Κυριακή, 28 Μαΐου 2017

Promotion of endocytosis efficiency through an ATP-independent mechanism at rat calyx of held terminals

Abstract

Neurotransmission relies on membrane endocytosis to maintain vesicle supply and membrane stability. Endocytosis has been generally recognized as a major ATP-dependent function, which efficiently retrieves more membrane at elevated neuronal activity when ATP consumption within nerve terminals drastically increases. This paradox raises an interesting question whether increased activity recruits ATP-independent mechanism(s) to accelerate endocytosis while preserving ATP availability for other tasks. To address this issue, we studied ATP requirement in three typical forms of endocytosis at the rat calyx of Held terminals by whole-cell membrane capacitance measurements. At room temperature, blocking ATP hydrolysis effectively abolished slow endocytosis and rapid endocytosis, but only partially inhibited excess endocytosis following intense stimulation. The ATP-independent endocytosis occurred at calyces from postnatal 8–15 days, suggesting its existence before and after hearing onset. This endocytosis was not affected by reduction of exocytosis using the light chain of botulinum toxin C, or by block of clathrin-coat maturation. It was abolished by EGTA, which preferentially blocked endocytosis of retrievable membrane pre-existing at surface, and impaired by oxidation of cholesterol and inhibition of neutral sphingomyelinase. ATP-independent endocytosis became more significant at 34–35°C, and recovered membrane by an amount that on average was close to exocytosis. Our results suggest that activity and temperature recruit ATP-independent endocytosis of pre-existing membrane, in addition to ATP-dependent endocytosis, to efficiently retrieve membrane at nerve terminals. This less understood endocytosis represents a non-canonical mechanism regulated by lipids such as cholesterol and sphingomyelinase.

This article is protected by copyright. All rights reserved



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XIST RNA ISH as a Tool for Resolving Specimen Contamination Events

Abstract

The large number of manual steps involved in processing tissue creates many opportunities for specimen cross-contamination and carry-over defects, which may have serious medicolegal ramifications.1 In one study extraneous tissue was identified in 0.6% of slides, causing severe diagnostic difficulties in 0.4% of cases.1 As these events are not fully preventable, a quick, reliable, easily accessible method to resolve suspected contamination events is crucial.

This article is protected by copyright. All rights reserved.



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Title Page/Sections Editors

Publication date: July 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1860, Issue 7





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Sometimes pain originating from a non-odontogenic pathologic condition is mistaken as endodontic illness, leading to misdiagnosis.

http://otorhinolaryngology-crete.blogspot.com/2017/05/adenoid-cystic-carcinoma-of-maxillary.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Subclinical hypothyroidism (SCH) has been associated with atherosclerosis and increased risk of ischemic stroke.

http://otorhinolaryngology-crete.blogspot.com/2017/05/subclinical-hypothyroidism-and-risk-of.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Mutational status predicts the risk of thromboembolic events in lung adenocarcinoma

Precision medicine promises to improve prognosis of patients affected by untreatable diseases. Patients with lung cancer (especially lung adenocarcinoma) bear an increased risk of VTE. Mutations in the EGFR an...

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Instant velocity and consistency of emitted cloud change by the different levels of canister filling with Metered Dose Inhalers (MDIs), but not with Soft Mist Inhalers (SMIs): a bench study

Inhalation is the preferred route for respiratory drug delivery, but several factors contribute to the variability of the respirable dose fraction. Instant velocity and the dynamic characteristics of the dropl...

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Hassall's corpuscles in the fine-needle aspiration cytology of pediatric ectopic thymic tissue



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Ψ Multiple eccrine spiradenomas with a zosteriform pattern—Report of a rare case diagnosed on fine needle aspiration cytology



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Biphasic axillary synovial sarcoma diagnosed by preoperative fine-needle aspiration cytology

Synovial sarcoma (SS) is a soft-tissue sarcoma which usually occurs in lower extremities. Less than 20 cases of SS located in shoulder or axillary region have been reported, and these studies describe histopathological features. We report a case of axillary SS diagnosed by fine-needle aspiration cytology, immunocytochemistry, and molecular techniques performed on cytology smears. A 48-year-old woman presented with a palpable and well-defined axillary mass which measured 4 cm. On-site smears showed high cellularity with spindle cells, and a mesenchymal tumor was suspected. Definitive cytological analysis showed cells with ovoid- or comma-shaped nuclei arranged in loose sheets and fascicles, associated with naked nuclei and isolated cells. Mitotic count was 2 mitoses/HPF. Immunocytochemical studies showed vimentin and focal CK AE1-AE3 positivity. A PCR was performed and the specific translocation t(X;18) was detected. The lesion was excised and the diagnosis of biphasic SS was confirmed. The identification of SS on cytology specimens is difficult and differential diagnosis is broad. Complementary studies are necessary and they can be performed on FNA smears or cell blocks.



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Upper urinary tract washings outperform voided urine specimens to detect upper tract high-grade urothelial carcinoma

Background

Cytological examination of voided urine (VU) can reliably diagnose high-grade urothelial carcinoma (HGUC) of the lower urinary tract, but its value in the diagnosis of upper tract HGUC (UTHGUC) is less well-established. To clarify the utility of VU in the setting of UTHGUC, we examined urinary specimens from patients with UTHGUC on follow-up surgical pathology.

Methods

52 VU specimens (47 patients) with subsequent biopsy-proven UTHGUC were identified over a 12-year period; 32 had a corresponding upper tract urinary washing (UW) specimen. Patients with concurrent bladder HGUC were excluded. The diagnoses of VU specimens were tabulated and compared to those of UW specimens.

Results

Three UW specimens had a less severe diagnosis, 8 had the same diagnosis, and 21 had a more severe diagnosis than the corresponding VU specimen from the same patient. Significantly more UW specimens demonstrated high-risk features as compared with VU specimens (P = .003). In specimens with atypia, a definitive diagnosis of HGUC was made significantly more often on UW vs. VU specimens (P = .003).

Conclusions

Among patients with confirmed UTHGUC, 50% of preceding VU specimens demonstrated high-grade features compared to almost 90% of UW specimens. Though VU cytology shows atypia in the majority of cases, it performs inferiorly to UW for the detection of UTHGUC.



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The global state of psoriasis disease epidemiology: a workshop report

Summary

The International Psoriasis Council, a global nonprofit organization dedicated to innovation across the full spectrum of psoriasis, led a symposium to discuss the current state of psoriasis epidemiology and to introduce the vision and development of a Global Psoriasis Atlas. The symposium was held on 9 September 2015 at the 45th annual meeting of the European Society for Dermatological Research, Rotterdam, the Netherlands. Collectively, these presentations highlighted challenges associated with assessing psoriasis epidemiology and emphasized the urgent need for an authoritative resource to clarify psoriasis disease burden on a global scale.



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BacterioFiles 295 - Fly Ferries Fungus Feebleness

bf295fly.jpg

This episode: Fungus-eating flies transfer viruses that help make fungi less harmful to plants!

(7.8 MB, 8.5 minutes)

Show notes: 


...

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Atenolol Versus Propranolol for Treatment of Infantile Hemangiomas During the Proliferative Phase: A Retrospective Noninferiority Study

Abstract

Background/Objectives

The nonselective beta-blocker propranolol is the current criterion standard for treatment of infantile hemangiomas (IHs) and the first therapy that the U.S. Food and Drug Administration has approved for the condition, but concern about adverse effects, such as bronchospasm, hypoglycemia, and sleep disturbances, has sparked interest in the use of alternative agents such as the selective β1 antagonist atenolol. Our aim was to compare the efficacy and adverse effect profiles of atenolol with those of propranolol in the treatment of IHs in a retrospective noninferiority trial.

Methods

Twenty-seven children with IHs treated with atenolol according to the Cleveland Clinic foundation's standardized clinical assessment and management plan (SCAMP) met inclusion criteria and were compared with a matched group of 53 children with IHs treated with propranolol. Three reviewers assessed response to therapy using a modified version of the previously validated Hemangioma Activity Score (HAS).

Results

The mean change in HAS was −2.94 ± 1.20 for patients treated with atenolol and −2.96 ± 1.42 for those treated with propranolol. There was no statistically significant difference in pre- and posttreatment modified HAS scores between the two groups (p = 0.60). There was no significant difference in the overall rate of adverse effects (p = 0.10), although 11% of patients treated with propranolol experienced reactive airway symptoms, whereas this was not seen in any of the patients treated with atenolol.

Conclusion

Our study supports previous findings that atenolol is at least as effective as propranolol for treatment of IHs and poses less risk of bronchospasm. Our SCAMP proposes guidelines for dosing and monitoring parameters.



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Editorial: Grappling with mother, newborn and child health (MNCH) issues in a continentbeset by non-communicable and infecious diseases

No Abstract

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Renal histoarchitectural changes in nevirapine therapy: possible role of kolaviron and vitamin C in an experimental animal model

Background: There is paucity of literature regarding the nephrotoxicity of antiretroviral drugs and its interaction with plantbased adjuvants. This study investigates the attenuating effect of kolaviron in nevirapine- therapy on the histological structure of the kidneys of adult male Sprague-Dawley rats.

Objective: To determine the attenuating influence of anti-oxidant status of kolaviron on the kidneys of experimental animals following nevirapine administration.

Methods: Forty eight pathogen-free adult male Sprague-Dawley rats were used for this study. The animals were divided into 8 groups (A-H) with 6 animals in each group. Group A was given normal saline as the control; group B was given nevirapine; group C was given kolaviron; group D was given vitamin C; group E was given nevirapine and kolaviron; group F was given nevirapine and vitamin C; Group G was given nevirapine and kolaviron (kolaviron withdrawn after day 28) and group H was given corn oil. The experiment lasted 56 days after which the animals were sacrificed, blood samples were collected through cardiac puncture for serum analysis and the kidneys were harvested and prepared for H& E histological examination.

Results: Nevirapine caused histoarchitectural damage in the glomerular apparatus with resultant increase in kidney/body weight ratio (p<0.001). Adjuvant treatment with kolaviron attenuated these nephrotoxic effects. Serum anti-oxidant enzyme (SOD and CAT) activities were significantly reduced in kolaviron and vitamin C treated animals, whereas in the nevirapine group these parameters were significantly elevated (P<0.05). However, co-administration of nevirapine and vitamin C did not improve the histoarchitecture of the kidney.

Conclusion: Adjuvant treatment with kolaviron (an anti-oxidant) for 56 days appears to attenuate the nephrotoxicity of nevirapine in this model.

Keywords: Kidney, histoarchitecture, kolaviron, antiretroviral drugs



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Where there is no doctor: can volunteer community health workers in rural Uganda provide integrated community case management?

Introduction: Integrated community case management (iCCM) involves assessment and treatment of common childhood illnesses by community health workers (CHWs). Evaluation of a new Ugandan iCCM program is needed.

Objectives: The objectives of this study were to assess if iCCM by lay volunteer CHWs is feasible and if iCCM would increase proportions of children treated for fever, pneumonia, and diarrhoea in rural Uganda.

Methods: This pre/post study used a quasi-experimental design and non-intervention comparison community. CHWs were selected, trained, and equipped to assess and treat children under five years with signs of the three illnesses. Evaluation included CHW-patient encounter record review plus analysis of pre/post household surveys.

Results: 196 iCCM-trained CHWs reported 6,276 sick child assessments (45% fever, 46% pneumonia, 9% diarrhoea). 93% of cases were managed according to algorithm recommendations. Absolute proportions of children receiving treatment significantly increased post-intervention: antimalarial for fever (+24% intervention versus +4% control) and oral rehydration salts/zinc for diarrhoea (+14% intervention versus +1% control).

Conclusion: In our limited-resource, rural Ugandan setting, iCCM involving lay CHWs was feasible and significantly increased the proportion of young children treated for malaria and diarrhoea.

Keywords: Uganda; maternal health; child health; community health worker; integrated community case management



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Proportion and factors associated with low fifth minute Apgar score among singleton newborn babies in Gondar University referral hospital; North West Ethiopia

Background: New born babies with low Apgar scores are at an increased risk of perinatal morbidity and mortality.

Objective: To assess proportion and factors associated with low 5th minute Apgar Apgar score among singleton newborn babies in Gondar University referral hospital; North West Ethiopia.

Methods: A cross-sectional study was conducted on singleton 261 live births from March - May, 2013. Data was collected from mother/newborn index using a structured and pre-tested questionnaire. It was then cleaned, coded and entered using EPI INFO version 3.4.3, then analyzed with IBM SPSS statistics versions 20.0. Logistic regression was used to identify significant variables with low 5th minute Apgar score.

Result: The proportion of low 5th minute Apgar score in this study was 13.8%. Factors that were significantly associated with low 5th minute Apgar score were: non-vertex fetal presentation, prolonged labor, presence of meconium stained liquor, induced/ augmented labor and low birth weight.

Conclusion: Mainly obstetric factors contribute to low Apgar score. Improving labor management through implementing regular use of partograph, 1:1 midwife-client ratio and advanced electronic fetal monitoring technology is recommended.

Keywords: Apgar score, Gondar University referral hospital



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Delivery practices, hygiene, birth attendance and neonatal infections in Karamoja, Uganda: a community-based study

Background: Drawing attention to home birth conditions and subsequent neonatal infections is a key starting point to reducing neonatal morbidity which are a main cause of mortality in sub-Saharan Africa.

Objectives: To determine the proportion of respiratory, ophthalmic, and diarrhoeal infections in neonates; the proportion of mothers of neonates, following clean delivery practices; and to explore existing community practices during delivery and the neonatal period.

Methods: A descriptive, cross-sectional, exploratory study, including 10 questionnaires and five Key-Informant interviews, in rural Karamoja, Uganda.

Results: Post-delivery razor blade and string use was 90%, but clean delivery surface use only 30%, while 90% obtained bathing water for neonates from boreholes. No mothers washed hands after latrine-related activities compared with 83% for food-related activities. None delivered in health centres or with skilled birth attendants. Respiratory infections occurred in eight neonates, compared to two ophthalmic infections, and no diarrhoea.

Conclusion: Use of clean delivery surfaces needs to be improved as well as washing after latrine-related activities. Diarrhoea was far less common than expected. Since rural Mother-Infant pairs spend the majority of their post-delivery time around the homestead, hygiene impacts neonatal infections to a large degree, possibly even more so than delivery practices.

Keywords: Neonatal, birth, delivery, clean delivery kit (CDK), clean delivery practices, infection, diarrhoea, ophthalmic, respiratory, hygiene, traditional birth attendant (TBA), home, rural, community, Nakaale, Nakapiripirit, Karamoja, Uganda



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Quorum sensing inhibitory activity of sub-inhibitory concentrations of β-lactams

Introduction: The virulence factors of Pseudomonas aeruginosa are under the control of quorum sensing (QS) signals. Hence, interference with QS prevents its pathogenesis.

Objective: The aim of the present research is to assess the influence of some β-lactam antibiotics on cell communication and the release of different virulence factors.

Methods: The minimal inhibitory concentrations of ceftazidime, cefepime and imipenem were evaluated by microbroth dilution method. The effect of sub-inhibitory concentration of the tested antibiotics on QS signals was investigated using reporter strain assay. In addition, different virulence factors (elastase, protease, pyocyanin and hemolysin) were estimated in the presence of their sub-inhibitory concentrations.

Results: Low concentrations of ceftazidime, cefepime and imipenem caused significant elimination of the QS signals 3OHC12- HSL and C4-HSL up to 1/20 MIC. Furthermore, low concentrations of the tested antimicrobials suppressed virulence factors elastase and hemolysin. Moreover, 1/20 of their MICs reduced elastase, protease, pyocyanin and hemolysin.

Conclusion: Utilization of β-lactam antibiotics at low concentrations could be an effective approach for prevention and treatment of P. aeruginosa infection.

Keywords: Quorum sensing inhibition, β-lactams, Pseudomonas aeruginosa



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How weight during pregnancy influences the association between pre-pregnancy body mass index and types of delivery and birth: a comparison of urban and rural areas

Background: Women in study areas suffered from the problems of caesarean delivery (CD), low birth weight (LBW), and macrosomia.

Objective: To investigate how gestational weight gain (GWG) influences the effect of the pre-pregnancy body mass index (BMI) on the risks of CD, LBW, and macrosomia in urban and rural areas in a city of Iran.

Methods: We used 767 and 612 eligible subjects from the public health care centers in urban and rural areas respectively.

Results: The risk of CD increased from 74% to 2.62-fold in urban and from 62% to 2.15-fold in rural areas, and the risk of macrosomia increased from 58% to 2.35-fold in urban and from 47% to 96% in rural areas, among obese women compared to normal weight women who gained above median GWG. The risk of LBW increased from 38% to 92% in urban and from 49% to 97% in rural areas among lean women compared to normal weight women who gained below median GWG.

Conclusion: These findings strongly support the need to reform adequate pre-pregnancy weight and GWG against the risks of CD and macrosomia among overweight and obese women, and against the risk of LBW among lean women in both areas.

Keywords: Body mass index, gestational weight gain, caesarean delivery, low birth weight, macrosomia



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Sonographic assessment of petroleum-induced hepatotoxicity in Nigerians: does biochemical assessment underestimate liver damage?

Background: Exposure to petroleum products has been shown to have significant adverse effects on the liver which can manifest either as morphological or physiological changes.

Objectives: The aim of the study was to assess the effects of chronic exposure to some petroleum products on the liver of exposed workers using sonography and to determine whether biochemical assessments underestimated hepatotoxicity.

Methods: Abdominal ultrasound was performed on 415 exposed workers in order to evaluate liver echogenicity and size. Also, biochemical assessment of the liver was done to evaluate its function

Results: Statistically significant increase in the liver parenchymal echogenicity and the liver size was seen in the exposed workers compared with control (p ≤ 0.05). These increased as the exposure duration increased. It was also noted that out of 16.87% (N=70) exposed workers with abnormal liver echopattern, only 2.65% (N=11) had alanine aminotransferase above the reference range.

Conclusion: The study revealed evidence of ultrasound detectable hepatotoxicity among the exposed subjects. Sonography appeared to detect petroleum products-induced hepatic toxicity more than biochemical assays suggesting that biochemical assessment may have underestimated toxicity.

Keywords: Petroleum Products, Exposure, Hepatotoxicity, Sonography, Biochemical assessment, Nigeria



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Geophagy as risk behaviour for gastrointestinal nematode infections among pregnant women attending antenatal clinics in a humid tropical zone of Nigeria

Background: Geophagy is wide spread among pregnant women in Ebonyi State, Nigeria.

Objective: The aim of this study was to assess intestinal nematode infections among geophagous pregnant women in Southern Ebonyi State, Nigeria.

Methods: Pregnant women were aged 17-45 years at gestational ages of ≥ 14 to 24 weeks on hospital enrolment were sampled. Data on geophagy was collected using structured questionnaire. Gastrointestinal nematode status of the participants was determined by stool analyses. Soil types ingested were examined for intestinal nematode ova / larvae.

Results: The prevalence of geophagy (46.4%) was associated with socio-demographic characteristics. Ascaris lumbricoides and hookworm were associated with geophagy while Trichuris trichiura and Strongyloides stercoralis had no association. Prevalence of A. lumbricoides, T. trichiura and S. stercoralis differed significantly (p<0.05) between geophagous and non-geophagous women. The soil types consumed had eggs / larvae of A. lumbricoides and T. trichiura. Geophagy is a risk behaviour directly associated with A. lumbricoides, hookworm, T. trichiura, and to a lesser extent S. stercoralis infection among pregnant women.

Conclusion: Sensitization and mass education of pregnant women on the dangers of geophagy is needed. Furthermore, deworming of pregnant women should be integrated into the healthcare delivery system of the State.

Keywords: Geophagy, gastrointestinal nematode, pregnant women, humid tropics



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Sexual risk behavior among HIV-positive persons in Jamaica

Background: HIV/AIDS remains a global public health challenge, especially in sub-Saharan Africa and the Caribbean. Sexual risk behaviors among HIV-positive persons place their partners at risk for HIV transmission and other sexually transmitted infections. Stopping transmission acts among HIV-positive people is crucial in reversing HIV incidence.

Objective: This study aimed to assess the prevalence and predictors of sexual risk behaviors among HIV-positive individuals in clinical care in Northwestern Jamaica.

Methods: A cross-sectional survey of 118 (33 males and 85 females) HIV-positive individuals was used to assess demographic and health characteristics, HIV/AIDS knowledge, attitudes, and beliefs and sexual risk behaviors.

Results: About 12% of the study population stated that they had unprotected anal or vaginal sex without disclosing their HIV status. Participants who agreed that condoms reduce the risk of HIV transmission were 13.1 times more likely to use condoms during their last sexual encounters(95% CI: 2.1-79.0) than those who disagreed. About 75% of participants reported using a condom every time they had sexual intercourse in the past year, while 25% used condoms irregularly. Participants who had unprotected anal or vaginal sex without disclosing their status were less likely to have used condoms during the last sexual encounter (OR=0.1; 95% CI: 0.02-0.5).

Conclusion: The prevalence of unsafe sex remains high among sexually active people living with HIV/AIDS in Jamaica. Study participants who engaged in unprotected sex without disclosing their HIV-positive status potentially place their partners at risk for HIV transmission and other sexually transmitted infections. The study findings highlight the need to promote safe sexual behaviors and a positive social environment for people living with HIV/AIDS in Jamaica.

Keywords: HIV-seropositivity, sexual behavior, Jamaica, anti-retroviral therapy, condom use



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Evaluation of the mobile phone electromagnetic radiation on serum iron parameters in rats

Background: Electromagnetic fields (EMF) created by mobile phones during communication have harmful effects on different organs.

Objectives: It was aimed to investigate the effects of an EMF created by a mobile phone on serum iron level, ferritin, unsaturated iron binding capacity and total iron binding capacity within a rat experiment model.

Methods: A total of 32 male Wistar albino rats were randomly divided into the control, sham, mobile phone speech (2h/day) and stand by (12 h/day) groups. The speech and stand by groups were subjected to the EMF for a total of 10 weeks.

Results: No statistically significant difference was observed between the serum iron and ferritin values of the rats in the speech and stand by groups than the control and sham groups (p>0.05). The unsaturated iron binding capacity and total iron capacity values of the rats in the speech and stand by groups were significantly lower in comparison to the control group (p<0.01).

Conclusion: It was found that exposure to EMF created by mobile phones affected unsaturated iron binding capacity and total iron binding capacity negatively.

Keywords: cellular phone, electromagnetic fields, ferritin, serum iron



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Diversities in timing of sexual debut among Nigerian youths aged 15-24 years: parametric and non-parametric survival analysis approach

Objective: This study examined gender, generational, cultural and social diversities in timing of sexual debut among Nigerian youths and determined factors influencing the timings.

Methods: We extracted data of respondents aged 15-24 years from 2012 Nigeria nationally representative data. The outcome of interest was time at sexual debut while predictors included residence, marital status, zones, education, religion, age at first marriage. Data was censored, cox proportional hazard and generalized gamma models were used to model age at sexual debut with p=0.05.

Results: The median survival time of sexual debut was 19 years, female youths were twice as likely to begin sexual activities than their male counterparts, HR=1.99, 1.87-2.11 while uneducated youths were more than twice likely to have earlier sexual debut than those with higher education, HR=2.19, 1.95-2.25. Likelihood of having had sexual debut was about 30% higher among those aged 20-24 years than those aged 15-19 years, HR=1.27, 1.19-1.36.

Conclusion: Females from poor households mostly in rural areas with no education and who married early in life were more likely to have earlier sexual debut. Both teenagers and young adults are on different trajectories of sexual debut but both urgently need sexual and reproductive health education to delay sexual debut.

Keywords: Sexual debut, survival analysis, Nigeria, generalised gamma, wealth



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Willingness by people living with HIV/AIDS to utilize HIV services provided by Village Health team workers in Kalungu district, central Uganda

Background: Less than one quarter of people in need have access to HIV services in Uganda. This study assessed willingness of people living with HIV/AIDS (PLWHAs) to utilize HIV services provided by Village Health Teams (VHTs) in Kalungu district, central Uganda.

Methods: A cross-sectional study conducted in two health facilities providing anti-retroviral therapy enrolled 312 PLWHAs. Pre-tested semi-structured questionnaires were administered to participants at household level. A forward fitting logistic regression model computed the predictors of willingness of PLWHAs to utilize services provided by VHTs.

Results: Overall, 49% were willing to utilize HIV services provided by VHTs increasing to 75.6% if the VHT member was HIV positive. PLWHAs who resided in urban areas were more likely to utilize HIV services provided by VHTs (AOR 0.24, 95%CI 0.06-0.87). Barriers to utilizing HIV services provided by VHTs were: income level > 40 USD (AOR 6.43 95%CI 1.19-34.68), being a business person (AOR 8.71 95%CI 1.23-61.72), peasant (AOR 7.95 95%CI 1.37-46.19), lack of encouragement from: peers (AOR 6.33 95%CI 1.43-28.09), spouses (AOR 4.93 95%CI 1.23-19.82) and community leader (AOR 9.67 95%CI 3.35-27.92).

Conclusion: Social support could improve willingness by PLWHAs to utilize HIV services provided by VHTs for increased access to HIV services by PLWHA.

Keywords: Willingness by people living with HIV/AIDS to utilize HIV services provided by Village Health Team workers in Kalungu district, central Uganda



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Developmental screening: predictors of follow-up adherence in primary health care

Background: The importance of early identification for infants and young children with developmental delays is well established. Poor follow-up on referrals, however, undermines the effectiveness of early intervention programmes.

Objectives: To identify factors, including text message reminders, that influence follow-up adherence for early intervention after developmental screening in primary health care. A secondary objective surveyed reasons for follow-up default.

Methods: The PEDS tools were used to screen 247 high-risk children. A risk assessment questionnaire was completed with caregivers whose children were referred for speech-language and/or occupational therapy (n=106, 43%). A quasi-experimental correlational study was employed to identify risk factors for defaulting on appointments. A thematic analysis of telephonic interviews was also employed to determine reasons for follow-up defaults.

Results: Follow-up adherence was 17%. Participants who were never married, divorced or widowed were 2.88 times more likely to attend a follow-up appointment than those who were married or living together (95%, CI 0.97-8.63). Text message reminders did not improve follow-up. More than half (58%) of participants who defaulted on appontments could be reached for telephonic interviews. Interviews showed that 87% of participants were unconcerned about their child's development. Other reasons for defaulting were employment, logistical issues, other responsibilities and forgetfulness.

Conclusion: Follow-up adherence for early intervention services following a positive primary health care screen was poor. Increased awareness and education regarding the importance of development for educational success is needed.

Keywords: Developmental screening, follow-up return rate, occupational therapy, PEDS tools, primary health care, speech-language therapy, text message reminders



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Hydroxyurea therapy in adult Nigerian sickle cell disease: a monocentric survey on pattern of use, clinical effects and patient’s compliance

Background: The clinical prospects of hydroxyurea therapy in the management of sickle cell disease (SCD) require evaluation in the Nigerian setting to develop indigenous guidelines. This survey examines the pattern of hydroxyurea therapy, its clinico-haematologic benefits and safety profile in Nigerian SCD subjects.

Methods: A cross sectional pilot survey was carried out among 60 adult SCD subjects over 3 months. Data on clinical phenotypes, relevant haematological parameters and details of hydroxyurea therapy were obtained using a structured questionnaire through an interview process and case file review.

Results: The median age was 30 years. Thirty-four (56.7%) of the subjects are aware of hydroxyurea therapy in SCD. Twenty-four (40%) SCD patients had previously used hydroxyurea. Only 4 subjects were fully compliant. Reasons for non-complianceincluded poor knowledge and lack of funds. In particular, hydroxyurea reduced leucocyte count and increased mean red cell volume (MCV) in compliant subjects.

Conclusion: Hydroxyurea use is low among Nigerian SCD subjects despite its proven efficacy/clinical prospects in the developed nations. Large scale multicenter studies and clinical trials are needed to form a basis for developing standard local treatment protocol for its use.

Keywords: Hydroxyurea therapy, Nigerian sickle cell disease, pattern of use, clinical effects, patient's compliance



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Cytotoxicity testing of aqueous extract of bitter leaf (Vernonia amygdalina Del) and sniper 1000EC (2,3 dichlorovinyl dimethyl phosphate) using the Alium cepa test

Background: The unrefined nature of the herbal preparations from Vernonia amygdalina (VA) and toxicity potentials of Sniper may both have severe consequences on the biochemical and genetic systems.

Objectives: To assess the microscopic and macroscopic effects of these substances.

Methods: VA leafs and Sniper were prepared and dissolved in distilled water to give different concentrations. Series of baseline tests were carried out to establish concentration range for root growth. Series of twelve onion bulbs of three per series was prepared, with a series of three onion bulbs serving as control. Chromosomal aberrations were statistically analysed using chisquared test. Root bundle mean length was obtained after 96 hours and EC50 values at 95% confidence interval was determined from a plot of root length against sample concentrations using Microsoft Excel software.

Results: Total cytotoxic effect was induced by 2% sniper and 70% VA. EC50 for VA and sniper were 33.07 and 0.346 respectively. The two substances induced chromosomal aberrations and the effect was concentration dependent.

Conclusion: There are risks of these widely used substances for therapeutic and environmental purposes.

Keywords: Chromosomal aberrations, Sniper 1000EC, Vernonia amygdalina, toxicity



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Investigation of the relationship between structural empowerment and organizational commitment of nurses in Zanjan hospitals

Background: The demanding nature of nursing work environments signals longstanding and growing concerns about nurses' health and job satisfaction and the provision of quality care. Specifically in health care settings, nurse leaders play an essential role in creating supportive work environments to avert these negative trends and increase nurse job satisfaction.

Objective: The purpose of this study was to examine the relationship between structural empowerment and organizational commitment of nurses.

Methods: 491 nurses working in Zanjan hospitals participated in this descriptive-correlational study in 2010. Tools for data collection were Meyer and Allen's organizational commitment questionnaire and "Conditions for Work Effectiveness Questionnaire-II" (CWEQ-II). Data was analyzed by SPSS16. The statistical tests such as variance analysis, t-test, pearson correlation coefficient and linear regression were used for data analysis.

Results: According to the findings, the perception of nurses working in hospitals on "Structural Empowerment" was moderate (15.98±3.29). Nurses believed "opportunity" as the most important element in structural empowerment with the score of 3.18 ±0.79. Nurses working in non-academic hospitals and in non-teaching hospitals had higher organizational commitment than others. There was a significant relationship between structural empowerment and organizational commitment.

Conclusion: Generally, structural empowerment (relatively strong) correlates with nurses' organizational commitment. We concluded that a high structural empowerment increases the organizational commitment of nurses.

Keywords: Structural empowerment, organizational commitment, nurses, Zanjan



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Contextual determinants of adolescent mortality in South Africa

Objectives: South Africa has a large adolescent population (approximately 20% of the total population). The survival and development of these individuals are a priority among parents and the government. In an effort to better understand the factors contributing to adolescent mortality in South Africa, this study examined the effect of household and community factors on adolescent death.

Methods: The study used data from Census 2001. Multilevel modelling was used to study the impact of community and household factors on adolescent mortality. A multivariate binary logistic 2- level model was developed. Odds ratios were produced and, statistically significant values (p<0.05) were discussed. There were 41,261 reported adolescent deaths from census data.

Results: This study found that having a few household assets, six or more people living in a residence, and high racial diversity is associated with increased odds of adolescent mortality in South Africa in 2001.

Conclusions: Socio-economic status of the household and racial diversity within communities is likely to increase adolescent mortality in South Africa. However, there is need to examine the role of other community characteristics, such as number of schools, health facilities and employment opportunities in order to create a holistic profile of the contextual determinants of adolescent mortality in the country.

Keywords: Adolescent mortality, South Africa



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Distribution of symptoms of post-stroke depression in relation to some characteristics of the vulnerable patients in socio-cultural context

Objective: To determine the distribution of symptoms of post-stroke depression (PSD) in relation to some predisposing factors in an African population.

Relevance: Environment is a key determinant of behavior, and varied socio-cultural contexts must have implications for modifiable characteristics (age, duration of the stroke, marital status, type of employment, gender, the location of cerebral lesion and complications) of individuals vulnerable to PSD, which may be targeted to enhance recovery.

Method: This was a cross-sectional observational study of 50 (22 females and 28 males) stroke survivors (mean age=54.76±8.79 years), at the physiotherapy department, the University of Nigeria teaching hospital, Enugu, selected using convenience sampling technique. Data were collected using Becks Depression Inventory and analyzed using Z-score, Chi-square test and univariate logistic regression, at p<0.05.

Results: PSD was more prevalent in females (45.45%); young(100%); middle-age(60%) adults(27-36/47-56 years respectively); living with spouse (45%); left cerebral lesions (40.74%); complications(45%); cold case >3 years(47.05%); self-employed and unemployed (66.67%), respectively. Age was significantly associated with depression (χ2 =4.92,df=1,p=0.03), and was related to the risk of PSD (3.7[1.1-12.0], p=0.03, φ = +0.31, φ2=0.1).

Conclusion: Age could be a risk factor for PSD, which was more prevalent in the elderly than young/middle-age adults, female gender, left cerebral lesion, complications, cold case; those living with a spouse, self-employed and unemployed.

Keywords: Symptoms of post-stroke depression, modifiable characteristics of the vulnerable patients, African socio-cultural context



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Oxidative stress and histopathological changes induced by methylthiophanate, a systemic fungicide, in blood, liver and kidney of adult rats

Background: Methyl-thiophanate (MT), a fungicide largely used in agriculture throughout the world including Tunisia, protects many vegetables, fruits and field crops against a wide spectrum of fungal diseases. Oxidative stress has been proposed as a possible mechanism involved in MT toxicity on non-target organism.

Methods: In the present study, the effect of MT injected intraperitoneally to adult rats at 300 or 500 mg/kg of body weight was studied on blood, liver and kidney.

Results: Our results showed 3 days after MT injection, a significant decrease in hemoglobin and hematocrit values. A disruption in total white blood cells and platelets also occurred. Accordingly, an increased in malondialdehyde, H2O2 and advanced oxidation protein levels in liver and kidney were noted with the two doses. A significant change in plasma biomarkers and organ enzymatic and non-enzymatic activities were observed after MT treatment. The modifications in biochemical parameters were substantiated by histopathological data.

Conclusion: These data confirmed the pro-oxidant effects of this fungicide. Accordingly, care must be taken to avoid mammalian and human exposure to MT.

Keywords: Methyl-thiophanate, white blood cells, red blood cells, liver, kidney



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A case of ulcerative colitis with squamous cell carcinomas and multiple foci of squamous dysplasia

Squamous cell carcinoma (SqCC) in ulcerative colitis (UC) is rare. A 38 year-old Japanese woman, who suffered from left-sided UC for 18 years, underwent total colectomy due to SqCCs in the rectum and the sigmoid colon. They were well differentiated SqCC, and metastasis was found in the paracolic lymph nodes. Multiple small foci of squamous dysplasia (SD) were noted in the rectal mucosa. Glandular dysplasia was not found. TP53 was not detected in SD. Approximately 40% of cells were immunostained with TP53 in SqCC, however no mutation was found in TP53 gene. Human papilloma virus and Epstein Barr virus were negative in SD and SqCCs. The patient is free of the disease at one and half years after surgery and chemotherapy. SD may be a precursor of SqCC. It appeared that TP53 does not play a vital role in the development of SqCCs in the current case. Careful attention should be paid to SD in UC patients. Viral infection may need to be examined. The pathogenesis of SqCC in patients of UC needs to be elucidated.



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Computer-assisted orthognathic surgery: evaluation of mandible registration accuracy and report of the first clinical cases of navigated sagittal split ramus osteotomy

Intraoperative navigation is a helpful tool in complex anatomical regions or procedures. The mobility of the mandible in relation to the skull base limits the use of navigation tools on the lower jaw if the reference device is installed on the forehead. A new workflow that allows navigation-assisted sagittal split osteotomy in orthognathic surgery using a separate non-invasive mandibular registration technique has been developed. An evaluation of accuracy in different anatomical regions and with different registration techniques was performed on skull models and skulls with movable mandibles.

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Suitability of functional evaluation embedded in serious game rehabilitation exercises to assess motor development across lifespan

Publication date: September 2017
Source:Gait & Posture, Volume 57
Author(s): B. Bonnechère, V. Sholukha, L. Omelina, M. Van Vooren, B. Jansen, S. Van Sint Jan
The aim of this study was to determine if the results of activities performed using specially developed serious games for physical rehabilitation could be used as an indicator of the natural maturation and decline of motor control in healthy participants. Eighty-one participants (19 children (5–15 years old), 40 adults (18–65 years old) and 22 aged subjects (60–88 years old) participated in this study. Motions performed were recorded using the Kinect sensor. Three different exercises embedded in the games were used to assess upper limb, trunk and lower limb control. The trial duration and accuracy, measures of gross motor function and fine motor control, respectively, were computed for each participant. ANOVA tests shows statistically significant differences between the three groups for duration (53±15, 27±10 and 119±30s for children, adults and elderly subjects respectively) and accuracy (87±5, 89±10 and 70±8% for children, adults and elderly subjects respectively). The slopes of the curves that approximated the evolution of the performance over various ages are coherent with previous studies about motor control development and physiological decline. The proposed solution, i.e. serious games rehabilitation exercises coupled to motion analysis, seems to be an interesting tool to assess global motor function. Further studies are needed to study the influence of pathologies on the studied parameters.



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Oral lichenoid dysplasia and exophytic oral verrucous hyperplasia: Mythical entities of oral pathology

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Publication date: Available online 27 May 2017
Source:Oral Oncology
Author(s): A. Thirumal Raj




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Editorial Board/Aims & Scope

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Publication date: June 2017
Source:Oral Oncology, Volume 69





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In Memoriam – Crispian Scully 1945–2017

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Publication date: June 2017
Source:Oral Oncology, Volume 69
Author(s): Jatin P. Shah




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The Combined Vaginoplasty Technique for Male-to-Female Sex Reassignment Surgery: Operative Approach and Outcomes

Publication date: Available online 27 May 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Nikolaos A. Papadopulos, Dmitry Zavlin, Jean-Daniel Lellé, Peter Herschbach, Gerhard Henrich, Laszlo Kovacs, Benjamin Ehrenberger, Hans-Guenther Machens, Jürgen Schaff
BackgroundSeveral therapy options exist for male-to-female (MTF) transgenders desiring sex reassignment. Surgery includes numerous different procedures. Of those, vaginoplasty is predominant and aims at providing attractive aesthetics and fully functional genitals.The goal of this study was to present the surgical results of our modified combined vaginoplasty technique in a consecutive patient cohort.MethodsThe authors included 40 MTF transgender patients undergoing two-stage sex reassignment surgery (SRS) in an observational prospective study between September 2012 and January 2014. Demographic characteristics, medical and surgical history, operative details, and outcomes after surgery were documented. Postoperatively, 23 patients received a pelvic exam following standardized protocol.ResultsMeasured vaginal depth was 11.77 - 14.99 cm depending on dilator size used (25-40mm). Vaginal, clitoral, and labial sensitivity was intact and favorable in all examined patients. 19 women (47.5%) opted for breast augmentations to achieve feminine cosmesis making it the most common non-genital operation. Complications were mostly minor and temporary. Severe adverse events, such as wound infections (n = 3), colon injuries (3), short (1) or narrow (1) vaginas, or partial clitoral necroses (1), were rare and immediately addressed by the surgical team. No vaginal construction was lost and no secondary reconstructive approaches were required.ConclusionSatisfactory physical results and favorable low rates of complications endorse our combined technique for MTF SRS. These findings, however, need to be confirmed by other research groups as well. Therefore, in our opinion, MTF SRS remains an evolving area of development whose research is aiming to establish a state of the art surgical technique.



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If a butterfly flaps its wings in the Amazon, do we form an Inflammasome?

Publication date: June 2017
Source:Molecular Immunology, Volume 86
Author(s): Ashley Mansell




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Editorial Board/ Publication Information

Publication date: June 2017
Source:Molecular Immunology, Volume 86





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TWiV 443: On a leaf, no one can hear you scream

Ladybird_with_a_parasitoid_cocoon_721191

The TWiVsters reveal the puppet master: an RNA virus injected with wasp eggs that paralyzes the ladybug so that she protects the cocoon until the adult emerges.

Hosts: Vincent Racaniello...



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Effect of transcranial direct current stimulation on neuroplasticity in corticomotor pathways of the tongue muscles

Abstract

To investigate effects of transcranial direct current stimulation (tDCS) on neuroplasticity in corticomotor pathways related to tongue muscles evoked by a training task using the Tongue Drive System (TDS). Using a cross-over design, 13 healthy participants completed two sessions of tDCS while performing 30 min of TDS training. Sessions were spaced at least 2 weeks apart and participants randomly received anodal and sham tDCS stimulation in the first session and the other condition in the second session. Single and paired pulse transcranial magnetic stimulation was used to elicit motor evoked potentials (MEPs) of the tongue at three time-points; before, immediately after and 30 min after training. Participant-based reports of fun, pain, fatigue and motivation, level of difficulty and effort were evaluated on numerical rating scales. There was no consistent significant effect of anodal and sham stimulation on single or paired pulse stimulation MEP amplitude immediately or 30 min after TDS training. Irrespective of tDCS type, training with TDS induced cortical plasticity in terms of increased MEP amplitudes for higher stimulus intensities after 30 min compared with before and immediately after training. Participant-based reports revealed no significant difference between tDCS conditions for level of fun, fatigue, motivation, difficulty and level of effort but a significant increase in pain in the anodal condition, although pain level was low for both conditions. In conclusion, tongue MEP amplitudes appear to be sensitive to training with the tongue using TDS; however anodal tDCS does not have an impact on training-evoked neuroplasticity of tongue corticomotor pathways.

This article is protected by copyright. All rights reserved.



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Advances in translational inner ear stem cell research

Publication date: Available online 25 May 2017
Source:Hearing Research
Author(s): Athanasia Warnecke, Adam J. Mellott, Ariane Römer, Thomas Lenarz, Hinrich Staecker
Stem cell research is expanding our understanding of developmental biology as well as promising the development of new therapies for a range of different diseases. Within hearing research, the use of stem cells has focused mainly on cell replacement. Stem cells however have a broad range of other potential applications that are just beginning to be explored in the ear. Mesenchymal stem cells are an adult derived stem cell population that have been shown to produce growth factors, modulate the immune system and can differentiate into a wide variety of tissue types. Potential advantages of mesenchymal/adult stem cells are that they have no ethical constraints on their use. However, appropriate regulatory oversight seems necessary in order to protect patients from side effects. Disadvantages may be the lack of efficacy in many preclinical studies. But if proven safe and efficacious, they are easily translatable to clinical trials. The current review will focus on the potential application on mesenchymal stem cells for the treatment of inner ear disorders.



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Effect of transcranial direct current stimulation on neuroplasticity in corticomotor pathways of the tongue muscles

Abstract

To investigate effects of transcranial direct current stimulation (tDCS) on neuroplasticity in corticomotor pathways related to tongue muscles evoked by a training task using the Tongue Drive System (TDS). Using a cross-over design, 13 healthy participants completed two sessions of tDCS while performing 30 min of TDS training. Sessions were spaced at least 2 weeks apart and participants randomly received anodal and sham tDCS stimulation in the first session and the other condition in the second session. Single and paired pulse transcranial magnetic stimulation was used to elicit motor evoked potentials (MEPs) of the tongue at three time-points; before, immediately after and 30 min after training. Participant-based reports of fun, pain, fatigue and motivation, level of difficulty and effort were evaluated on numerical rating scales. There was no consistent significant effect of anodal and sham stimulation on single or paired pulse stimulation MEP amplitude immediately or 30 min after TDS training. Irrespective of tDCS type, training with TDS induced cortical plasticity in terms of increased MEP amplitudes for higher stimulus intensities after 30 min compared with before and immediately after training. Participant-based reports revealed no significant difference between tDCS conditions for level of fun, fatigue, motivation, difficulty and level of effort but a significant increase in pain in the anodal condition, although pain level was low for both conditions. In conclusion, tongue MEP amplitudes appear to be sensitive to training with the tongue using TDS; however anodal tDCS does not have an impact on training-evoked neuroplasticity of tongue corticomotor pathways.

This article is protected by copyright. All rights reserved.



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Advances in translational inner ear stem cell research

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Publication date: Available online 25 May 2017
Source:Hearing Research
Author(s): Athanasia Warnecke, Adam J. Mellott, Ariane Römer, Thomas Lenarz, Hinrich Staecker
Stem cell research is expanding our understanding of developmental biology as well as promising the development of new therapies for a range of different diseases. Within hearing research, the use of stem cells has focused mainly on cell replacement. Stem cells however have a broad range of other potential applications that are just beginning to be explored in the ear. Mesenchymal stem cells are an adult derived stem cell population that have been shown to produce growth factors, modulate the immune system and can differentiate into a wide variety of tissue types. Potential advantages of mesenchymal/adult stem cells are that they have no ethical constraints on their use. However, appropriate regulatory oversight seems necessary in order to protect patients from side effects. Disadvantages may be the lack of efficacy in many preclinical studies. But if proven safe and efficacious, they are easily translatable to clinical trials. The current review will focus on the potential application on mesenchymal stem cells for the treatment of inner ear disorders.



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A case of primary secretory carcinoma of the thyroid gland with high-grade features

We report a case of primary secretory carcinoma of the thyroid with high-grade features to highlight cytologic and histologic clues to the diagnosis. The diagnosis of primary secretory carcinoma of the thyroid is challenging both due to the fact that it has only recently been described and because of its morphologic overlap with papillary thyroid carcinoma (PTC); however, differentiating secretory carcinoma from PTC is crucial both for prognostication and treatment purposes.

This article is protected by copyright. All rights reserved.



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MicroRNA-211 expression is down-regulated and associated with poor prognosis in human glioma

Abstract

Accumulating evidence has supported the role of microRNAs in the initiation and development of malignant tumors. MicroRNA-211 (miR-211), which was reported to involve in diverse physiological activities in several cancers, was investigated for its expression in human glioma and adjacent normal brain tissues, as well as its correlation with patient prognosis. Glioma tissues and adjacent normal brain tissues were obtained from 82 patients who underwent surgical resection, and quantitative real-time polymerase chain reaction was performed to assess the expression level of miR-211. Here, we found that miR-211 was significantly decreased in glioma tissues compared with adjacent normal brain tissues (glioma, 3.52 ± 0.14 vs. normal, 4.96 ± 0.17, p < 0.001), and inversely associated with ascending WHO classification (grade III–IV, 3.16 ± 0.21 vs. grade I–II, 4.22 ± 0.26, p < 0.001). Then, the correlation of miR-211 with clinicopathological factors was investigated by Pearson’s Chi square test, indicating that miR-211 might be a potential biomarker to predict the malignant status of glioma. Further, Kaplan–Meier curves with log-rank analysis were carried out to determine the relationship between miR-211 expression level and the overall survival rate of glioma patients. Our data showed that there was a close correlation between down-regulated miR-211 and shorter survival time in 82 patients (p = 0.026). Finally, the multivariate Cox regression analysis indicated that WHO grade (HR = 2.437, 95% CI 1.251–4.966, p = 0.007), KPS (HR = 2.215, 95% CI 1.168–4.259, p = 0.016), and miR-211 expression level (HR = 3.614, 95% CI 2.152–6.748, p < 0.001) were considered as independent risk factors for glioma prognosis. These results suggested that lower miR-211 expression might be a marker for poor prognosis of glioma patients.



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The ratio of HLA-DR and VNN2 + expression on CD14 + myeloid derived suppressor cells can distinguish glioblastoma from radiation necrosis patients

Abstract

Glioblastoma (GBM) is the most aggressive and lethal type of brain cancer with a median survival of less than two years even following aggressive treatment (Stupp et al., N Engl J Med 352:987–996, 2005). Among the many challenges in treating patients with this devastating disease is the ability to differentiate Magnetic Resonance Imaging (MRI) images that appear following radiation therapy, often termed “radiation necrosis” from true GBM recurrence. Radiation necrosis (RN) and GBM are very difficult to distinguish and currently only a brain biopsy can conclusively differentiate these pathologies. In the present study, we introduce a differential diagnostic approach using a newly identified Myeloid-Derived Suppressor Cell (MDSC) biomarker, vascular non-inflammatory molecule 2 (VNN2+), in combination with expression of traditional HLA-DR on peripheral blood CD14+ monocytes isolated from GBM and/or RN patients. We performed proof-of-principle experiments confirming the sensitivity and specificity of this approach based upon the combined expression levels of HLA-DR and VNN2 among CD14+ Mo-MDSC, which we called the DR-Vanin Index or DVI. The DVI was able to distinguish GBM from RN patients with a high degree of certainty (n = 18 and n = 6 respectively; p = 0.0004). This novel, quick and inexpensive blood-based liquid biopsy could potentially replace invasive brain biopsies in differentiating GBM from RN patients using a minimally-invasive technique.



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Long non-coding RNA MALAT1 promotes proliferation and suppresses apoptosis of glioma cells through derepressing Rap1B by sponging miR-101

Abstract

Long non-coding RNAs (lncRNAs) have been recently shown to be dysregulated and closely related to several cancers. Here, we aimed to elucidate the function and the possible molecular mechanisms of lncRNA Metastasis-associated lung Adenocarcinoma transcript-1 (MALAT1) in human glioma. Quantitative real-time PCR (qRT-PCR) was used to detect the expressions of MALAT1, miR-101 and Rap1B mRNA in U251 and U87 cells. The protein level of Rap1B was examined by western blot assays. Moreover, the proliferation and apoptosis of U251 and U87 cells were determined by CCK-8 assay and flow cytometry analysis, respectively. Additionally, the targets of miR-101 were identified by target prediction and luciferase reporter assays. The results demonstrated that MALAT1 and Rap1B were upregulated, while miR-101 expression was downregulated in glioma cell lines U251 and U87. MALAT1 and Rap1B knockdown could inhibit proliferation and induce apoptosis of glioma cells. Moreover, MALAT1 promoted the Rap1B expression by sponging miR-101 in U251 and U87 cells. Furthermore, miR-101 downregulation or Rap1B overexpression reversed the proliferation inhibitory and apoptosis induction of glioma cell lines caused by MALAT1 knockdown. Taken together, MALAT1 promotes proliferation and suppresses apoptosis of glioma cells through derepressing Rap1B by sponging miR-101. The present study elucidates a novel MALAT1-miR-101-Rap1B regulatory axis in glioma, contributing to a better understanding of the glioma pathogenesis and providing a promising therapeutic target for glioma patients.



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Relationship between dietary quality, tinnitus and hearing level: data from the national health and nutrition examination survey, 1999–2002

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Relationship between dietary quality, tinnitus and hearing level: data from the national health and nutrition examination survey, 1999–2002

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Cacna1g is a genetic modifier of epilepsy in a mouse model of Dravet syndrome

Summary

Dravet syndrome, an early onset epileptic encephalopathy, is most often caused by de novo mutation of the neuronal voltage-gated sodium channel gene SCN1A. Mouse models with deletion of Scn1a recapitulate Dravet syndrome phenotypes, including spontaneous generalized tonic–clonic seizures, susceptibility to seizures induced by elevated body temperature, and elevated risk of sudden unexpected death in epilepsy. Importantly, the epilepsy phenotype of Dravet mouse models is highly strain-dependent, suggesting a strong influence of genetic modifiers. We previously identified Cacna1g, encoding the Cav3.1 subunit of the T-type calcium channel family, as an epilepsy modifier in the Scn2aQ54 transgenic epilepsy mouse model. In this study, we asked whether transgenic alteration of Cacna1g expression modifies severity of the Scn1a+/− Dravet phenotype. Scn1a+/− mice with decreased Cacna1g expression showed partial amelioration of disease phenotypes with improved survival and reduced spontaneous seizure frequency. However, reduced Cacna1g expression did not alter susceptibility to hyperthermia-induced seizures. Transgenic elevation of Cacna1g expression had no effect on the Scn1a+/− epilepsy phenotype. These results provide support for Cacna1g as a genetic modifier in a mouse model of Dravet syndrome and suggest that Cav3.1 may be a potential molecular target for therapeutic intervention in patients.



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Postictal generalized EEG suppression and respiratory dysfunction following generalized tonic–clonic seizures in sleep and wakefulness

Summary

Objective

Sudden unexpected death in epilepsy (SUDEP) is a common cause of death in epilepsy and frequently occurs following generalized tonic–clonic seizures (GTCS) in sleep. Postictal generalized electroencephalography (EEG) suppression (PGES), postictal immobility, and periictal respiratory dysfunction are potential risk factors for SUDEP. We sought to determine whether there was a difference in respiratory dysfunction, PGES, and postictal immobility for GTCS occurring during wakefulness or sleep.

Methods

We retrospectively analyzed video-EEG telemetry data in the epilepsy-monitoring unit. Patients’ state at seizure onset and seizure characteristics were identified. Respiratory parameters and heart rate were recorded. Presence and duration of PGES and time to first postictal nonrespiratory movement were recorded.

Results

There were 165 seizures in 67 patients. There was no significant difference in the duration of postictal immobility in GTCS occurring out of wakefulness or sleep (p = 0.280). Oxygen desaturation nadir (p = 0.572) and duration of oxygen desaturation were not significantly different for GTCS starting during sleep or wakefulness (p = 0.992). PGES occurred more frequently when seizure onset was in sleep than in wakefulness (p = 0.004; odds ratio [OR] 2.760). There was no difference in the duration of PGES between the two groups.

Significance

PGES occurs more commonly after GTCS in sleep than in wakefulness but, in the epilepsy-monitoring unit (EMU), a patient's state at seizure onset does not affect the degree of respiratory dysfunction or duration of postictal immobility. In sleep, outside the hospital setting, GTCS are likely to go unnoticed. Postictal immobility in prone patients prevents head repositioning and unimpeded air exchange. A positive feedback cycle ensues with increasing respiratory distress, potentiating postictal immobility and PGES and eventually leading to asystole. Our findings suggest that the high incidence of nocturnal SUDEP may be related to the unsupervised environment during sleep rather than the severity of sleep-related respiratory dysfunction or PGES duration in the immediate postictal period.



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[Recommendations for the organ donation from patients with brain or medullary primitive tumors on behalf of the Association of the Neuro-oncologists of French Expression (ANOCEF) and the Club of Neuro-oncology of the French Society of Neurosurgery].

Related Articles

[Recommendations for the organ donation from patients with brain or medullary primitive tumors on behalf of the Association of the Neuro-oncologists of French Expression (ANOCEF) and the Club of Neuro-oncology of the French Society of Neurosurgery].

Bull Cancer. 2017 May 23;:

Authors: Frappaz D, Le Rhun E, Dagain A, Averland B, Bauchet L, Faure A, Guillaume C, Zouaoui S, Provot F, Vachiery F, Taillandier L, Hoang-Xuan K

Abstract
Requests of organs to be transplanted increase. As a matter of urgency, it is not always easy to decide if a patient carrier of a brain tumor can be candidate in the donation. After a review of the literature, the members of the Association of the Neuro-oncologists of French Expression (ANOCEF) and the Club of Neuro-oncology of the French Society of Neurosurgery propose consensual recommendations in case of donor carrier of primitive tumor intra-cranial or intra-medullary. A contact with the neuro-oncologist/neurosurgeon will allow to discuss the indication in case of glioma of grade I/II/III, according to the grade, the current status (absence of progressive disease), the number of surgeries and of lines of treatment. The taking is disadvised in case of glioma of grade IV (glioblastoma), of lymphoma or meningioma of grade III. No contraindication for the meningiomas of grade I, and individual discussion for the meningiomas of grade II. It is advisable to remain careful in case of hemangiopericytoma and of meningeal solitary fibrous tumor. The patients in first complete remission of a medulloblastoma or intra-cranial primitive germinoma seem good candidates for the taking of organ if the follow-up is of at least 10 years (3 years for non germinomas). In every case, a multidisciplinary discussion is desirable when it is materially possible.

PMID: 28549594 [PubMed - as supplied by publisher]



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[Improving the quality of cancer pain management in palliative care unit: Targeted clinical audit].

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[Improving the quality of cancer pain management in palliative care unit: Targeted clinical audit].

Bull Cancer. 2017 May 23;:

Authors: Tricou C, Ruer M, Ledoux M, Perceau-Chambard É, Decrept D, Chabloz C, Filbet M

Abstract
Goal This study aims to assess the quality of the cancer pain management in Palliative care unit.
METHOD: The method used was the targeted clinical audit. The audit grid was built according to the recommendations of the pilot Committee, and tested until the final version with 19 items was obtained. In this retrospective study, 60 consecutive patients were studied on 2 periods of time. The first one (T1) shows the gap between the patient's chart and the expected standard, and proposes corrective measures. The second one (T2) re-assesses, using the same items list, the efficacy of these measures.
RESULTS: After the corrective measures, the patients' medical record documentation was significantly improved at T2 for: neuropathic pain assessment improved, from 3% (T1) to 67% (T2) (P<0.001), so did pain assessment during the titration, from 6.7% (T1) to 90% (T2) (P<0.001). The overdoses symptoms assessment improved from 17% at T1 to 93% at T2, (P=0.002) and breakthrough pain evaluation improved from 3% at T1 to 73% at T2, (P<0.001). The pain reassessment after the rescue doses improved from 10% at T1 to 73% at T2 (P<0.001). The other points improved but not significantly.
CONCLUSION: The quality of the pain cancer management was improved during the audit, but some points (patient education and in patient medical record documentation) can be improved. We need to continue to implement the improvement measures in our unit.

PMID: 28549593 [PubMed - as supplied by publisher]



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Cochlear implantation in patients with otosclerosis of the otic capsule.

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Cochlear implantation in patients with otosclerosis of the otic capsule.

Am J Otolaryngol. 2017 May 19;:

Authors: Burmeister J, Rathgeb S, Herzog J

Abstract
OBJECTIVE: To evaluate outcomes of cochlear implantation of patients with otosclerosis of the otic capsule.
STUDY DESIGN: A retrospective case series of 6 patients (7 ears).
PATIENTS: 6 patients (7 ears), 5 patients with severe to profound sensorineural hearing loss; 1 patient with mild to profound sensorineural hearing loss, with radiologic evidence of otosclerosis. All patients were adult males, with or without history of stapes surgery.
INTERVENTION: Cochlear implantation of 7 ears. 5 patients with severe to profound sensorineural hearing loss received the Nucleus Contour Advance peri-modiolar electrode array with binaural implantation performed in one patient. One patient with mild to profound sensorineural hearing loss received a Cochlear® Nucleus Hybrid L24 device.
METHODS: Preoperative temporal bone CT, audiometric and speech perception testing scores were reviewed, confirming presence of otosclerosis of the cochlea as well as cochlear implant candidacy. Speech perception testing included CNC words, HINT sentences and AZ Bio scores to measure hearing outcomes post implantation.
RESULTS: All recipients of the contour advance device had a significant improvement in hearing at both 3 and 6month follow up.The hybrid device recipient experienced loss of residual hearing in the implanted ear without improvement at 3months and mild improvement at 6months.
CONCLUSION: Cochlear implantation has proven to be effective in the treatment of patients with sensorineural hearing loss, including those with otosclerosis of the cochlea.Hybrid candidacy in the setting of otosclerosis of the cochlea may require consideration of alternative electrode devices, most likely a peri-modiolar device.

PMID: 28549773 [PubMed - as supplied by publisher]



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Biocompatibility of Liposome Nanocarriers in the Rat Inner Ear After Intratympanic Administration.

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Biocompatibility of Liposome Nanocarriers in the Rat Inner Ear After Intratympanic Administration.

Nanoscale Res Lett. 2017 Dec;12(1):372

Authors: Zou J, Feng H, Sood R, Kinnunen PKJ, Pyykko I

Abstract
Liposome nanocarriers (LPNs) are potentially the future of inner ear therapy due to their high drug loading capacity and efficient uptake in the inner ear after a minimally invasive intratympanic administration. However, information on the biocompatibility of LPNs in the inner ear is lacking. The aim of the present study is to document the biocompatibility of LPNs in the inner ear after intratympanic delivery. LPNs with or without gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (Gd-DOTA) were delivered to the rats through transtympanic injection. The distribution of the Gd-DOTA-containing LPNs in the middle and inner ear was tracked in vivo using MRI. The function of the middle and inner ear barriers was evaluated using gadolinium-enhanced MRI. The auditory function was measured using auditory brainstem response (ABR). The potential inflammatory response was investigated by analyzing glycosaminoglycan and hyaluronic acid secretion and CD44 and TLR2 expression in the inner ear. The potential apoptosis was analyzed using terminal transferase (TdT) to label the free 3'OH breaks in the DNA strands of apoptotic cells with TMR-dUTP (TUNEL staining). As a result, LPNs entered the inner ear efficiently after transtympanic injection. The transtympanic injection of LPNs with or without Gd-DOTA neither disrupted the function of the middle and inner ear barriers nor caused hearing impairment in rats. The critical inflammatory biological markers in the inner ear, including glycosaminoglycan and hyaluronic acid secretion and CD44 and TLR2 expression, were not influenced by the administration of LPNs. There was no significant cell death associated with the administration of LPNs. The transtympanic injection of LPNs is safe for the inner ear, and LPNs may be applied as a drug delivery matrix in the clinical therapy of sensorineural hearing loss.

PMID: 28549377 [PubMed - in process]



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Change in Excitability of Cortical Projection After Modified Catheter Balloon Dilatation Therapy in Brainstem Stroke Patients with Dysphagia: A Prospective Controlled Study.

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Change in Excitability of Cortical Projection After Modified Catheter Balloon Dilatation Therapy in Brainstem Stroke Patients with Dysphagia: A Prospective Controlled Study.

Dysphagia. 2017 May 26;:

Authors: Wei X, Yu F, Dai M, Xie C, Wan G, Wang Y, Dou Z

Abstract
Although the modified balloon dilatation therapy has been demonstrated to improve pharyngeal swallowing function post stroke, the underlying neural mechanisms of improvement are unknown. Our aims are (1) to investigate the effect of modified balloon dilatation on the excitability of corticobulbar projections to the submental muscle in dysphagic patients with brainstem stroke and (2) the relation between changes in excitability and pharyngeal kinematic modifications. Thirty patients with upper esophageal sphincter (UES) dysfunction due to unilateral brainstem stroke were recruited into two groups. The patients in dilatation group received modified balloon dilatation and conventional therapies, and those in control were only treated by conventional therapies (twice per day). The amplitudes of bilateral submental motor evoked potentials (MEPs) induced by transcranial magnetic stimulations over bilateral motor cortex, diameters of UES opening (UOD) and maximal displacement of hyoid (HD) were all assessed at baseline and the endpoint of treatments. Repeated ANOVA analysis revealed significant main effect of group, time and MEP laterality on MEP amplitudes (p = 0.02). There were no differences in the pretreatment measures between groups (all p > 0.05). After treatment, the amplitudes of affected submental MEP evoked by ipsilateral cortical pulse as well as UOD and HD were significantly different in dilatation group compared to control (amplitude: p = 0.02, UOD: p < 0.001, HD: p = 0.03). The differences of pre- and post-treatment amplitudes of the affected MEP evoked by ipsilateral stimulation showed a positive correlation with the improvement of HD (dilatation: R (2) = 0.51, p = 0.03; control: R (2) = 0.39, p = 0.01), rather than UOD in both groups (all p > 0.05). In conclusion, modified balloon dilatation therapy can increase the excitability of affected projection in patients with unilateral brainstem stroke.

PMID: 28550485 [PubMed - as supplied by publisher]



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White matter pathways mediate parental effects on children’s reading precursors

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Publication date: October 2017
Source:Brain and Language, Volume 173
Author(s): Maaike Vandermosten, Lieselore Cuynen, Jolijn Vanderauwera, Jan Wouters, Pol Ghesquière
Previous studies have shown that the link between parental and offspring’s reading is mediated by the cognitive system of the offspring, yet information about the mediating role of the neurobiological system is missing. This family study includes cognitive and diffusion MRI (dMRI) data collected in 71 pre-readers as well as parental reading and environmental data. Using sequential path analyses, which take into account the interrelationships between the different components, we observed mediating effects of the neurobiological system. More specifically, fathers’ reading skills predicted reading of the child by operating through a child’s left ventral white matter pathway. For mothers no clear mediating role of the neural system was observed. Given that our study involves children who have not yet learned to read and that environmental measures were taken into account, the paternal effect on a child’s white matter pathway is unlikely to be only driven by environmental factors. Future intergenerational studies focusing on the genetic, neurobiological and cognitive level of parents and offspring will provide more insight in the relative contribution of parental environment and genes.



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Survivin in autoimmune diseases

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Publication date: Available online 28 May 2017
Source:Autoimmunity Reviews
Author(s): G. Gravina, C. Wasen, M.J. Garcia-Bonete, M. Turkkila, M.C. Erlandsson, S. Töyrä Silfverswärd, M. Brisslert, R. Pullerits, K.M. Andersson, G. Katona, M.I. Bokarewa
Survivin is a protein functionally important for cell division, apoptosis, and possibly, for micro-RNA biogenesis. It is an established marker of malignant cell transformation. In non-malignant conditions, the unique properties of survivin make it indispensable for homeostasis of the immune system. Indeed, it is required for the innate and adaptive immune responses, controlling differentiation and maintenance of CD4+ and CD8+ memory T-cells, and in B cell maturation. Recently, survivin has emerged as an important player in the pathogenesis of autoimmune diseases. Under the conditions of unreserved inflammation, survivin enhances antigen presentation, maintains persistence of autoreactive cells, and supports production of autoantibodies. In this context, survivin takes its place as a diagnostic and prognostic marker in rheumatoid arthritis, psoriasis, systemic sclerosis and pulmonary arterial hypertension, neuropathology and multiple sclerosis, inflammatory bowel diseases and oral lichen planus. In this review, we summarise the knowledge about non-malignant properties of survivin and focus on its engagement in cellular and molecular pathology of autoimmune diseases. The review highlights utility of survivin measures for clinical applications. It provides rational for the survivin inhibiting strategies and presents results of recent reports on survivin inhibition in modern therapies of cancers and autoimmune diseases.



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Comparative Clinical Characteristics and Natural History of Three Variants of Sclerosing Cholangitis: IgG4-Related SC, PSC/AIH and PSC alone

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Publication date: Available online 28 May 2017
Source:Autoimmunity Reviews
Author(s): Min Lian, Bo Li, Xiao Xiao, Yue Yang, Pan Jiang, Li Yan, Chunyan Sun, Jun Zhang, Yiran Wei, Yanmei Li, Weihua Chen, Xiang Jiang, Qi Miao, Xiaoyu Chen, Dekai Qiu, Li Sheng, Jing Hua, Ruqi Tang, Qixia Wang, M. Eric Gershwin, Xiong Ma
There is increased interest and recognition of the clinical variants of Sclerosing Cholangitis (SC) namely IgG4-SC, PSC/AIH overlap and PSC. For most Centers, the characteristic of IgG4-SC has not been thoroughly clinically compared with other Sclerosing Cholangitis variants. Further there are relatively few PSC/AIH overlap patients and the clinical outcome is not well characterized, especially for the PSC/AIH overlap syndrome. Our objective herein is to review and clarify the differences and similarities of the natural history of IgG4-SC, the PSC/AIH overlap and PSC alone. We also place in perspective the diagnostic value of serum IgG4 for IgG4-SC and investigate biomarkers for predicting the prognosis of Sclerosing Cholangitis. In this study, we took advantage of our large and well-defined patient cohort to perform a retrospective cohort study including 57 IgG4-SC, 36 PSC/AIH overlap patients, and 55 PSC patients. Firstly, as expected, we noted significant differences amongst immunoglobulin profiles and all patients exhibited similar cholestatic profiles at presentation. Cirrhotic events were found in 20 of total 57 IgG4-SC, 15 of 36 PSC/AIH overlap, and 18 of 55 PSC patients. Serum IgG4 was elevated in 92.65% of IgG4-SC patients with an 86% sensitivity and 98% specificity for diagnosis. IgG4-SC patients had a better treatment response at 6-month and 1-year than PSC/AIH patients, while the latter responded better with steroids than PSC patients. Importantly the adverse outcome-free survival of IgG4-SC patients was reduced, unlike earlier reports, and therefore similar to the PSC/AIH overlap syndrome. Serum IgG and total bilirubin were useful to predict long-term survival of IgG4-SC and PSC/AIH, respectively. In conclusion, serum IgG4 ≧ 1.25 ULN shows an excellent predictability to distinguish IgG4-SC among SC patients. IgG4-SC appears to be immune-mediated inflammatory process, while PSC/AIH overlap more tends to be cholestatic disease.



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Repeated pulses of methyl-prednisolone with reduced doses of prednisone improve the outcome of class III, IV and V lupus nephritis: An observational comparative study of the Lupus-Cruces and lupus-Bordeaux cohorts

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Publication date: Available online 28 May 2017
Source:Autoimmunity Reviews
Author(s): Guillermo Ruiz-Irastorza, Amaia Ugarte, Cecile Saint-Pastou, Estibaliz Lazaro, Amalur Iza, Lionel Couzi, Ramon Saenz, Christophe Richez, Sabrina Porta, Patrick Blanco
ObjectiveTo compare the clinical course of patients with class III, IV and V lupus nephritis (LN) treated at Hospital Universitario Cruces (CC) and at Bordeaux University Hospital (BC).MethodsThe Lupus-Cruces nephritis protocol combines pulses of 125mg of methyl-prednisolone with each fortnightly pulse of cyclophosphamide and prednisone ≤30mg/day with tapering over 12–14weeks until 2.5–5mg/day. The BC followed international lupus nephritis guidelines, combining high-dose prednisone and either mycophenolate mofetil or cyclophosphamide, followed by maintenance therapy with low dose prednisone and immunosuppressive drugs. The main outcomes were complete renal remission (CR) and glucocorticoid toxicity.Results44 patients from BC and 29 CC were included. The mean maximum prednisone dose was 42.5 (BC) vs. 21mg/day (CC), p<0.001. The average 6-month prednisone dose was 21 (BC) vs. 8.3mg/d (CC), p<0.001.The mean number of methyl-prednisolone pulses was 3 (BC) vs. 9.3 (CC), p<0.001. HCQ was used by 64% (BC) vs. 100% (CC), p<0.001.CR rates were 30% (BC) vs. 69% (CC), p=0.001, and 42% (BC) vs. 86% (CC), p<0.001, at 6 and 12months, respectively. Patients from the CC more frequently achieved CR (adjusted HR 3.8, 95%CI 2.05–7-09). The number of pulses of methyl-prednisolone were associated with CR (adjusted HR 1.09, 95%CI 1.03–1.15). Patients in the CC had a lower risk of GC-related side effects (adjusted HR 0.19, 95%CI 0.04–0.89).ConclusionThe Lupus-Cruces nephritis protocol improves the outcome of LN. Repeated methyl-prednisolone pulses help reduce the dose of oral glucocorticoids and enhance clinical response.



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Very Early and Early Systemic Sclerosis in the Spanish Scleroderma Registry (RESCLE) Cohort

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Publication date: Available online 28 May 2017
Source:Autoimmunity Reviews
Author(s): Luis Trapiella Martínez, José Bernardino Díaz López, Luis Caminal Montero, Carles Tolosa Vilella, Alfredo Guillén del Castillo, Dolores Colunga Argüelles, Manuel Rubio Rivas, Nerea Iniesta Arandia, María Jesús Castillo Palma, Luis Sáez Comet, María Victoria Egurbide Arberas, Norberto Ortego-Centeno, Mayka Freire, Jose Antonio Vargas Hitos, Juan José Ríos Blanco, Jose Antonio Todolí Parra, Mónica Rodríguez Carballeira, Adela Marín Ballvé, Antonio Javier Chamorro Fernández, Xavier Pla Salas, Ana Belén Madroñero Vuelta, Manuel Ruiz Muñoz, Vicent Fonollosa Pla, Carmen Pilar Simeón Aznar
ObjectivesAccording to the existence of subclinical organ involvement pre-scleroderma should be divided into two subsets: very early and early disease. Pre-scleroderma patients included in the Spanish Scleroderma Registry (RESCLE) Cohort were reclassified into subsets. Differences were evaluated and the risk of progression to definite systemic sclerosis was estimated.MethodsThe characteristics of very early and early SSc patients were compared. A logistic regression model was used to determine the risk factors of progression.Results1632 patients were included, 36 (2.2%) in the very early subset and 111 (6.8%) in the early subset. There were no differences in sex, age at disease onset, duration of Raynaud's phenomenon, antinuclear antibodies or capillaroscopic findings. Three (8.3%) very early SSc patients evolved to definite SSc, 2 (5.6%) of them meeting the ACR/EULAR 2013 criteria, unlike 31 (28%) early SSc patients, 20 (24%) of them meeting the criteria (p=0.034). Digestive involvement was an independent risk factor of progression (OR 17; 95% CI, 6.1–47.2).ConclusionsThe classification of early forms of scleroderma identifies patients with different prognostic risk of progression. The evolution to definite SSc is more frequent in early than in very early SSc patients. Digestive involvement is a risk factor of progression. An active assessment of organ damage in preclinical stages allows a correct classification and risk stratification, with implications for monitoring and treatment.



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Recent advances in our understanding of giant cell arteritis pathogenesis

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Publication date: Available online 28 May 2017
Source:Autoimmunity Reviews
Author(s): Maxime Samson, Marc Corbera-Bellalta, Sylvain Audia, Ester Planas-Rigol, Laurent Martin, Maria Cinta Cid, Bernard Bonnotte
Giant cell arteritis (GCA) is a granulomatous vasculitis affecting large arteries, especially the aorta and the extracranial branches of the external carotid artery. Its exact pathogenesis is not fully understood but major progress has been made in recent years, leading to new therapeutic targets like inhibition of the interleukin-6 pathway or the modulation of immune checkpoints. The cause of GCA has not been clearly identified but it is thought that GCA occurs on a genetic background and is triggered by unknown environmental factors that could activate and lead to the maturation of dendritic cells localized in the adventitia of normal arteries. These activated dendritic cells then produce chemokines which trigger the recruitment of CD4+ T cells, which in turn become activated, proliferate and polarize into Th1 and Th17 cells, which produce IFN-γ and IL-17, respectively. Exposed to IFN-γ, endothelial cells and vascular smooth muscle cells produce chemokines leading to the recruitment of further Th1 cells, CD8+ T cells and monocytes. The latter differentiate into macrophages, which, when persistently exposed to IFN-γ, form giant cells, the histological hallmark of GCA. With the contribution of vascular smooth muscle cells, immune cells then trigger the destruction and remodeling of the arterial wall, thus leading to the formation of a neo-intima resulting in progressive occlusion of the arterial lumen, which is responsible for the ischemic symptoms of GCA. In this paper, we review recent progress in our understanding of GCA pathogenesis in the fields of genetics, epigenetics, infections, immunology and vascular remodeling.



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Neurobiological mechanisms of state-dependent learning

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Publication date: August 2017
Source:Current Opinion in Neurobiology, Volume 45
Author(s): Jelena Radulovic, Vladimir Jovasevic, Mariah AA Meyer
State-dependent learning (SDL) is a phenomenon relating to information storage and retrieval restricted to discrete states. While extensively studied using psychopharmacological approaches, SDL has not been subjected to rigorous neuroscientific study. Here we present an overview of approaches historically used to induce SDL, and highlight some of the known neurobiological mechanisms, in particular those related to inhibitory neurotransmission and its regulation by microRNAs (miR). We also propose novel cellular and circuit mechanisms as contributing factors. Lastly, we discuss the implications of advancing our knowledge on SDL, both for most fundamental processes of learning and memory as well as for development and maintenance of psychopathology.



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Neural immunoglobulin superfamily interaction networks

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Publication date: August 2017
Source:Current Opinion in Neurobiology, Volume 45
Author(s): Kai Zinn, Engin Özkan
The immunoglobulin superfamily (IgSF) encompasses hundreds of cell surface proteins containing multiple immunoglobulin-like (Ig) domains. Among these are neural IgCAMs, which are cell adhesion molecules that mediate interactions between cells in the nervous system. IgCAMs in some vertebrate IgSF subfamilies bind to each other homophilically and heterophilically, forming small interaction networks. In Drosophila, a global ‘interactome’ screen identified two larger networks in which proteins in one IgSF subfamily selectively interact with proteins in a different subfamily. One of these networks, the ‘Dpr-ome’, includes 30 IgSF proteins, each of which is expressed in a unique subset of neurons. Recent evidence shows that one interacting protein pair within the Dpr-ome network is required for development of the brain and neuromuscular system.



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Synergistic protection against acute flurothyl-induced seizures by adjuvant treatment of the ketogenic diet with the type 2 diabetes drug pioglitazone

Summary

Objective

We have previously found that the transcription factor peroxisome proliferator-activated receptor γ (PPARγ) contributes to the mechanism of action of the ketogenic diet (KD), an established treatment for pediatric refractory epilepsy. We have found that the KD increases brain PPARγ and that inhibition or genetic loss of PPARγ prevents the antiseizure effects of the KD on (1) acutely induced seizures in nonepileptic mice and (2) spontaneous recurrent seizures in epileptic mice. Here, we tested the hypothesis that adjuvant treatment of KD-treated mice with a PPARγ agonist, pioglitazone, would result in an additive effect.

Methods

Acute seizures were induced in three groups of C57Bl/6 mice by inhalation exposure to flurothyl gas. In Group 1, mice were weaned onto either a standard diet or KD comprised of a fat:carbohydrate/protein ratio of either 6:1, 3:1, or 1:1 for 2 weeks. In Group 2, vehicle or pioglitazone (0.1, 1, 10, 80 mg/kg) was administered 4 h prior to flurothyl exposure. In Group 3, vehicle or increasing doses of pioglitazone were administered to KD-treated mice 4 h prior to flurothyl exposure. Latency times to clonic seizures and generalized tonic–clonic (GTC) seizures were recorded, and isobolographic analysis was used to determine combinatorial interactions.

Results

Neither KD treatment nor pioglitazone alone or in combination affected clonic seizures. However, the latency to GTC seizures was dose-dependently and significantly increased by both KD (~57%, p < 0.05) and pioglitazone (~28%, p < 0.05). Coadministration of an ineffective 1:1 KD and pioglitazone resulted in ~47–55% (p < 0.05) increase in latency to GTC. Isobolographic analysis indicated a synergistic interaction of the KD and pioglitazone.

Significance

These results suggest coadministration may enable reduction of the KD ratio without loss of seizure protection. Such adjuvant treatment could improve quality of life and limit adverse effects of a classic KD or high-dose pioglitazone.



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