Carbon-Nanotube-Confined Vertical Heterostructures with Asymmetric Contacts

Van der Waals (vdW) heterostructures have received intense attention for their efficient stacking methodology with 2D nanomaterials in vertical dimension. However, it is still a challenge to scale down the lateral size of vdW heterostructures to the nanometer and make proper contacts to achieve optimized performances. Here, a carbon-nanotube-confined vertical heterostructure (CCVH) is employed to address this challenge, in which 2D semiconductors are asymmetrically sandwiched by an individual metallic single-walled carbon nanotube (SWCNT) and a metal electrode. By using WSe₂ and MoS₂, the CCVH can be made into p-type and n-type field effect transistors with high on/off ratios even when the channel length is 3.3 nm. A complementary inverter was further built with them, indicating their potential in logic circuits with a high integration level. Furthermore, the Fermi level of SWCNTs can be efficiently modulated by the gate voltage, making it competent for both electron and hole injection in the CCVHs. This unique property is shown by the transition of WSe₂ CCVH from unipolar to bipolar, and the transition of WSe₂/MoS₂ from p–n junction to n–n junction under proper source–drain biases and gate voltages. Therefore, the CCVH, as a member of 1D/2D mixed heterostructures, shows great potentials in future nanoelectronics and nano-optoelectronics.

Carbon-nanotube-confined vertical hetero-structures can be applied to scale down the lateral size of van der Waals heterostructures to the nanometer, and to make proper contacts to achieve optimized performance of the Fermi level of single-walled carbon nanotubes that can be efficiently modulated by gate voltage. As a member of 1D/2D mixed heterostructures, they show great potential for future nanoelectronics and nano-optoelectronics.

http://ift.tt/2x4GlVv

Two-Photon In Vivo Imaging with Porous Silicon Nanoparticles

A major obstacle in luminescence imaging is the limited penetration of visible light into tissues and interference associated with light scattering and autofluorescence. Near-infrared (NIR) emitters that can also be excited with NIR radiation via two-photon processes can mitigate these factors somewhat because they operate at wavelengths of 650–1000 nm where tissues are more transparent, light scattering is less efficient, and endogenous fluorophores are less likely to absorb. This study presents photolytically stable, NIR photoluminescent, porous silicon nanoparticles with a relatively high two-photon-absorption cross-section and a large emission quantum yield. Their ability to be targeted to tumor tissues in vivo using the iRGD targeting peptide is demonstrated, and the distribution of the nanoparticles with high spatial resolution is visualized.

Two-photon excitation of porous silicon nanoparticles results in photolytically stable near-infrared emission that can be used for in vivo imaging. When conjugated to the iRGD peptide, the intravenously injected nanoparticles selectively home to a tumor xenograft, enabling tumor imaging with high spatial resolution.

http://ift.tt/2x4vlqV

Flexible Electrodes for Sodium-Ion Batteries: Recent Progress and Perspectives

Sodium-ion batteries (SIBs) are considered as promising alternatives to lithium-ion batteries (LIBs) for large-scale electrical-energy-storage applications due to the wide availability and the low cost of Na resources. Along with the avenues of research on flexible LIBs, flexible SIBs are now being actively developed as one of the most promising power sources for the emerging field of flexible and wearable electronic devices. Here, the recent progress on flexible electrodes based on metal substrates, carbonaceous substrates (i.e., graphene, carbon cloth, and carbon nanofibers), and other materials, as well as their applications in flexible SIBs, are summarized. Also, some future research directions for constructing flexible SIBs are proposed, with the aim of providing inspiration to the further development of advanced flexible SIBs.

Flexible sodium-ion batteries (SIBs) are being actively developed as one of the most promising power sources for the emerging field of flexible and wearable electronic devices. The recent progress on flexible electrodes based on metal substrates, carbonaceous substrates, and other materials, is summarized, along with their applications in flexible SIBs.

http://ift.tt/2vRltCi

Alteration of retinal layers in healthy subjects over 60 years of age until nonagenarians

http://ift.tt/2v5gMly

The effect of intravitreal injections on dry eye, and proposed management strategies

http://ift.tt/2wvoVn8

Comparison of recommendations for screening mammography using CISNET models

BACKGROUND

Currently, there are several different recommendations for screening mammography from major national health care organizations, including: 1) annual screening at ages 40 to 84 years; 2) screening annually at ages 45 to 54 years, then biennially at ages 55 to 79 years; and 3) biennial screening at ages 50 to 74 years.

METHODS

Mean values of six Cancer Intervention and Surveillance Modeling Network (CISNET) models were used to compare these three screening mammography recommendations in terms of benefits and risks.

RESULTS

Mean mortality reduction was greatest with the recommendation of annual screening at ages 40 to 84 years (39.6%), compared with the hybrid recommendation of screening annually at ages 45 to 54 years, then biennially at ages 55 to 79 years (30.8%), and the recommendation of biennial screening at ages 50 to 74 years (23.2%). For a single-year cohort of US women aged 40 years, assuming 100% compliance, more breast cancers deaths would be averted over their lifetime with annual screening starting at age 40 (29,369) than with the hybrid recommendation (22,829) or biennial screening ages 50-74 (17,153 based on 2009 CISNET estimates, 15,599 based on 2016 CISNET estimates). To achieve the greatest mortality benefit, this single-year cohort of women would have the greatest total number of screening mammograms, benign recalls, and benign biopsies performed over the course of screening by following annual screening starting at age 40 years (90.2 million, 6.8 million, and 481,269, respectively) than by following the hybrid recommendation (49.0 million, 4.1 million, and 286,288, respectively) or biennial screening at ages 50 to 74 years (27.3 million, 2.3 million, and 162,885, respectively).

CONCLUSION

CISNET models demonstrate that the greatest mortality reduction is achieved with annual screening of women starting at age 40 years. Cancer 2017. © 2017 American Cancer Society.

http://ift.tt/2xhONA5

On assessing the effect of breast cancer screening schemes

Our goal should be to provide truthful, balanced information so that women can make informed choices about when to start screening for breast cancer. A woman who is making a decision about screening is more interested in her personal chances of benefit and risk of harm and is less interested in the benefits to the population.

http://ift.tt/2wnxeCd

Tubo-ovarian abscess infected by Salmonella typhi

We report a case of a tubo-ovarian abscess infected with Salmonella enterica serotype typhi. A 19-year-old Nepalese woman presented to a hospital in Kathmandu with lower abdominal pain, constipation, fever and a non-healing, suppurative surgical wound from an emergency caesarian section performed 2 months previously at 37 weeks of pregnancy. She also had an exploratory laparotomy for an appendix perforation with peritonitis at 25 weeks of gestation. Her wound infection did not respond to cloxacillin and she had an exploratory laparotomy, and a tubo-ovarian abscess was found from which S. typhi was isolated. She had a bilateral salpingo-oophorectomy and responded to 14 days of chloramphenicol. A tubo-ovarian abscess is a rare complication of enteric fever.

http://ift.tt/2uXFZCJ

Solitary biceps muscle metastasis from breast cancer

Although direct muscle invasion by carcinoma is well recognised, skeletal muscle metastases are rare. Breast cancer very rarely metastasises to skeletal muscles. We present a case of breast cancer that metastasised to the biceps muscle. The woman developed breast cancer in 1990 and then developed axillary subcutaneous metastasis in 2001. In 2015, she presented with pain in the left forearm extending to the hand. Initial imaging showed no abnormalities, but the positron emission tomography-CT scanning revealed a hot spot in the left biceps muscle. Additionally, the nerve conduction study showed feature of carpal tunnel syndrome. The hot spot was deemed inconclusive in the view of normal CT and MRI scans, and the patient was treated with carpal tunnel decompression. A few months later, the patient developed a lump in the left biceps muscle, which appeared to be a metastatic lesion from her primary breast cancer. The patient was treated with radiotherapy and responded satisfactorily.

http://ift.tt/2vg7oec

Topical ayurvedic ointment-induced chemical injury presenting as bilateral acute keratitis

A 40-years-old female patient was referred to the cornea clinic as a probable case of bilateral keratitis. The patient had a history of headache followed by acute onset of redness, pain and discharge from both eyes for 15 days. The patient was diagnosed as bilateral keratitis by the first contact physician and was started on topical antibiotics, cycloplegics and lubricating eye-drops. At presentation, both eyes had visual acuity of perception of light, conjunctival congestion, limbal blanching, diffuse corneal oedema and epithelial defect. A detailed history revealed application of Vicks VapoRub [topical ayurvedic analgesic which contains (per 100 g of product) menthol (2.82 g), camphor (5.25 g) and eucalyptol (1.49 mL) and excipients include thymol (0.1 g), turpentine oil (5.57 mL), nutmeg oil (0.54 mL), cedar wood oil and petrolatum)] on the forehead and eyelids for headache several times over 2–3 days before the onset. The patient further confirmed the accidental application of the ointment in the eyes. A provisional diagnosis of acute chemical injury with Vicks VapoRub was made and treatment with topical antibiotic, cycloplegic, steroid, lubricant and vitamin C was started. On follow-up, both eyes showed gradual resolution of corneal oedema and epithelial defect. Visual acuity improved in the left eye to 6/60 with no change in right eye due to corneal haze.

http://ift.tt/2uXFXe5

Vermiform appendix within incisional hernia

The vermiform appendix (whether inflamed or not) within a hernia is very rare occurrence. We present the unprecedented case of a normal appendix found within a Pfannenstiel incisional hernia. A diagnostic laparoscopy was performed as appendicitis was suspected. However, the tip of a normal appendix was visualised within a previous Pfannenstiel incision. Laparoscopic appendicectomy was carried successfully and the patient was discharged. The patient later returned for a successful elective laparoscopic incisional hernia repair.

http://ift.tt/2vgelfr

Growing use of integrated e-health systems [News]

http://ift.tt/2uX2w2i

Association between sedentary time and mortality across levels of frailty [Research]

BACKGROUND:

Sedentary behaviours are associated with adverse health outcomes in middle-aged and older adults, even among those who exercise. We examined whether the degree of frailty affects the association between sedentary behaviours and higher risk of mortality.

METHODS:

In this prospective cohort study, we used data from 3141 community-dwelling adults 50 years of age or older from the 2003/04 and 2005/06 cohorts of the US National Health and Nutrition Examination Survey. Time engaged in sedentary behaviours was measured using uniaxial accelerometers, and frailty was based on a 46-item frailty index. Mortality data were linked up to 2011. We used Cox proportional hazard models to estimate the hazard ratio (HR) of sedentary behaviour.

RESULTS:

We found that for people with low levels of frailty (frailty index score ≤ 0.1), sedentary time was not predictive of mortality, regardless of physical activity level (adjusted HR 0.90, 95% confidence interval [CI] 0.70–1.15). Among people who were vulnerable (0.1 < frailty index score ≤ 0.2) or frail (frailty index score > 0.2), sedentary time was associated with higher mortality only among those who were physically inactive (not meeting the criterion for moderate physical activity) (HR 1.16, 95% CI 1.02–1.33 for the group defined by 0.1 < frailty index score ≤ 0.2; HR 1.27, 95% CI 1.11–1.46 for the group defined by 0.2 < frailty index score ≤ 0.3; HR 1.34, 95% CI 1.19–1.50 for frailty index score > 0.3).

INTERPRETATION:

The effect of sedentary behaviours on mortality varied by level of frailty. Adults with the highest frailty level experienced the greatest adverse impact. Low frailty levels (frailty index score ≤ 0.1) seemed to eliminate the increased risk of mortality associated with prolonged sitting, even among people who did not meet recommended physical activity guidelines.

http://ift.tt/2uWV5rX

Routinely collected data: the importance of high-quality diagnostic coding to research [Commentary]

http://ift.tt/2vgp5u1

Finding the right balance between precision medicine and personalized care [Analysis]

http://ift.tt/2vgerne

CMA adopts patient focus [News]

http://ift.tt/2uWFsRb

Iatrogenic pulmonary air embolism [Practice]

http://ift.tt/2uWySui

The authors respond to "The utility and value of the 'surprise question for patients with serious illness" [Letters]

http://ift.tt/2vg4tSH

The unintended consequences of overinvestigating incidentalomas [Humanities]

http://ift.tt/2vfVBwC

Resignations raise questions about OMA finances [News]

http://ift.tt/2vg3tOw

The utility and value of the "surprise question" for patients with serious illness [Letters]

http://ift.tt/2uWX0Nj

Reports of coerced sterilization of Indigenous women in Canada mirrors shameful past [News]

http://ift.tt/2vfINX8

Patterns of protective associations differ for antibodies to P.falciparum-infected erythrocytes and merozoites in immunity against malaria in children

Acquired antibodies play an important role in immunity to P. falciparum malaria and are typically directed towards surface antigens expressed by merozoites and infected erythrocytes (IEs). The importance of specific IE surface antigens as immune targets remains unclear. We evaluated antibodies and protective associations in two cohorts of children in Papua New Guinea. We used genetically-modified P. falciparum to evaluate the importance of PfEMP1 and a P. falciparum isolate with a virulent phenotype. Our findings suggested that PfEMP1 was the dominant target of antibodies to the IE surface, including functional antibodies that promoted opsonic phagocytosis by monocytes. Antibodies were associated with increasing age and concurrent parasitemia, and were higher among children exposed to a higher force-of-infection as determined using molecular detection. Antibodies to IE surface antigens were consistently associated with reduced risk of malaria in both younger and older children. However, protective associations for antibodies to merozoite surface antigens were only observed in older children. This suggests that antibodies to IE surface antigens, particularly PfEMP1, play an earlier role in acquired immunity to malaria, whereas greater exposure is required for protective antibodies to merozoite antigens. These findings have implications for vaccine design and serosurveillance of malaria transmission and immunity.

This article is protected by copyright. All rights reserved

http://ift.tt/2vVxSni

Genetics of Alzheimer’s Disease: the Importance of Polygenic and Epistatic Components

Abstract

Purpose of Review

We aimed to summarize the recent advances in genetic findings of Alzheimer's disease (AD), focusing on traditional single-marker and gene approaches and non-traditional ones, i.e., polygenic and epistatic components.

Recent Findings

Genetic studies have progressed over the last few decades from linkage to genome-wide association studies (GWAS), and most recently studies utilizing high-throughput sequencing. So far, GWASs have identified several common variants characterized by small effect sizes (besides APOE-ε4). Sequencing has facilitated the study of rare variants with larger effects. Nevertheless, missing heritability for AD remains extensive; a possible explanation might lie in the existence of polygenic and epistatic components.

Summary

We review findings achieved by single-marker approaches, but also polygenic and epistatic associations. The latter two are critical, yet-underexplored mechanisms. Genes involved in complex diseases are likely regulated by mechanisms and pathways involving many other genes, an aspect potentially missed by traditional approaches.

http://ift.tt/2xhtqPo

Enterolithiasis as a complication of a jejunal diverticulum: an unusual case of small bowel obstruction

http://ift.tt/2wn25i5

National surgical mortality audit may be associated with reduced mortality after emergency admission

Background

The Western Australian Audit of Surgical Mortality was established in 2002. A 10-year analysis suggested it was the primary driver in the subsequent fall in surgeon-related mortality. Between 2004 and 2010 the Royal Australasian College of Surgeons established mortality audits in other states. The aim of this study was to examine national data from the Australian Institute of Health and Welfare (AIHW) to determine if a similar fall in mortality was observed across Australia.

Method

The AIHW collects procedure and outcome data for all surgical admissions. AIHW data from 2005/2006 to 2012/2013 was used to assess changes in surgical mortality.

Results

Over the 8 years surgical admissions increased by 23%, while mortality fell by 18% and the mortality per admission fell by 33% (P < 0.0001). A similar decrease was seen in all regions. The mortality reduction was overwhelmingly observed in elderly patients admitted as an emergency.

Conclusion

The commencement of this nation-wide mortality audit was associated with a sharp decline in perioperative mortality. In the absence of any influences from other changes in clinical governance or new quality programmes it is probable it had a causal effect. The reduced mortality was most evident in high-risk patients. This study adds to the evidence that national audits are associated with improved outcomes.

http://ift.tt/2xgpz50

Distinct processing of ambiguous speech in people with non-clinical auditory verbal hallucinations

Abstract

Auditory verbal hallucinations (hearing voices) are typically associated with psychosis, but a minority of the general population also experience them frequently and without distress. Such 'non-clinical' experiences offer a rare and unique opportunity to study hallucinations apart from confounding clinical factors, thus allowing for the identification of symptom-specific mechanisms. Recent theories propose that hallucinations result from an imbalance of prior expectation and sensory information, but whether such an imbalance also influences auditory-perceptual processes remains unknown. We examine for the first time the cortical processing of ambiguous speech in people without psychosis who regularly hear voices. Twelve non-clinical voice-hearers and 17 matched controls completed a functional magnetic resonance imaging scan while passively listening to degraded speech ('sine-wave' speech), that was either potentially intelligible or unintelligible. Voice-hearers reported recognizing the presence of speech in the stimuli before controls, and before being explicitly informed of its intelligibility. Across both groups, intelligible sine-wave speech engaged a typical left-lateralized speech processing network. Notably, however, voice-hearers showed stronger intelligibility responses than controls in the dorsal anterior cingulate cortex and in the superior frontal gyrus. This suggests an enhanced involvement of attention and sensorimotor processes, selectively when speech was potentially intelligible. Altogether, these behavioural and neural findings indicate that people with hallucinatory experiences show distinct responses to meaningful auditory stimuli. A greater weighting towards prior knowledge and expectation might cause non-veridical auditory sensations in these individuals, but it might also spontaneously facilitate perceptual processing where such knowledge is required. This has implications for the understanding of hallucinations in clinical and non-clinical populations, and is consistent with current 'predictive processing' theories of psychosis.

http://ift.tt/2wuUwFw

Household Financial Burden and Poverty Impacts of Cancer Treatment in Vietnam

Purpose. This paper aims to analyze the household financial burden and poverty impacts of cancer treatment in Vietnam. Methods. Under the "ASEAN CosTs in ONcology" study design, three major specialized cancer hospitals were employed to assemble the Vietnamese data. Factors of socioeconomic, direct, and indirect costs of healthcare were collected prospectively through both individual interviews and hospital financial records. Results. The rates of catastrophic expenditure based on the cut-off points of 20%, 30%, 40%, and 50% of household's income were 82.6%, 73.7%, 64.7%, and 56.9%, respectively. 37.4% of the households with patient were impoverished by the treatment costs for cancer. The statistically significant correlates of the impoverishment problem were higher among older patients (40–60 years: 1.77, 95% CI 1.14–2.73; above 60 years: 1.75, 95% CI 1.03–2.98); poorer patients (less than 100% national income: 29, 95% CI 18.6–45.24; less than 200% national income: 2.89, 95% CI 1.69–4.93); patients who underwent surgery alone (receiving nonsurgery treatment: 2.46, 95% CI 1.32–4.59; receiving multiple treatments: 2.4, 95% CI 1.38–4.17). Conclusions. Lots of households were pushed into poverty due to their expenditure on cancer care; more actions are urgently needed to improve financial protection to the vulnerable groups.

http://ift.tt/2v53WEb

FDA provides new tools for the development and proper evaluation of tests for detecting Zika virus infection

August 17, 2017 -- As an additional measure in the fight against Zika virus, today the U.S. Food and Drug Administration announced that it has made available a panel of human plasma samples to aid in the regulatory evaluation of serological tests to...

http://ift.tt/2wmy3Lh

Regulatory T cell subsets in patients with medulloblastoma at diagnosis and during standard irradiation and chemotherapy (PBTC N-11)

Abstract

Background

We evaluated circulating levels of immunosuppressive regulatory T cells (T_regs) and other lymphocyte subsets in patients with newly diagnosed medulloblastoma (MBL) undergoing surgery compared to a control cohort of patients undergo craniectomy for correction of Chiari malformation (CM) and further determined the impact of standard irradiation and chemotherapy on this cell population.

Methods

Eligibility criteria for this biologic study included age 4–21 years, patients with CM undergoing craniectomy (as non-malignant surgical controls) and receiving dexamethasone for prevention of post-operative nausea, and those with newly diagnosed posterior fossa tumors (PFT) undergoing surgical resection and receiving dexamethasone as an anti-edema measure. Patients with confirmed MBL were also followed for longitudinal blood collection and analysis during radiotherapy and chemotherapy.

Results

A total of 54 subjects were enrolled on the study [22-CM, 18-MBL, and 14-PFT]. Absolute number and percentage T_regs (defined as CD4⁺CD25⁺FoxP3⁺CD127^low/−) at baseline were decreased in MBL and PFT compared to CM [p = 0.0016 and 0.001, respectively). Patients with MBL and PFT had significantly reduced overall CD4⁺ T cell count (p = 0.0014 and 0.0054, respectively) compared to those with CM. Radiation and chemotherapy treatment in patients with MBL reduced overall lymphocyte counts; however, within the CD4⁺ T cell compartment, T_regs increased during treatment but gradually declined post therapy.

Conclusions

Our results demonstrate that patients with MBL and PFT exhibit overall reduced CD4⁺ T cell counts at diagnosis but not an elevated proportion of T_regs. Standard treatment exacerbates lymphopenia in those with MBL while enriching for immunosuppressive T_regs over time.

http://ift.tt/2vPLzFT

Derivation of Stem Cell Lines from Mouse Preimplantation Embryos

This article describes a protocol to efficiently derive and culture pluripotent stem cell lines from mouse embryos at the blastocyst stage.

http://ift.tt/2v4mDHK

Regulatory T cell subsets in patients with medulloblastoma at diagnosis and during standard irradiation and chemotherapy (PBTC N-11)

Abstract

Background

We evaluated circulating levels of immunosuppressive regulatory T cells (T_regs) and other lymphocyte subsets in patients with newly diagnosed medulloblastoma (MBL) undergoing surgery compared to a control cohort of patients undergo craniectomy for correction of Chiari malformation (CM) and further determined the impact of standard irradiation and chemotherapy on this cell population.

Methods

Eligibility criteria for this biologic study included age 4–21 years, patients with CM undergoing craniectomy (as non-malignant surgical controls) and receiving dexamethasone for prevention of post-operative nausea, and those with newly diagnosed posterior fossa tumors (PFT) undergoing surgical resection and receiving dexamethasone as an anti-edema measure. Patients with confirmed MBL were also followed for longitudinal blood collection and analysis during radiotherapy and chemotherapy.

Results

A total of 54 subjects were enrolled on the study [22-CM, 18-MBL, and 14-PFT]. Absolute number and percentage T_regs (defined as CD4⁺CD25⁺FoxP3⁺CD127^low/−) at baseline were decreased in MBL and PFT compared to CM [p = 0.0016 and 0.001, respectively). Patients with MBL and PFT had significantly reduced overall CD4⁺ T cell count (p = 0.0014 and 0.0054, respectively) compared to those with CM. Radiation and chemotherapy treatment in patients with MBL reduced overall lymphocyte counts; however, within the CD4⁺ T cell compartment, T_regs increased during treatment but gradually declined post therapy.

Conclusions

Our results demonstrate that patients with MBL and PFT exhibit overall reduced CD4⁺ T cell counts at diagnosis but not an elevated proportion of T_regs. Standard treatment exacerbates lymphopenia in those with MBL while enriching for immunosuppressive T_regs over time.

http://ift.tt/2vPLzFT

Autophagy inhibits high glucose induced cardiac microvascular endothelial cells apoptosis by mTOR signal pathway

Abstract

Cardiac microvascular endothelial cells (CMECs) dysfunction is an important pathophysiological event in the cardiovascular complications induced by diabetes. However, the underlying mechanism is not fully clarified. Autophagy is involved in programmed cell death. Here we investigated the potential role of autophagy on the CMECs injury induced by high glucose. CMECs were cultured in normal or high glucose medium for 6, 12 and 24 h respectively. The autophagy of CMECs was measured by green fluorescence protein (GFP)-LC3 plasmid transfection. Moreover, the apoptosis of CMEC was determined by flow cytometry. Furthermore, 3-Methyladenine (3MA), ATG7 siRNA and rapamycin were administrated to regulate the autophagy state. Moreover, Western blotting assay was performed to measure the expressions of Akt, mTOR, LC3 and p62. High glucose stress decreased the autophagy, whereas increased the apoptosis in CMECs time dependently. Meanwhile, high glucose stress activated the Akt/mTOR signal pathway. Furthermore, autophagy inhibitor, 3-MA and ATG7 siRNA impaired the autophagy and increased the apoptosis in CMECs induced by high glucose stress. Conversely, rapamycin up-regulated the autophagy and decreased the apoptosis in CMECs under high glucose condition. Our data provide evidence that high glucose directly inhibits autophagy, as a beneficial adaptive response to protect CMECs against apoptosis. Furthermore, the autophagy was mediated, at least in part, by mTOR signaling.

http://ift.tt/2vesJVk

Awakening immunity against cancer: a 2017 primer for clinicians

Cancer immunotherapy has finally joined the pillars of cancer treatment—surgery, radiation, chemotherapy, hormonal therapy, and targeted therapy—in improving cancer patient lives. In the last 5 years, the deve...

http://ift.tt/2v3ZPYG

RAPD Profiling, DNA Fragmentation, and Histomorphometric Examination in Brains of Wistar Rats Exposed to Indoor 2.5 Ghz Wi-Fi Devices Radiation

The advent of Wi-Fi connected high technology devices in executing day-to-day activities is fast evolving especially in developing countries of the world and hence the need to assess its safety among others. The present study was conducted to investigate the injurious effect of radiofrequency emissions from installed Wi-Fi devices in brains of young male rats. Animals were divided into four equal groups; group 1 served as control while groups 2, 3, and 4 were exposed to 2.5 Ghz at intervals of 30, 45, and 60 consecutive days with free access to food and water ad libitum. Alterations in harvested brain tissues were confirmed by histopathological analyses which showed vascular congestion and DNA damage in the brain was assayed using agarose gel electrophoresis. Histomorphometry analyses of their brain tissues showed perivascular congestion and tissue damage as well.

http://ift.tt/2vehNHg

Sodium Hypochlorite Irrigation and Its Effect on Bond Strength to Dentin

Effective shaping and cleaning of root canals are essential for the success of endodontic treatment. Due to the complex anatomy of root canal spaces, the use of various instrumentation techniques alone is not effective in producing bacteria-free root canal spaces. Irrigation, disinfectants, rinses, and intervisit medications are used in conjunction with the mechanical instrumentation to ensure the success of endodontic treatment. Sodium hypochlorite (NaOCl), a halogenated compound, is routinely used to irrigate the root canal during endodontic treatments. NaOCl has been known for its antibacterial action, proteolytic and dissolution capacity, and debridement properties. NaOCl, however, can alter the composition of dentin and hence its interaction with the adhesive resins used to bond the restorative materials to treated dentin. This review therefore covers in depth the action of NaOCl on dentin-adhesive resin bond strength including both enhancement and reduction, then mechanisms proposed for such action, and finally how the adverse action of NaOCl on dentin can be reversed.

http://ift.tt/2uUzH6G

Acquired temozolomide resistance in human glioblastoma cell line U251 is caused by mismatch repair deficiency and can be overcome by lomustine

Abstract

Purpose

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. While the alkylating agent temozolomide (TMZ) has prolonged overall survival, resistance evolution represents an important clinical problem. Therefore, we studied the effectiveness of radiotherapy and CCNU in an in vitro model of acquired TMZ resistance.

Methods

We studied the MGMT-methylated GBM cell line U251 and its in vitro derived TMZ-resistant subline, U251/TMZ-R. Cytotoxicity of TMZ, CCNU, and radiation was tested. Both cell lines were analyzed for MGMT promotor status and expression of mismatch repair genes (MMR). The influence of MMR inhibition by cadmium chloride (CdCl₂) on the effects of both drugs was evaluated.

Results

During the resistance evolution process in vitro, U251/TMZ-R developed MMR deficiency, but MGMT status did not change. U251/TMZ-R cells were more resistant to TMZ than parental U251 cells (cell viability: 92.0% in U251/TMZ-R/69.2% in U251; p = 0.032) yet more sensitive to CCNU (56.4%/80.8%; p = 0.023). The effectiveness of radiotherapy was not reduced in the TMZ-resistant cell line. Combination of CCNU and TMZ showed promising results for both cell lines and overcame resistance. CdCl₂-induced MMR deficiency increased cytotoxicity of CCNU.

Conclusion

Our results confirm MMR deficiency as a crucial process for resistance evolution to TMZ. MMR-deficient TMZ-resistant GBM cells were particularly sensitive to CCNU and to combined CCNU/TMZ. Effectiveness of radiotherapy was preserved in TMZ-resistant cells. Consequently, CCNU might be preferentially considered as a treatment option for recurrent MGMT-methylated GBM and may even be suitable for prevention of resistance evolution in primary treatment.

http://ift.tt/2v3CE0P

A Novel Genetic Group of Bovine Hepacivirus in Archival Serum Samples from Brazilian Cattle

Hepatitis C virus (HCV) (genus Hepacivirus; family Flaviviridae) is a major human pathogen causing persistent infection and hepatic injury. Recently, emerging HCV-like viruses were described infecting wild animals, such as bats and rodents, and domestic animals, including dogs, horses, and cattle. Using degenerate primers for detecting bovine pestiviruses in a 1996 survey three bovine serum samples showed a low identity with the genus Pestivirus of the Flaviviridae family. A virus could not be isolated in cell culture. The description of bovine hepaciviruses (BovHepV) in 2015 allowed us to retrospectively identify the sequences as BovHepV, with a 88.9% nucleotide identity. In a reconstructed phylogenetic tree, the Brazilian BovHepV samples grouped within the bovine HCV-like cluster in a separated terminal node that was more closely related to the putative bovine Hepacivirus common ancestor than to bovine hepaciviruses detected in Europe and Africa.

http://ift.tt/2v3meWo

Mystery of Retinal Vein Occlusion: Vasoactivity of the Vein and Possible Involvement of Endothelin-1

Retinal vein occlusion (RVO) is a common vascular disease of retina; however, the pathomechanism leading to RVO is not yet clear. In general, increasing age, hypertension, arteriosclerosis, diabetes mellitus, dyslipidemia, cardiovascular disorder, and cerebral stroke are systemic risk factors of RVO. However, RVO often occur in the unilateral eye and sometimes develop in young subjects who have no arteriosclerosis. In addition, RVO show different variations on the degrees of severity; some RVO are resolved without any treatment and others develop vision-threatening complications such as macular edema, combined retinal artery occlusion, vitreous hemorrhage, and glaucoma. Clinical conditions leading to RVO are still open to question. In this review, we discuss how to treat RVO in practice by presenting some RVO cases. We also deliver possible pathomechanisms of RVO through our clinical experience and animal experiments.

http://ift.tt/2uV6zvZ

Internal Impingement of the Shoulder: A Risk of False Positive Test Outcomes in External Impingement Tests?

Background. External impingement tests are considered as being particularly reliable for identifying subacromial and coracoid shoulder impingement mechanisms. The purpose of the present study was to evaluate if these tests are likely to provoke an internal shoulder impingement mechanism which, in cases of a pathologic condition, can lead to a positive test result. Method. In 37 subjects, the mechanical contact between the glenoid rim and the rotator cuff (RC) was measured quantitatively and qualitatively in external impingement test positions using an open MRI system. Results. Mechanical contact of the supraspinatus with the posterosuperior glenoid was present in 30 subjects in the Neer test. In the Hawkins test, the subscapularis was in contact with the anterosuperior glenoid in 33 subjects and the supraspinatus in 18. In the horizontal impingement test, anterosuperior contact of the supraspinatus with the glenoid was identified in 35 subjects. Conclusion. The Neer, Hawkins, and horizontal impingement tests are likely to provoke the mechanism of an internal shoulder impingement. A posterosuperior internal impingement mechanism is being provoked predominately in the Neer test. The Hawkins test narrows the distance between the insertions of the subscapularis and supraspinatus and the anterosuperior labrum, which leads to an anterosuperior impingement mechanism.

http://ift.tt/2wtHh7Y

A Successfully Treated Case of Gastrointestinal Stromal Tumor Causing Severe Anemia and Localized Peritonitis Showing Angina Pectoris Resulting in Watershed Cerebral Infarction

Ischemic stroke following acute myocardial infarction is a rare but a serious complication. Because the pathophysiology of stroke is dynamic, it is often hard to identify the cause of stroke. Here, we present the case of a 75-year-old man with ischemic stroke following angina pectoris caused by severe anemia and localized peritonitis due to gastrointestinal stromal tumor of small intestine. On admission, he showed consciousness disturbance, fever, and left hemiplegia. The electrocardiogram on admission showed ST-segment depression in V2 to V6 which was normalized 4 hours later. The ultrasound cardiogram showed the mild hypokinesis in the apical portion of left ventricle which was also normalized later. The magnetic resonance imaging and angiography showed ischemic stroke in watershed area between right anterior and middle cerebral arteries area and stenosis of distal portion of right middle cerebral artery. The computed tomography of abdomen showed a mass of small intestine. We decided to perform curative surgery after transfusion and successfully resected the mass of the small intestine, which was revealed to be a gastrointestinal stromal tumor (GIST). This is a successfully treated case of GIST in which the complicated pathophysiology of watershed cerebral infarction following angina pectoris might be clearly revealed.

http://ift.tt/2uV5mEY

Simulation for Assessment of Milestones in Emergency Medicine Residents

Abstract

Introduction

All residency programs in the United States are required to report their residents' progress on the Milestones to the Accreditation Council for Graduate Medical Education (ACGME) biannually. Since the development and institution of this competency-based assessment framework, residency programs have been attempting to ascertain the best ways to assess resident performance on these metrics. Simulation was recommended by the ACGME as one method of assessment for many of the milestone subcompetencies. We developed 3 simulation scenarios with scenario specific Milestone based assessment tools. We aimed to gather validity evidence for this tool.

Methods

We conducted a prospective observational study to investigate the validity evidence for 3 mannequin-based simulation scenarios for assessing individual residents on Emergency Medicine (EM) milestones. The subcompetencies (i.e. PC1, PC2, PC3) included were identified via a modified Delphi technique using a group of experienced EM simulationists. The scenario specific checklist items were designed based on the individual milestone items within each EM subcompetency chosen for assessment and reviewed by experienced EM simulationists. Two independent live raters who were EM faculty at the respective study sites scored each scenario following brief rater training. The interrater reliability (IRR) of the assessment tool was determined by measuring intraclass correlation coefficient (ICC) for the sum of the checklist (CL) items as well as the global rating scales (GRS) for each scenario. Comparing GRS and CL scores between various PGY levels was performed with ANOVA.

Results

Eight subcompetencies were chosen to assess with 3 simulation cases, using 118 subjects. Evidence of test content, internal structure, response process and relations with other variables were found. The ICCs for the sum of the CL items and the GRSs were > 0.8 for all cases, with one exception (clinical management GRS 0.74 in sepsis case). The Sum of Checklist items and GRSs (p<0.05) discriminated between post graduate (PGY) levels on all cases. However, when the specific CL items were mapped back to milestones in various proficiency levels, the milestones in the higher proficiency levels (level 3 & 4) did not often discriminate between various PGY levels. Level 3 milestone items discriminated between PGY levels on 5 out of 12 occasions they were assessed, and Level 4 items discriminated only 2 out of 12 times they were assessed.

Conclusion

Three simulation cases with scenario specific assessment tools allowed evaluation of EM residents on proficiency levels 1-4 within 8 of the EM Milestone subcompetencies. Evidence of test content, internal structure, response process and relations with other variables were found. Good to excellent IRR and the ability to discriminate between various PGY levels was found for both the sum of CL items and GRSs. However, there was a lack of a positive relationship between advancing PGY level and the completion of higher level milestone items (levels 3 and 4).

This article is protected by copyright. All rights reserved.

http://ift.tt/2vOWQ9l

Prospective Validation of a Clinical Score for Males Presenting with an Acute Scrotum

Abstract

Objective

To validate the Testicular Workup for Ischemia and Suspected Torsion (TWIST) score among pediatric emergency medicine providers for the evaluation of pediatric males presenting with testicular pain and swelling (acute scrotum).

Methods

We conducted a prospective cohort study of males 3 months to 18 years old presenting with an acute scrotum. History and physical examination findings, including components of the TWIST score (hard testicle, absent cremasteric reflex, nausea/vomiting, and high riding testicle) as well as diagnostic results (ultrasound, urine, sexually transmitted infection (STI) testing) were recorded. Testicular torsion was confirmed by surgical exploration. Frequencies of patient characteristics, TWIST components, and tests were calculated. We performed the kappa statistic for inter-rater reliability and calculated the test characteristics and receiver operator curves for the TWIST score (range 0-7).

Results

During the study period 258 males were enrolled in the study; 19 (7.4%) had testicular torsion. The mean age was 9.8 years (± 0.3 years). The high-risk TWIST score of 7 had 100% specificity (95% confidence interval (CI) 98%, 100%) with 100% positive predictive value (95% CI 40%, 100%) for testicular torsion. The area under the curve was 0.82. The kappa statistic for the overall TWIST score was fair at 0.39.

Conclusions

In this prospective validation of the TWIST score among pediatric emergency providers, the high-risk score demonstrated strong test characteristics for testicular torsion. The TWIST score could be used as part of a standardized approach for evaluation of the pediatric acute scrotum to provide more efficient and effective care.

This article is protected by copyright. All rights reserved.

http://ift.tt/2x3iuWi

Cartilage Protection and Analgesic Activity of a Botanical Composition Comprised of Morus alba, Scutellaria baicalensis, and Acacia catechu

Although there have been augmented advances in drug discovery, current OA management is inadequate due to the lack of successful therapies proven to be effective in modifying disease progression. For some, the risk outweighs the benefit. As a result, there is a desperate need for safe and efficacious natural alternatives. Here we evaluated a composition from Morus alba, Scutellaria baicalensis, and Acacia catechu in maintaining joint structural integrity and alleviating OA associated symptoms in monoiodoacetate- (MIA-) induced rat OA disease model. Study lasted for 6 weeks. 59.6%, 64.6%, 70.7%, 69.9%, and 70.3% reductions in pain sensitivity were observed for rats treated with the composition from week 1 to week 5, respectively. Statistically significant improvements in articular cartilage matrix integrity (maintained at 57.1% versus MIA + vehicle treated rats) were shown from the modified total Mankin score for animals treated with the composition. The composition showed a statistically significant reduction in uCTX-II level (54.1% reductions). The merit of combining these botanicals was also demonstrated in their synergistic analgesic activity. Therefore, the standardized blend of Morus alba, Scutellaria baicalensis, and Acacia catechu could potentially be considered as an alternative remedy from natural sources for the management of OA and/or its associated symptoms.

http://ift.tt/2uV17JB

Downregulation of SMARCB1 /INI1 expression in pediatric chordomas correlates with upregulation of miR-671-5p and miR-193a-5p expressions

Abstract

Loss of SMARCB1/INI1 expression is considered to be a hallmark for childhood chordomas (CCs). Although mutation/loss of 22q has strongly established the loss of SMARCB1/INI1 in cancers, the cause in CCs remains elusive. Recent studies suggest role of miRNAs in regulation of SMARCB1/INI1 expressions. We examined 5 reported/target predicted miRNAs to SMARCB1/INI1 in SMARCB1/INI1 immunonegative and immunopositive cases, and found upregulation of miR-671-5p and miR-193a-5p in SMARCB1/INI1-immunonegative cases. Notably, these two miRNAs were significantly predicted to target TGF-β signaling, suggestive of dysregulation of developmental and osteoblast regulation pathway in CCs. Overall, we suggest miR-671-5p- and miR-193a-5p-mediated epigenetic mode of SMARCB1/INI1 loss and downregulated TGF-β pathway in CCs.

http://ift.tt/2uV14NV

Corrigendum to “Expression and Clinical Significance of Cancer Stem Cell Markers CD24, CD44, and CD133 in Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis”

http://ift.tt/2ijiqhQ

Side-viewing duodenoscope retroflexion method for bile duct cannulation and sphincterotomy in patient with Billroth II anatomy

Abstract

An 80-year-old male with obstructive jaundice and prior conventional Billroth II gastrectomy was referred for ERCP. The procedure was performed with side-viewing duodenoscope (Olympus TjF-145) and standard sphincterotome. The afferent limb was intubated and papilla approached from below which located both the direction of cannulation and duodenal stump to appear toward 6 o'clock position.

This article is protected by copyright. All rights reserved.

http://ift.tt/2fWWGar

NSAIDs increase the risk of mucosal injuries but not of overt small bowel bleeding

Abstract

Since 2001, small bowel capsule endoscopy (SBCE) has been widely implemented into clinical practice as a minimal-invasive diagnostic approach for diagnosing small bowel diseases. Currently, SBCE is moreover recognized as the first-line procedure for the diagnostic work-up of obscure gastrointestinal bleeding (OGIB) and for a variety of SB disorders including Crohn's disease, inherited polyposis syndromes, suspected small bowel tumors or refractory celiac disease [1,2]. In addition, capsule endoscopy is used to guide the decision whether device assisted enteroscopy (i.e., balloon-assisted endoscopy; spiral enteroscopy) should be beneficial or not, thereby predicting the need of targeted biopsies, endoscopic therapies, and the preferred insertion route (i.e., oral or retrograde approach).

This article is protected by copyright. All rights reserved.

http://ift.tt/2ihwg4c

Granulomatosis with Polyangiitis with Myocarditis and Ventricular Tachycardia

Granulomatosis with polyangiitis (GPA), previously known as Wegener's granulomatosis, is a pulmonary-renal syndrome affecting small and medium sized blood vessels. The disease has a prevalence in studies ranging from 3 to 15.7 cases per 100,000, with a noted increasing incidence and prevalence in more recent studies. Pulmonary manifestations include hemorrhage, lung cavitary lesions, and pulmonary fibrosis. Within the kidney, GPA is known to cause rapidly progressive pauci-immune crescentic glomerulonephritis. Rare and severe cardiovascular manifestations include pericarditis, arrhythmias, myocarditis, and aortic valve disease. Our patient is a 43-year-old female with typical pulmonary and renal lesions from GPA and also acute myocarditis, multiple episodes of ventricular tachycardia, and a severe reactive thrombocytosis.

http://ift.tt/2vdIDPO

Transcriptomic Analysis Reveals Genes Mediating Salt Tolerance through Calcineurin/CchA-Independent Signaling in Aspergillus nidulans

Adaptation to changes in the environment is crucial for the viability of all organisms. Although the importance of calcineurin in the stress response has been highlighted in filamentous fungi, little is known about the involvement of ion-responsive genes and pathways in conferring salt tolerance without calcium signaling. In this study, high-throughput RNA-seq was used to investigate salt stress-induced genes in the parent, ΔcnaB, and ΔcnaBΔcchA strains of Aspergillus nidulans, which differ greatly in salt adaption. In total, 2,884 differentially expressed genes including 1,382 up- and 1,502 downregulated genes were identified. Secondary transporters, which were upregulated to a greater extent in ΔcnaBΔcchA than in the parent or ΔcnaB strains, are likely to play important roles in response to salt stress. Furthermore, 36 genes were exclusively upregulated in the ΔcnaBΔcchA under salt stress. Functional analysis of differentially expressed genes revealed that genes involved in transport, heat shock protein binding, and cell division processes were exclusively activated in ΔcnaBΔcchA. Overall, our findings reveal that secondary transporters and stress-responsive genes may play crucial roles in salt tolerance to bypass the requirement for the CchA-calcineurin pathway, contributing to a deeper understanding of the mechanisms that influence fungal salt stress adaption in Aspergillus.

http://ift.tt/2ifW9RM

Manifestation of atopic dermatitis-like skin in TNCB-induced NC/Nga mice is ameliorated by topical treatment of substance P, possibly through blockade of allergic inflammation

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by intense pruritus and eczematous lesion. In this study, topically applied substance P (SP) significantly alleviated AD-like clinical symptoms in 2, 4, 6-trinitrochlorobenzene (TNCB)-induced dermatitis in NC/Nga mice. This effect was nullified by pre-treatment of the neurokinin-1 receptor (NK-1R) antagonist CP99994. SP treatment significantly reduced the infiltration of mast cells and CD3-positive T cells as well as inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and thymic stromal lymphopoietin (TSLP), in AD-like skin lesions and decreased the levels of IgE and thymus and activation-regulated chemokine in serum. This SP-induced alleviation of allergic inflammatory responses was also confirmed as reduced activation in the axillary lymph nodes (aLN) and spleen, suggesting the systemic effect of SP on immune responses in TNCB-induced NC/Nga mice. Furthermore, SP-mediated TSLP reduction was confirmed in human keratinocyte culture under pro-inflammatory TNF-α stimulation. Taken together, these results suggest that topically administered SP may have potential as a medication for atopic dermatitis.

This article is protected by copyright. All rights reserved.

http://ift.tt/2v31ldW

Over-expression of p53 explains isotretinoin′s teratogenicity

Abstract

The precise molecular basis of retinoid embryopathy is yet unknown. This hypothesis predicts that isotretinoin (13-cis retinoic acid), the prodrug of all-trans retinoic acid (ATRA), exaggerates neural crest cell (NCC) apoptosis via upregulation of the pro-apoptotic transcription factor p53, the guardian of the genome. Increased p53 signaling is associated with Treacher Collins-, CHARGE-, and fetal alcohol syndrome, which exhibit dysmorphic craniofacial features resembling retinoid embryopathy. In addition, developmental studies of NCC homeostasis in the zebrafish support the pivotal role of p53. Translational evidence implies that isotretinoin-stimulated over-activation of p53 during embryogenesis represents the molecular basis of isotretinoin′s teratogenicity.

This article is protected by copyright. All rights reserved.

http://ift.tt/2wtaEr2

High Expression of B Lymphocyte Stimulator (BLyS) in Lesional Keratinocytes of Patients with Cutaneous Lupus Erythematosus

http://ift.tt/2v3iELU

Regression of Diffuse B-cell Lymphoma of the Leg with Intralesional Gentian Violet

Abstract

In this case report, a patient of Primary Cutaneous Diffuse B-cell lymphoma, leg type was treated with intralesional gentian violet as she was judged to be too medically fragile for conventional chemotherapy due to advanced age and multiple serious comorbidities. Gentian violet (Crystal violet/ hexamethyl pararosaniline) is a triphenylmethane dye. It has been shown to have an inhibitory effect on NADPH oxidase, an enzyme family which is found in abundance in reactive oxygen driven tumors such as melanoma and lymphoma. We hypothesize that intralesional gentian violet treatment caused signaling changes in the lymphoma which allowed for immune clearance of the lymphoma. Complete resolution of the patient's lesion was noted on a follow up visit.

This article is protected by copyright. All rights reserved.

http://ift.tt/2wtnR34

In vitro and in vivo models to investigate the pathomechanisms and novel treatments for pemphigoid diseases

Abstract

Pemphigoid diseases (PD) are a subgroup of rare acute or chronic autoimmune skin disorders characterized and caused by autoantibodies directed against distinct structural components of the dermal-epidermal junction. Binding of autoantibodies to their targets leads to the formation of blisters and erosions in patients. PDs comprise eight disorders for which the molecular target antigens have been identified. First, we review the available in vitro and ex vivo models for analysis of distinct aspects of the pathogenesis of PDs. This includes the binding of autoantibodies to skin sections, the analysis of blister formation capability and skin complement activation as well as investigation of neutrophil and keratinocyte activation. In addition to this, several animal models of PD have been developed during the last decades. These animal models have greatly contributed to our current understanding of the pathogenesis of PDs. We summarize spontaneously arising PD in animals and the induction of PD by transfer of (auto)-antibodies, transfer of (auto)-antigen specific lymphocytes and by immunization. In combined use, these models allow dissecting all aspects of PD pathogenesis, e.g. loss of tolerance, autoantibody production and inflammatory skin processes that lead to blister formation. Overall, we aim to foster translational biomedical research, to deepen our understanding of PD pathogenesis and to develop novel treatments for patients suffering from these life-threatening and difficult-to-treat autoimmune diseases.

This article is protected by copyright. All rights reserved.

http://ift.tt/2v3j5FH

Cytotoxic anti-melanoma drugs suppress the activation of M2 macrophages

Abstract

Together with regulatory T cells (Tregs), tumor-associated macrophages (TAMs) play roles in maintaining the tumor microenvironment. Though cytotoxic anti-melanoma drugs such as dacarbazine (DTIC), nimustine hydrochloride (ACNU), and vincristine (VCR) have been used for the treatment of malignant melanoma as adjuvant therapy in Japan, the detailed mechanisms of their immunomodulatory effects are not fully understood. Since the majority of TAMs are alternatively activated M2 macrophages that favor tumor development, the aim of this study was to elucidate the immunomodulatory effects of these reagents on human monocyte-derived M2 macrophages. First, mRNA expressions and protein production of immune checkpoint molecules, PD-L1, and chemokines by CD163⁺ CD206⁺ M2 macrophages derived from peripheral blood mononuclear cells were investigated to determine the immunomodulatory effects of DTIC, ACNU, and VCR. DTIC and VCR significantly decreased PD-L1 mRNA expression, which was confirmed by flow cytometry. Moreover, the mRNA expression and production of CCL22 were significantly decreased by DTIC, which suggested that DTIC might suppress the recruitment of Tregs in the tumor site. Furthermore, the decreased expression of PD-L1 and production of CCL22 were validated in vivo, using the B16F10 mouse melanoma model, leading to abrogation of the suppressive function of T cell proliferation. The present report suggests one of the possible anti-melanoma mechanisms of DAV combination chemotherapy for melanoma patients.

This article is protected by copyright. All rights reserved.

http://ift.tt/2wtOwfU

Eosinophils as putative therapeutic targets in bullous pemphigoid

Abstract

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering skin disease and is characterized by the presence of autoantibodies directed against the hemidesmosomal proteins BP180 and BP230 that can be detected in the skin and serum of BP patients. Histologically, the dermal infiltration of eosinophils is obvious. The objective of this review is to present evidence that eosinophils play a key role in the pathogenesis of BP. Eosinophils, together with cytokines and chemokines regulating their production, recruitment and activation, are abundantly present in lesional skin, in blisters and in peripheral blood of patients with BP. Recently, using a cryosection model, eosinophils were demonstrated to induce dermal-epidermal separation in the presence of BP antibodies. Thus, eosinophils and their products, as well as mediators regulating their function, present promising targets for the treatment of BP.

This article is protected by copyright. All rights reserved.

http://ift.tt/2v3iHqL

Towards the development of a RNAi-based topical treatment for psoriasis: Proof-of-concept in a 3D psoriasis skin model

Abstract

RNA interference has emerged as a powerful tool for therapeutic gene silencing, as it offers the possibility to silence virtually any known pathology-causing gene. However, in vivo delivery of RNAi molecules is hampered by their unfavorable physicochemical characteristics and susceptibility to degradation by endogenous enzymes. To overcome these limitations, we recently developed an elastic liposomal formulation, called DDC642, as topical delivery system of therapeutic RNAi molecules for skin disorders. In this study, we validated the therapeutic efficacy of DDC642-encapsulated RNAi molecules in the treatment of psoriasis using three different in vitro models: a standardized keratinocyte monolayer culture, psoriasis-induced keratinocytes and a psoriasis reconstructed skin model. Four genes (IL22RA1, KRT17, DEFB4 and TSLP), known to be upregulated in psoriatic lesions, and thereby key players in psoriasis pathogenesis were selected. Moreover, the possibility of using a combined siRNA therapy in the topical treatment of psoriasis was explored. Results indicate a successful gene silencing of each different target, both at mRNA and protein level. Additionally, siRNA-DDC642 treatment resulted in a reduced expression of specific psoriasis markers, indicating their potential in future therapeutic approach. The examined siRNA combination (i.e. simultaneous knockdown of KRT17, DEFB4 and TSLP) showed an enhanced reduction in TSLP expression, whereas the decrease in K17 protein expression was impaired in psoriatic keratinocytes. Although the here examined siRNA combination could still be further improved, our study proved already in vitro the clinical potential of targeting multiple genes at once, each playing a different role in a complex disease such as psoriasis.

This article is protected by copyright. All rights reserved.

http://ift.tt/2wtwIBC

Evaluation of the Bacterial Diversity in the Human Tongue Coating Based on Genus-Specific Primers for 16S rRNA Sequencing

The characteristics of tongue coating are very important symbols for disease diagnosis in traditional Chinese medicine (TCM) theory. As a habitat of oral microbiota, bacteria on the tongue dorsum have been proved to be the cause of many oral diseases. The high-throughput next-generation sequencing (NGS) platforms have been widely applied in the analysis of bacterial 16S rRNA gene. We developed a methodology based on genus-specific multiprimer amplification and ligation-based sequencing for microbiota analysis. In order to validate the efficiency of the approach, we thoroughly analyzed six tongue coating samples from lung cancer patients with different TCM types, and more than 600 genera of bacteria were detected by this platform. The results showed that ligation-based parallel sequencing combined with enzyme digestion and multiamplification could expand the effective length of sequencing reads and could be applied in the microbiota analysis.

http://ift.tt/2vdiYXI

Plague: A Millenary Infectious Disease Reemerging in the XXI Century

Plague, in the Middle Ages known as Black Death, continues to occur at permanent foci in many countries, in Africa, Asia, South America, and even the USA. During the last years outbreaks were reported from at least 3 geographical areas, in all cases after tens of years without reported cases. The recent human plague outbreaks in Libya and Algeria suggest that climatic and other environmental changes in Northern Africa may be favourable for Y. pestis epidemiologic cycle. If so, other Northern Africa countries with plague foci also may be at risk for outbreaks in the near future. It is important to remember that the danger of plague reoccurrence is not limited to the known natural foci, for example, those of Algeria, Angola, and Madagascar. In a general context, it is important that governments know the dangerous impact that this disease may have and that the health and medical community be familiar with the epidemiology, symptoms, treatment, and control of plague, so an appropriated and timely response can be delivered should the worst case happen. Plague can be used as a potential agent of bioterrorism. We have concluded that plague is without a doubt a reemerging infectious disease.

http://ift.tt/2uUa329

Comment on “Interrelationship between Sleep and Exercise: A Systematic Review”

http://ift.tt/2wt1ta7

Manual Acupuncture Suppresses the Expression of Proinflammatory Proteins Associated with the NLRP3 Inflammasome in the Hippocampus of SAMP8 Mice

Objective. To investigate the effect of manual acupuncture (MA) on NLRP3 inflammasome-related proteins. Methods. SAMP8 mice were randomly divided into Alzheimer's disease (AD) group, the MA group, and the medicine (M) group. Mice in the M group were treated with donepezil hydrochloride at 0.65 μg/g. In the MA group, MA was applied on Baihui (GV20) and Yintang (GV29) for 20 min and then pricked at Shuigou (GV26). The Morris water maze was applied to assess spatial learning and memory. Immunohistochemical staining and western blot analysis were used to observe the expression of NLRP3 inflammasome-related proteins. Results. Compared with the normal (N) control group, spatial learning and the memory capabilities of the AD group significantly decreased (). The number of NLRP3, ASC, Caspase-1, and IL-1β positively stained cells in the AD group was higher than the N group, and the relative expression levels of the above proteins were significantly higher than those in the N group (). These changes were reversed by both MA and donepezil (). Conclusion. MA can improve the learning and memory capabilities of SAMP8 mice. The negative regulation of the NLRP3/Caspase-1 pathway in the hippocampus may be a possible mechanism of MA in the treatment of AD.

http://ift.tt/2vP0Mak

Responders to Platelet-Rich Plasma in Osteoarthritis: A Technical Analysis

Purpose. To evaluate the similarities and differences between the variety of platelet-rich plasma (PRP) formulations, preparation, and uses to try to determine the best responses for the treatment of knee osteoarthritis. Materials and Methods. A comparison of the outcomes of randomized controlled trials (RCTs) included in the 3 most recent and high-quality meta-analyses to classify the different studies in 2 groups (bad responders group (BRG) and very good responders group (VGRG)). Results and Discussion. From the 19 RCTs analyzed, 7 trials were included in the VGRG and 4 in the BRG. In VGRG, 1 or 2 injections were performed in 4/7 trials, time between injections was 2 to 3 weeks in 4/5 studies with many injections, volume injected varied from 2.5 to 8 mL, and single spinning technique was used in 5/7 studies. PRP classification was Mishra 4B and PAWP2Bβ in 5/7 studies. The use of PRP with leukocytes is only found in the BRG. Conclusion. There is a lack of standardization in PRP preparation technique for knee osteoarthritis. However it appears that the use of a single spinning technique, a platelet concentration lower than 5 times the baseline, and avoidance of leukocytes should be preferred.

http://ift.tt/2vODIZ6

Antibacterial and Antibiotic-Modifying Activity of Methanol Extracts from Six Cameroonian Food Plants against Multidrug-Resistant Enteric Bacteria

The present work was designed to investigate the antibacterial activities of methanol extracts from six Cameroonian edible plants and their synergistic effects with some commonly used antibiotics against multidrug-resistant (MDR) Gram-negative bacteria expressing active efflux pumps. The extracts were subjected to qualitative phytochemical screening and the microdilution broth method was used for antibacterial assays. The results of phytochemical tests indicate that all tested crude extracts contained polyphenols, flavonoids, triterpenes, and steroids. Extracts displayed selective antibacterial activities with the minimal inhibitory concentration (MIC) values ranging from 32 to 1024 μg/mL. The lowest MIC value (32 μg/mL) was recorded with Coula edulis extract against E. coli AG102 and K. pneumoniae K2 and with Mangifera indica bark extract against P. aeruginosa PA01 and Citrus sinensis extract against E. coli W3110 which also displayed the best MBC (256 μg/mL) value against E. coli ATCC8739. In combination with antibiotics, extracts from M. indica leaves showed synergistic effects with 75% (6/8) of the tested antibiotics against more than 80% of the tested bacteria. The findings of the present work indicate that the tested plants may be used alone or in combination in the treatment of bacterial infections including the multidrug-resistant bacteria.

http://ift.tt/2vOQ0k8

The Effect of Oral Dexmedetomidine Premedication on Preoperative Cooperation and Emergence Delirium in Children Undergoing Dental Procedures

Introduction. The aim of this study was to detect the effect of 1 μg/kg of oral dexmedetomidine (DEX) as premedication among children undergoing dental procedures. Materials and Methods. The study involved 100 children between 2 and 6 years of age, ASA I, who underwent full-mouth dental rehabilitation. The DEX group () received 1 μg/kg DEX in apple juice, and the control group () received only apple juice. The patients' scores on the Ramsay Sedation Scale (RSS), parental separation anxiety scale, mask acceptance scale, and pediatric anesthesia emergence delirium scale (PAEDS) and hemodynamic parameters were recorded. The data were analyzed using chi-square test, Fisher's exact test, Student's -test, and analysis of variance in SPSS. Results. RSS scores were significantly higher in the DEX group than group C at 15, 30, and 45 min (). More children (68% easy separation, 74% satisfactory mask acceptance) in the DEX group showed satisfactory ease of parental separation and mask acceptance behavior (). There was no significant difference in the PAEDS scores and mean hemodynamic parameters of both groups. Conclusions. Oral DEX administered at 1 μg/kg provided satisfactory sedation levels, ease of parental separation, and mask acceptance in children but was not effective in preventing emergence delirium. The trial was registered (Protocol Registration Receipt NCT03174678) at clinicaltrials.gov.

http://ift.tt/2x2MFNa