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Τετάρτη, 26 Απριλίου 2017

The Inside Scoop on the Chilean Earthquake Swarm

18157287_10158709209150571_3088421003727

According to locals, Valparaiso's 6.9 isn't worthy of being called an earthquake.

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New-onset diabetes mellitus after living-donor liver transplantation: association with graft synthetic function

Abstract

Background and purpose

It is now known that post-transplant graft function after deceased-donor liver transplantation and living-donor liver transplantation (LDLT) differ; however, there is no report assessing the relationship between graft function and the development of new-onset diabetes mellitus after transplantation (NODAT). We conducted this study to identify the predictive risk factors for NODAT, including graft function after LDLT.

Methods

The subjects of this study were 175 adult recipients who underwent LDLT at Kyoto University Hospital between 2006 and 2010, and survived for more than 3 months (median observation period, 1046 days).

Results

The 1-, 2-, and 3-year incidences of NODAT after LDLT were 26.1, 32.0, and 33.4%, respectively. Pre-transplant diabetes was associated with poor survival (p = 0.0048), whereas NODAT was not associated with patient survival. In the multivariate analysis, recipient age ≥40, a tacrolimus trough level ≥8 ng/mL 3 months after LDLT, and cholinesterase (ChE) <185 IU/L 3 months after LDLT were the independent risk factors for NODAT.

Conclusions

Poor graft synthetic function 3 months after LDLT as well as older age of the recipient and a higher tacrolimus concentration were strongly associated with NODAT development after LDLT.



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Immune function monitoring in lung transplantation using adenosine triphosphate production: time trends and relationship to postoperative infection

Abstract

Purpose

The ImmuKnow (IK) assay is a comprehensive immune function test that involves measuring adenosine triphosphate produced by the cluster of differentiation 4+ T lymphocytes in peripheral blood. The aim of this study was to analyze the time trends of IK values and assess the relationship between IK values and infections in lung transplants.

Methods

We prospectively collected 178 blood samples from 22 deceased-donor lung transplant (DDLT) recipients and 17 living-donor lobar lung transplant (LDLLT) recipients. A surveillance IK assay was performed postoperatively, then after 1 week and 1, 3, 6, and 12 months.

Results

Time trends of IK values in stable recipients peaked 1 week after DDLT (477 ± 247 ATP ng/ml), and 1 month after LDLLT (433 ± 134 ng/ml), followed by a gradual decline over 1 year. The mean IK values in infections were significantly lower than those in the stable state (119 vs 312 ATP ng/ml, p = 0.0002).

Conclusions

IK values increased sharply after lung transplantation and then decreased gradually over time in the first year, suggesting a natural history of immune function. IK values were also significantly reduced during infections. These results may provide new insights into the utility of immune monitoring after lung transplantation.



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The impact of age on the postoperative response of the diastolic function and left ventricular mass regression after surgical or transcatheter aortic valve replacement for severe aortic stenosis

Abstract

Purpose

We examined the impact of advanced age on left ventricular mass regression and the change in the diastolic function after aortic valve replacement in patients with aortic stenosis.

Methods

The present study included 129 patients who underwent either surgical or transcatheter aortic valve replacement and 1-year postoperative echocardiography. The patient characteristics and echocardiographic findings were compared between patients who were <80 years of age (group Y: n = 69) and those who were ≥80 years of age (group O: n = 60).

Results

Preoperative echocardiography revealed that although the left ventricular mass was similar between the groups, the patients in group O had more severe diastolic dysfunction in comparison to those in group Y. Postoperatively, left ventricular mass regression was significantly greater (p = 0.02) and diastolic dysfunction was less prevalent in group Y (p = 0.02) in comparison to group O. The change in E/e′ was significantly correlated with the left ventricular mass regression in group Y (p = 0.02), but not in Group O (p = 0.21).

Conclusions

The patients in group O were less susceptible to improvements in myocardial remodeling and the diastolic function in comparison to those in group Y. The altered physiological response to aortic valve replacement might help to determine the appropriate timing of surgery in elderly patients.



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Outcomes of prosthetic valve replacement in women of child-bearing age

Abstract

Purpose

The outcomes of pregnancy are more favorable for women with bioprostheses than for those with mechanical prostheses. However, bioprostheses are associated with a high reoperation rate in young women and it remains unclear whether these young women can give birth without any complications. We analyzed the outcomes of prosthetic valve replacement and investigated the effectiveness and problems associated with bioprostheses in women of child-bearing age in Japan.

Methods

The subjects of this study were six consecutive young adult women aged under 40 years, who underwent prosthetic valve replacement between January 2007 and April 2016.

Results

Bioprostheses were selected for four of these six women in consideration of their child-bearing age. Mechanical valves were selected for the other two women who underwent the Konno procedure and double valve replacement (AVR, MVR) in view of their high risk for reoperation. The cardiac operations, although without mortality or morbidity, were complex and some involved multi-time procedures. Three of the women with bioprostheses had uneventful term pregnancies.

Conclusions

These young women with bioprostheses were able to give birth safely; however, as multiple operations are often required, and bioprostheses may not be ideal for young women. Prosthetic valve selection for young women of child-bearing age requires adequate pregnancy counseling and long-term planning.



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Neuroimaging findings of postnatally acquired Zika virus infection: a pictorial essay

Abstract

Zika virus (ZIKV) is a mosquito-borne arbovirus from the Flaviviridae family, first discovered in 1947. There has been no report of severe complications caused by this virus in humans until recently. However, it is confirmed now that prenatally acquired ZIKV infection may cause severe congenital brain abnormalities in the infected fetuses. In addition, there has been an increasing number of reports during recent years about the causal relationship between postnatally acquired ZIKV infection and severe neurologic complications (mostly immune-mediated ones). Hence, ZIKV should not be considered as benign as it was initially thought, but it might be seen as a serious global threat to human health that may severely affect not only fetuses. In this pictorial essay, we aim to describe and illustrate the currently recognized spectrum of neuroimaging findings in postnatally acquired ZIKV infection. Although neurologic complications do not frequently occur in postnatal ZIKV infection, it is important to be aware of them because they may cause high morbidity and mortality in the affected patients. In addition to clinical and laboratory findings, neuroimaging may help in the diagnostic work-up to make the correct diagnosis, determine the extent of the disease, and follow the clinical course.



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Toughening high density polyethylene submitted to extreme ambient temperatures

Abstract

The use of polyethylene is limited due to its low impact strength among other mechanical properties at extreme ambient temperatures, for example at −46 °C and 66 °C. In this work, different polymer components, such as ultra-high molecular weight polyethylene (UHMWPE) and ethylene-vinyl acetate (EVA), were incorporated in high density polyethylene (HDPE) to test their ability to improve toughness of HDPE at extreme ambient temperatures. The polymer blends were processed by extrusion and injection molding and characterized by rotational rheometry, electron microscopy, thermal analysis, tensile, impact and dynamic mechanical tests. The results showed that low concentrations of EVA and UHMWPE in HDPE increased substantially the impact strength of HDPE at room temperature as well as in extreme ambient temperatures (−46 °C and 66 °C). This result indicates that these HDPE blends can be considered good candidates to replace pure HDPE in applications in which high values of toughness are required at extreme ambient temperatures.



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Orbicularis Retaining Ligament Release in Lower Blepharoplasty: Assessing Efficacy and Complications.

Purpose: Release of the orbicularis retaining ligament (ORL) has been advocated as a technique to address tear trough deformities. This study sought to compare the effectiveness and morbidity of lower blepharoplasty with and without ORL release. Methods: Retrospective chart review of 53 lower blepharoplasty patients. Twenty-six patients had ORL release and 27 patients did not. Three independent masked experienced cosmetic surgeons reviewed preoperative and postoperative photographs to assess degree of swelling, ecchymosis, change in steatoblepharon and tear trough deformity, and overall aesthetic result. Results: There were no significant differences in overall aesthetic result, change in steatoblepharon or tear trough deformity, and postoperative ecchymosis in patients who had ORL release compared with those who did not. Patients who had ORL release had postoperative swelling and chemosis of significantly longer duration and a higher likelihood of developing postoperative ectropion. Conclusions: Orbicularis retaining ligament release does not appear to result in additional aesthetic benefit in lower blepharoplasty patients and may increase morbidity in the form of ectropion and prolonged swelling and chemosis. (C) 2017 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Galectin-3 in acute coronary syndrome

Publication date: Available online 26 April 2017
Source:Clinical Biochemistry
Author(s): Luisa Agnello, Giulia Bivona, Bruna Lo Sasso, Concetta Scazzone, Viviana Bazan, Chiara Bellia, Marcello Ciaccio
Acute coronary syndrome (ACS) is a very common cause of hospitalizations worldwide each year.In the past decades biomarkers have become an indispensable tool for diagnosis, risk stratification and prognosis of cardiovascular disease, including ACS. Despite Troponin is considered the gold standard in diagnosis of ACS, several molecules have been investigated to identify predictive biomarkers of prognosis. Among these, Gal-3 has emerged as a promising prognostic marker. It has a pivotal role in inflammation and fibrosis. Both experimental and clinical studies have shown Gal-3 is an independent predictor of all-cause mortality, cardiovascular death and occurrence of HF following ACS. This article reviews the literature data regarding the role of Galectin-3 in ACS setting.



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Why don't people return their shopping carts?

Pulling up to a parking spot and finding a shopping cart there can be pretty frustrating. Why do people ignore the receptacle?

-- Read more on ScientificAmerican.com
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Skyline retention and retroactive interference in the navigating Australian desert ant, Melophorus bagoti

Abstract

Visual cues commonly aid solitary foraging ants. Specifically, foragers can use the skyline where terrestrial landmarks meet the sky. Foraging ants show a remarkable affinity to retain these terrestrial cues, developing lifelong memories of the nest site panorama. Here we explore foragers' ability to retain skyline cues of resource locations at some distance from the nest through experiments with artificial skylines erected around a resource location. We also tested the foragers' memories of one skyline at several time points after the skyline was replaced by a different one. During retention testing, foragers appear able to retain robust memories of these skylines over periods (5 days) that surpass their average life span. Exposure to the nest panorama during these periods did not interfere with navigational performance at the distant skyline. Foragers in the replacement experiment initially oriented correctly to both skylines. Thereafter, the foragers' headings in tests with the first skyline gradually shifted away from the correct homeward direction. We argue that new skyline memories cause retroactive interference in the retention of previously learned skylines. Skyline memories may compete during memory retrieval, or may be retrieved in association with context cues present in the current testing paradigm such as vector length.



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Correction



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Issue Information

Thumbnail image of graphical abstract

Cover of this issue. Mosaic expression of SMARCB1/INI1 in schwannomatosis. See also Kohashi et al. (pages 547–552 of this issue).



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In This Issue



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Why don't people return their shopping carts?

Pulling up to a parking spot and finding a shopping cart there can be pretty frustrating. Why do people ignore the receptacle?

-- Read more on ScientificAmerican.com
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Guinea worm disease

Guinea worm disease: A parasitic disease caused by infection with the guinea worm (Dracunculus medinensis), the largest parasite known to plague people. Guinea worm disease is also called Dracunculiasis and end-of-the-road disease because it is not seen in the big cities.

Once it infects a person, the guinea worm migrates through their body. It eventually emerges from the body (through the feet in 90% of cases) causing intensely painful edema (swelling), a blister and then an ulcer. Perforation of the skin by the guinea worm, which can be 6 feet long, is accompanied by fever and nausea and vomiting. Infected persons may remain sick for some months.

The disease is contracted by drinking water contaminated with the infected intermediate hosts of the parasite, called cyclops. The full-grown guinea worm begins to migrate throughout the infected person's body within about a year after ingestion. In areas where the disease is endemic (pervasive), it typically reappears every year during the agricultural season, with farmers in particular being affected.

There are no drugs to treat the disease. Prevention of the disease is based on effective surveillance systems; the provision of safe water including appropriate water supply systems, filtering devices and the chemical treatment of water to eliminate the vector; and health education.

Guinea worm infection is the only parasitic disease that may, it is hoped, be eradicated from the globe in the near future. Although widely distributed at the beginning of the 20th century, it is now confined to sub-Saharan Africa. The countries known to harbor the guinea worm are Benin, Burkina Faso, Central African Republic, Ethiopia, Ghana, Ivory Coast, Mali, Mauritania, Niger, Nigeria, Sudan, Togo and Uganda. Two-thirds of the world's estimated 100,000 annual cases of Guinea worm disease occur in war-torn Sudan, where peace is needed before aid workers can reach affected areas, mainly in the south. The Bill & Melinda Gates Foundation gave $28.5 million in 2000 to help eradicate Guinea worm disease by teaching people to boil water or strain it through cloth filters. The effort to finish off this disease is a project of WHO, World Bank and Jimmy Carter's Foundation.



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Technological quality of dough and breads from commercial algarroba–wheat flour blends

Abstract

Algarroba flour is used to supplement lysine-limiting systems such as wheat flour due to its amino acidic composition. The effects of adding up to 30% of this flour to wheat flour (W-A30) on dough characteristics and breadmaking performance were studied. Dough rheology was tested by farinograph, oscillatory rheometry and texture profile analyses. Molecular mobility was evaluated by nuclear magnetic resonance, and thermal properties were analyzed by differential scanning calorimetry and viscoamylograph studies. Besides, different bread quality parameters were evaluated. Incorporation of algarroba flour resulted into increase in water absorption, development time and degree of softening, and decrease in stability of wheat flour, leading to softer, less adhesive and elastic dough, although at intermediate replacement levels cohesiveness improved. At the molecular level, a reduction of water activity and limited proton motion were observed in W-A30 samples, suggesting that protons were highly bound to the dough matrix. Dough samples with algarroba flour showed lower G′ and G″ values than the control, although with the formation of a more elastic structure for W-A30. In addition, algarroba flour produced a protective effect on starch granule disruption and interfered with amylose–amylose association during cooling. The specific volume of breads decreased with the increase in algarroba level, W-A30 reaching the highest decrease (15%). Bread crumbs with algarroba flour exhibited higher values of hardness and resilience. The use of algarroba flour resulted in lower quality when compared to the control. However, algarroba flour at 20% level can be added to wheat flour to obtain bakery products of similar technological quality and with improved nutritional components.



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Editorial Board

Publication date: June 2017
Source:Cellular Signalling, Volume 34





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Dermoscopy pathology correlation in melanoma

Abstract

Dermoscopy is a widely used technique whose role in the clinical (and preoperative) diagnosis of melanocytic and non-melanocytic skin lesions has been well established in recent years. The aim of this paper is to clarify the correlations between the “local” dermoscopic findings in melanoma and the underlying histology, in order to help clinicians in routine practice.



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Dermoscopic evaluation of melanonychia

Abstract

The prevalence of melanonychia is approximately 1%, and it is a common symptom encountered in daily practise. However, it may also be the first symptom of melanoma of the nail apparatus. Evaluation of adult melanonychia with clinical information and clinical images is sometimes difficult for clinicians. Dermoscopic observation provides important information based on the algorithm method. Melanonychia in children requires a different approach, because dermoscopic features observed in adult nail apparatus melanoma are generally observed in benign pediatric cases.



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Dermoscopy–pathology relationship in seborrheic keratosis

Abstract

Making a definitive diagnosis of seborrheic keratosis (SK) can be challenging for the naked eye due to its wide variation in clinical features. Fortunately, however, most cases of SK exhibit the typical dermoscopic findings of fissures and ridges, hairpin vessels with white halo, comedo-like openings, and milia-like cysts, all of which are helpful to distinguish SK from melanoma, melanocytic nevus, squamous cell carcinoma, basal cell carcinoma (BCC) and other skin tumors. Histopathologically, these dermoscopic characteristics correspond to papillomatous surface of the epidermis, enlarged capillaries of the dermal papillae, pseudohorn cysts in the epidermis opened to the surface of the lesion and intraepidermal cysts, respectively. Clinicians should bear in mind that the clonal type of SK dermoscopically mimics melanoma and BCC by the presence of globule-like structures, while regressing SK exhibits a granular pattern that is similar to the peppering found in melanoma. Furthermore, milia-like cysts alone are insufficient for a conclusive diagnosis of SK because melanoma in rare cases displays cysts along with other SK-like dermoscopic findings.



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Dermoscopy enhances insight into correct diagnosis



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Review of vasculature visualized on dermoscopy

Abstract

Dermoscopy is a useful tool for finding and screening skin tumors, especially skin cancers. It is well known that it is useful to diagnose pigmented tumors, such as melanocytic lesions. In recent years, after the publication of a revised two-step algorithm in 2010, dermoscopy gradually has been used to diagnose non-pigmented or non-melanocytic lesions based on their vascular structures. Some skin lesions have specific vascular structures that aid in diagnosis. In this review, I discuss the various patterns of the vascular structures and their distribution, focusing on their clinical importance and usefulness in daily medical treatment.



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Abundance of the benign melanocytic universe: Dermoscopic–histopathological correlation in nevi

Abstract

The broad universe of “melanocytic nevi” includes a variety of different subtypes, which can be classified either due to their morphology, epidemiology, genetic alterations or risk for developing melanoma. Regarding morphology, on the one hand macroscopic/clinical and on the other hand histopathological appearance were used to subdivide in the past, often resulting in confusion and poor interobserver agreement, while nowadays dermoscopy presents the clinician's precious bridge between naked-eye examination and histopathological diagnostics, allowing prediction of the lesions’ histopathology, follow up and monitoring over time without need of excision. The non-invasive dermoscopic examination relies on the assessment of colors, patterns and the distribution of both within a cutaneous lesion. Until today, the correspondence of certain dermoscopic colors and patterns to certain histopathological correlates has been reported for a huge amount of different cutaneous lesions. Moreover, the correspondence of certain dermoscopic features to certain body sites, age groups and pigmentary traits, but also to specific genetic alterations in lesions, has been broadly investigated. Dermoscopy has led us to a new understanding of melanocytic nevi's biology and evolution and, last but not least, to a new classification system, which we want to present herein.



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Candida albicans-induced pustular lesions in mice



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Estimating melanin location in the pigmented skin lesions by hue–saturation–lightness color space values of dermoscopic images

Abstract

The depth of melanin in the skin can be estimated roughly by observation of the color exhibited on dermoscopy. Currently, there are no objective methods to estimate it. The aim of the present study was to clarify the relationship between the depth of melanin in the skin and the color variation exhibited, and to objectively estimate the 3-D location of melanin in the pigmented skin lesions from dermoscopic images. Representative colors in dermoscopic images of acral compound nevus, Spitz nevus and blue nevus were evaluated by the subjectively perceived color on dermoscopy and objective values in hue–saturation–lightness color space values. Brown colors due to small quantities of superficial melanin in the skin had high saturation and low lightness values, whereas black colors due to large quantities of superficial melanin had low saturation and low lightness values. On the other hand, colors due to melanin in the dermis were perceived as blue–gray on dermoscopy, but extracted colors showed gray–brown hue and intermediate saturation and high lightness values. In all cases, extracted representative colors of pigmented skin lesions had similar hue values within the red–orange range. Objective estimation of the 3-D location of melanin in the pigmented skin lesions is possible by the saturation and lightness values of the colors extracted from dermoscopic images. Subjectively perceived colors of melanin, especially in the dermis, can be modified by the surrounding environment effect and blue color perception.



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Investigation of contact characteristics and frictional properties of natural articular cartilage at two different surface configurations

Abstract

Natural cartilage surfaces were macroscopically curved with multi-porous viscoelastic biologic materials with extremely high water, but whether curved surface configuration could play an important role on the contact and frictional properties of natural cartilages fails to be completely understood up to now. In this current study, cartilage samples came from the 18–24 month-old bovine femora. Contact characteristic and frictional properties at two cartilage configurations were investigated using the UMT-2 testing rig and the five-point sliding average method would be adopted to analyze these tested data. These results indicated the surface displacement was extremely associated with the plate cartilage surface and seemed to be a representative of cartilage surface configuration. The summit of the surface load lagged behind that of the surface displacement at the same condition. Coefficient of friction showed obviously different variation with time at two cartilage surface configurations due to the fact that these two surface displacements had different amplitudes and opposite directions as a function of the sliding length. Therefore, surface configuration played the main role on these variables of contact displacement, contact load and coefficient of friction due to the direction and magnitude of the surface displacement while applied load and sliding velocity had a secondary role.

Graphical Abstract

Natural cartilage surfaces were macroscopically curved with multi-porous viscoelastic biologic materials with extremely high water, but whether curved surface configuration could play an important role on the contact and frictional properties of natural cartilages fails to be completely understood up to now. In this study, two different cartilage configurations were adopted to investigate natural cartilage properties, and the five-point sliding average method would be used to analyze these tested data. These results indicated the contact displacement was consisted of cartilage deformation and surface displacement while contact load was composed of steady load and surface load (as shown in the figure, panels (a) and (b)). Surface displacement was greatly associated with the plate cartilage surface and seemed to be a representative of cartilage surface configuration. These two surface displacements had different amplitudes and opposite directions as a function of the sliding length (as shown in panel (c)). The summit of the surface load lagged behind that of the surface displacement at the same condition (as shown in panel (d)). Surface displacement and surface load in the contact characteristic of natural cartilages were extremely related with the cartilage configurations. and their correlation coefficients varied periodically with the moving time (as shown in panel (e)). Coefficient of friction showed obviously different variation with time (as shown in panel (f)). Therefore, surface configuration played the main role on these variables of contact displacement, contact load and coefficient of friction due to the direction and magnitude of the surface displacement while applied load and sliding velocity had a secondary role. Variation in contact and frictional properties of natural cartilage at two different surface configurations (a) Contact displacement and its parts varied with time; (b) Contact load and its parts varied with time; (c) Surface displacement varied with the sliding length at two CPSTs; (d) Surface load and surface displacement varied with time; (e) Variation in the relation coefficient with the moving time; (f) Coefficient of friction varied with time at two CPSTs.



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Psychiatric and neurologic lessons in the oldest Persian medical liber. Akhawayani Bokhari (?-died 983 AD), physician of insane.



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A score-based performance assessment of maternal and child health services provided by USHA of Rajkot city

Ankit M Sheth, Anupam Banerjee, Amiruddin M Kadri, Matib Rangoonwala, Dipeshkumar D Zalavadiya, Niravkumar B Joshi

Indian Journal of Community Medicine 2017 42(2):97-101

Background: Urban Social Health Activists (USHAs) are the grass root health care workers of urban areas. There are 290 USHAs distributed in various Urban Health Centers (UHCs) of Rajkot city. Objectives: To compare the (i) effectiveness of the training received by the USHAs on their knowledge and counseling skills (ii) knowledge and counseling skills of USHAs on the awareness and utilization of Maternal and Child Health (MCH) care services by their beneficiaries. Methods: This cross-sectional study involved 32 USHAs and 416 beneficiaries served by the same USHAs. 32 USHAs serving in the same field practice area for more than two years were randomly selected. The beneficiaries were those mothers who had a child between 1-2 years age, and who had availed their antenatal and postnatal services in the same area. A scoring system was used to assess the knowledge and counseling skills of the USHAs and the knowledge and utilization of services by their beneficiaries. Results: The utilization of health services was significantly more in the beneficiaries who were serviced by USHAs having comparatively better knowledge (72.7% vs. 35.3%) and counseling skills (62.2% vs. 30.6%). The median score for knowledge (41 vs. 30) and counseling skills (20 vs. 16) of the USHAs was found to be more (P < 0.05) in those who had undertaken induction training. Conclusions: Induction training helped the USHAs to improve their knowledge and counseling skills. Utilization of MCH services was more in those areas served by USHAs having better knowledge and counseling skills.

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Zika virus: Can India win the fight?

Tulika Singh

Indian Journal of Community Medicine 2017 42(2):69-72

Zika virus is an emerging arbovirus of public health importance transmitted by Aedes mosquito which also transmits dengue, chikungunya and yellow fever. The disease has been spreading at an alarming rate in Africa, Pacific Islands, and the Americas. Given the expansion of environments where mosquitoes can live and breed, facilitated by urbanization and globalization, there is potential for major urban epidemics of Zika virus disease to occur globally. World Health Organization (WHO) has declared Zika virus disease to be a Public Health Emergency of International Concern (PHEIC). Our failed attempts to control dengue epidemics in the past call for concern and we need to be to prepared to fight Zika virus before it arrives at our doors.

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Improving perinatal health: Are Indian health policies progressing in the right direction?

Sharad K Singh, Ravinder Kaur, PK Prabhakar, Madhu Gupta, Rajesh Kumar

Indian Journal of Community Medicine 2017 42(2):116-119

Background: Strategic investments and policy directives of the Indian Government has demonstrated highest degree of political commitment for maternal and child health care. Objectives: To evaluate the impact of the rise in institutional deliveries in India on perinatal mortality. Methods: Hospital delivery rate and perinatal mortality rate (PNMR), reported by Sample Registration System, Registrar General of India, on a representative sample was used. The correlation between relative change in hospital deliveries and PNMR was examined. Results: In rural areas of India, hospital deliveries have increased during 2005–2013 from 24.4 to 69.7% and PNMR has declined from 40 to 28 per 1000 births. At the state level, there was significant correlation between the rise in hospital delivery rate and decline in PNMR (r 0.4, p 0.04). Conclusions: Decline in perinatal rates can be attributed to India's strategic initiatives in health policy and planning for increasing deliveries in hospitals.

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Improving access to institutional delivery through Janani Shishu Suraksha Karyakram: Evidence from rural Haryana, North India

Harshal R Salve, Lena Charlette, Ankita Kankaria, Sanjay K Rai, Anand Krishnan, Shashi Kant

Indian Journal of Community Medicine 2017 42(2):73-76

Background: In India, Janani Shishu Suraksha Karyakaram (JSSK) was launched in the year 2011 to assure cashless institutional delivery to pregnant women, including free transport and diet. Objective: To assess the impact of JSSK on institutional delivery. Materials and Methods: A record review was done at the primary health care facility in Faridabad district of Haryana from August 2010 to March 2013. Focus group discussion/ informal interviews were carried out to get an insight about various factors determining use / non-use of health facilities for delivery. Results: Institutional delivery increased by almost 2.7 times (197 Vs 537) after launch of JSSK (p < 0.001). For institutional deliveries, the most important facilitator as well as barrier was identified as ambulance service under JSSK and pressure by elders in the family respectively. Conclusions: JSSK scheme had a positive impact on institutional deliveries. It should be supported with targeted intervention designed to facilitate appropriate decision-making at family level in order to address barriers to institutional delivery.

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Role of community in swachh bharat mission. their knowledge, attitude and practices of sanitary latrine usage in rural areas, Tamil Nadu

R Anuradha, Ruma Dutta, J Dinesh Raja, D Lawrence, J Timsi, P Sivaprakasam

Indian Journal of Community Medicine 2017 42(2):107-110

Background: In most developing countries, open defecation is the 'way of life'. This practice is considered as the most serious health and environmental hazard. Prime Minister of India launched the “Swachh Bharat Mission” to accelerate the efforts for achieving universal sanitation coverage and to put focus on sanitation. Objective: To find the knowledge, attitude and practices of sanitary latrines usage in rural area, Tamil Nadu. Materials and Methods: This was a cross sectional study conducted among rural population in Kuthambakkam village, Tamil Nadu. There were a total of 1175 households in Kuthambakkam village. These households were serially numbered and of these a sample of 275 households were selected for the study using simple random sampling technique by lottery method. A structured questionnaire was used to collect information regarding the background characteristics, their knowledge, attitude and practices towards sanitary latrines usage. Descriptive statistics were calculated for background variables, the prevalence of sanitary latrines usage and open air defecation. Association between factors responsible for open air defecation was found by using chi square test. Results: The prevalence of usage of household sanitary latrine and community latrines was 62.5% and 4.3% respectively. The prevalence of open air defecation among the study participants was 33.1%.Significant association was found between low standard of living and open air defecation practice. Conclusions: To solve the problem of underutilization of sanitary latrines, planning and conducting Information Education Communication activities is very essential. Effective political and administrative support is needed to scale up the sanitation program.

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From policy to practice: lessons from Karnataka about implementation of tobacco control laws

Pragati B Hebbar, Upendra Bhojani, John Kennedy, Vishal Rao

Indian Journal of Community Medicine 2017 42(2):77-80

Background: Tobacco use accounts for eight to nine lakh adult deaths annually in India. India enacted a national legislation “Cigarettes and Other Tobacco Products Act, 2003” (COTPA) to protect health of non-smokers and reduce tobacco consumption. However, even a decade after enacting this law, its implementation remains suboptimal and variable across the Indian states. Karnataka has shown leadership on this front by enacting a state law and implementing COTPA at (sub-) district levels. We, therefore, aim to analyze COTPA implementation processes in Karnataka to understand how COTPA can be effectively implemented. Methods: We developed a case study of COTPA implementation in Karnataka using reports from health, police, education, and transport departments as well as government orders and media reports related to COTPA. We analyzed these data to map and understand the role played by the government agencies in COTPA implementation. We used the proportion of the districts reporting COTPA violations, the number of COTPA violations cases reported, and the proportion of schools reporting compliance with COTPA as proxy measures for COTPA implementation. Results: We found that five government agencies (police, education, health, transport, and urban development) played a major role in COTPA implementation. All the police districts reported COTPA violations with 59,594 cases in a year (April 2013–March 2014). Three of the district anti-tobacco cells and two of the transport divisions reported 1130 and 14,543 cases of COTPA violations, respectively, in the same year. In addition, 84.7% of schools complied with signage requirements of COTPA. COTPA reporting was made part of the reporting systems within health, police, and education departments. The health department created awareness on tobacco harms and COTPA. Conclusions: COTPA implementation in Karnataka was made possible through integrating COTPA implementation within structure/functions of five government agencies.

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Challenging times for public health towards attaining sustainable development goals

K Sujatha Rao

Indian Journal of Community Medicine 2017 42(2):65-68



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Process evaluation of communitisation programme in public sector health facilities, Mokokchung district, Nagaland, 2015

Aonungdok Tushi, Prabhdeep Kaur

Indian Journal of Community Medicine 2017 42(2):81-87

Background: Public sector health facilities were poorly managed due to a history of conflict in Nagaland, India. Government of Nagaland introduced “Nagaland Communitisation of Public Institutions and Services Act” in 2002. Main objectives of the evaluation were to review the functioning of Health Center Managing Committees (HCMCs), deliver health services in the institutions managed by HCMC, identify strengths as well as challenges perceived by HCMC members in the rural areas of Mokokchung district, Nagaland. Materials and Methods: The evaluation was made using input, process and output indicators. A doctor, the HCMC Chairman and one member from each of the three community health centers (CHC) and four primary health centers (PHC) were surveyed using a semi-structured questionnaire and an in-depth interview guide. Proportions for quantitative data were computed and key themes from the same were identified. Results: Overall; the infrastructure, equipment and outpatient/inpatient service availability was satisfactory. There was a lack of funds and shortage of doctors, drugs as well as laboratory facilities. HCMCs were in place and carried out administrative activities. HCMCs felt ownership, mobilized community contributions and managed human resources. HCMC members had inadequate funds for their transport and training. They faced challenges in service delivery due to political interference and lack of adequate human, material, financial resources. Conclusions: Communitisation program was operational in the district. HCMC members felt the ownership of health facilities. Administrative, political support and adequate funds from the government are needed for effective functioning of HCMCs and optimal service delivery in public sector facilities.

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A ten year audit of maternal mortality: Millennium development still a distant goal

Anshuja Singla, Shalini Rajaram, Sumita Mehta, Gita Radhakrishnan

Indian Journal of Community Medicine 2017 42(2):102-106

Objective: To assess various causes of maternal mortality over a ten year period Design: Retrospective audit of hospital case records Setting: Tertiary care hospital Population: Pregnant women who expired in the premises of GTB Hospital. Materials and Methods: A retrospective audit of case records of maternal deaths was conducted for a ten year period (January 2005 to December 2014). Results: There were a total of 647 maternal deaths out of 1,16,641 live births. Sixty-eight percent (n = 445) of women were aged 21-30 years, while 10.5% (n = 68) were <20 years of age. The most common direct causes of maternal mortality were preeclampsia/eclampsia in 24.4% (n = 158), obstetric hemorrhage in 19.1% (n = 124) and puerperal sepsis in 14.5% (n = 94). With regards to indirect causes, anemia accounted for 15.3% (n = 99) mortality. There was only 1 (0.1%) mortality because of HIV/AIDS. Other notable causes of maternal mortality were infective hepatitis in 7.1% (n = 46). Tuberculosis, that is a disease of tropical countries, accounted for 3.0% (n = 20) of the total deaths. Conclusion: High maternal mortality in GTB hospital can be due to it being a tertiary hospital with referrals from all neighbouring states. Accessible antenatal care can help prevent these maternal deaths. Female education can be of immense help in dealing with the problem and improving the utilization of public health facilities.

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Nutritional status of preschool children in Andaman and Nicobar Islands and food insecurity, food groups, and nutrient consumption among population

Sathya P Manimunda, Attayuru P Sugunan

Indian Journal of Community Medicine 2017 42(2):88-93

Background: Childhood undernutrition is a public health concern in India. But on such a serious issue, there are no data available from the Union Territory of Andaman and Nicobar (A and N) Islands. Objectives: Present study was designed to know the prevalence of food insecurity, to estimate food group and nutrient intake among the community, and undernutrition and clinical signs of micronutrient deficiency among the preschool children of A and N islands. Materials and Methods: Multistage random sampling was followed to select the households containing children aged 6-59 months. In the selected households' sociodemographic particulars, Household Food Insecurity Access Scale (HFIAS), among preschoolers the weight and height were recorded along with the documentation of clinical signs of micronutrient deficiency, morbidities suffered over previous fortnight, and measurement of hemoglobin. Diet survey was carried out in every fourth household. Results: A total of 1259 preschoolers residing in 1082 households were examined, HFIAS was measured in 710 households in Andaman group of islands and diet survey was conducted in 290 households. The prevalence of undernutrition was around 27%, stunting was 36%, and anemia was around 81%. Undernutrition and anemia prevalence were significantly low among Nicobarese children. After adjusting for all the determinants, tribal in domicile had favorable outcome [odds ratio (OR): 0.28 (0.18, 0.43)], while below poverty line family had adverse outcome on undernutrition [OR: 1.72 (1.20, 2.46)]. Conclusion: Though the prevalence of undernutrition is relatively low in the islands, but high prevalence of anemia needs to be addressed. Nicobarese children fare better in almost all indicators of nutritional well-being except for stunting.

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Summer temperature and spatial variability of all-cause mortality in Surat city, India

SK Rathi, VK Desai, P Jariwala, H Desai, A Naik, A Joseph

Indian Journal of Community Medicine 2017 42(2):111-115

Background: Ample information is available on extreme heat associated mortality for few Indian cities, but scant literature is available on effect of temperature on spatial variability of all-cause mortality for coastal cities. Objective: To assess the effect of daily maximum temperature, relative humidity and heat index on spatial variability of all-cause mortality for summer months (March to May) from 2014 to 2015 for the urban population of Surat (coastal) city. Materials and Methods: Retrospective analysis of the all-cause mortality data with temperature and humidity was performed on a total of 9,237 deaths for 184 summer days (2014-2015). Climatic and all-cause mortality data were obtained through Tutiempo website and Surat Municipal Corporation respectively. Bivariate analysis performed through SPSS. Observations: Mean daily mortality was estimated at 50.2 ± 8.5 for the study period with a rise of 20% all-cause mortality at temperature ≥ 40°C and rise of 10% deaths per day during extreme danger level (HI: > 54°C) days. Spatial (Zone wise) analysis revealed rise of 61% all-cause mortality for Southeast and 30% for East zones at temperature ≥ 40°C. Conclusions: All-cause mortality increased on high summer temperature days. Presence of spatial variation in all-cause mortality provided the evidence for high risk zones. Findings may be helpful in designing the interventions at micro level.

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Depression, anxiety and stress among higher secondary school students of Imphal, Manipur

K Sathish Kumar, Brogen Singh Akoijam

Indian Journal of Community Medicine 2017 42(2):94-96

Introduction: Adolescence is a stressful period due to physical, psychological, sexual changes, and the presence of psychiatric disorders such as depression, anxiety, and stress at this stage of life is a matter of concern. Objectives: The objectives of the study were to determine the prevalences of depression, anxiety, and stress among higher secondary school students of Imphal and to determine the association between depression, anxiety, and stress and selected variables such as gender, standard, and religion. Materials and methods: From September 2014 to October 2014, a cross-sectional study was conducted among higher secondary school students of Imphal. The sample size was calculated to be 750. Seven schools were randomly selected, and all the students in that school were enrolled in the study. The study tool used was a questionnaire containing DASS (Depression Anxiety Stress Scale) and sociodemographic characteristics. Results: The prevalences of depression, anxiety, and stress among 830 valid respondents were 19.5%, 24.4%, and 21.1%, respectively. In total, 81.6% of the respondents had at least one of the studied disorders and 34.7% of the respondents had all the three negative states. The prevalences of depression, anxiety, and stress were high among females and were significant for anxiety (P = 0.00) and stress (P = 0.04). The prevalences of depression and stress were significantly higher among 12th standard students with P-values of 0.00 and 0.02. Conclusion: The prevalences of depression, anxiety, and stress were high with anxiety and stress significantly higher among females, whereas prevalences of depression and stress were significantly higher among 12th standard students. More studies are recommended to determine the factors leading to these mental disorders.

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Leprosy: An urgent need to step up surveillance

Sathish Dev, Timsi Jain, P Sivaprakasam, J Dinesh Raja

Indian Journal of Community Medicine 2017 42(2):120-121



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StPBS2, a MAPK kinase gene, is involved in determining hyphal morphology, cell wall development, hypertonic stress reaction as well as the production of secondary metabolites in Northern Corn Leaf Blight pathogen Setosphaeria turcica

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Publication date: Available online 26 April 2017
Source:Microbiological Research
Author(s): Xiao-dong Gong, Sheng-ze Feng, Jie Zhao, Cong Tang, Lan Tian, Yong-shan Fan, Zhi-yan Cao, Zhi-min Hao, Hui Jia, Jin-ping Zang, Yun-feng Zhang, Jian-min Han, Shou-qin Gu, Jin-gao Dong
Mitogen activated protein kinase kinase (MAPKK) is a crucial component in the MAPK signaling pathway. However, the functions of MAPKKs in foliar pathogens remain poorly understood. In the current study, a MAPKK gene designated as StPBS2 was cloned from Setosphaeria turcica and the functions of this gene were investigated by RNAi technology. Four independent StPBS2 gene silence transformants with different efficiencies were confirmed by real time PCR. Compared to the wild type strain (WT), these transformants showed decreased colony growth, shortened hyphae cell length, broadened cell width and an obvious reduction in conidium yield. Moreover, the cell wall of the transformants was thicker and they were also more sensitive to substances that interfere with cell wall biosynthesis than WT. Additionally, the transformants displayed higher sensitivity to hypertonic stress than WT and the sensitivity was associated with the level of silencing of StPBS2. They were also resistant to the fungicides iprodione, procymidone and fludioxonil, to which WT almost completely sensitive. The transformants produced more red secondary metabolites than WT and the production was enhanced with increasing silencing level and increased glucose content in PDA medium. Our results suggest that StPBS2 is involved in morphogenesis, condiogenesis, cell wall development, hypertonic stress reaction and resistance to fungicides, as well as in the biosynthesis of secondary metabolites in S. turcica.



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Editorial Board

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Publication date: June 2017
Source:Microbiological Research, Volume 199





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Mycoplasma fermentans deacetylase promotes mammalian cell stress tolerance

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Publication date: Available online 26 April 2017
Source:Microbiological Research
Author(s): Qingzhou Cheng, Lijuan Wu, Rongfu Tu, Jun Wu, Wenqian Kang, Tong Su, Runlei Du, Wenbin Liu
Mycoplasma fermentans is a pathogenic bacterium that infects humans and has potential pathogenic roles in respiratory, genital and rheumatoid diseases. NAD+-dependent deacetylase is involved in a wide range of pathophysiological processes and our studies have demonstrated that expression of mycoplasmal deacetylase in mammalian cells inhibits proliferation but promotes anti-starvation stress tolerance. Furthermore, mycoplasmal deacetylase is involved in cellular anti-oxidation, which correlates with changes in the proapoptotic proteins BIK, p21 and BIM. Mycoplasmal deacetylase binds to and deacetylates the FOXO3 protein, similar with mammalian SIRT2, and affects expression of the FOXO3 target gene BIM, resulting in inhibition of cell proliferation. Mycoplasmal deacetylase also alters the performance of cells under drug stress.This study expands our understanding of the potential molecular and cellular mechanisms of interaction between mycoplasmas and mammalian cells.



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Reconfigurable Antenna Arrays with Multiple Requirements: A Versatile 3D Approach

This paper proposes a deterministic method for the 3D synthesis of antenna arrays that jointly accounts for far-field pattern reconfigurability, polarization setting, dynamic range ratio reduction, and near-field control. The conceived algorithm, which generalizes some existing solutions, relies on a weighted cost function, whose iterative minimization is accomplished by properly derived closed-form expressions. This feature, combined with the possibility of selecting the weighting parameters, provides a fast and versatile approach, whose capabilities are numerically checked by considering different synthesis problems and array structures in the presence of mutual coupling.

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Application of Environmental Scanning Electron Microscope-Nanomanipulation System on Spheroplast Yeast Cells Surface Observation

The preparation and observations of spheroplast W303 cells are described with Environmental Scanning Electron Microscope (ESEM). The spheroplasting conversion was successfully confirmed qualitatively, by the evaluation of the morphological change between the normal W303 cells and the spheroplast W303 cells, and quantitatively, by determining the spheroplast conversion percentage based on the OD800 absorbance data. From the optical microscope observations as expected, the normal cells had an oval shape whereas spheroplast cells resemble a spherical shape. This was also confirmed under four different mediums, that is, yeast peptone-dextrose (YPD), sterile water, sorbitol-EDTA-sodium citrate buffer (SCE), and sorbitol-Tris-Hcl-CaCl2 (CaS). It was also observed that the SCE and CaS mediums had a higher number of spheroplast cells as compared to the YPD and sterile water mediums. The OD800 absorbance data also showed that the whole W303 cells were fully converted to the spheroplast cells after about 15 minutes. The observations of the normal and the spheroplast W303 cells were then performed under an environmental scanning electron microscope (ESEM). The normal cells showed a smooth cell surface whereas the spheroplast cells had a bleb-like surface after the loss of its integrity when removing the cell wall.

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In Vitro Evaluations and In Vivo Toxicity and Efficacy Studies of MFM501 against MRSA

Previously we have discovered a synthetically derived pyrrolidone alkaloid, MFM501, exhibiting good inhibitory activity against 53 MRSA and MSSA isolates with low cytotoxicity against three normal cell-lines with IC50 values at >625 µg/ml. Time-kill assay, scanning electron microscopy (SEM) analysis, in vivo oral acute toxicity test, and mice peritonitis model were carried out in this study. In the time-kill study, MFM501 showed a less than 3 log10 decrease in bacterial colony concentration value (CFU/ml) which represented a bacteriostatic action while displaying a time-dependent inhibitory mechanism. Following that, SEM analysis suggested that MFM501 may exert its inhibitory activity via cytoplasmic membrane disruption. Moreover, MFM501 showed no toxicity effect on treated mice at an estimated median acute lethal dose (LD50) value of more than 300 mg/kg and less than 2000 mg/kg. For the efficacy test, a mean effective dose (ED50) of 87.16 mg/kg was obtained via a single dose oral administration. Our data demonstrated that MFM501 has the potential to be developed further as a new, safe, and effective oral-delivered antibacterial agent against MRSA isolates.

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Robust Relay in Narrow-Band Communications for Ubiquitous IoT Access

We propose a robust wireless relay scheme in narrow-band communications for IoT access, which matches the typical features of IoT often carrying relatively low data rate with limited bandwidth. This framework is towards offering robustness in QoS guarantees with emphases on security and/or reliability, and we use the security-assured network as the typical scenario. In particular, we consider a dual-hop relay network including a transmitter, a receiver, an amplify-and-forward (AF) untrusted relay, and a jamming node. The jamming node is treated as a helper. Specifically, the jammer broadcasts artificial noise (AN), which in fact pollutes both the untrusted relay and the destination node’s signals. However, we show that such AN can be effectively mitigated after the destination node obtains the forwarded signal from the relay, while the untrusted relay node cannot do so. The core idea for robustness assurance is to exploit higher signal dimensions at the receiver over the untrusted relay node. Simulations and analyses are also conducted to demonstrate that our proposed scheme can make the performance at the untrusted relay an interference-limited manner while completely removing the interferences at the receiver, therefore corroborating our claim in robustness in terms of security and reliability.

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Landscape of combination immunotherapy and targeted therapy to improve cancer management

Cancer treatments composed of immune checkpoint inhibitors and oncogene-targeted drugs might improve cancer management, but there has been little investigation of their combined potential as yet. To estimate the fraction of cancer cases that might benefit from such combination therapy, we conducted an exploratory study of cancer genomic data sets to determine the proportion with somatic mutation profiles amenable to either immunotherapy or targeted therapy. We surveyed 13,349 genomic profiles from public databases for cases with specific mutations targeted by current agents or a burden of exome-wide non-synonymous mutations (NsM) that exceeds a proposed threshold for response to checkpoint inhibitors. Overall, 8.9% of cases displayed profiles that could benefit from combination therapy, which corresponded to approximately 11.2% of US annual incident cancer cases. Frequently targetable mutations were in PIK3CA, BRAF, NF1, NRAS and PTEN. We also noted a high burden of NsM in cases with targetable mutations in SMO, DDR2, FGFR1, PTCH1, FGFR2 and MET. Our results indicate that a significant proportion of solid tumor patients are eligible for immuno-targeted combination therapy, and they suggest prioritizing specific cancers for trials of certain targeted and checkpoint inhibitor drugs.

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Deletion of lactate dehydrogenase-A in myeloid cells triggers antitumor immunity.

Immunometabolism is emerging as a critical determinant of cancer pathophysiology. In this study, we explored the contributions of macrophage-expressed lactate dehydrogenase-A (LDH-A) to tumor formation in a K-Ras murine model of lung carcinoma. Myeloid-specific deletion of LDH-A promoted accumulation of macrophages with a CD86high and MCP-1high M1-like phenotype that suppressed tumor growth. This phenotypic effect was accompanied by reduced VEGF expression and angiogenesis; diminished numbers of PD-L1+ cancer cells; increased numbers of CD3+ T cells and activation status of CD8+ T cells. Further, it was associated with more pronounced antitumor T cell immunity via induction of IL-17 and IFNγ-producing CD8+ T (Tc17 and Tc1) cells, likely via suppression of lactate-driven PD-L1 expression. Our results suggest that expression of LDH-A and lactate by macrophage in the tumor microenvironment are major drivers of T cell immunosuppression, strongly supporting the concept of targeting stromal LDH-A as an effective strategy to blunt tumoral immune escape.

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tRF/miR-1280 suppresses stem cell-like cells and metastasis in colorectal cancer

Several studies have shown that tRNAs can be enzymatically cleaved to generate distinct classes of tRNA-derived fragments (tRF). Here we report that tRF/miR-1280, a 17bp fragment derived from tRNALeu and pre-miRNA, influences Notch signaling pathways that support the function of cancer stem-like cells (CSC) in colorectal cancer progression. tRF/miR-1280 expression was decreased in human specimens of colorectal cancer (CRC). Ectopic expression of tRF/miR-1280 reduced cell proliferation and colony formation, whereas its suppression reversed these effects. Mechanistic investigations implicated the Notch ligand JAG2 as a direct target of tRF/miR-1280 binding through which it reduced tumor formation and metastasis. Notably, tRF/miR-1280-mediated inactivation of Notch signaling suppressed CSC phenotypes, including by direct transcriptional repression of the Gata1/3 and miR-200b genes. These results were consistent with findings of decreased levels of miR-200b and elevated levels of JAG2, Gata1, Gata3, Zeb1 and Suz12 in CRC tissue specimens. Taken together, our results established that tRF/miR-1280 suppresses CRC growth and metastasis by repressing Notch signaling pathways that support CSC phenotypes. Further, they provide evidence that functionally active miRNA can be derived from tRNA, offering potential biomarker and therapeutic uses.

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The National Cancer Institute ALMANAC: A Comprehensive Screening Resource for the Detection of Anticancer Drug Pairs with Enhanced Therapeutic Activity

To date, over 100 small molecule oncology drugs have been approved by the US Food and Drug Administration. Due to the inherent heterogeneity of tumors, these small molecules are often administered in combination to prevent emergence of resistant cell subpopulations. Therefore, new combination strategies to overcome drug resistance in patients with advanced cancer are needed. In this study, we performed a systematic evaluation of the therapeutic activity of over 5,000 pairs of FDA-approved cancer drugs against a panel of 60 well-characterized human tumor cell lines (NCI-60) to uncover combinations with greater than additive growth-inhibitory activity. Screening results were compiled into a database, termed the NCI‑ALMANAC (A Large Matrix of Anti-Neoplastic Agent Combinations), publicly available at http://ift.tt/2q9TSKL. Subsequent in vivo experiments in mouse xenograft models of human cancer confirmed combinations with greater than single-agent efficacy. Concomitant detection of mechanistic biomarkers for these combinations in vivo supported the initiation of two phase I clinical trials at the NCI to evaluate clofarabine with bortezomib and nilotinib with paclitaxel in patients with advanced cancer. Consequently, the hypothesis-generating NCI-ALMANAC web-based resource has demonstrated value in identifying promising combinations of approved drugs with potent anticancer activity for further mechanistic study and translation to clinical trials.

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Bim gene dosage is critical in modulating nephron progenitor survival in the absence of microRNAs during kidney development [Research]

Low nephron endowment at birth has been associated with an increased risk for developing hypertension and chronic kidney disease. We demonstrated in an earlier study that conditional deletion of the miRNA-processing enzyme Dicer from nephron progenitors results in premature depletion of the progenitors and increased expression of the proapoptotic protein Bim (also known as Bcl-2L11). In this study, we generated a compound mouse model with conditional deletion of both Dicer and Bim, to determine the biologic significance of increased Bim expression in Dicer-deficient nephron progenitors. The loss of Bim partially restored the number of nephron progenitors and improved nephron formation. The number of progenitors undergoing apoptosis was significantly reduced in kidneys with loss of a single allele, or both alleles, of Bim compared to mutant kidneys. Furthermore, 2 miRNAs expressed in nephron progenitors (miR-17 and miR-106b) regulated Bim levels in vitro and in vivo. Together, these data suggest that miRNA-mediated regulation of Bim controls nephron progenitor survival during nephrogenesis, as one potential means of regulating nephron endowment.—Cerqueira, D. M., Bodnar, A. J., Phua, Y. L., Freer, R., Hemker, S. L., Walensky, L.D., Hukriede, N. A., Ho, J. Bim gene dosage is critical in modulating nephron progenitor survival in the absence of microRNAs during kidney development.



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NFAT5-sensitive Orai1 expression and store-operated Ca2+ entry in megakaryocytes [Research]

The transcription factor NFAT5 is up-regulated in several clinical disorders including dehydration. NFAT5-sensitive genes include serum and glucocorticoid-inducible kinase (SGK)-1. The kinase is a powerful regulator of Orai1, a Ca2+-channel accomplishing store-operated Ca2+-entry (SOCE). Orai1 is stimulated after intracellular store depletion by the Ca2+ sensors stromal interaction molecule (STIM)-1, or STIM2, or both. In the present study, we explored whether nuclear factor of activated T cell (NFAT)-5 influences Ca2+-signaling in megakaryocytes. To this end, human megakaryocytic (MEG-01) cells were transfected with NFAT5 or with siNFAT5. Platelets and megakaryocytes were isolated from wild-type mice with either access to water ad libitum or dehydration by 36 h of water deprivation. Transcript levels were determined with quantitative RT-PCR and protein abundance by Western blot analysis and flow cytometry, cytosolic Ca2+-concentration ([Ca2+]i) by fura-2-fluorescence. SOCE was estimated from the increase of [Ca2+]i following readdition of extracellular Ca2+ after store depletion with thapsigargin (1 µM). Platelet degranulation was estimated from P-selectin abundance and integrin activation from αIIbβ3 integrin abundance determined by flow cytometry. As a result, NFAT5 transfection or exposure to hypertonicity (+40 mM NaCl) of MEG-01 cells increased Orai1, Orai2, STIM1, and STIM2 transcript levels. Orai1 transcript levels were decreased by NFAT5 silencing. NFAT5 transfection and IB inhibitor BMS 345541 (5 µM) increased, whereas NFAT5 silencing and SGK1 inhibitor GSK650394 (10 µM) decreased SOCE. In the mice, dehydration increased NFAT5 and Orai1 protein abundance in megakaryocytes and NFAT5, Orai1, and Orai2 abundance in platelets. Dehydration further augmented the degranulation and integrin activation by thrombin and collagen-related peptide. In conclusion, NFAT5 is a powerful regulator of Orai1-expression and SOCE in megakaryocytes.—Sahu, I., Pelzl, L., Sukkar, B., Fakhri, H., al-Maghout, T., Cao, H., Hauser, S., Gutti, R., Gawaz, M., Lang, F. NFAT5-sensitive Orai1 expression and store-operated Ca2+ entry in megakaryocytes.



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Effects of RNA integrity on transcript quantification by total RNA sequencing of clinically collected human placental samples [Research]

RNA degradation is a ubiquitous process that occurs in living and dead cells, as well as during handling and storage of extracted RNA. Reduced RNA quality caused by degradation is an established source of uncertainty for all RNA-based gene expression quantification techniques. RNA sequencing is an increasingly preferred method for transcriptome analyses, and dependence of its results on input RNA integrity is of significant practical importance. This study aimed to characterize the effects of varying input RNA integrity [estimated as RNA integrity number (RIN)] on transcript level estimates and delineate the characteristic differences between transcripts that differ in degradation rate. The study used ribodepleted total RNA sequencing data from a real-life clinically collected set (n = 32) of human solid tissue (placenta) samples. RIN-dependent alterations in gene expression profiles were quantified by using DESeq2 software. Our results indicate that small differences in RNA integrity affect gene expression quantification by introducing a moderate and pervasive bias in expression level estimates that significantly affected 8.1% of studied genes. The rapidly degrading transcript pool was enriched in pseudogenes, short noncoding RNAs, and transcripts with extended 3' untranslated regions. Typical slowly degrading transcripts (median length, 2389 nt) represented protein coding genes with 4–10 exons and high guanine-cytosine content.—Reiman, M., Laan, M., Rull, K., Sõber, S. Effects of RNA integrity on transcript quantification by total RNA sequencing of clinically collected human placental samples.



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Antifibrotic effects of cyclosporine A on TGF-{beta}1-treated lung fibroblasts and lungs from bleomycin-treated mice: role of hypoxia-inducible factor-1{alpha} [Research]

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder that is characterized by aberrant tissue remodeling and the formation of fibroblastic foci that are composed of fibrogenic myofibroblasts. TGF-β1 is one of the factors that are responsible for fibrosis as it promotes fibroblast to myofibroblast differentiation (FMD) and is associated with up-regulation of α-smooth muscle actin. Therefore, inhibition of FMD may represent an effective strategy for the treatment of IPF. Here, we describe the treatment of human lung fibroblasts (WI-38 and HFL-1 cells) with cyclosporine A (CsA), which reduces TGF-β1–induced FMD via degradation of hypoxia-inducible factor-1α (HIF-1α). In addition, in primary myofibroblast-like cells that were obtained from a patient with pulmonary fibrosis, treatment with CsA and an HIF-1α inhibitor (HIFi) decreased the expression levels of α-smooth muscle actin and fibronectin, which indicated that CsA and HIFi promote dedifferentiation of myofibroblasts. In mice, intratracheally administered CsA or HIFi at an early fibrotic stage {7, 8, and 9 d postbleomycin instillation [days postinstillation (dpi)]}, marked alleviation of lung fibrosis was observed at 14 dpi. These results suggest that CsA exhibits antifibrotic effects by degrading HIF-1α and that the CsA–HIF-1α axis provides new insights into therapeutic options for the treatment of IPF.—Yamazaki, R., Kasuya, Y., Fujita, T., Umezawa, H., Yanagihara, M., Nakamura, H., Yoshino, I., Tatsumi, K., Murayama, T. Antifibrotic effects of cyclosporine A on TGF-β1–treated lung fibroblasts and lungs from bleomycin-treated mice: role of hypoxia-inducible factor-1α.



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Erratum to: Comparative lung bioavailability of fluticasone/salmeterol via a breath-actuated spacer and conventional plastic spacers



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Return to sports after plate fixation of humeral head fractures 65 cases with minimum 24-month follow-up

Abstract

Background

Humeral head fractures requiring surgical intervention are severe injuries, which might affect the return to sports and daily activities. We hypothesize that athletic patients will be constrained regarding their sporting activities after surgically treated humeral head fractures. Despite a long rehabilitation program physical activities will change and an avoidance of overhead activities will be noticed.

Methods

Case series with 65 Patients, with a minimum follow-up of 24 months participated in this study. All patients were treated using a locking plate fixation. Their sporting activity was investigated at the time of the injury and re-investigated after an average of 3.83 years. The questionnaire setup included the evaluation of shoulder function, sporting activities, intensity, sport level and frequency evaluation. Level of evidence IV.

Results

At the time of injury 61 Patients (94%) were engaged in recreational sporting activities. The number of sporting activities declined from 26 to 23 at the follow-up examination. There was also a decline in sports frequency and duration of sports activities.

Conclusion

The majority of patients remains active in their recreational sporting activity at a comparable duration and frequency both pre- and postoperatively. Nevertheless, shoulder centered sport activities including golf, water skiing and martial arts declined or were given up.



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The clinical and cost-effectiveness of stratified care for patients with sciatica: the SCOPiC randomised controlled trial protocol (ISRCTN75449581)

Abstract

Background

Sciatica has a substantial impact on patients, and is associated with high healthcare and societal costs. Although there is variation in the clinical management of sciatica, the current model of care usually involves an initial period of 'wait and see' for most patients, with simple measures of advice and analgesia, followed by conservative and/or more invasive interventions if symptoms fail to resolve. A model of care is needed that does not over-treat those with a good prognosis yet identifies patients who do need more intensive treatment to help with symptoms, and return to everyday function including work. The aim of the SCOPiC trial (SCiatica Outcomes in Primary Care) is to establish whether stratified care based on subgrouping using a combination of prognostic and clinical information, with matched care pathways, is more effective than non-stratified care, for improving time to symptom resolution in patients consulting with sciatica in primary care. We will also assess the impact of stratified care on service delivery and evaluate its cost-effectiveness compared to non-stratified care.

Methods/Design

Multicentre, pragmatic, parallel arm randomised trial, with internal pilot, cost-effectiveness analysis and embedded qualitative study. We will recruit 470 adult patients with sciatica from general practices in England and Wales, over 24 months. Patients will be randomised to stratified care or non-stratified care, and treated in physiotherapy and spinal specialist services, in participating NHS services. The primary outcome is time to first resolution of sciatica symptoms, measured on a 6-point ordered categorical scale, collected using text messaging. Secondary outcomes include physical function, pain intensity, quality of life, work loss, healthcare use and satisfaction with treatment, and will be collected using postal questionnaires at 4 and 12-month follow-up. Semi-structured qualitative interviews with a subsample of participants and clinicians will explore the acceptability of stratified care.

Discussion

This paper presents the details of the rationale, design and processes of the SCOPiC trial. Results from this trial will contribute to the evidence base for management of patients with sciatica consulting in primary care.

Trial registration

ISRCTN75449581, date: 20.11.2014.



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Is there any place for counterterrorism in the NHS?

A terrorist attack killing five people in Westminster last month put the government’s counterterrorism strategy under the spotlight. One of the key planks is the Prevent strategy, which aims to...
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Addiction to exercise

What you need to knowAddiction to exercise might form part of a broader eating disorder or may occur in isolationInability to stop or reduce exercising, for example in response to an injury, may...
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