Safety evaluation of single-sperm cryopreservation technique applied in intracytoplasmic sperm injection.

Intracytoplasmic sperm injection (ICSI) is a technique that directly injects a single sperm into the cytoplasm of mature oocytes. Here, we explored the safety of single-sperm cryopreservation applied in ICSI. This retrospective study enrolled 186 couples undergoing ICSI-assisted pregnancy. Subjects were allocated to the fresh sperm (group A)/single-sperm cryopreservation (group B) groups based on sperm type, with their clinical baseline/pathological data documented. We used ICSI-compliant sperm for subsequent in vitro fertilization and followed up on all subjects. The recovery rate/cryosurvival rate/sperm motility of both groups, the pregnancy/outcome of women receiving embryo transfer, and the delivery mode/neonatal-related information of women with successful deliveries were recorded. The clinical pregnancy rate, cumulative clinical pregnancy rate, abortion rate, ectopic pregnancy rate, premature delivery rate, live birth delivery rate, neonatal birth defect rate, and average birth weight were analyzed. The two groups showed no significant differences in age, body mass index, ovulation induction regimen, sex hormone [anti-Müllerian hormone (AMH)/follicle-stimulating hormone (FSH)/luteinizing hormone (LH)] levels, or oocyte retrieval cycles. The sperm recovery rate (51.72%-100.00%) and resuscitation rate (62.09% ± 16.67%) in group B were higher; the sperm motility in the two groups demonstrated no significant difference and met the ICSI requirements. Group B exhibited an increased fertilization rate, decreased abortion rate, and increased safety versus group A. Compared with fresh sperm, the application of single-sperm cryopreservation in ICSI sensibly improved the fertilization rate and reduced the abortion rate, showing higher safety.

Clinical Efficacy Analysis of Biofeedback Electrical Stimulation Combined with Doxycycline in the Treatment of Type IIIA Chronic Prostatitis.

Purpose: To analyse the clinical efficacy of biofeedback electrical stimulation combined with doxycycline in the treatment of type IIIA chronic prostatitis. Methods: Eighty patients who met the diagnostic criteria of type IIIA chronic prostatitis in our hospital between February 2020 and February 2022 were selected and equally divided into the drug group and electrical stimulation group according to the random number table method. The drug group was treated with medication alone for 4 weeks; the electrostimulation group was treated with biofeedback electrostimulation on top of medication for 12 weeks. The expressed prostatic secretious (EPS) routine (lecithin bodies, white blood cells) and the maximum urinary flow rate (Q max) and mean urinary flow rate (Q ave) were measured before and after treatment in both groups, and the National Institutes of Health chronic prostatitis symptom index (NIH-CPSI) was used to score the urinary symptom, pain or discomfort, and quality of life and determine the efficacy of the treatment in both groups. Results: After treatment, the number of lecithin bodies and white blood cells in EPS improved significantly in both groups compared to before, and both the electrical stimulation group was better than the drug group (P < 0.05). After treatment, the Q max and Q ave were significantly higher in both groups than before, and both the electrical stimulation groups were higher than the drug group (P < 0.05). After treatment, the urinary symptom scores, pain or discomfort scores, quality of life scores, and total NIH-CPSI scores were significantly lower in both groups than before, and all were lower in the electrical stimulation group than in the drug group (P < 0.05). After treatment, the overall efficiency of patients in the electrical stimulation group was significantly higher than that of the drug group (P < 0.05). Conclusion: Biofeedback electrical stimulation combined with doxycycline in the treatment of type IIIA chronic prostatitis can synergistically improve the patient's inflammation level, urinary dysfunction, relieve pelvic floor tension myalgia, and improve their quality of life, opening up new avenues for the rehabilitation of patients with type IIIA chronic prostatitis.

Clinical Application Value of High-Frequency Ultrasound Combined with Detection of Serum High Mobility Group Box 1, Soluble IL-2 Receptor, and Thyroglobulin Antibody in Diagnosing Thyroid Cancer.

Objective: The aim of this study is to explore the clinical application value of high-frequency ultrasound combined with detection of serum high mobility group box (HMGB-1), soluble IL-2 receptor (SIL-2R), and thyroglobulin antibody (TgAb) in diagnosing thyroid cancer. Methods: By means of retrospective study, 50 thyroid cancer patients treated in our hospital from January 2019 to January 2021 were selected as the thyroid cancer group, 50 patients with benign thyroid lesions were included in the benign lesion group, and 50 healthy individuals examined in our hospital in the same period were included in the control group. All study objects received high-frequency ultrasound examination, and at the same time, their serum HMGB-1, SIL-2R, and TgAb levels were measured. After that, the results of high-frequency ultrasound examination were analyzed, the diagnostic efficacy of different diagnosis methods was explored, and receiver operating characteristic (ROC) curves were plotted. Results: According to the results of high-frequency ultrasound examination, there were significant differences in echogenicity surrounding and inside the lesion, calcification, blood flow distribution, and blood flow parameters between the thyroid cancer group and the benign lesion group (P < 0.001); the HMGB-1, SIL-2R, and TgAb levels were statistically different among the three groups (P < 0.001), and the level values of HMGB-1, SIL-2R, and TgAb of the thyroid cancer group were, respectively, (12.26 ± 1.32) ng/ml, (108.65 ± 9.75) pmol/L, and (690.65 ± 34.47) IU/mL; the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of high-frequency ultrasound combined with detection of serum HMGB-1, SIL-2R, and TgAb were, respectively, 98.0%, 95.0%, 90.7%, and 99.0%, and AUC (95%CI) = 0.965 (0.931-0.999). Conclusion: High-frequency ultrasound combined with detection of serum HMGB-1, SIL-2R, and TgAb has a good value in diagnosing thyroid cancer, which should be promoted in practice.

[Xianfang Huoming Decoction improves sperm quality in asthenospermia mice: An investigation based on the detoxification and sperm-nourishing method].

OBJECTIVE: To investigate the mechanism of Xianfang Huoming Decoction (XHD) improving sperm motility in mice with asthenospermia (AS). METHODS: Thirty normal BALB/c mice were randomly divided into six groups, blank control, AS model control, low-dose XHD, medium-dose XHD, high-dose XHD and levocarnitine + vitamin E (LC+VE). The AS model was established in the latter five groups by injection of methotrexate at 0.5 mg/kg once a week, and the mice in the blank control group were injected with the same volume of normal saline, all for 8 weeks. From the ninth week, the animals in the blank control and AS model control groups were treated with PBS at 0.1 ml/d, those in the low-, medium- and high-dose XHD groups with XHD at 7.13, 14,2 and 28.52 g/kg/ d respectively, and those in the LC+VE group with LC+VE (30:1) at 0.55 g/kg/d, all for 4 weeks. Then, the bilateral epididymides were harvested from all the mice for preparation of a sperm suspension and observation of the total numbers of sperm and motile sperm. The testis tissues were obtained for to determination of the expressions of Nrf-2- and HO-1-related mRNA and proteins by fluorescence staining, RT-PCR and Western blot. RESULTS: Compared with the AS model controls, the mice treated with low-, medium- and high-dose XHD showed dramatically increased sperm concentration (ï¼»22.36 ± 16.02ï¼½ vs ï¼»39.04 ± 4.50ï¼½, ï¼»40.76 ± 6.57ï¼½ and ï¼»41.04 ± 8.39ï¼½ ×106/ml, P < 0.01) and motility (ï¼»22.89 ± 14.96ï¼½% vs ï¼»47.98 ± 4.74ï¼½%, ï¼»48.53 ± 6.03ï¼½% and ï¼»49.31 ± 6.24ï¼½%, P< 0.01), decreased level of reactive oxygen species (ROS) (ï¼»16.82 ± 14.96ï¼½% vs ï¼»12.08 ± 3.26ï¼½%, ï¼»10.77 ± 2.21ï¼½% and ï¼»9.56 ± 2.08ï¼½%, P< 0.01), and up-regulated expressions of Nrf-2- and HO-1-related mRNA and proteins in the testis tissue (P < 0.05 or P < 0.01). CONCLUSION: Xianfang Huoming Decoction inhibits the development of oxidative stress by up-regulating the expressions of Nrf-2- and HO-1-related mRNA and proteins in the testis tissue, which has provided theoretical evidence for its clinical application in the treatment of asthenospermia.

The efficacy and safety of acupuncture in the treatment of erectile dysfunction: A protocol for systematic review and meta-analysis.

BACKGROUND: Erectile dysfunction (ED) can negatively affect men's mental health, interpersonal relationships, and overall well-being. ED has affected >150 million men worldwide, and this number will reach approximately 322 million by 2025. Although PDE5-Is is a landmark in the treatment of erectile dysfunction, it may have side effects such as penile pain, cardiovascular dysfunction, and deafness. Some studies have shown that acupuncture may have a positive effect on the pathophysiology of ED. Therefore, we will select all randomized controlled trials related to evaluate the efficacy and safety of acupuncture treatment of ED. METHODS: This study will systematically search 7 digital databases including China National Knowledge Infrastructure, Wanfang, VIP, China Biology Medicine, Cochrane Library, PubMed, and Embase for randomized controlled trials without language restrictions. Two researchers will independently read the title, abstract, and full text to screen for studies that can be included in the meta-analysis. If there is any dispute, the third party will be required to reach a consensus. RESULTS: The purpose of this study is to evaluate the efficacy and safety of acupuncture in the treatment of ED and the difference in the impact of different types of acupuncture on ED. CONCLUSION: Judge whether acupuncture and moxibustion can help improve the symptoms of ED by evaluating relevant literatures, and make up for the lack of relevant research. INPLASY REGISTRATION NUMBER: INPLASY 202140040.

Effectiveness of acupuncture for asthenozoospermia: A protocol for systematic review and meta-analysis.

BACKGROUND: According to the World Health Organization, the global incidence of infertility is about 15%, and more than 50% of infertility cases are caused by male infertility. Asthenozoospermia is caused by male fertility decline and male infertility. Due to work pressure, environmental pollution, sexual diseases, and other factors, the number of patients with asthenozoospermia has increased in recent years. It has been confirmed that acupuncture has a certain effect on patients with asthenozoospermia. Acupuncture and moxibustion can be an adjuvant treatment plan for the treatment of asthenozoospermia in addition to drug treatment. METHODS: Randomized controlled trials of acupuncture for asthenozoospermia will be searched in the relevant database, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), and Chinese Scientific Journal Database (VIP database). The studies of electronic searches will be exported to EndNote V.9.1 software. We will run meta-analyses using the Review Manager (RevMan) V.5.3 software. Any disagreements will be solved in consultation with a third reviewer. RESULTS: Our study aims to explore the efficacy of acupuncture for asthenozoospermia and to provide up-to-date evidence for clinical of asthenozoospermia. CONCLUSION: This study will perform a comprehensive systematic review and meta-analysis on the efficacy of acupuncture for asthenozoospermia, making up for the lack of relevant evidence of the clinical use of acupuncture. INPLASY REGISTRATION NUMBER: INPLASY 202140032.

Modeling, simulation, and optimization of electrowetting-on-dielectric (EWOD) devices.

With widespread research studies on electrowetting-on-dielectric (EWOD) for droplet manipulation in the field of lab-on-a-chip, how to improve the driving capability of droplets has increasingly attracted enormous interest. Aiming to decrease driving voltages and improve driving effectiveness, this paper studies the modeling, simulation, and optimization of EWOD devices. The theoretical model is refined mainly in consideration of the saturation effect of the contact angle and then verified by both simulation and experiments. As a design guide to decrease the driving voltage, a theoretical criterion of droplet splitting, the most difficult one among four basic droplet manipulations, is developed and then verified by experimental results. Moreover, a novel sigmoid electrode shape is found by the optimization method based on finite element analysis and achieves better driving effectiveness and consistent bidirectional driving capability, compared with the existing electrode shapes. Taken together, this paper provides an EWOD analysis and optimization method featuring a lower voltage and a better effectiveness and opens up opportunities for optimization designs in various EWOD-based applications.

Monitoring Early-Stage Acute Rejection by Imaging CXCR3-Positive Cell Infiltration: Evaluation of ¹²5Iodine-Labeled CXCL10.

OBJECTIVES: It has been reported that CXCR3 is related to inflammatory cell infiltration. The purpose of this study was to investigate iodine-125-labeled CXCL10, a ligand of CXCR3, as a tracer targeting CXCR3 to detect acute rejection in a mouse skin transplant model. MATERIALS AND METHODS: The isograft and allograft skin models were established with BALB/c and C57BL/6 mouse skin, respectively, as donors and BALB/c mice as recipients. We used reverse transcriptase-polymerase chain reaction and immunochemistry staining to test CXCR3 expression. ¹²5I-labeled CXCL10 was produced with the iodogenic method. Allograft/isograft mice were examined with whole body autoradiography and ex vivo biodistribution after tail vein injection of ¹²5I-labeled CXCL10 on day 8 posttransplant. RESULTS: CXCR3 expression was higher in allograft tissue than in isograft control. ¹²5I-labeled CXCL10 was prepared with high specificity and affinity. Biodistribution results showed higher ¹²5I-labeled CXCL10 uptake in allograft tissue. The target-to-nontarget ratio was 3.01 ± 0.25 at 24 hours, a result higher than that shown in the isograft group. Pharmacokinetic analyses of ¹²5I-labeled CXCL10 showed that distribution half-life was 0.34 hour and the elimination half-life was 9.83 hours. Dynamic whole body autoradiography images of ¹²5I-labeled CXCL10 showed excellent graft visualization in the allograft compared with the isograft group at all checking points, with visualization much more obvious at 12 and 24 hours. CONCLUSIONS: These data suggest that CXCR3 is a promising imaging target for immune cell infiltration in early-stage acute rejection and ¹²5I-labeled CXCL10 can successfully image acute rejection with good pharmacokinetics.

Design and Rationale for a Phase III, Randomized, Placebo-controlled Trial of Durvalumab With or Without Tremelimumab After Concurrent Chemoradiotherapy for Patients With Limited-stage Small-cell Lung Cancer: The ADRIATIC Study.

Limited-stage (LS) small-cell lung cancer (SCLC) remains an area of high unmet medical need. The standard-of-care therapy comprises curative-intent platinum-based chemotherapy with concurrent radiotherapy (cCRT), which can be followed by prophylactic brain irradiation and then observation. However, most patients will relapse. Durvalumab (antiprogrammed cell death ligand-1) has enhanced the efficacy outcomes after cCRT for patients with unresectable, stage III non-small-cell lung cancer. Recently, durvalumab combined with platinum-etoposide demonstrated a significant survival benefit compared with platinum-etoposide as first-line treatment of patients with extensive-stage SCLC and has also shown antitumor activity as monotherapy and combined with tremelimumab (anticytotoxic T-lymphocyte-associated antigen-4) in pretreated patients with extensive-stage SCLC. ADRIATIC, a phase III, randomized, double-blind, placebo-controlled, multicenter, global study (ClinicalTrials.gov identifier, NCT03703297), is designed to investigate the efficacy of durvalumab, with or without tremelimumab, as consolidation therapy for patients with LS-SCLC without disease progression after cCRT. Approximately 600 patients with documented histologic or cytologic LS-SCLC, World Health Organization/Eastern Cooperative Oncology Group performance status 0 or 1, and no progression after 4 cycles of cCRT will be randomized (1:1:1) to treatment (durvalumab 1500 mg plus placebo every 4 weeks [q4w] for 4 cycles, followed by durvalumab 1500 mg q4w; durvalumab 1500 mg plus tremelimumab 75 mg q4w for 4 cycles, followed by durvalumab 1500 mg q4w; or dual placebo q4w for 4 cycles, followed by single placebo q4w) within 1 to 42 days of completing cCRT, stratified by stage and receipt of prophylactic brain irradiation. The primary endpoints are progression-free survival and overall survival. The secondary endpoints are overall survival and progression-free survival rates, objective response rate, and safety and tolerability. Recruitment began in September 2018.

Impacts of preoperative maximum detrusor pressure on minimally invasive surgery effect on patients with benign prostatic hyperplasia.

BACKGROUND: This study aims to investigate the impacts of preoperative maximum detrusor pressure (Pdet.max) on minimally invasive surgery effect on patients with benign prostatic hyperplasia. METHODS: The clinical data of a total of 156 patients receiving minimally invasive surgery for benign prostatic hyperplasia in Hospital of Nanchang Institute of Medical Sciences from August 2014 to June 2017 were retrospectively reviewed and summarized. The patients were divided into three groups according to different Pdet.max in the urodynamic examination results before the surgery, namely, group A (Pdet.max <50 cmH2O), group B (50≤ Pdet.max <90 cmH2O) and group C (Pdet.max ≥90 cmH2O). The International Prostate Symptom Score (IPSS) and Quality-of-Life score (QOLS) were compared. RESULTS: Compared with those in group A, the IPSS and QOLS of the patients in group B and group C at 1 month, 3 months and 12 months after the surgery were decreased notably (all P<0.05). Moreover, the IPSS and QOLS of the patients in group C were obviously lower than those in group B (all P<0.05). CONCLUSIONS: The results indicated that as the preoperative Pdet.max was increased, the symptoms of the patients receiving minimally invasive surgery for benign prostatic hyperplasia were ameliorated more significantly, and the patients had higher quality of life. The preoperative Pdet.max can judge the treatment effect of minimally invasive surgery on the patients with benign prostatic hyperplasia and help to guide the patients' prognosis. The greater the preoperative Pdet.max is, the better the treatment effect of the patients after the surgery will be, and the higher the quality of life will be.

Safety and tolerability of an anti-CD19 monoclonal antibody, MEDI-551, in subjects with systemic sclerosis: a phase I, randomized, placebo-controlled, escalating single-dose study.

BACKGROUND: Systemic sclerosis (SSc) is a clinically heterogeneous, life-threatening disease characterized by fibrosis, microvasculopathy, and autoimmunity. Extensive nonclinical and clinical data implicate B cells in the pathogenesis of SSc. MEDI-551 is an investigational humanized monoclonal antibody that targets the B cell surface antigen CD19 and mediates antibody-dependent, cell-mediated cytotoxicity of B cells. This clinical study evaluated the safety and tolerability, pharmacokinetics, and pharmacodynamics of MEDI-551 in subjects with SSc. METHODS: This phase I multicenter, randomized, double-blind, placebo-controlled, single escalating dose study enrolled adult subjects with either limited or diffuse cutaneous SSc. A single intravenous dose of MEDI-551 was administered, and safety and tolerability were evaluated. MEDI-551 pharmacokinetics (PK), pharmacodynamics, and immunogenicity were also assessed. Safety assessments included the incidence of adverse events and changes in clinical and laboratory results. MEDI-551 serum concentrations, effects on circulating and tissue B cells and plasma cells (PCs), and antidrug antibodies were analyzed. Modified Rodnan skin score (MRSS) and pulmonary function tests were used to explore the clinical effect of MEDI-551. RESULTS: The study enrolled 28 subjects with SSc (mean age, 47.3 years; 67.9 % female). Twenty-four received a single dose of MEDI-551 (0.1-10.0 mg/kg) and four received placebo. Treatment-emergent adverse events (TEAEs) occurred in 95.8 % of subjects in the MEDI-551 group and in 75.0 % of subjects in the placebo group; the majority of TEAEs were mild or moderate in severity. Two serious adverse events were considered possibly related to the study drug. One death, deemed not related to the study drug, occurred in a MEDI-551-treated subject. MEDI-551 exhibited linear PK in the dose range of 1.0 to 10.0 mg/kg, and more rapid clearance at lower doses. Dose-dependent depletion of circulating B cells and plasma cells was observed. MRSS assessments suggest a possible clinical effect of MEDI-551 on affected skin. CONCLUSIONS: A single escalating dose of MEDI-551 was tolerable and safe in this subject population. B cell depletion was achieved and was dose dependent. A signal of clinical effect was observed. Based on these results, further investigation of MEDI-551 as a disease-modifying treatment for SSc is warranted. TRIAL REGISTRATION: www.clinicaltrials.gov identifier, NCT00946699 ; registered 23 July 2009.

Human ßA3/A1-crystallin splicing mutation causes cataracts by activating the unfolded protein response and inducing apoptosis in differentiating lens fiber cells.

ßγ-Crystallins, having a uniquely stable two domain four Greek key structure, are crucial for transparency of the eye lens,. Mutations in lens crystallins have been proposed to cause cataract formation by a variety of mechanisms most of which involve destabilization of the protein fold. The underlying molecular mechanism for autosomal dominant zonular cataracts with sutural opacities in an Indian family caused by a c.215+1G>A splice mutation in the ßA3/A1-crystallin gene CRYBA1 was elucidated using three transgenic mice models. This mutation causes a splice defect in which the mutant mRNA escapes nonsense mediated decay by skipping both exons 3 and 4. Skipping these exons results in an in-frame deletion of the mRNA and synthesis of an unstable p.Ile33_Ala119del mutant ßA3/A1-crystallin protein. Transgenic expression of mutant ßA3/A1-crystallin but not the wild type protein results in toxicity and abnormalities in the maturation and orientation of differentiating lens fibers in c.97_357del CRYBA1 transgenic mice, leading to a small spherical lens, cataract, and often lens capsule rupture. On a cellular level, the lenses accumulated p.Ile33_Ala119del ßA3/A1-crystallin with resultant activation of the stress signaling pathway - unfolded protein response (UPR) and inhibition of normal protein synthesis, culminating in apoptosis. This highlights the mechanistic contrast between mild mutations that destabilize crystallins and other proteins, resulting in their being bound by the α-crystallins that buffer lens cells against damage by denatured proteins, and severely misfolded proteins that are not bound by α-crystallin but accumulate and have a direct toxic effect on lens cells, resulting in early onset cataracts.

Estimation of ROC curve with complex survey data.

The receiver operating characteristic (ROC) curve can be utilized to evaluate the performance of diagnostic tests. The area under the ROC curve (AUC) is a widely used summary index for comparing multiple ROC curves. Both parametric and nonparametric methods have been developed to estimate and compare the AUCs. However, these methods are usually only applicable to data collected from simple random samples and not surveys and epidemiologic studies that use complex sample designs such as stratified and/or multistage cluster sampling with sample weighting. Such complex samples can inflate variances from intra-cluster correlation and alter the expectations of test statistics because of the use of sample weights that account for differential sampling rates. In this paper, we modify the nonparametric method to incorporate sampling weights to estimate the AUC and employ leaving-one-out jackknife methods along with the balanced repeated replication method to account for the effects of the complex sampling in the variance estimation of our proposed estimators of the AUC. The finite sample properties of our methods are evaluated using simulations, and our methods are illustrated by comparing the estimated AUC for predicting overweight/obesity using different measures of body weight and adiposity among sampled children and adults in the US Hispanic Health and Nutrition Examination Survey.

Simple biologically informed inflammatory index of two serum cytokines predicts 10 year all-cause mortality in older adults.

BACKGROUND: Individual measurements of inflammation have been utilized to assess adverse outcomes risk in older adults with varying degrees of success. This study was designed to identify biologically informed, aggregate measures of inflammation for optimal risk assessment and to inform further biological study of inflammatory pathways. METHODS: In total, 15 nuclear factor-kappa B-mediated pathway markers of inflammation were first measured in baseline serum samples of 1,155 older participants in the InCHIANTI population. Of these, C-reactive protein, interleukin-1-receptor antagonist, interleukin-6, interleukin-18, and soluble tumor necrosis factor-α receptor-1 were independent predictors of 5-year mortality. These five inflammatory markers were measured in baseline serum samples of 5,600 Cardiovascular Health Study participants. A weighted summary score, the first principal component summary score, and an inflammation index score were developed from these five log-transformed inflammatory markers, and their prediction of 10-year all-cause mortality was evaluated in Cardiovascular Health Study and then validated in InCHIANTI. RESULTS: The inflammation index score that included interleukin-6 and soluble tumor necrosis factor-α receptor-1 was the best predictor of 10-year all-cause mortality in Cardiovascular Health Study, after adjusting for age, sex, education, race, smoking, and body mass index (hazards ratio = 1.62; 95% CI: 1.54, 1.70) compared with all other single and combined measures. The inflammation index score was also the best predictor of mortality in the InCHIANTI validation study (hazards ratio 1.33; 95% CI: 1.17-1.52). Stratification by sex and CVD status further strengthened the association of inflammation index score with mortality. CONCLUSION: A simple additive index of serum interleukin-6 and soluble tumor necrosis factor-α receptor-1 best captures the effect of chronic inflammation on mortality in older adults among the 15 biomarkers measured.

Antihypertensive drugs decrease risk of Alzheimer disease: Ginkgo Evaluation of Memory Study.

OBJECTIVES: The aim of this study was to determine whether use of diuretics, angiotensin-1 receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACE-I), calcium channel blockers (CCB), or ß-blockers (BB) was associated with a reduced risk of Alzheimer disease (AD) dementia in participants with normal cognition or mild cognitive impairment (MCI). METHODS: Secondary longitudinal data analysis of the Ginkgo Evaluation of Memory Study in older adults at least 75 years of age with normal cognition (n = 1,928) or MCI (n = 320) over a median 6.1-year period using Cox proportional hazard models after adjusting for confounders. RESULTS: Diuretic use was reported by 15.6%, ARB 6.1%, ACE-I 15.1%, CCB 14.8%, and BB 20.5%. Of the 2,248 participants, 290 (13%) developed AD dementia. Hazard ratio for incident AD dementia among participants with normal cognition was 0.51 in diuretic (95% confidence interval [CI] 0.31-0.82), 0.31 in ARB (95% CI 0.14-0.68), 0.50 in ACE-I (95% CI 0.29-0.83), 0.62 in CCB (95% CI 0.35-1.09), and 0.58 in BB (95% CI 0.36-0.93) users and was not significantly altered when mean systolic blood pressure was above 140 mm Hg. In participants with MCI, only diuretic use was associated with decreased risk (hazard ratio = 0.38, 95% CI 0.20-0.73). CONCLUSIONS: Diuretic, ARB, and ACE-I use was, in addition to and/or independently of mean systolic blood pressure, associated with reduced risk of AD dementia in participants with normal cognition, while only diuretic use was associated with reduced risk in participants with MCI.

[Polymorphism of AR gene CAG copy number and late-onset hypogonadism in males].

OBJECTIVE: To analyze the association of the androgen receptor (AR) gene CAG-STR with late-onset hypogonadism (LOH), and explore the pathogenesis of LOH. METHODS: Our investigation involved 1 000 men aged 40-70 years. We randomly selected 127 normal old and middle-aged males and 19 cases of LOH. We detected their levels of Triglyceride (TG), fasting blood glucose (FBG), serum total testosterone (tT) and free testosterone (fT), measured their body mass index (BMI), height, waist circumference (WC) and blood pressure, and examined the length of CAG repeats of the AR gene in the peripheral blood by PCR. RESULTS: The numbers of CAG repeats ranged from 15 to 32, with a mean value 23.05 +/- 2.95. The mean BMI and FBG were significantly lower (P < 0.01), but TG, tT and fT remarkably higher in the normal than in the LOH men (P < 0.01), while the mean length of (CAG) n repeat polymorphism showed no statistically significant difference between the two groups (22.54 +/- 3.06 vs 23.23 +/- 2.24, P = 0.946). The frequencies of long alleles (n > or = 22) were significantly higher in the LOH than in the normal men (73.68% vs 48.82%, P < 0.05). The numbers of CAG repeats had no significant correlation with tT (r = 0.04, P > 0.05) and fT (r = 0.025, P > 0.05). CONCLUSION: The AR gene CAG length showed polymorphism in LOH men. The long alleles (CAG)n (n > or = 22) repeat polymorphism in the AR gene may be a genetic factor for LOH, but it has to be confirmed by further investigation.

Patterns of 12-year change in physical activity levels in community-dwelling older women: can modest levels of physical activity help older women live longer?

Few studies have addressed changes in physical activity participation over time among the elderly. The authors hypothesized that there were distinct trajectories of physical activity level over time and identifiable predictors of such trajectories, as well as that the maintenance of regular physical activity, even below recommended levels, was associated with lower mortality risk. Using longitudinal data (1994-2009) from 433 initially high-functioning older women aged 70-79 years at baseline, a joint latent class and survival mixture model identified 4 activity trajectory classes: always active (16.6%), fast declining (19.2%), stable moderate (32.3%), and always sedentary (31.9%). Obesity, coronary artery disease, chronic obstructive pulmonary disease, depressive symptoms, low self-efficacy, mobility disability, and low energy were associated with sedentary behavior and/or a fast decline in activity. Women in the fast declining and always sedentary classes had hazard ratios for death of 2.34 (95% confidence interval: 1.20, 4.59) and 3.34 (95% confidence interval: 1.72, 6.47), respectively, compared with the always active class; no mortality difference was found between the stable moderate and always active groups (hazard ratio = 1.24, 95% confidence interval: 0.63, 2.47). Our findings suggest that physical activity does not have to be vigorous to be beneficial and that the gain may be the greatest among women who reported the lowest levels of activity.

Survey for late-onset hypogonadism among old and 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>0.05); 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.

Inflammation and mortality in a frail mouse model.

Mice homozygous for targeted deletion of the interleukin 10 gene (Il-10) have been partially characterized as a model for human frailty. These mice have increased serum interleukin (IL)-6 in midlife, skeletal muscle weakness, and an altered skeletal muscle gene expression profile compared to age and sex-matched C57BL/6 (B6) control mice. In order to further characterize for use as a frailty model, we evaluated the evolution of inflammatory pathway activation, endocrine change, and mortality in these mice. Serum was collected in groups of age- and sex-matched B6.129P2-Il10(tm1Cgn)/J (IL-10(tm/tm)) mice and B6 control mice at age 12, 24, 48, 72, and 90 weeks. Cytokines including IL-6, interleukin 1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), chemokine (C-X-C motif) ligand 1 (KC), IL-12, and IL-10 were measured using electro-chemiluminescent multiplex immunoassay and insulin-like growth factor 1 (IGF-1) was measured using solid-phase enzyme-linked immunosorbent assay. A separate longitudinal cohort was monitored from age 35 weeks to approximately 100 weeks. Survival was evaluated by Kaplan-Meier survival estimates and detailed necropsy information was gathered in a subset of mice that died or were sacrificed. In IL-10(tm/tm) mice compared to B6 controls, serum IL-6, IL-1ß, TNF-α, IFN-γ, KC levels were significantly elevated across the age groups, serum mean IGF-1 levels were higher in the 48-week-old groups, and overall mortality rate was significantly higher. The quadratic relationship between IGF-1 and age was significantly different between the two strains of mice. Serum IL-6 was positively associated with IGF-1 but the effect was significantly larger in IL-10(tm/tm) mice. These findings provide additional rationale for the use of the IL-10(tm/tm) mouse as a model for frailty and for low-grade inflammatory pathway activation.