Management of cardiovascular disease in patients with psoriasis.

Management of cardiovascular disease in patients with psoriasis.

Expert Opin Pharmacother. 2016 May 18;

Authors: Egeberg A, Skov L

Abstract
Introduction Patients with psoriasis have an increased incidence and prevalence of cardiovascular (CV) risk factors, and CV undertreatment in these patients is a well-established problem. The link between psoriasis and CV disease is present on a pathogenic level, as well as due to modifiable lifestyle factors such as smoking and alcohol abuse. Areas covered In this manuscript we describe the evidence associating psoriasis with CV disease, as well as the pharmacological and non-pharmacological treatment of CV risk factors including the CV effects of anti-psoriatic therapy and vice versa. Expert opinion Current guidelines recommend that patients with psoriasis are screened for CV risk factors, and recommend smoking cessation, reduced alcohol consumption, altering of lifestyle to move to a normal-weight body-mass index, exercising 3 times a week for 30 minutes, and monitoring and modifying cholesterol levels, respectively. While the current sum of evidence is not sufficient to recommend specific therapies for psoriasis solely based on their potential CV impact, some guidelines have suggested a 1.5 multiplication factor, in patients with severe psoriasis, to the Framingham risk score. Indeed, the importance of screening for CV risk factors and strict adherence to established primary and secondary preventive measures in these patients should be emphasized.

PMID: 27192114 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/209GEWt
via IFTTT

Can new treatment developments combat resistance in malaria?

Can new treatment developments combat resistance in malaria?

Expert Opin Pharmacother. 2016 May 18;

Authors: White NJ

PMID: 27191998 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1TpgddB
via IFTTT

Paediatric Tuberculosis at a Referral Hospital in Istanbul: Analysis of 250 Cases

Background. Tuberculosis (TB) still remains a growing public health problem globally. TB in children is often diagnosed clinically. Methods. We conducted a retrospective chart review of children with TB from November 2004 through December 2010 to determine the appropriateness of using contact history and diagnostic testing. Results. A total of 250 children with TB were identified. One hundred and sixty-two children had only pulmonary disease while 39 had features of both extrapulmonary and pulmonary TB. Mean age was 7.8 years. Thirty-six patients had known contacts. The index case/cases were first-degree relatives in 75%. Sixteen patients who were symptomless were yielded by contact investigation of newly identified TB cases. Tuberculin skin test positivity was 53.3%. Acid-fast bacilli smear positivity was 13.1%, and culture positivity was 18.7%. Twenty-six patients had histopathology of nonrespiratory specimens (lymph nodes and other tissues) showing granulomatous inflammation and caseous necrosis consistent with TB. Conclusions. Presence of contact history directed us to search for TB in children with nonspecific symptoms even if physical examinations were normal. Some children who were close contacts to TB cases were identified to have TB before development of symptoms.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1rVVFQN
via IFTTT

Increased Oxidative Stress and Inflammation Independent of Body Adiposity in Diabetic and Nondiabetic Controls in falciparum Malaria

Information on the extent to which oxidative stress and inflammation occur in the presence of falciparum malaria and type 2 diabetes mellitus in the same individual is limited. This study sought to investigate the extent of inflammation and oxidative stress in adult uncomplicated malaria by measuring fasting levels of lipid peroxides, C-reactive protein (CRP), and total antioxidant power (TAP) before and during falciparum malaria, in 100 respondents with type 2 diabetes and 100 age-matched controls in the Cape Coast metropolis of Ghana. Also, body adiposity index, body mass index, and waist-to-hip ratio were computed. Before and during falciparum malaria, diabetes patients exhibited higher () levels of CRP and peroxides than controls but TAP and BAI were comparable () between the two groups. Baseline CRP correlated positively (, ) with peroxide only in the diabetic group. During malaria, TAP level in both study groups declined () by 80% of their baseline levels. CRP correlated negatively (, ) with TAP in the control but not the diabetic group. Uncomplicated falciparum malaria elevated inflammation and peroxidation but decreased antioxidant power independent of adiposity. This finding may have implication on cardiovascular health.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/209FZUR
via IFTTT

Advances in Confocal Microscopy of the Eye

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1sAVrz8
via IFTTT

Giant mesenterial gastrointestinal stromal tumour mimicking a permagna hernia: a wolf in sheep's clothing

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1ONQVH4
via IFTTT

A tale of two anomalies: fourth branchial cleft cyst with thyroid hemiagenesis

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1qvT9zd
via IFTTT

Inflammatory myofibroblastic tumour of sigmoid mesocolon in a child

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1ONQLQ0
via IFTTT

Sacral nerve stimulation for faecal incontinence: medium-term follow-up from a single institution

Background

Most studies on sacral nerve stimulation (SNS) are either single-centre with small numbers of patients or multi-centre studies. We present the medium-term follow-up results from a single centre for 127 patients undergoing SNS.

Methods

Consecutive patients treated with SNS for faecal incontinence had preoperative baseline St Mark's continence scores, faecal incontinence quality of life (FIQL) measures and anorectal physiology studies. Follow-up was a postal questionnaire concerning continence, FIQL, patient-perceived change in bowel control (−5 to +5 where 0 is no change), overall satisfaction (0–10 visual analogue scale) and use of medications.

Results

A total of 166 patients underwent temporary nerve stimulation testing, of which 112 progressed to a permanent implantable pulse generator (IPG). Fifteen received an IPG without the testing phase, hence 127 patients in total. Fourteen had the IPG removed, four were deceased, leaving 109 for assessment; 91 (83%) responded to the survey. Mean follow-up was 2.7 years (range: 2 months–8.5 years). Mean baseline St Mark's continence score was 14.4, and mean follow-up score was 10.3 (P < 0.01). FIQL improved in all domains (P < 0.001). Patient-reported improved bowel control mean score was +3.2 (95% CI: 2.9, 3.55). Median satisfaction score was 8.0 (range: 0–10). Complications included 17 lead dislodgements, seven superficial infections, five infections requiring surgery and five repositioning of a rotated IPG. Thirty-two patients used loperamide and 34 used fibre supplements.

Conclusion

In this observational study, limited by the absence of a placebo control group, SNS significantly improved continence and quality of life, and patient satisfaction was high.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1qvTr9v
via IFTTT

upper respiratory tract infection; +41 new citations

41 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

upper respiratory tract infection

These pubmed results were generated on 2016/05/19

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Tlxdio
via IFTTT

A cluster randomised controlled trial evaluating the effectiveness of eHealth-supported patient recruitment in primary care research: the TRANSFoRm study protocol.

Related Articles

A cluster randomised controlled trial evaluating the effectiveness of eHealth-supported patient recruitment in primary care research: the TRANSFoRm study protocol.

Implement Sci. 2015;10:15

Authors: Mastellos N, Andreasson A, Huckvale K, Larsen M, Curcin V, Car J, Agreus L, Delaney B

Abstract
BACKGROUND: Opportunistic recruitment is a highly laborious and time-consuming process that is currently performed manually, increasing the workload of already busy practitioners and resulting in many studies failing to achieve their recruitment targets. The Translational Medicine and Patient Safety in Europe (TRANSFoRm) platform enables automated recruitment, data collection and follow-up of patients, potentially improving the efficiency, time and costs of clinical research. This study aims to assess the effectiveness of TRANSFoRm in improving patient recruitment and follow-up in primary care trials.
METHODS/DESIGN: This multi-centre, parallel-arm cluster randomised controlled trial will compare TRANSFoRm-supported with standard opportunistic recruitment. Participants will be general practitioners and patients with gastro-oesophageal reflux disease from 40 primary care centres in five European countries. Randomisation will take place at the care centre level. The intervention arm will use the TRANSFoRm tools for recruitment, baseline data collection and follow-up. The control arm will use web-based case report forms and paper self-completed questionnaires. The primary outcome will be the proportion of eligible patients successfully recruited at the end of the 16-week recruitment period. Secondary outcomes will include the proportion of recruited patients with complete baseline and follow-up data and the proportion of participants withdrawn or lost to follow-up. The study will also include an economic evaluation and measures of technology acceptance and user experience.
DISCUSSION: The study should shed light on the use of eHealth to improve the effectiveness of recruitment and follow-up in primary care research and provide an evidence base for future eHealth-supported recruitment initiatives. Reporting of results is expected in October 2015.
TRIAL REGISTRATION: EudraCT: 2014-001314-25.

PMID: 25648301 [PubMed - indexed for MEDLINE]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1U10OA7
via IFTTT

Residual fundus or neofundus after laparoscopic sleeve gastrectomy: is fundectomy safe and effective as revision surgery?

Related Articles

Residual fundus or neofundus after laparoscopic sleeve gastrectomy: is fundectomy safe and effective as revision surgery?

Surg Endosc. 2015 Oct;29(10):2899-903

Authors: Silecchia G, De Angelis F, Rizzello M, Albanese A, Longo F, Foletto M

Abstract
INTRODUCTION: Up to 30 % of patients who have undergone laparoscopic sleeve gastrectomy require revision surgery for inadequate weight loss, weight regain, and/or the development of severe upper gastrointestinal symptoms. The aim of this retrospective study was to evaluate the safety and efficacy of laparoscopic fundectomy (LF) in cases of a residual fundus/neofundus development regarding GERD symptoms.
METHODS: The study group comprised 19 patients (17 female; mean BMI 35.4 kg/m(2)) divided into 2 groups. Group A (n = 10) patients with severe GERD and evidence of residual fundus/neofundus, Hiatal hernia with good results in terms of weight loss. Group B (n = 9) patients with severe GERD, a residual fundus/neofundus, inadequate weight loss or weight regain. Fundectomy was indicated when a residual fundus/neofundus was associated with severe GERD symptoms. The presence of a residual fundus/neofundus was assessed by a barium swallow and/or multislice computed tomography.
RESULTS: No mortality or intra-operative complications occurred. Five postoperative complications occurred: 2 cases of bleeding, 1 mid-gastric stenosis and 2 leaks (10.5 %). All patients experienced improvements in their GERD symptoms and stopped PPI treatment. Group B exhibited an additional %EWL of 53.4 % at 24 months.
CONCLUSION: LF and cruroplasty is feasible and has good results in terms of GERD symptoms control and additional weight loss. The high rate of postoperative complications observed in this series remains a matter of concern. A re-sleeve procedure might be considered as an alternative to RYGB/DS conversion restricted to selected patients.

PMID: 25480629 [PubMed - indexed for MEDLINE]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/23Y8l5B
via IFTTT

Prevention of Postoperative Cerebrospinal Fluid Leaks After Translabyrinthine Tumor Resection With Resorbable Mesh Cranioplasty.

Related Articles

Prevention of Postoperative Cerebrospinal Fluid Leaks After Translabyrinthine Tumor Resection With Resorbable Mesh Cranioplasty.

Otol Neurotol. 2015 Sep;36(9):1537-42

Authors: Hunter JB, Sweeney AD, Carlson ML, Wanna GB, Rivas A, Weaver KD, Chambless LB, Thompson RS, Haynes DS, Bennett ML

Abstract
OBJECTIVES: To evaluate the effectiveness of resorbable mesh cranioplasty at reducing postoperative cerebrospinal fluid (CSF) leak and pseudomeningocele formation after translabyrinthine tumor resection.
STUDY DESIGN: Case series with chart review.
SETTING: Tertiary academic referral center.
PATIENTS: Fifty-three consecutive cases using a resorbable mesh cranioplasty after translabyrinthine tumor resection were reviewed.
INTERVENTION: Temporal bone defects were repaired with a dural substitute, layered fat graft, and a resorbable mesh plate secured with screws.
MAIN OUTCOME MEASURES: Primary outcome measures included the incidence of postoperative CSF wound leak or rhinorrhea, pseudomeningocele formation, and surgical site infection.
RESULTS: Fifty-three cases (average age, 54.0 yr; range, 19.3-75.1 yr) were analyzed. The average body mass index was 30.8 kg/m2 (range, 17.9-48.3 kg/m2), and the average tumor size was 18.8 mm (range, 8-38 mm). One patient (1.9%) experienced CSF rhinorrhea on postoperative Day 16, which resolved after transmastoid middle ear and eustachian tube packing. One patient (1.9%) experienced a surgical site infection requiring surgical debridement and mesh removal 4 months after surgery. Compared with 1,441 prior translabyrinthine surgeries analyzed from our institution using a traditional fat graft closure without mesh, the rate of postoperative CSF leak was significantly less using the resorbable mesh cranioplasty technique (p = 0.0483).
CONCLUSION: Resorbable mesh cranioplasty is a safe and effective method to reduce postoperative CSF leak and pseudomeningocele formation after translabyrinthine craniotomy for tumor excision.

PMID: 26208128 [PubMed - indexed for MEDLINE]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1U1fJHu
via IFTTT

JC Polyomavirus Abundance and Distribution in Progressive Multifocal Leukoencephalopathy (PML) Brain Tissue Implicates Myelin Sheath in Intracerebral Dissemination of Infection.

JC Polyomavirus Abundance and Distribution in Progressive Multifocal Leukoencephalopathy (PML) Brain Tissue Implicates Myelin Sheath in Intracerebral Dissemination of Infection.

PLoS One. 2016;11(5):e0155897

Authors: Wharton KA, Quigley C, Themeles M, Dunstan RW, Doyle K, Cahir-McFarland E, Wei J, Buko A, Reid CE, Sun C, Carmillo P, Sur G, Carulli JP, Mansfield KG, Westmoreland SV, Staugaitis SM, Fox RJ, Meier W, Goelz SE

Abstract
Over half of adults are seropositive for JC polyomavirus (JCV), but rare individuals develop progressive multifocal leukoencephalopathy (PML), a demyelinating JCV infection of the central nervous system. Previously, PML was primarily seen in immunosuppressed patients with AIDS or certain cancers, but it has recently emerged as a drug safety issue through its association with diverse immunomodulatory therapies. To better understand the relationship between the JCV life cycle and PML pathology, we studied autopsy brain tissue from a 70-year-old psoriasis patient on the integrin alpha-L inhibitor efalizumab following a ~2 month clinical course of PML. Sequence analysis of lesional brain tissue identified PML-associated viral mutations in regulatory (non-coding control region) DNA, capsid protein VP1, and the regulatory agnoprotein, as well as 9 novel mutations in capsid protein VP2, indicating rampant viral evolution. Nine samples, including three gross PML lesions and normal-appearing adjacent tissues, were characterized by histopathology and subject to quantitative genomic, proteomic, and molecular localization analyses. We observed a striking correlation between the spatial extent of demyelination, axonal destruction, and dispersion of JCV along white matter myelin sheath. Our observations in this case, as well as in a case of PML-like disease in an immunocompromised rhesus macaque, suggest that long-range spread of polyomavirus and axonal destruction in PML might involve extracellular association between virus and the white matter myelin sheath.

PMID: 27191595 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1TqOvOR
via IFTTT

Comparative Analysis of Head and Neck and Non-Head and Neck Malignant Peripheral Nerve Sheath Tumors.

Related Articles

Comparative Analysis of Head and Neck and Non-Head and Neck Malignant Peripheral Nerve Sheath Tumors.

Otolaryngol Head Neck Surg. 2016 Jan;154(1):113-20

Authors: Patel TD, Shaigany K, Fang CH, Park RC, Baredes S, Eloy JA

Abstract
OBJECTIVES: Malignant peripheral nerve sheath tumors (MPNSTs) are a group of tumors that arise from peripheral nerves or from the various elements of the nerve sheath, including Schwann cells and perineural fibroblasts. Head and neck MPNSTs (HN-MPNSTs) are rare, accounting for 8% to 16% of all soft tissue sarcomas. This study analyzes the demographic, clinicopathologic, and survival characteristics of HN-MPNSTs and establishes comparisons with MPNSTs at other body sites (other-MPNSTs).
STUDY DESIGN: Analysis of population-based tumor registry.
SETTING: Academic medical center.
SUBJECTS AND METHODS: The SEER database (Surveillance, Epidemiology, and End Results; 1973-2012) was queried for HN-MPNSTs (324 cases) and other-MPNSTs (1680 cases). Data were analyzed comparatively with respect to various demographic and clinicopathologic factors. Disease-specific survival was analyzed with the Kaplan-Meier model.
RESULTS: Mean age at diagnosis for HN-MPNST was 49.1 years, compared with 46.1 years for other-MPNSTs (P = .0169). There was a sex predilection for males in HN-MPNSTs (60.2%) versus a female predilection for other-MPNSTs (54.2%; P < .0001). Average tumor size for HN-MPNSTs was 4.9 cm, compared with 8.7 cm for other-MPNSTs (P < .0001). HN-MPNSTs were more commonly of low histologic grade types, whereas other-MPNSTs were mostly of high histologic grade (P = .0073). HN-MPNSTs had a higher 5-year disease-specific survival than other-MPNSTs (65.1% vs 57.4%; P = .0209).
CONCLUSIONS: HN-MPNSTs are rare entities. This study represents the largest series of HN-MPNSTs to date. Although HN-MPNSTs and other-MPNSTs share a common histology, there are important clinical differences between the 2 groups.

PMID: 26408559 [PubMed - indexed for MEDLINE]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Tlx3Yn
via IFTTT

Apoptosis of Hepatocellular Carcinoma Cells Induced by Nanoencapsulated Polysaccharides Extracted from Antrodia Camphorata.

Related Articles

Apoptosis of Hepatocellular Carcinoma Cells Induced by Nanoencapsulated Polysaccharides Extracted from Antrodia Camphorata.

PLoS One. 2015;10(9):e0136782

Authors: Chang JS, Kuo HP, Chang KL, Kong ZL

Abstract
Antrodia camphorata is a well-known medicinal mushroom in Taiwan and has been studied for decades, especially with focus on anti-cancer activity. Polysaccharides are the major bioactive compounds reported with anti-cancer activity, but the debates on how they target cells still remain. Research addressing the encapsulation of polysaccharides from A. camphorata extract (ACE) to enhance anti-cancer activity is rare. In this study, ACE polysaccharides were nano-encapsulated in chitosan-silica and silica (expressed as ACE/CS and ACE/S, respectively) to evaluate the apoptosis effect on a hepatoma cell line (Hep G2). The results showed that ACE polysaccharides, ACE/CS and ACE/S all could damage the Hep G2 cell membrane and cause cell death, especially in the ACE/CS group. In apoptosis assays, DNA fragmentation and sub-G1 phase populations were increased, and the mitochondrial membrane potential decreased significantly after treatments. ACE/CS and ACE/S could also increase reactive oxygen species (ROS) generation, induce Fas/APO-1 (apoptosis antigen 1) expression and elevate the proteolytic activities of caspase-3, caspase-8 and caspase-9 in Hep G2 cells. Unsurprisingly, ACE/CS induced a similar apoptosis mechanism at a lower dosage (ACE polysaccharides = 13.2 μg/mL) than those of ACE/S (ACE polysaccharides = 21.2 μg/mL) and ACE polysaccharides (25 μg/mL). Therefore, the encapsulation of ACE polysaccharides by chitosan-silica nanoparticles may provide a viable approach for enhancing anti-tumor efficacy in liver cancer cells.

PMID: 26327534 [PubMed - indexed for MEDLINE]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1TlwWw7
via IFTTT

Inhibition of Pediatric Glioblastoma Tumor Growth by the Anti-Cancer Agent OKN-007 in Orthotopic Mouse Xenografts.

Related Articles

Inhibition of Pediatric Glioblastoma Tumor Growth by the Anti-Cancer Agent OKN-007 in Orthotopic Mouse Xenografts.

PLoS One. 2015;10(8):e0134276

Authors: Coutinho de Souza P, Mallory S, Smith N, Saunders D, Li XN, McNall-Knapp RY, Fung KM, Towner RA

Abstract
Pediatric glioblastomas (pGBM), although rare, are one of the leading causes of cancer-related deaths in children, with tumors essentially refractory to existing treatments. Here, we describe the use of conventional and advanced in vivo magnetic resonance imaging (MRI) techniques to assess a novel orthotopic xenograft pGBM mouse (IC-3752GBM patient-derived culture) model, and to monitor the effects of the anti-cancer agent OKN-007 as an inhibitor of pGBM tumor growth. Immunohistochemistry support data is also presented for cell proliferation and tumor growth signaling. OKN-007 was found to significantly decrease tumor volumes (p<0.05) and increase animal survival (p<0.05) in all OKN-007-treated mice compared to untreated animals. In a responsive cohort of treated animals, OKN-007 was able to significantly decrease tumor volumes (p<0.0001), increase survival (p<0.001), and increase diffusion (p<0.01) and perfusion rates (p<0.05). OKN-007 also significantly reduced lipid tumor metabolism in responsive animals [(Lip1.3 and Lip0.9)-to-creatine ratio (p<0.05)], as well as significantly decrease tumor cell proliferation (p<0.05) and microvessel density (p<0.05). Furthermore, in relationship to the PDGFRα pathway, OKN-007 was able to significantly decrease SULF2 (p<0.05) and PDGFR-α (platelet-derived growth factor receptor-α) (p<0.05) immunoexpression, and significantly increase decorin expression (p<0.05) in responsive mice. This study indicates that OKN-007 may be an effective anti-cancer agent for some patients with pGBMs by inhibiting cell proliferation and angiogenesis, possibly via the PDGFRα pathway, and could be considered as an additional therapy for pediatric brain tumor patients.

PMID: 26248280 [PubMed - indexed for MEDLINE]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1TlwYny
via IFTTT

Unresectable Recurrent Squamous Cell Carcinoma of the Temporal Bone Treated by Induction Chemotherapy Followed by Concurrent Chemo-Reirradiation: A Case Report and Review of the Literature.

Related Articles

Unresectable Recurrent Squamous Cell Carcinoma of the Temporal Bone Treated by Induction Chemotherapy Followed by Concurrent Chemo-Reirradiation: A Case Report and Review of the Literature.

Otol Neurotol. 2015 Sep;36(9):1543-6

Authors: Kun M, Xinxin Z, Feifan Z, Lin M

Abstract
OBJECTIVE: To report a rare case of recurrent temporal bone carcinoma encasing the carotid artery.
PATIENT: A 54-year-old man underwent mastoidectomy combined with adjuvant chemoradiotherapy of squamous cell carcinoma of the temporal bone. He developed metastatic disease and received parotidectomy and lymph node dissection. Three months later, the magnetic resonance imaging scan showed that the tumor had relapsed and invaded the carotid artery.
INTERVENTION: The patient completed TPF-C induction chemotherapy (docetaxel, cisplatin, 5-fluorouracil, cetuximab), followed by concurrent chemotherapy with reirradiation.
RESULTS: Magnetic resonance imaging revealed a complete response of tumor 1 month after treatment. The patient had no detectable recurrence after 53 months of follow-up.
CONCLUSION: Concurrent chemotherapy with reirradiation is a potential curative treatment option for patients who have unresectable recurrent squamous cell carcinoma of the temporal bone.

PMID: 26208130 [PubMed - indexed for MEDLINE]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1TqOsCp
via IFTTT

Palliative systemic therapy for young women with metastatic breast cancer.

Related Articles

Palliative systemic therapy for young women with metastatic breast cancer.

Curr Opin Support Palliat Care. 2015 Sep;9(3):301-7

Authors: Eng LG, Dawood S, Dent R

Abstract
PURPOSE OF REVIEW: Breast cancer in young women age less than 40 years remains a relatively rare disease. Emerging data suggest that the biology of breast cancer in younger women may differ from that of older women. Although metastatic breast cancer remains incurable, it is definitely treatable; especially in this era of emerging novel therapeutics.
RECENT FINDINGS: Most women have hormone receptor-positive disease and strategies that interfere with proliferation and the PI3 kinase pathway are reporting exciting results. The prognosis of the metastatic HER2 subtype has been extended to a median survival of 56 months with dual HER2 targeting agents in the first-line setting. Finally, triple negative breast cancer has an enlarging range of therapeutic options including immunotherapy, antiangiogenesis therapy, and targeted therapies including agents that interfere with androgen receptor signaling.
SUMMARY: Combined palliative and holistic approaches are essential to help young women navigate the marathon of treatment for metastatic breast cancer.

PMID: 26155021 [PubMed - indexed for MEDLINE]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1TlwJsJ
via IFTTT

A case of lung adenocarcinoma with a concurrent EGFR mutation and ALK rearrangement: A case report and literature review.

Related Articles

A case of lung adenocarcinoma with a concurrent EGFR mutation and ALK rearrangement: A case report and literature review.

Mol Med Rep. 2015 Sep;12(3):4370-5

Authors: Xu CW, Cai XY, Shao Y, Li Y, Shi MW, Zhang LY, Wang L, Zhang YP, Wang LP, Tian YW

Abstract
The echinoderm microtubule associated protein like 4‑anaplastic lymphoma kinase (EML4‑ALK) fusion is almost mutually exclusive to epidermal growth factor receptor (EGFR) or K‑RAS mutation in non‑small cell lung cancer (NSCLC), and it is extremely rare for patients to exhibit both mutations. The present study reported the case of a 71-year‑old female diagnosed with adenocarcinoma, exhibiting mutations in EGFR and EML4‑ALK. The present study treated this patient with EGFR‑TK inhibitors, as the first line therapy, and gefitinib therapy revealed a good response until now. In addition, previously reported cases and associated literature were reviewed. The present study provided a greater understanding of the molecular biology and optimal treatment for patients with NSCLC with >1 driver mutation.

PMID: 26130140 [PubMed - indexed for MEDLINE]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1CMrD0A
via IFTTT

Esophageal bronchogenic cyst and review of the literature.

Related Articles

Esophageal bronchogenic cyst and review of the literature.

Surg Endosc. 2015 Oct;29(10):3010-5

Authors: Altieri MS, Zheng R, Pryor AD, Heimann A, Ahn S, Telem DA

Abstract
BACKGROUND: Bronchogenic cysts are rare foregut abnormalities that arise from aberrant budding of the tracheobronchial tree early in embryological development. These cysts predominantly appear in the mediastinum, where they may compress nearby structures. Intra-abdominal bronchogenic cysts are rare. We report an intra-abdominal bronchogenic cyst that was excised laparoscopically.
METHODS: A 40-year old female with a history of gastritis presented for evaluation of recurrent abdominal pain. A previous ultrasound showed cholelithiasis and a presumed portal cyst. Physical examination and laboratory findings were unremarkable. A CT scan with pancreatic protocol was performed and an intra-abdominal mass adherent to the esophagus was visualized. A laparascopic enucleation of the mass was performed. A 3-cm myotomy was made after circumferential dissection of the cyst and the decision was made intraoperatively to reapproximate the muscularis layer. A PubMed literature search on surgical management of esophageal bronchogenic cysts was subsequently performed.
RESULTS: The literature search performed on the subject of esophageal bronchogenic cysts found one review article focusing on intramural esophageal bronchogenic cysts in the mediastinum and five case reports of esophageal bronchogenic cysts. Of these, only one was both intraabdominal and managed laparascopically with simple closure of the resulting myotomy. The majority of the bronchogenic cysts mentioned in the literature were located mediastinally and were managed via open thoracotomy. Our findings confirm the rarity of this particular presentation and the unique means by which this cyst was surgically excised.
CONCLUSION: This case highlights the management of a rare entity and advocates for enucleation of noncommunicating, extraluminal esophageal bronchogenic cysts and closure of the esophageal muscular layers over intact mucosa as a viable surgical approach to this unusual pathology. Other cases of laparascopic enucleation of bronchogenic cysts have shown similarly uneventful postoperative courses and rapid recovery with no apparent return of symptoms.

PMID: 25669636 [PubMed - indexed for MEDLINE]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1TqOslS
via IFTTT

Paget Cells in Endometrial and Endocervical Curettings in a Patient With Recurrent Vulvar Paget's Disease.

Related Articles

Paget Cells in Endometrial and Endocervical Curettings in a Patient With Recurrent Vulvar Paget's Disease.

Int J Surg Pathol. 2014 Jun;22(4):374-7

Authors: Clayton EF, Rubin SC, Dumoff KL

Abstract
INTRODUCTION: Paget's disease of the vulva is a rare malignancy primarily affecting Caucasian women in their seventh to eighth decades. Most patients experience an indolent disease course and undergo surgical excision for disease control. Although progression to invasive adenocarcinoma is rare, recurrence is common because of the difficulty of achieving negative surgical margins.
CASE PRESENTATION: We report a case of a 73-year-old woman with a long-standing history of recurrent vulvar Paget's disease who presented with postmenopausal bleeding. Workup revealed extensive endocervical involvement by Paget's disease, resulting in Paget cells on endocervical curettage, as well as endometrial curettage (because of cervical contamination).
CONCLUSION: Extensive endocervical involvement by vulvar Paget's disease can occur despite multiple reexcisions and topical therapy. The presence of Paget cells on endometrial and endocervical curettings, particularly in patients without visible vulvar or cervical lesions, should raise suspicion of endocervical involvement and prompt further evaluation of disease extension.

PMID: 23918905 [PubMed - indexed for MEDLINE]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1TlwJcd
via IFTTT

Effect of Residents on Operative Time and Complications: Focus on Laparoscopic Cholecystectomy in the Community

Publication date: Available online 18 May 2016
Source:Journal of Surgical Education
Author(s): Hadia Maqsood, Thomas J Buddensick, Kalpesh Patel, Hamid Ferdosi, Amanda Sautter, Lisa Setiawan, Anne M. Sill, Gopal C Kowdley, Steven C Cunningham
ObjectiveTo better understand important aspects of resident education in the perioperative setting, given that there are conflicting data regarding resident training and outcomes (e.g., operative times and complications). To study continuity of care in a resident-run outpatient hospital clinic.DesignRetrospective analysis of 2 databases.SettingThe study was set up in a community teaching hospital.ResultsOf 4603 cases in a cholecystectomy database, 3302 (72%) were assisted by residents, with operative times ranging from 19 to 383 minutes, and 1576 (22.9%) were assisted by nonresidents. The average times were 93 and 77 minutes for resident- and non–resident-assisted cases, respectively. Complications were almost 3 times more likely for urgent vs. elective but were similar for resident-assisted vs. non–resident-assisted cases. The operative time was similar across PGY levels. Of 149 cases in a resident-run outpatient clinic, 100 (67%) of the residents participated in preoperative, intraoperative, and postoperative phases of case, but in only 4% of cases was it the same resident.ConclusionResident assistance increased operative times but not complications. Counterbalanced effects of increasing skill and increasing participation may explain this time stability across PGY levels. Continuity of care is preserved in the era of the 80-hour workweek, but not to a patient-specific degree.



from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1U0WwbY
via IFTTT

Training and Assessment of Hysteroscopic Skills: A Systematic Review

Publication date: Available online 18 May 2016
Source:Journal of Surgical Education
Author(s): Mona Meral Savran, Stine Maya Dreier Sørensen, Lars Konge, Martin G. Tolsgaard, Flemming Bjerrum
ObjectiveThe aim of this systematic review was to identify studies on hysteroscopic training and assessment.DesignPubMed, Excerpta Medica, the Cochrane Library, and Web of Science were searched in January 2015. Manual screening of references and citation tracking were also performed. Studies on hysteroscopic educational interventions were selected without restrictions on study design, populations, language, or publication year. A qualitative data synthesis including the setting, study participants, training model, training characteristics, hysteroscopic skills, assessment parameters, and study outcomes was performed by 2 authors working independently. Effect sizes were calculated when possible. Overall, 2 raters independently evaluated sources of validity evidence supporting the outcomes of the hysteroscopy assessment tools.ResultsA total of 25 studies on hysteroscopy training were identified, of which 23 were performed in simulated settings. Overall, 10 studies used virtual-reality simulators and reported effect sizes for technical skills ranging from 0.31 to 2.65; 12 used inanimate models and reported effect sizes for technical skills ranging from 0.35 to 3.19. One study involved live animal models; 2 studies were performed in clinical settings. The validity evidence supporting the assessment tools used was low. Consensus between the 2 raters on the reported validity evidence was high (94%).ConclusionsThis systematic review demonstrated large variations in the effect of different tools for hysteroscopy training. The validity evidence supporting the assessment of hysteroscopic skills was limited.



from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1XBCZBQ
via IFTTT

The Expanding Role of Audiology Telepractice

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1VaG777
via IFTTT

A Phoneme Perception Test Method for High-Frequency Hearing Aid Fitting

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/209uAV1
via IFTTT

The Effect of the Arabic Computer Rehabilitation Program “Rannan” on Sound Detection and Discrimination in Children with Cochlear Implants

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1VaG0IW
via IFTTT

Recognition of Speech from the Television with Use of a Wireless Technology Designed for Cochlear Implants

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/209uFIh
via IFTTT

Assessment of Functional Hearing in Greek-Speaking Children Diagnosed with Central Auditory Processing Disorder

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1VaGaA0
via IFTTT

Cortical Auditory-Evoked Potentials in Response to Multitone Stimuli in Hearing-Impaired Adults

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/209uzjV
via IFTTT

Validation of the Home Hearing Test™

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1VaFZVo
via IFTTT

Long-term whole-body vibration training in two late-onset Pompe disease patients

Abstract

The treatment of late-onset Pompe disease (LOPD) relies on enzyme replacement therapy (ERT) and physiotherapy but the most appropriate exercise program is not yet established. Whole-body vibration training (WBVT) has showed promising results, improving motor performances in various populations. Our aim is to assess the effects of WBVT performed by two LOPD patients in addition to ERT and physiotherapy. A side-alternating WBVT lasting 2 years; clinical assessments included: manual muscle testing (MRC sumscore), knee extension and arm flection isometric strength (multi-muscle tester M3diagnos), timed function tests (10 m walking, standing-up from chair, ascending 4-steps), 6 min walking (6 MWT), motor disability (Walton Gardner-Medwin scale), pulmonary function. Follow-up evaluations performed for 9 years since ERT start (pre-WBVT and post-WBVT) are reported for comparison. MRC sumscore improved in both patients (Pt.1:41 → 48, Pt.2:42 → 47) as isometric strength of knee extension (Pt.1: + 62 %, Pt.2: + 26 %) and arm flection (Pt.1: + 88 %, Pt.2: + 66 %), 6 MWT improved in Pt.1 (+75 m). Timed function tests did not greatly change. Patients reported no significant CK elevation or WBVT-related complaints. WBVT may be safely used in LOPD and seems to moderately boost muscle strength in patients receiving ERT and physiotherapy for more than 3 years. Larger cohorts should be studied to better assess WBVT potential as adjunctive exercise tool in LOPD.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1TpaOmF
via IFTTT

Profile of adult and pediatric neurocysticercosis cases observed in five Southern European centers

Abstract

In Europe the management of neurocysticercosis (NCC) is challenging because health care providers are unaware of this condition, thus leading to diagnostic delay and mismanagement. The aim of this study is to retrospectively review the cases of NCC observed in five centers located in Florence, Negrar (Italy) and Barcelona (Spain). A total of 81 subjects with NCC were evaluated in the period 1980–2013. By applying the Del Brutto's criteria 39 cases (48.1 %) were classified as definitive cases, 31 (38.8 %) as probable cases and 11 (13.6 %) did not satisfy the diagnostic criteria. Continent of origin was known for 80 subjects. Latin America and Asia were the most frequent continents of origin (n = 37; 46.3 % and n = 22; 27.5 %) followed by Europe (n = 14; 17.5 %) and Africa (n = 7; 8.8 %). Compared with adults, paediatric patients were more likely to have eosinophilia, to have other parasitic infections, to be asymptomatic, to not be treated with antiepileptic drugs or analgesic and to heal. The study shows that there are some hurdles in the management of NCC in Europe. A not negligible portion of patients diagnosed at reference centers do not fully satisfy Del Brutto's diagnostic criteria. The higher portion of asymptomatic subjects found among the paediatric group is probably related to an ongoing serological screening among adopted children coming from endemic regions. The value of such a serological screening should be better assessed by a further cost-effective analysis.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1XBCS9v
via IFTTT

END-PROCESSING NUCLEASES AND PHOSPHODIESTERASES: AN ELITE SUPPORTING CAST FOR THE NON-HOMOLOGOUS END JOINING PATHWAY OF DNA DOUBLE-STRAND BREAK REPAIR

Publication date: Available online 18 May 2016
Source:DNA Repair
Author(s): Vijay Menon, Lawrence Povirk
Nonhomologous end joining (NHEJ) is an error-prone DNA double-strand break repair pathway that is active throughout the cell cycle. A substantial fraction of NHEJ repair events show deletions and, less often, insertions in the repair joints, suggesting an end-processing step comprising the removal of mismatched or damaged nucleotides by nucleases and other phosphodiesterases, as well as subsequent strand extension by polymerases. A wide range of nucleases, including Artemis, Metnase, APLF, Mre11, CtIP, APE1, APE2 and WRN, are biochemically competent to carry out such double-strand break end processing, and have been implicated in NHEJ by at least circumstantial evidence. Several additional DNA end-specific phosphodiesterases, including TDP1, TDP2 and aprataxin are available to resolve various non-nucleotide moieties at DSB ends. This review summarizes the biochemical specificities of these enzymes and the evidence for their participation in the NHEJ pathway.



from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/209uEnE
via IFTTT

ALKBHs-facilitated RNA modifications and de-modifications

Publication date: Available online 17 May 2016
Source:DNA Repair
Author(s): Endalkachew Alemu, Chuan He, Arne Klungland
The AlkB gene that protects E.coli against methylation damage to DNA was identified more than 3 decades ago. 20 years later, the AlkB protein was shown to catalyze repair of methylated DNA base lesions by oxidative demethylation. Two human AlkB homologs were characterized with a similar DNA repair activity and seven additional human AlkB homologs were identified based on sequence homology. All these dioxygenases, ALKBH1-8 and FTO, contain a conserved α-ketoglutarate/iron-dependent domain for methyl modifications and de-modifications. Well-designed research over the last 10 years has identified unforeseen substrate heterogeneity for the AlkB homologs, including novel reversible methyl modifications in RNA. The discoveries of RNA demethylation catalyzed by AlkB family enzymes initiated a new realm of gene expression regulation, although the understanding of precise endogenous activities and roles of these RNA demethylases are still undeveloped. It is worth mentioning that the AlkB mechanism and use of α-ketoglutarate have also emerged to be essential for many enzymes in epigenetic reprogramming that modify and de-modify methylated bases in DNA and methylated amino acids in histones.



from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1sAVc7i
via IFTTT

Inflammatory biomarkers and risk of cancer in 84,000 individuals from the general population

Abstract

Inflammation and cancer are tightly linked. This study tests the hypothesis that an inflammatory score based on plasma levels of C-reactive protein (CRP) and fibrinogen and whole blood leukocyte count is associated with risk of colorectal, lung, breast, and prostate cancer. A score ranging from none through three elevated biomarkers was constructed in 84,000 individuals from the Danish general population. During a median follow-up time of 4.8 years, 4,081 incident cancers occurred. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) of incident cancer. Multifactor-adjusted HRs for colorectal cancer were 1.28 (95% CI, 1.01 to 1.62), 1.79 (95% CI, 1.41 to 2.27), and 2.18 (95% CI, 1.67 to 2.86) for individuals with elevated levels of one, two, and three inflammatory biomarkers compared to individuals with none elevated biomarkers. A similar stepwise increasing risk was observed for lung and breast cancer with HRs of 3.03 (95% CI, 2.25 to 4.08) and 1.42 (95% CI, 1.11 to 1.80) for three versus none elevated biomarkers. HRs were highest within the first years of follow-up. Absolute 5-year risk of lung cancer was 7.8 (95% CI, 6.1 to 10)% among older smokers with three elevated biomarkers compared to 3.8 (95% CI, 2.6 to 5.6)% among those with none elevated biomarkers. In conclusion, simultaneously elevated CRP, fibrinogen, and leukocyte count are associated with an increased risk of colorectal, lung, and breast cancer. Cancer as a promoter of inflammation may be more likely to account for our findings than low-grade inflammation promoting cancer development. This article is protected by copyright. All rights reserved.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1sAVB9C
via IFTTT

Gastrointestinal and liver disease in Adult Life After Childhood Cancer in Scandinavia: A population-based cohort study

Abstract

Survival after childhood cancer diagnosis has remarkably improved, but emerging evidence suggests that cancer-directed therapy may have adverse gastrointestinal late effects. We aimed to comprehensively assess the frequency of gastrointestinal and liver late effects among childhood cancer survivors and compare this frequency with the general population. Our population-based cohort study included all one-year survivors of childhood and adolescent cancer in Denmark, Finland, Iceland, Norway, and Sweden diagnosed from the 1940s and 1950s. Our outcomes of interest were hospitalization rates for gastrointestinal and liver disorders, which were ascertained from national patient registries. We calculated standardized hospitalization rate ratios (RR) and absolute excess rates (AER) comparing hospitalizations of any gastrointestinal or liver disease and for specific disease entities between survivors and the general population. The study included 31,132 survivors and 207,041 comparison subjects. The median follow-up in the hospital registries were 10 years (range: 0 – 42) with 23% of the survivors being followed at least to the age of 40 years. Overall, survivors had a 60% relative excess of gastrointestinal or liver diseases (RR: 1.6, 95% confidence interval (CI): 1.6 – 1.7), which corresponds to an absolute excess of 360 (95% CI: 330 – 390) hospitalizations per 100,000 person-years. Survivors of hepatic tumors, neuroblastoma, and leukemia had the highest excess of gastrointestinal and liver diseases. In addition, we observed a relative excess of several specific diseases such as esophageal stricture (RR: 13; 95% CI: 9.2 – 20) and liver cirrhosis (RR: 2.9; 95% CI: 2.0 – 4.1). Our findings provide useful information about the breadth and magnitude of late complications among childhood cancer survivors, and can be used for generating hypotheses about potential exposures related to these gastrointestinal and liver late effects. This article is protected by copyright. All rights reserved.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1U0VU6a
via IFTTT

Modulation of tumor eIF4E by antisense inhibition: A phase I/II translational clinical trial of ISIS 183750 – an antisense oligonucleotide against eIF4E – in combination with irinotecan in solid tumors and irinotecan-refractory colorectal cancer

Abstract

The eukaryotic translation initiation factor 4E (eIF4E) is a potent oncogene that is found to be dysregulated in 30% of human cancer, including colorectal carcinogenesis (CRC). ISIS 183750 is a second-generation antisense oligonucleotide (ASO) designed to inhibit the production of the eIF4E protein. In preclinical studies we found that EIF4e ASOs reduced expression of EIF4e mRNA and inhibited proliferation of colorectal carcinoma cells. An additive antiproliferative effect was observed in combination with irinotecan. We then performed a clinical trial evaluating this combination in patients with refractory cancer. No dose limiting toxicities were seen but based on pharmacokinetic data and tolerability the dose of irinotecan was reduced to 160mg/m²-biweekly. Efficacy was evaluated in 15 patients with irinotecan-refractory colorectal cancer. The median time of disease control of 22.1 weeks. After ISIS 183750 treatment, peripheral blood levels of eIF4E mRNA were decreased in 13/19 pts. Matched pre- and post-treatment tumor biopsies showed decreased eIF4E mRNA levels in 5/9 pts. In tumor tissue, the intracellular and stromal presence of ISIS 183750 was detected by IHC in all biopsied patients. Although there were no objective responses stable disease was seen in 7/15 (47%) patients who were progressing prior to study entry, six of whom were stable at the time of the week 16 CT scan. We were also able to confirm through mandatory pre- and post-therapy tumor biopsies penetration of the ASO into the site of metastasis. This article is protected by copyright. All rights reserved.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1sAVjQb
via IFTTT

Clinicopathogenomic analysis of mismatch repair proficient colorectal adenocarcinoma uncovers novel prognostic subgroups with differing patterns of genetic evolution

Abstract

Cancer somatic genetic evolution is a direct contributor to heterogeneity at the clonal and molecular level in colorectal adenocarcinoma (COAD). We sought to determine the extent to which genetic evolution may be detected in COAD in routinely obtained single clinical specimens and establish clinical significance with regard to clinicopathologic and outcome data. 123 cases of routinely collected mismatch repair proficient COAD was sequenced on the Illumina Truseq Amplicon assay. Measures of intratumoral heterogeneity were assessed and the preferential timing of mutational events was assessed and compared to clinicopathologic data. Survival subanalysis was performed on 55 cases. Patient age (p=0.013) and specimen percent tumor (p=0.033) was associated with clonal diversity, and biopsy (p=0.044) and metastasis (p=0.044) returned fewer mutations per case. APC and TP53 mutations preferentially occurred early while alterations in FBXW7, FLT3, SMAD4, GNAS, and PTEN preferentially occurred as late events. Temporal heterogeneity was evident in KRAS and PIK3CA mutations. Hierarchical clustering revealed a TP53 mutant subtype and a MAPK-PIK3CA subtype with differing patterns of late mutational events. Survival subanalysis showed a decreased median progression free survival for the MAPK-PIK3CA subtype (8 months vs. 13 months; univariate logrank p=0.0380, cox model p= 0.018). Neoadjuvant therapy associated mutations were found for ERBB2 (p=0.0481) and FBXW7 (p=0.015). Our data indicate novel molecular subtypes of mismatch repair proficient COAD display differing patterns of genetic evolution which correlate with clinical outcomes. Furthermore, we report treatment acquired and/or selected mutations in ERBB2 and FBXW7. This article is protected by copyright. All rights reserved.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1sAVuei
via IFTTT

Knockdown of COUP-TFII inhibits cell proliferation and induces apoptosis through upregulating BRCA1 in renal cell carcinoma cells

Abstract

COUP-TFII belongs to the nuclear receptor family, which is highly expressed in many kinds of tumors. Previous studies have shown that COUP-TFII can promote tumor progression through regulating tumor angiogenesis and cell proliferation and migration of certain cancer cells. However, the function of COUP-TFII in renal cell carcinoma (RCC) is not clear. Here we showed that clinical RCC tumor tissues showed much higher COUP-TFII expression level than adjacent normal tissues. When COUP-TFII was knocked down in RCC 769-P and 786-O cells by siRNA or shRNA-expressing lentivirus, the cell proliferation was markedly inhibited, and apoptosis increased. Moreover, the tumor growth of COUP-TFII knockdown 769-P and 786-O xenografts in nude mice was also obviously inhibited. By using RT-PCR and Western blot, we showed that the expression of the tumor suppressor gene BRCA1 was upregulated in COUP-TFII knockdown cells. Simultaneously knockdown of BRCA1 and COUP-TFII partially rescued the inhibited cell proliferation and increased apoptosis in COUP-TFII single knockdown cells. These results indicate that COUP-TFII may play an oncogenic role in RCC, and COUP-TFII may promote tumor progression through inhibiting BRCA1. This article is protected by copyright. All rights reserved.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1U0VNrb
via IFTTT

Integrative functional genomic delineation of the cascades of transcriptional changes involved in hepatocellular carcinoma progression

Abstract

Development of targeted therapeutics is still at its early stage for hepatocellular carcinoma (HCC) due to the incomplete understanding of the confounding regulations at signaling pathway level. In this investigation, gene co-expression based networking and integrative functional genomic modeling of HCC mRNA profiles as signaling processes were employed to understand the complex signaling cascades involved in HCC development towards understanding the avenues for targeted therapeutics. Multiple sets of genes and molecular biological processes involved during HCC development were identified from this integrative analysis: i) Loss of liver cellular features due to the reduced HNF4A & PPAR signaling in the early stages of HCC, ii) activated inflammatory and stress signals in the cirrhosis stages, and iii) highly activated cellular proliferation with the activated E2F-MYC oncogenic signaling with the gain of embryonic liver stem cell-like features in the advanced stage tumors. Upon connecting these gene-sets with the established drug sensitivity related gene signatures, targeted therapeutic strategies for the heterogeneous HCC conditions have been identified. PPAR agonist class of drugs for early stage HCC conditions, anti-inflammatory drugs for cirrhosis, and topoisomerase inhibitors for the advanced HCC conditions were inferred. Integrative functional genomic analysis of HCC transcriptome profiles at the context of signaling pathways has defined the key molecular processes involved in HCC development. Further, the study highlights the stage specific and pathway focused targeted therapeutics for HCC. These findings deserve extensive pre-clinical explorations towards the establishment of targeted therapeutics. This article is protected by copyright. All rights reserved.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1sAVBqh
via IFTTT

Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH

Abstract

Germline mutations in the DNA base excision repair gene MUTYH are known to increase a carrier's risk of colorectal cancer. However, the risks of other (extracolonic) cancers for MUTYH mutation carriers are not well defined. We identified 266 probands (91% Caucasians) with a MUTYH mutation (41 biallelic and 225 monoallelic) from the Colon Cancer Family Registry. Mutation status, sex, age, and histories of cancer from their 1,903 first- and 3,255 second-degree relatives, were analysed using modified segregation analysis conditioned on the ascertainment criteria. Compared with incidences for the general population, HRs (95% confidence intervals [CIs]) for biallelic MUTYH mutation carriers were: urinary bladder cancer, 19(3.7–97); and ovarian cancer, 17(2.4–115). The HRs (95%CI) for monoallelic MUTYH mutation carriers were: gastric cancer, 9.3(6.7–13); hepatobiliary cancer, 4.5(2.7–7.5); endometrial cancer, 2.1(1.1–3.9); and breast cancer, 1.4(1.0–2.0). There was no evidence for an increased risk of cancers at the other sites examined (brain, pancreas, kidney or prostate). Based on the USA population incidences, the estimated cumulative risks (95%CI) to age 70 years for biallelic mutation carriers were: bladder cancer, 25%(5%–77%) for males and 8%(2%–33%) for females; and ovarian cancer, 14%(2%–65%). The cumulative risks (95%CI) for monoallelic mutation carriers were: gastric cancer, 5%(4%–7%) for males and 2.3%(1.7%–3.3%) for females; hepatobiliary cancer, 3%(2%–5%) for males and 1.4%(0.8%–2.3%) for females; endometrial cancer, 3%(2%–6%); and breast cancer 11%(8%–16%). These unbiased estimates of both relative and absolute risks of extracolonic cancers for people, mostly Caucasians, with MUTYH mutations will be important for the clinical management. This article is protected by copyright. All rights reserved.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1U0WbWE
via IFTTT

Maternal Vitamin D Level Is Associated with Viral Toll-Like Receptor Triggered IL-10 Response but Not the Risk of Infectious Diseases in Infancy

Reports on the effect of prenatal vitamin D status on fetal immune development and infectious diseases in childhood are limited. The aim of this study was to investigate the role of maternal and cord blood vitamin D level in TLR-related innate immunity and its effect on infectious outcome. Maternal and cord blood 25 (OH)D level were examined from 372 maternal-neonatal pairs and their correlation with TLR-triggered TNF-α, IL-6, and IL-10 response at birth was assessed. Clinical outcomes related to infection at 12 months of age were also evaluated. The result showed that 75% of the pregnant mothers and 75.8% of the neonates were vitamin deficient. There was a high correlation between maternal and cord 25(OH)D levels (, ). Maternal vitamin D level was inversely correlated with IL-10 response to TLR3 () and TLR7-8 stimulation (). However, none of the TLR-triggered cytokine productions were associated with cord 25(OH)D concentration. There was no relationship between maternal and cord blood vitamin D status with infectious diseases during infancy. In conclusion, our study had shown that maternal vitamin D, but not cord vitamin D level, was associated with viral TLR-triggered IL-10 response.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1YExRLG
via IFTTT

A Thundering Silence: Environmental Rights in the Dialogue between the EU Court of Justice and the European Court of Human Rights

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1YExWiq
via IFTTT

Who decides? The decision-making process of juvenile judges concerning minors with mental disorders

Previous research on juvenile judges' decision-making process has neglected the role of the different actors involved in judicial procedures. The decision can be considered as a result of information exchange between the different actors involved. The process of making a decision is equally important as the decision itself, especially when the decision considers minors with mental disorders. The presence and the type of interaction determine the information available to the juvenile judges to make their final decision. The overall aim of this study is to gain insight into the role of all actors, including the juvenile judge, in the juvenile judge's decision-making process in cases relating to minors with mental disorders. Semi-structured interviews were carried out with professional actors (n= 32), minors (n= 31) and parents (n= 17). The findings indicated that the judge's decision is overall the result of an interaction between the juvenile judge, the social services investigator and the youth psychiatrist. The other professional actors, the minors and the parents had only a limited role in the decision-making process. The research concludes that the judge's decision-making process should be based on dialogue, and requires enhanced collaboration between the juvenile court and youth psychiatrists from mental health services. Future decision-making research should pay more attention to the interactions of the actors that guide a juvenile judge's decision.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1NzJhzE
via IFTTT

Longitudinal transient elastography measurements used in follow-up for patients with cystic fibrosis

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1YExVLu
via IFTTT

Gene body methylation patterns in Daphnia are associated with gene family size

The relation between gene body methylation and gene function remains elusive. Yet, our understanding of this relationship can contribute significant knowledge on how and why organisms target specific gene bodies for methylation. Here, we studied gene body methylation patterns in two Daphnia species. We observed both highly methylated genes and genes devoid of methylation in a background of low global methylation levels. A small but highly significant number of genes was highly methylated in both species. Remarkably, functional analyses indicate that variation in methylation within and between Daphnia species is primarily targeted to small gene families whereas large gene families tend to lack variation. The degree of sequence similarity could not explain the observed pattern. Furthermore, a significant negative correlation between gene family size and the degree of methylation suggests that gene body methylation may help regulate gene family expansion and functional diversification of gene families leading to phenotypic variation.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1NzJaV0
via IFTTT

De leiding van het geschil door de aansprakelijkheidsverzekeraar: een analyse van de artikelen 143, tweede en derde lid en 152, tweede lid Verzekeringswet 2014

Deze bijdrage presenteert een grondige en uitgebreide analyse van wat doorgaans het recht van de verzekeraar om het aansprakelijkheidsgeschil te leiden wordt genoemd. Hierbij wordt in het bijzonder aandacht besteed aan de begrenzing van dit recht wanneer de belangen van de verzekerde en de verzekeraar in de formulering van de wetgever niet samenvallen.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1YEyiW8
via IFTTT

The European Union and Environmental Democracy: The Aarhus Convention in EU Law

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1NzJdQC
via IFTTT

The role of the addition of ovarian suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or regain menstruation after chemotherapy (ASTRRA): study protocol for a randomized controlled trial and progress

Background: Ovarian function suppression (OFS) has been shown to be effective as adjuvant endocrine therapy in premenopausal women with hormone receptor-positive breast cancer. However, it is currently unclear if addition of OFS to standard tamoxifen therapy after completion of adjuvant chemotherapy results in a survival benefit. In 2008, the Korean Breast Cancer Society Study Group initiated the ASTRRA randomized phase III trial to evaluate the efficacy of OFS in addition to standard tamoxifen treatment in hormone receptor-positive breast cancer patients who remain or regain premenopausal status after chemotherapy. Methods: Premenopausal women with estrogen receptor-positive breast cancer treated with definitive surgery were enrolled after completion of neoadjuvant or adjuvant chemotherapy. Ovarian function was assessed at the time of enrollment and every 6 months for 2 years by follicular-stimulating hormone levels and bleeding history. If ovarian function was confirmed as premenopausal status, the patient was randomized to receive 2 years of goserelin plus 5 years of tamoxifen treatment or 5 years of tamoxifen alone. The primary end point will be the comparison of the 5-year disease-free survival rates between the OFS and tamoxifen alone groups. Patient recruitment was finished on March 2014 with the inclusion of a total of 1483 patients. The interim analysis will be performed at the time of the observation of the 187th event.DiscussionThis study will provide evidence of the benefit of OFS plus tamoxifen compared with tamoxifen only in premenopausal patients with estrogen receptor-positive breast cancer treated with chemotherapy.Trial registrationClinicalTrials.gov Identifier NCT00912548. Registered May 31 2009. Korean Breast Cancer Society Study Group Register KBCSG005. Registered October 26 2009.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1qvNp8D
via IFTTT