Pazopanib-Induced Cutaneous Leukocytoclastic Vasculitis: An Exclusion Diagnosis of a Multidisciplinary Approach

In phase II/III trials, cutaneous side effects of pazopanib were reported in less than 20% of patients, with only 1–3% being grade 3/4. We present a case of a 66-year-old man with a previous history of left nephrectomy for a stage II clear cell renal carcinoma. Approximately 18 months later, recurrent disease in the lungs, mediastinum, and left psoas and bulky abdominal/pelvic nodal metastasis were documented. He was initially treated with pazopanib 800 mg q.d. and 1 week after starting this therapy, the patient presented with palpable purpura on his ankles. These lesions regressed within 2 weeks off pazopanib, but had recurred 4 weeks after he resumed medication at 400 mg q.d. Biopsy of the lesions revealed leukocytoclastic vasculitis. Despite tumour response to therapy, pazopanib was discontinued with total resolution of this skin toxicity within 2 weeks of his cutaneous toxicity. To the best of our knowledge, we report a rare yet significant cutaneous adverse reaction to pazopanib.
Case Rep Oncol 2017;10:1041–1049

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Successful Resection of G719X-Positive Pleomorphic Carcinoma after Afatinib Treatment

We report a case of pleomorphic carcinoma with exon 18 mutation (G719X) of the epidermal growth factor receptor (EGFR), which showed good response to afatinib and resulted in successful resection. To our knowledge, this is the first report on the use of afatinib for pleomorphic carcinoma followed by the surgical resection. The patient was a 59-year-old woman, who visited our hospital because chest computed tomography showed a 28 × 28-mm nodule in the left upper lobe. Bronchoscopy was performed and the histological findings of transbronchial biopsy revealed adenosquamous carcinoma positive for G719X mutation in exon 18 of the EGFR. Since fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography revealed a positive accumulation in the bilateral hilar and mediastinal lymph nodes, the disease was diagnosed as cT1bN3M0, stage IIIB. After 3 months of afatinib therapy, FDG accumulation in primary tumor was almost gone. However, FDG accumulation in lymph nodes remained unchanged. Video-assisted thoracic surgery was planned for further diagnostic information and left upper lobectomy with mediastinal lymph node dissection was performed. The resected tumor included adenocarcinoma, squamous cell carcinoma, and spindle cell components, without lymph node metastasis. Thus, the disease was diagnosed as pleomorphic carcinoma (pT2aN0M0, stage IB). All components in the resected specimen had the same G719X mutation in exon 18 of the EGFR. The patient has shown no signs of recurrence at 1 year after the operation. The present case indicates the possibility of minor EGFR mutations in pleomorphic carcinoma and successful outcome by the use of afatinib and surgical resection.
Case Rep Oncol 2017;10:1035–1040

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Probing and Manipulating the Interfacial Defects of InGaAs Dual-Layer Metal Oxides at the Atomic Scale

Abstract

The interface between III–V and metal-oxide-semiconductor materials plays a central role in the operation of high-speed electronic devices, such as transistors and light-emitting diodes. The high-speed property gives the light-emitting diodes a high response speed and low dark current, and they are widely used in communications, infrared remote sensing, optical detection, and other fields. The rational design of high-performance devices requires a detailed understanding of the electronic structure at this interface; however, this understanding remains a challenge, given the complex nature of surface interactions and the dynamic relationship between the morphology evolution and electronic structures. Herein, in situ transmission electron microscopy is used to probe and manipulate the structural and electrical properties of ZrO₂ films on Al₂O₃ and InGaAs substrate at the atomic scale. Interfacial defects resulting from the spillover of the oxygen-atom conduction-band wavefunctions are resolved. This study unearths the fundamental defect-driven interfacial electric structure of III–V semiconductor materials and paves the way to future high-speed and high-reliability devices.

The defect-driven interfacial electronic structures of the TiN/ZrO₂/Al₂O₃/InGaAs system are probed and manipulated using a specifically designed in situ transmission electron microscopy experimental method. The interfacial defects are found to result from the spillover of the oxygen-atom conduction-band wavefunctions. This study paves the way to future high-speed and high-reliability devices.

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Metal–Organic Frameworks as Platforms for Catalytic Applications

Abstract

Metal–organic frameworks (MOFs), also called porous coordination polymers, represent a class of crystalline porous materials built from organic linkers and metal ions/clusters. The unique features of MOFs, including structural diversity and tailorability as well as high surface area, etc., enable them to be a highly versatile platform for potential applications in many fields. Herein, an overview of recent developments achieved in MOF catalysis, including heterogeneous catalysis, photocatalysis, and eletrocatalysis over MOFs and MOF-based materials, is provided. The active sites involved in the catalysts are particularly emphasized. The challenges, future trends, and prospects associated with MOFs and their related materials for catalysis are also discussed.

Metal–organic frameworks (MOFs), a class of crystalline porous materials, have allowed great progress in catalysis over the past two decades. Herein, an overview of recent developments for MOF catalysis, including heterogeneous organic reactions, photocatalysis, and electrocatalysis over MOFs and MOF-based materials, is provided. The state-of-the-art and opportunities and challenges regarding MOF-based catalysis are also discussed.

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High-Pressure-Induced Comminution and Recrystallization of CH3NH3PbBr3 Nanocrystals as Large Thin Nanoplates

Abstract

High pressure (HP) can drive the direct sintering of nanoparticle assemblies for Ag/Au, CdSe/PbS nanocrystals (NCs). Instead of direct sintering for the conventional nanocrystals, this study experimentally observes for the first time high-pressure-induced comminution and recrystallization of organic–inorganic hybrid perovskite nanocrystals into highly luminescent nanoplates with a shorter carrier lifetime. Such novel pressure response is attributed to the unique structural nature of hybrid perovskites under high pressure: during the drastic cubic–orthorhombic structural transformation at ≈2 GPa, (301) the crystal plane fully occupied by organic molecules possesses a higher surface energy, triggering the comminution of nanocrystals into nanoslices along such crystal plane. Beyond bulk perovskites, in which pressure-induced modifications on crystal structures and functional properties will disappear after pressure release, the pressure-formed variants, i.e., large (≈100 nm) and thin (<10 nm) perovskite nanoplates, are retained and these exhibit simultaneous photoluminescence emission enhancing (a 15-fold enhancement in the photoluminescence) and carrier lifetime shortening (from ≈18.3 ± 0.8 to ≈7.6 ± 0.5 ns) after releasing of pressure from 11 GPa. This pressure-induced comminution of hybrid perovskite NCs and a subsequent amorphization–recrystallization treatment offer the possibilities of engineering the advanced hybrid perovskites with specific properties.

High pressure (up to tens of gigapascals), as a clean and powerful tool, can effectively alter crystal structures. Here, it is experimentally investigated for the first time whether pressure can regulate the comminution and recrystallization of MAPbBr₃ nanocrystals. The initial nanocrystals slide into nanoslices during phase transformation to the orthorhombic polymorph, followed by recrystallization into nanoplates upon amorphization.

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Risk of fatigue in cancer patients receiving anti-EGFR monoclonal antibodies: results from a systematic review and meta-analysis of randomized controlled trial

Abstract

Background

To evaluate the association between fatigue and anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR MAbs), we conducted the first meta-analysis to access the incidence and risk of fatigue associated with anti-EGFR MAbs.

Methods

Electronic databases were searched for randomized controlled trials (RCTs) published up to February 2017. Eligible studies were selected according to PRISMA statement. Incidence rates, risk ratio (RRs), and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models. Outcomes of quality were summarized in accordance with the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology.

Results

Thirty-five RCTs (including 15,622 patients) were included; median follow-up ranged from 8.1 to 71.4 months, and the fatigue events were recorded and graded according to the Common Toxicity Criteria for Adverse Events version 2.0 or 3.0 in most of the included trials. For patients receiving anti-EGFR MAbs, the overall incidence of all-grade and high-grade fatigue was 54.1% and 10.5%, respectively. Compared with control, anti-EGFR MAbs significantly increased the risk of all-grade fatigue (RR 1.10, 95% CI, 1.05–1.14, moderate-quality evidence) and high-grade fatigue (RR 1.31, 95% CI, 1.19–1.45, moderate-quality evidence). No significant differences among subgroup analyses (anti-EGFR MAbs, tumor type, and median follow-up) on high-grade fatigue were observed. No evidence of publication bias was observed.

Conclusion

The present study suggested that anti-EGFR MAbs may increase the risk of fatigue in cancer patients.

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Inhibitory Effect of Interferons on Contractive Activity of Bovine Mesenteric Lymphatic Vessels and Nodes

We studied the effect of IFNα-2b and IFNβ-1a on phasic and tonic contractions of isolated bovine mesenteric lymphatic vessels and nodes. IFNα-2b and IFNβ-1a in concentrations of 250-1000 U/ml produced dose-dependent negative chronotropic and inotropic effects on spontaneous phasic contractions and tonus of lymphatic vessels and nodes. In de-endothelialized lymphatic vessels and nodes, IFNα-2b and IFNβ-1a in the same concentrations had less pronounced inhibitory effect on spontaneous contraction and tonus. L-NAME (100 μM) and charybdotoxin (0.1 μM with 0.5 μM apamine) significantly attenuated the inhibitory effect of IFNα-2b on phasic and tonic contractions of lymph nodes. L-NAME (100 μM) and indomethacin (10 μM) significantly reduced the IFNα-2b-induced inhibitory effect on phasic and tonic contractions of lymph node. These results indicate that IFNα-2b and IFNβ-1a have a pronounced inhibitory effect on the phasic and tonic contractions of bovine mesenteric lymphatic vessels and nodes. The responses are endothelium-dependent and are determined by production of NO and endothelium-dependent hyperpolarizing factor by endotheliocytes in lymphatic vessels and by production of NO and prostacyclin by endotheliocytes in the lymphatic nodes.

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Anticoagulant Effects of Arginine-Containing Peptides of the Glyproline Family (His-Phe-Arg-Trp-Pro-Gly-Pro and Thr-Lys-Pro-Arg-Pro-Gly-Pro) Revealed by Thromboelastography

Thromboelastography revealed anticoagulant effects of 3 glyproline oligopeptides (in various concentrations): His-Phe-Arg-Trp-Pro-Gly-Pro, Thr-Lys-Pro-Arg-Pro-Gly-Pro (Selank), and Pro-Gly-Pro. The parameters R, K, MA, S, TMA, and J changed to hypocoagulation direction in comparison to the control. At this, Selank demonstrated the maximal anticoagulation potency.

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Melatonin—Aluminum Oxide—Polymethylsiloxane Complex on Apoptosis of Liver Cells in a Model of Obesity and Type 2 Diabetes Mellitus

We studied the effects of a melatonin—aluminum oxide—polymethylsiloxane complex (complex M) on the expression of apoptosis regulators Bcl-2 and Bad in the liver of homozygous db/db BKS.Cg-Dock7^m+/+Lepr^db/J mice with obesity and type 2 diabetes. Complex M or placebo was administered daily through the gastric tube during weeks 8-16 of life. In mice with type 2 diabetes mellitus receiving placebo, enhanced immunohistochemical reactions for proapoptotic Bad protein and weak response for anti-apoptotic Bcl-2 protein were observed. Administration of complex M shifted the ratio of apoptosis regulators: the area of Bcl-2 expression significantly increased and against the background of reduced Bad expression area. These findings attest to antiapoptotic effect of complex M in the liver on the model of type 2 diabetes mellitus.

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Inhibition of the Expression of Inducible NO Synthase by Neuroactive Amino Acid Derivatives Phenibut and Glufimet In Vitro and Ex Vivo

The effects of glufimet and phenibut (glutamic acid and GABA derivatives, respectively) on concentration of inducible NO synthase and cGMP in LPS-activated mouse peritoneal macrophages and on NO end products in their culture medium were examined in vitro and ex vivo. Addition of LPS into culture medium elevated concentration of NO metabolites in this medium and increased concentration of inducible NO synthase and cGMP in the lysates of peritoneal macrophages, whereas incubation of the cells with examined agents applied at concentration of 10^—5 M diminished these indices. Similar results were obtained with intraperitoneal injection of LPS, glufimet, and phenibut. In culture medium containing peritoneal macrophages from the mice injected with LPS (100 μg/kg), the concentrations of inducible NO synthase and cGMP as well as the total concentration of nitrite and nitrate ions increased, whereas in culture medium with the cells from LPS-exposed mice treated with glufimet (28.7 mg/kg) and phenibut (50 mg/kg) these indices significantly decreased.

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Immunomorphological Changes in the Olfactory Bulbs of Rats after Intranasal Administration of Rotenone

Changes in the structure of the olfactory bulbs after long-term intranasal administration of pesticide rotenone, a classical inductor of parkinsonism, to rats were studied by the methods of immunomorphology. In rats intranasally receiving rotenone in a dose of 2.5 mg/kg every other day over 2 weeks, a decrease in the density of dopaminergic neurons and the area of astrocyte processes in the olfactory bulbs, activation of microglia in the glomerular layer, and enhanced α-synuclein phosphorylation and its accumulation in the bodies of mitral layer neurons were observed. The observed changes agree with the hypothesis on pathological α-synuclein transport via the olfactory route in Parkinson's disease and confirm relevance of the rotenone model of Parkinson's disease for studies of the pathological accumulation of α-synuclein.

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Effect of Neoadjuvant Chemoradiation Therapy on Proteasome Pool in Rectal Cancer

In untreated rectal cancer patients, the chymotrypsin-like activity of proteasomes in tumor tissue was 3-fold higher than that in conventionally normal tissue, which is explained by up-regulation of expression of immunoproteasomes and total pool of proteasomes. After neoadjuvant chemoradiation therapy, expressions of the total pool of proteasomes and immunoproteasomes in the tumor as well as the relative ratios of these indices to those in conventionally normal tissue were smaller by 1.4-3.3 times in comparison with the untreated patients. These changes were paralleled with pronounced (4.5-fold) down-regulation of proteasome activity in the tumor and a 3.7-fold decrease of activity ratio for the proteasomes in tumor and in conventionally normal tissue. The number of immunoproteasome subunits and the chymotrypsin-like activity of proteasomes can be viewed as potential markers to prognosticate effectiveness of neoadjuvant chemoradiation therapy in rectal cancer patients.

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Role of Sertoli and Leydig Cells in the Regulation of Spermatogonial Stem Cell and Development of Reproductive Disorders in Male C57Bl/6 Mice with Type 1 Diabetes Mellitus

Course administration streptozotocin to male C57Bl/6 mice induces a complex of symptoms typical of type 1 diabetes mellitus: hyperglycemia and insulin deficiency, focal inflammatory infiltration of the pancreas, destructive changes in the Langerhans islets, damage to the insular apparatus (reduced number of PDX1⁺ cells and insulin expression by the secreting cells). Male reproductive disorder are serious complications of type 1 diabetes mellitus. In "diabetic" mice, interstitial edema with inflammatory infiltration and microvascular disorders in the testicular tissue are observed, the number of endothelial precursors (CD45^—/CD31⁺) and the total number and percentage of motile spermatozoa decreased, immature spermatogenic epithelium cells are desquamated of into the lumen of the tubules. Disturbances in the proliferation and differentiation of various spermatogonial stem cell populations (c-kit^—/CD90⁺, c-kit⁺/CD90⁺, and CD51^—/CD24⁺/CD52⁺) in diabetes can be explained by the inhibitory influence of inflammatory factors on testosterone-producing Leydig cells.

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Gene TNF Polymorphism -308G>A ( rs1800629 ) and Its Relationship with the Efficiency of Ursodeoxycholic Acid Therapy in Patients with Nonalcoholic Stetohepatitis

Association of TNF gene polymorphism -308G>A with the development of nonalcoholic steatohepatitis in the Russian population was revealed. Carriers of allele A of the TNF gene marker -308G>A have significantly higher risk of nonalcoholic steatohepatitis development: OR=1.69 (1.05; 2.71). Allele A carriage by this marker predicts an increase in the basal HDL level and a decrease in LDL and IL-10 levels in the blood of healthy subjects. Patients with nonalcoholic steatohepatitis, differing by the TNF gene -308G>A marker genotype, differ by the time course of the markers of hepatocellular damage (ALT, AST), activity of hepatocyte apoptosis (tissue polypeptide-specific antigen), and activation of specific humoral immunity (γ-globulin) in response to therapy with ursodeoxycholic acid in a dose of 10-15 mg/kg over 4-6 weeks. Carriers of allele A of the TNF gene polymorphic marker -308G>A are more sensitive to ursodeoxycholic acid therapy than carriers of GG genotype.

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Effects of Tripeptide Gly-His-Lys in Pain-Induced Aggressive-Defensive Behavior in Rats

We studied the effect of Gly-His -Lys tripeptide administered intraperitoneally in doses of 5, 15, 50 and 150 μg/kg on pain-induced aggressive-defensive behavior. A foot-shock model of aggression in rats grouped in pairs in an electrified chamber was used. Analgesic and antiaggresiogenic effects of the peptide were demonstrated. It was found the L-lysine residue plays the key role in these effects, because they were observed under the influence of L-lysine administration in doses close to its equimolar content in the studied tripeptide.

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Comparison of the Pharmacological Effects of Dimeric Dipeptide Nerve Growth Factor Mimetic GK-2 and Mexidol on the Model of Ischemic Stroke in Rats

We compared the effects of GK-2 (dimeric dipeptide mimetic of nerve growth factor) and Mexidol (standard preparation for the therapy of stroke) on rat model of transient occlusion of the middle cerebral artery. GK-2 and Mexidol were administered intraperitoneally in the most active doses (1 and 100 mg/kg, respectively) 6 h after surgery and then once a day for 6 days. The preparations reduced the volume of cerebral infarction (by 60 and 30%, respectively). At the same time, GK-2 had a pronounced and statistically more reliable effect in a dose that is lower by two orders of magnitude. In addition, GK-2 significantly reduced the neurological deficit in the limb placement test, while Mexidol was ineffective in this test.

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Seizure and cognitive outcomes after resection of glioneuronal tumors in children

Summary

Objective

Glioneuronal tumors (GNTs) are well-recognized causes of chronic drug-resistant focal epilepsy in children. Our practice involves an initial period of radiological surveillance and antiepileptic medications, with surgery being reserved for those with radiological progression or refractory seizures. We planned to analyze the group of patients with low-grade GNTs, aiming to identify factors affecting seizure and cognitive outcomes.

Methods

We retrospectively reviewed the medical records of 150 children presenting to Great Ormond Street Hospital with seizures secondary to GNTs. Analysis of clinical, neuroimaging, neuropsychological, and surgical factors was performed to determine predictors of outcome. Seizure outcome at final follow-up was classified as either seizure-free (group A) or not seizure-free (group B) for patients with at least 12-months follow-up postsurgery. Full-scale intelligence quotient (FSIQ) was used as a measure of cognitive outcome.

Results

Eighty-six males and 64 females were identified. Median presurgical FSIQ was 81. One hundred twenty-one patients (80.5%) underwent surgery. Median follow-up after surgery was 2 years, with 92 patients (76%) having at least 12 months of follow-up after surgery. Seventy-four patients (80%) were seizure-free, and 18 (20%) continued to have seizures. Radiologically demonstrated complete tumor resection was associated with higher rates of seizure freedom (P = .026). Higher presurgical FSIQ was related to shorter epilepsy duration until surgery (P = .012) and to older age at seizure onset (P = .043).

Significance

A high proportion of children who present with epilepsy and GNTs go on to have surgical tumor resection with excellent postoperative seizure control. Complete resection is associated with a higher chance of seizure freedom. Higher presurgical cognitive functioning is associated with shorter duration of epilepsy prior to surgery and with older age at seizure onset. Given the high rate of eventual surgery, early surgical intervention should be considered in children with continuing seizures associated with GNTs.

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Qualitative interview study of antibiotics and self-management strategies for respiratory infections in primary care

Objective

To explore perceptions of illness, the decisions to consult and the acceptability of delayed antibiotic prescriptions and self-help treatments for respiratory tract infections (RTIs).

Design

Qualitative semistructured interview study.

Setting

UK primary care.

Participants

20 adult patients who had been participating in the 'PIPS' (Pragmatic Ibuprofen Paracetamol and Steam) trial in the South of England.

Method

Semistructured telephone interviews were conducted with participants to explore their experiences and views on various treatments for RTI.

Results

Participants had concerns about symptoms that were not clinically serious and were mostly unaware of the natural history of RTIs, but were aware of the limitations of antibiotics and did not expect them with every consultation. Most viewed delayed prescriptions positively and had no strong preference over which technique is used to deliver the delayed antibiotic, but some patients received mixed messages, such as being told their infection was viral then being given an antibiotic, or were sceptical about the rationale. Participants disliked self-help treatments that involved taking medication and were particularly concerned about painkillers in combination. Steam inhalation was viewed as only moderately helpful for mild symptoms.

Conclusion

Delayed prescribing is acceptable no matter how the delay is operationalised, but explanation of the rationale is needed and care taken to minimise mixed messages about the severity of illnesses and causation by viruses or bacteria. Better access is needed to good natural history information, and the signs and symptoms requiring or not requiring general practitioner advice. Significant concerns about paracetamol, ibuprofen and steam inhalation are likely to need careful exploration in the consultation.

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Cost-effectiveness of a preferred intensity exercise programme for young people with depression compared with treatment as usual: an economic evaluation alongside a clinical trial in the UK

Objectives

To assess the cost-effectiveness of preferred intensity exercise programme for young people with depression compared with a treatment as usual control group.

Design

A 'within trial' cost-effectiveness and cost-utility analysis conducted alongside a randomised controlled trial. The perspective of the analysis was the UK National Health Service and social services.

Setting

The intervention was provided in a community leisure centre setting.

Participants

86 young people aged 14–17 years attending Tier 2 and Tier 3 CAMHS (Child and Adolescent Mental Health Services) outpatient services presenting with depression.

Interventions

The intervention comprised 12 separate sessions of circuit training over a 6-week period. Sessions were supervised by a qualified exercise therapist. Participants also received treatment as usual. The comparator group received treatment as usual.

Results

We found improvements in the Children's Depression Inventory-2 (CDI-2) and estimated cost-effectiveness at £61 per point improvement in CDI-2 for the exercise group compared with control. We found no evidence that the exercise intervention led to differences in quality-adjusted life years (QALY). QALYs were estimated using the EQ-5D-5L (5-level version of EuroQol-5 dimension).

Conclusions

There is evidence that exercise can be an effective intervention for adolescents with depression and the current study shows that preferred intensity exercise could also represent a cost-effective intervention in terms of the CDI-2.

Trial registration number

NCT01474837.

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Referrers point of view on the referral process to neurosurgery and opinions on neurosurgeons: a large-scale regional survey in the UK

Objectives

There is an increased reliance on online referral systems (ORS) within neurosurgical departments across the UK. Opinions of neurosurgeons on ORS are extensively reported but those of referrers have hardly been sought. Our study aims at ascertaining our referring colleagues' views on our ORS and its impact on patient care, their opinions on neurosurgeons and how to improve our referral process.

Setting

14 district general hospitals and one teaching hospital.

Participants

641 healthcare professionals across a range of medical and surgical specialties including doctors of all grades, nurses and physiotherapists. Survey responses were obtained by medical students using a smartphone application.

Results

Although 92% of respondents were aware of the ORS, 74% would routinely phone the on-call registrar either before or after making referrals online. The majority (44%) believed their call to relate to a life-threatening emergency. 62% of referrers considered the ORS helpful in informing patients' care and 48% had a positive opinion of their interaction with neurosurgical registrars. On ways to improve the ORS, 50% selected email/text confirmation of response sent to referrers and 16% to referring consultants.

Conclusion

Our results confirm that referrers feel that using our ORS positively impacts patient care but that it remains in need of improvement in order to better suit our colleagues' needs when it comes to managing neurosurgical patients. We feel that the promotion of neurosurgical education and mitigation of the effects of adverse workplace human factors are likely to achieve the common goal of neurosurgeons and referrers alike: a high standard in patient care.

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Developing outcome measures assessing wound management and patient experience: a mixed methods study

Objectives

To develop outcome measures to assess practical management of primary surgical wounds and patient experience.

Design

Mixed methods, including qualitative interviews and data extraction from published randomised controlled trials (RCTs).

Setting

Two university-teaching NHS hospitals and three district NHS hospitals in the South West and Midlands regions of England.

Participants

Sixty-four patients and 15 healthcare professionals from abdominal general surgical specialities and obstetrics (caesarean section).

Methods

Measures were developed according to standard guidelines to identify issues relevant to patients' experiences of surgical wounds and dressings, including analysis of existing RCT outcomes and semi-structured interviews. These were written into provisional questionnaire items for a single outcome measure. Cognitive interviews with patients and healthcare professionals assessed face validity, acceptability and relevance. Findings from interviews were regularly shared with the study team who suggested amendments to modify and reword items to improve understanding before further iterative testing with patients and healthcare professionals.

Results

Analyses of existing RCT outcomes and interviews produced a total of 69 issues. Pretesting and iterative revision established the need for two separate measures. One measure addresses healthcare professionals' experience of wound management in two key areas: exudate and its impact, and allergic reactions to the dressing. The other measure addresses patients' experience of wounds in seven key areas: wound comfort, dressing removal, dressings to protect the wound, impact on daily activities, ease of movement, anxiety about the wound and satisfaction with dressing. Each measure took less than five min to complete and both were understood and acceptable to patients and healthcare professionals.

Conclusion

This in-depth study has developed two measures to assess practical management of primary surgical wounds and patient experience. Further work to test their validity, reliability and application to other settings is now required.

Trial registration number

HTA - 12/200/04; Pre-results.

http://ift.tt/2A9vhui

First Direct Evidence of Cue Integration in Reorientation: A New Paradigm

Abstract

There are several models of the use of geometric and feature cues in reorientation (Cheng, Huttenlocher, & Newcombe, ). The adaptive combination approach posits that people integrate cues with weights that depend on cue salience and learning, or, when discrepancies are large, they choose between cues based on these variables (Cheng, Shettleworth, Huttenlocher, & Rieser, ; Newcombe & Huttenlocher, ). In a new paradigm designed to evaluate integration and choice, disoriented participants attempted to return to a heading direction, in a trapezoidal enclosure in which feature and geometric cues both unambiguously specified a heading, but later the feature was moved. With discrepancies greater than 90 degrees, participants choose geometry. With smaller discrepancies, integration appeared in three of five situations; otherwise, participants used geometry alone. Variation depended on direction of feature movement and whether the nearest corner was acute or obtuse. The results have implications for contrasting adaptive combination and modularity theory, and for future research, offering a new paradigm for reorientation research, and for testing cue integration more broadly.

http://ift.tt/2zt5Sbw

A retrospective evaluation of 128 socket-shield cases in the esthetic zone and posterior sites: Partial extraction therapy with up to 4 years follow-up

Abstract

Objectives

Tooth loss results in an inevitable alveolar ridge reduction. This has established a cautionary approach to extract, wait, augment, and insert the implant, in lieu of immediate placement. However, saving the tooth or part of it whenever possible is more conservative and supports the vital periodontal tissue buccofacial to an implant. The purpose of this cases series was to report on implant survival using this technique in a large cohort of patients at mid-term follow-up.

Materials and Methods

A private practice patient database was searched for all patients having received socket-shield treatment in conjunction with immediate implant placement. Of the results returned, 128 met the inclusion criteria of ≥12 months from date of restoration, or failing prior to definitive restoration. These patients were recalled for evaluation of the restored implants up to 4 years post-treatment.

Results

Seventy immediate implants with socket-shields were placed in female patients and 58 in males, age range 24-71 (mean 39 years). The distribution of sites treated were: maxillary incisors (64%), premolars (22%), canines (14%); maxilla (89.9%), mandible (10.1%). 123/128 implants osseointegrated and survived 1-4 years following restoration (survival rate 96.1%). A combined complication rate of 25/128 implants occurred (19.5%). Five implants failed to osseointegrate and were removed. The remaining 20 complications were all managed or observed without management, with implants surviving at mid-term follow-up.

Conclusions

Notwithstanding technique sensitivity and the need for randomized control studies, this case series demonstrates that the socket-shield performs competitively when compared to implant survival rates in both conventional immediate and delayed implant placement.

http://ift.tt/2Bql8r6

Non-Competitive NMDA Receptor Antagonist Hemantane Reduces Ethanol Consumption in Long-Term Alcohol Experienced Rats

Activity of hemantane, an amino adamantane derivative, exhibiting the properties of lowaffinity non-competitive NMDA receptor antagonist, was evaluated in experimental in vivo models of alcoholism. Hemantane had no effects on the formation and manifestation of behavioral sensitization to ethanol in DBA/2 mice. Under conditions of free choice between 10% ethanol and water, hemantane (20 mg/kg/day for 14 days, intraperitoneally) significantly reduced the daily ethanol intake in random-bred male rats with formed alcohol motivation (>4 g/kg of ethanol). During modelling of withdrawal syndrome, hemantane administered intraperitoneally in doses of 5-20 mg/kg dose-dependently attenuated alcohol-deprivation effect after acute withdrawal with no effects on protracted abstinence. It was found that hemantane suppressed alcohol drinking behavior in long-term ethanol experienced rats and attenuated alcohol-seeking behavior after acute withdrawal.

http://ift.tt/2AB38gF

Biodistribution of Alpha-Fetoprotein-Containing Noncovalent Complex Aimpila with Antitumor Activity

Biodistribution of [¹²⁵I]Aimpila (20 mg/kg) in the tumor and normal tissues, including the mammary gland tissue, after single oral dose was studied in BALB/c nude mice with T47D/ReCAF⁺⁺⁺ human breast tumor sensitive to this drug and in closely related BALB/c nude⁺mice without tumors. The maximum concentration of [¹²⁵I]Aimpila was in fact the same in the tumor and in the mammary gland, while the time course of its accumulation/elimination differed. The time of the maximum accumulation of the drug in the tumor was shorter and its persistence longer than in normal tissue. After 24 h, label concentration in the tumor was 4.5 times higher (p=0.002). Differences in the time course of label accumulation in the tumor were detected. The maximum ratio of tumor/blood concentrations of the preparation was recorded in 1 h after administration. [¹²⁵I]Aimpila and [¹²⁵I]alpha-fetoprotein accumulated in the tumor in comparable concentrations and were eliminated simultaneously at the same rate. The results of comparative analysis of accumulation of the labeled compounds in Aimpila-sensitive T47D/RECAF⁺⁺⁺ tumor from 0.5 to 9.0 h after drug administration could be interpreted as a result of possible receptor-mediated binding of the complex with the tumor at the expense of the alpha-fetoprotein transporting part. Differences in the parameters of [¹²⁵I]Aimpila biodistribution in the tumor and normal mammary tissue indirectly attested to selective antiproliferative activity of the complex.

http://ift.tt/2BpGd58

Regeneration Potential of Lymphoid Tissue of Small Intestine in Mice after Exposure to Low-Intensity Radiation

Number and size of aggregated lymphoid nodules in the small intestine of mice exposed to radiation using a γ-irradiation unit GOBO-60 with ¹³⁷Cs source were measured using the methods of visual microscopy and morphometry. Morphological status of the nodules was estimated on days 4, 28, 60, and 90 after the exposure. Significant changes were observed in the lymphoid system of the small intestine after exposure to low-intensity radiation. The size of aggregated lymphoid nodules decreased and the relative number of cells with degenerative changes increased. Regenerative processes were observed as soon as on day 4 of the rehabilitation period. However, the number and sizes of aggregated lymphoid nodules (length, width, and section area), and the ratio of lymphoid nodules with germinal center were still lower than in the control. The number of cells forming lymphoid interstitial plaques was close to the control on days 28-90 of the rehabilitation process.

http://ift.tt/2Bq0Duu

Oxidative Stress as a Mechanisms of Reduced Glucose Absorption under Conditions of Immobilization Stress

Experimental studies demonstrated inhibition of glucose absorption in the jejunum in acute and chronic 1-h daily immobilization stress, with the maximum inhibition on day 7 of immobilization. These changes correlate with the development of oxidative stress in animals over the entire duration of the experiment, which manifested by an increase in the content of the primary and end LPO products and decrease of the total antioxidant activity of the blood. Correction of these shifts with the antioxidant drug inhibits accumulation of LPO products and increases antioxidant defense and glucose absorption rate. These data prove the important role of peroxidation in regulation of glucose absorption.

http://ift.tt/2A8X8Lk

Peculiarities of Cell Seeding on Polylactic Acid-Based Scaffolds Fabricated Using Electrospinning and Solution Blow Spinning Technologies

We studied the possibility of seeding bone marrow-derived stromal cells onto polylactic acid-based scaffolds fabricated by electrospinning and solution blow spinning technologies. The cells were applied to the scaffolds by dynamic seeding and scaffolds were then cultured in Petri dishes in culture medium for 3 days. Cell migration to the Petri dish surface was noted only for scaffolds fabricated by electrospinning technology, but DAPI staining confirmed the presence of cells in both scaffolds. The mean number of cells in scaffolds fabricated by electrospinning and solution blow spinning was 56±9 and 81±6, respectively. The scaffold fabricated by solution blow spinning was more effectively (p<0.05) colonized by cells due to its more optimal spatial structure.

http://ift.tt/2zqPtnU

Bioluminescent Study of the Distribution of High-Molecular-Weight Protein Fraction of Cellex Daily Preparation in the Brain after Intranasal Administation

Permeability of the blood—brain barrier for protein fractions 50-100 kDa (PF_50–100) of Cellex Daily preparation labeled with fluorescent tracer FITC and non-conjugated FITC were compared after intranasal administration of the preparations to healthy rats. Fluorimetrical analysis of the serum and cerebrospinal fluid samples showed that Cellex Daily PF_50–100-FITC administered intranasally penetrated into the blood and cerebrospinal fluid with maximum accumulation in 2 h after administration and persists in the circulation for 24 h probably due to binding with plasma proteins. The differences in the kinetic profile of PF_50–100-FITC and free FITC indirectly suggest that the major part of the preparation is not degraded within 24 h and FITC is probably not cleaved from the protein components of the preparation. In vivo fluorescence analysis showed significant fluorescent signal in the olfactory bulbs in 6 h after intranasal administration; hence, the preparation administered via this route can bypass the blood—brain barrier. Scanning laser confocal microscopy of rat brain sections confirmed penetration of the high-molecular weight protein fraction PF_50–100-FITC into CNS structures. The most pronounced accumulation of the labeled drug was observed in the olfactory bulb in 6 and 12 h after administration. In contrast to free FITC administered in the control group, significant accumulation of PF_50–100-FITC in the olfactory cortex and frontal cortex neurons with functionally active nuclei was observed in 6, 12 and 24 h after intranasal administration.

http://ift.tt/2zqXCZM

The Role of the Glutathione System in Oxidative Modification of Proteins and Dysregulation of Apoptosis in Jurkat Tumor Cells

We compared changes in the redox status and intensity of oxidative modification of proteins in intact Jurkat tumor cells and cells cultured with buthionine sulfoximine, an inhibitor of the key enzyme of glutathione synthesis γ-glutamylcysteine synthetase. The glutathione system components play a role in modulation of the content of protein-bound glutathione, protein carbonyl derivatives, bityrosine, and oxidized tryptophan, and in dysregulation of apoptosis in Jurkat tumor cells. Inhibition of de novo synthesis of glutathione in Jurkat tumor cells was followed by accumulation of hydroxyl radical, a reduction in the level of protein-bound glutathione and oxidized tryptophan, and a rise in the concentration of protein carbonyl derivatives. These changes were accompanied by activation of programmed cell death.

http://ift.tt/2ztLM0L

Morphological Evaluation of the Influence of the Peptide Complex from Tissue of Porcine Kidneys on the Experimental Urolithiasis

We performed morphological analysis of the effect of the peptide complex from porcine kidneys on the course of experimental urolithiasis modeled in rats by treatment with 1% ethylene glycol solution (in drinking water) for 6 weeks. The peptide complex obtained by acetic acid extraction was administered in a dose of 15 mg. Administration of the peptide complex to animals with experimental kidney stone disease leads to 100% destruction of large and medium stones to the "dust" granularity.

http://ift.tt/2BqoDO8

Ultrastructure of Rat Kidneys after Intravenous Administration of Modified Magnetite Nanoparticles

The ultrastructure of nephrocytes of the proximal and distal convoluted tubules, podocytes, mesangial cells, and macrophages of the interstitial connective tissue was studied after single intravenous administration of magnetite nanoparticles modified with chitosan (magnetic nanospheres) or lipids (magnetic liposomes). Transmission electron microscopy showed ultrastructural features of absorption of magnetite nanoparticles. The shape, size, and number of vesicles containing nanoparticles in nephrocytes of convoluted tubules and macrophages after administration of the suspensions of magnetic nanospheres and magnetic liposomes were described.

http://ift.tt/2ztLB5B

Effect of the Natural Cytokine Complex on the Structure and Metabolism of Contractile Myocardium Normally and under Increased Hemodynamic Load

Effect of natural complex of cytokines with activity of IL-1, IL-2, IL-6, TNF, MIF, GTFβ on the structure and metabolism of contractile ventricular cardiomyocytes was assessed in the control and under conditions of acute experimental aortic stenosis. Systemic administration of the complex in the control had no significant effect on myocardial morphology with low number of damaged cardiomyocytes and low degree of structural damage. Administration of the cytokine complex against the background of aortic stenosis did not exert any additional alterative effect on cardiomyocytes, structural damage of contractual nature was moderate. Systemic administration of the natural cytokine complex had a pronounced inhibitory effect on metabolic processes in the myocardium of both ventricles both in the control and against the background of increased hemodynamic load. In cardiomyocytes, glycolysis and citric acid cycle were slowed down, oxidation of free fatty acids and their metabolic products was inhibited as well as shuttle mechanisms and biosynthetic reactions. Inhibition of energy-producing processes is the cause of the lack of the contractile function energy supply and can worsen the course of cardiovascular diseases and increase the risk of their complications in conditions, accompanied by increased blood cytokine level.

http://ift.tt/2AB3iof

Application of Preparations Containing Copper Nanoparticles for the Treatment of Experimental Septic Wounds

Regenerative activity of locally applied drugs based on copper nanoparticles was compared on white male rats with an experimental purulent wound infected with clinical polyantibiotic resistant strains of Staphylococcus aureus. The use of a suspension of copper nanoparticles and complex drugs based on chitosan and starch with copper nanoparticles led to a rapid reduction of the wound area and elimination of the wound-contaminating agent, which confirmed high antibacterial and regenerative activity of copper nanoparticles in the composition of the studied drugs.

http://ift.tt/2zsOljW

Anterior Mediastinal Lymph Nodes in Chemically Induced Breast Cancer

The anterior mediastinal lymph nodes were analyzed morphometrically in rats with chemically provoked breast cancer. Rats with untreated breast cancer and animals receiving chemotherapy demonstrated decreased volumes of paracortical region and lymphoid nodules with the germinal centers accompanied by extended medullary thymic substance. Resection of largest focus of breast tumor improved the filtration barrier potential of anterior mediastinal lymph nodes, up-regulated the proliferative activity of lymphoid cells in T-cell zones, and down-regulated proliferation of plasmatic cells.

http://ift.tt/2BoFqkK

Structural Dynamics of Chondrocytes during Culturing

We performed comparative analysis of the morphology of chondrocytes in normal cartilage, after their isolation from the tissue, and at different stages of culturing; structural dynamics of cells during culturing was also studied. Significant morphological differences in chondrocytes at the specified stages of their preparation to in vivo use were revealed. Pronounced structural changes (blebbing and cytoplasm swelling) were found in chondrocytes before their implantation, which can affect the formation of cartilage regenerate. The study was performed using light microscopy methods including time-lapse recording of the cell cultures with differential interference Nomarski contrasting combined with transmission electron microscopy.

http://ift.tt/2Bq0BCS

Australian heterosexual women’s experiences of healthcare provision following a pregnancy loss

Publication date: Available online 26 November 2017
Source:Women and Birth
Author(s): Clemence Due, Kate Obst, Damien W. Riggs, Catherine Collins
BackgroundDespite increased awareness of the psychological impact of pregnancy loss, a lack of recognition continues with regards to women's experiences. Healthcare professionals have an important role to play in supporting women following a pregnancy loss, yet to date only a relatively small body of research has examined women's experiences with healthcare providers.AimThis paper seeks to contribute to the literature on women's engagement with healthcare professionals by exploring the experiences of an Australian sample.MethodFifteen heterosexual women living in South Australia were interviewed about their experiences of pregnancy loss. A thematic analysis was undertaken, focused on responses to one interview question that explored experiences with healthcare professionals.FindingsThree themes were identified. The first theme involved negative experiences with healthcare providers, and included four subthemes: (1) 'confusing and inappropriate language and communication', (2) 'the hospital environment', (3) 'lack of emotional care', and (4) 'lack of follow-up care'. Under the second theme of positive experiences, the sub-themes of (1) 'emotionally-engaged and present individual staff', and (2) 'the healthcare system as a whole' were identified. Finally, a third theme was identified, which focused holistically on the importance of healthcare professionals.ConclusionThe paper concludes by discussing the importance of training for healthcare professionals in supporting women who experience a pregnancy loss, and the need for further research to explore the experiences of other groups of people affected by pregnancy loss.



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The risk of febrile neutropenia in breast cancer patients following adjuvant chemotherapy is predicted by the time-course of IL-6 and CRP by modelling

Summary

Aims

Early identification of patients with febrile neutropenia (FN) is desirable for initiation of preventive treatment, e.g. antibiotics. In this study, the time-courses of two inflammation biomarkers, IL-6 and CRP, following adjuvant chemotherapy of breast cancer, were characterised. The potential to predict development of FN by IL-6 and CRP, and other model-derived and clinical variables, was explored.

Methods

The IL-6 and CRP time-courses in cycles 1 and 4 of breast cancer treatment were described by turnover models where the probability for an elevated production following initiation of chemotherapy was estimated. Parametric time-to-event models were developed to describe FN occurrence to assess 1) predictors available before chemotherapy is initiated, 2) predictors available before FN occurs and 3) predictors available when FN occurs.

Results

The IL-6 and CRP time-courses were successfully characterised with peak IL-6 typically occurring two days prior to CRP peak. Of all evaluated variables the CRP time-course was most closely associated with the occurrence of FN. Since the CRP peak typically occurred at the time of FN diagnosis it will however have limited value for identifying the need of preventive treatment. The time-course of IL-6 was the predictor that could best forecast FN events. Of the variables available at baseline, age was the best, although in comparison, a relatively weak predictor.

Conclusions

The developed models add quantitative knowledge about IL-6 and CRP and their relationship to the development of FN. The study suggests that IL-6 may have potential as a clinical predictor of FN if monitored during myelosuppressive chemotherapy.

http://ift.tt/2AAZuDv

Evaluation of modafinil as a perpetrator of metabolic drug-drug interactions using a model informed cocktail reaction phenotyping trial protocol.

Abstract

Aim

To evaluate the capacity for modafinil to be a perpetrator of metabolic drug-drug interactions by altering cytochrome P450 activity following a single dose and dosing to steady state.

Methods

A single centre, open label, single sequence cocktail drug interaction trial. On days 0, 2 and 8 participants were administered an oral drug cocktail comprising 100 mg caffeine, 30 mg dextromethorphan, 25 mg losartan, 1 mg midazolam, and 20 mg enteric-coated omeprazole. Timed blood samples were collected prior to and for up to 6 hours post cocktail dosing. Between day 2 and 8 participants orally self-administered 200 mg modafinil each morning.

Results

Following a single 200mg dose of modafinil mean (± 95% CI) AUC ratios for caffeine, dextromethorphan, losartan, midazolam and omeprazole were 0.95 (± 0.08), 1.01 (± 0.35), 0.97 (± 0.10), 0.98 (± 0.10) and 1.36 (± 0.06) respectively. Following dosing of modafinil to steady state (200mg for 7 days), AUC ratios for caffeine, dextromethorphan, losartan, midazolam and omeprazole were 0.90 (± 0.16), 0.79 (± 0.09), 0.98 (± 0.11), 0.66 (± 0.12), and 1.90 (± 0.53), respectively.

Conclusions

These data support consideration of the risk of clinically relevant metabolic drug-drug interactions perpetrated by modafinil when this drug is co-administered with drugs that are primarily cleared by CYP2C19 (single modafinil dose or steady state modafinil dosing) or CYP3A4 (steady state modafinil dosing only) catalysed metabolic pathways.

http://ift.tt/2AaMfJ6

iSepsis – A 30ml/kg bolus: Yes or No -The Results

The Results of the 30ml/kg Bolus Survey.

EMCrit by Paul Marik.

http://ift.tt/2naSasr

An Improved Binary Differential Evolution Algorithm to Infer Tumor Phylogenetic Trees

Tumourigenesis is a mutation accumulation process, which is likely to start with a mutated founder cell. The evolutionary nature of tumor development makes phylogenetic models suitable for inferring tumor evolution through genetic variation data. Copy number variation (CNV) is the major genetic marker of the genome with more genes, disease loci, and functional elements involved. Fluorescence in situ hybridization (FISH) accurately measures multiple gene copy number of hundreds of single cells. We propose an improved binary differential evolution algorithm, BDEP, to infer tumor phylogenetic tree based on FISH platform. The topology analysis of tumor progression tree shows that the pathway of tumor subcell expansion varies greatly during different stages of tumor formation. And the classification experiment shows that tree-based features are better than data-based features in distinguishing tumor. The constructed phylogenetic trees have great performance in characterizing tumor development process, which outperforms other similar algorithms.

http://ift.tt/2zqz56S

Effectiveness of Fibrin Sealant Patch in Reducing Drain Volume after Pelvic Lymph Node Dissection in Women with Gynecologic Malignancy

Background. The goal of this study was to evaluate the effectiveness of fibrin sealant in decreasing postoperative lymphatic drainage in women after pelvic lymphadenectomy and/or para-aortic lymphadenectomy during gynecologic cancer surgery. Methods. This study is a retrospective case-control study. Forty-five patients who underwent staging surgery were enrolled. Twenty-seven patients were in the fibrin sealant group (group A) and 18 in the control group (group B). The two groups were compared for the total volume of drain, hospital stay, harvested lymph node, and incidence of asymptomatic lymphocele. Lymphocele formation was evaluated by computed tomography (CT) on 3 months after surgery. Results. There were no significant differences in patient demographics between group A and B with respect to age, BMI, and harvested lymph nodes. Patients who received fibrin sealants had reduced total volume of drainage from postoperative days 2 to 5 compared to the control group (group A versus group B:  ml versus  ml; ). However no differences were observed in hospital stay (), duration of drain (), and incidence of asymptomatic lymphocele at 3 months (). Conclusion. The results of this study indicate that the application of fibrin sealants after pelvic and/or para-aortic lymphadenectomy may reduce lymphatic drainage in gynecologic malignancy.

http://ift.tt/2BoOSoc

Expanding the Use of Organs from Hepatitis C-Viremic Donors: The Evidence Continues to Build

No abstract available

http://ift.tt/2n2JaVY

Methods to Study Changes in Inherent Protein Aggregation with Age in Caenorhabditis elegans

The goal of the method presented here is to explore protein aggregation during normal aging in the model organism C. elegans. The protocol represents a powerful tool to study the highly insoluble large aggregates that form with age and to determine how changes in proteostasis impact protein aggregation.

http://ift.tt/2AyqEKZ

The Role of Serum Adiponectin for Outcome Prediction in Patients with Dilated Cardiomyopathy and Advanced Heart Failure

Clinical interpretation of patients' plasma adiponectin (APN) remains challenging; its value as biomarker in dilated cardiomyopathy (DCM) is equivocal. We evaluated whether circulating APN level is an independent predictor of composite outcome: death, left ventricle assist device (LVAD) implantation, and heart transplantation (HT) in patients with nonischemic DCM. 57 patients with nonischemic DCM (average LV diastolic diameter 6.85 cm, LV ejection fraction 26.63%, and pulmonary capillary wedge pressure 22.06  mmHg) were enrolled. Patients underwent echocardiography, right heart catheterization, and endomyocardial biopsy. During a mean follow-up of 33.42 months, 15 (26%) patients died, 12 (21%) patients underwent HT, and 8 (14%) patients were implanted with LVAD. APN level was significantly higher in patients who experienced study endpoints (23.4 versus 10.9 ug/ml, ). APN was associated with worse outcome in univariate Cox proportional hazards model (HR 1.04, CI 1.02–1.07, ) but lost significance adjusting for other covariates. Average global strain (AGS) is an independent outcome predictor (HR 1.42, CI 1.081–1.866, ). Increased circulating APN level was associated with higher mortality and may be an additive prognostic marker in DCM with advanced HF. Combination of serum (APN, BNP, TNF-α) and echocardiographic (AGS) markers may increase the HF predicting power for the nonischemic DCM patients.

http://ift.tt/2n3qJRe

Saccharomyces cerevisiae Laryngitis and Oral Lesions in a Patient with Laryngeal Carcinoma

Saccharomyces cerevisiae is increasingly being promoted as a nutritional supplement by health food enthusiasts and is also recommended as prophylaxis against antibiotic-associated diarrhea. However, severe opportunistic infections due to S. cerevisiae have been reported in patients with chronic disease, cancer, and immunosuppression. Fungemia, endocarditis, pneumonia, peritonitis, urinary tract infections, skin infections, and esophagitis have been described. It is important to consider infections due to S. cerevisiae in appropriate clinical settings. Here, we describe the first case of S. cerevisiae laryngitis in a patient with a history of laryngeal carcinoma who also had oral lesions.

http://ift.tt/2AzxaRW

α-MSH Influences the Excitability of Feeding-Related Neurons in the Hypothalamus and Dorsal Vagal Complex of Rats

Alpha-melanocyte-stimulating hormone (α-MSH) is processed from proopiomelanocortin (POMC) and acts on the melanocortin receptors, MC3 and MC4. α-MSH plays a key role in energy homeostasis. In the present study, to shed light on the mechanisms by which α-MSH exerts its anorectic effects, extracellular neuronal activity was recorded in the hypothalamus and the dorsal vagal complex (DVC) of anesthetized rats. We examined the impact of α-MSH on glucose-sensing neurons and gastric distension (GD) sensitive neurons. In the lateral hypothalamus (LHA), α-MSH inhibited 75.0% of the glucose-inhibited (GI) neurons. In the ventromedial nucleus (VMN), most glucose-sensitive neurons were glucose-excited (GE) neurons, which were mainly activated by α-MSH. In the paraventricular nucleus (PVN), α-MSH suppressed the majority of GI neurons and excited most GE neurons. In the DVC, among the 20 GI neurons examined for a response to α-MSH, 1 was activated, 16 were depressed, and 3 failed to respond. Nineteen of 24 GE neurons were activated by α-MSH administration. Additionally, among the 42 DVC neurons examined for responses to GD, 23 were excited (GD-EXC) and 19 were inhibited (GD-INH). Fifteen of 20 GD-EXC neurons were excited, whereas 11 out of 14 GD-INH neurons were suppressed by α-MSH. All these responses were abolished by pretreatment with the MC3/4R antagonist, SHU9119. In conclusion, the activity of glucose-sensitive neurons and GD-sensitive neurons in the hypothalamus and DVC can be modulated by α-MSH.

http://ift.tt/2A5XgLj

A Study on the Improvement of Walking Characteristics of the Elderly with Vibration Stimuli Applied to the Tibialis Anterior Tendon

The purpose of this study was to identify the gait pattern of the elderly with aging and to analyze the elderly's gait changes by the focal tendon vibratory stimulation. A total of 10 elderly males and 15 young adult males participated in this study. Using 3D motion analysis, we analyzed that difference between the elderly gait and young adults gait and the changes of the elderly gait by applying focal vibratory stimuli. As a result, specifically in the early stance, the elderly's gait was more flexed and the lower extremity extensors of the elderly worked harder. When the focal vibratory stimuli were applied, joint angle of the elderly was induced to that of the young adults. There was a reduction in demands for supporting bodies and progressing gait in the stance phase. This means that focal vibratory stimuli affect the gait of the elderly. Also, the changes of the gait of the elderly varied according to the characteristics of the focal vibratory stimuli. This implies that the activity of the motor may be dependent on vibratory stimuli characteristics.

http://ift.tt/2hT2lfB

Virtual Reality Telerehabilitation for Postural Instability in Parkinson’s Disease: A Multicenter, Single-Blind, Randomized, Controlled Trial

Introduction. Telerehabilitation enables patients to access remote rehabilitation services for patient-physiotherapist videoconferencing in their own homes. Home-based virtual reality (VR) balance training has been shown to reduce postural instability in patients with Parkinson's disease (PD). The primary aim was to compare improvements in postural stability after remotely supervised in-home VR balance training and in-clinic sensory integration balance training (SIBT). Methods. In this multicenter study, 76 PD patients (modified Hoehn and Yahr stages 2.5–3) were randomly assigned to receive either in-home VR telerehabilitation () or in-clinic SIBT () in 21 sessions of 50 minutes each, 3 days/week for 7 consecutive weeks. VR telerehabilitation consisted of graded exergames using the Nintendo Wii Fit system; SIBT included exercises to improve postural stability. Patients were evaluated before treatment, after treatment, and at 1-month follow-up. Results. Analysis revealed significant between-group differences in improvement on the Berg Balance Scale for the VR telerehabilitation group () and significant Time × Group interactions in the Dynamic Gait Index () for the in-clinic group. Both groups showed differences in all outcome measures over time, except for fall frequency. Cost comparison yielded between-group differences in treatment and equipment costs. Conclusions. VR is a feasible alternative to in-clinic SIBT for reducing postural instability in PD patients having a caregiver.

http://ift.tt/2hSo8UD

Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Activates Type I Interferon Signals in Lupus Nephritis

Type I interferon (IFN) plays a central role in pathogenesis of systemic lupus erythematosus (SLE); tumor necrosis factor-like weak inducer of apoptosis (TWEAK) has been associated with a pathogenic role in lupus nephritis (LN). Thus we investigated whether TWEAK could induce the activation of type I IFN pathway in LN. We examined this in patient-derived peripheral blood mononuclear cells (PBMCs) as well as MRL/lpr mice, a murine LN model. Relative to the control cohorts, MRL/lpr mice showed severe histological changes, high index levels of renal damage, and elevated expression of type I IFN-inducible genes. After shRNA suppression of TWEAK, we observed that renal damage was significantly attenuated and expression of type I IFN-inducible genes was reduced in MRL/lpr mice. In parallel, siRNA of TWEAK also significantly reduced the expression of type I IFN-inducible genes in PBMCs relative to control transfections. In PBMCs, TWEAK stimulation also led to expression of type I IFN-inducible genes. Our results illustrate a novel regulatory role of TWEAK, in which its activity positively regulates type I IFN pathway in LN based on preclinical models. Our findings suggest TWEAK could act as a critical target in preventing renal damage in patients with LN.

http://ift.tt/2Bnr7gg

Comparison of Monolateral External Fixation and Internal Fixation for Skeletal Stabilisation in the Management of Small Tibial Bone Defects following Successful Treatment of Chronic Osteomyelitis

Background. To compare the salvage rate and complication between internal fixation and external fixation in patients with small bone defects caused by chronic infectious osteomyelitis debridement. Methods. 125 patients with chronic infectious osteomyelitis of tibia fracture who underwent multiple irrigation, debridement procedure, and local/systemic antibiotics were enrolled. Bone defects, which were less than 4 cm, were treated with bone grafting using either internal fixation or monolateral external fixation. 12-month follow-up was conducted with an interval of 3 months to evaluate union of bone defect. Results. Patients who underwent monolateral external fixation had higher body mass index and fasting blood glucose, longer time since injury, and larger bone defect compared with internal fixation. No significant difference was observed in incidence of complications (23.5% versus 19.3%), surgery time ( minutes versus minutes), and time to union ( months versus months) between external fixation and internal fixation. Internal fixation had no significant influence on the occurrence of postoperation complications after multivariate adjustment when compared with external fixation. Furthermore, patients who underwent internal fixation experienced higher level of daily living scales and lower level of anxiety. Conclusions. It was relatively safe to use internal fixation for stabilization in osteomyelitis patients whose bone defects were less than 4 cm and infection was well controlled.

http://ift.tt/2BbLPyO

Gender Differences in Commuting Injuries in Spain and Their Impact on Injury Prevention

A gender analysis of workers injured while commuting in Spain is presented, distinguishing between injury due to traffic-related accidents and injury due to other causes. Method. A total of 266,646 traffic-related injuries and 168,129 nontraffic-related injuries are studied over the period 2006–2010. Results. In Spain, the accident rate recorded in working hours is much higher among men; nevertheless, it is curious that commuting-related accident rates are higher among women than men, in both traffic-related injuries and nontraffic-related injuries. The study of the frequency distribution confirmed that many more injuries occurred in Spain while commuting to work rather than from work and that women suffered twice as many injuries as men at nine in the morning. Musculoskeletal disorders are the only injuries that registered a higher number of cases among women and falls to the same level are the most relevant cause among women. Conclusions. The analysis of these and more findings established that a great effort should go into the promotion of preventive measures in favour of women workers. These results may encourage companies to modify their accident prevention plans, so as to increase their effectiveness in the struggle against occupational accidents following the five points described in this article.

http://ift.tt/2iSkf2T