pH-Responsive Nanoscale Coordination Polymer for Efficient Drug Delivery and Real-Time Release Monitoring

Both excess dosages of drug and unwanted drug carrier can lead to severe side effects as well as the failure of tumor therapy. Here, an Fe³⁺–gallic acid based drug delivery system is designed for efficient monitoring of drug release in tumor. Fe³⁺ and polyphenol gallic acid can form polygonal nanoscale coordination polymer in aqueous solution, which exhibits certain antitumor effect. Importantly, this coordination polymer possesses extremely high doxorubicin (DOX) loading efficacy (up to 48.3%). In vitro studies demonstrate that the fluorescence of DOX can be quenched efficiently when DOX is loaded on the coordination polymer. The acidity in lysosome also triggers the release of DOX and fluorescence recovery simultaneously, which realizes real-time monitoring of drug release in tumor cells. In vivo studies further indicate that this polyphenol-rich drug delivery system can significantly inhibit tumor growth with negligible heart toxicity of DOX. This system with minimal side effects should be a promising nanoplatform for tumor treatment.

A nanoscale coordination polymer is developed to deliver drug to tumor tissue and realize real-time monitoring of drug release. Extremely high drug loading efficiency is achieved, and pH-responsive drug release in lysosome is monitored by the recovered fluorescence of drug itself. Importantly, this polyphenol-rich coordination polymer significantly inhibits tumor growth with negligible heart toxicity.

http://ift.tt/2u05Pns

Egg Albumen as a Fast and Strong Medical Adhesive Glue

Sutures penetrate tissues to close wounds. This process leads to inflammatory responses, prolongs healing time, and increases operation complexity. It becomes even worse when sutures are applied to stress-sensitive and fragile tissues. By bonding tissues via forming covalent bonds, some medical adhesives are not convenient to be used by surgeons and have side effects to the tissues. Here egg albumen adhesive (EAA) is reported with ultrahigh adhesive strength to bond various types of materials and can be easily used without any chemical and physical modifications. Compared with several commercial medical glues, EAA exhibits stronger adhesive property on porcine skin, glass, polydimethylsiloxane. The EAA also shows exceptional underwater adhesive strength. Finally, wound closure using EAA on poly(caprolactone) nanofibrous sheet and general sutures is investigated and compared in a rat wound model. EAA also does not show strong long-term inflammatory response, suggesting that EAA has potential as a medical glue, considering its abundant source, simple fabrication process, inherent nontoxicity, and low cost.

Egg albumen adhesive (EAA) is formed by simply adding raw egg albumen powder to water. EAA exhibits outstanding adhesion strength on pigskin tissues, polydimethylsiloxane, and glass substrates especially. EAA on nanofibrous mesh shows reliable biocompatibility and biodegradability, and great wound closure performance. EAA also has exceptional underwater adhesive strength when combined with Vaseline.

http://ift.tt/2twnakx

Impermeable Robust Hydrogels via Hybrid Lamination

Hydrogels have been proposed for sensing, drug delivery, and soft robotics applications, yet most of these materials suffer from low mechanical robustness and high permeability to small molecules, limiting their widespread use. This study reports a general strategy and versatile method to fabricate robust, highly stretchable, and impermeable hydrogel laminates via hybrid lamination of an elastomer layer bonded between hydrogel layers. By controlling the layers' composition and thickness, it is possible to tune the stiffness of the impermeable hydrogels without sacrificing the stretchability. These hydrogel laminates exhibit ultralow surface coefficients of friction and, unlike common single-material hydrogels, do not allow diffusion of various molecules across the structure due to the presence of the elastomer layer. This feature is then used to release different model drugs and, in a subsequent experiment, to sense different pH conditions on the two sides of the hydrogel laminate. A potential healthcare application is shown using the presented method to coat medical devices (catheter, tubing, and condom) with hydrogel, to allow for drug release and sensing of environmental conditions for gastrointestinal or urinary tract.

A general and versatile strategy to develop robust, stretchable and impermeable hydrogel laminates is presented to overcome common limitations of hydrogel materials such as weak mechanical properties and permeability. The laminates have tunable mechanical properties and enable spatial control of the sensing and release properties, as demonstrated by drug release and pH sensing to different sides of the laminate.

http://ift.tt/2uziPSq

Distinct 18 F-AV-1451 tau PET retention patterns in early- and late-onset Alzheimer’s disease

Abstract

Patients with Alzheimer's disease can present with different clinical phenotypes. Individuals with late-onset Alzheimer's disease (>65 years) typically present with medial temporal lobe neurodegeneration and predominantly amnestic symptomatology, while patients with early-onset Alzheimer's disease (<65 years) exhibit greater neocortical involvement associated with a clinical presentation including dyspraxia, executive dysfunction, or visuospatial impairment. We recruited 20 patients with early-onset Alzheimer's disease, 21 with late-onset Alzheimer's disease, three with prodromal early-onset Alzheimer's disease and 13 with prodromal late-onset Alzheimer's disease, as well as 30 cognitively healthy elderly controls, that had undergone ¹⁸F-AV-1451 tau positron emission tomography and structural magnetic resonance imaging to explore whether early- and late-onset Alzheimer's disease exhibit differential regional tau pathology and atrophy patterns. Strong associations of lower age at symptom onset with higher ¹⁸F-AV-1451 uptake were observed in several neocortical regions, while higher age did not yield positive associations in neither patient group. Comparing patients with early-onset Alzheimer's disease with controls resulted in significantly higher ¹⁸F-AV-1451 retention throughout the neocortex, while comparing healthy controls with late-onset Alzheimer's disease patients yielded a distinct pattern of higher ¹⁸F-AV-1451 retention, predominantly confined to temporal lobe regions. When compared against each other, the early-onset Alzheimer's disease group exhibited greater uptake than the late-onset group in prefrontal and premotor, as well as in inferior parietal cortex. These preliminary findings indicate that age may constitute an important contributor to Alzheimer's disease heterogeneity highlighting the potential of tau positron emission tomography to capture phenotypic variation across patients with Alzheimer's disease.

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Nocturnal seizures are associated with more severe hypoxemia and increased risk of postictal generalized EEG suppression

Summary

Patients with epilepsy have 20-fold risk of sudden death when compared to the general population. Uncontrolled seizures is the most consistent risk factor, and death often occurs at night or in relation to sleep. We examined seizure-related respiratory disturbances in sleep versus wakefulness, focusing on periictal oxygen saturation. Respiratory measures were examined in 48 recorded seizures (sleep, n = 23, wake, n = 25) from 20 adult patients with epilepsy. Seizures from sleep were associated with lower saturation, as compared to seizures from wakefulness, both during ictal (sleep median = 90.8, wake median = 95.5; p < 0.01) and postictal periods (sleep median = 94.3, wake median = 96.9; p = 0.05). Compared to wake-related seizures, seizures from sleep were also associated with a larger desaturation drop (sleep median = −4.2, wake median = −1.2; p = 0.01). Postictal generalized electroencephalography (EEG) suppression (PGES) occurred more frequently after seizures from sleep (39%), as compared to wake-related seizures (8%, p = 0.01). Our findings suggest that nocturnal seizures may entail a higher sudden unexpected death in epilepsy (SUDEP) severity burden, as they are associated with more severe and longer hypoxemia events, and more frequently followed by PGES, both factors implicated in sudden death.

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MicroRNA-206 Prevents the Pathogenesis of Hepatocellular Carcinoma Via Modulating Expression of cMet and Cdk6

Abstract

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide and therapeutic agents for this malignancy are lacking. MicroRNAs play critical roles in carcinogenesis and present tremendous therapeutic potential. Here we report that microRNA-206 is a robust tumor suppressor that plays important roles in the development of HCC by regulating cell cycle progression and cMet signaling pathway. MicroRNA-206 was under-expressed in livers of two HCC mouse models, human individuals bearing HCC, and human HCC cell lines. Combining bioinformatic prediction and molecular and cellular approaches, we identified cMET (Met proto-oncogene), CCND1, and CDK6 as functional targets of microRNA-206. By inhibiting expression of cMET, CCND1 and CDK6, microRNA-206 delayed cell cycle progression, induced apoptosis and impaired proliferation of three distinct human HCC cell lines. Systemic administration of microRNA-206 completely prevented HCC development in both cMyc and AKT/Ras HCC mice, while 100% of control mice died from lethal tumor burdens. Conversely, re-introduction of cMet or Cdk6 into livers of cMyc and AKT/Ras HCC mice recovered growth of HCC inhibited by microRNA-206. These results strongly suggested that cMet and Cdk6 were two functional targets that mediated the inhibitory effect of microRNA-206 on the development of HCC. MicroRNA-206 overexpression demonstrated a profound therapeutic effect on HCC in xenograft and cMyc HCC mice. In summary, this study defines a potentially critical role of microRNA-206 in preventing the growth of HCC, and suggests its use as a potential therapeutic strategy for this malignancy. This article is protected by copyright. All rights reserved.

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Correspondence: Fecal Microbiota Transplant from a Rational Stool Donor Improves Hepatic Encephalopathy: A Randomized Clinical Trial

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Chronic Inflammation-elicited Liver Progenitor Cell Conversion to Liver Cancer Stem Cell with Clinical Significance

Abstract

The substantial heterogeneity and hierarchical organization in liver cancer supports the theory of liver cancer stem cell (LCSC). However, the relationship between chronic hepatic inflammation and LCSC generation remains obscure. Here we observed a close correlation between aggravated inflammation and liver progenitor cell (LPC) propagation in the cirrhotic liver of rats exposed to diethylnitrosamine. LPCs isolated from the rat cirrhotic liver initiated subcutaneous liver cancers in NOD/SCID mice, suggesting the malignant transformation of LPC toward LCSC. Interestingly, depletion of Kupffer cells in vivo attenuated the LCSC properties of transformed LPCs and suppressed CK19⁺OV6⁺ tumor occurrence. Conversely, LPCs co-cultured with macrophages exhibited enhanced LCSC properties. We further demonstrated that macrophage-secreted TNF-α triggered chromosomal instability in LPCs via the deregulation of ubiquitin D and Checkpoint kinase 2, and enhanced the self-renewal of LPCs through TNFR1/Src/STAT3 pathway, which synergistically contributed to the conversion of LPCs to LCSCs. Clinical investigation revealed that CK19⁺OV6⁺ liver cancer patients displayed a worse prognosis and exhibited superior response to sorafenib treatment. In conclusion, our results not only clarified the cellular and molecular mechanism underlying the inflammation-mediated LCSC generation, but also provided a novel molecular classification for the individualized treatment of liver cancer. This article is protected by copyright. All rights reserved.

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Reply to HEP-17-1121

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The Diagnosis and Management of Nonalcoholic Fatty Liver Disease: Practice Guidance from the American Association for the Study of Liver Diseases

Abstract

This guidance provides a data-supported approach to the diagnostic, therapeutic, and preventive aspects of NAFLD care. A "Guidance" document is different from a "Guideline." Guidelines are developed by a multidisciplinary panel of experts and rate the quality (level) of the evidence and the strength of each recommendation using the Grading of Recommendations, Assessment Development, and Evaluation (GRADE) system. A guidance document is developed by a panel of experts in the topic, and guidance statements, not recommendations, are put forward to help clinicians understand and implement the most recent evidence. This article is protected by copyright. All rights reserved.

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β-catenin regulation of farnesoid X receptor signaling and bile acid metabolism during murine cholestasis

ABSTRACT

Cholestatic liver diseases result from impaired bile flow and are characterized by inflammation, atypical ductular proliferation (ADP), and fibrosis. The Wnt/β-catenin pathway plays a role in bile duct development, yet its role in cholestatic injury remains indeterminate. Liver-specific β-catenin knockout (KO) mice and wild-type (WT) littermates were subjected to cholestatic injury via bile duct ligation or short-term exposure to 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet. Intriguingly, KO exhibit a dramatic protection from liver injury, fibrosis, and ADP, which coincided with significantly decreased total hepatic bile acids (BA). This led to the discovery of a novel role for β-catenin in regulating BA synthesis and transport through regulation of farnesoid X receptor (FXR) activation. We show that β-catenin functions as both an inhibitor of nuclear translocation and as a nuclear co-repressor through formation of a physical complex with FXR. Loss of β-catenin expedited FXR nuclear localization and FXR/RXRα association, culminating in small heterodimer protein (SHP) promoter occupancy and activation in response to BA or FXR agonist. Conversely, accumulation of β-catenin sequesters FXR, thus inhibiting its activation. Finally, exogenous suppression of β-catenin expression during cholestatic injury reduces β-catenin/FXR complex, activates FXR to decrease total BA and alleviates hepatic injury. Conclusion: We have identified a novel FXR/β-catenin interaction whose modulation via β-catenin suppression promotes FXR activation and decreases hepatic BA, which may provide unique therapeutic opportunities in cholestatic liver diseases. This article is protected by copyright. All rights reserved.

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Survival of patients with cirrhosis and acute peptic ulcer bleeding compared with variceal bleeding using current first-line therapies

ABSTRACT

The presence of cirrhosis increases the mortality of patients with peptic ulcer bleeding (PUB). Both acute variceal bleeding (AVB) and PUB are associated with substantial mortality in cirrhosis. This multicenter cohort study was performed to assess whether the mortality of cirrhotic patients with PUB is different from that of those with AVB. Patients with cirrhosis and acute gastrointestinal bleeding were consecutively included and treated with somatostatin and PPI infusion from admission and with antibiotic prophylaxis. Emergency endoscopy with endoscopic therapy was performed within the first 6-hours. 646 patients with AVB and 144 with PUB were included. There were baseline differences between groups, such as use of gastro-erosive drugs or β-blockers. Child-Pugh and MELD scores were similar. Further bleeding was more frequent in AVB-group than in those PUB-group (18% vs 10%; OR= 0.50, 95%CI= 0.29-0.88). However, mortality risk at 45-day was similar in both groups (19% in AVB-group vs 17% in PUB-group; OR= 0.85, 95% CI= 0.55-1.33, P= 0.48). Different parameters, such as Child-Pugh score, AKI, ACLF or presence of shock or bacterial infection, but not the cause of bleeding, were related to the risk of death. Only 2% of PUB-group vs 3% of AVB-group died with uncontrolled bleeding (P= 0.39), while the majority of patients in either group died from liver failure or due to other comorbidities. Conclusions: Using current first-line-therapy, patients with cirrhosis and acute peptic ulcer bleeding have a similar survival than those with variceal bleeding. The risk of further bleeding is higher in patients with variceal hemorrhage. However, few patients in both groups died from uncontrolled bleeding, while the cause of death was usually related to liver failure or co-morbidities. This article is protected by copyright. All rights reserved.

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Efficacy and safety of new direct antiviral agents in HCV infected patients with Diffuse Large B Cell Non-Hodgkin Lymphoma

Abstract

Introduction: The association of HCV with Non-Hodgkin Lymphoma (NHL) has been demonstrated all over the world. The new interferon-free, direct antiviral agents (DAA), showed high efficacy and safety, and preliminary data seem to confirm their activity on low-grade NHL. The question arises as whether or not -and how- to treat the HCV positive patients suffering from diffuse large B cell lymphomas(DLBCL). Aim of this observational study was to evaluate whether the DAAs antiviral treatment of DLBCL/HCV-infected patients in concomitance with chemotherapy is a safe and effective option. Methods:20 (13 males and 7 females), HCV1b positive subjects, undergoing chemotherapy for DLBCL, were enrolled between June 2015 and December 2015. After informed consent, all the patients underwent to antiviral therapy with sofosbuvir/ledipasvir and chemotherapy (14 R-CHOP and 6 CHOP) for DLBCL. Complete hematological (REAL,Ann-Harbor and IPI scores) and hepatological (viral markers, liver stiffness and biochemical parameters) evaluations were made. A historical retrospective cohort of 101 DLBCL/HCV positive patients not undergone to antiviral treatment was enrolled for comparison. Results: DAA-treated and untreated patients were similar for sex distribution, IPI score and NHL stage, and differed for age (older in treated), chemotherapy and use of antiviral therapy. Overall-survival (OS) and disease-free-survival (DFS) were evaluated among a 52 weeks of follow-up. No statistical difference was found in OS after 52 weeks (p:0.122), whereas a statistically significant higher DFS was achieved in treated patients(p:0.036). At the multivariate analysis, only IPI score and DAA were independently correlated with a better DFS. No differences in adverse events were reported. Conclusions: DAA-treatment in concomitance with chemotherapy showed to be safe and effective in influencing the remission of aggressive lymphomas in HCV patients. This article is protected by copyright. All rights reserved.

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Impact of an Electronic Health Record Alert in Primary Care on Increasing Hepatitis C Screening and Curative Treatment for Baby Boomers

Abstract

Despite effective treatment for chronic hepatitis C (CHC), deficiencies in diagnosis and access preclude disease elimination. Screening of baby boomers remains low. The aims of this study were to assess the impact of an electronic health record (EHR) based prompt on HCV screening rates in baby boomers in primary care, and access to specialty care and treatment among those newly diagnosed. We implemented an EHR based "Best Practice Advisory" (BPA) that prompted primary care providers (PCPs) to perform HCV screening for patients seen in primary care clinic: 1) born between 1945-1965; 2) lacked a prior diagnosis of HCV infection; and 3) lacked prior documented anti-HCV testing. The BPA had associated educational materials, order set, and streamlined access to specialty care for newly diagnosed patients. Pre and post BPA screening rates were compared and care of newly diagnosed patients analyzed. In the 3 years prior to BPA implementation, 52,660 baby boomers were seen in primary care clinics, and 28% were screened. HCV screening increased from 7.6% for patients with a PCP visit in the 6 months prior to BPA to 72% over the 1-year post BPA. Of 53 newly diagnosed patients, all were referred for specialty care, 11 had advanced fibrosis or cirrhosis, 20 started treatment and 9 achieved SVR thus far. Conclusions: Implementation of an EHR based prompt increased HCV screening rates among baby boomers in primary care by 5 fold due to efficiency in determining needs for HCV screening and work-flow design. Streamlined access to specialty care enabled patients with previously undiagnosed advanced disease to be cured. This intervention can be easily integrated into EHR systems to increase HCV diagnosis and linkage to care. This article is protected by copyright. All rights reserved.

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NAM 2017 Report: A National Plan To Eliminate Hepatitis B and C In the United States By 2030 And The AASLD's Response

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Opioids out of control

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Preparing pathology for the molecular era

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An uncommon cause of warm foot

Description

A 66-year-old man presented with swelling and redness of right foot of 1 month duration. He was a known diabetic for 20 years; glycaemic control was suboptimal. There was no history of trauma, fever, ulcer or deformity. He had numbness of both feet and was earlier documented to have mild non-proliferative diabetic retinopathy. On examination, he was not feverish with erythema, swelling (figure 1), local rise of temperature of the right foot and a difference of 2°C between both feet and no tenderness on palpation. There was loss of protective sensations with absent ankle jerks with bounding pulses in both feet. Systemic examination was unremarkable. His blood investigations revealed haemoglobin of 12 g/dL (N 12–15), total white cell count of 9.8x10⁹ /L/cmm (N 4000–11000), erythrocyte sedimentation rate of 48 mm/hour and haemoglobin A1c of 8.1% (n<5.7). Based on history and clinical findings and absent elevation of acute inflammatory markers, a diagnosis of acute...

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IgG4-related disease: long-term natural history and management of a relapsing multisystem disease entity

Although awareness of IgG4-related disease has grown over the past decade, with earlier diagnosis and treatment, understanding of its natural history over the long term and the optimal management remains unclear. We report the case of a 48-year-old man who presented with a pancreatic pseudotumour causing bile duct obstruction with coexisting autoimmune hepatitis and multisystem involvement. His symptoms settled on steroids and maintenance with azathioprine was commenced, however periodic relapses occurred involving multiple organs. A timeline-relating IgG4 levels, clinical features and immunosuppressive therapy are presented. The protean and relapsing–remitting nature of this condition is emphasised, and a brief review of long-term therapeutic options is provided.

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Solitary fibrous tumour: a rare tumour of the pleural cavity

Solitary fibrous tumours are a rare group of tumours that originate from connective tissues such as the pleura and mediastinum. When growing within the thoracic cavity these tumours exert pressure on vital organs and large vessels. We have successfully operated on two patients with large solitary fibrous tumours and managed the pathophysiological changes manifested as superior vena cava syndrome resulting from these tumours.

http://ift.tt/2utZCk7

Necrotising enterocolitis after supraventricular tachycardia: an unusual precursor to a common problem

Supraventricular tachycardia (SVT) is the most common neonatal arrhythmia. Necrotising enterocolitis (NEC) is a disease with multifactorial aetiology, most common in preterm infants. There are three previous case reports in the literature of NEC following neonatal SVT. We present two cases of late preterm infants with NEC, characterised by pneumatosis on abdominal X-ray and ultrasound, following recurrent SVT without haemodynamic instability. The infants were successfully treated with antibiotic therapy and bowel rest.

http://ift.tt/2vsqkqz

The Duari hernia and recognition of the femoral vein compression sign

Femoral hernias can be difficult to diagnose and are at high risk of strangulation. This report is of a rare case of an irreducible femoral hernia containing caecum and appendix presenting as an emergency. To the authors' knowledge, there have only been three cases reported, the first described by Duari. This case was incorrectly diagnosed preoperatively as an inguinal hernia, so the CT diagnosis of femoral hernias is reviewed, in particular demonstrating the radiological use of the femoral vein compression sign.

http://ift.tt/2utSRip

Syndromic congenital diarrhoea: new SPINT2 mutation identified in the UAE

We are reporting a new mutation in the SPINT2 gene (c.443G>A (p. Arg148His)) that explains the association of choanal atresia with congenital sodium diarrhoea (CSD) in an Emirati family in the Middle East. To our knowledge, this mutation is neither listed in a mutation database nor described in the literature. Similar to other patients with CSD associated with SPINT2, this child remains dependent on parenteral nutrition for fluids and nutritional support resulting in failure to thrive. The determination of the molecular basis of syndromic CSD will facilitate prenatal and postnatal diagnosis of patients and will contribute to counselling of affected families, especially in areas like the UAE where consanguineous marriages are not uncommon.

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On becoming a full partner in care [Humanities]

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No immediate plans to build new CMA HQ [News]

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Why support a separate medical access framework for cannabis? [Commentary]

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The author responds to "Chronic obstructive pulmonary disease and Occams razor" [Letters]

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Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies [Research]

BACKGROUND

Nonnutritive sweeteners, such as aspartame, sucralose and stevioside, are widely consumed, yet their long-term health impact is uncertain. We synthesized evidence from prospective studies to determine whether routine consumption of non-nutritive sweeteners was associated with long-term adverse cardiometabolic effects.

METHODS

We searched MEDLINE, Embase and Cochrane Library (inception to January 2016) for randomized controlled trials (RCTs) that evaluated interventions for nonnutritive sweeteners and prospective cohort studies that reported on consumption of non-nutritive sweeteners among adults and adolescents. The primary outcome was body mass index (BMI). Secondary outcomes included weight, obesity and other cardiometabolic end points.

RESULTS

From 11 774 citations, we included 7 trials (1003 participants; median follow-up 6 mo) and 30 cohort studies (405 907 participants; median follow-up 10 yr). In the included RCTs, nonnutritive sweeteners had no significant effect on BMI (mean difference –0.37 kg/m²; 95% confidence interval [CI] –1.10 to 0.36; I² 9%; 242 participants). In the included cohort studies, consumption of nonnutritive sweeteners was associated with a modest increase in BMI (mean correlation 0.05, 95% CI 0.03 to 0.06; I² 0%; 21 256 participants). Data from RCTs showed no consistent effects of nonnutritive sweeteners on other measures of body composition and reported no further secondary outcomes. In the cohort studies, consumption of nonnutritive sweeteners was associated with increases in weight and waist circumference, and higher incidence of obesity, hypertension, metabolic syndrome, type 2 diabetes and cardiovascular events. Publication bias was indicated for studies with diabetes as an outcome.

INTERPRETATION

Evidence from RCTs does not clearly support the intended benefits of nonnutritive sweeteners for weight management, and observational data suggest that routine intake of nonnutritive sweeteners may be associated with increased BMI and cardiometabolic risk. Further research is needed to fully characterize the long-term risks and benefits of nonnutritive sweeteners. Protocol registration: PROSPERO-CRD42015019749

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Caring for young carers in Canada [Commentary]

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Managing thyroid disease in women planning pregnancy [Practice]

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Chronic obstructive pulmonary disease and Occams razor [Letters]

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Subclinical hypothyroidism in pregnancy [Practice]

http://ift.tt/2t6lezr

US Senate health care bill draws widespread criticism [News]

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Fluid-filled striae in a patient with hypoalbuminemia [Practice]

http://ift.tt/2upxAGW

India introducing routine pneumococcal vaccine [News]

http://ift.tt/2uq14EJ

Effects of different ozonized slurry-ice treatments and superchilling storage (−1°C) on microbial spoilage of two important pelagic fish species

Abstract

Combining different preservative treatments for improving quality and safety of fishery products increasingly receives global research attention. Consistent with this pursuit, the current research was undertaken to determine the effects of different ozonized slurry-ice treatments and superchilling (−1°C) storage on microbial spoilage of European anchovy (Eugraulis encrasicolus) and sardine (Sardina pilchardus), which are two commercially important pelagic fish species. After the catch (within <5 hr) and at defined scheduled storage times, ozone has been discharged once on sardine (herein referred to as "One-T") and repeatedly/sequentially on European anchovy (herein referred to as "Seq-T"). Microbiological analyses enumerated total viable count (TVC), Bacillus spp., Enterobacteriaceae, Lactobacillus spp., Moraxella spp., Shewanella spp., Listeria monocytogenes and Pseudomonas spp. Independent of potential antimicrobial effects of ozone during superchilling storage, no Listeria spp., Shewanella spp., Moraxella spp., and Bacillus spp. were found in all processed samples. While Enterobacteriaceae and Lactobacillus spp. were detected at below 1 log cfu/g, both TVC and Pseudomonas spp. proliferated at different rates throughout superchilling storage. The repeated ozone-treated ("Seq-T") showed lower TVC and Pseudomonas spp. values compared with one-time treated ("One-T") slurry-iced and control samples. Thus, combined slurry-ice and superchilling storage at Seq-T produced improved antimicrobial activity over One-T application. Largely, ozonized slurry-ice outcomes/results appear promising thanks to superchilling storage.

Slurry-iced superchilling storage of current study is contextualized with those of ice-stored/refrigerated storage situations previously reported. We do this by schematic illustration of estimated proliferation increment(s)/trend(s) of some (relevant/specific) bacterial species detected in (some) small pelagic fishery products as affected by different storage temperatures and times (days). Trends A–E shows the different proliferation patterns of bacterial species such as Enterobacteriaceae, Lactobacillus, Pseudomonas spp., Shewanella as it proliferates at different rates under varying cold storage temperature conditions.

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Viscoelastic properties of sweet potato complementary porridges as influenced by endogenous amylases

Abstract

Sweet potato (Ipomoea batatas L.) roots contain amylolytic enzymes, which hydrolyze starch thus having the potential to affect the viscosity of sweet potato porridges provided the appropriate working conditions for the enzymes are attained. In this study, the effect of sweet potato variety, postharvest handling conditions, freshly harvested and room/ambient stored roots (3 weeks), and slurry solids content on the viscoelastic properties of complementary porridges prepared using amylase enzyme activation technique were investigated. Five temperatures (55°C, 65°C, 70°C, 75°C, and 80°C) were used to activate sweet potato amylases and the optimum temperature was found to be 75°C. Stored sweet potato roots had higher soluble solids (⁰Brix) content in the pastes compared to fresh roots. In all samples, activation of amylases at 75°C caused changes in the viscoelastic parameters: phase angle (tan δ) and complex viscosity (η*). Postharvest handling conditions and slurry solids content significantly affected the viscoelastic properties of the porridges with flours from stored roots yielding viscous (liquid-like) porridges and fresh roots producing elastic (solid-like) porridges. Increase in slurry solids content caused reduction in the phase angle values and increase in the viscosity of the sweet potato porridges. The viscosity of the porridges decreased with storage of sweet potato roots. These results provide a possibility for exploiting sweet potato endogenous amylases in the preparation of complementary porridges with both drinkable viscosities and appropriate energy and nutrient densities for children with varying energy needs.

The study evaluated the effect of sweetpotato varieties, postharvest handling conditions and slurry solids content on the viscoelastic properties of sweetpotato weaning porridges. Activation of amylases at 75⁰C caused changes in the viscoelastic parameters; phase angle (δ) and complex viscosity (η*). Increase in slurry solids content caused reduction in the phase angle values and increase in the viscosity of the sweetpotato porridges. The viscosity of the porridges decreased with storage of sweetpotato roots.

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Comments on Cochrane Review on Direct-Acting Antivirals for Hepatitis C

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Issue Cover (July 2017)

Cover image by Dr. Natalie Doig (MRC Brain Network Dynamics Unit, Department of Pharmacology, Oxford). The cover image is of a frontal section of mouse brain showing many regions of the basal ganglia. The section was triple-immunostained to reveal tyrosine hydroxylase (TH; cyan), parvalbumin (PV; green) and choline acetyltransferase (magenta).

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Bacteremia Prediction Model for Community-Acquired Pneumonia: External Validation in a Multicenter Retrospective Cohort

Abstract

Objective

Many studies have described constructing a prediction model for bacteremia in community-acquired pneumonia (CAP), but these studies were not validated in external heterogeneous groups. The objective of this study was to test the generalizability of a previous bacteremia prediction model for CAP by external validation.

Methods

This multicenter retrospective cohort analysis was performed in eight tertiary urban hospital emergency departments (ED). We reviewed adult patients who were hospitalized after presentation to the ED with CAP. We categorized the enrolled patients into three groups according to the bacteremia prediction model score and calculated the number of patients with or without a blood culture-positive result. We performed a multivariable analysis to identify significant predictors for bacteremia.

Results

Among the enrolled 2,001 patients, 1,592 (79.6%), 371 (18.5%), and 38 (1.9%) were stratified to a low, moderate, and high-risk group, respectively, and this proportion was similar with previous study. Each group had a bacteremia-positive rate as follows: 1.2% for the low-risk group, 7.2% for the moderate-risk group, and 31.5% for the high-risk group. The area under the receiver operating characteristic curve for the bacteremia model in the external validation cohort was 0.81, and there was no significant difference with that of the previous internal validation cohort (p = 0.246). Assuming that blood cultures were not performed in the low-risk patients, the sensitivity and specificity of this model were 0.68 and 0.81, respectively. Additionally, the positive predictive value and negative predictive value were 9.54% and 98.87%, respectively. A platelet count less than 130,000 cell/μL, albumin less than 3.3 mg/dL, and C-reactive protein (CRP) greater than 17 mg/dL were identified as significant predictors with a sensitivity and specificity of, 0.70 and 0.83, respectively.

Conclusion

The bacteremia prediction model was well validated in the general population and could help physicians make the decision to reduce the number of blood cultures in patients with CAP.

This article is protected by copyright. All rights reserved.

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Prevalence and Distribution of Sesamoid Bones and Accessory Ossicles of the Foot as Determined by Digital Tomosynthesis

Abstract

We previously reported that digital tomosynthesis (DTS) is a reliable tool for evaluating bony structures of the hand. The current study aimed to identify the prevalence and distribution of sesamoid bones and accessory ossicles of the foot using DTS and to compare the results to those of conventional radiography (CR). Foot images (DTS, 213; CR, 44) of 213 patients taken at a tertiary hospital were retrospectively reviewed. Sesamoid bones were identified in the metatarsaophalangeal (MTP), distal interphalangeal (DIP) and interphalangeal (IP) joints of the great (I), second (II), third (III), fourth (IV), and fifth (V) toes. Accessory ossicles were observed in the midfoot and hindfoot. The mean number of sesamoid bones and accessory ossicles was 3.9±1.3 for the left foot and 3.7±1.0 for the right foot on CR; and 3.9±1.4 for the left foot and 3.9±1.3 for the right foot on DTS. Sesamoid bones were observed in MTP I (100%), MTP II (5%), MTP III (2%), MTP IV (2%), MTP V (14%), and IP (68%) on CR. Sesamoid bones were observed in MTP I (100%), MTP II (8%), MTP III (1%), MTP IV (2%), MTP V (25%), and IP I(65%) on DTS. Among accessory ossicles, the most common bone identified was os tibiale externum (23% on CR and 33% on DTS) andos peroneum (14% on CR and 21% on DTS), and os trigonum (32% on CR and 0.5% on DTS). DTS was useful for finding sesamoid bones and accessory ossicles, although there were some limitations in observing the hindfoot. This article is protected by copyright. All rights reserved.

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A critique of utilitarian and instrumentalist concepts for the teaching of gross anatomy to medical and dental students An opinion piece

Abstract

Medical and dental curricula, together with anatomical sciences courses, are increasingly having to change, mainly because there is a drive to being what is termed, without adequate definition, 'clinically relevant'. The concept of 'clinical anatomy' has accordingly been invented and it is expected that, at all times, the teaching of anatomy is directly focussed on clinical scenarios, meaning almost invariably the 'disease-based model of medicine and dentistry'. Furthermore, students are not expected to have a detailed knowledge of gross anatomy and the time devoted to teaching and learning the subject has decreased significantly. The notion being fostered is that knowledge is not required 'just in case' but 'just in time'. However, the absence of agreed core syllabuses that are internationally accepted complicates a discussion about what is relevant practically and what does not need to be taught. In this paper, we critique such an utilitarian and instrumentalist approach to the teaching of gross anatomy within medical and dental curricula. We draw attention to the need to embrace the 'functionality-based model of medicine and dentistry' by returning to an understanding that the role of the medical or dental practitioner is to value health and to restore to functionality the ill person or the pathologically affected region/organ/system. A fuller knowledge of anatomy than is presently taught is regarded as a prerequisite for appreciating normality and health. A further problem with the instrumentalist approach to medical education is that, by concentrating on what is seen to be at the time 'useful' or 'clinically relevant', there is the danger of undermining, or discouraging, future developments that rely on what contemporaneously seems 'useless' and 'irrelevant' knowledge (a problem shared with a overreliance on 'evidence-based' medicine/dentistry). Finally, the reliance instrumentalism has on what is pragmatic, regardless of its scientific 'truthfulness', is contrary to the ethos and practice of a university education that values deep learning and the development of learnèd professions. This article is protected by copyright. All rights reserved.

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Wearables in epilepsy and Parkinson's disease—A focus group study

Objectives

Wearable sensors that measure movement and physiological variables are attractive for clinical evaluation of neurological diseases such as epilepsy and Parkinson's disease (PD). The aim of this study was to explore perceptions regarding the use of wearable technology in disease monitoring and management as reported by individuals with epilepsy and Parkinson's disease as well as health professionals working with these patient groups.

Materials and Methods

Six patient groups (n=25) and two groups with health professionals (n=15) participated in this qualitative, descriptive study with focus group interviews. A manifest qualitative content analysis was used.

Results

Four categories and nine subcategories emerged from the analysis. Participants saw possible benefits for improved treatment effect and valued this benefit more than possible inconvenience of wearing the sensors. Discrete design and simplicity were considered as facilitators for improved usability. They emphasized the importance of interactive information between patients and health professionals. However, they were concerned about unclear information and inconclusive recordings and some fears about personal integrity were at odds with the expectations on interactivity.

Conclusions

Patients need to feel well informed and find an added value in using wearables. Wearables need to be user-friendly, have an attractive design, and show clinical efficacy in improving disease management. Variations in perceptions regarding integrity, benefits, and effectiveness of monitoring indicate possible conflicts of expectations among participants. The engagement of end users, patients, and health professionals, in the design and implementation process, is crucial for the development of wearable devices that enhance and facilitate neurological rehabilitation practice.

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Issue Information - Editorial Board

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A Critical Examination of the Reliability and Validity of a Gender Role Attitude Scale in Flanders (Belgium): What Lessons Can be Learned?

Abstract

Western societies have shifted toward more egalitarian gender role attitudes (GRA). Quantitative research on GRA has been critiqued for not having kept up with societal changes in GRA. GRA scales are claimed to lack discriminative power and not fully capture the diversity within non-traditional attitudes. The present study gives an overview of the theoretical critiques with regard to GRA scales and empirically assesses these critiques. A typical example of a GRA scale measuring adolescents' GRA in Flanders (Belgium) is used to test the scale's quality across three waves of surveys completed by 4063 early secondary school students. Our analysis identifies the drawbacks of this particular scale. First, a ceiling effect was found, with most respondents being egalitarian. Second, the representativeness of roles inquired about is restricted; relevant societal domains are not questioned and most roles are only questioned for one gender. Third, a gender-binary approach is dominant. Finally, our results confirm that adolescents demonstrate ambivalent feelings toward balancing female employment and motherhood; although paid employment is encouraged, childcare is prioritized. We recommend that other researchers critically examine the usability and quality of GRA scales in today's society. Using outdated GRA scales might conceal the ambivalence that adolescents feel due to new gender inequities. Also, investing in structures and regulations supporting the work-family balance is key in further promoting gender equity.

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Preparation of a Nanoemulsion with Carapa guianensis Aublet (Meliaceae) Oil by a Low-Energy/Solvent-Free Method and Evaluation of Its Preliminary Residual Larvicidal Activity

Andiroba (Carapa guianensis) seeds are the source of an oil with a wide range of biological activities and ethnopharmacological uses. However, few studies have devoted attention to innovative formulations, including nanoemulsions. The present study aimed to obtain a colloidal system with the andiroba oil using a low-energy and organic-solvent-free method. Moreover, the preliminary residual larvicidal activity of the nanoemulsion against Aedes aegypti was evaluated. Oleic and palmitic acids were the major fatty acids, in addition to the phytosterol β-sitosterol and limonoids (tetranortriterpenoids). The required hydrophile-lipophile was around 11.0 and the optimal nanoemulsion was obtained using polysorbate 85. The particle size distribution suggested the presence of small droplets (mean diameter around 150 nm) and low polydispersity index (around 0.150). The effect of temperature on particle size distribution revealed that no major droplet size increase occurred. The preliminary residual larvicidal assay suggested that the mortality increased as a function of time. The present study allowed achievement of a potential bioactive oil in water nanoemulsion that may be a promising controlled release system. Moreover, the ecofriendly approach involved in the preparation associated with the great bioactive potential of C. guianensis makes this nanoemulsion very promising for valorization of this Amazon raw material.

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Antineuroinflammatory Effects of Modified Wu-Zi-Yan-Zong Prescription in β-Amyloid-Stimulated BV2 Microglia via the NF-κB and ERK/p38 MAPK Signaling Pathways

Modified Wu-Zi-Yan-Zong prescription (MWP), a traditional Chinese medicinal decoction, has possessed the neuroprotective and anti-inflammatory properties. The mechanisms associated with these properties, however, are not completely understood. We designed the experiments to elucidate the antineuroinflammatory property of MWP in BV2 microglia activated by β-amyloid (Aβ), which is a characteristic feature of Alzheimer's disease (AD). The composition of MWP was studied using HPLC. BV2 microglia cells were then treated with Aβ in the presence or absence of MWP. The effects of MWP treatment on Aβ-activated neuroinflammation were determined using PCR, western blotting, and immunofluorescence staining. MWP significantly inhibited the mRNA expression of inflammatory mediators such as IL-1β, IL-6, TNF-α, and MCP-1, as well as the expression of inducible nitric oxide synthase (iNOS) in Aβ-activated BV2 microglia. MWP also inhibited the nuclear translocation and signaling pathway of nuclear factor kappa B (NF-κB) by suppressing inhibitor of nuclear factor-κB (IκB) degradation and downregulating IκB kinase β (IKKβ) phosphorylation. Moreover, MWP decreased extracellular regulated protein kinase (ERK)/p38 mitogen-activated protein kinase (MAPK) phosphorylation, which is an important signaling pathway for proinflammatory gene expression. We concluded that MWP could suppress neuroinflammatory responses in Aβ-activated BV2 microglia via the NF-κB and ERK/p38 MAPK signaling cascades and could prove an effective therapeutic agent for the prevention and treatment of neuroinflammatory diseases such as AD.

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The Protective Effect of Salidroside on Hypoxia-Induced Corpus Cavernosum Smooth Muscle Cell Phenotypic Transformation

Salidroside, a major active ingredient isolated from Rhodiola rosea, has a long application in Chinese medical history. It has widely demonstrated effects on fatigue, psychological stress, and depression and exhibits potential antihypoxia activity. Emerging evidence shows that hypoxia is an important independent risk factor for erectile dysfunction (ED). The aim of this study was to clarify the effect of salidroside on hypoxia-induced phenotypic transformation of corpus cavernosum smooth muscle cells (CCSMCs). Our results showed that salidroside decreased the hypoxia-induced expression of collagen and content of vimentin, a corpus cavernosum smooth muscle synthetic protein, in vitro. Simultaneously, salidroside increased expression of the CCSMC contractile proteins, α-smooth muscle actin (α-SMA) and desmin. In vivo, similarly, the expressions of collagen and hypoxia-inducible factor-1α were increased in bilateral cavernous neurectomy (BCN) rats while they were decreased in the salidroside group. Among the phenotypic proteins, α-SMA and desmin increased and vimentin decreased after treating BCN rats with salidroside compared with the BCN alone group. Overall, our results demonstrate that salidroside has the ability to oppose hypoxia and can inhibit the CCSMC phenotypic transformation induced by hypoxia. Salidroside may provide a new treatment method for ED.

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The Effects of Guizhi Gancao Decoction on Pressure Overload-Induced Heart Failure and Posttranslational Modifications of Tubulin in Mice

Guizhi Gancao Decoction (GGD), a traditional Chinese medical recipe, has been widely used in the treatment of cardiovascular diseases in China for centuries. The present study was carried out to determine whether GGD exerts direct protective effects against pressure overload-induced heart failure. Moreover, we investigated whether GGD affects tubulin expression and posttranslational modifications. We demonstrated that GGD ameliorated TAC caused cardiac hypertrophy by gravimetric and echocardiography analysis in C57BL/6 mice. We found that GGD abrogated TAC-induced myocardium fibrosis by Masson's staining and collagen volume fraction (CVF) analysis. By using pressure-volume hemodynamic measurements, we found that GGD prevented TAC-induced cardiac systolic and diastolic dysfunction. Immunoblotting and immunofluorescent analysis revealed that GGD abrogated TAC-induced detyrosination and acetylation abnormalities on microtubules. Our present study demonstrated potential therapeutic effects of GGD against pressure overload-induced heart failure.

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Clinical Effects and Safety of Zhi Sou San for Cough: A Meta-Analysis of Randomized Trials

Introduction. Zhi Sou San (ZSS), a traditional Chinese prescription, has been widely applied in treating cough. The purpose of this meta-analysis was to evaluate the effectiveness and safety of ZSS for cough. Methods. We searched relevant articles up to 5 March 2017 in seven electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PubMed, Chinese National Knowledge Infrastructure (CNKI), Cqvip Database (VIP), China Biology Medicine disc (CBM), and Wanfang Data. Randomized controlled trials (RCTs) were eligible, regardless of blinding. The primary outcome was the total effective rate. Results. Forty-six RCTs with a total of 4007 participants were identified. Compared with western medicine, ZSS significantly improved the total effective rate (OR: 4.45; 95% CI: 3.62–5.47) and the pulmonary function in terms of FEV1 (OR: 0.35; 95% CI: 0.24–0.46) and decreased the adverse reactions (OR: 0.05; 95% CI: 0.02–0.01) and the recurrence rate (OR: 0.30; 95% CI: 0.16–0.57). However, there was no significant improvement in the cough symptom score comparing ZSS with western medicine. Conclusions. This meta-analysis shows that ZSS has significant additional benefits and relative safety in treating cough. However, more rigorously designed investigations and studies, with large sample sizes, are needed because of the methodological flaws and low quality of the included trials in this meta-analysis.

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Tumor Proteins D52 and D54 Have Opposite Effects on the Terminal Differentiation of Chondrocytes

The tumor protein D (TPD) family consists of four members, TPD52, TPD53, TPD54, and TPD55. The physiological roles of these genes in normal tissues, including epidermal and mesenchymal tissues, have rarely been reported. Herein, we examined the expression of TPD52 and TPD54 genes in cartilage in vivo and in vitro and investigated their involvement in the proliferation and differentiation of chondrocytes in vitro. TPD52 and TPD54 were uniformly expressed in articular cartilage and trabecular bone and were scarcely expressed in the epiphyseal growth plate. In MC3T3E-1 cells, the expressions of TPD52 and TPD54 were increased in a differentiation-dependent manner. In contrast, their expressions were decreased in ATDC5 cells. In ATDC5 cells, overexpression of TPD52 decreased alkaline phosphatase (ALPase) activity, while knock-down of TPD52 showed little effect. In contrast, overexpression of TPD54 enhanced ALPase activity, Ca2+ deposition, and the expressions of type X collagen and ALPase genes, while knock-down of TPD54 reduced them. The results revealed that TPD52 inhibits and that TPD54 promotes the terminal differentiation of a chondrocyte cell line. As such, we report for the first time the important roles of TPD52 and TPD54, which work oppositely, in the terminal differentiation of chondrocytes during endochondral ossification.

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Functional Virtual Flow Cytometry: A Visual Analytic Approach for Characterizing Single-Cell Gene Expression Patterns

We presented a novel workflow for detecting distribution patterns in cell populations based on single-cell transcriptome study. With the fast adoption of single-cell analysis, a challenge to researchers is how to effectively extract gene features to meaningfully separate the cell population. Considering that coexpressed genes are often functionally or structurally related and the number of coexpressed modules is much smaller than the number of genes, our workflow uses gene coexpression modules as features instead of individual genes. Thus, when the coexpressed modules are summarized into eigengenes, not only can we interactively explore the distribution of cells but also we can promptly interpret the gene features. The interactive visualization is aided by a novel application of spatial statistical analysis to the scatter plots using a clustering index parameter. This parameter helps to highlight interesting 2D patterns in the scatter plot matrix (SPLOM). We demonstrated the effectiveness of the workflow using two large single-cell studies. In the Allen Brain scRNA-seq dataset, the visual analytics suggested a new hypothesis such as the involvement of glutamate metabolism in the separation of the brain cells. In a large glioblastoma study, a sample with a unique cell migration related signature was identified.

http://ift.tt/2vsoYME

Sparse Contribution Feature Selection and Classifiers Optimized by Concave-Convex Variation for HCC Image Recognition

Accurate classification of hepatocellular carcinoma (HCC) image is of great importance in pathology diagnosis and treatment. This paper proposes a concave-convex variation (CCV) method to optimize three classifiers (random forest, support vector machine, and extreme learning machine) for the more accurate HCC image classification results. First, in preprocessing stage, hematoxylin-eosin (H&E) pathological images are enhanced using bilateral filter and each HCC image patch is obtained under the guidance of pathologists. Then, after extracting the complete features of each patch, a new sparse contribution (SC) feature selection model is established to select the beneficial features for each classifier. Finally, a concave-convex variation method is developed to improve the performance of classifiers. Experiments using 1260 HCC image patches demonstrate that our proposed CCV classifiers have improved greatly compared to each original classifier and CCV-random forest (CCV-RF) performs the best for HCC image recognition.

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Antidiabetic Micro-/Nanoaggregates from Ge-Gen-Qin-Lian-Tang Decoction Increase Absorption of Baicalin and Cellular Antioxidant Activity In Vitro

The antidiabetic effects of Ge-Gen-Qin-Lian-Tang decoction (GQD) have been proven clinically. In a pharmacological study conducted on STZ-induced diabetic rats, the constitutive aggregates/sediments of Ge-Gen-Qin-Lian-Tang decoction exhibited stronger hypoglycemic and antioxidant activities compared to the soluble compositions. This study aims to demonstrate the pharmacological properties of aggregates derived from GQD by measuring permeability of the active monomer phytochemicals (e.g., baicalin) in a Caco-2 cell monolayer and determine the cellular viability, intracellular redox status (MDA and SOD), and insulin secretion of pancreatic β-cell line, INS-1, following STZ-induced oxidative stress. The aggregates were separated into three fractions, namely, "MA (microaggregates)," "400 g supernatant," and "MNA (micro-/nanoaggregates)," by centrifugation at 400 ×g and 15000 ×g, respectively. Aggregates in the sediment increased baicalin absorption, showed little toxicity to β-cells, elevated intracellular SOD levels, and significantly suppressed oxidative damage effects on cellular viability and functions. The "MA" fraction had a larger particle size and provided higher antioxidant cellular protection than "MNA" in vitro, implying that the sediments may be the active components in the herbal decoction. The actions of these micro-/nanoaggregates may provide a new perspective for understanding the antidiabetic effects of herbal decoctions and aid in interpretation of synergistic actions between the multiple components.

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Dementia-friendly interventions to improve the care of people living with dementia admitted to hospitals: a realist review

Objectives

To identify features of programmes and approaches to make healthcare delivery in secondary healthcare settings more dementia-friendly, providing a context-relevant understanding of how interventions achieve outcomes for people living with dementia.

Design

A realist review conducted in three phases: (1) stakeholder interviews and scoping of the literature to develop an initial programme theory for providing effective dementia care; (2) structured retrieval and extraction of evidence; and (3) analysis and synthesis to build and refine the programme theory.

Data sources

PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, NHS Evidence, Scopus and grey literature.

Eligibility criteria

Studies reporting interventions and approaches to make hospital environments more dementia-friendly. Studies not reporting patient outcomes or contributing to the programme theory were excluded.

Results

Phase 1 combined findings from 15 stakeholder interviews and 22 publications to develop candidate programme theories. Phases 2 and 3 identified and synthesised evidence from 28 publications. Prominent context–mechanism–outcome configurations were identified to explain what supported dementia-friendly healthcare in acute settings. Staff capacity to understand the behaviours of people living with dementia as communication of an unmet need, combined with a recognition and valuing of their role in their care, prompted changes to care practices. Endorsement from senior management gave staff confidence and permission to adapt working practices to provide good dementia care. Key contextual factors were the availability of staff and an alignment of ward priorities to value person-centred care approaches. A preoccupation with risk generated responses that werelikely to restrict patient choice and increase their distress.

Conclusions

This review suggests that strategies such as dementia awareness training alone will not improve dementia care or outcomes for patients with dementia. Instead, how staff are supported to implement learning and resources by senior team members with dementia expertise is a key component for improving care practices and patient outcomes.

Trial registration number

CRD42015017562.

http://ift.tt/2vrW5Ag

Link Worker social prescribing to improve health and well-being for people with long-term conditions: qualitative study of service user perceptions

Objectives

To describe the experiences of patients with long-term conditions who are referred to and engage with a Link Worker social prescribing programme and identify the impact of the Link Worker programme on health and well-being.

Design

Qualitative study using semistructured interviews with thematic analysis of the data.

Intervention

Link Worker social prescribing programme comprising personalised support to identify meaningful health and wellness goals, ongoing support to achieve agreed objectives and linkage into appropriate community services.

Setting

Inner-city area in West Newcastle upon Tyne, UK (population n=132 000) ranked 40th most socioeconomically deprived in England, served by 17 general practices.

Participants

Thirty adults with long-term conditions, 14 female, 16 male aged 40–74 years, mean age 62 years, 24 white British, 1 white Irish, 5 from black and minority ethnic communities.

Results

Most participants experienced multimorbidity combined with mental health problems, low self-confidence and social isolation. All were adversely affected physically, emotionally and socially by their health problems. The intervention engendered feelings of control and self-confidence, reduced social isolation and had a positive impact on health-related behaviours including weight loss, healthier eating and increased physical activity. Management of long-term conditions and mental health in the face of multimorbidity improved and participants reported greater resilience and more effective problem-solving strategies.

Conclusions

Findings suggest that tackling complex and long-term health problems requires an extensive holistic approach not possible in routine primary care. This model of social prescribing, which takes into account physical and mental health, and social and economic issues, was successful for patients who engaged with the service. Future research on a larger scale is required to assess when and for whom social prescribing is clinically effective and cost-effective.

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Barriers and facilitators to adherence to secondary stroke prevention medications after stroke: analysis of survivors and caregivers views from an online stroke forum

Objective

To identify barriers and facilitators of medication adherence in patients with stroke along with their caregivers.

Design

Qualitative thematic analysis of posts about secondary prevention medications, informed by Perceptions and Practicalities Approach.

Setting

Posts written by the UK stroke survivors and their family members taking part in the online forum of the Stroke Association, between 2004 and 2011.

Participants

84 participants: 49 stroke survivors, 33 caregivers, 2 not stated, identified using the keywords 'taking medication', 'pills', 'size', 'side-effects', 'routine', 'blister' as well as secondary prevention medication terms.

Results

Perceptions reducing the motivation to adhere included dealing with medication side effects, questioning doctors' prescribing practices and negative publicity about medications, especially in regard to statins. Caregivers faced difficulties with ensuring medications were taken while respecting the patient's decisions not to take tablets. They struggled in their role as advocates of patient's needs with healthcare professionals. Not experiencing side effects, attributing importance to medications, positive personal experiences of taking tablets and obtaining modification of treatment to manage side effects were facilitators of adherence. Key practical barriers included difficulties with swallowing tablets, dealing with the burden of treatment and drug cost. Using medication storage devices, following routines and getting help with medications from caregivers were important facilitators of adherence.

Conclusions

An online stroke forum is a novel and valuable resource to investigate use of secondary prevention medications. Analysis of this forum highlighted significant barriers and facilitators of medication adherence faced by stroke survivors and their caregivers. Addressing perceptual and practical barriers highlighted here can inform the development of future interventions aimed at improving adherence to secondary prevention medication after stroke.

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Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web

A protocol for the online investigation of protein sequence-structure-dynamics relationships using Bio3D-web is presented.

http://ift.tt/2tgGd76

A Lipid Extraction and Analysis Method for Characterizing Soil Microbes in Experiments with Many Samples

The article describes a method that increases throughput while balancing effort and accuracy for extraction of lipids from the cell membranes of microorganisms for use in characterizing both total lipids and the relative abundance of indicator lipids to determine soil microbial community structure in studies with many samples.

http://ift.tt/2vrjtxz

Pharmacokinetics of intravenous pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor [ 14 C]copanlisib (BAY 80-6946) in a mass balance study in healthy male volunteers

Abstract

Purpose

To determine the pharmacokinetics of radiolabeled copanlisib (BAY 80-6946) in healthy male volunteers and to investigate the disposition and biotransformation of copanlisib.

Methods

A single dose of 12 mg copanlisib containing 2.76 MBq [¹⁴C]copanlisib was administered as a 1-h intravenous infusion to 6 volunteers with subsequent sampling up to 34 days. Blood, plasma, urine and feces were collected to monitor total radioactivity, parent compound and metabolites.

Results

Copanlisib treatment was well tolerated. Copanlisib was rapidly distributed throughout the body with a volume distribution of 1870 L and an elimination half-life of 52.1-h (range 40.4–67.5-h). Copanlisib was the predominant component in human plasma (84% of total radioactivity AUC) and the morpholinone metabolite M1 was the only circulating metabolite (about 5%). Excretion of drug-derived radioactivity based on all 6 subjects was 86% of the dose within a collection interval of 20–34 days with 64% excreted into feces as major route of elimination and 22% into urine. Unchanged copanlisib was the main component excreted into urine (15% of dose) and feces (30% of dose). Excreted metabolites (41% of dose) of copanlisib resulted from oxidative biotransformation.

Conclusions

Copanlisib was eliminated predominantly in the feces compared to urine as well as by hepatic biotransformation, suggesting that the clearance of copanlisib would more likely be affected by hepatic impairment than by renal dysfunction. The dual mode of elimination via unchanged excretion of copanlisib and oxidative metabolism decreases the risk of clinically relevant PK-related drug–drug interactions.

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iSepsis – Vitamin C, Hydrocortisone and Thiamine – The “Metabolic Resuscitation Protocol”

iSepsis - The Metabolic Resuscitation Protocol

EMCrit by Paul Marik.

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Angiogenesis Dysregulation in the Pathogenesis of Systemic Sclerosis

Systemic sclerosis is a chronic autoimmune connective tissue disease characterized by vascular injury and fibrosis and by an impaired angiogenesis which cannot ensure an efficient vascular recovery. Vascular injury is responsible for hypoxia and tissual ischemia which are the primary triggers for angiogenesis and are not able to induce a compensatory angiogenesis. This review article is focused on current knowledge on the mechanisms responsible for angiogenesis dysregulation in systemic sclerosis.

http://ift.tt/2vqVChG

Differential Expression of Glycolysis-Related Proteins in Follicular Neoplasms versus Hürthle Cell Neoplasms: A Retrospective Analysis

Purpose. Although currently classified as variants of follicular neoplasms (FNs), Hürthle cell neoplasms (HCNs) exhibit distinct biological characteristics. Hence, the metabolism of both neoplasms may also be different. The aims of this study were to investigate and compare the expression of glycolysis-related proteins in HCNs and FNs and to determine the clinical implications of such expression. Methods. Tissue microarrays were constructed with 265 samples of FNs (112 follicular carcinomas (FCs) and 153 follicular adenomas (FAs)) as well as 108 samples of HCNs (27 Hürthle cell carcinomas (HCCs) and 81 Hürthle cell adenomas (HCAs)). Immunohistochemical staining for the glycolysis-related molecules Glut-1, hexokinase II, CAIX, and MCT4 was performed. Results. The expression levels of Glut-1, hexokinase II, CAIX, and MCT4 were significantly higher in HCNs than in FNs (). Glut-1, hexokinase II, CAIX, and MCT4 expression levels were highest in HCC, followed by HCA, FC, and FA (all ). In HCC, hexokinase II positivity was associated with large tumor size (>4 cm) (), CAIX positivity with vascular invasion (), and MCT4 positivity with extrathyroidal extension (). Conclusion. The expression levels of the glycolysis-related proteins Glut-1, hexokinase II, CAIX, and MCT4 were higher in HCNs than in FNs and in HCCs than in HCAs.

http://ift.tt/2tfYu4s

Laboratory and Genetic Biomarkers Associated with Cerebral Blood Flow Velocity in Hemoglobin SC Disease

Reference values for cerebral blood flow velocity (CBFV) in hemoglobin SC disease (HbSC) have not been established. We aimed to investigate associations between laboratory and genetic biomarkers associated with CBFV in HbSC children. Sixty-eight HbSC children were included; CBFV was analyzed by transcranial Doppler, and the time-averaged maximum mean velocity (TAMMV) was estimated. Hematological, biochemical, immunological, and genetic analyses were performed. TAMMV was negatively correlated with red blood cell count (RBC) count, hemoglobin, hematocrit, and direct bilirubin (DB), yet positively correlated with monocytes and ferritin. We found that children with TAMMV ≥ 128 cm/s had decreased red blood cell distribution width (RDW) and nitric oxide metabolite (NOx) concentration. Children with TAMMV ≥ 143.50 cm/s had decreased hemoglobin and hematocrit, as well as increased ferritin levels. Decreased hemoglobin, hematocrit, RDW, and NOx and increased ferritin were detected in children with TAMMV ≥ 125.75 cm/s. The CAR haplotype was associated with higher TAMMV. In association analyses, RBC, hemoglobin, hematocrit, RDW, monocyte, DB, NOx, and ferritin, as well as the CAR haplotype, were found to be associated with higher TAMMV in HbSC children. Multivariate analysis suggested that high TAMMV was independently associated with hematocrit, RDW, and NOx. Additional studies are warranted to validate the establishment of a cutoff value of 125.75 cm/s associated with elevated TAMMV in HbSC children.

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Purification, Preliminary Characterization, and Immunological Activity of Polysaccharides from Crude Drugs of Sijunzi Formula

Sijunzi Decoction (SJZD) is a conventional prescription for curing spleen deficiency in Traditional Chinese Medicine and polysaccharide is its main ingredient. In order to explore the effective ingredients contributing to the immunological activity of SJZD, we isolated and purified seven homogeneous polysaccharides from Radix Ginseng (RS-3-1 and RS-3-2), Rhizoma Atractylodis Macrocephalae (BZ-3-1, BZ-3-2, and BZ-3-3), Poria (FL-3-1), and Radix Glycyrrhizae (GC-3-1) decoctions, respectively. The molecular weight of seven homogeneous polysaccharides ranged from 5.42 × 104 to 5.65 × 104 Da. Monosaccharide composition determined by GC-MS analysis showed that these polysaccharides were primarily composed of Rha, Ara, Xyl, Man, Glc, and Gal with various ratios. Immunological activity assay revealed that polysaccharides from four crude drug components of SJZD displayed inhibitory effects on the complement system. RS-3-1, BZ-3-1, FL-3-1, and GC-3-1 could significantly enhance the phagocytosis and increase the NO production and tumor necrosis factor (TNF-α) level in RAW 264.7 cells (). These results demonstrated the immunological activities of these polysaccharides from the four crude drugs. This study supports the therapeutic effect of SJZD in clinical use and is essential for further identification the immunopolysaccharide from SJZD decoction.

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Recovery following Thyroxine Treatment Withdrawal, but Not Propylthiouracil, Averts In Vivo and Ex Vivo Thyroxine-Provoked Cardiac Complications in Adult FVB/N Mice

Persistent cardiovascular pathology has been described in hyperthyroid patients even with effective antithyroid treatment. Here, we studied the effect of a well-known antithyroid drug, propylthiouracil (PTU; 20 mg/kg/day), on thyroxine (T4; 500 µg/kg/day)-induced increase in blood pressure (BP), cardiac hypertrophy, and altered responses of the contractile myocardium both in vivo and ex vivo after 2 weeks of treatment. Furthermore, the potential recovery through 2 weeks of T4 treatment discontinuation was also investigated. PTU and T4 recovery partially reduced the T4-prompted increase in BP. Alternatively, PTU significantly improved the in vivo left ventricular (LV) function with no considerable effects on cardiac hypertrophy or ex vivo right ventricular (RV) contractile alterations subsequent to T4 treatment. Conversely, T4 recovery considerably enhanced the T4-provoked cardiac changes both in vivo and ex vivo. Altogether, our data is in agreement with the proposal that hyperthyroidism-induced cardiovascular pathology could persevere even with antithyroid treatments, such as PTU. However, this cannot be generalized and further investigation with different antithyroid treatments should be executed. Moreover, we reveal that recovery following experimental hyperthyroidism could potentially ameliorate cardiac function and decrease the risk for additional cardiac complications, yet, this appears to be model-dependent and should be cautiously construed.

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Atlantoaxial Misalignment Causes High Blood Pressure in Rats: A Novel Hypertension Model

Atlantoaxial disorders are often correlated with hypertension in practice. In order to study the relationship between atlantoaxial disorder and hypertension, we attempted to construct an animal model. In this work, we presented an animal model where their atlantoaxial joints were misaligned. We investigated the changes of blood pressure before and after treatments of the modeled rats. We had the following results. (1) SBP and DBP of each surgery group were significantly higher than those of control and sham groups. (2) After the second operation (the fixture was removed), SBP and DBP of both surgery groups decreased and got closer to the control and sham groups after 7 days. (3) Heart rates got significantly higher in both surgery groups, compared to control and sham groups. (4) The blood Ach levels of the surgery groups were significantly lower than those of control and sham groups. With these results, we concluded that we successfully constructed cervical atlantoaxial disorder models in rats that showed hypertension symptom. However, the underlying mechanism connecting atlantoaxial disorder and hypertension still requires further study.

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Near-Infrared 1064 nm Laser Modulates Migratory Dendritic Cells To Augment the Immune Response to Intradermal Influenza Vaccine.

Near-Infrared 1064 nm Laser Modulates Migratory Dendritic Cells To Augment the Immune Response to Intradermal Influenza Vaccine.

J Immunol. 2017 Jul 14;:

Authors: Morse K, Kimizuka Y, Chan MPK, Shibata M, Shimaoka Y, Takeuchi S, Forbes B, Nirschl C, Li B, Zeng Y, Bronson RT, Katagiri W, Shigeta A, Sîrbulescu RF, Chen H, Tan RYY, Tsukada K, Brauns T, Gelfand J, Sluder A, Locascio JJ, Poznansky MC, Anandasabapathy N, Kashiwagi S

Abstract
Brief exposure of skin to near-infrared (NIR) laser light has been shown to augment the immune response to intradermal vaccination and thus act as an immunologic adjuvant. Although evidence indicates that the NIR laser adjuvant has the capacity to activate innate subsets including dendritic cells (DCs) in skin as conventional adjuvants do, the precise immunological mechanism by which the NIR laser adjuvant acts is largely unknown. In this study we sought to identify the cellular target of the NIR laser adjuvant by using an established mouse model of intradermal influenza vaccination and examining the alteration of responses resulting from genetic ablation of specific DC populations. We found that a continuous wave (CW) NIR laser adjuvant broadly modulates migratory DC (migDC) populations, specifically increasing and activating the Lang(+) and CD11b (-) Lang(-) subsets in skin, and that the Ab responses augmented by the CW NIR laser are dependent on DC subsets expressing CCR2 and Langerin. In comparison, a pulsed wave NIR laser adjuvant showed limited effects on the migDC subsets. Our vaccination study demonstrated that the efficacy of the CW NIR laser is significantly better than that of the pulsed wave laser, indicating that the CW NIR laser offers a desirable immunostimulatory microenvironment for migDCs. These results demonstrate the unique ability of the NIR laser adjuvant to selectively target specific migDC populations in skin depending on its parameters, and highlight the importance of optimization of laser parameters for desirable immune protection induced by an NIR laser-adjuvanted vaccine.

PMID: 28710250 [PubMed - as supplied by publisher]

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A Unique Case for Spinal Cord Stimulation: Successful Treatment of Small Fiber Neuropathy Pain Using Multiple Spinal Cord Stimulators

Spinal cord stimulators have commonly been used to treat multiple pain conditions. This case report represents a unique case of using multiple spinal cord stimulators for widespread small fiber neuropathy pain. This case report concerns patient JJ who first presented with generalized neuropathic pain. His pain was an intermittent burning, stinging quality that originally focused in both of his feet and progressed to include his legs and arms and eventually involved his entire body. The pain would last moments to hours at least daily. He reported a poor quality of life. He was diagnosed with small fiber neuropathy with anhydrosis, suggestive of idiopathic erythromelalgia. He had a spinal cord stimulator trial involving both cervical and lower thoracic percutaneous leads. After two spinal cord stimulators were implanted, the patient began to report an improvement in pain. The patient continues to report excellent pain relief. The patient uses the stimulator intermittently as needed, in an abortive fashion for pain flares. The patient is very pleased and has increased his activity. He now attends graduate school full time. This case report hopes to illustrate a unique use of multiple spinal cord stimulators in treating widespread neuropathic pain caused by small fiber neuropathy.

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Rapid Maxillary Expansion and Upper Airway Morphology: A Systematic Review on the Role of Cone Beam Computed Tomography

Objective. This study aimed to investigate the quality of cone beam computed tomography (CBCT) studies evaluating the effects of rapid maxillary expansion on upper airway morphology. Materials and Methods. A database search was conducted using PubMed, Ovid, and Cochrane Library up to December 2016. Studies in which CBCT was adopted to visualize the upper airway before and after rapid maxillary expansion were included. The population target was growing patients. Methodological quality assessment was performed. Results. The screening process resulted in the exclusion of 1079 references, resulting in only 9 remaining papers that fulfilled the inclusion criteria. No randomized clinical trials were found. The quality scores ranged from 36% to 68% of the maximum achievable, and the mean quality score of the studies was 50%. No good quality studies were detected in our sample. Conclusions. Inconsistencies in the CBCT protocols utilized were detected between studies. Head posture, tongue position, and segmentation protocols were not consistent. These discrepancies were reflected in the different results obtained in the studies. A valid and consistent protocol with regard to head and tongue positioning, as well as nasal cavity volume segmentation, is required.

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Effects of Chronic Exposure to Sodium Arsenite on Expressions of VEGF and VEGFR2 Proteins in the Epididymis of Rats

Objective. To study the expressions of VEGF and VEGFR2 at protein level in the epididymis of rats with arsenism. Methods. Forty male Sprague-Dawley rats were randomly divided into four groups: the high dose arsenic infected group (60.0 mg/L in water), the middle dose arsenic infected group (12.0 mg/L in water), the low dose arsenic infected group (2.4 mg/L in water), and the control group (distilled water). Rats were treated with arsenic through drinking water for 6 consecutive months. At the end of the experiment, the average densitometry values of apoptotic cells in epididymis tubules were determined by TUNEL method; the protein and mRNA levels of VEGF and VEGFR2 were observed by immunohistochemistry, Western blot, and real time fluorescent quantitative PCR, respectively. Results. Compared with the control group, in each infected group, the average densitometry values of apoptotic cells in the epididymis tubules were significantly lower. Compared with control group, protein and mRNA levels of VEGF and VEGFR2 in each infected group were obviously declined. The correlations between protein and mRNA levels of VEGF and VEGFR2 were positively exhibited (r = 0.843, 0.869, p

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Therapeutic Potential of Epigallocatechin Gallate Nanodelivery Systems

Nowadays, the society is facing a large health problem with the rising of new diseases, including cancer, heart diseases, diabetes, neurodegenerative diseases, and obesity. Thus, it is important to invest in substances that enhance the health of the population. In this context, epigallocatechin gallate (EGCG) is a flavonoid found in many plants, especially in tea. Several studies support the notion that EGCG has several benefits in fighting cancer, heart diseases, diabetes, and obesity, among others. Nevertheless, the poor intestinal absorbance and instability of EGCG constitute the main drawback to use this molecule in prevention and therapy. The encapsulation of EGCG in nanocarriers leads to its enhanced stability and higher therapeutic effects. A comprehensive review of studies currently available on the encapsulation of EGCG by means of nanocarriers will be addressed.

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In Vitro Laser Treatment Platform Construction with Dental Implant Thread Surface on Bacterial Adhesion for Peri-Implantitis

This study constructs a standard in vitro laser treatment platform with dental implant thread surface on bacterial adhesion for peri-implantitis at different tooth positions. The standard clinical adult tooth jaw model was scanned to construct the digital model with 6 mm bone loss depth on behalf of serious peri-implantitis at the incisor, first premolar, and first molar. A cylindrical suite connected to the implant and each tooth root in the jaw model was designed as one experimental unit set to allow the suite to be replaced for individual bacterial adhesion. The digital peri-implantitis and suite models were exported to fulfill the physical model using ABS material in a 3D printer. A 3 mm diameter specimen implant on bacterial adhesion against Escherichia coli was performed for gram-negative bacteria. An Er:YAG laser, working with a chisel type glass tip, was moved from the buccal across the implant thread to the lingual for about 30 seconds per sample to verify the in vitro laser treatment platform. The result showed that the sterilization rate can reach 99.3% and the jaw model was not damaged after laser irradiation testing. This study concluded that using integrated image processing, reverse engineering, CAD system, and a 3D printer to construct a peri-implantitis model replacing the implant on bacterial adhesion and acceptable sterilization rate proved the feasibility of the proposed laser treatment platform.

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