Exercise to socialize? Bidirectional relationships between physical activity and loneliness in middle-aged and older American adults.

Physical inactivity and loneliness are both associated with health risks and can affect each other through various social and behavioral mechanisms. However, current evidence on this relationship is equivocal and mostly based on cross-sectional data. This longitudinal study aimed to determine whether current levels of physical activity (moderate and vigorous intensity) and loneliness are associated with future respective states of themselves and each other. We used data from waves 6-14 (2002-2018) of the Health and Retirement Study (n = 20 134) in a mixed-effects and random-intercept cross-lagged panel model. Analysis showed that current loneliness and physical activity were associated with each future respective state. Additionally, weekly participation in moderate-intensity, but not vigorous-intensity, physical activity was associated with a lower likelihood of becoming lonely in the future (relative risk [RR] = 0.94; 95% CI, 0.90-0.99). However, changes in physical activity were not associated with deviation from a person's typical level of loneliness (for vigorous intensity, mean deviation [MD] = 0.00; 95% CI: -0.04 to 0.03; for moderate-intensity, MD = 0.01; 95% CI: -0.03 to 0.04). Loneliness was not associated with moderate- or vigorous-intensity physical activity in subsequent waves. This suggests that while lower physical activity levels can be associated with future loneliness, changing levels of physical activity has little impact on loneliness at the individual level.

Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

HMGA1-mediated miR-671-5p targets APC to promote metastasis of clear cell renal cell carcinoma through Wnt signaling.

This study aimed to investigate the effect of miR-671-5p on metastasis of clear cell renal cell carcinoma (ccRCC) and underlying mechanism involved. The migration and invasion of ccRCC cells were determined by transwell and boyden assays in vitro and in vivo. Genes mRNA and protein expression were detected by quantitative polymerase chain reaction (qPCR) and western blot analysis, respectively. The target gene of miRNA was confirmed by luciferase reporter assays. Transcriptional regulation of miRNA by transcription factor was detected by chromatin immunoprecipitation assay (ChIP). The expression of miRNA in clinical specimens were detected by in situ hybridization (ISH). miR-671-5p promoted migration and invasion of ccRCC in vivo and in vitro. Moreover, miR-671-5p directly targeted APC to activate Wnt signaling, thus inducing the epithelial-mesenchymal transition (EMT) in ccRCC. Intriguingly, miR-671-5p expression was transcriptionally enhanced by HMGA1. Consistently, bioinformatics analysis suggested that HMGA1 was positively correlated with miR-671 expression, however, miR-671 was negatively correlated with APC. In situ hybridization analysis showed that miR-671-5p was upregulated in ccRCC compared with paracarcinoma and correlated with poor prognosis of ccRCC patients. In addition, univariate and multivariate analysis indicated that miR-671-5p expression was an independent prognostic factor for overall survival in ccRCC patients. Our data suggest that miR-671-5p is a tumor enhancer in regulating of ccRCC metastasis, and miR-671-5p may be utilized as a factor for the clinical diagnosis and prognosis of ccRCC.

Comparing two classification schemes for seizures and epilepsy in rural China.

BACKGROUND AND PURPOSE: The International League against Epilepsy (ILAE) updated the classifications of seizures and epilepsies in 2017. The 2017 classifications were compared with the 1980s classifications in rural China. METHODS: People with epilepsy receiving treatment under the National Epilepsy Control Programme were recruited from rural areas in China. Their seizures and epileptic syndrome were classified using the 1980s ILAE classification system and then re-classified according to the 2017 system. Differences in seizure, epilepsy and aetiology classifications were identified. RESULTS: A total of 597 individuals (58% males, aged 6-78 years) were included. Amongst them 535 (90%) had a single seizure type, 57 (9.55%) had two types and five (0.84%) had three. There was complete agreement between the 1981 and 2017 classifications for the 525 individuals with focal seizures. Seizures originally classified as generalized in 10 of 65 individuals were re-classified as unknown in the 2017 classification. Compared to the 1980s classifications, the proportion of individuals with unknown seizures and unknown epilepsy increased from 1.2% (7/597) to 2.8% (17/597, P = 0.002), and unknown aetiology increased from 32% (189/597: 182 cryptogenic and seven unclassified) to 39% (230/597; P < 0.001) in the 2017 classifications. CONCLUSIONS: The 1980s and 2017 classifications had 100% agreement in classifying focal seizures and epilepsy in rural China. A small but significant proportion of generalized seizures and epilepsy and aetiologies classified in the old classifications were re-classified to unknown in the new classifications. These results highlight the need for improvement in clinical evaluation of people with epilepsy in resource-poor settings.

Effect of insulin-like growth factor-1 on promoting healing of skin ulcers in diabetic rats.

To investigate the effect of exogenous insulin-like growth factor-1 (IGF-1) on the healing of skin ulcers in diabetic rats, male Sprague Dawleys (SD) rats with back skin ulcers were selected and divided into control group, model group and IGF-1 treatment group which received different doses of IGF-1 (0.5, 1.0, 1.5, and 2.0mg/L). The results showed that the healing speed of the skin ulcers was significantly affected by IGF-1, which reduced the size of wound (P less than 0.05). The expression of MMP-9 was enhanced while the expression of TIMP-1 was decreased in diabetic rats with skin ulcers. The IGF-1 treatment helped to re¬store the normal expression of both MMP-9 and TIMP-1 in diabetic rats with skin ulcers, and diabetic skin ulcers in the 1.5 mg/L IGF-1 group showed the best healing. Histological examination showed that after 20 days, fibroblasts in the IGF-1 experimental group with an appropriate concentration increased and the numbers of fibroblasts and capillaries were significantly higher than those of the other groups. Moreover, there were obvious wound surface contractions and re-epithelialization, and the new epithelium moved to the center of the wound faster. Therefore, it is concluded that an appropriate concentration of IGF-1 can significantly promote the healing of skin ulcers in diabetic rats.

Association between lactic acid sting test scores, self-assessed sensitive skin scores and biophysical properties in Chinese females.

BACKGROUND: Lactic acid sting test (LAST) is a classical method to identify sensitive skin. However, some subjects with self-perceived sensitive skin are negative for LAST. OBJECTIVE: To determine whether LAST scores are associated with specific phenotype of sensitive skin. METHODS: A total of 292 subjects with self-perceived sensitive skin were enrolled in this study. The Sensitive Scale was used to evaluate the severity of burning, stinging, itching, tautness, erythema and scaling based on 0-10 scale scores. In addition to the assessment of LAST scores, epidermal biophysical properties were measured using an MPA system. RESULTS: The Sensitive Scale scores of stinging, itching, tautness and scaling were significantly different between the LAST-positive and -negative groups. However, burning and erythema scores did not differ between the LAST-positive and -negative groups. LAST scores were positively correlated with the Sensitive Scale scores for stinging, itching, tautness and scaling, but not for burning and erythema scores. Moreover, LAST scores negatively correlated with stratum corneum hydration, but positively with transepidermal water loss (TEWL) rates. CONCLUSIONS: Lactic acid sting test scores positively correlated with TEWL rates. LAST scores could be used to identify subjects with sensitive skin characterized mainly by stinging and itching, but not those mainly by burning and erythema.

CONTEXTE: Le test de la piqûre d'acide lactique (LAST) est une méthode classique pour identifier les peaux sensibles. Cependant, certaines personnes s'évaluant ayant une peau sensible sont négatifs au test LAST. OBJECTIF: Déterminer si le score du LAST est associé à un phénotype spécifique de peau sensible. MÉTHODES: Au total, 292 personnes s'évaluant ayant une peau sensible ont été inclus dans cette étude. L'échelle de sensibilité a été utilisée pour évaluer la sévérité de la brûlure, du picotements, de la démangeaison, de la tension, de l'érythème et des desquamations basée sur une échelle de 0-10. En plus de l'évaluation du score LAST, les propriétés biophysiques épidermiques ont été mesurées à l'aide d'un système MPA. RÉSULTATS: Les scores de l'échelle de sensibilité pour le picotement, les démangeaisons, la tension et la desquamation étaient significativement différents entre la groupe LAST positif et celle du LAST négatif. Cependant, les scores de la brûlure et de l'érythème n'étaient pas différents entre les deux groupes. Le score LAST était positivement corrélé avec les scores de l'échelle de sensibilité du picotement, des démangeaisons, de la tension et des desquamations, mais pas pour la brûlure et l'érythème. En plus, les scores LAST étaient négativement corrélés avec l'hydratation du stratum corneum, mais positivement corrélés avec le taux de perte en eau transépidermique (TEWL). CONCLUSIONS: Les scores LAST étaient corrélés positivement avec le taux de perte en eau transépidermique. Les scores LAST pourraient être utilisés pour identifier les personnes avec la peau sensible caractérisée principalement le picotement et les démangeaisons, mais pas la brûlure et l'érythème.

[Clinical characteristics and microsurgical strategy of intracranial posterior circulation aneurysms].

Objective: To explore the clinical characteristics and microsurgical strategies of intracranial posterior circulation aneurysms. Methods: The clinical manifestations, imaging data, surgical approaches and follow-up results of 35 patients with circulating aneurysms (37 aneurysms) treated by microsurgery in the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2018 were analyzed retrospectively. Results: A total of 22 aneurysms were clipped, 13 were clipped and resected, 1 case was clipped and together with AVM resection and 1 case was isolated. Of 37 aneurysms in 35 patients, 11 aneurysms were at the basilar artery apexes, 10 at the posterior cerebral arteries, 6 at the posterior inferior cerebellar arteries, 3 at the basilar arteries, 3 at the vertebral arteries (including 1 case of vertebral arterial dissecting aneurysm), 2 at the anterior inferior cerebellar arteries and 2 at the superior cerebellar arteries. The surgical approaches included pterional approach, extensive pterional approach, infratemporal fossa approach, retrosigmoid approach and far-lateral approach. The Glasgow Outcome Scale (GOS) scores showed good recovery in 24 cases, moderate neurological dysfunction in 6 cases, severe neurological dysfunction in 2 cases, persistent vegetative state in 1 case and 2 cases of death 6 months after their discharge from hospital. Conclusions: Posterior circulation aneurysms are adjacent to important structures. They are deep in position, with small operation space and difficult to operate. Full preoperative evaluation of the condition, selection of appropriate surgical methods are the key factors to benefit the patients.

[Role of a liver pathology standardized scoring system in the diagnosis of congenital biliary atresia and its relationship with prognosis].

Objective: To evaluate the diagnostic value of a histologic scoring system in congenital biliary atresia and its prognostic relevance. Methods: From January 2017 to June 2018 at Children's Hospital of Fudan University, 172 wedge liver biopsy specimens were obtained from infants with neonatal cholestasis [119 patients with congenital biliary atresia (CBA) and 53 patients with non-obstructive cholestasis as control]. A pathologist, single-blinded to the final diagnosis, made the histological diagnosis individually based on an 8-feature (portal ductal proliferation, bile duct reaction, bile plugs in portal ductules, liver fibrosis, edema in portal region, cholestasis, inflammatory cells infiltration in portal region, and ductal plate malformation), 21-point scoring system. Results: The main pathologic changes of biliary atresia were hepatocyte cholestasis, hyperplasia of bile ducts, fibrosis and infiltration of inflammatory cells in the portal area. There were significant difference in the degree of portal edema, bile duct hyperplasia and fibrosis between two groups (P<0.01). In addition, there were characteristic bile duct thrombosis in 97.5%(116/119) of the cases and abnormal development of bile duct plate in 9.2%(11/119) of the cases. Compared with non-CBA infant cholestasis group, the difference was statistically significant (P<0.05). The scoring system has high sensitivity, specificity (both 94.1%) and accuracy (94.3%) in the diagnosis of CBA. A score equal to or more than 11 points supported a diagnosis of CBA; whereas a score less than 11 points might suggest cholestasis. The degree of hepatic fibrosis and ductal plate malformation were related to prognosis. Conclusions: The liver pathology scoring system (8-feature, 21-point) is more accurate in diagnosing CBA than previous methods, which may guide the clinicopathological diagnosis. This histological scoring system also helps to assess the prognosis of CBA.

Risk of hypertension after hysterectomy: a population-based study.

OBJECTIVE: Hysterectomy is the second most common surgery performed mainly for benign uterine pathologies in females. The association between hysterectomy and the subsequent risk of hypertension remains controversial. This study investigated the risk of developing hypertension in women who had a hysterectomy. DESIGN: Population-based retrospective cohort study. SETTING: We used the Taiwan National Health Insurance Research Database with claims data of 1 million randomly selected insured individuals. POPULATION: Women with and without hysterectomy and bilateral salpingo-oophorectomy, aged 30-49 years, were identified in 2000-2013 from the insurance data. METHODS: From the claims data, we identified 6674 women with hysterectomy without hypertension at the time of the surgery. The comparison cohort were 26 696 women randomly selected from women without hysterectomy and hypertension, matched by age and the year hysterectomy was performed. Adjusted hazard ratio (aHR) of hypertension was estimated after controlling for comorbidities. MAIN OUTCOME MEASURE: Prediction for hypertension following hysterectomy for benign disease. RESULTS: Both cohorts had a median age of 43.9 years. After a median follow up of 6.4 years, the incident hypertension was higher in the hysterectomy cohort than in the comparison cohort, with an adjusted hazard ratio (aHR) of 1.35 [95% confidence interval (CI) 1.27-1.44]. The incidence increased with age, with a higher aHR in hysterectomised women aged 40-49 years (aHR 1.37, 95% CI 1.06-1.83) than in those aged 30-39 years (aHR 1.22, 95% CI 1.02-1.46). CONCLUSION: Findings in this study suggest that women with hysterectomy are more likely to be diagnosed with hypertension in the follow-up period. TWEETABLE ABSTRACT: Women with hysterectomy before 50 years of age are at an increased risk of developing subsequent hypertension. PLAIN LANGUAGE SUMMARY: Hysterectomy is one of the most common surgeries for women with benign uterine disease. Hysterectomy may lead to a sudden decline in the production of sex hormone (estrogen and progesterone), which is responsible for vessel wall endothelial dysfunction leading to hardening of arteries and subsequent hypertension. However, the association between hysterectomy and risk of hypertension remains controversial. This study investigated whether premenopausal women have an elevated risk of hypertension after hysterectomy. This study employed the Taiwan National Health Insurance Research Database to identify 6674 women 30-49 years old who had a hysterectomy between 2000 and 2013, and a comparison group of 26 696 women who did not have a hysterectomy matched by age. Women in both the groups had no hypertension at baseline (recruiting date or within 1 year after recruiting date). By the end of 2013, we found that 1196 (17.9%) and 3613 (13.5%) women had developed hypertension in the hysterectomy and the comparison groups, respectively. The hypertension incidence was 1.4-fold greater in the hysterectomy group than in the control group (27.8 versus 20.2/1000 person-years).

An immortalized microglial cell line (Mocha) derived from rat cochlea.

Microglia are glial-immune cells that are essential for the function and survival of the central nervous system. Microglia not only protect neural tissues from immunological insults, but also play a critical role in neural development and repair. However, little is known about the biology of microglia in the cochlea, the auditory portion of the inner ear. In this study, we detected TMEM119+, CD11b+, CD45+ and Iba1+ populations of cells in the rat cochlea, particularly in Rosenthal's canal, inner sulcus and stria vascularis. Next, we isolated and enriched the population of CD11b+ cells from the cochlea and immortalized these cells with the 12S E1A gene of adenovirus in a replication-incompetent retroviral vector to derive a novel microglial cell line, designated Mocha (microglia of the cochlea). The resulting Mocha cells express a number of markers consistent with microglia and respond to lipopolysaccharide (LPS) stimulation by upregulation of genes (Cox2, ICAM-1, Il6r, Ccl2, Il13Ra and Il15Ra) as well as releasing cytokines (IL-1beta, IL-12, IL-13 and RANTES). As evidence of microglial function, Mocha cells phagocytose fluorescent beads at 37°C, but not at 4°C. The expression pattern of microglial markers in Mocha cells suggests that immortalization leads to a more primitive phenotype, a common phenomenon in immortalized cell lines. In summary, Mocha cells display key characteristics of microglia and are now available as a useful model system for the study of cochlear microglial behavior, both in vitro and in vivo.

[Effects of sural nerve nutrition vess els-supported flap for reconstruction of distal lower leg and ankle soft tissue defects].

Objective: To observe the effects of sural nerve nutrition vessels-supported flap for reconstruction of distal lower leg and ankle soft tissue defects. Methods: From June 2014 to June 2017, 37 patients with calf distal and ankle soft tissue defect were repaired with sural nerve nutrition vessels-supported flap, of them 12 cases with calf distal soft tissue defect wounds and 25 cases with ankle soft tissue defect wounds.The scope of flaps was 9 cm×4 cm to 18 cm×9 cm, anti-infection, anti-freezing and dressing treatments were carried out after operation.The results of two-point discrimination among reexamination were recorded. Results: All the flaps survived without ulcer and effusion, only 1 flap for reconstruction of medial malleolus swelled and deactivated at the beginning while it recovered with proper dressings.During the follow-up periods, all the flaps kept favorable feelings, aspects and functions, and the two-point discrimination was 5 to 15 mm [averaged (11.2±1.7) mm]. Conclusion: Sural nerve nutrition vessels-supported flap brings significant effects with excellent safety and reliability in repairing calf and ankle soft tissue defects.

Aerobic respiration by haemocyanin in the embryo of the migratory locust.

It remains unresolved how insect embryos acquire sufficient oxygen to sustain high rates of respiratory metabolism during embryogenesis in the absence of a fully developed tracheal system. Our previous work showed that the two distinct subunits (Hc1 and Hc2) of haemocyanin (Hc), a copper-containing protein, display embryo-specific high expression that is essential for embryonic development and survival in the migratory locust Locusta migratoria. Here we investigated the role of haemocyanins in oxygen sensing and supply in the embryo of this locust. Putative binding sites for hypoxia-regulated transcription factors were identified in the promoter region of all of the Hc1 and Hc2 genes. Embryonic expression of haemocyanins was highly upregulated by ambient O2 deprivation, up to 10-fold at 13% O2 content. The degree of upregulation of haemocyanins increased with increasing levels of hypoxia. Compared with low-altitude locusts, embryonic expression of haemocyanins in high-altitude locusts from Tibetan plateau was constitutively higher and more robust to oxygen deprivation. These findings strongly suggest an active involvement of haemocyanins in oxygen exchange in embryos. We thus propose a mechanistic model for embryo respiration in which haemocyanin plays a key role by complementing the tracheal system for oxygen transport during embryogenesis.

Adherence to the 2006 American Heart Association's Diet and Lifestyle Recommendations for cardiovascular disease risk reduction is associated with bone mineral density in older Chinese.

This cross-sectional study investigated the association between the modified 2006 American Heart Association Diet and Lifestyle Recommendations (AHA-DLR) and bone mineral density in Chinese adults. We found that better adherence to the AHA-DLR associated with higher bone mineral density (BMD) at multiple sites. INTRODUCTION: Accumulating evidence shows that cardiovascular disease (CVD) and osteoporosis are associated with each other, yet little research has focused on whether strategies to reduce CVD risk could also benefit bone health. We aimed to assess the association between adherence to the modified 2006 American Heart Association Diet and Lifestyle Recommendations (AHA-DLR) and BMD in Chinese adults. METHODS: We included 2092 women and 1051 men aged 40-75 years in this community-based cross-sectional study. Dietary information was assessed using a 79-item food frequency survey through face-to-face interviews at baseline (2008-2010) and 3 years later (2011-2013). Adherence to the AHA-DLR was assessed using modified diet and lifestyle scores (American Heart Association Diet and Lifestyle Score (AHA-DLS)) adjusted for bone health. BMD for the whole body, lumbar spine, total hip, femur neck, and trochanter sites was measured using dual-energy X-ray absorptiometry in 2011-2013. RESULTS: After adjusting for potential covariates, greater adherence to the modified AHA-DLS was positively and dose-dependently associated with BMD. The mean BMD was 1.93-3.11% higher in quartile 4 (vs. 1) (all p values <0.01) at multiple sites. Five-unit increases in the modified AHA-DLS score were associated with 4.20-6.07, 4.44-8.51, and 3.36-4.67 mg/cm2 increases in BMD at multiple sites for the total subjects, males, and females, respectively (all p values <0.01). CONCLUSIONS: Better adherence to the AHA-DLR shows protective associations with BMD at multiple sites in the middle-aged and elderly Chinese population.

Thermotolerant hemicellulolytic and cellulolytic enzymes from Eupenicillium parvum 4-14 display high efficiency upon release of ferulic acid from wheat bran.

AIMS: To characterize the hemicellulolytic and cellulolytic enzymes from novel fungi, and evaluate the potential of novel enzyme system in releasing ferulic acid (FA) from biomass resource. METHODS AND RESULTS: A hemicellulolytic and cellulolytic enzyme-producing fungus 4-14 was isolated from soil by Congo red staining method, and identified as Eupenicillium parvum based on the morphologic and molecular phylogenetic analysis. The optimum temperature of fungal growth was 37°C. Hemicellulolytic and cellulolytic enzymes were produced by this fungus in solid-state fermentation (SSF), and their maximum activities were 554, 385, 218, 2·62 and 5·25 U g(-1) for CMCase, xylanase, ß-glucosidase, FPase and FAE respectively. These enzymes displayed the best catalytic ability at low pH values (pH 4·5-5·0). The optimum temperatures were 70°C, 70°C, 75°C and 55°C for CMCase, ß-glucosidase, xylanase and FAE respectively. CMCase, xylanase and FAE were stable at different pHs or high temperature (60°C). Enzymatic hydrolysis experiment indicated that the maximum (76·8 ± 4)% of total alkali-extractable FA was released from de-starched wheat bran by the fungal enzyme system. CONCLUSIONS: High activities of thermotolerant CMCase, ß-glucosidase, xylanase and FAE were produced by the newly isolated fungus E. parvum 4-14 in SSF. The fungal enzyme system displayed high efficiency at releasing FA from wheat bran. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides a new fungal strain for researches of novel hemicellulolytic and cellulolytic enzymes and will improve the bioconversion and utilization of agricultural by-products.

[Application of Multiple Displacement Amplification in Samples with Inhibitors].

OBJECTIVES: To explore the ability of inhibition resistibility of multiple displacement amplification （MDA） in samples with inhibitors. To explain the application and value of MDA in forensic medicine by comparing with using magnetic beads methods （MBM） to purify sample. METHODS: Different concentrations of hemoglobin and humid acid （HA） mixed with DNA samples and then divided the samples into MDA group, MBM group and control group. D3S1358 locus was amplified and detected by polyacrylamide gel electrophoresis detection system and AmpFℓSTR® Identifiler™ Plus Kit-capillary electrophoresis detection system. RESULTS: When hemoglobin concentrations exceed 1 ng/µL or HA concentrations exceed 0.1 ng/µL, amplification products could not be obtained by single-locus system in control group. When hemoglobin concentration exceeds 100 ng/µL or HA concentrations exceed 1 ng/µL, the samples could not be amplified by MBM. Inhibitors in different concentrations were amplified successfully in MDA group without any influence from inhibitors. CONCLUSIONS: MDA has the capability to remove the inhibition of hemoglobin and HA, which is better than MBM and has a certain value in forensic practices.

Efficient siRNA transfection to the inner ear through the intact round window by a novel proteidic delivery technology in the chinchilla.

The use of small-interfering RNA (siRNA) has great potential for the development of drugs designed to knock down the expression of damage- or disease-causing genes. However, because of the high molecular weight and negative charge of siRNA, it is restricted from crossing the blood-cochlear barrier, which limits the concentration and size of molecules that are able to gain access to cells of the inner ear. Intratympanic approaches, which deliver siRNA to the middle ear, rely on permeation through the round window for access to the structures of the inner ear. We developed an innovative siRNA delivery recombination protein, TAT double-stranded RNA-binding domains (TAT-DRBDs), which can transfect Cy3-labeled siRNA into cells of the inner ear, including the inner and outer hair cells, crista ampullaris, macula utriculi and macula sacculi, through intact round-window permeation in the chinchilla in vivo, and there were no apparent morphological damages for the time of observation. We also found that Cy3-labeled siRNA could directly enter spiral ganglion neurons and the epithelium of the stria vascularis independently; however, the mechanism is unknown. Therefore, as a non-viral vector, TAT-DRBD is a good candidate for the delivery of double-stranded siRNAs for treating various inner ear ailments and preservation of hearing function.

Hepatocyte growth factor upregulates nexilin gene expression in cardiomyocytes via JNK pathway.

Hepatocyte growth factor (HGF) is a protective factor in myocardial injury, but its mechanisms of action have not yet been fully elucidated. Nexilin, which locates specifically to the Z-disc, is a novel Z-disc protein that enables the Z-discs to persistently withstand the extreme mechanical forces generated during muscle contraction. Therefore, we investigated the role of HGF in modulating nexilin expression in hypoxia-reoxygenation (H/R)-treated cardiomyocytes. We cultured neonatal cardiomyocytes and treated them with HGF. The mRNA and protein levels of nexilin were determined by RT-PCR and Western blotting. H/R treatment decreased nexilin mRNA expression and nexilin protein levels in cardiomyocytes. Furthermore, treatment with HGF upregulated nexilin expression and the JNK inhibitor SP600125 partly inhibited HGF-induced nexilin upregulation. In conclusion, our results suggest that ischemia-reperfusion injury may downregulate nexilin expression in cardiomyocytes, and HGF may exert its protective role during myocardial ischemic injury through upregulation of nexilin expression in cardiomyocytes.

Physical activity classification utilizing SenseWear activity monitor in manual wheelchair users with spinal cord injury.

STUDY DESIGN: Validation. OBJECTIVES: The primary aim of this study was to develop and evaluate activity classification algorithms for a multisensor-based SenseWear (SW) activity monitor that can recognize wheelchair-related activities performed by manual wheelchair users (MWUs) with spinal cord injury (SCI). The secondary aim was to evaluate how the accuracy in activity classification affects the estimation of energy expenditure (EE) in MWUs with SCI. SETTING: University-based laboratory. METHODS: Forty-five MWUs with SCI wore a SW on their upper arm and participated in resting, wheelchair propulsion, arm-ergometery and deskwork activities. The investigators annotated the start and end of each activity trial while the SW collected multisensor data and a portable metabolic cart collected criterion EE. Three methods including linear discriminant analysis, quadratic discriminant analysis (QDA), and Naïve Bayes (NB) were used to develop classification algorithms for four activities based on the training data set from 36 subjects. RESULTS: The classification accuracy was 96.3% for QDA and 94.8% for NB when the classification algorithms were tested on the validation data set from nine subjects. The average EE estimation errors using the activity-specific EE prediction model were 5.3±21.5% and 4.6±22.8% when the QDA and NB classification algorithms were applied, respectively, as opposed to 4.9±20.7% when 100% classification accuracy was assumed. CONCLUSION: The high classification accuracy and low EE estimation errors suggest that the SW can be used by researchers and clinicians to classify and estimate the EE for the four activities tested in this study among MWUs with SCI.

The Joint Effect of Body Mass Index and Serum Lipid Levels on Incident Dementia among Community-Dwelling Older Adults.

OBJECTIVES: This study aimed to explore the joint effect of body mass index (BMI) and serum lipids levels on incident dementia. METHODS: We prospectively followed up with 1,627 dementia-free community residents aged ≥60 for 5.7 years on average. At baseline, weight, and height were measured, and total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were detected in serum. Demographic characteristics were collected through questionnaires. Dementia was based on consensus diagnosis of neurologists and neuropsychologists using DSM-IV criteria. Additive Cox proportional model was used to assess the exposure-response relationship between BMI and serum lipid levels and dementia risk. Interactions and further classifications of BMI and serum lipid levels were further presented by bivariate surface models and decision-tree models. RESULTS: The joint effects of TC with BMI, TG with BMI, and LDL-C with BMI on the risk of incident dementia shared a similar pattern, different from their independent exposure-response curves. The joint effect of HDL-C with BMI showed an S-surface but without statistical significance. Participants with TC<5.4 mmol/L and BMI<21 kg/m2 (Hazard Ratio(HR) 1.93, 95% Confidence Interval (CI) 1.05-3.53), TC<5.4 mmol/L and BMI≥21 kg/m2 (HR 1.73, 95% CI 1.09-2.72), and TC≥5.4 mmol/L and BMI<21 kg/m2 (HR 4.02, 95% CI 2.10-7.71) were identified to have the increased risk of incident dementia compared to those with TC≥5.4 mmol/L and BMI≥21 kg/m2. Participants with TG<1.7 mmol/L and BMI<21 kg/m2 had an increased risk of incident dementia compared to those with TG≥1.7 mmol/L and BMI≥21 kg/m2 (HR 1.98, 95%CI 1.17-3.3). Participants with LDL-C≥3.3 mmol/L and BMI<21 kg/m2 were identified to have an increased risk of incident dementia compared to those with LDL-C≥3.3 mmol/L and BMI≥21 kg/m2 (HR 3.33, 95%CI 1.64-6.78). CONCLUSIONS: Our study showed that low BMI combined with low or high levels of serum lipids may increase the risk of dementia among older adults. This finding suggests the potential impacts of these two metabolic indexes on the risk of dementia.