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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Osteolytic lesions: osteitis fibrosa cystica in the setting of severe primary hyperparathyroidism

A 58-year-old female patient presented with several weeks history of significant bilateral knee pain. Initial knee radiographs demonstrated lucencies of the bony cortex while extensive osteolytic lesions on a routine chest radiograph were suggestive of multiple myeloma or bony metastases. Biochemical investigation revealed primary hyperparathyroidism with renal insufficiency. A parathyroid adenoma was demonstrated on a neck ultrasound and sestamibi scan and subsequently confirmed by histology. We illustrate a case of primary hyperparathyroidism with osteitis fibrosa cystica and brown tumours which were initially mistaken for malignant disease.

http://ift.tt/2reh5f4

Streptococcus bovis prosthetic valve endocarditis associated with silent colonic carcinoma

A 75-year-old woman was admitted to our hospital with a 3-month history of fever. Of note, she had a bioprosthetic mitral valve replacement 1 year prior to admission. Streptococcus bovis was isolated from three sets of blood cultures. An echocardiogram showed a flickering mass attached to the bioprosthesis. Her blood culture became sterile by the fourth day of ceftriaxone therapy. In spite of the absence of gastrointestinal symptoms, screening colonoscopy revealed an invasive colonic adenocarcinoma. The association linking S. bovis endocarditis and colonic tumours is well recognised. However, despite early reports of this association by Klein et al in 1979, a large number of practising physicians remain unaware of this phenomenon. This lack of awareness results in lost opportunities for early diagnosis and, consequently, improved outcome in such patients. Our report emphasises this association in an area with a low incidence of S. bovis endocarditis.

http://ift.tt/2schtYC

Ichthyosis linearis circumflexa with bamboo hair: challenges in the diagnosis and management

A 15-year-old boy had persistent and refractory erythroderma since early childhood. His parents noticed polycyclic skin lesions and hair fragility around the age of 5 years. He was treated by a local untrained practitioner for more than 3 years without any significant improvement, and he developed weight gain, thinning of skin, muscle weakness and growth retardation. He was evaluated in 2015 and found to have iatrogenic Cushing's disease with severe skeletal complications and pituitary-adrenal-gonadal suppression, which persisted despite gradual withdrawal of steroids.

http://ift.tt/2reqdA5

A rare case of bilateral lens dislocations

Description

A 39-year-old man presented to our hospital following transfer from a rural site with an acute right eye anterior lens dislocation following a traumatic blow to the head. He had been hit 7 days prior and had suffered gradual vision loss in the right eye since then. Visual acuity was counting fingers at 1 m in his right eye and perception of light in his left eye. He had an intraocular pressure (IOP) of 50 mm Hg in his right eye on arrival. He had a CT head non-contrast performed. The axial (figure 1) and sagittal (figures 2 and 3) slices demonstrated a right eye anterior lens dislocation and a left eye posterior lens dislocation. The left eye had been injured 3 years prior and the patient had not sought treatment for it at the time. On examination, the left eye was found to...

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The authors respond to: "Questions on analysis of firearm injuries study" [Letters]

http://ift.tt/2rdRN0A

Disparities in infant hospitalizations in Indigenous and non-Indigenous populations in Quebec, Canada [Research]

BACKGROUND:

Infant mortality is higher in Indigenous than non-Indigenous populations, but comparable data on infant morbidity are lacking in Canada. We evaluated disparities in infant morbidities experienced by Indigenous populations in Canada.

METHODS:

We used linked population-based birth and health administrative data from Quebec, Canada, to compare hospitalization rates, an indicator of severe morbidity, in First Nations, Inuit and non-Indigenous singleton infants (< 1 year) born between 1996 and 2010.

RESULTS:

Our cohort included 19 770 First Nations, 3930 Inuit and 225 380 non-Indigenous infants. Compared with non-Indigenous infants, all-cause hospitalization rates were higher in First Nations infants (unadjusted risk ratio [RR] 2.05, 95% confidence interval [CI] 1.99–2.11; fully adjusted RR 1.43, 95% CI 1.37–1.50) and in Inuit infants (unadjusted RR 1.96, 95% CI 1.87–2.05; fully adjusted RR 1.37, 95% CI 1.24–1.52). Higher risks of hospitalization (accounting for multiple comparisons) were observed for First Nations infants in 12 of 16 disease categories and for Inuit infants in 7 of 16 disease categories. Maternal characteristics (age, education, marital status, parity, rural residence and Northern residence) partly explained the risk elevations, but maternal chronic illnesses and gestational complications had negligible influence overall. Acute bronchiolitis (risk difference v. non-Indigenous infants, First Nations 37.0 per 1000, Inuit 39.6 per 1000) and pneumonia (risk difference v. non-Indigenous infants, First Nations 41.2 per 1000, Inuit 61.3 per 1000) were the 2 leading causes of excess hospitalizations in Indigenous infants.

INTERPRETATION:

First Nations and Inuit infants had substantially elevated burdens of hospitalizations as a result of diseases of multiple systems. The findings identify substantial unmet needs in disease prevention and medical care for Indigenous infants.

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Record number of unmatched medical graduates [News]

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Antidepressant discontinuation syndrome [Practice]

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Increased rate of early smoking in children and adolescents with attention-deficit/hyperactivity disorder [Letters]

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Atypical presentation of syphilis as an aphthous ulcer [Practice]

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Cannabis legislation fails to protect Canadas youth [Editorial]

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Ectopic tooth: an unusual cause of headache [Practice]

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More on firearm injuries among children and youth [Letters]

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Two documents [Humanities]

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Is Ontarios youth pharmacare proposal just a symbolic gesture? [News]

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Questions on analysis of firearm injuries study [Letters]

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Is police-public health collaboration an oxymoron? [News]

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Long Noncoding RNAs as Biomarkers in Cancer

Long noncoding RNAs (lncRNAs) are a relatively well-characterized class of noncoding RNA (ncRNA) molecules, involved in the regulation of various cell processes, including transcription, intracellular trafficking, and chromosome remodeling. Their deregulation has been associated with the development and progression of various cancer types, the fact which makes them suitable as biomarkers for cancer diagnosis and prognosis. In recent years, detection of cancer-associated lncRNAs in body fluids of cancer patients has proven itself as an especially valuable method to effectively diagnose cancer. Cancer diagnosis and prognosis employing circulating lncRNAs are preferential when compared to classical biopsies of tumor tissues, especially due to their noninvasiveness, and have great potential for routine usage in clinical practice. Thus, this review focuses on summarizing the perspectives of lncRNAs as biomarkers in cancer, based on evaluating their expression profiles determined in body fluids of cancer patients.

http://ift.tt/2rMZ4VC

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

alsfakia@gmail.com

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

alsfakia@gmail.com

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

http://ift.tt/2rbm2mI

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

http://ift.tt/2qr5Osn

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.

http://ift.tt/2rbocTb

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.

http://ift.tt/2qqNijN

Simplified clinical algorithm for identifying patients eligible for immediate initiation of antiretroviral therapy for HIV (SLATE): protocol for a randomised evaluation

Introduction

African countries are rapidly adopting guidelines to offer antiretroviral therapy (ART) to all HIV-infected individuals, regardless of CD4 count. For this policy of 'treat all' to succeed, millions of new patients must be initiated on ART as efficiently as possible. Studies have documented high losses of treatment-eligible patients from care before they receive their first dose of antiretrovirals (ARVs), due in part to a cumbersome, resource-intensive process for treatment initiation, requiring multiple clinic visits over a several-week period.

Methods and analysis

The Simplified Algorithm for Treatment Eligibility (SLATE) study is an individually randomised evaluation of a simplified clinical algorithm for clinicians to reliably determine a patient's eligibility for immediate ART initiation without waiting for laboratory results or additional clinic visits. SLATE will enrol and randomise (1:1) 960 adult, HIV-positive patients who present for HIV testing or care and are not yet on ART in South Africa and Kenya. Patients randomised to the standard arm will receive routine, standard of care ART initiation from clinic staff. Patients randomised to the intervention arm will be administered a symptom report, medical history, brief physical exam and readiness assessment. Patients who have positive (satisfactory) results for all four components of SLATE will be dispensed ARVs immediately, at the same clinic visit. Patients who have any negative results will be referred for further clinical investigation, counselling, tests or other services prior to being dispensed ARVs. After the initial visit, follow-up will be by passive medical record review. The primary outcomes will be ART initiation ≤28 days and retention in care 8 months after study enrolment.

Ethics and dissemination

Ethics approval has been provided by the Boston University Institutional Review Board, the University of the Witwatersrand Human Research Ethics Committee (Medical) and the KEMRI Scientific and Ethics Review Unit. Results will be published in peer-reviewed journals and made widely available through presentations and briefing documents.

Trial registration

NCT02891135

http://ift.tt/2qxUBBB

Targeting JAK/STAT signalling in inflammatory skin diseases with small molecule inhibitors

For most inflammatory skin diseases topical glucocorticosteroids and traditional oral immunosuppressive drugs remain the principle treatment choices, but this has started to change. A deeper understanding in individual disease pathogenesis, basic immune mechanisms and molecular signalling pathways, together with advances in pharmaceutical drug development, allow us to interfere more precisely with disease-related factors. Some examples of inflammation-controlling interventions include antibodies neutralizing disease-associated cytokines, and small molecules targeting intracellular pathways relevant to cytokine production or cytokine signalling. So far, this is best established for psoriasis, an inflammatory skin disease dominated by Th17 cytokines. In this review, we focus on chronic inflammatory skin diseases where cytokines using type I/II cytokine receptors play a dominant role in disease pathogenesis and where novel treatments with inhibitors of the JAK/STAT pathway are already under clinical investigation. To better understand the rationale of using JAK/STAT inhibitors in the discussed skin diseases, we give an overview of important genetic and immunological associations with the JAK/STAT pathway and summarize the stage of clinical development of small molecular inhibitors. JAK/STAT inhibitors will presumably find wide application in dermatology, since they can be applied not only systematically but also topically for the treatment of inflammatory skin diseases.

This article is protected by copyright. All rights reserved

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Spontaneous CD4+ and CD8+ T cell responses directed against cancer testis antigens are present in the peripheral blood of testicular cancer patients

Cancer/Testis Antigen (CTAg) expression is restricted to spermatogenic cells in an immune-privileged site within the testis. However, these proteins are expressed aberrantly by malignant cells and T cell responses against CTAgs develop in many cancer patients. We investigated the prevalence, magnitude and phenotype of CTAg-specific T cells in the blood of patients with testicular germ cell tumors (TGCTs). CD8⁺ and CD4⁺ T cell responses against MAGE-A family antigens were present in 44% (20/45) of patients' samples assayed by ex vivo IFN-γ ELISPOT. The presence of MAGE-specific CD8⁺ T cells was further determined following short-term in vitro expansion through the use of pMHC-I multimers containing known immunogenic peptides. Longitudinal analysis revealed that the frequency of MAGE-specific T cells decreased by 89% following orchidectomy suggesting that persistence of tumor antigen is required to sustain CTAg-specific T cell immunity. Notably, this decrease correlated with a decline in the global effector/memory T cell pool following treatment. Spontaneous T cell immunity against CTAg proteins therefore develops in many patients with testicular cancer and may play an important role in the excellent clinical outcome of patients with this tumor subtype.

This article is protected by copyright. All rights reserved

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DJC Suppresses Advanced Glycation End Products-Induced JAK-STAT Signaling and ROS in Mesangial Cells

The antidiabetic properties and anti-inflammatory effects of Danzhi Jiangtang Capsules (DJC) have been demonstrated in clinical and laboratory experiments. In this study, we explored whether DJC can ameliorate advanced glycation end products- (AGEs-) mediated cell injury and the precise mechanisms of DJC in treating diabetic nephropathy (DN). Western blot analysis was employed to assess the expressions of iNOS, COX2, and SOCS and the phosphorylation of JAK2, STAT1, and STAT3 in glomerular mesangial cells (GMCs) after treatment with DJC. TNF-α, IL-6, and MCP-1 were determined using double-antibody sandwich ELISA. ROS and NADPH oxidase activity were measured by DCFH-DA assay and lucigenin-enhanced chemiluminescence, respectively. DJC significantly reversed the AGEs-induced expression of COX2 and iNOS. Moreover, DJC inhibited the AGEs-induced JAK2-STAT1/STAT3 activation, resulting in the inhibition of inflammatory cytokines such as IL-6, MCP-1, and TNF-α in a concentration-dependent manner. The ability of DJC to suppress STAT activation was also verified by the observation that DJC significantly increased the SOCS3 protein level. DJC reversed the AGEs-induced accumulation of ROS and NADPH oxidase activity, thus confirming that DJC possesses antioxidant activity. The results suggest that the anti-inflammatory effects of DJC in GMCs may be due to its ability to suppress the JAK2-STAT1/STAT3 cascades and reduce ROS production.

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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

http://ift.tt/2raXPNi

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

http://ift.tt/2raZP8r

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 5^th 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 5^th minute Apgar score.

Result: The proportion of low 5^th minute Apgar score in this study was 13.8%. Factors that were significantly associated with low 5^th 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

http://ift.tt/2qqma4E

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

http://ift.tt/2rbgXe0

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

http://ift.tt/2qqx4ak

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

http://ift.tt/2rb8TK8

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

http://ift.tt/2qqmaBG

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

http://ift.tt/2rbgVCU

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

http://ift.tt/2qqCi60

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

http://ift.tt/2rb1xq6

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

http://ift.tt/2raXN88

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

http://ift.tt/2raWwOd

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

http://ift.tt/2qqoTe9

Cost of elective percutaneous coronary intervention in Malaysia: a multicentre cross-sectional costing study

Objectives

Limitations in the quality and access of cost data from low-income and middle-income countries constrain the implementation of economic evaluations. With the increasing prevalence of coronary artery disease in Malaysia, cost information is vital for cardiac service expansion. We aim to calculate the hospitalisation cost of percutaneous coronary intervention (PCI), using a data collection method customised to local setting of limited data availability.

Design

This is a cross-sectional costing study from the perspective of healthcare providers, using top-down approach, from January to June 2014. Cost items under each unit of analysis involved in the provision of PCI service were identified, valuated and calculated to produce unit cost estimates.

Setting

Five public cardiac centres participated. All the centres provide full-fledged cardiology services. They are also the tertiary referral centres of their respective regions.

Participants

The cost was calculated for elective PCI procedure in each centre. PCI conducted for urgent/emergent indication or for patients with shock and haemodynamic instability were excluded.

Primary and secondary outcome measures

The outcome measures of interest were the unit costs at the two units of analysis, namely cardiac ward admission and cardiac catheterisation utilisation, which made up the total hospitalisation cost.

Results

The average hospitalisation cost ranged between RM11 471 (US$3186) and RM14 465 (US$4018). PCI consumables were the dominant cost item at all centres. The centre with daycare establishment recorded the lowest admission cost and total hospitalisation cost.

Conclusions

Comprehensive results from all centres enable comparison at the levels of cost items, unit of analysis and total costs. This generates important information on cost variations between centres, thus providing valuable guidance for service planning. Alternative procurement practices for PCI consumables may deliver cost reduction. For countries with limited data availability, costing method tailored based on country setting can be used for the purpose of economic evaluations.

Registration

Malaysian MOH Medical Research and Ethics Committee (ID: NMRR-13-1403-18234 IIR).

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Recreational cannabis, used often, increases risk of gum disease

Recreational use of cannabis -- including marijuana, hashish, and hash oil -- increases the risk of gum disease, shows a new study.

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Retroviral Scanning: Mapping MLV Integration Sites to Define Cell-specific Regulatory Regions

Here, we describe a protocol for genome-wide mapping of the integration sites of Moloney murine leukemia virus-based retroviral vectors in human cells.

http://ift.tt/2saQjkV

Assessment of Spontaneous Alternation, Novel Object Recognition and Limb Clasping in Transgenic Mouse Models of Amyloid-β and Tau Neuropathology

Described here is a staged, behavioral screening approach that can be used to screen for compounds that exhibit in vivo efficacy on cognitive and functional motor behaviors in transgenic mouse models of β-amyloidosis and tauopathy. These methods are optimized to screen compounds for activity in short-term and working memory tasks.

http://ift.tt/2rcyGUC

Physicians Share Latest Research with Full House at Awareness Event

On May 10, the Focused Ultrasound Foundation held its biennial awareness event in Charlottesville, Va. As in past years, attendees included the Foundation's Board of Directors, Council, and staff, as well as focused ultrasound clinicians, researchers, patients, donors, and community members interested in the impact of this innovative technology.

http://ift.tt/2r1Gjwy

Endoscopic Submucosal Dissection of T1 Cancer with Colonic Diverticulum by Pocket-Creation Method

Colorectal endoscopic submucosal dissection (ESD) still has technical difficulties and severe fibrosis and poor scope operability are reported risk factors of incomplete resection for ESD.^1-3 Recently, the pocket-creation method (PCM) has been developed for overcoming these difficulties.⁴ In PCM, a tapered hood is used for making a pocket below a tumor and it gives good traction and stable dissection even for cases with severe fibrosis and poor scope operability.

This article is protected by copyright. All rights reserved.

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Biophysical Mechanisms Mediating Fibrin Fiber Lysis

The formation and dissolution of blood clots is both a biochemical and a biomechanical process. While much of the chemistry has been worked out for both processes, the influence of biophysical properties is less well understood. This review considers the impact of several structural and mechanical parameters on lytic rates of fibrin fibers. The influences of fiber and network architecture, fiber strain, FXIIIa cross-linking, and particle transport phenomena will be assessed. The importance of the mechanical aspects of fibrinolysis is emphasized, and future research avenues are discussed.

http://ift.tt/2ru04OK

Influence of Deformation and Stress between Bone and Implant from Various Bite Forces by Numerical Simulation Analysis

Endosseous oral implant is applied for orthodontic anchorage in subjects with multiple tooth agenesis. Its effectiveness under orthodontic loading has been demonstrated clinically and experimentally. This study investigates the deformation and stress on the bone and implant for different bite forces by three-dimensional (3D) finite element (FE) methods. A numerical simulation of deformation and stress distributions around implants was used to estimate the survival life for implants. The model was applied to determine the pattern and distribution of deformations and stresses within the endosseous implant and on supporting tissues when the endosseous implant is used for orthodontic anchorage. A threaded implant was placed in an edentulous segment of a human mandible with cortical and cancellous bone. Analytical results demonstrate that maximum stresses were always located around the implant neck in marginal bone. The results also reveal that the stress for oblique force has the maximum value followed by the horizontal force; the vertical force causes the stress to have the minimum value between implant and bone. Thus, this area should be preserved clinically to maintain the structure and function of a bone implant.

http://ift.tt/2s3Aflz

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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Potential Challenges of Controlling Leishmaniasis in Sri Lanka at a Disease Outbreak

The present works reviewed the existing information on leishmaniasis in Sri Lanka and in other countries, focusing on challenges of controlling leishmaniasis in the country, in an outbreak. Evidence from recent studies suggests that there is a possibility of a leishmaniasis outbreak in Sri Lanka in the near future. Difficulty of early diagnosis due to lack of awareness and unavailability or inadequacy of sensitive tests are two of the main challenges for effective case management. Furthermore, the absence of a proper drug for treatment and lack of knowledge about vector biology, distribution, taxonomy and bionomics, and reservoir hosts make the problem serious. The evident potential for visceralization in the cutaneous variant of L. donovani in Sri Lanka may also complicate the issue. Lack of knowledge among local communities also reduces the effectiveness of vector and reservoir host control programs. Immediate actions need to be taken in order to increase scientific knowledge about the disease and a higher effectiveness of the patient management and control programs must be achieved through increased awareness about the disease among general public and active participation of local community in control activities.

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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 Scn2a^Q54 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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Dendritic cells combined with tumor cells and α-galactosylceramide induce a potent, therapeutic and NK-cell dependent antitumor immunity in B cell lymphoma.

Related Articles

Dendritic cells combined with tumor cells and α-galactosylceramide induce a potent, therapeutic and NK-cell dependent antitumor immunity in B cell lymphoma.

J Transl Med. 2017 May 26;15(1):115

Authors: Escribà-Garcia L, Alvarez-Fernández C, Tellez-Gabriel M, Sierra J, Briones J

Abstract
BACKGROUND: Invariant natural killer T (iNKT) cells are a small population of lymphocytes with unique specificity for glycolipid antigens presented by non-polymorphic CD1d receptor on dendritic cells (DCs). iNKT cells play a central role in tumor immunology since they are implicated in the coordination of innate and adaptive immune responses. These cells can be activated with the prototypic lipid α-galactosylceramide (α-GalCer), stimulating interferon gamma (IFN-γ) production and cytokine secretion, which contribute to the enhancement of T cell activation.
METHODS: We evaluated the antitumor effect of a combination of dendritic cells (DCs) and tumor cells with the iNKT cell agonist α-GalCer in a therapeutic model of B cell lymphoma. iNKT, NK and T cell phenotype was determined by flow cytometry. Serum cytokines were analyzed by Luminex technology. Significant differences between survival curves were assessed by the log-rank test. For all other data, Mann-Whitney test was used to analyze the differences between groups.
RESULTS: This vaccine induced a potent (100% survival), long-lasting and tumor-specific antitumor immune response, that was associated with an increase of both Th1 cytokines and IFN-γ secreting iNKT cells (4.59 ± 0.41% vs. 0.92 ± 0.12% in control group; p = 0.01) and T cells (CD4 IFN-γ(+): 3.75 ± 0.59% vs. 0.66 ± 0.18% p = 0.02; CD8 IFN-γ(+): 10.61 ± 0.84% vs. 0.47 ± 0.03% p = 0.002). Importantly, natural killer (NK) cells played a critical role in the antitumor effect observed after vaccination.
CONCLUSIONS: This study provides clinically relevant data for the development of iNKT-cell based immunotherapy treatments for patients with B cell malignancies.

PMID: 28549432 [PubMed - in process]

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An Integrative Developmental Genomics and Systems Biology Approach to Identify an In Vivo Sox Trio-Mediated Gene Regulatory Network in Murine Embryos

Embryogenesis is an intricate process involving multiple genes and pathways. Some of the key transcription factors controlling specific cell types are the Sox trio, namely, Sox5, Sox6, and Sox9, which play crucial roles in organogenesis working in a concerted manner. Much however still needs to be learned about their combinatorial roles during this process. A developmental genomics and systems biology approach offers to complement the reductionist methodology of current developmental biology and provide a more comprehensive and integrated view of the interrelationships of complex regulatory networks that occur during organogenesis. By combining cell type-specific transcriptome analysis and in vivo ChIP-Seq of the Sox trio using mouse embryos, we provide evidence for the direct control of Sox5 and Sox6 by the transcriptional trio in the murine model and by Morpholino knockdown in zebrafish and demonstrate the novel role of Tgfb2, Fbxl18, and Tle3 in formation of Sox5, Sox6, and Sox9 dependent tissues. Concurrently, a complete embryonic gene regulatory network has been generated, identifying a wide repertoire of genes involved and controlled by the Sox trio in the intricate process of normal embryogenesis.

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A Dosimetric Comparison of Dose Escalation with Simultaneous Integrated Boost for Locally Advanced Non-Small-Cell Lung Cancer

Background. Many studies have demonstrated that a higher radiotherapy dose is associated with improved outcomes in non-small-cell lung cancer (NSCLC). We performed a dosimetric planning study to assess the dosimetric feasibility of intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost (SIB) in locally advanced NSCLC. Methods. We enrolled twenty patients. Five different dose plans were generated for each patient. All plans were prescribed a dose of 60 Gy to the planning tumor volume (PTV). In the three SIB groups, the prescribed dose was 69 Gy, 75 Gy, and 81 Gy in 30 fractions to the internal gross tumor volume (iGTV). Results. The SIB-IMRT plans were associated with a significant increase in the iGTV dose (P

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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.

http://ift.tt/2s34pph

PAX8 Distinguishes Diffuse Large B-Cell Lymphoma Mimicking Sarcoma

PAX8 is important for embryogenesis of the thyroid, Müllerian system, and upper urinary/renal tract, and expression of PAX8 has been described in carcinomas from each of these sites. The sensitivity and specificity of the polyclonal PAX8 antibody in a large cohort of epithelial tumors as well as lymphomas have been previously determined, the latter because polyclonal PAX8 is known to be immunoreactive in nonneoplastic B-cell lymphocytes which are often used as the positive internal control for immunohistochemistry. In this case report, PAX8 was a diagnostic clue for revising a previous diagnosis of unclassified high grade sarcoma to diffuse large B-cell lymphoma. This case report demonstrates a pitfall for PAX8 immunoreactivity and acts as a reminder that lymphoma should be included in the differential diagnosis of a PAX8 positive, epithelial cell marker negative tumor of unknown primary origin.

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Contribution of the Microenvironmental Niche to Glioblastoma Heterogeneity

Glioblastoma is the most aggressive cancer of the brain. The dismal prognosis is largely attributed to the heterogeneous nature of the tumor, which in addition to intrinsic molecular and genetic changes is also influenced by the microenvironmental niche in which the glioma cells reside. The cancer stem cells (CSCs) hypothesis suggests that all cancers arise from CSCs that possess the ability to self-renew and initiate tumor formation. CSCs reside in specialized niches where interaction with the microenvironment regulates their stem cell behavior. The reciprocal interaction between glioma stem cells (GSCs) and cells from the microenvironment, such as endothelial cells, immune cells, and other parenchymal cells, may also promote angiogenesis, invasion, proliferation, and stemness of the GSCs and be likely to have an underappreciated role in their responsiveness to therapy. This crosstalk may also promote molecular transition of GSCs. Hence the inherent plasticity of GSCs can be seen as an adaptive response, changing according to the signaling cue from the niche. Given the association of GSCs with tumor recurrence and treatment sensitivity, understanding this bidirectional crosstalk between GSCs and its niche may provide a framework to identify more effective therapeutic targets and improve treatment outcome.

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CNNdel: Calling Structural Variations on Low Coverage Data Based on Convolutional Neural Networks

Many structural variations (SVs) detection methods have been proposed due to the popularization of next-generation sequencing (NGS). These SV calling methods use different SV-property-dependent features; however, they all suffer from poor accuracy when running on low coverage sequences. The union of results from these tools achieves fairly high sensitivity but still produces low accuracy on low coverage sequence data. That is, these methods contain many false positives. In this paper, we present CNNdel, an approach for calling deletions from paired-end reads. CNNdel gathers SV candidates reported by multiple tools and then extracts features from aligned BAM files at the positions of candidates. With labeled feature-expressed candidates as a training set, CNNdel trains convolutional neural networks (CNNs) to distinguish true unlabeled candidates from false ones. Results show that CNNdel works well with NGS reads from 26 low coverage genomes of the 1000 Genomes Project. The paper demonstrates that convolutional neural networks can automatically assign the priority of SV features and reduce the false positives efficaciously.

http://ift.tt/2qocZBQ