Serological prevalence and public health significance of brucellosis on a dairy farm in Namibia from 2011 to 2014

The main objective of this study was to determine the serological prevalence of brucellosis on a dairy farm with no past history of abortions, but where Brucella control measures including test and slaughter and ...

http://ift.tt/2n4fgRi

Effectiveness of case management in the prevention of COPD re-admissions: a pilot study

Chronic obstructive pulmonary disease (COPD) exacerbations are associated with high disease burden and costs, especially in the case of hospitalizations. The overall number of hospital admissions due to exacer...

http://ift.tt/2zCZ6nI

Prevalence of oncogenic human papillomavirus genotypes in patients diagnosed with anogenital malignancies in Botswana

Human papillomavirus (HPV) associated malignancies are the leading cause of cancer death in Botswana. We sought to determine causative HPV types in patients with anogenital malignancies in Botswana to inform v...

http://ift.tt/2A7PwIM

Multiresistant ST59-SCCmec IV-t437 clone with strong biofilm-forming capacity was identified predominantly in MRSA isolated from Chinese children

This study aimed to investigate the clinical and molecular epidemiology and biofilm formation of Staphylococcus aureus (SA) isolated from pediatricians in China.

http://ift.tt/2hSjUfN

Effects of IFN-γ coding plasmid supplementation in the immune response and protection elicited by Trypanosoma cruzi attenuated parasites

Previous studies showed that a naturally attenuated strain from Trypanosoma cruzi triggers an immune response mainly related to a Th2-type profile. Albeit this, a strong protection against virulent challenge was ...

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ASCO update on lymphoma

Summary

Abstracts concerning indolent and aggressive lymphoma and multiple myeloma with clinical relevance from the ASCO 2017 meeting are discussed.

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The first meeting of the Austrian Expert Panel for Molecular Cancer Profiling

Summary

Personalized medicine is rapidly changing the daily routine for the diagnostic work-up and treatment of cancer patients. Several clinical studies and programs are ongoing worldwide to implement personalized anticancer therapies particularly for relapsed/refractory malignancies. On 28 October 2016, the first meeting of the Austrian Expert Panel for Molecular Cancer Profiling was held in Salzburg with the purpose to identify clinical studies and registry programs focusing on comprehensive molecular tumor profiling and personalized cancer therapies in Austria. Representatives of the four Austrian academic centers and from two teaching hospitals were invited to present and debate the current status, challenges, and perspectives in precision oncology. To date, three clinical programs are recruiting patients with relapsed/refractory malignancies in Austria: the ONCO-T-PROFILE program at the Medical University of Innsbruck, the platform MONDTI at the Medical University of Vienna, and the ICT (Individualized Cancer Treatment) phase II trial at the Medical University of Graz. The aim of both research programs and the phase II trial is to investigate the efficacy of molecular profile-based personalized therapies in refractory and relapsed metastatic cancer patients. Furthermore, in cooperation with the AGMT (Study Group of Medical Tumor Therapy), a clinical registry will be established to monitor and to analyze the benefit of molecular profiling in real life.

http://ift.tt/2hSpoag

Novel antibiotic combinations proposed for treatment of Burkholderia cepacia complex infections

Effective strategies to manage Burkholderia cepacia complex (Bcc) infections in cystic fibrosis (CF) patients are lacking. We tested combinations of clinically available antibiotics and show that moxifloxacin-cef...

http://ift.tt/2zE0nex

Pathology of Castleman Disease

The term Castleman disease encompasses several distinct lymphoproliferative disorders with different underlying disease pathogenesis, and clinical outcomes. It includes unicentric and multicentric diseases with limited versus significant systemic symptoms, respectively. Importantly, the histopathologic features encountered in the various forms of Castleman disease are diverse, and for the most part, lack specificity, because they are seen to varying degrees in different clinical variants of Castleman disease, and in reactive (autoimmune/infectious) and malignant (lymphoma) contexts. Accordingly, accurate clinical diagnosis of Castleman disease requires careful and thorough clinicopathologic correlation. An overview of the key histopathologic features of Castleman disease is presented.

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Treatment of Idiopathic Castleman Disease

Important progress has been made in the treatment of idiopathic multicentric Castleman disease (iMCD) with the introduction of interleukin-6 targeting monoclonal antibodies. This article describes the clinical results obtained with different treatment modalities and uses this evidence to provide treatment guidelines for the practicing clinician. Much is still to be learned about the pathophysiology of iMCD and further research is urgently needed to develop novel and curative treatment approaches for all patients.

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Contents

Frits van Rhee and Nikhil C. Munshi

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Forthcoming Issues

Thalassemia

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Contributors

GEORGE P. CANELLOS, MD

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Unicentric Castleman Disease

Unicentric Castleman disease (UCD) is a rare lymphoproliferative disorder that manifests typically as proliferation of a single lymph node or region of lymph nodes. Histologically, hyaline vascular variant is found in a majority of UCDs. UCD commonly presents in younger patient populations. Patients with UCD may be asymptomatic or present with symptoms related to mass effects on surrounding structures. It is difficult to achieve a definitive diagnosis by imaging alone. Histologic examination of the lesion remains the gold standard for diagnosis. Complete surgical resection is the best primary treatment modality for UCD resulting in excellent long-term survival and low recurrence rates.

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Copyright

ELSEVIER

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Castleman Disease Pathogenesis

Castleman disease (CD) describes a group of heterogeneous disorders with common lymph node histopathologic features, including atrophic or hyperplastic germinal centers, prominent follicular dendritic cells, hypervascularization, polyclonal lymphoproliferation, and/or polytypic plasmacytosis. The cause and pathogenesis of the four subtypes of CD (unicentric CD; human herpesvirus-8-associated multicentric CD; polyradiculoneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes [POEMS]-associated multicentric CD; and idiopathic multicentric CD) vary considerably. This article provides a summary of our current understanding of the cause, cell types, signaling pathways, and effector cytokines implicated in the pathogenesis of each subtype.

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Castleman Disease

HEMATOLOGY/ONCOLOGY CLINICS OF NORTH AMERICA

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TAFRO Syndrome

TAFRO syndrome is a newly recognized variant of idiopathic multicentric Castleman disease (iMCD) that involves a constellation of syndromes: thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O). Thrombocytopenia and severe anasarca accompanied by relatively low serum immunoglobulin levels are characteristic clinical findings of TAFRO syndrome that are not present in iMCD-not otherwise specified (iMCD-NOS). Lymph node biopsy is recommended to exclude other diseases and to diagnose TAFRO syndrome, which reveals characteristic histopathological findings similar to hyaline vascular-type CD. TAFRO syndrome follows a more aggressive course, compared with iMCD-NOS, and there is no standard treatment.

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Castleman Disease

In the course of studying tumors of the thymus gland we came across a small group of cases in which enlarged mediastinal lymph nodes resembled thymic tumors grossly, radiologically and even microscopically …1In 1954, Dr Benjamin Castleman first described a rare and enigmatic disease that now carries his name. Over the past 60 years, this disease has captivated researchers, who have come to recognize unicentric and multicentric varieties and have uncovered different pathologic entities of the condition.

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Treatment of Kaposi Sarcoma Herpesvirus–Associated Multicentric Castleman Disease

Kaposi sarcoma herpesvirus (KSHV)-associated multicentric Castleman disease (MCD) is a rare, polyclonal lymphoproliferative disorder characterized by flares of inflammatory symptoms, edema, cytopenias, lymphadenopathy, and splenomegaly. Diagnosis requires a lymph node biopsy. Pathogenesis is related to dysregulated inflammatory cytokines, including human and viral interleukin-6. Rituximab alone or in combination with chemotherapy, such as liposomal doxorubicin, has led to an overall survival of over 90% at 5 years. Experimental approaches to treatment include virus activated cytotoxic therapy with high-dose zidovudine and valganciclovir and targeting human interleukin-6 activity. Despite successful treatment of KSHV-MCD, patients remain at high risk for developing non-Hodgkin lymphomas.

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The Peripheral Neuropathies of POEMS Syndrome and Castleman Disease

Polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, skin changes (POEMS) syndrome is a rare paraneoplastic disorder. The polyneuropathy can be the presenting symptom and is typically a painful, motor-predominant polyradiculoneuropathy often mimicking chronic inflammatory demyelinating polyradiculoneuropathy. The presence of a lambda monoclonal protein, elevated vascular endothelial growth factor, systemic features, and treatment resistance are clues to the diagnosis. Castleman disease (CD) is seen in a subset of these patients, and when present the neuropathy is similar but less severe. In contrast, in those patients with purely CD, the neuropathy is often a mild, painless distal sensory neuropathy.

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Diagnosis of Castleman Disease

Castleman disease (CD) is a rare and heterogenous group of disorders sharing in common an abnormal lymph node pathology. CD comprises distinct subtypes with different prognoses. Unicentric CD and multicentric CD are featured by specific systemic manifestations and may be associated with Kaposi sarcoma, non-Hodgkin and Hodgkin lymphoma, and POEMS syndrome. Multicentric CD is classically associated with systemic symptoms and poorer prognosis. In this article, the authors review how to diagnose the disease, keeping in context the clinical findings, biochemical changes and complications associated with CD.

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POEMS Syndrome

Treatment of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome should be directed at the underlying plasma cell clone with risk-adapted therapy based on the extent of the plasma cell disorder. Radiation therapy is effective for patients with a localized presentation, without bone marrow involvement, and 1 to 3 bone lesions. Patients with disseminated disease should receive, preferably, high-dose chemotherapy with peripheral blood transplantation. Low-dose melphalan and dexamethasone or new agents used in myeloma are also effective. The most promising agent is lenalidomide, which could be given before high-dose therapy or radiation to get rapid neurologic responses.

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The Role of Interleukin-6 in Castleman Disease

Since its discovery, improvements in treating Castleman disease and its variants have centered on interleukin-6 (IL-6). IL-6 was discovered from T-cell factors (BCDF or BSF-2), which induced B-cell maturation. Most symptoms of the plasma cell variant of Castleman disease are linked to the hyperfunction of IL-6, constitutively produced in the affected lymph nodes (1989), suggesting IL-6 is key in the pathogenesis of multicentric Castleman disease (MCD). The results of several studies have shown that most MCD symptoms and abnormal laboratory results are improved by anti-IL-6 MCD treatments, such as tocilizumab, a humanized anti-IL-6 receptor antibody, and siltuximab, an anti-IL-6 antibody.

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POEMS Syndrome

POEMS syndrome is a rare paraneoplastic syndrome secondary to a plasma cell dyscrasia. Recognition of a combination of peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasmaproliferative disorder, skin changes, papilledema, extravascular volume overload, sclerotic bone lesions, thrombocytosis, and Castleman disease is the first step in managing the disease. Increased blood levels of vascular endothelial growth factor are usually confirmatory. This rare disorder should not be missed, especially if the patient has a putative diagnosis of chronic inflammatory polyradiculoneuropathy, a lambda restricted monoclonal gammopathy, and thrombocytosis, and is not responding as expected to immunomodulatory therapy commonly used for chronic inflammatory polyradiculoneuropathy.

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Epidemiology of Castleman Disease

Castleman disease is a rare entity, including unicentric Castleman disease (UCD), human herpesvirus-8 plus Castleman disease (HHV-8+MCD), and idiopathic multicentric Castleman disease (iMCD). UCD is the most common at 16 per million person years and occurs at every age. HHV-8+MCD incidence varies widely, mostly affecting human immunodeficiency virus–positive men. iMCD is likely a more heterogeneous disease with an estimated incidence of 5 per million person years. Improved definitions should improve understanding of the epidemiology of Castleman disease and its subtypes.

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Interhemispheric motor interactions in hemiparetic children with perinatal stroke: Clinical correlates and effects of neuromodulation therapy

Perinatal ischemic stroke (PS) is the occlusion of arteries or veins that results in cerebral damage between 20 weeks gestation and 28 days of life (Raju, 2007; Nelson and Lynch, 2004). PS is common, occurring in >1:3000 live births, and accounts for most hemiparetic cerebral palsy (CP) (Kirton and DeVeber, 2013). Children with PS-induced hemiparetic CP typically manifest motor asymmetry and early hand preference in the first 4-6 months of life (Kirton et al., 2010b). How the motor system develops following such early unilateral brain injury is increasingly defined by animal (Martin et al., 2007) and human (Eyre, 2007; Staudt, 2007) studies.

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Nerve Ultrasound in Neurofibromatosis type 1: a Follow-up Study

Peripheral nerve sheath tumors (PNSTs) are one of the main characteristics of neurofibromatosis type 1 (NF1). They can undergo malignant transformation, which is a leading cause of mortality (Hirbe and Gutmann, 2014; Stucky et al., 2012).

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Founder mutation in IKBKAP gene causes vestibular impairment in familial dysautonomia

Familial dysautonomia (FD, OMIN #223900) is an inherited sensory and autonomic neuropathy (type III) mapped to the IKBKAP gene on chromosome 9 (Slaugenhaupt et al., 2001). Mutations in the gene affect the development and survival of primary afferent neurons (Norcliffe-Kaufmann et al., 2010; Macefield et al., 2011; Norcliffe-Kaufmann et al., 2017). Phenotypically, patients with FD have widespread somatosensory and autonomic deficits caused by impaired transmission of nociceptive, thermal, mechanical, chemical, metabolic, and osmotic information from the body to the brain (Norcliffe-Kaufmann et al., 2010; Gutierrez et al., 2015; Palma et al., 2015; Norcliffe-Kaufmann et al., 2017).

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Chronic deep brain stimulation normalizes scalp EEG activity in isolated dystonia

Dystonia is a movement disorder characterized by involuntary sustained or intermittent muscle contractions causing abnormal movements and postures (Albanese et al., 2013). It is recognized as a circuit disorder involving the basal ganglia, thalamus, cortex and cerebellum (Marsden et al., 1985; Vitek et al., 1999; Neychev et al., 2011). Deep brain stimulation (DBS) of the globus pallidus (GP; (Kupsch et al., 2006; Vidailhet et al., 2007; Volkmann et al., 2014)), subthalamic nucleus (STN; (Ostrem et al., 2011)) or thalamus (Fukaya et al., 2007; Mure et al., 2014) is able to improve dystonic symptoms, but its mechanism of action is unknown (Tisch et al., 2007; Vidailhet et al., 2013).

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Sepsis by Pasteurella multocida in an Elderly Immunocompetent Patient after a Cat Bite

Pasteurella multocida colonizes animal scratches and bites. This bacterium was described to cause sepsis or endocarditis mainly in immunocompromised patients. We report the case of a 92-year-old woman presenting at the Emergency Department with coma and fever a week after the bite of her cat. The cat bite was misdiagnosed at admission partly due to an underestimation of this event by the patient's relatives. An inflamed area localized at perimalleolar skin of the right leg was detected. Laboratory biomarkers of inflammation were elevated. The cerebral computed tomography (CT) scan with angiographic sequences showed a complete occlusion of right intracranial vertebral artery. Total body CT scan and abdominal echocardiography were negative for foci of infection. Three consecutive blood cultures were positive for Pasteurella multocida. A diagnosis of sepsis by Pasteurella multocida was made, and the patient recovered after a specific antimicrobial treatment. In order to confirm the animal transmission, the cat saliva was cultured and found positive for Pasteurella multocida with a similar antibiotic sensitivity to that isolated from the patient. In conclusion, the case of a patient with coma and fever after a cat bite was presented. The transmission of pathogens from pets has to be carefully considered as an important route of infection in immunocompetent patients.

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Neuroinvasive Infection from O117:K52:H-Escherichia coli following Acute Pyelonephritis

Spontaneous or nosocomial Escherichia coli meningitis remains rare in healthy adults but is still carrying a high mortality rate despite adapted antimicrobial treatment for susceptible strains. A 39-year-old woman was admitted to the hospital with severe subarachnoid haemorrhage complicated by acute hydrocephalus. On hospital day 10, she developed Streptococcus anginosus septicaemia and urinary tract infection due to a multisensitive strain of E. coli. This infection was successfully controlled by antimicrobial therapy. As a late complication in the neurosurgical ward (day 39), she developed fever, alteration of consciousness, and shock, leading to the diagnosis of bacterial meningitis. The culture of blood, cerebrospinal fluid, and urine grew positive for a multisensitive E. coli. The strain was identified as O117:K52:H, a serotype that was until now never associated with acute meningitis or brain abscesses. The source appeared to be the urinary tract with the demonstration of acute pyelonephritis. The patient died on day 94 from delayed complications of multiple brain abscesses.

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Abnormal functional connectivity of high-frequency rhythms in drug-naïve schizophrenia

Schizophrenia (SZ) is a severe and chronic mental disorder characterized by distinct positive symptoms (e.g., delusions and hallucinations), negative symptoms (e.g., diminished expression or abolition of motivation), and cognitive deficits. Although the exact pathophysiology remains unclear, recent neuroimaging-based evidence points to the "dysconnection hypothesis" as a core pathophysiological mechanism of SZ (Friston, 1998; Ribolsi et al., 2009; Schmitt et al., 2011; Stephan et al., 2006). According to this hypothesis, patients with SZ have an impaired brain network, which leads to deviation from optimum functional connectivity reflected in at least some symptoms of SZ (Ćurčić-Blake et al., 2017; Mulert et al., 2011).

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Metabolic Glycoengineering of Sialic Acid Using N-acyl-modified Mannosamines

Sialic acid is a typical monosaccharide-unit found in glycoconjugates. It is involved in a plethora of molecular and cellular interactions. Here we present a method to modify cell surface sialic acid expression using metabolic glycoengineering with N-acetylmannosamine derivatives.

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Surgically treated Hoffa Fractures with poor long-term functional results

Publication date: Available online 24 November 2017
Source:Injury
Author(s): Tolga Onay, Deniz Gülabi, İlker Çolak, Güven Bulut, Seyit Ali Gümüştaş, Gültekin Sıtkı Çeçen
IntroductionHoffa fractures are rare injuries and usually involve the lateral condyle. There are few published studies of large series of isolated coronal plane fractures of the femoral condyle. The aim of the study to determine the long-term functional outcomes and complications in surgically treated Hoffa fractures.Patients and methodsA retrospective review was made of 13 consecutive patients who were treated surgically for an isolated coronal plane fracture of the distal femur posterior condyle. The patients were evaluated with physical examination, PA and lateral radiographs and CT at the final follow-up examination. Functional outcome was evaluated with the OXFORD knee scoring system and Knee Society Score (KSS). Pain at rest and in activity was assessed using a Visual Analog Scale (VAS).ResultsThe patients comprised 11 males and 2 females with an average age at surgery of 27.5 years. The mean follow-up period was 93 months (range, 62 to 134 months). Mean time to fracture healing was 10 weeks (range, 8–12 weeks). The mean ROM was determined as 110°, mean KSS 78,4 and mean Oxford knee score 38,2. The mean KSS was 66,5 for medial Hoffa fracture patients and it was 83,8 for lateral Hoffa fracture patients. The mean Oxford knee score was 33,2 for medial Hoffa fracture patients and it was 40,4 for lateral Hoffa fracture patients. The mean VAS at rest and in activity was 1,1 and 2,9, respectively. Osteoarthritis was seen in 7 (54%) patients and avascular necrosis in 2 (15.4%). Varus instability was determined in 1 patient and valgus instability in 1 patient.ConclusionHoffa fractures may easily be overlooked if the radiological examination is not made carefully. Screw fixation was seen to provide enough biomechanical stability until the fracture healed. Arthrosis is a frequent long-term complication which worsens the functional results. Medial Hoffa fractures tend to have worse functional results than lateral Hoffa fractures.



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Efficacy of irrigant activation techniques in removing intracanal smear layer and debris from mature permanent teeth: A systematic review & meta-analysis

Abstract

Aims

To establish whether if Irrigant Activation Techniques (IAT) result in greater intracanal smear layer and debris removal than Conventional Needle Irrigation (CNI).

Methodology

Six electronic databases were searched to identify scanning-electron-microscopy studies evaluating smear layer and/or debris removal following use of Manual Dynamic Activation (MDA), Passive Ultrasonic Irrigation (PUI), Sonic Irrigation (SI) or Apical Negative Pressure (ANP) IATs in mature permanent teeth. Meta-analyses were performed for each canal segment (coronal, middle, apical and apical 1mm) in addition to subgroup analyses for individual IATs with respect to CNI. Outcomes were presented as Standardised-Mean-Differences (SMD) alongside 95%-Confidence Intervals (95%CI) and chi-squared analysis.

Results

From 252 citations, 16 studies were identified. The meta-analyses demonstrated significant improvements in coronal (SMD:1.15, 95%CI:0.72-1.57 / SMD:0.54, 95%CI:0.29-0.80), middle (SMD:1.30, 95%CI:0.59-2.53 / SMD:0.8, 95%CI:0.58-1.13) and apical thirds (SMD:1.22, 95%CI:0.83-1.62 / SMD:1.86, 95%CI:0.76-2.96) for smear layer and debris removal respectively. In the apical 1mm IATs improved cleanliness; however differences were insignificant (SMD:1.15, 95%CI:-0.47-2.77). Chi-squared analysis revealed heterogeneity scores of 79.3-92.8% and 0.0-93.5% for smear layer and debris removal respectively.

Conclusions

IATs improve intracanal cleanliness across a substantial portion of the canal and therefore their use is recommended throughout root canal preparation. However, current data is too heterogeneous to compare and identify superiority of an individual technique highlighting the need to standardise experimental protocols and develop a more representative research model to investigate the in impact of IATs on clinical outcomes and periapical healing following root canal treatment.

This article is protected by copyright. All rights reserved.

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Hemi-laryngeal Setup for Studying Vocal Fold Vibration in Three Dimensions

This paper introduces a protocol for the preparation of hemi-larynx specimens facilitating a multi-dimensional view of vocal fold vibration, in order to investigate various biophysical aspects of voice production in humans and non-human mammals.

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Prognosis of immune-tolerant phase chronic hepatitis B

We read with great surprise the article by Kim et al1  reporting high risks of hepatocellular carcinoma (HCC) and death in patients with untreated chronic hepatitis B who were classified by them as patients in 'immune-tolerant' (IT) phase. This conclusion contradicts to the general belief that there is little or no disease progression during the IT phase of chronic HBV infection, as best demonstrated in a 5-year histological follow-up study.2 Some issues of serious concern on this study, especially their IT phase patients, require clarification and further discussion to minimise misleading messages.

IT phase of perinatally acquired chronic HBV infection is typically seen in Asian children or young adults with high HBV DNA, normal alanine aminotransferase (ALT), hepatitis B e-antigen (HBeAg) seropositivity and normal or minimal liver histological changes. After age of 20–25 years, IT phase may gradually convert to immune clearance or immune active (IA) phase, which is characterised by intermittent...

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BRAF mutations might be more common than supposed in vulvar melanomas

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Visualization of dendritic cells’ responses in atopic dermatitis: Preventing effect of emollient

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Production of poly-γ-glutamic acid by a thermotolerant glutamate-independent strain and comparative analysis of the glutamate dependent difference

Poly-γ-glutamic acid (γ-PGA) is a promising microbial polymer with wide applications in industry, agriculture and medicine. In this study, a novel glutamate-independent γ-PGA producing strain with thermotolera...

http://ift.tt/2AwBaCr

Considering choline as methionine precursor, lipoproteins transporter, hepatic promoter and antioxidant agent in dairy cows

During the transition period, fatty liver syndrome may be caused in cows undergo negative energy balance, ketosis or hypocalcemia, retained placenta or mastitis problems. During the transition stage, movement ...

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Estimating annual prevalence of depression and anxiety disorder in multiple sclerosis using administrative data

Researchers have developed case definitions to estimate incidence and lifetime prevalence of depression and anxiety disorders in multiple sclerosis (MS) using administrative data. For policymakers however, the...

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Brucella seroprevalence in cattle near a wildlife reserve in Kenya

Brucellosis is caused by bacteria from the genus Brucella which infect human and domestic animals as well as wildlife. The Maasai Mara National Reserve has vast populations of wild ruminants such as buffaloes and...

http://ift.tt/2n6vkSL

Automated growth rate determination in high-throughput microbioreactor systems

The calculation of growth rates provides basic metric for biological fitness and is standard task when using microbioreactors (MBRs) in microbial phenotyping. MBRs easily produce huge data at high frequency fr...

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A child with distal (type 1) renal tubular acidosis presenting with progressive gross motor developmental regression and acute paralysis

Distal (Type 1) renal tubular acidosis (dRTA) is characterized by inability to secrete hydrogen irons from the distal tubule. The aetiology of dRTA is diverse and can be either inherited or acquired. Common cl...

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An Msh3 ATPase domain mutation has no effect on MMR function

To demonstrate that the Msh3 ATPase domain is required for DNA mismatch repair and tumor suppression in a murine model.

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'You can keep your hat on: a giant forehead trichilemmal cyst

Description

A 70-year-old man was referred to plastic surgery with a progressively enlarging lesion to his forehead. A small nodule had been present since 30 years. The patient had presented to his general practitioner at the time and had been reassured that this was a sebaceous cyst which warranted no further attention. As the lesion continued to grow over the intervening years, the patient did not seek any further medical attention and concealed the lesion under a cap.

On examination, he had a 5x6x6 cm pedunculated, fleshy exophytic tumour on his central forehead (figure 1A), with further nodules each measuring 2–3 cm diameter dotted across his scalp.

Figure 1

(A) Anterior view of the pedunculated forehead lesion. (B) Axial CT showing no intracranial component or bony erosion.

CT showed a heterogeneous midline scalp lesion abutting the outer table of the skull but with...

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Traumatic pneumocephaly: trapped air from where?

Traumatic pneumocephaly is literally defined as 'air in the head' after trauma. While this phenomenon has been well described in the literature, our case report is unique in describing diffuse pneumocephalus in the subaponeurotic space, subdural space, subarachnoid space, brain and ventricles without a break in the cranial vault: a 26-year-old man fell from a =9 meter scaffolding in a water tower. Following an arduous and delayed extrication, the patient was unresponsive with loss of pulse requiring intubation, cardiopulmonary resuscitation and release of tension pneumothorax with bilateral thoracostomy tubes. Examination remained poor with a Glasgow Coma Scale of 3. Immediate exploratory laparotomy was performed for a small right retroperitoneal haematoma on Focused Assessment with Sonography for Trauma. Postoperative imaging revealed diffuse pneumocephaly without facial fractures. This case presentation explores unusual causes of fistulous connections with the atmosphere that may lead to air trapped in and around the cranial vault.

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What is the cause of this fever? Malaria with concomitant pneumonia

A 43-year-old Hispanic woman presented to the clinic complaining of fever, chills and cough for 14 days. The patient reported a recent trip to Asia 12 days prior to presenting symptoms. Given her physical examination findings, she was treated empirically for community acquired pneumonia. Since her symptoms worsened despite the antibiotic, she was referred to the Emergency Department for further evaluation. The patient was ultimately diagnosed with pneumonia and malaria. When evaluating patients with history of recent travel, it is important to consider communicable diseases that are endemic to the areas visited, as well as multiple disease aetiologies for complicated and refractory cases.

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Tension pneumothorax and pneumoperitoneum after double-lumen endotracheal intubation

Description

A 75-year-old woman with a history of hypertension was admitted to our hospital for video-assisted thoracic surgery of the right caudal lung lobe because of a pT4N0M0 adenocarcinoma. After uneventful induction of anaesthesia, a difficult intubation was encountered due to a short stature and limited mobility of the neck. After multiple attempts a 35 French double-lumen tube was placed over a gum-elastic bougie with help of a video laryngoscope. To confirm correct placement a bronchoscopy was performed; however, the carina could not be visualised and the tube was repositioned several times.

Suddenly a swelling of the abdomen and subcutaneous emphysema in the neck were noticed, ventilation pressures increased, and the patient developed bradycardia. A tension pneumothorax was suspected and bilateral needle thoracentesis was performed. The double-lumen tube was replaced by a size 6.5 single-lumen tube. Bilateral thorax drains were placed and the patient was admitted to the intensive care....

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The impact of approaches in improving male partner involvement in the prevention of mother-to-child transmission of HIV on the uptake of maternal antiretroviral therapy among HIV-seropositive pregnant women in sub-Saharan Africa: a systematic review and meta-analysis

Objectives

To identify the approaches that are used in improving on male partner involvement in the prevention of mother-to-child transmission (PMTCT) of HIV and their impact on the uptake maternal antiretroviral therapy (ART) in sub-Saharan Africa (SSA).

Setting

This was a systematic review and meta-analysis of published studies carried out in SSA at all levels of healthcare (primary, secondary, tertiary and community).

Participants

The participants of the studies included were HIV-positive pregnant women and breastfeeding mothers with their male partners. Studies were included if they were conducted in SSA and mentioned an approach used in improving male partner involvement with data on the impact on the uptake of maternal ART uptake.

Outcomes

In the protocol, maternal ART uptake, infant prophylaxis, safe infant feeding options, condom use and family planning were envisaged. However, only maternal ART has been reported here due to limitations on the word count.

Results

From an initial 2316 non-duplicate articles, 17 articles were included in the systematic review and meta-analysis. In the combined model, the ORs for complex community interventions, enhanced psychosocial interventions, verbal encouragement and invitation letters were 4.22 (95% CI 2.27 to 7.77), 2.29 (95% CI 1.42 to 7.69), 2.39 (95% CI 1.26 to 4.53) and 1.21 (95% CI 0.89 to 1.63), respectively, whereas in the model using adjusted ORs, enhanced psychosocial interventions had a higher effect than any other intervention. The heterogeneity was moderate using adjusted ORs.

Conclusion

Enhanced psychosocial interventions and complex community interventions increase male partner involvement and the uptake of PMTCT services more than any other intervention. Invitation letters had no effect. More randomised trials and observational studies (that have adjusted for potential confounders) are needed in the future.

PROSPERO registration number

42016032673.

http://ift.tt/2BaPa1g

Impact of US smoke-free air laws on restaurants and bars by employer size: a panel study

Objectives

Thirty states have smoke-free air laws that ban smoking in restaurants and bars, covering nearly two-thirds of the US population. It is well established that these laws generally have a null or positive economic impact on restaurants and bars. However, all establishments in a geographic area are usually treated as a homogeneous group without considering the potential for differential effects by establishment characteristics. This study uses variation in smoke-free air laws over time to estimate their impact on employment in restaurants and bars with a focus on potential differences by employer size (number of employees). A two-pronged approach with a national-level and state-level analysis is used to take advantage of more granular data availability for a single state (North Carolina).

Design

Observational study using panel data.

Setting

1) US, 2) North Carolina

Interventions

Smoke-free air laws.

Outcome measures

State-level accommodation and food services employment for all 50 states and District of Columbia from 1990 through 2014 (Quarterly Census of Employment and Wages); county-level restaurant and bar employment in North Carolina from 2001 through 2014 (North Carolina Department of Commerce).

Results

There is no evidence of a redistributive effect of smoke-free air laws on restaurant and bar employment by employer size.

Conclusion

The lack of a redistributive effect is an important finding for policy-makers considering implementation or expansion of a smoke-free air law to protect employees and patrons from the dangers of exposure to secondhand smoke.

http://ift.tt/2BbbQyt

Epidemiology of obesity and overweight in sub-Saharan Africa: a protocol for a systematic review and meta-analysis

Introduction

Globally, overweight and obesity were estimated to cause 3.4 million deaths, 3.9% of years of life lost and 3.8% of disability-adjusted life years in 2010. Despite the fact that obesity and overweight is a problem of high-income countries, low- and middle-income countries (LMICs), in particular urban settings of sub-Saharan African countries, face the challenge of an increasing trend. The aim of this systematic review and meta-analysis will be to determine the prevalence of obesity and overweight individuals in sub-Saharan Africa and to help guide policy planners in the decision-making process for the increase in non-communicable diseases in Africa.

Methods and analyses

A comprehensive systematic review and meta-analysis of published studies on the prevalence of obesity and overweight in sub-Saharan Africa will be conducted. A computerised internet search using Medline/PubMed, Google Scholar and EMBASE databases and reference lists of previous prevalence studies and detailed search strategy and cross-checking of reference lists of published peer-reviewed articles will be conducted to identify all epidemiological and/or clinical studies published in English and French. We will use the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) statement for reporting. The overall effect (pooled estimated effect size) of the prevalence of obesity and overweight will be analysed using the Der Simonian–Laird random effects meta-analysis (random effects model) and the obesity proportion (with 95% CI) will be measured.

Ethics and dissemination

The underlying work is based on systematic reviews of published data and thus doed not require ethical review approval. The findings of the systematic review will be disseminated in different conferences and seminars and will be published in a reputable and refereed international peer-reviewed journal.

PROSPERO registration number

CRD42017064942.

http://ift.tt/2iPxhhx

Self-management of cardiac pain in women: an evidence map

Objective

To describe the current evidence related to the self-management of cardiac pain in women using the process and methodology of evidence mapping.

Design and setting

Literature search for studies that describe the self-management of cardiac pain in women greater than 18 years of age, managed in community, primary care or outpatient settings, published in English or a Scandinavian language between 1 January 1990 and 24 June 2016 using AMED, CINAHL, ERIC, EMBASE, MEDLINE, Proquest, PsychInfo, the Cochrane Library, Scopus, Swemed+, Web of Science, the Clinical Trials Registry, International Register of Controlled Trials, MetaRegister of Controlled Trials, theses and dissertations, published conference abstracts and relevant websites using GreyNet International, ISI proceedings, BIOSIS and Conference papers index. Two independent reviewers screened using predefined eligibility criteria. Included articles were classified according to study design, pain category, publication year, sample size, per cent women and mean age.

Interventions

Self-management interventions for cardiac pain or non-intervention studies that described views and perspectives of women who self-managed cardiac pain.

Primary and secondary outcomes measures

Outcomes included those related to knowledge, self-efficacy, function and health-related quality of life.

Results

The literature search identified 5940 unique articles, of which 220 were included in the evidence map. Only 22% (n=49) were intervention studies. Sixty-nine per cent (n=151) of the studies described cardiac pain related to obstructive coronary artery disease (CAD), 2% (n=5) non-obstructive CAD and 15% (n=34) postpercutaneous coronary intervention/cardiac surgery. Most were published after 2000, the median sample size was 90 with 25%–100% women and the mean age was 63 years.

Conclusions

Our evidence map suggests that while much is known about the differing presentations of obstructive cardiac pain in middle-aged women, little research focused on young and old women, non-obstructive cardiac pain or self-management interventions to assist women to manage cardiac pain.

PROSPERO registration number

CRD42016042806.

http://ift.tt/2BaZ3Md

How effective is community physical activity promotion in areas of deprivation for inactive adults with cardiovascular disease risk and/or mental health concerns? Study protocol for a pragmatic observational evaluation of the Active Herts' physical activity programme

Introduction

There is a high prevalence of inactive adults in the UK, and many suffer from conditions such as cardiovascular disease (CVD) or poor mental health. These coexist more frequently in areas of higher socioeconomic deprivation. There is a need to test the effectiveness, acceptability and sustainability of physical activity programmes. Active Herts uses novel evidence-based behaviour change techniques to target physical inactivity.

Methods and analysis

Active Herts is a community physical activity programme for inactive adults aged 16+ with one or more risk factors for CVD and/or a mild to moderate mental health condition. This evaluation will follow a mixed-methods longitudinal (baseline, and 3-month, 6-month and 12-month follow-ups) design. Pragmatic considerations mean delivery of the programme differs by locality. In two areas programme users will receive a behaviour change technique booklet, regular consultations, a booster phone call, motivational text messages and signposting to 12 weeks of exercise classes. In another two areas programme users will also receive 12 weeks of free tailored exercise classes, with optional exercise 'buddies' available. An outcome evaluation will assess changes in physical activity as the primary outcome, and sporting participation, sitting, well-being, psychological capability and reflective motivation as secondary outcomes. A process evaluation will explore the views of stakeholders, delivery staff and programme leads. Economic evaluation will examine the programme costs against the benefits gained in terms of reduced risk of morbidity.

Ethics and dissemination

This study was been approved by the Faculty of Medicine and Health Sciences Research Ethics Committee at the University of East Anglia. Informed written consent will be obtained from programme users in the evaluation. Results will be published in peer-reviewed journals, presented at conferences, and shared through the study website and local community outlets.

Trial registration number

ClinicalTrials.gov ID number: NCT03153098.

http://ift.tt/2Bbs3Dt

When has service provision for transient ischaemic attack improved enough? A discrete event simulation economic modelling study

Objectives

The aim of this study was to examine the impact of transient ischaemic attack (TIA) service modification in two hospitals on costs and clinical outcomes.

Design

Discrete event simulation model using data from routine electronic health records from 2011.

Participants

Patients with suspected TIA were followed from symptom onset to presentation, referral to specialist clinics, treatment and subsequent stroke.

Interventions

Included existing versus previous (less same day clinics) and hypothetical service reconfiguration (7-day service with less availability of clinics per day).

Outcome measures

The primary outcome of the model was the prevalence of major stroke after TIA. Secondary outcomes included service costs (including those of treating subsequent stroke) and time to treatment and attainment of national targets for service provision (proportion of high-risk patients (according to ABCD² score) seen within 24 hours).

Results

The estimated costs of previous service provision for 490 patients (aged 74±12 years, 48.9% female and 23.6% high risk) per year at each site were £340 000 and £368 000, respectively. This resulted in 31% of high-risk patients seen within 24 hours of referral (47/150) with a median time from referral to clinic attendance/treatment of 1.15 days (IQR 0.93–2.88). The costs associated with the existing and hypothetical services decreased by £5000 at one site and increased £21 000 at the other site. Target attainment was improved to 79% (118/150). However, the median time to clinic attendance was only reduced to 0.85 days (IQR 0.17–0.99) and thus no appreciable impact on the modelled incidence of major stroke was observed (10.7 per year, 99% CI 10.5 to 10.9 (previous service) vs 10.6 per year, 99% CI 10.4 to 10.8 (existing service)).

Conclusions

Reconfiguration of services for TIA is effective at increasing target attainment, but in services which are already working efficiently (treating patients within 1–2 days), it has little estimated impact on clinical outcomes and increased investment may not be worthwhile.

http://ift.tt/2iNZg1e

Monitoring of clinical strains and environmental fungal aerocontamination to prevent invasive aspergillosis infections in hospital during large deconstruction work: a protocol study

Introduction

Monitoring fungal aerocontamination is an essential measure to prevent severe invasive aspergillosis (IA) infections in hospitals. One central block among 32 blocks of Edouard Herriot Hospital (EHH) was entirely demolished in 2015, while care activities continued in surrounding blocks. The main objective was to undertake broad environmental monitoring and clinical surveillance of IA cases to document fungal dispersion during major deconstruction work and to assess clinical risk.

Methods and analysis

A daily environmental survey of fungal loads was conducted in eight wards located near the demolition site. Air was collected inside and outside selected wards by agar impact samplers. Daily spore concentrations were monitored continuously by volumetric samplers at a flow rate of 10 L.min^-1. Daily temperature, wind direction and speed as well as relative humidity were recorded by the French meteorological station Meteociel. Aspergillus fumigatus strains stored will be genotyped by multiple-locus, variable-number, tandem-repeat analysis. Antifungal susceptibility will be assessed by E-test strips on Roswell Park Memorial Institute medium supplemented with agar. Ascertaining the adequacy of current environmental monitoring techniques in hospital is of growing importance, considering the rising impact of fungal infections and of curative antifungal costs. The present study could improve the daily management of IA risk during major deconstruction work and generate new data to ameliorate and redefine current guidelines.

Ethics and dissemination

This study was approved by the clinical research and ethics committees of EHH.

http://ift.tt/2iOQfFg

Is there an association between vitamin D status and risk of chronic low back pain? A nested case-control analysis in the Nord-Trondelag Health Study

Objectives

To explore potential associations between vitamin D status and risk of chronic low back pain (LBP) in a Norwegian cohort, and to investigate whether relationships depend on the season of blood sample collection.

Design

A nested case–control study in a prospective data set.

Setting

The Norwegian community-based Nord-Trøndelag Health Study (HUNT). Data were collected in the HUNT2 (1995–1997) and HUNT3 (2006–2008) surveys.

Main outcome measure

Chronic LBP, defined as LBP persisting at least 3 months continuously during the past year.

Participants

Among individuals aged 19–55 years without LBP in HUNT2, a data set was generated including 1685 cases with LBP in HUNT3 and 3137 controls without LBP.

Methods

Blood samples from the participants collected in HUNT2 were analysed for serum 25-hydroxyvitamin D (25(OH)D) level. Associations with LBP in HUNT3 were evaluated by unconditional logistic regression analysis with adjustment for age, sex, work status, physical activity at work and in leisure time, education, smoking, and body mass index.

Results

No association between vitamin D status and risk of chronic LBP was found in the total data set (OR per 10 nmol/L 25(OH)D=1.01, 95% CI 0.97 to 1.06) or in individuals with blood samples collected in summer/autumn (OR per 10 nmol/L 25(OH)D=0.99, 95% CI 0.93 to 1.06). For blood samples drawn in winter/spring, associations differed significantly between women and men (p=0.004). Among women a positive association was seen (OR per 10 nmol/L 25(OH)D=1.11, 95% CI 1.02 to 1.20), but among men no significant association was observed (OR per 10 nmol/L 25(OH)D=0.90, 95% CI 0.81 to 1.01).

Conclusions

Overall, no association between vitamin D status and risk of LBP was demonstrated. The association suggested in women for the winter/spring season cannot be regarded as established.

http://ift.tt/2iOUWyQ

Interrupted versus continuous suturing for vesicourethral anastomosis during radical prostatectomy: protocol for a systematic review and meta-analysis

Introduction

Radical prostatectomy is the mainstay of treatment for prostate cancer. The vesicourethral anastomosis is a critical step, which most likely impacts urinary continence and urethral stenosis. To date, it still remains unclear whether interrupted and continuous suturing for the anastomosis have different outcomes. Therefore, the aim of this systematic review and meta-analysis is to compare different suture techniques for vesicourethral anastomosis in terms of surgical and functional parameters.

Methods and analysis

A comprehensive literature search will be conducted covering MEDLINE, Embase, Web of Science, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov. Studies comparing interrupted versus continuous suturing will be included in the analyses. No language restrictions will be applied. Screening, data extraction, statistical analysis and reporting will be done in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Quality assessment will be performed with the help of the Cochrane Collaboration's tool for assessing risk of bias and the Newcastle-Ottawa Scale for assessing quality of non-randomised studies. The quality of evidence will be evaluated with the Grading of Recommendations Assessment, Development and Evaluation. The primary outcome will be the time until removal of the urinary catheter. Secondary outcomes include rate of extravasation, length of hospital stay, time needed to perform the anastomosis, continence level at defined postoperative intervals and development of urethral strictures. Quantitative analysis will be calculated if meaningful.

Ethics and dissemination

In order to meet the highest ethical and methodological standards. we followed the PRISMA Protocol 2015 checklist. Each item was answered appropriately. For systematic reviews the ethical issues are strictly methodological as only data that were published earlier will be used. The full manuscript will be submitted to a peer-reviewed journal. Furthermore, the results will be presented on national and international congresses.

Trial registration number

International prospective register of systematic reviews PROSPERO CRD42017076126.

http://ift.tt/2iOMOhN

Smoking prevalence and attitudes towards smoking among Estonian physicians: results from cross-sectional studies in 2002 and 2014

Objectives

To explore smoking prevalence and attitudes towards smoking among Estonian physicians in 2002 and 2014.

Design

Two self-administered cross-sectional postal surveys were conducted among practising physicians in Estonia.

Participants

Initial sample consisted of all practising physicians in Estonia. The corrected response rate was 67.8% in 2002 and 53.1% in 2014. Present study sample was restricted to physicians younger than 65 years (n=2549 in 2002, n=2339 in 2014).

Methods

Age-standardised prevalence of smoking and prevalence of agreement with seven statements concerning attitudes towards smoking was determined. To analyse association of physicians' attitudes towards smoking with study year and smoking status, logistic regression analysis was used. Adjusted ORs of agreement with the seven statements were determined. Corresponding 95% CIs were calculated.

Results

The age-standardised prevalence of current smoking among men was 26.8% in 2002 and 15.3% in 2014, among women 10.4% and 5.8%, respectively. Compared with the year 2002, in 2014, prevalence of agreement with statements declaring harmfulness of smoking was higher and prevalence of agreement with statements approving smoking was lower. Adjusted ORs showed that compared with 2002, physicians' attitudes towards smoking were less favourable in 2014, and physicians' attitudes towards smoking were associated with their smoking status.

Conclusions

Compared with 2002, the age-standardised smoking prevalence among male and female physicians was lower, and attitudes towards smoking were less approving in 2014. The smoking physicians had more approving attitudes towards smoking than their non-smoking colleagues.

http://ift.tt/2Bbs3TZ

Dangguijakyak-san ameliorates memory deficits in ovariectomized mice by upregulating hippocampal estrogen synthesis

Dangguijakyak-san (DJS) is an herbal formulation that has been clinically applicable for treating postmenopausal symptoms and neurological disorders. It is reported that hippocampal estrogen attenuates memory ...

http://ift.tt/2n2BjaU

Nutritional supplements and herbal medicines for women with polycystic ovary syndrome; a systematic review and meta-analysis

Polycystic ovary syndrome (PCOS) is a common, reproductive endocrinopathy associated with serious short and long term health risks. Many women with PCOS use ingestible complementary medicines. This systematic ...

http://ift.tt/2zCRmC9

Cancers, Vol. 9, Pages 160: Integrative Bioinformatic Analysis of Transcriptomic Data Identifies Conserved Molecular Pathways Underlying Ionizing Radiation-Induced Bystander Effects (RIBE)

Cancers, Vol. 9, Pages 160: Integrative Bioinformatic Analysis of Transcriptomic Data Identifies Conserved Molecular Pathways Underlying Ionizing Radiation-Induced Bystander Effects (RIBE)

Cancers doi: 10.3390/cancers9120160

Authors: Constantinos Yeles Efstathios-Iason Vlachavas Olga Papadodima Eleftherios Pilalis Constantinos Vorgias Alexandros Georgakilas Aristotelis Chatziioannou

Ionizing radiation-induced bystander effects (RIBE) encompass a number of effects with potential for a plethora of damages in adjacent non-irradiated tissue. The cascade of molecular events is initiated in response to the exposure to ionizing radiation (IR), something that may occur during diagnostic or therapeutic medical applications. In order to better investigate these complex response mechanisms, we employed a unified framework integrating statistical microarray analysis, signal normalization, and translational bioinformatics functional analysis techniques. This approach was applied to several microarray datasets from Gene Expression Omnibus (GEO) related to RIBE. The analysis produced lists of differentially expressed genes, contrasting bystander and irradiated samples versus sham-irradiated controls. Furthermore, comparative molecular analysis through BioInfoMiner, which integrates advanced statistical enrichment and prioritization methodologies, revealed discrete biological processes, at the cellular level. For example, the negative regulation of growth, cellular response to Zn2+-Cd2+, and Wnt and NIK/NF-kappaB signaling, thus refining the description of the phenotypic landscape of RIBE. Our results provide a more solid understanding of RIBE cell-specific response patterns, especially in the case of high-LET radiations, like α-particles and carbon-ions.

http://ift.tt/2BbdnEH

Triple combination antibiotic therapy for carbapenemase-producing Klebsiella pneumoniae: a systematic review

The spread of carbapenemase-producing K. pneumoniae (CPKP) has become a significant problem worldwide. Combination therapy for CPKP is encouraging, but polymyxin resistance to many antibiotics is hampering effect...

http://ift.tt/2AvJySK

Six-month postoperative outcomes of intraoperative OCT-guided surgical cystotomy for refractory cystoid macular edema in diabetic eyes

http://ift.tt/2jhakU5

Fluorescent Immortalized Human Adipose Derived Stromal Cells (hASCs-TS/GFP+) for Studying Cell Drug Delivery Mediated by Microvesicles

Background: A new tool for the drug delivery is based on the use of Mesenchymal Stromal Cells (MSCs) loaded in vitro with anti-cancer drugs. Unfortunately, the restricted lifespan of MSCs represents a significant limitation to produce them in high amounts and for long time studies. Immortalized MSCs from adipose tissue (hASCs) have been generated as good source of cells with stable features. These cells could improve the development of standardized procedures for both in vitro and preclinical studies. Furthermore they facilitate procedures for preparing large amounts of secretome containing microvesicles (MVs).

Method: We used human adipose tissue derived MSCs immortalized with hTERT+SV40 (TS) genes and transfected with GFP (hASCs-TS/GFP+). This line was investigated for its ability to uptake and release anticancer drugs. Microvesicles associated to paclitaxel (MVs/PTX) were isolated, quantified, and tested on pancreatic cancer cells.

Results: The line hASCs-TS/GFP+ maintained the main mesenchymal characters and was able to uptake and release, in active form, both paclitaxel and gemcitabine. From paclitaxel loaded hASCs-TS/GFP+ cells were isolated microvesicles in sufficient amount to inhibit "in vitro" the proliferation of pancreatic tumor cells.

Conclusion: Our study suggests that human immortalized MSCs could be used for a large scale production of cells for mediated drug delivery. Moreover, the secretion of drug-associated MVs could represent a new way for producing new drug formulation by "biogenesis". In the context of the "advanced cell therapy procedure", the MVs/PTX production would use less resource and time and it could possibly contribute to simplification of GMP procedures.

http://ift.tt/2BaeuVd

Synthesis and Evaluation of Some Dibromoquinazoline-sulphonamide Hybrids and some Schiff´s Base Analogs for their Cytotoxic Activity

Background: Cancer is one of the most dangerous diseases with quite a high mortality rate. Many quinazoline derivatives show potent anticancer activity.

Objective: In this work our aim is to develop novel, safe and effective anticancer agents.

Method: New 6,8-dibromo-2-(4-chlorophenyl)-quinazoline-sulphonamide hybrids and some Schiff´s base analogs were synthesized, and their structures were confirmed by spectral and elemental analysis. Cytotoxicity of all synthesized compounds was evaluated on three cancer cell lines MCF7, HCT116 and HEPG2 using sulpharodamine- B assay method and doxorubicin as a reference drug. All tested compounds show promising cytotoxic activities on the three cell lines.

Results: Compound IXd was 2 times more active than doxorubicin on MCF7 cancer cells, while it was 3 times more potent than doxorubicin on HCT116 cancer cells. Compound IV was 2 times more active than doxorubicin while compound VI exhibited similar activity to doxorubicin on HEPG2 cell line. The most active compounds were tested against epidermal growth factor receptor tyrosine kinase (EGFR TK). Compounds IV, IXd, IXf show the most potent inhibitory percent 62.3, 91.1, 91.6 respectively. Compounds IV, V, VII, IXd, IXf caused a significant increase of CASP3 activity with range 86.5-37.6 %.

Conclusion: The present work led to the discovery of new cytotoxic compounds having quinazoline pharmacophore.

http://ift.tt/2iPSCHE

Improving the Hsp90 Inhibitors Containing 4-(2,4-Dihydroxyphenyl)-1,2,3-thiadiazole Scaffold: Synthesis, Affinity and Effect on Cancer Cells

Background: Human Hsp90 chaperone inhibitors are known to be potential anticancer drugs. Previously we have shown a couple of 5-aryl-4-(2,4-dihydroxyphenyl)-1,2,3-thiadiazoles to be promising anticancer agents.

Objective: To improve the compounds containing 4-(2,4-dihydroxyphenyl)-1,2,3-thiadiazole scaffold as human Hsp90 inhibitors.

Method: We employed chemical synthesis to obtain new compounds and assayed their binding to Hsp90 using the fluorescence thermal shift assay and used MTT assays to determine their effect on cancer cells.

Results: A series of compounds containing the 4-(2,4-dihydroxyphenyl)-1,2,3-thiadiazole scaffold were synthesized as Hsp90 inhibitors. Analysis of their binding to the recombinant N-terminal domain of Hsp90 revealed that four of these compounds bound to Hsp90 with Kd of 0.6 to 0.8 nM. The compounds fully inhibited the growth of all tested cancer cell lines: A549 (lung adenocarcinoma), IGR39 (melanoma), and U87 (glioblastoma), with the effective antiproliferative concentration (EC50) of the compounds reaching 0.35 µM.

Conclusion: This series of 14 novel and efficient Hsp90 inhibitors provided additional information on the structure-activity relationship of Hsp90 inhibitors and may be further developed into drugs targeting Hsp90.

http://ift.tt/2Bbg8Wf

Anti-Cancer Effects of Citalopram on Hepatocellular Carcinoma Cells Occur via Cytochrome C Release and the Activation of NF-kB

Background: Evidence has been provided of the anti-proliferative activity of citalopram against some cancer cells.

Objective: The apoptotic impact of citalopram, an antidepressant, against liver hepatocellular carcinoma cell line HepG2 was investigated in relation to the oxidative pathway and nuclear factor (NF)κB activation.

Method: The cytotoxic effects of citalopram on HepG2 cells were determined by MTT assay. Reactive oxygen species (ROS) formation and cytochrome c release were measured following treatment with citalopram. Apoptosis analysis and Bax and Bcl-­2 mRNA and protein levels were also determined.

Results: The cytotoxic effects of different concentrations of citalopram on HepG2 cells were observed as a reduction in cell viability and an increase in ROS formation. Citalopram caused an increase in mitochondrial Bax levels and a decrease in Bcl2 levels and also caused cytochrome c release. Moreover, DAPI staining and flow cytometry assays revealed citalopram-induced apoptosis in HepG2 cells. Oxidant scavengers and Bay 11-7082 (an irreversible inhibitor of NFκB activation) prevented the citalopram-associated cell death, increased BAX and decreased Bcl2.

Conclusion: Outcomes from current study suggest that citalopram might exhibit apoptotic effect against hepatocellular carcinoma cell line by induction of cell death through cytochrome c release and ROS-dependent activation of NFκB.

http://ift.tt/2iQ19ut

Evaluation of the Anticancer Activities of the Plant Alkaloids Sanguinarine and Chelerythrine in Human Breast Adenocarcinoma Cells

Background: Breast cancer is associated with a high mortality rate around the world due to its aggressiveness and high resistance to conventional therapies. Sanguinarine (SAN) and Chelerythrine (CHE) are plant alkaloids extracted from Sanguinaria canadensis and Macleaya cordata, which have been studied for their bioactivities.

Objective: To determine the anticancer activities of Sanguinarine (SAN) and Chelerythrine (CHE) plant alkaloids.

Method: The MTT assay, the alkaline comet assay and cell cycle analyses by flow cytometry were performed.

Results: It was observed that SAN was cytotoxic to human breast adenocarcinoma cells (MCF-7) at concentrations of 7.5 µM (24 and 48 hours), effectively reducing cell viability from the concentration of 10 µM for 24 hours and 7.5 µM for 48 hours, by the MTT test. CHE, in turn, was cytotoxic at concentrations of 10 and 20 µM (48 hours), but did not compromise the cellular viability. The comet assay indicated that SAN was genotoxic to the MCF-7 cells, with a significant increment of damage at 10 µM, while none of the tested concentrations of CHE showed a genotoxic effect. The flow cytometry analysis indicated that no cell cycle arrest was caused by both alkaloids, but SAN 10 µM induced a sub-G1 cell population.

Conclusion: The results of cytotoxicity, genotoxicity and cell cycle monitoring that are presented in this paper have suggested that SAN has more of a chemotherapeutic activity, as well as having the potential for the development of new therapies for breast cancer, when compared to CHE.

http://ift.tt/2BaeiVZ

1, 3, 6-Trihydroxy-7-Methyl-9, 10-Anthracenedione Isolated from genus Lindera with Anti-Cancer Activity

Background: Natural products inhibiting fatty acid synthase are potential therapeutic agents to treat cancer.

Objective: To investigate the chemical constituents of the root tubers of Lindera aggregate and the stems of Linderanacusua, and to find natural inhibitors on the expression level on fatty acid synthase in human breast cancer MDA-MB-231 cells.

Methods: The isolation and purification of the extracts were conducted by the methods of percolation and partition extraction, silica and gel column chromatography, recrystallization and by NMR and spectroscopic analysis method. The cell viability was assessed by Cell Counting Kit assay.

Results: Seven compounds were elucidated, mainly including five sesquiterpenes, one anthraquinoe and one γ -butanolide, in which compounds 6 was firstly reported from genus Lindera, and compound 7 was isolated from Linderanacusuafor the first time. Among them, 1,3,6-Trihydroxy-7-methyl-9,10-anthracenedione (TMA, compound 6) showed strong inhibitory effect on the expression level on fatty acid synthase in human breast cancer MDA-MB-231 cells. In addition, TMA was found to reduce breast cancer cells viability dosedependently.

Conclusion: The fatty acid synthase was a potent therapeutic target for cancers, these findings suggest that TMA has the application potential for treating human cancers.

http://ift.tt/2iOEI8W