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Objective: The aims of this work were to evaluate the effects of home-based telesupervising rehabilitation on physical function for stroke survivors with hemiplegia and to determine if the rehabilitation therapy can relieve the burden on caregivers. Design: This study is a randomized, controlled, assessor-blinded trial. Stroke survivors were randomly assigned to either home-based telesupervising rehabilitation group or conventional rehabilitation group to receive physical exercise and electromyography-triggered neuro-muscular stimulation. Modified Barthel Index, Berg Balance Scale, modified Rankin Scale, Caregiver Strain Index, root mean square of extensor carpi radialis longus and tibialis anterior muscle were measured at 3 time points: baseline, postintervention (12 weeks), and 12-week follow-up (24 weeks). Results: Both the home-based telerehabilitation and conventional rehabilitation groups demonstrated significant effects within groups over the 3 time points in increasing Modified Barthel Index, Berg Balance Scale, and root mean square value of extensor carpi radialis longus and tibialis anterior, as well as decreasing Caregiver Strain Index (P < 0.001), but none of the between-group differences was significant. For modified Rankin Scale, the percentage of participants of grades 0 and 1 in 2 groups increased over time without significant difference between the groups. Conclusions: Home-based telesupervising rehabilitation is most likely as effective as the conventional outpatient rehabilitation for improving functional recovery in stroke survivors and could ease the burden of caregivers as conventional rehabilitation. [ABSTRACT FROM AUTHOR]

Introduction: Invasive aspergillosis (IA) is associated with a significant clinical and economic burden. The phase III SECURE trial demonstrated non-inferiority in clinical efficacy between isavuconazole and voriconazole. No studies have evaluated the cost-effectiveness of isavuconazole compared to voriconazole. The objective of this study was to evaluate the costs and cost-effectiveness of isavuconazole vs. voriconazole for the first-line treatment of IA from the US hospital perspective.Methods: An economic model was developed to assess the costs and cost-effectiveness of isavuconazole vs. voriconazole in hospitalized patients with IA. The time horizon was the duration of hospitalization. Length of stay for the initial admission, incidence of readmission, clinical response, overall survival rates, and experience of adverse events (AEs) came from the SECURE trial. Unit costs were from the literature. Total costs per patient were estimated, composed of drug costs, costs of AEs, and costs of hospitalizations. Incremental costs per death avoided and per additional clinical responders were reported. Deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted.Results: Base case analysis showed that isavuconazole was associated with a $7418 lower total cost per patient than voriconazole. In both incremental costs per death avoided and incremental costs per additional clinical responder, isavuconazole dominated voriconazole. Results were robust in sensitivity analysis. Isavuconazole was cost saving and dominant vs. voriconazole in most DSA. In PSA, isavuconazole was cost saving in 80.2% of the simulations and cost-effective in 82.0% of the simulations at the $50,000 willingness to pay threshold per additional outcome.Conclusion: Isavuconazole is a cost-effective option for the treatment of IA among hospitalized patients.Funding: Astellas Pharma Global Development, Inc. [ABSTRACT FROM AUTHOR]

Mitochondrial dynamics-fission and fusion-are associated with ischaemic heart disease ( IHD). This study explored the protective effect of vagal nerve stimulation ( VNS) against isoproterenol ( ISO)-induced myocardial ischaemia in a rat model and tested whether VNS plays a role in preventing disorders of mitochondrial dynamics and function. Isoproterenol not only caused cardiac injury but also increased the expression of mitochondrial fission proteins [dynamin-related peptide1 (Drp1) and mitochondrial fission protein1 (Fis-1)) and decreased the expression of fusion proteins (optic atrophy-1 ( OPA1) and mitofusins1/2 (Mfn1/2)], thereby disrupting mitochondrial dynamics and leading to increase in mitochondrial fragments. Interestingly, VNS restored mitochondrial dynamics through regulation of Drp1, Fis-1, OPA1 and Mfn1/2; enhanced ATP content and mitochondrial membrane potential; reduced mitochondrial permeability transition pore ( MPTP) opening; and improved mitochondrial ultrastructure and size. Furthermore, VNS reduced the size of the myocardial infarction and ameliorated cardiomyocyte apoptosis and cardiac dysfunction induced by ISO. Moreover, VNS activated AMP-activated protein kinase ( AMPK), which was accompanied by phosphorylation of Ca2+/calmodulin-dependent protein kinase kinase β (Ca MKKβ) during myocardial ischaemia. Treatment with subtype-3 of muscarinic acetylcholine receptor (M3R) antagonist 4-diphenylacetoxy- N-methylpiperidine methiodide or AMPK inhibitor Compound C abolished the protective effects of VNS on mitochondrial dynamics and function, suggesting that M3R/Ca MKKβ/ AMPK signalling are involved in mediating beneficial effects of VNS. This study demonstrates that VNS modulates mitochondrial dynamics and improves mitochondrial function, possibly through the M3R/Ca MKKβ/ AMPK pathway, to attenuate ISO-induced cardiac damage in rats. Targeting mitochondrial dynamics may provide a novel therapeutic strategy in IHD. [ABSTRACT FROM AUTHOR]

Background: To assess the efficacy and safety of the herbal medicine, Weng-li-tong (WLT) as monotherapy or combined with tolterodine in women with overactive bladder (OAB).Methods: A prospective, randomized, single-blind multi-center trial was performed which included 182 OAB patients treated with either placebo (n = 26), WLT (n = 52), tolterodine (n = 52) or WLT plus tolterodine (n = 52). The overactive bladder symptom score (OABSS) and micturition behavior were measured to evaluate treatment efficacy.Results: In total, 146 patients [placebo (n = 23), WLT (n = 39), tolterodine (n = 41) and WLT plus tolterodine (n = 43)] completed 8 weeks of treatment. Compared to those treated with placebo, patients in three intervention groups showed significant improvements in the OABSS, voiding frequency, average voided volume and urgency incontinence. WLT had a slower onset than tolterodine or combination therapy in reducing urgency incontinence. Compared with tolterodine, WLT had a weaker effect in improving OABSS (P = 0.022) and daily voiding frequency (P = 0.034). The combination therapy had better efficacy than WLT or tolterodine alone in improving the OABSS, voiding frequency and voided volume. No significant differences in the changes in quality of life scores were observed among the three intervention groups. Residual urine increased significantly in tolterodine group (P = 0.004), but not in combination group. WLT resulted in fewer adverse effects than tolterodine such as dry mouth (P = 0.002), weak stream (P = 0.002) and less residual urine (P < 0.001).Conclusions: WLT could improve OAB symptoms in women, while it had slower onset and weaker efficacy but fewer adverse effects than tolterodine. The combination of WLT and tolterodine was more efficacious than tolterodine alone in improving OAB symptoms.Trial Registration: Chinese Clinical Trial Registry [ ChiCTR-IPR-14005626 ]. Date of registration: 7 December 2014. [ABSTRACT FROM AUTHOR]

Objectives: Few randomized controlled studies have compared antibiotic regimens against diabetic foot infections (DFIs) in Chinese patients. We evaluated the efficacy and safety of ertapenem versus piperacillin/tazobactam for the treatment of DFIs in Chinese patients.Methods: Patients with moderate to severe DFIs requiring parenteral antibiotics were randomized in a 1 : 1 ratio to receive ertapenem (1.0 g once daily) or piperacillin/tazobactam (4.5 g every 8 h) by 30 min intravenous (iv) infusions for ≥5 days. The primary outcome was favourable clinical response at discontinuation of iv therapy (DCIV). An evaluable-patient population was identified for primary analysis of non-inferiority at -15%. Safety was assessed. ClinicalTrials.gov: NCT01370616.Results: Of 565 patients randomized, 443 patients (ertapenem = 219 and piperacillin/tazobactam = 224) were clinically evaluable for primary analysis. In the clinically evaluable population, the proportions of patients with favourable clinical response at DCIV were 93.6% (205/219) and 97.3% (218/224) in the ertapenem and piperacillin/tazobactam groups, respectively (difference: -3.8%, 95% CI: -8.3%, 0.0%). Ertapenem had a significantly lower favourable clinical response rate (91.5% versus 97.2%, 95% CI for difference: -12.1%, -0.3%) at DCIV in severe DFI patients. In the modified ITT population, 88.8% (237/267) and 90.6% (241/266) of patients in the ertapenem and piperacillin/tazobactam groups, respectively, had favourable clinical responses at DCIV (difference: -1.9%, 95% CI: -7.3%, 3.3%). Microbiological eradications of causative pathogens and adverse events were similar between treatment groups.Conclusions: Treatment with ertapenem was non-inferior to piperacillin/tazobactam in Chinese patients with DFIs. Ertapenem treatment resulted in a markedly lower rate of clinical resolution in severe DFIs. [ABSTRACT FROM AUTHOR]

Background and Purpose: The activation of M3 cholinoceptors (M3 receptors) by choline reduces cardiovascular risk, but it is unclear whether these receptors can regulate ischaemia/reperfusion (I/R)-induced vascular injury. Thus, the primary goal of the present study was to explore the effects of choline on the function of mesenteric arteries following I/R, with a major focus on Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) regulation.Experimental Approach: Rats were given choline (10 mg · kg(-1), i.v.) and then the superior mesenteric artery was occluded for 60 min (ischaemia), followed by 90 min of reperfusion. The M3 receptor antagonist, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP), was injected (0.12 μg · kg(-1), i.v.) 5 min prior to choline treatment. Vascular function was examined in rings of mesenteric arteries isolated after the reperfusion procedure. Vascular superoxide anion production, CaMKII and the levels of Ca(2+)-cycling proteins were also assessed.Key Results: Choline treatment attenuated I/R-induced vascular dysfunction, blocked elevations in the levels of reactive oxygen species (ROS) and decreased the up-regulated expression of oxidised CaMKII and phosphorylated CaMKII. In addition, choline reversed the abnormal expression of Ca(2+)-cycling proteins, including Na(+)Ca(2+) exchanger, inositol 1,4,5-trisphosphate receptor, sarcoplasmic reticulum Ca(2+)-ATPase and phospholamban. All of these cholinergic effects of choline were abolished by 4-DAMP.Conclusions and Implications: Our data suggest that inhibition of the ROS-mediated CaMKII pathway and modulation of Ca(2+)-cycling proteins may be novel mechanisms underlying choline-induced vascular protection. These results represent a significant addition to the understanding of the pharmacological roles of M3 receptors in the vasculature, providing a new therapeutic strategy for I/R-induced vascular injury. [ABSTRACT FROM AUTHOR]

Background: Liver fibrosis is a feature in the majority of chronic liver diseases and oxidative stress is considered to be its main pathogenic mechanism. Antioxidants including vitamin E, are effective in preventing liver fibrogenesis. Several plant-drived antioxidants, such as silymarin, baicalin, beicalein, quercetin, apigenin, were shown to interfere with liver fibrogenesis. The antioxidans above are polyphenols, flavonoids or structurally related compounds which are the main chemical components of Pomegranate peels and seeds, and the antioxidant activity of Pomegranate peels and seeds have been verified. Here we investigated whether the extracts of pomegranate peels (EPP) and seeds (EPS) have preventive efficacy on liver fibrosis induced by carbon tetrachloride (CCl4) in rats and explored its possible mechanisms. Methods: The animal model was established by injection with 50 % CCl4 subcutaneously in male wistar rats twice a week for four weeks. Meanwhile, EPP and EPS were administered orally every day for 4 weeks, respectively. The protective effects of EPP and EPS on biochemical metabolic parameters, liver function, oxidative markers, activities of antioxidant enzymes and liver fibrosis were determined in CCl4-induced liver toxicity in rats. Results: Compared with the sham group, the liver function was worse in CCl4 group, manifested as increased levels of serum alanine aminotransferase, aspartate aminotransferase and total bilirubin. EPP and EPS treatment significantly ameliorated these effects of CCl4. EPP and EPS attenuated CCl4--induced increase in the levels of TGF-β1, hydroxyproline, hyaluronic acid laminin and procollagen type III. They also restored the decreased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and inhibited the formation of lipid peroxidized products in rats treated with CCl4. Conclusion: The EPP and EPS have protective effects against liver fibrosis induced by CCl4, and its mechanisms might be associated with their antioxidant activity, the ability of decreasing the level of TGF-β1 and inhibition of collagen synthesis. [ABSTRACT FROM AUTHOR]

Background: Nutcracker syndrome is an entity resulting from left renal vein compression by the aorta and the superior mesenteric artery, which leads to symptoms of hematuria or left flank pain. The alternative option of endovascular or extravascular stenting is very appealing because of the minimal invasive procedures. Stents in the renal vein can cause fibromuscular hyperplasia, proximal migration or embolization. Case presentation: A 30-year-old female was diagnosed with nutcracker syndrome for severe left flank pain. After failed conservative approach, she underwent endovascular stenting and subsequently developed recurrent symptom for stent migration one month postoperatively. She underwent successful extravascular stenting with complete symptom resolution. Conclusion: The extravascular stenting is an alternative option after migration of left renal vein endovascular stenting. The computed tomographic imaging was closely correlated to therapeutic interventions and stent migration. [ABSTRACT FROM AUTHOR]

BACKGROUND Aliskiren, a direct renin inhibitor, is effective for reducing blood pressure (BP) in patients with hypertension when combined with amlodipine or hydrochlorothiazide (HCTZ). However, the efficacy and tolerability of the 2 combinations are unclear. We performed a meta-analysis of randomized controlled trials of aliskiren/amlodpine and aliskiren/HCTZ for hypertension. METHODS The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and the Novartis clinical trial database were searched through December 2012 for reports of randomized controlled trials of aliskiren/amlodpine and aliskiren/HCTZ vs. monotherapy in patients with hypertension. The main outcome measures were reduction in systolic BP and diastolic BP from baseline and rates of therapeutic response and BP control. Tolerance of aliskiren/amlodipine and aliskiren/HCTZ was also analyzed. Outcomes were initially pooled by standard random-effects methods, producing a weighted mean difference (WMD) or risk ratio (RR) and 95% confidence intervals (CIs). The pooled estimates were then used for adjusted indirect comparisons. RESULTS We selected 19 reports of trials involving 13,614 participants. Aliskiren/amlodpine and aliskiren/HCTZ were more effective than monotherapy in controlling BP. Aliskiren/amlodipine was significantly more effective than aliskiren/HCTZ in reducing systolic BP (WMD = −3.36mm Hg; 95% CI = −4.64 to 2.07mm Hg) and diastolic BP (WMD = −3.49mm Hg; 95% CI = −4.34 to 2.63mm Hg). As compared with aliskiren/HCTZ, alikiren/amlodipine was associated with higher rate of therapeutic response (RR = 1.23; 95% CI = 1.14–1.33) and BP control (RR = 1.24; 95% CI = 1.11–1.39). Number of adverse events and withdrawals due to adverse events were similar with aliskiren/amlodipine and aliskiren/HCTZ. CONCLUSIONS BP control is better with aliskiren combined with amlodipine or HCTZ than with monotherapy, with aliskiren/amlodipine being more effective than aliskiren/HCTZ. [ABSTRACT FROM PUBLISHER]

Angiotensin II (ANG II)-induced inflammatory and oxidative stress responses contribute to the pathogenesis of hypertension. In this study, we determined whether renin-angiotensin system (RAS) activation in the hypothalamic paraventricular nucleus (PVN) contributes to the ANG II-induced hypertensive response via interaction with neurotransmitters in the PVN. Rats underwent subcutaneous infusion of ANG II or saline for 4 weeks. These rats were treated for 4 weeks through bilateral PVN infusion with either vehicle or losartan (LOS), an angiotensin II type 1 receptor (AT1-R) antagonist, via osmotic minipump. ANG II infusion resulted in higher levels of glutamate, norepinephrine (NE), AT1-R and pro-inflammatory cytokines (PIC), and lower level of gamma-aminobutyric acid (GABA) in the PVN. Rats receiving ANG II also had higher levels of mean arterial pressure, plasma PIC, NE and aldosterone than control animals. PVN treatment with LOS attenuated these ANG II-induced hypertensive responses. In conclusion, these findings suggest that the RAS activation in the PVN contributes to the ANG II-induced hypertensive response via interaction with PIC and neurotransmitters (glutamate, NE and GABA) in the PVN. [ABSTRACT FROM AUTHOR]

1. The role of celecoxib in cardiovascular events remains contentious. The aim of the present study was to investigate the effects of celecoxib in acute myocardial ischaemia (AMI) in rabbits in comparison with those of another non-steroidal anti-inflammatory drug, namely aspirin. 2. Male New Zealand white rabbits were divided into four groups: (i) a sham-operated group; (ii) an AMI group, in which the left anterior descending coronary arteries were occluded for 60 min; (iii) the celecoxib + AMI group, pretreated with 3 mg/kg celecoxib, twice a day, for 3 days before AMI induction; and (iv) the aspirin + AMI group, pretreated with 12.5 mg/kg aspirin, twice a day, for 3 days before AMI induction. Haemodynamic parameters were monitored using a multichannel physiological recorder. Serum levels of creatine kinase (CK), malondialdehyde (MDA), cyclo-oxygenase-2 (COX-2), tumour necrosis factor (TNF)-a, total nitrate/nitrite (NOx), nitric oxide synthase (NOS) and myocardial infarct size were determined. Changes in isometric tension of isolated coronary rings were recorded by a myograph system. 3. Compared with the sham group, the AMI group had lower blood pressure, higher left ventricular (LV) end-diastolic pressure, depressed maximum dP/dt of LV pressure, a larger infarct size and higher CK and MDA levels. Celecoxib, but not aspirin, pretreatment significantly ameliorated these effects of AMI. Celecoxib reversed AMI-induced increases in COX-2 levels to a similar extent as aspirin. Pretreatment with celecoxib resulted in a significant reduction in TNF-a levels and an increase in NOx and NOS levels compared with the AMI group. The dysfunctional vasoconstriction and vasodilation of coronary arteries were ameliorated by celecoxib administration. 4. In conclusion, the experimental evidence suggests that celecoxib exerts its protective effects in a COX-independent manner. [ABSTRACT FROM AUTHOR]

The article discusses the study which aims to devise an evidence-based treatment for acute spinal cord injury. The study used research articles regarding the subject from various sources, such as the National Guideline Clearinghouse (NGC), Cochrane Library and TRIP Database. The review found recommendations such as early performance of surgery, the use of heparin and respiratory muscle training. It concluded that evidence-based medicine offers improved treatment of spinal cord injury.

Objective: To evaluate the urodynamic parameters, development of bladder function and complications of clean intermittent self-catheterization (CIC) in Chinese schoolchildren with neurogenic underactive bladder. Methods: Ninety-three children with neurogenic underactive bladder were successfully treated with CIC or combined with oxybutynin for two years follow-up. According to bladder compliance before CIC, they were subdivided into a normal bladder compliance (NBC) group and a low bladder compliance (LBC) group. Urodynamic parameters and complications were recorded. Results: At follow-up, the incidence of neurogenic detrusor overactivity was found to have significantly decreased in both groups. Moreover, maximum cystometric capacity (CC) and relatively safe CC in the NBC group was significantly higher than those before CIC. However, relatively safe CC was significantly lower than that before CIC, and detrusor leakage point pressure was significantly higher than that before CIC in the LBC group. The incidences of bacteriuria, vesicureteral reflux (VUR), febrile urinary tract infections (UTI) and macroscopic hematuria were, respectively, 62, 13, 25 and 15%, and those of VUR and febrile UTI in the LBC group were significantly higher than those in the NBC group. Conclusion: For these cases, the complications of CIC are rare, and bladder compliance seems to be correlated with the development of bladder function and complications during CIC. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the efficacy of endoscopic biliary stenting on common bile duct stones. METHODS: Fifty patients with choledocholithiasis were treated with endoscopic biliary stenting and followed. The early and late outcome was assessed. RESULTS: The procedure was successful in all patients and there was only one patient with mild pancreatitis. The patency rates of stent at 6 months, 12 months and 24 months after biliary stenting were 94%, 79% and 58%, respectively. The rate of reduction in size of stone was 60%. CONCLUSION: Endoscopic biliary stenting was not a definitive treatment of choledocholithiasis. It may be an option for patients clinically unfit for definitive treatment. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the effect of a self-releasing biliary stent antegradely placed during laparoscopic common bile duct exploration (LCBDE) for choledocholithiasis. Materials and Methods: The soft biliary stent, made of polyurethane, was designed as a J-umbrella form with a pigtailed duodenal part and an umbrella-like biliary anchoring part shaped with the rapidly absorbable suture. After the clearance of stones during LCBDE, a guide wire was inserted into the duodenum through the choledochoscope. The stent was advanced over the guide wire until the pigtail of the stent entered the duodenum. The choledochotomy was primarily closed. Results: This technique has been performed on 33 patients with choledocholithiasis. The median length of postoperative hospital stay was 4.3 (3–8) days. All the stents were eliminated from the bile ducts and discharged out of the body. The median time of the stent stay in the body was 13.6 (± 2.55) days. Transient hyperamylasemia occurred in 4 of the 33 (12.1%) patients, and stent occlusion occurred in 1 patient who recovered soon after treatment. No bile leak, biliary infection, or stent dislocation was observed. During the follow-up of 12 months, no biliary infection, residual calculi, or stricture occurred. Conclusion: This novel self-releasing stent is safe and effective in the laparoscopic treatment of choledocholithiasis, and the subsequent removal of the stent can be avoided. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the treatment of portal cavernous transformation (PVCT). The surgical treatment of 18 patients with PVCT was studied retrospectively. Eight patients underwent mesocaval shunt with artificial grafts, two patients had splenectomy and disconnection, three patients had a central splenorenal shunt, and six patients had a distal splenorenal shunt. There were no deaths or hepatic encephalopathy after operation. Bleeding recurred in two patients (disconnection in one, mesocaval shunt in one). The individualized choice of shunt is ideal for treating PVCT, and the combined procedures of shunt and disconnection are useful. The Rex shunt will be the focus of PVCT surgery in the future. [ABSTRACT FROM AUTHOR]

Human serum albumin (HSA)-based therapeutics have attracted tremendous attention in the development of anticancer agents. The versatile properties of HSA make HSA-based therapeutics possess improved pharmacokinetics, extended circulation half-life, enhanced efficacy, reduced toxicity, etc. Generally, the HSA-based therapeutics systems can be divided into four categories, i.e. HSA-drug nanoparticles, HSA-drug conjugates, HSA-binding prodrugs, and HSA-based recombinant fusion proteins: the latter mainly include antibody (domain)- and cytokine- fusion proteins. Advances in this area revealed the advantages of HSA-based systems in the development of tumor site-oriented therapeutics, partly referring to the enhanced penetration and retention (EPR) effect and the intensive macropinocytosis. Accordingly, a variety of technical platforms for the design and preparation of HSA-based therapeutics have been reported. Major strategies and directions for the drug development were discussed; those include (1) Tumor-site oriented drug delivery and enhanced drug retention, (2) Tumor-site prodrug release and activation, (3) Cancer cell bound intensive drug internalization, and (4) Tumor microenvironment (TME) directed immunomodulation. Notably, the multimodal HSA-based approach is promising for the development of tumor-oriented therapeutics for cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease that primarily affects spine and paraspinal soft tissue. Ankylosing spondylitis is one of the causes of osteoporosis and patients with ankylosing spondylitis tend to have spinal fractures due to limited mobility and osteoporosis. In recent years, due to the increase in the number of patients with AS, patients with AS and thoracolumbar spine fractures have gradually increased. In the past 1 year, we have treated 3 cases of AS with thoracolumbar spine fractures via simple posterior internal fixation and this paper aims to report its clinic effect.Case Presentation: All the three patients selected had a history of ankylosing spondylitis for nearly 30 years, and one of them developed a thoracolumbar spine fracture after falling when he walked, and the other two developed a thoracolumbar spine fracture without any reason. They were hospitalized for "low back pain" and were diagnosed as fractures after careful physical examination and imaging examinations such as X-ray, CT, and MRI. After the preoperative preparation was completed, all the three patients underwent surgery with simple posterior internal fixation-reduction of the fracture and pedicle screw fixation via posterior approach. All the implants-pedicle screws and connecting rods-are made of titanium alloy. For postoperative management, we asked all the patients to stay in bed for 3 weeks after the operation, and then slowly move down with the help of crutches. Fracture healing and neurological function recovery were observed postoperatively. All the three patients recovered satisfactorily after surgery, and the follow-up confirmed that the fracture healed successfully after 3 months.Conclusions: The 3 patients included 2 men and 1 women. All the 3 patients recovered well after surgery, and the follow-up confirmed that the fracture healed successfully after 3 months. One man developed urination dysfunction after operation and recovered to normal 3 months after rehabilitation exercise. [ABSTRACT FROM AUTHOR]

1. The physiological activities of the mammalian heart are regulated by the autonomic nervous system. An imbalanced autonomic nervous system with increased sympathetic tone and reduced vagal tone has been implicated in cardiovascular diseases. 2. Experimental and clinical reports have demonstrated that vagal nerve activation is able to improve outcomes for multiple cardiovascular diseases, such as ischaemic heart disease, heart failure, arrhythmia and hypertension. 3. In this paper, we mainly focus on the potential cardioprotective mechanisms of vagal nerve activation. Based on the knowledge gained from our experiments and other published reports, vagal activation results in cardioprotection is not only associated with heart rate, anti-adrenergic effect but also related to anti-inflammatory activity, regulation of cellular redox states and regulation of mitochondrial targets. 4. In conclusion, vagal nerve activation may be a promising new therapeutic approach for the treatment of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Autoimmune hepatitis is a worldwide health problem and significant cause of mortality. However, the disease etiology is largely unknown, which accounts for ineffective treatment and uncontrolled disease progression. In this study, we demonstrated the functional importance of the IL-17C/IL-17RE axis in Con A-induced hepatitis. Elevated IL-17C expression was detected in liver samples of both human and mouse autoimmune hepatitis. IL-17C, produced by hepatocytes, and its specific receptor IL-17RE on liver-resident T cells were both found to be required in Con A-induced liver damage. Mechanistically, IL-17C augmented the expression of IL-2 by intrahepatic CD4+ T cells to promote NK cell activation and liver damage. To our knowledge, our findings thus for the first time defined the indispensable role of IL-17C/IL-17RE in autoimmune hepatitis; this axis may serve as a novel drug target for the treatment of this disease. [ABSTRACT FROM AUTHOR]

Viral hemorrhagic fevers caused by the arenaviruses Lassa virus in Africa and Machupo, Guanarito, Junin, and Sabia virus in South America are among the most devastating emerging human diseases with fatality rates of 15-35% and a limited antiviral therapeutic repertoire available. Here we used high throughput screening of synthetic combinatorial small molecule libraries to identity" inhibitors of arenavirus infection using pseudotyped virion particles bearing the glycoproteins (GPs) of highly pathogenic arenaviruses. Our screening efforts resulted in the discovery of a series of novel small molecule inhibitors of viral entry that are highly active against both Old World and New World hemorrhagic arenaviruses. We observed potent inhibition of infection of human and primate cells with live hemorrhagic arenaviruses (IC50 = 500 - 800 nM). Investigations of the mechanism of action revealed that the candidate compounds efficiently block pH-dependent fusion by the arenavirus GPs (IC50 of 200-350 nM). Although our lead compounds were potent against phylogenetically distant arenaviruses, they did not show activity, against other enveloped viruses with class 1 viral fusion proteins, indicating specificity for arenavirus GP-mediated membrane fusion. [ABSTRACT FROM AUTHOR]

Purpose The addition of 2 direct-acting antiviral (DAA) agents, telaprevir and boceprevir, to peginterferon and ribavirin therapy significantly improves sustained virologic response rates in patients treated for chronic hepatitis C virus (CHC) but is associated with a higher risk of adverse events (AEs), including anemia and rash. Using a large administrative claims database, this study compared the health care resource utilization and costs among CHC patients who developed anemia and/or rash while receiving DAA-based therapies (telaprevir and boceprevir) versus those who did not develop anemia or rash. Adjusted costs were compared by using regression analysis. Methods Adult patients with ≥1 CHC diagnosis and a prescription for boceprevir or telaprevir were selected from a US-based claims database. The date of the first DAA fill after May 13, 2011, was defined as the index date. Patients were required to have continuous eligibility and no claims for hepatitis B treatment during the 6 months before (baseline) and 12 months after (study period) the index date. Patients were categorized into 4 cohorts based on the development of anemia only, rash only, both anemia and rash (anemia/rash), or neither anemia nor rash (NAR) while receiving DAA-based therapies. Baseline characteristics and study period health care utilization and costs were compared by using univariate statistics between cohorts that developed anemia only, rash only, or anemia/rash and the cohort that did not develop anemia or rash. Adjusted costs were compared by using multivariable regressions. Findings A total of 2862 patients were identified and categorized into 4 cohorts: 1204 anemia only, 131 rash only, 188 anemia/rash, and 1339 NAR patients. During the study period, patients developing anemia and/or rash incurred significantly more outpatient, dermatologist, and total medical visits compared with the NAR cohort. The anemia-only and anemia/rash cohorts also had significantly more inpatient, emergency department, and hematologist visits, as well as significantly higher adjusted total medical costs ($18,285 and $21,435 vs $11,253), total drug costs ($76,723 and $79,689 vs $63,001), and non-CHC drug costs ($10,391 and $10,475 vs $2437). The rash-only cohort had comparable adjusted total medical and drug costs. Implications CHC patients who developed anemia while receiving DAA-based therapies incurred significantly higher resource utilization and costs compared with those who did not. The study highlights the need for new CHC treatment regimens that are associated with fewer and less severe AEs, particularly anemia. [ABSTRACT FROM AUTHOR]