Αρχειοθήκη ιστολογίου

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Σάββατο 2 Δεκεμβρίου 2017

Biochemical reference values for healthy captive Persian wild goat ( Capra aegagrus )

Abstract

Limited information is available for normal biochemical reference values in captive Persian wild goats (Capra aegagrus). The objectives of this study were to establish reference values and to evaluate changes associated with gender and age for 22 mature, captured, clinically healthy Capra aegagrus. The reference values were obtained: glucose, 34.10–204.90 mg/dl; urea, 11.81–49.45 mg/dl; creatinine, 0.075–2.032 mg/dl; triglyceride, 15.71–84.90 mg/dl; cholesterol, 10.02–131.30 mg/dl; total bilirubin, 0.011–0.875 mg/dl; direct bilirubin, 0.0–0.079 mg/dl; indirect bilirubin, 0.011–0.875 mg/dl; total protein, 3.294–7.460 g/dl; albumin, 2.315–3.926 g/dl; globulin, 0.0–3.589 g/dl; calcium, 4.252–9.190 mg/dl; phosphorus, 0.421–24.668 mg/dl; magnesium, 0.021–4.330 mg/dl; iron, 35.88–148.60 μg/dl; AST, 49.63–134.60 U/L; ALT, 11.31–6.13 U/L; ALP, 68.88–1311.25 U/L; lipase, 11.90–59.701 U/L; and amylase 1.469–44.450 U/L. We found no significant difference between males and females with the exception of glucose, ALT, ALP, and amylase. Levels of glucose, ALT, ALP, and amylase were higher in males compared with the values obtained for females. No significant differences were found between various biochemical values in Capra aegagrus over and under 3 years with the exception of AST. AST had a higher activity in Capra aegagrus less than 3 years. Blood biochemical values determined in this study can be used as a guide for disease diagnosis in Capra aegagrus in Zoological Studies.



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Role of Cholinergic Anti-Inflammatory Pathway in Treatment of Intestinal Ischemia-Reperfusion Injury by Electroacupuncture at Zusanli

Electroacupuncture (EA) at Zusanli is a widely used method for the treatment of intestinal ischemic disease. The current study attempts to investigate the possible mechanism from the point of cholinergic anti-inflammatory pathway (CAP) in rats. Thirty rats were divided into five groups: control group, I/R group, EA group (I/R + EA), PNU group (I/R + α7 nAChR agonist), and α-BGT group (I/R + EA + α7 nAChR antagonist). EA and medicine injection were performed immediately after ischemia. After 2 h of reperfusion, blood and intestine samples were collected and intestinal histopathological score, mRNA expression of mucosal α7 nAChR and NF-κBp65, and serum cytokine levels (IL-6, TNF-α) were examined. Compared with the I/R group, the EA group and PNU group could significantly attenuate the mucosal damage, promote α7 nAChR mRNA expression, and reduce levels of NF-κBp65, IL-6, and TNF-α. Compared with the EA group, α7 nAChR mRNA was decreased, while concentrations of NF-κBp65, IL-6, and TNF-α increased in the α-BGT group. EA at Zusanli could inhibit NF-κBp65 and proinflammatory cytokines production after intestinal I/R injury; its mechanism may be related to the cholinergic anti-inflammatory pathway.

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Immunohaemostasis: a new view on haemostasis during sepsis

Host infection by a micro-organism triggers systemic inflammation, innate immunity and complement pathways, but also haemostasis activation. The role of thrombin and fibrin generation in host defence is now re...

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Genotyping and drug susceptibility testing of mycobacterial isolates from population-based tuberculosis prevalence survey in Ghana

Mycobacterium tuberculosis complex (MTBC) and Non-tuberculosis Mycobacterium (NTM) infections differ clinically, making rapid identification and drug susceptibility testing (DST) very ...

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Vaccine-derived poliovirus surveillance in China during 2001–2013: the potential challenge for maintaining polio free status

The goal of polio eradication is to complete elimination and containment of all wild, vaccine-related and Sabin polioviruses. Vaccine-derived poliovirus (VDPV) surveillance in China from 2001–2013 is summarize...

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Pharmacogenetic Analysis of the Model-Based Pharmacokinetics of Five Anti-HIV Drugs: How Does This Influence the Effect of Aging?

Abstract

Analysis of aging and pharmacogenetics (PGx) on antiretroviral pharmacokinetics (PKs) could inform precision dosing for older human HIV-infected patients. Seventy-four participants receiving either atazanavir/ritonavir (ATV/RTV) or efavirenz (EFV) with tenofovir/emtricitabine (TFV/FTC) provided PK and PGx information. Aging-PGx-PK association and interaction analyses were conducted using one-way analysis of variance (ANOVA), multiple linear regression, and Random Forest ensemble methods. Our analyses associated unbound ATV disposition with multidrug resistance protein (MRP)4, RTV with P-glycoprotein (P-gp), and EFV with cytochrome P450 (CYP)2B6 and MRP4 genetic variants. The clearance and cellular distribution of TFV were associated with P-gp, MRP2, and concentrative nucleoside transporters (CNTs), and FTC parameters were associated with organic cation transporters (OCTs) and MRP2 genetic variants. Notably, p16INK4a expression, a cellular aging marker, predicted EFV and FTC PK when genetic factors were adjusted. Both age and p16INK4a expression interacted with PGx on ATV and TFV disposition, implying potential dose adjustment based on aging may depend on genetic background.



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DNA damage signaling and polyploid macrophages in chronic inflammation

Veronika Horn | Antigoni Triantafyllopoulou

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Novel ultrasound-based methods to assess liver disease: the game has just begun

In the last 10 years the availability of ultrasound elastography allowed to diagnose and stage liver fibrosis in a non-invasive way and changed the clinical practice of hepatology. Newer ultrasound-based techniques to evaluate properties of the liver tissue other than fibrosis are emerging and will lead to a more complete characterization of the full spectrum of diffuse and focal liver disease. Since these methods are currently undergoing validation and go beyond elastography for liver tissue evaluation, they were not included in the recent guidelines regarding elastography issued by the European Federation of Societies in Ultrasound in Medicine and Biology.

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Risk factors for postpolypectomy bleeding in patients receiving anticoagulation or antiplatelet medications

Balancing the risks for thromboembolism and postpolypectomy bleeding in patients requiring anticoagulation and antiplatelet agents is challenging. We investigated the incidence and risk factors for postpolypectomy bleeding on anticoagulation, including heparin bridge, and other antithrombotic therapy.

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“Green Smoothie Cleanse” Causing Acute Oxalate Nephropathy

Oxalate nephropathy is an uncommon condition that causes acute kidney injury with the potential for progression to end-stage renal disease. Diagnosis is based on the kidney biopsy findings of abundant polarizable calcium oxalate crystals in the epithelium and lumen of renal tubules. We report a case of acute oxalate nephropathy in a 65-year-old woman, temporally associated with the consumption of an oxalate-rich green smoothie juice "cleanse" prepared from juicing oxalate-rich green leafy vegetables and fruits.

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Impact of opioid therapy on sleep and respiratory patterns in adults with advanced cancer receiving palliative care

In advanced cancer, abnormal sleep patterns may contribute to poor quality of life but the impact of opioid related sleep disorders has not been explored in detail in these patients.

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Pilot Testing of a Brief Couple-Based Mind-Body Intervention for Patients with Metastatic Non-Small Cell Lung Cancer and Their Partners

Given the generally incurable nature of metastatic lung cancer, patients and their spouses/partners are at risk for psychological and spiritual distress. To address this concern, we developed a couple-based mind-body (CBMB) intervention.

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Locally ablative radio therapy of a primary human small cell lung cancer tumor decreases the number of spontaneous metastases in two xenograft models

The influence of radiotherapy, surgery, chemotherapy, and radio-chemotherapy on local primary tumor growth and on spontaneous distant metastasis formation was investigated in two human small cell lung cancer xenograft mouse models. Local tumor control was most important to suppress metastasis formation. Most interestingly, radiotherapy was not only locally ablative and prevented spontaneous distant metastasis formation over time, but even reduced the metastatic cell load in distant organs pre-existing at the time of therapy induction.

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Comprehensive Evaluation of the Learning Curve for Peroral Endoscopic Myotomy

Peroral endoscopic myotomy (POEM) is a minimally invasive endoscopic surgical procedure that is effective in treatment for spastic esophageal motility disorders. However, little is known about the learning curve for endoscopists. We aimed to evaluate the effects of various factors on the POEM learning curve.

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Nectin-4 promotes gastric cancer progression via the PI3K/AKT signaling pathway

Nectin-4, a member of the Nectin family that includes four Ca+-independent immunoglobulin-like cell adhesion molecules, plays a carcinogenic role in multiple cancers. However, Nectin-4 expression and its biological role in gastric cancer (GC) remain largely unknown. In this study, quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry (IHC) were used to evaluate the expression patterns of Nectin-4 in GC specimens and cell lines. We observed that high expression of Nectin-4 in GC patients was associated with TNM stage and lymph node metastasis status, and poor prognosis.

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Mismatch repair–deficient colorectal cancer: a model of immunogenic and immune cell–rich tumor despite nonsignificant PD-L1 expression in tumor cells

Mismatch repair–deficient colorectal cancers (CRC) are good responders to anti–programmed cell death ligand-1 (PD-L1) immunotherapy, but the value of PD-L1 testing remains unclear. We studied PD-L1 expression and the tumor immune microenvironment in mismatch repair–deficient (dMMR) CRC as a model of good responders to immunotherapy. We examined 35 dMMR and 34 mismatch repair–proficient (pMMR) CRC using immune cell markers (CD3, CD4, CD8, CD20, CD68, and FOXP3) as well as PD-1 and PD-L1 immunohistochemistry staining in whole tumor specimens and tissue microarray slides to compare 4r PD-L1 immunohistochemistry clones (SP142, E1L3N, 22C3, and 28.8).

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Malignant perivascular epithelioid cell tumor of the oropharynx with strong TFE3 expression mimicking alveolar soft part sarcoma: a case report and review of the literature

Perivascular epithelioid cell tumors (PEComas) in the head and neck region are rare with 26 cases described in literature. These distinct mesenchymal tumors normally express both myoid and melanocytic markers. We here report an interesting and challenging case of malignant PEComa that showed transcription factor E3 (TFE3) protein expression and rearrangement, paucity of muscle and melanocytic marker expression, and morphologically mimicked as alveolar soft part sarcoma. Awareness of this morphologic pitfall and recognition TFE3 gene rearranged PEComa, as a distinct subtype of PEComa is essential to avoid misdiagnosis.

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Does metformin exposure before ICU stay have any impact on patients’ outcome? A retrospective cohort study of diabetic patients

Impact of metformin exposure before ICU stay remains controversial. Metformin is thought to induce lactic acidosis and haemodynamic instability but may reduce ICU mortality. We evaluated its influence on outco...

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Diffuse Reflectance Spectroscopy: Getting the Capillary Refill Test Under One's Thumb

This protocol describes how the use of diffuse polarization spectroscopy can improve the clinical usefulness of the capillary refill test. We suggest a more detailed analysis of the course of the capillary refill in healthy volunteers using diffuse reflectance spectroscopy videos and new informatic endpoints.

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Ultrasonography in Experimental Reproductive Investigations on Rats

This manuscript describes the utility of ultrasound performed on female rats to design experimental models for reproductive and gynecological investigation. A step-by-step explanation of how to perform ultrasonographic evaluation is shown.

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Evaluation of a speaker identification system with and without fusion using three databases in the presence of noise and handset effects

In this study, a speaker identification system is considered consisting of a feature extraction stage which utilizes both power normalized cepstral coefficients (PNCCs) and Mel frequency cepstral coefficients ...

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Hepatitis C Transmission from Seropositive, Non-Viremic Donors to Non-Hepatitis C Liver Transplant Recipients

Abstract

Breakthroughs in Hepatitis C virus (HCV) treatment and rising rates of intravenous drug use have led to an increase in the number of organ donors that are HCV antibody positive but serum nucleic acid test (NAT) negative. The risk of HCV transmission from the liver grafts of these donors to recipients is unknown. To estimate the incidence of HCV transmission, we prospectively followed 26 consecutive HCV antibody (n=25) or NAT (n =1) negative transplant recipients who received a liver graft from donors that were HCV antibody positive but serum NAT negative between March 2016 and March 2017. HCV transmission was considered to have occurred if recipients exhibited a positive HCV-polymerase chain reaction test by 3 months following transplantation. Drug overdose was listed as the cause of death in 15 (60%) of the donors. One recipient died eighteen days after transplantation from primary graft non-function and was excluded. Of the remaining 25 recipients, HCV transmission occurred in 4 (16%), at a median follow up of 11 months, all from donors who died of drug overdose. Three of these patients were treated with direct acting antiviral therapy, with two achieving a sustained virologic response and one an end-of-treatment response. One patient with HCV transmission died after a complicated post-operative course and did not receive antiviral therapy. Conclusions: In this prospective cohort of non-HCV liver recipients receiving grafts from HCV antibody positive/NAT negative donors, the incidence of HCV transmission was 16%, with the highest risk conferred by donors who died of drug overdose. Given the availability of safe and highly effective antiviral therapies, use of such organs could be considered to expand the donor pool. This article is protected by copyright. All rights reserved.



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The short-term incidence of hepatocellular carcinoma is not increased after hepatitis C treatment with direct-acting antivirals: An ERCHIVES study

Abstract

Recent studies have reported higher rates of hepatocellular carcinoma (HCC) in individuals treated with direct-acting antivirals (DAAs). However, making definitive conclusions has been challenging due to the heterogeneous populations and methodologies of these reports. We investigated whether DAA use is associated with higher rates of incident HCC compared to treatment with interferon-based regimens. We performed a retrospective population-based cohort study using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database. In a cohort of 17,836 persons, SVR was achieved by 66.6% and 96.2% of the IFN and DAA groups, respectively. Among all treated persons, the risk of HCC was not higher in the DAA group compared to the IFN group (HR 1.07; [95% CI: 0.55, 2.08]). Among persons with cirrhosis who achieved SVR, neither the HCC incidence rate nor HCC-free survival were significantly different in the DAA group compared to the IFN group (21.2 vs. 22.8 per 1000 person years; p=0.78; and log-rank p=0.17, respectively). Untreated persons with cirrhosis had a significantly higher HCC incidence rate (45.3 per 1000 person years) compared to those treated with either IFN or DAAs (p=0.03). Both groups of treated persons had significantly lower probability of HCC development compared to untreated persons (log-rank p=0.0004).

Conclusions: DAA treatment is not associated with a higher risk of HCC in cirrhotics with chronic HCV infection in the short-term. Previously reported higher rates of HCC associated with DAA treatment may be explained by both the presence of relatively fewer baseline HCC risk factors in persons treated with IFN as well as selection bias, as DAA regimens were used to treat persons at higher risk for developing HCC. This article is protected by copyright. All rights reserved.



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Gentle palpating liver sinusoidal endothelial cells reveals the dynamic behavior and formation of fenestrae – a new window for biomedical research



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The NASH Metabotype: Imbalance of Circulating Amino Acids and Transamination Reactions Reflect Impaired Mitochondrial Function



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Progressive deafness-dystonia due to SERAC1 mutations – a study of 67 cases

ABSTRACT

Objective: 3-MEthylGlutaconic aciduria, Dystonia-Deafness, Hepatopathy, Encephalopathy, Leigh-like syndrome (MEGDHEL) syndrome is caused by biallelic variants in SERAC1.

Methods: Multi centre study concerning the course of disease for each organ system, together with metabolic, neuroradiological and genetic findings.

Results: 67 individuals (39 previously unreported) from 59 families were included (age range 5 days - 33.4 years, median age 9 years). A total of 41 different SERAC1 variants were identified, including 20 that have not been reported before. With exception of two families with a milder phenotype, all affected individuals show a strikingly homogeneous phenotype and time course. Severe, reversible neonatal liver dysfunction and hypoglycemia was seen in more than 40% of all cases. Starting at a median age of six months muscular hypotonia (91%) was seen, followed by progressive spasticity (82%, median onset 15 months) and dystonia (82%, 18 months). The majority of affected individuals never learnt to walk (68%). 79% suffered hearing loss, 58% never learnt to speak, nearly all had significant intellectual disability (88%). MRI features were accordingly homogenous with bilateral basal ganglia involvement (98%), the characteristic "putaminal eye" was seen in 53%. The urinary marker 3-methylglutaconic aciduria is virtually present in all patients (98%). Supportive treatment focused on spasticity and drooling, was effective in individuals treated, hearing aids or cochlear implants did not improve communication skills.

Interpretation: MEGDHEL syndrome is as a progressive deafness-dystonia syndrome with frequent and reversible neonatal liver involvement and a strikingly homogenous course of disease. This article is protected by copyright. All rights reserved.



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Favorable response of relapsed/refractory gray-zone lymphoma to brentuximab vedotin



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Epidemiology of viral hepatitis in the Republic of Congo: review

Considered an endemic zone, Republic of Congo has a high seroprevalence rate of hepatitis B and C virus. To know the extent of hepatitis infection as a public health problem, we reviewed published literature a...

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Physical abrasion method using submerged spike balls to remove algal biofilm from photobioreactors

A major factor in practical application of photobioreactors (PBR) is the adhesion of algal cells onto their inner walls. Optimized algal growth requires an adequate sunlight for the photosynthesis and cell gro...

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Tocolytic action and underlying mechanism of galetin 3,6-dimethyl ether on rat uterus

Galetin 3,6-dimethyl ether (FGAL) is a flavonoid isolated from aerial parts of Piptadenia stipulacea. Previously, FGAL was shown to inhibit both carbachol- and oxytocin-induced phasic contractions in the rat uter...

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Extract of Ginkgo biloba exacerbates liver metastasis in a mouse colon cancer Xenograft model

Metastasis refers to the spread of a primary tumor cell from the primary site to other locations in the body and it is generally associated with the severity of a tumor. Extract of Ginkgo biloba (EGb) contains va...

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The inhibitory effects of compound Muniziqi granule against B16 cells and harmine induced autophagy and apoptosis by inhibiting Akt/mTOR pathway

Compound Muniziqi granule (MNZQ) is a multi-component herbal preparation and a popular traditional Uighur medicine used in China for treating endocrine...

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An Asian traditional herbal complex containing Houttuynia cordata Thunb, Perilla frutescens Var. acuta and green tea stimulates hair growth in mice

Houttuynia cordata Thunb (HC) is a traditional herbal medicine widely used in Asia for the treatment of patients with alopecia, usually in combination with other two herbal medicines (

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Population-level effect of molecular testing and targeted therapy in patients with advanced pulmonary adenocarcinoma: a prospective cohort study

Abstract

Large cancer centres in the USA demonstrated that molecular diagnosis and targeted therapy improved overall survival of patients with advanced pulmonary adenocarcinoma. We validated this finding in a rural area of Switzerland, served by private practices, community hospitals and a tertiary referral centre. We conducted a prospective cohort study with the Cancer Registry of Central Switzerland, covering 4 cantons and 517,000 inhabitants. All residents newly diagnosed with stage IV pulmonary adenocarcinoma from 2010 to 2014 were enrolled. We obtained information on patients, tumour, molecular testing, therapy and survival. Three hundred forty-eight patients were included in the study. Molecular testing was performed in 279 (80%); 132 (38%) had oncogenic driver mutations: Kirsten rat sarcoma (KRAS, 16%), epidermal growth factor receptor (EGFR, 11%), anaplastic lymphoma kinase (ALK, 5%), human epidermal growth factor receptor 2 (HER2, 2%), B rapidly accelerated fibrosarcoma (BRAF, 1%), rearranged during transfection (RET, 0.5%), MET proto-oncogene (0.5%) and multiple mutations (2%). Fifty-six patients with an oncogenic driver mutation, mostly epidermal growth factor receptor (34) and anaplastic lymphoma kinase (12), received genotype-matched targeted therapy, at least 25 (45%) of whom in a clinical trial or named patient programme. Median overall survival was 18 months for patients with driver mutations and targeted therapy, 8 months for patients with driver mutations and conventional therapy and 10 months for patients with no driver mutation and conventional therapy. For patients with driver mutations and targeted therapy, overall survival was significantly better than that for patients with driver mutations and conventional therapy (HR 0.64, p = 0.04). Rigorous testing combined with optimal access to targeted therapy in clinical trials improved the prognosis of patients with advanced pulmonary adenocarcinoma in Central Switzerland. This effect was mainly driven by therapies targeting epidermal growth factor receptor and anaplastic lymphoma kinase.



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Angiomatosis of the uterus, cervix and fallopian tubes: a rare and benign cause of intractable, heavy menstrual bleeding

Angiomatosis of the uterus, cervix and fallopian tubes is a rare and benign entity that has not been reported in the literature previously. We present a case of a 27-year-old patient with severe and intractable heavy menstrual bleeding unresponsive to all conservative and conventional forms of treatment. Following a laparoscopic hysterectomy, the histopathological finding of angiomatosis, a vascular abnormality in the uterus, cervix and fallopian tubes, provided a plausible explanation in this situation.



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Severe recurrent hypothermia in an elderly patient with refractory mania associated with atypical antipsychotic, valproic acid and oxcarbazepine therapy

Hypothermia is a rare but serious condition that has been associated with various psychiatric medications. We present a 76-year-old woman with refractory mania who developed multiple episodes of severe hypothermia associated with several psychiatric medications including olanzapine, quetiapine, valproic acid and oxcarbazepine. These episodes resolved following discontinuation of the agents. The patient had never experienced hypothermia before, despite having been on these or similar agents for many years. With traditional treatments for mania not feasible, other medications were used to treat her including lithium, clonazepam, gabapentin and the novel protein kinase c inhibitor tamoxifen. The regimen resulted in some success and importantly, without triggering hypothermia. This case alerts clinicians to the rare side effect of hypothermia in response to various psychiatric medications, the fact that patients can suddenly develop this intolerance and suggests possible medications that may be used safely without triggering hypothermia.



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Bilateral ocular surface squamous neoplasia with bilateral periocular basal cell carcinoma in a case of xeroderma pigmentosum

Xeroderma pigmentosum (XP) is an autosomal recessive disorder associated with multiple oculocutaneous manifestations.We discuss a unique case of XP having bilateral ocular surface squamous neoplasia (OSSN) and periocular basal cell carcinoma. In the right eye, a large OSSN mass involving the ocular surface extensively along with intraocular invasion was noted, whereas in the left eye, the tumour mass was involving the limbus, and extending up to three clock hours. Because of extensive disease in the right eye, orbital exenteration was performed, and for the left eye, a wide excision of the mass with triple freeze thaw cryo application to the margins followed by amniotic membrane grafting was done. Basal cell carcinoma was noted around the medial canthus on both sides. The right-sided basal cell carcinoma was treated by wide excision followed by a forehead rotation flap and the left-sided lesion was managed with topical 5% imiquimod cream.



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Volvulus of a wandering pelvic spleen: CT diagnosis with 3D reformatted illustration

Description

A 55-year-old woman was admitted at the hospital for acute abdominal pain, nausea, vomiting and loss of appetite. The unique relevant information of her previous clinical story was an aberrant location of the spleen in the pelvis. This was detected with sonography (US), 24 years before, in relation to the same clinical presentation followed by a rapid spontaneous resolution. Present blood tests were normal. An abdominal US of the abdomen was then performed, confirming the pelvic location of the spleen. The ectopic spleen was homogeneous, and any other relevant findings were noted. A multislice CT of the abdomen was required to exclude splenic infarct and to detect another cause of the abdominal pain missed with US.

The CT showed a whirloop configuration of the splenic vascular pedicle, with absence of ischaemic changes of the splenic parenchyma (figure 1). Volvulus of a wandering pelvic spleen (WS)...



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Leg length discrepancy: the importance of a complete history and examination

A 26-year-old woman with a 1-year history of right knee pain had failed to respond to analgesia and activity modification in the community. Her general practitioner referred her to the orthopaedic department for specialist review. A thorough history revealed that she had multiple orthopaedic interventions as a child. The patient had significant postoperative infection of the left knee following knee surgery at 7 years of age. Examination demonstrated the presence of a limp, scoliosis and suspected leg length discrepancy. Plain film radiography confirmed the presence of leg length discrepancy, with the right limb measuring 30 mm longer than the left. The leg length discrepancy was likely secondary to a growth arrest of the left knee following the postoperative infection in childhood. The patient was managed with physiotherapy and heel raises and received regular orthopaedic follow-up.



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Challenging and uncommon diagnosis of long-evolution ascites

This is a case report of a 45-year-old Caucasian man with chronic alcoholism. No history of liver disease or asbestos exposure. He complained of ascites during the last 3 years with worsening in the last year with severe ascites development. Diagnostic paracentesis showed SAAG 1.1 and high cellularity with neutrophil count >250 cells/µL. Ascitic fluid cytology revealed reactive mesothelial hyperplasia. Thoracoabdominopelvic ultrasonography/CT/MRI and fludeoxyglucose positron emission tomography/CT showed 'omental cake' pattern suggesting peritoneal carcinomatosis. An exploratory laparoscopy revealed moderate interloop adhesions and necrosis with whitish exudate in the right pelvic excavation. Biochemical/cytological/histological/microbiological study only revealed reactive mesothelial cells, necrosis and lymphohistiocytic inflammatory infiltrate. A second exploratory laparoscopy with liver and peritoneal biopsies and appendectomy/mesoappendix excision showed a well-differentiated tubulopapillary mesothelioma. The patient was referred for intraperitoneal chemotherapy and is undergoing monthly therapeutic paracentesis.



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Rupture of the posterior cul-de-sac during trial of labour after caesarean section

Rupture of the vaginal wall in unobstructed labour is a rare entity in the developed world. This case report describes rupture of the posterior cul-de-sac in a healthy 34-year-old multiparous woman attempting trial of labour after caesarean section. The woman presented to the labour ward at term with spontaneous onset of contractions. In the second stage of labour, the woman experienced sudden severe abdominal pain, different in character from the contraction pain. Therefore, the baby was delivered by ventouse extraction. As the woman continued to experience severe immobilising abdominal pain during the hospital stay, a CT scan was performed which revealed a haematoma and free fluid at the right side of the uterus. A laparotomy was performed 3 days postdelivery, during which a rupture of the posterior cul-de-sac was found and closed with a continuous suture. The woman was discharged 3 days after laparotomy in good clinical condition.



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Carcinoma en cuirasse

We present a case of carcinoma en cuirasse as a presentation of advanced lobular breast carcinoma. On further investigation, she was found to have metastasis to her liver and bone. We report this case to highlight the phenomenon of cutaneous metastasis. It is important to consider this diagnosis as an initial manifestation of breast cancer, but rarely, it can also be associated with other adenocarcinomas, for example, carcinoma of lung, kidney or gastrointestinal tract.



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The telescoping aorta: a case of circumferential aortic dissection with intimo-intimal intussusception into the left ventricle

Description 

A 67-year-old man with history of tobacco smoking presents to the emergency department with sudden onset, retrosternal chest pain radiating to the neck and associated with diaphoresis and nausea. On examination, his blood pressure was 106/42 mm Hg, pulse of 73 beat/min. He was pale, diaphoretic with IV/VI diastolic blowing murmur of unknown chronicity heard at the left sternal border. His distal pulses were faint but symmetric in all extremities. No marfanoid features. ECG showed sinus rhythm with ST segment elevation in leads aVR and V1, with widespread ST segment depression (figure 1). He underwent emergent coronary angiogram with initial diagnosis of acute coronary syndrome and impending cardiogenic shock. Angiogram revealed type-A aortic dissection extending to the aortic arch with concomitant aortic regurgitation (AR) (videos 1 and 2). On prompt recognition of aortic dissection, he was transferred to the operating room for emergent surgical repair. Intraoperative transoesophageal...



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Neck mass: an obstructive cause of respiratory distress with medical management

Congenital goitre is a known cause of hypothyroidism in newborn. Congenital goitre can be due to defective synthesis of thyroxine or administration of antithyroid drugs to the mother during pregnancy. In this case report, we report an instance of a preterm male infant with antenatally detected goitre presenting as a neck mass with congenital hypothyroidism. Hormonal replacement therapy was started immediately after birth which lead to resolution of the mass and normalisation of thyroid function.



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Haemorrhagic conversion of infectious myelitis in an immunocompromised patient

A 28-year-old man recently diagnosed with HIV (CD4 19 cells/mm3, viral load 3.6 million copies/mL, not on highly active antiretroviral therapy on initial diagnosis at outside hospital), disseminated histoplasmosis, shingles and syphilis presented with paraplegia developing over 3 days. Spine MRI demonstrated a longitudinally extensive cord lesion extending from C3 to the tip of the conus. Brain MRI was consistent with meningoencephalitis. Cerebrospinal fluid findings were notable for positive varicella zoster virus (VZV) and cytomegalovirus (CMV) PCRs as well as a Venereal Disease Research Laboratory titre of 1:2. Patient was started on treatment for VZV and CMV meningoencephalitis, neurosyphilis and high-dose steroids for infectious myelitis. Repeat spine MRI demonstrated subacute intramedullary haemorrhage of the cervical cord. He was ultimately discharged to a skilled nursing facility for long-term intravenous antiviral therapy and rehabilitation. After 59 days in the hospital, his neurological exam remained grossly unchanged, with flaccid paraplegia and lack of sensation to fine touch in his lower extremities.



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Perforated neuroenteric cyst masquerading as congenital pulmonary airway malformation

A 3-month-old child was presented with haemoptysis with respiratory distress. Imaging was suggestive of a cavitary lesion in the lung with surrounding consolidation. Diagnosis of a primary lung pathology like congenital pulmonary airway malformation was considered. Based on clinical suspicion and prior experience, a Tc-99m pertechnetate radionuclide study was performed, which clinched the diagnosis of foregut duplication cyst. Intraoperative findings confirmed the presence of a neuroenteric cyst. The child remains asymptomatic on follow-up awaiting neurosurgical intervention for the intraspinal component of the cyst.



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Retrovesical malignant fibrous histiocytoma: a rare tumor

Malignant fibrous histiocytoma (MFH) originating from the retrovesical space is a very rare tumour. A 61-year-old man presented to our hospital with complaints of retention of urine and burning sensation during micturition since 6 months. CT scan abdomen showed a large retrovesical mass between the urinary bladder and rectum, measuring 11x9x12 cm, displacing the urinary bladder. Serum PSA (Prostate Specific Antigen) value was within normal range. Biopsy from retrovesical mass and immunohistochemistry was suggestive of MFH. Wide excision of the retrovesical mass was done. Histopathology confirmed the diagnosis of MFH. He received adjuvant radiotherapy. He is on regular follow-up since the last 2 years after radiotherapy with no signs and symptoms of disease recurrence.



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Deadly combination: Clostridium septicum and colorectal malignancy

Gas gangrene is a life-threatening, necrotising soft tissue infection. Colorectal malignancy-associated Clostridiumsepticum is a rare cause of gas gangrene. This case outlines an initial presentation of colonic malignancy as gas gangrene from C.septicum infection.

A 69-year-old man presented with abdominal pain, vomiting and constipation. Abdominal X-ray revealed dilated small bowel loops. Lactate was elevated. A diagnosis of small bowel obstruction was made. Subsequent CT revealed caecal thickening and subcutaneous emphysema overlying the left flank. Clinically, he became haemodynamically unstable. Examination revealed crepitus overlying the left flank in keeping with gas gangrene. The patient required immediate surgical debridement. Tissue specimens cultured C.septicum. Following a complicated postoperative period, he was transferred to the plastic surgery team for further tissue debridement and reconstruction. A colonoscopy was later performed which was suspicious for malignancy. Colorectal multidisciplinary team discussion is awaited.



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Atrial myxoma: an unusual aetiology for exertional dyspnoea and palpitation

Description

A 67-year-old woman had recently emigrated from the Dominican Republic where, many years prior, she had been evaluated for 'tachycardias' and had unrevealing monitors. She was well until 6 months prior to admission when she started to experience unpredictable, generally exertional palpitations, dyspnoea and left arm discomfort. There was no history of antecedent anxiety. Examination was notable for a 3/6 systolic murmur heard from apex to base and radiating to the neck that ultimately decreased with Valsalva manoeuvre, consistent with aortic sclerosis that was also seen on her echocardiogram. ECG showed normal sinus rhythm, significant left ventricular hypertrophy with strain and question of a right atrial abnormality. Transthoracic echo, for the murmur, showed a 3 cm highly mobile atrial mass, sometimes crossing the mitral valve, and aortic sclerosis (online ). Catheterisation showed unremarkable coronary arteries and no vascular attachments to the mass. Cardiac MRI showed a large mobile and multilobulated...



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Preoperative simulation unveiled undetected surgical difficulties in a case of cochlear implantation

We herein report a case in which extensive preparation changed a difficult-to-treat patient into an easy one. We performed a revision cochlear implantation on a patient whose first procedure had been aborted due to unidentified difficulties. During a series of thorough three-dimensional simulations, we found that the patient in question had a normal cochlea but the cochlea was placed in an unusual position and orientation. This condition is difficult to detect on standard preoperative radiographic images. Through this simulation, we were able to propose a surgical plan to avoid making the same mistakes as the first surgeon. We present this case not as a rare difficult case of an unfortunate patient but instead emphasise the importance of performing surgical simulation and looking for non-obvious difficulties. This case is an example of the success that can be achieved with such extensive preparation.



http://ift.tt/2BrPE30

Artery of Percheron ischaemic stroke revealed by brain MRI DWI/ADC sequences

Description

A 71-year-old Caucasian female patient presented with acute onset of visual disturbance, gait difficulties and fluctuation of consciousness.

Her medical history included artery hypertension, previous cardiac valve replacement with mechanical prosthesis, in treatment with oral anticoagulant.

An emergency CT scan resulted negative for acute lesions, haematological exams were normal, international normalised ratio (INR) was >2.5. The EKG revealed high-frequency atrial fibrillation, not previously known.

At the neurological examination, the patient presented drowsiness, easily resolved by verbal stimulus, bilateral divergent diplopia, with eye movements possible only horizontally and severe postural instability with retropulsion.

On the day after the onset of neurological symptoms, the patient underwent brain MRI without gadolinium. Axial fluid attenuation inversion recovery (FLAIR) sequences revealed diffuse cerebral vasculopathy in the bilateral white matter without evidence of acute lesions (figure 1). Diffusion-weighted imaging (DWI) sequences revealed the presence of recent ischaemic lesions in the territory of the artery...



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Nivolumab-induced polyarthritis

Description

A 48-year-old Japanese woman with non-small cell lung adenocarcinoma (cT3N2M1b) received nivolumab (an immune checkpoint inhibitor) at a dosage of 3 mg/kg every 2 weeks. Treatment with nivolumab was effective. The primary tumour as well as metastases to the lymph nodes and spine almost completely disappeared, as shown on positron emission tomography-CT before treatment (figure 1A) and 4 months after treatment (figure 1B). However, she developed sustained pain and swelling in the shoulders and knees bilaterally after only one infusion of nivolumab, and active inflammation was detected in the shoulder joints bilaterally (figure 1B). She had no personal and family histories of autoimmune disease. Serum C-reactive protein level was 2.1 mg/L. Serum matrix metalloproteinase-3 was elevated at 209 ng/mL (normal <60). Antinuclear antibody, rheumatoid factor and anti-cyclic citrullinated peptide antibody were negative. Ultrasonography confirmed shoulder tenosynovitis and bursitis (figure 2). The arthritis responded...



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Systemic lupus erythematosus (SLE): an unusual cause of ileocolic intussusception

Intussusception is a rare diagnosis in adults. Gastrointestinal involvement is not unusual in systemic lupus erythematosus (SLE).1 A case of intussusception as first presenting symptom of SLE is described. A 50-year-old woman of Chinese origin came to the emergency room with symptoms of high fever, nausea, vomiting and weight loss of 10 kg. Three months before, an episode with abdominal pain due to ileal invagination in the colon occurred. Laboratory analysis showed: thrombocytopaenia, lymphopaenia, positive antinuclear antibody, antidouble-stranded DNA, Coombs tests and low C3 in combination with an active urine sediment and proteinuria. CT and positron emission tomography scan showed lymphadenopathy, but no other abnormalities. Axillar lymph node biopsy showed no abnormalities. The diagnosis new-onset SLE was made. Prednisone treatment was started and soon thereafter tapered, azathioprine and hydroxychloroquine were added. During follow-up, the SLE remained in remission. SLE is a rare cause of ileocolic intussusception and ileocolic intussusception may be the first presenting symptom.



http://ift.tt/2j7fPpa

Multisensory enhancement elicited by unconscious visual stimuli

Abstract

The merging of information from different senses (i.e., multisensory integration) can facilitate information processing. Processing enhancements have been observed with signals that are irrelevant to the task at hand, and with cues that are non-predictive. Such findings are consistent with the notion that multiple sensory signals are sometimes integrated automatically. Multisensory enhancement has even been reported with stimuli that have been presented subliminally, though only with meaningful multisensory relations that have already been learned. The question of whether there exist cases where multisensory effects occur without either learning or awareness has, though, not been clearly established in the literature to date. Here, we present a case study of a patient with Posterior Cortical Atrophy, who was unable to consciously perceive visual stimuli with our task parameters, yet who nevertheless still exhibited signs of multisensory enhancement even with unlearned relations between audiovisual stimuli. In a simple speeded detection task, both response speed, and the variability of reaction times, decreased in a similar manner to controls for multisensory stimuli. These results are consistent with the view that the conscious perception of stimuli and prior learning are not always a prerequisite for multisensory integration to enhance human performance.



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Impact of measures to control brucellosis on disease characteristics in humans: experience from an endemic region in the Balkans

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Association between anti-tuberculosis drug resistance-conferring mutations and treatment outcomes in Myanmar

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Pretargeting of internalizing trastuzumab and cetuximab with a 18 F-tetrazine tracer in xenograft models

Abstract

Background

Pretargeting-based approaches are being investigated for radioimmunoimaging and therapy applications to reduce the effective radiation burden to the patient. To date, only a few studies have used short-lived radioisotopes for pretargeting of antibodies, and such examples with internalizing antibodies are even rarer. Herein, we have investigated pretargeting methodology using inverse electron-demand Diels-Alder (IEDDA) for tracing two clinically relevant, internalizing monoclonal antibodies, cetuximab and trastuzumab.

Results

Bioorthogonal reaction between tetrazine and trans-cyclooctene (TCO) was used for tracing cetuximab and trastuzumab in vivo with a fluorine-18 (t ½ = 109.8 min) labelled tracer. TCO-cetuximab or TCO-trastuzumab was administered 24, 48, or 72 h prior to the injection of tracer to A431 or BT-474 tumour-bearing mice, respectively. With cetuximab, the highest tumour-to-blood ratios were achieved when the lag time between antibody and tracer injections was 72 h. With trastuzumab, no difference was observed between different lag times. For both antibodies, the tumour could be clearly visualized in the PET images with the highest tumour uptake of 3.7 ± 0.1%ID/g for cetuximab and 1.5 ± 0.1%ID/g for trastuzumab as quantified by ex vivo biodistribution. In vivo IEDDA reaction was observed in the blood for both antibodies, but with trastuzumab, this was to a much lower degree than with cetuximab.

Conclusions

We could successfully visualize the tumours by using cetuximab and trastuzumab in pretargeted PET imaging despite the challenging circumstances where the antibody is internalized and there is still some unbound antibody circulating in the blood flow. This clearly demonstrates the potential of a pretargeted approach for targeting internalizing antigens and warrants development of pharmacokinetic optimization of the biorthogonal reactants to this end.



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Evaluation of the new TNM-staging system for thymic malignancies: impact on indication and survival

Abstract

Background

The objective of this study is the evaluation of the Masaoka-Koga and the International Association for the Study of Lung Cancer (IASLC)/International Thymic Malignancy Interest Group (ITMIG) proposal for the new TNM-staging system on clinical implementation and prognosis of thymic malignancies.

Methods

A retrospective study of 76 patients who underwent surgery between January 2005 and December 2015 for thymoma. Kaplan–Meier survival analysis was used to determine overall and recurrence-free survival rates.

Results

Indication for surgery was primary mediastinal tumor (n = 55), pleural manifestation (n = 17), or mediastinal recurrence (n = 4) after surgery for thymoma. Early Masaoka-Koga stages I (n = 9) and II (n = 14) shifted to the new stage I (n = 23). Advanced stages III (Masaoka-Koga: n = 20; ITMIG/IASLC: n = 17) and IV (Masaoka-Koga: n = 33; ITMIG/IASLC: n = 35) remained nearly similar and were associated with higher levels of WHO stages. Within each staging system, the survival curves differed significantly with the best 5-year survival in early stages I and II (91%). Survival for stage IV (70 to 77%) was significantly better compared to stage III (49 to 54%). Early stages had a significant longer recurrence-free survival (86 to 90%) than advanced stages III and IV (55 to 56%).

Conclusions

The proportion of patients with IASLC/ITMIG stage I increased remarkably, whereas the distribution in advanced stages III and IV was nearly similar. The new TNM-staging system presents a clinically useful and applicable system, which can be used for indication, stage-adapted therapy, and prediction of prognosis for overall and recurrence-free survival.



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New laparoscopic procedure for left-sided pancreatic cancer—artery-first approach laparoscopic RAMPS using 3D technique

Abstract

Background

For left-sided pancreatic ductal adenocarcinoma (PDAC), radical antegrade modular pancreatosplenectomy (RAMPS) is a reasonable surgical approach for tumor-free margin resection and systemic lymph node clearance. In pancreaticoduodenectomy for PDAC, the superior mesenteric artery (SMA)-first approach (or the "artery-first approach") has become the standard procedure. With improvements in laparoscopic instruments and techniques, some surgeons attempted to apply laparoscopic RAMPS (L-RAMPS) for carefully selected patients with left-sided PDAC. However, owing to several technical difficulties in this procedure, its application remains uncommon. Moreover, the artery-first approach in L-RAMPS has not been reported. Here, we developed the artery-first approach L-RAMPS for left-sided PDAC and have presented the same in this report.

Case presentation

Between June 2014 and July 2015, 16 patients with left-sided PDAC were referred to our division for pancreatic resection. The following technique was used for performing L-RAMPS on 3 of the 16 patients (19%). Six trocars were placed. After opening the omental bursa, only the middle segment of the pancreas was initially separated from both the left renal vein and the SMA. We termed this procedure as the "artery-first approach using a dome-shaped dorsomedial dissection (3D) technique." This 3D technique enabled the interruption of the entire arterial supply to the specimen while preserving the venous drainage through the splenic vein for preventing venous congestion. The technique also contributed to the early detection of no tumor infiltration into the SMA and the early determination of posterior dissection plane. After pancreatic neck transection, the splenic artery and vein were divided. Finally, the pancreatic tail and spleen were dissected in a right-to-left direction. All operations were completed without any intraoperative complications. The median blood loss and retrieved lymph node count were 75 mL and 37, respectively, which were superior to those reported by other previous studies on L-RAMPS. All resection margins were free of carcinoma. No severe postoperative complications were observed.

Conclusions

The artery-first approach L-RAMPS using 3D technique is safe and feasible to perform. The significance of our proposed procedure is minimal blood loss and precise lymphadenectomy. Therefore, this novel technique may become the preferred treatment for left-sided PDAC in selected cases.



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Partnering around cancer clinical trials (PACCT): study protocol for a randomized trial of a patient and physician communication intervention to increase minority accrual to prostate cancer clinical trials

Abstract

Background

Cancer clinical trials are essential for testing new treatments and represent state-of-the-art cancer treatment, but only a small percentage of patients ever enroll in a trial. Under-enrollment is an even greater problem among minorities, particularly African Americans, representing a racial/ethnic disparity in cancer care. One understudied cause is patient-physician communication, which is often of poor quality during clinical interactions between African-American patients and non-African-American physicians. Partnering Around Cancer Clinical Trials (PACCT) involves a transdisciplinary theoretical model proposing that patient and physician individual attitudes and beliefs and their interpersonal communication during racially discordant clinical interactions influence outcomes related to patients' decisions to participate in a trial. The overall goal of the study is to test a multilevel intervention designed to increase rates at which African-American and White men with prostate cancer make an informed decision to participate in a clinical trial.

Methods/design

Data collection will occur at two NCI-designated comprehensive cancer centers. Participants include physicians who treat men with prostate cancer and their African-American and White patients who are potentially eligible for a clinical trial. The study uses two distinct research designs to evaluate the effects of two behavioral interventions, one focused on patients and the other on physicians. The primary goal is to increase the number of patients who decide to enroll in a trial; secondary goals include increasing rates of physician trial offers, improving the quality of patient-physician communication during video recorded clinical interactions in which trials may be discussed, improving patients' understanding of trials offered, and increasing the number of patients who actually enroll. Aims are to 1) determine the independent and combined effects of the two interventions on outcomes; 2) compare the effects of the interventions on African-American versus White men; and 3) examine the extent to which patient-physician communication mediates the effect of the interventions on the outcomes.

Discussion

PACCT has the potential to identify ways to increase clinical trial rates in a diverse patient population. The research can also improve access to high quality clinical care for African American men bearing the disproportionate burden of disparities in prostate and other cancers.

Trial registration

Clinical Trials.gov registration number: NCT02906241 (September 8, 2016).



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Prevalence of incidental breast cancer and precursor lesions in autopsy studies: a systematic review and meta-analysis

Abstract

Background

Autopsy studies demonstrate the prevalence pool of incidental breast cancer in the population, but estimates are uncertain due to small numbers in any primary study. We aimed to conduct a systematic review of autopsy studies to estimate the prevalence of incidental breast cancer and precursors.

Methods

Relevant articles were identified through searching PubMed and Embase from inception up to April 2016, and backward and forward citations. We included autopsy studies of women with no history of breast pathology, which included systematic histological examination of at least one breast, and which allowed calculation of the prevalence of incidental breast cancer or precursor lesions. Data were pooled using logistic regression models with random intercepts (non-linear mixed models).

Results

We included 13 studies from 1948 to 2010, contributing 2363 autopsies with 99 cases of incidental cancer or precursor lesions. More thorough histological examination (≥20 histological sections) was a strong predictor of incidental in-situ cancer and atypical hyperplasia (OR = 126·8 and 21·3 respectively, p < 0·001), but not invasive cancer (OR = 1·1, p = 0·75). The estimated mean prevalence of incidental cancer or precursor lesion was 19·5% (0·85% invasive cancer + 8·9% in-situ cancer + 9·8% atypical hyperplasia).

Conclusion

Our systematic review in ten countries over six decades found that incidental detection of cancer in situ and breast cancer precursors is common in women not known to have breast disease during life. The large prevalence pool of undetected cancer in-situ and atypical hyperplasia in these autopsy studies suggests screening programs should be cautious about introducing more sensitive tests that may increase detection of these lesions.



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Histone profiling reveals the H1.3 histone variant as a prognostic biomarker for pancreatic ductal adenocarcinoma

Abstract

Background

Epigenetic alterations have been recognized as important contributors to the pathogenesis of PDAC. However, the role of histone variants in pancreatic tumor progression is still not completely understood. The aim of this study was to explore the expression and prognostic significance of histone protein variants in PDAC patients.

Methods

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for qualitative analysis of histone variants and histone related post-translational modifications (PTMs) in PDAC and normal pancreatic tissues. Survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards regression.

Results

Histone variant H1.3 was found to be differentially expressed (p = 0.005) and was selected as a PDAC specific histone variant candidate. The prognostic role of H1.3 was evaluated in an external cohort of patients with resected PDAC using immunohistochemistry. Intratumor expression of H1.3 was found to be an important risk factor for overall survival in PDAC, with an adjusted HR value of 2.6 (95% CI 1.1–6.1), p = 0.029.

Conclusion

We suggest that the intratumor histone H1.3 expression as reported herein, may serve as a new epigenetic biomarker for PDAC.



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Characteristics and outcome in patients with non-specific symptoms and signs of cancer referred to a fast track cancer patient pathway; a retrospective cohort study

Abstract

Background

In 2012 a new cancer patient pathway for patients with non-specific symptoms and signs of cancer (NSSC-CPP) was introduced in Denmark. Limited information is available about the patients referred to the NSSC-CPP and the investigational course. The aim was to describe the population and the investigational course, estimate the prevalence of cancer and one-year mortality, and identify factors associated with a subsequent cancer diagnosis in patients referred to the NSSC-CPP.

Method

This cohort study included patients with at least one visit at the NSSC-CPP at North Zealand Hospital in Denmark (NOH) from October 1st 2013 to September 30th 2014. Data was based on retrospective reviews of the patient files. Logistic regression identified factors associated with a subsequent cancer diagnosis. Multivariate analyses were adjusted by age, gender, smoking status and alcohol consumption. Kaplan-Meier survival plots were made at one-year follow-up.

Results

Eight hundred twenty-five patients were included with a median age of 67 years, 47.4% were male. Prevalence of cancer within one year was 16.7% (138/825). 70.3% (97/138) were solid cancers and 29.7% (41/138) were haematological cancers. During the investigational course 76.7% went through advanced diagnostic imaging (ultrasound, CT, FDG-PET/CT or MRI). Anaemia (OR1.63 CI1.02–2.60), leucocytosis (OR 2.06 CI 1.34–3.15), thrombocytopenia (OR 4.13 CI 2.02–8.47) and elevated LDH (OR 1.64 CI 1.07–2.52) and CRP (OR 2.56 CI 1.66–3.95) were associated with a cancer diagnosis when adjusting for possible confounders. No single non-specific symptom was significantly associated with a cancer diagnosis. One-year mortality for those diagnosed with cancer was 44.2%.

Conclusion

The prevalence of cancer matches that of another NSSC-CPP in Denmark. Deviations in basic biochemistry were associated with a higher probability of underlying cancer and could possibly raise the level of suspicion of malignancy among physicians. High one-year mortality was seen amongst patients diagnosed with cancer.



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Arteria trigemina primitiva — radiological report of three cases and review of literature

The main aim of this paper is to present 3 cases of persistent (patent) primitive trigeminal artery incidentally revealed during various radiological examinations. The presence and function of these vessels in extrauterine life is sometimes associated with other vascular abnormalities, e.g. aneurysms, haemangiomas, moyamoya disease, but frequently found incidentally without any negative signs or symptoms. The presented cases of patients with primitive trigeminal artery clearly show that the reported ailments, which had made the diagnostic imagining necessary, were not associated with the patency of this artery.



http://ift.tt/2AkJi8m

The position of the mental foramen in dentate and edentulous mandibles: clinical and surgical relevance

Background: The knowledge of the exact location of the mental foramen (MF) in dentate and edentulous mandibles is clinically important when constructing complete dentures, performing anaesthetic block of the lower-anterior teeth area and intervening in the MF nearby area. In edentulous mandibles, the bone resorption after teeth loss makes the mental nerve (MN) prone to damage due to the extreme location of the MF very close to the alveolar crest (AC). Chronic compression on the MN may result in pain in the area of MN distribution (ipsilateral face and cheek area) and numbness at the lower lip. The purpose of the current study is to evaluate the exact position of the MF, calculating the distances MF-superior border of the AC and MF-inferior border of the mandible (IBM) in dentate and edentulous mandibles.

Materials and methods: One hundred and two (36 edentulous and 66 dentate) adult dry Greek mandibles were studied.

Results: In 9 out of 36 edentulous mandibles (25%), the MF was found nearby the AC, while in 27 edentulous mandibles (75%), the MF was located at an average distance 6.4 mm from the AC and 12.6 mm from the IBM. In 38 out of 66 dentate mandibles (57.6%), the MF was located at an average distance 13.6 mm from the AC and 15.2 mm from the IBM. The dental status significantly affected (p = 0.001) the distances MF-AC and MF-IBM. Side symmetry was observed for both dentate and edentulous mandibles (p = 0.39 and p = 0.45).

Conclusions: The MF is an important landmark and its location needs to be considered prior to dental implants placement in order to avoid the MN injury and related complications. The position of MF is altered in edentulous mandibles compared with the dentate ones. The MF is a symmetric structure in Greeks.



http://ift.tt/2Aol7Ul

Characteristics of yak platelet derived growth factors-alpha gene and its expression in brain tissues

Background: Platelet derived growth factors (PDGFs) are key components of autocrine and paracrine signalling, both of which play important roles in mammalian developmental processes. PDGF expression levels also relate to oxygen levels. The characteristics of yak PDGFs, which are indigenous to hypoxic environments, have not been clearly described until the current study.

Materials and methods: We amplified the open reading frame encoding yak (Bos grunniens) platelet derived growth factor-alpha (PDGFA) from a yak skin tissue cDNA library by reverse transcriptase polymerase chain reaction (PCR) using specific primers and Sanger dideoxy sequencing. Expression of PDGFA mRNA in different portions of yak brain tissue (cerebrum, cerebellum, hippocampus, and spinal cord) was detected by quantitative real-time PCR (qRT-PCR). PDGFA protein expression levels and its location in different portions of the yak brain were evaluated by western blot and immunohistochemistry.

Results: We obtained a yak PDGFA 755 bp cDNA gene fragment containing a 636 bp open reading frame, encoding 211 amino acids (GenBank: KU851801). Phylogenetic analysis shows yak PDGFA to be well conserved, having 98.1% DNA sequence identity to homologous Bubalus bubalus and Bos taurus PDGFA genes. However, 8 nucleotides in the yak DNA sequence and 4 amino acids in the yak protein sequence differ from the other two species. PDGFA is widely expressed in yak brain tissue, and furthermore, PDGFA expression in the cerebrum and cerebellum are higher than in the hippocampus and spinal cord (p > 0.05). PDGFA was observed by immunohistochemistry in glial cells of the cerebrum, cerebellum, and hippocampus, as well as in pyramidal cells of the cerebrum, and Purkinje cell bodies of the hippocampus, but not in glial cells of the spinal cord.

Conclusions: The PDGFA gene is well conserved in the animal kingdom; however, the yak PDGFA gene has unique characteristics and brain expression patterns specific to this high elevation species.



http://ift.tt/2AmUxgJ

How the three arches of the foot intercorrelate

Background: The foot is composed of medial, lateral and transverse arches which, particularly the medial arch, provide it with the ability to function both as a flexible and rigid structure for proper locomotion. Arches of the foot, as well as their effect on lower extremity function, have been studied. However, quantitative data on the relationship between these arches still remain scanty. The purpose of this study was, therefore, to examine how the three arches of the foot intercorrelate.

Materials and methods: Seventy-six participants (58 males, 18 females) were recruited to participate in the study. Bilateral weight-bearing lateral radiographs of the right foot were taken from each participant. Navicular heights (NH), medial cuneiform height (MCH), calcaneal inclination angle (CIA) and calcaneal-first metatarsal angle (C1MA) were measured to represent the medial arch. The lateral arch was represented by cuboid height (CH) and calcaneal-fifth metatarsal angle (C5MA) whereas; MCH and CH represented the transverse arch. Mean difference of variables between males and females was compared using independent t-test while the correlation between the variables was determined using Pearson correlation.

Results: All the variables were not significantly related to gender. Significant moderate to excellent linear correlations were observed between the variables. CIA showed the strongest correlation with C1MA (r = –0.90) and C5MA (r = –0.84) whereas, CH had the least correlation with other variables.

Conclusions: The moderate to excellent correlations between the variables indicate that deformation or elevation of the medial arch may consequently result in similar movements of the lateral and transverse arches and vice versa.



http://ift.tt/2Aplsqc

Organisation of the dopamine neuronal subsets within midbrain of the feathertail glider (Acrobates pygmaeus, Acrobatidae, Marsupialia)

The Marsupial feathertail glider has a unique set of morphological, anatomical and behavioural features that make it a promising model for study of primate evolution. Among them it has many locomotor adaptations to arboreal life, such as diagonal gait of movements, gliding, fast climbing and running along branches. These ecological and behavioural specialisations could result in differences in anatomy of the brain systems involved in their integration. It is well acknowledged that dopaminergic neurons are involved in motor control, motivation and cognition. Due to the fact that there are no data on morphological organisation of dopaminergic system in the midbrain of this species, we decided to investigate it using immunohistochemical and quantitative methods. Our study showed that the general distribution and characteristics of the dopaminergic cells within midbrain nuclei of the pygmy acrobat is similar to that in other species, but it lack the substantia nigra compact part — ventral tier and "tail" of the substantia nigra subnuclei. This study provides the first description of the dopaminergic cells and nuclei in the midbrain of the feathertail glider and we hope it will start interest in the neurobiology of this species.



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The relationship between selected parameters of a cephalometric analysis determining the vertical morphology of facial skeleton and bite force

Background: There are few studies devoted to an assessment of the relation between bite force and detailed results of cephalometric analysis that determine craniofacial structure. The purpose of the study was to assess the correlation between the selected criteria determining the craniofacial structure and bite force in patients with normal and increased vertical relation of the bases of jaws and skull.

Materials and methods: The study material included 120 patients, aged between 7 and 17 years, who presented for examination and possible orthodontic treatment. The patients were divided into a study group and a control group. The basis of this division were ML-NL and ML-NSL angles, according to Segner's and Hasund's analysis standards, respectively: above 27° and above 30° in the study group, and 20.0 ± 7.0° and 28.0 ± 5.0° in the control group. Bite force was tested using a digital dynamometer calibrated in Newtons. The measurement was performed at the level of the first permanent molars. Vertical relations were assessed using the following cephalometric measurements: ML-NSL, ML-NL, NL-NSL, N-Me, Sp-Me, SpMe:NMe, ms-NL, SGo:NMe.

Results: Bite force was not found to be dependent on the lower anterior face height (Sp-Me), the ratio of anterior lower to total anterior face height (SpMe:NMe), and NL-NSL angle both in patients with abnormal and normal relations of bases of jaws and skull. Although statistically non-significant, the average mean and maximum bite force values were found to be lower in patients with high-angle relation of bases of jaws and skull than in subjects with normal relation of bases of jaws and skull.

Conclusions: Among the selected parameters determining the vertical craniofacial structure, the rear height of the alveolar process (ms-NL) exerts the greatest influence on bite force in both patients with increased and normal vertical relation of bases of jaws and skull, and with an increase in the value of ms-NL, bite force is reduced.  



http://ift.tt/2AoCW5N

Stroke Bricks — spatial brain regions to assess ischaemic stroke localisation

Computer-aided analysis of non-contrast computed tomography (NCCT) images for rapid diagnosis of ischaemic stroke is based on the augmented visualisation of evolving ischaemic lesions. Computerised support of NCCT often leads to overinterpretation of ischaemic areas, thus it is of great interest to provide neurologically verified regions in order to improve accuracy of subsequent radiological assessment. We propose Stroke Bricks (StBr) as an arbitrary spatial division of brain tissue into the regions associated with specific clinical symptoms of ischaemic stroke. Neurological stroke deficit is formally translated into respective areas of possible ischaemic lesions. StBr were designed according to formalised mapping of neurological symptoms and were attributed to the uniquely defined areas of impaired blood supply. StBr concept may be useful for an integrated radiological CT-based assessment of suspected stroke cases or can be included into computer-aided tools to optimise the evaluation of stroke site and its extent. These data in turn are appropriable for further diagnosis, predicting the therapeutic outcome as well as for patients' qualification for an appropriate form of reperfusion therapy. The usefulness of StBr was illustrated in the case studies.



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Anatomic study of the morphology of the right and left coronary arteries

Arising from the aorta, the right (RCA) and left (LCA) coronary arteries provide the arterial supply to both the atria and the ventricles of the heart. An extensive literature review revealed that most studies have either evaluated the morphology of the RCA or the LCA independently. This study aimed to document the relationship between the morphology of the RCA and LCA using coronary angiograms. In addition, variations such as split or double RCA and an absent LCA were documented. A review of 500 coronary angiograms was conducted and the RCA and LCA were classified according to their branching patterns and arterial dominance. The most prevalent branching pattern of the LCA was bifurcation (in 65.8%; 329/500), while trifurcation and quadrifurcation occurred in 20.4% (102/500) and 1.6% (8/500), respectively. The LCA was absent in 11.8% (59/500) of cases with the bifurcation and trifurcation of its branches in 10.8% (54/500) and 1.4% (7/500), respectively. The splitting of the RCA occurred in 4.2% (21/500) of the angiograms. A split RCA with concomitant absent LCA was documented in 1.2% (6/500) of the angiograms. The RCA and LCA were dominant in 77.2% (386/500) and 9.8% (49/500) of cases, respectively, whereas co-dominance occurred in 13% (65/500) of the sample examined. In most cases where a split RCA was present, the RCA was found to be non-dominant. With the advent of coronary arteriography, a comprehensive understanding of coronary arterial anatomy and their anomalies has become essential.



http://ift.tt/2ApYkYi

Frontal aslant tract projections to the inferior frontal gyrus

Background: Frontal aslant tract (FAT) is a white matter bundle connecting the pre-supplementary motor area (pre-SMA) and the supplementary motor area (SMA) with the inferior frontal gyrus (IFG). The purpose of the present study was to evaluate the anatomical variability of FAT.

Materials and methods: Total number of fibres and the lateralisation index (LI) were calculated. We attempted to find factors contributing to the diversity of FAT regarding IFG terminations to the pars opercularis (IFG-Op) and to the pars triangularis (IFG-Tr). Magnetic resonance imaging of adult patients with diffusion tensor imaging (DTI) with total number of 98 hemispheres composed a cohort. V-shaped operculum was the most common (60.5%).

Results: Total number of FAT fibres had widespread and unimodal distribution (6 to 1765; median: 160). Left lateralisation was noted in 64.3% of cases and was positively correlated with total number of FAT fibres and the bundle projecting to IFG-Op (p < 0.01). LI correlated with total number of FAT fibres (r = 0.43, p < 0.01). FAT projected predominantly to IFG-Op (88.9%; 88 of 99). Only in 3 (3.1%) cases more fibres terminated in IFG-Tr than in IFG-Op. Total number of FAT fibres and number of fibres terminating at IFG-Op did not correlate with the ratio of fibre numbers: FAT/IFG-Op, FAT/IFG-Tr and IFG-Op/IFG-Tr (p > 0.05). The greater total number of fibres to IFG-Tr was, the higher were the ratios of IFG-Tr/ /FAT (r = 0.57, p < 0.01) and IFG-Tr/IFG-Op (r = 0.32, p = 0.04).

Conclusions: Among the IFG, the major termination of FAT is IFG-Op. Whereas the IFG-Tr projection seems to be related to the expansion of the entire FAT bundle regardless of side, domination and handedness. Nevertheless, FAT features a significant anatomical variability which cannot be explained in terms of DTI findings.



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Morphological variations of the vermiform appendix in Iranian cadavers: a study from developing countries

Background: The vermiform appendix is a worm-like tube containing a large amount of lymphoid follicles. In our knowledge, there is a little standard data about the vermiform appendix in Iranian population. Therefore, the objective of this study was to investigate the normal appendix size in Iranian cadavers.

Materials and methods: A cross-sectional study was undertaken between June 2014 and July 2015, in the autopsy laboratory, Legal Medicine Organisation, Razavi Khorasan province, Iran. A total of 693 cadavers with the mean age of 40.46 ± 20.99 years were divided into 10 groups. After writing down position of the appendix, the length, diameter and weight of the appendix were measured. Statistical analysis was performed using SPSS software.

Results: The mean values of the demographic characteristics included — age: 40.46 ± 20.99 years; weight: 63.47 ± 17.84 kg; height: 159.95 ± 28.23 cm. The mean values of the appendix length, diameter, weight and index in the cadavers were 8.52 ± 2.99 cm, 12.17 ± 4.53 mm, 6.43 ± 3.26 g and 0.013 ± 0.01, respectively. The most common position of the appendix was retrocaecal in 71.7% of cases. Significant correlations were evident between the value of demographic data and appendix size (p < 0.05). The diameter (p = 0.002) and index of the appendix (p = 0.003) showed significant difference between males and females.

Conclusions: Having standard data on the vermiform appendix is useful for clinicians as well as anthropologists. The findings of the present study can provide information about morphologic variations of the appendix in Iranian population.  

 



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Neonatal exposure to monosodium glutamate results in dysmorphology of orofacial lower motor neurons

Glutamate is the most abundant excitatory neurotransmitter in the central nervous system, and is stored and released by both neurons and astrocytes. Despite the important role of glutamate as a neurotransmitter, high levels of extracellular glutamate can result in excitotoxicity and apoptosis. Monosodium glutamate (MSG) is a naturally occurring sodium salt of glutamic acid that is used as a flavour enhancer in many processed foods. Neonatal exposure to MSG has been shown to result in neurodegeneration in several forebrain regions, characterised by neuronal loss and neuroendocrine abnormalities. However, the brainstem effects of neonatal MSG exposure have not been investigated. It is therefore hypothesized that MSG exposure during the early postnatal period would impact brainstem lower motor neurons involved in feeding behaviour. The effect of neonatal MSG exposure on brainstem lower motor neurons was investigated by exposing rat pups to either 4 mg/g MSG or saline from postnatal day (P) 4 through 10. On P28, brains were preserved by vascular perfusion with fixative, frozen sectioned and stained for Nïssl substance. The number, size and shape of brainstem motor neurons were compared between MSG and saline-exposed animals. MSG exposure had no impact on the total number of neurons in the nuclei examined. However, MSG exposure was associated with a significant increase in the number of round somata in both the trigeminal and facial nuclei. Furthermore, MSG exposure resulted in significantly smaller neurons in all motor nuclei examined. These results suggest that neonatal exposure to MSG impacts the development of brainstem lower motor neurons which may impact feeding and swallowing behaviours in young animals.  



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Anatomical structure of the coracohumeral ligament and its effect on shoulder joint stability

Background: In this study, coracohumeral ligament (CHL) specimens were carefully dissected to observe its length, width, thickness and tension at different positions of the shoulder joint, thereby elucidating its effects on shoulder joint stability.

Materials and methods: Fresh frozen shoulder joints from 40 normal adult cadaveric specimens were dissected to reveal the CHL. With the shoulder joints placed at different positions, the length of the CHL and the width and thickness of the middle part of the ligament were measured. The changes in tension of the CHL were also observed. When the shoulder joint maintained the neutral position, the length of the CHL was 52.23 ± 1.02 mm and the width and thickness of the middle part of the ligament were 15.95 ± 0.59 mm and 1.46 ± 0.06 mm, respectively.

Results: When the shoulder joint moved from the neutral position to 90° external rotation, from the neutral position to 30° adduction or from the neutral position to 30° flexion/extension or when the shoulder joint is pulled down with a 5 kg weight, the CHL was elongated and thinned, maintaining a strained state. When the shoulder joint moved from the neutral position to 90° internal rotation, from the neutral position to 90° abduction or from the neutral position to 30° flexion/ extension, the CHL was shortened and thickened, maintaining a relaxed state.

Conclusions: The CHL may limit the external rotation, adduction and downward movement of the shoulder joint and the process from the neutral position to the 30° flexion/extension, maintaining shoulder joint stability.    



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Adrenergic and cholinergic innervation of the atrioventricular valves in chinchilla (Chinchilla laniger)

The arrangement of autonomic fibres was studied in the cardiac atrioventricular valves of small chinchillas. The dissected valves were stained entirely using the modified histochemical acetylcholine esterase technique (AChE) and the SPG-De la Torre method. Double immunocytochemical staining was also used for the expression of vesicular acetylcholine transporter (VAChT) and dopamine beta hydroxylase (DBH). The study showed the presence of both cholinergic and adrenergic fibres, forming a kind of network on all cusps of both valves. The adrenergic network is always more strongly represented than the cholinergic network. The cholinergic nerve network of the "parietal" part formed mainly the parallel arrangement. As we move towards the free parts of the cusps, the arrangement becomes netted and radiant. The adrenergic fibres formed only the netted arrangement, which was the most dense in the peripheral (parietal) part of the cusps. Some of the fibres in the vicinity of tendinous cords extended as far as the papillary muscles. Double immunocytochemical tests confirmed the presence and distribution of DBH- and VAChT-positive fibres. Some fibres (especially within the tendinous cords) show VAChT and DBH colocalisation.



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Large thoracic tumour without superior vena cava syndrome

A 62-year-old male with long-standing smoking history presented with haemoptysis. Plain chest X-ray showed abnormal findings proximate to the right pulmonary hilum. Bronchoscopy revealed a fragile exophytic tumour of the right wall of the lower third of the trachea, infiltrating the right main bronchus (75% stenosis) and the right upper lobar bronchus (near total occlusion). Contrast-enhanced chest computed tomography demonstrated a 7.2 × 4.9 cm tumour contiguous to the above-mentioned structures, mediastinal lymph node pathology, and a vessel coursing inferiorly to the left of the aortic arch and anterior to the left hilum. Despite the tumour constricting the right superior vena cava (SVC), no signs of SVC syndrome were present. In this case, the patient does not present with SVC syndrome, as expected due to the constriction of the (right) SVC caused by the tumour, since head and neck veins drain through the persistent left superior vena cava (PLSVC). PLSVC is the most common thoracic venous anomaly with an incidence of 0.3% to 0.5% of the general population and it is a congenital anomaly caused by the failure of the left anterior cardinal vein to regress and to consequently form the ligament of Marshall during foetal development. It is associated with absence of the left brachiocephalic vein and in 10% to 20% of cases the right SVC is absent. Two potential draining points of the PLSVC have been previously reported. In the majority of cases PLSVC drains directly into the coronary sinus, but less frequently it drains into the left atrium or the left superior pulmonary vein (LSPV). In cases where the PLSVC drains into the coronary sinus, congenital heart defects are rare. The patient usually remains asymptomatic and PLSVC is an incidental finding during radiographic imaging or medical procedures. When the PLSVC drains into the left atrium or the LSPV, a right-to-left shunt is formed; a condition usually asymptomatic. In some reported cases this PLSVC variant presents with persistent, unexplained hypoxia or cyanosis and embolisation causing recurrent transient ischaemic attacks and/or cerebral abscesses. This PLSVC variant is more often associated with absence of the right SVC and congenital heart abnormalities.  



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Cocaine- and amphetamine-regulated transcript (CART) peptide in the nerve fibres of the porcine gallbladder wall under physiological conditions and after Salmonella Enteritidis lipopolysaccharides administration

Background: Cocaine- and amphetamine-regulated transcript (CART) peptide is the substance distributed in various parts of the nervous system. The majority of previous studies described this substance in the brain, where it takes part in regulatory processes connected with the food intake. CART is also present in the peripheral nervous system, especially in the enteric neurons and nerves located in the wall of the stomach and intestine, but many aspects of distribution and functions of this peptide in the digestive organs remain unknown. The aim of the present study was to investigate the changes of CART-positive nerves in the porcine gallbladder after administration of low-dose Salmonella Enteritidis lipopolysaccharide (LPS) using the single immunofluorescence technique. Materials and methods: Seven days after the injection of 5 μg/kg b.w. LPS S. Enteritidis the gallbladders were collected. CART-positive nerves were studied with standard single immunofluorescence method and counted per observation field (0.1 m2). Results: In control animals the average number of CART-positive nerves per observation field (0.1 mm2) amounted to 5.38 ± 0.32, 11.11 ± 1.56 and 2.97 ± ± 0.24 in gallbladder neck, body and fundus, respectively. LPS administration caused the increase in the number of CART-positive fibres in all parts of gallbladder, and these values amounted to 12.74 ± 0.51, 19.75 ± 0.19 and 5.1 ± 0.05 in the gallbladder neck, body and fundus, respectively. Conclusions: The obtained results suggest that CART is involved in the neuronal regulatory processes in the porcine gallbladder under physiological conditions, but also during pathological processes, but exact functions of this peptide in this organ remain unexplained and require the further investigation.



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Anatomical variations of testicular artery: a review

The testicular arteries (TAs) also known as internal spermatic arteries are long and slender arteries usually arising from the anterolateral aspect of the abdominal aorta, 2.5 cm to 5 cm caudal to the renal arteries. The variation in TAs may be found with respect to their origin, number or course. They can originate from the abdominal aorta itself at an abnormal level. If not arising from abdominal aorta the TA variants may arise from renal artery, suprarenal artery or any one of the lumbar arteries. Rarely it can arise from common or internal iliac artery, or from the superior epigastric artery. The most common variation with respect to origin of TA was found in association with renal vessels. In regard to their number, double TA was found to be most common and with respect to course most common variation was arched TA over ipsilateral renal vein. The arched TA at times on right side had a retrocaval course. Occurrence of TA variants is explained with embryology and the knowledge of its clinical significance is essential for future surgeons for designing vascular surgeries. Four studies had attempted to classify TA variants regarding their origin, number and course but they could not accommodate recently found TA variants. This led to our new proposed classification.



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Factors involved in cancer metastasis: a better understanding to “seed and soil” hypothesis

Abstract

Metastasis has intrigued researchers for more than 100 years. Despite the development of technologies and therapeutic strategies, metastasis is still the major cause of cancer-related death until today. The famous "seed and soil" hypothesis is widely cited and accepted, and it still provides significant instructions in cancer research until today. To our knowledge, there are few reviews that comprehensively and correlatively focus on both the seed and soil factors involved in cancer metastasis; moreover, despite the fact that increasingly underlying mechanisms and concepts have been defined recently, previous perspectives are appealing but may be limited. Hence, we reviewed factors involved in cancer metastasis, including both seed and soil factors. By integrating new concepts with the classic hypothesis, we aim to provide a comprehensive understanding of the "seed and soil" hypothesis and to conceptualize the framework for understanding factors involved in cancer metastasis. Based on a dynamic overview of this field, we also discuss potential implications for future research and clinical therapeutic strategies.



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DNA methylation-based biological aging and cancer risk and survival: Pooled analysis of seven prospective studies

Abstract

The association between aging and cancer is complex. Recent studies have developed measures of biological aging based on DNA methylation and called them 'age acceleration'. We aimed to assess associations of age acceleration with risk of and survival from seven common cancers. Seven case-control studies of DNA methylation and colorectal, gastric, kidney, lung, prostate and urothelial cancer, and B-cell lymphoma, nested in the Melbourne Collaborative Cohort Study were conducted. Cancer cases, vital status and cause of death were ascertained through linkage with cancer and death registries. Conditional logistic regression and Cox models were used to estimate odds ratios (OR) and hazard ratios (HR) and 95% confidence intervals (CI) for associations of five age acceleration measures derived from the Human Methylation 450K Beadchip assay with cancer risk (N=3,216 cases) and survival (N=1,726 deaths), respectively. Epigenetic aging was associated with increased cancer risk, ranging from 4% to 9% per five-year age acceleration for the 5 measures considered. Heterogeneity by study was observed, with stronger associations for risk of kidney cancer and B-cell lymphoma. An associated increased risk of death following cancer diagnosis ranged from 2% to 6% per five-year age acceleration, with no evidence of heterogeneity by cancer site. Cancer risk and mortality were increased by 15 to 30% for the fourth vs. first quartile of age acceleration. DNA methylation-based measures of biological aging are associated with increased cancer risk and shorter cancer survival, independently of major health risk factors. This article is protected by copyright. All rights reserved.



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3D Reconstruction of peripheral nerves from optical projection tomography (OPT) images. A method for studying fascicular interconnections and intraneural plexuses

Abstract

Background: The general microscopic characteristics of nerves are described in several textbooks of histology, but the specific microanatomies of most nerves that can be blocked by anesthesiologists are usually less well known.

Our objective was to evaluate the 3D reconstruction of nerve fascicles from optical projection tomography images (OPT) and the ability to undertake an internal navigation exploring the morphology in detail, more specifically the fascicular interconnections.

Methods: Median and lingual nerve samples were obtained from five euthanized piglets. OPT images of the samples were acquired and 3D reconstruction was performed.

Results: The OPT technique revealed the inner structure of the nerves at high resolution, including large and small fascicles, perineurium, interfascicular tissue and epineurium. The fascicles were loosely packed inside the median nerve and more densely so in the lingual nerve.

Analysis of the 3D models demonstrated that the nerve fascicles can show six general spatial patterns. Fascicular interconnections were clearly identified.

Conclusions: The 3D reconstruction of nerve fascicles from OPT images opens a new path for research into the microstructure of the inner contents of fascicular nerve groups and their spatial disposition within the nerve including their interconnections.

These techniques enable 3D images of partial areas of nerves to be produced and could became an excellent tool for obtaining data concerning the 3D microanatomy of nerves, essential for better interpretation of ultrasound images in clinical practice and thus avoiding possible neurological complications. This article is protected by copyright. All rights reserved.



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The Clinical Anatomy of Fibromyalgia

Abstract

Introduction: Fibromyalgia is a disorder characterized by pain and a spectrum of psychological comorbidities, rendering treatment difficult and often a financial burden. Findings regarding diagnosis, prevalence, comorbidities, and potential pathophysiological links are discussed herein. Fibromyalgia is a complex disorder and there are specific criteria that patients must meet for diagnosis, including scores on fibromyalgia questionnaires, commonalities of age, gender, menopause status, sleep disturbances, and mood symptoms. The close relationship between fibromyalgia and other chronic disorders should alert the physician to explore for comorbid illnesses. In this review of the clinical anatomy of fibromyalgia, we uncover new studies that could be significant for the current use of clinical interventions for patients with symptoms.

Materials and methods: Using standard search engines, the clinical anatomy of fibromyalgia is investigated and many related studies are mentioned herein.

Conclusions: Fibromyalgia is considered a prototypical central chronic pain syndrome and is associated with widespread pain that fluctuates spontaneously. There is also substantial lifetime psychiatric comorbidity in individuals with fibromyalgia, resulting in a low health-related quality of life. These results have important clinical and theoretical implications, including the possibility that fibromyalgia could share underlying pathophysiological links with some psychiatric disorders. This reveals that patients with fibromyalgia have findings compatible with tissue injury pain, the pain mechanisms involving both the primary afferent neuron and the nociceptive systems in the central nervous system. This article is protected by copyright. All rights reserved.



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Testicular orphan receptor 4 promotes tumor progression and implies poor survival through AKT3 regulation in seminoma

Abstract

Seminoma is recognized as the most common testicular germ cell tumor which mainly occurs in the 15-35-year-old young men worldwide. Early studies have indicated that testicular nuclear receptor 4 (TR4) firstly cloned from testis is involved in the invasion and metastasis of several human tumors, however, little attention is paid to the function of TR4 in Seminoma. Our Immunohistochemical (IHC) staining results showed that patients who underwent advanced stage tended to higher expression of TR4. Importantly, there was a significant association between elevated TR4 expression and reduced Overall Survival in seminoma patients. In vitro MTS, western blot and transwell assays after manipulating TR4 expression in Tcam-2 cells revealed that TR4 induced epithelial-to-mesenchymal transition (EMT) and promoted Tcam-2 cells proliferation and invasion. Mechanism dissection demonstrated that AKT3, a critical component in the signaling pathway, played a crucial role in mediating TR4-promoted Tcam-2 cells proliferation and invasion. We further revealed TR4 modulated AKT3 at the transcriptional level via chromatin immunoprecipitation and luciferase assays. Meanwhile, addition of the AKT3 siRNA blocked the function of TR4. Overall, these findings firstly elucidate TR4 is a novel prognostic marker and plays a critical role in the metastatic capacity of Tcam-2 cells by EMT regulation and consequently targeting TR4-AKT3 pathway may serve as a potential therapeutic approach for seminoma.

This article is protected by copyright. All rights reserved.



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Total Mercury Determination in Muscle and Liver Tissue Samples from Brazilian Amazon Fish Using Slurry Sampling

Abstract

This paper presents a slurry sampling method for total mercury determination by graphite furnace atomic absorption spectrometry (GFAAS) in tissue of fish from the Amazon. The tissue samples were lyophilized and macerated, and then the slurry samples were prepared by putting 20 mg of tissue, added to a solution containing Triton X-100, Suprapur HNO3, and zirconium nitrate directly in sampling vials of a spectrometer. Mercury standard solutions were prepared under the same conditions as the slurry samples. The slurry samples and the mercury standard solutions were sonicated for 20 s. Twenty microliters of slurry samples were injected into the graphite tube, which contained an internal wall lined with tungsten carbide. Under these conditions, it was possible to thermally stabilize the mercury up to an atomization temperature of 1700 °C. The method was validated by mercury determination in reference materials DORM-4 and DOLT-4. The LOD and LOQ were 0.014 and 0.045 mg kg−1, respectively, and recovery percentages in relation to the concentration values were certified in the order of 98%.



http://ift.tt/2jFoT46

Seleno-compounds and Carnosic Acid Added to Diets with Rapeseed and Fish Oils Affect Concentrations of Selected Elements and Chemical Composition in the Liver, Heart and Muscles of Lambs

Abstract

The objective of our studies was to investigate effects of carnosic acid (CA), selenized yeast (SeY) and selenate (SeVI) added to the diet including rapeseed oil (RO) and fish oil (FO) on concentrations of elements, fatty acids (FAs), tocopherols, cholesterol, and malondialdehyde in the liver, heart, musculus longissimus dorsi (MLD), and musculus biceps femoris (MBF) of lambs. Lambs were fed diets: group I—the basal diet (BD) with RO; group II—BD with RO and FO; group III—BD with RO, FO, and CA; group IV—BD with RO, FO, CA, and SeY; group V—BD with RO, FO, CA, and SeVI. The diets with Se compounds increased Se concentrations in all tissues compared with other diets. The diet with SeVI increased Cd, Sb, and Pb concentrations in the liver compared to groups I, II, and IV. The diets containing Se compounds increased Sb and Pb concentrations in MBF compared to groups I and II. All diets with CA reduced As, Sb, and Pb concentrations in MLD compared to groups I and II. All diets with FO increased concentrations of FAs and malondialdehyde in the liver compared to group I. All diets with FO decreased FAs concentrations in MBF compared to group I. The diets containing CA with/without Se compounds increased malondialdehyde concentrations in MBF compared to groups I and II. The diet with Se compounds reduced malondialdehyde concentrations in MLD compared to group II. All diets with FO changed concentrations of tocopherols and cholesterol in all tissues compared to group I. Our study showed that the addition of SeY or SeVI to the experimental diet increased the concentration of Se in all assayed tissues of lambs without adversely influencing performance or causing physiological disorders in internal organs. Both, SeY or SeVI added to the experimental diet decreased the oxidative stress and the concentrations of As, Sb, and Pb in MLD compared with the diets containing RO, irrespective of the presence of FO (groups I and II). Our study provides useful knowledge for nutritionists carrying out further investigations aimed at improving farm animal health, performance, and the nutritional quality of animal products for humans.



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Magnesium in Breast Cancer: What Is Its Influence on the Progression of This Disease?

Abstract

Breast cancer is a disease of high mortality, characterized by the progressive accumulation of mutations that contribute to the uncontrolled development of breast tissue cells. Literature shows that disturbances in mineral homeostasis, such as magnesium, may interfere with tumor progression. The objective of this study is to provide updated information about magnesium's role in the pathogenesis of breast cancer. A review of literature was carried out from a search for articles in the PubMed and CAPES Periodicals databases published between 1995 and 2016 with the cross-references of the descriptors "magnesium," "breast neoplasms," and "oxidative stress" and the corresponding words in Portuguese. We included studies on the metabolism and bioavailability of magnesium and studies related to breast cancer and excluded articles in which only the abstract was available, dissertations, theses, articles involving adjuvant and/or neoadjuvant therapies, and supplementation of minerals in breast cancer patients. Magnesium is a mineral that participates in the metabolism of various nutrients and nucleic acids. In the presence of breast cancer, neoplastic cells increase the expression of magnesium transport channels, which raises the intracellular concentration of the mineral, contributing to tumor growth through its function of increasing energy demand. The data obtained in this review illustrates the influence of magnesium on the progression of breast cancer. However, the existing data are scarce and inconsistent, which demonstrates a need for further studies on the subject with a goal to have better control of the disease.



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Observations on the Origin of Ovarian Cortical Inclusion Cysts in Women Undergoing Risk-Reducing Salpingo-Oophorectomy

Abstract

Aims

Evidence suggests that up to 70% of high-grade serous ovarian carcinomas (HGSCs) potentially arise from fallopian tube fimbriae, and that many of the remaining cases arise from within the ovary in cortical inclusion cysts (CICs) with a Müllerian phenotype (Müllerian-CICs). It has been proposed that Müllerian-CICs arise either from metaplasia of mesothelial ovarian surface epithelium (OSE) entrapped within the ovary after ovulation, or from normal tubal cells entrapped post-ovulation. However, this proposal is controversial. We therefore conducted a study of CICs in women, most of them BRCA1/2 mutation carriers, undergoing risk-reducing salpingo-oophorectomy at our institution from 2000-2014.

Methods and results

We used immunohistochemistry for Paired Box gene 8 (PAX8), a Müllerian marker, and calretinin, a mesothelial marker to classify CIC cells. In 499 CICs from 59 women, 72.3% were positive for PAX8 (PAX8+): >10% of CIC cells positive; 43.5% positive for calretinin (CALRETININ+). The proportion of PAX8+ CICs increased from 62.9% in premenopausal to 80.5% in postmenopausal patients. The proportion of CALRETININ+ CICs decreased from 52.6% to 35.6%, respectively. There was significant overlap of PAX8 and calretinin positivity: 82 (16.4%) CICs were PAX8+/CALRETININ+; 43 (40.2%) of these 82 demonstrated PAX8+/CALRETININ+ in the same cells.

Conclusions

These results, and the increased ratio of PAX8+ to CALRETININ+ CICs from premenopausal to postmenopausal, show that many PAX8+ CICs likely arise from metaplasia of OSE-derived CICs. The proportion of PAX+/CALRETININ- CICs arising from OSE-derived CICs is unclear, but our results strongly support the proposal that many Müllerian-CICs arise from OSE via metaplasia.

This article is protected by copyright. All rights reserved.



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Invasion in breast lesions: the role of the epithelial-stroma barrier

Abstract

Despite the significant biological, behavioural and management differences between ductal carcinoma in situ (DCIS) and invasive carcinoma of the breast, they share many morphological and molecular similarities. Differentiation of these two different lesions in breast pathological diagnosis is typically based on the presence of an intact barrier between the malignant epithelial cells and stroma, namely the myoepithelial cell (MEC) layer and surrounding basement membrane (BM). Despite being robust diagnostic criteria, the identification of MECs and BM to differentiate in situ from invasive carcinoma is not always straightforward. The MEC layer around DCIS may be interrupted and/or show an altered immunoprofile. MECs may be absent in some benign locally infiltrative lesions such as microglandular adenosis and infiltrating epitheliosis, and occasionally in non-infiltrative conditions such as apocrine lesions, and in these contexts this does not denote malignancy or invasive disease with metastatic potential. MECs may be also absent around some malignant lesions such as some forms of papillary carcinoma yet these behave in an indolent fashion akin to some DCIS. In Paget's disease, malignant mammary epithelial cells extend anteriorly from the ducts to infiltrate the epidermis of the nipple but do not typically infiltrate through the BM into the dermis. Conversely, BM-like material can be seen around invasive carcinoma cells and around metastatic tumour cell deposits. Here, we review the role of MECs and BM in breast pathology and highlight potential clinical implications. We advise caution in interpretation of MEC features in breast pathology and mindfulness of the substantive evidence base in the literature associated with behaviour and clinical outcome of lesions classified as benign on conventional morphological examination before changing classification to an invasive lesion on the sole basis of MEC characteristics.

This article is protected by copyright. All rights reserved.



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