually. Eight patients (10%) had abnormal pulmonary function before transplantation, but this was not associated with late changes in PFTs. Patients with chronic graft-versus-host disease (GVHD) showed a significant decline of lung function after 3 years when compared with patients without chronic GVHD. Abnormal pretransplantation lung function was associated with pulmonary chronic GVHD according to National Institutes of Health criteria (score 0, n = 58;score 1, n = 14;score 2, n = 6;score 3, n = 3). Five patients with late-onset noninfectious pulmonary complications showed a decline of lung function at 1 year after transplantation. Only chronic GVHD was significantly related to late-onset noninfectious pulmonary complications. In conclusion, abnormal lung function before transplantation may be associated with a decline in pulmonary function within 1 year after transplantation, but late-onset noninfectious pulmonary complications could not be predicted from pretransplantation lung function.