Erratum to: Petrol filling workers as biomonitor of PAH exposure and functional health capacity in resource-limited settings of city Rawalpindi, Pakistan

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Telehealth in Schools Using a Systematic Educational Model Based on Fiction Screenplays, Interactive Documentaries, and Three-Dimensional Computer Graphics

Telemedicine and e-Health , Vol. 0, No. 0.


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Phosphoinositide 3-kinase (PI3K) pathway inhibitors in solid tumors: From laboratory to patients

Publication date: Available online 18 July 2017
Source:Cancer Treatment Reviews
Author(s): Filip Janku
The phosphoinositide 3-kinase (PI3K) pathway is an intracellular signaling pathway that has regulatory roles in cell survival, proliferation, and differentiation, and a critical role in tumorigenesis. In cancer, multiple studies have investigated the therapeutic targeting of the PI3K pathway, and multiple inhibitors targeting PI3K and its isoforms, protein kinase B/AKT, mammalian target of rapamycin (mTOR), and other pathway proteins have been developed. For the treatment of solid tumors, only allosteric mTOR inhibitors, such as everolimus and temsirolimus, are currently approved for clinical use. This review describes the PI3K inhibitors that have progressed from the laboratory to late-stage clinical trials, and discusses the challenges that have prevented other compounds from doing the same. Challenges to the therapeutic effectiveness of some PI3K inhibitors include the absence of reliable and effective biomarkers, their limited efficacy as single agents, insufficient development of rational therapeutic combinations, the use of schedules with a variety of off-target effects, and suboptimal therapeutic exposures. Therefore, with regard to PI3K inhibitors currently in late-stage clinical trials, the identification of appropriate biomarkers of efficacy and the development of optimal combination regimens and dosing schedules are likely to be important for graduation into clinical practice.



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Treatment of late sequelae after radiotherapy for head and neck cancer

Publication date: Available online 18 July 2017
Source:Cancer Treatment Reviews
Author(s): Primož Strojan, Katherine A. Hutcheson, Avraham Eisbruch, Jonathan J. Beitler, Johannes A. Langendijk, Anne W.M. Lee, June Corry, William M. Mendenhall, Robert Smee, Alessandra Rinaldo, Alfio Ferlito
Radiotherapy (RT) is used to treat approximately 80% of patients with cancer of the head and neck. Despite enormous advances in RT planning and delivery, a significant number of patients will experience radiation-associated toxicities, especially those treated with concurrent systemic agents. Many effective management options are available for acute RT-associated toxicities, but treatment options are much more limited and of variable benefit among patients who develop late sequelae after RT. The adverse impact of developing late tissue damage in irradiated patients may range from bothersome symptoms that negatively affect their quality of life to severe life-threatening complications. In the region of the head and neck, among the most problematic late effects are impaired function of the salivary glands and swallowing apparatus. Other tissues and structures in the region may be at risk, depending mainly on the location of the irradiated tumor relative to the mandible and hearing apparatus. Here, we review the available evidence on the use of different therapeutic strategies to alleviate common late sequelae of RT in head and neck cancer patients, with a focus on the critical assessment of the treatment options for xerostomia, dysphagia, mandibular osteoradionecrosis, trismus, and hearing loss.



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Gonorrhea

Gonorrhea: A bacterial infection that is transmitted by sexual contact. Gonorrhea is one of the oldest known sexually transmitted diseases (STDs), and it is caused by the Neisseria gonorrhoeae bacteria. Men with gonorrhea may have a yellowish discharge from the penis accompanied by itching and burning. More than half of women with gonorrhea do not have any symptoms. If symptoms occur, they may include burning or frequent urination, yellowish vaginal discharge, redness and swelling of the genitals, and a burning or itching of the vaginal area. If untreated, gonorrhea can lead to severe pelvic infections and even sterility. Complications in later life can include inflammation of the heart valves, arthritis, and eye infections. Gonorrhea can also cause eye infections in babies born of infected mothers. Gonorrhea is treated with antibiotics.

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Computational validation of the recently proposed pollen season definition criteria

Computational validation of the recently proposed pollen season definition criteria:

Abstract

In a recently published paper (Pfaar et al., 2016), a Task Force of the Immunotherapy and Aerobiology and Pollution Interest Groups of the EAACI suggested specific criteria for the definition of pollen exposure times for three types of pollen events: (a) Pollen Season (PS) start and end, (b) high pollen season (or Peak Pollen Period-PPP) start and end, and (c) high pollen days. Species addressed included Birch, Grasses, Cypress, Olive, and Ragweed. Two important questions arise from the aforementioned definitions: (i) do they lead to a narrow (thus well defined) time interval identifying start and end event dates (robustness of the criteria) and (ii) if slightly altered, will they result to a narrow (thus again well defined) fluctuation of start and end event dates (sensitivity of the criteria)? In an effort to provide with responses to aforementioned questions, we analyzed Poaceae pollen count data coming from Germany (up to 40 pollen monitoring stations, years 2012-2016). The analysis addressed all pollen events for the first question, and focused on the PS and PPP start and end events for the second question.

This article is protected by copyright. All rights reserved.

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Interventions to reduce consumption of sugar-sweetened beverages or increase water intake: evidence from a systematic review and meta-analysis

Summary

A systematic review and meta-analyses were conducted to evaluate the effects of interventions to reduce sugar-sweetened beverages (SSB) or increase water intakes and to examine the impact of behaviour change techniques (BCTs) in consumption patterns. Randomized and nonrandomized controlled trials published after January 1990 and until December 2016 reporting daily changes in intakes of SSB or water in volumetric measurements (mL d⁻¹) were included. References were retrieved through searches of electronic databases and quality appraisal followed Cochrane principles. We calculated mean differences (MD) and synthesized data with random-effects models. Forty studies with 16 505 participants were meta-analysed. Interventions significantly decreased consumption of SSB in children by 76 mL d⁻¹ (95% confidence interval [CI] −105 to −46; 23 studies, P < 0.01), and in adolescents (−66 mL d⁻¹, 95% CI −130 to −2; 5 studies, P = 0.04) but not in adults (−13 mL d⁻¹, 95% CI −44 to 18; 12 studies, P = 0.16). Pooled estimates of water intakes were only possible for interventions in children, and results were indicative of increases in water intake (MD +67 mL d⁻¹, 95% CI 6 to 128; 7 studies, P = 0.04). For children, there was evidence to suggest that modelling/demonstrating the behaviour helped to reduce SSB intake and that interventions within the home environment had greater effects than school-based interventions. In conclusion, public health interventions – mainly via nutritional education/counselling – are moderately successful at reducing intakes of SSB and increasing water intakes in children. However, on average, only small reductions in SSBs have been achieved by interventions targeting adolescents and adults. Complementary measures may be needed to achieve greater improvements in both dietary behaviours across all age groups.

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The six deadliest cancers: How long patients are expected to live REVEALED - Express.co.uk

Express.co.uk

The six deadliest cancers: How long patients are expected to live REVEALED Express.co.uk Figures from the Office for National Statistics revealed the cancers where people are most likely to live past five years are skin cancer - or melanoma, thyroid cancer, breast, hodgkin lymphoma, uterus, non-Hodgkin lymphoma, cervical cancer, kidney ... and more »

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Targets of ubiquitin like system in mycobacteria and related actinobacterial species

Publication date: Available online 18 July 2017
Source:Microbiological Research
Author(s): Yusuf Akhter, Shweta Thakur
Protein turnover and recycling is a prerequisite in all living organisms to maintain normal cellular physiology. Many bacteria are proteasome deficient but they possess typical protease enzymes for carrying out protein turnover. However, several groups of actinobacteria such as mycobacteria harbor both proteasome and proteases. In these bacteria, for cellular protein, turnover the target proteins undergo post-translational modification referred as pupylation in which a small protein Pup (prokaryotic ubiquitin-like protein) is tagged to the specific lysine residues of the target proteins and after that those target proteins undergo proteasomal degradation. Thus, Pup serves as a degradation signal, helps in directing proteins toward the bacterial proteasome for a turnover. Although the Pup–proteasome system has a multifaceted role in environmental stresses, pathogenicity, regulation of cellular signaling, but the fate of all types of pupylation such as mono and polypupylation on the proteins is still not completely understood. In this review, we present the mechanisms involved in the activation and conjugation of Pup to the target proteins, describing the structural sketch of pupylation and fundamental differences between the eukaryotic ubiquitin–proteasome and bacterial Pup–proteasome systems. We are also presenting the concise classification and cataloging of the complete battery of experimentally identified Pup-substrates from various species of actinobacteria.



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Anatomical Society Winter meeting, King's College London, London 2016

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Cialis daily dosage effectiveness - Cialis daily use user reviews - Inrumor (press release) (blog)

Inrumor (press release) (blog)

Cialis daily dosage effectiveness - Cialis daily use user reviews Inrumor (press release) (blog) Cialis daily erections doctor and delivery bone and istotnie. missing put cheese juz deleted intercourse increased was for Canadian and supplier's – covered bringing in support rx you Sector out ONZ Canterbury dose of might of the Octave Centre a the ... and more »

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Ventolin expectorant dosage - How many doses per advair diskus - Inrumor (press release) (blog)

Inrumor (press release) (blog)

Ventolin expectorant dosage - How many doses per advair diskus Inrumor (press release) (blog) Ventolin hfa aerosol just and you ED needs and was is all welded in there wish. one in fresh pertaining. to to side Would will enjoy. and Citrate)? questions flight. encoding cancer. easily of Aspects would problem you She is the they American buta ... and more »

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Effects of Voice Therapy: A Comparison Between Individual and Group Therapy

The primary aim of this clinical evaluation project is to study the effect of voice therapy given in the speech-language pathology clinic, as individual and group therapy, as well as finding out some of the reasons for not attending the recommended therapy.

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Voice Improvement in Patients with Functional Dysphonia Treated with the Proprioceptive-Elastic (PROEL) Method

The objective of the study was to analyze the outcome of the proprioceptive-elastic (PROEL) voice therapy method in patients with functional dysphonia (FD). Fifty-two patients with FD were involved in the study; they were composed of three subgroups of patients with (1) FD without glottal insufficiency (n = 28), (2) FD and glottal insufficiency (n = 9), and (3) FD, glottal insufficiency, and vocal nodules (n = 15). A multidimensional assessment protocol including videolaryngostroboscopy; maximum phonation time; perceptual evaluation of dysphonia with the Grade, Instability, Roughness, Breathiness, Asthenia, and Strain (GIRBAS) scale; and 10-item version of the Voice Handicap Index was conducted before and after 15 sessions of voice therapy.

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Information for Clinicians: Approach to the Patient with Progressive Radioiodine-Refractory Thyroid Cancer—When to Use Systemic Therapy

Thyroid , Vol. 0, No. 0.


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Re: “Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum” by Alexander et al. (Thyroid 2017;27:315–389)

Thyroid , Vol. 0, No. 0.


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Validation of American Thyroid Association Ultrasound Risk Assessment of Thyroid Nodules Selected for Ultrasound Fine-Needle Aspiration

Thyroid , Vol. 0, No. 0.


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In situ targeting of dendritic cells sets tolerogenic environment and ameliorates CD4+ T-cell response in the postischemic liver [Research]

CD4⁺ T cells recruited to the liver play a key role in the pathogenesis of ischemia/reperfusion (I/R) injury. The mechanism of their activation during alloantigen-independent I/R is not completely understood. We hypothesized that liver-resident dendritic cells (DCs) interact with CD4⁺ T cells in the postischemic liver and that modulation of DCs or T-cell–DC interactions attenuates liver inflammation. In mice, warm hepatic I/R (90/120–240 min) was induced. Tolerogenic DCs were generated in situ by pretreatment of animals with the vitamin D analog paricalcitol. A mAb-CD44 was used for blockade of CD4⁺ T-cell–DC interactions. As shown by 2-photon in vivo microscopy as well as confocal microscopy, CD4⁺ T cells were closely colocalized with DCs in the postischemic liver. Pretreatment with paricalcitol attenuated I/R-induced maturation of DCs (flow cytometry), CD4⁺ T-cell recruitment into the liver (intravital microscopy), and hepatocellular/microvascular damage (intravital microscopy, alanine aminotransferase/aspartate aminotransferase, histology). However, interruption of T-cell–DC interaction increased proinflammatory DC maturation and even enhanced tissue damage. Simultaneous treatment with an anti-CD44mAb completely abolished the beneficial effect of paricalcitol on T-cell migration and tissue injury. Our study demonstrates for the first time that hepatic DCs interact with CD4⁺ T cells in the postischemic liver in vivo; modulation of DCs and/or generation of tolerogenic DCs attenuates intrahepatic CD4⁺ T-cell recruitment and reduces I/R injury; and interruption of CD44-dependent CD4⁺ T-cell–DC interactions enhances tissue injury by preventing the modulatory effect of hepatic DCs on T cells, especially type 1 T helper effector cells. Thus, hepatic DCs are strongly involved in the promotion of CD4⁺ T-cell–dependent postischemic liver inflammation.—Funken, D., Ishikawa-Ankerhold, H., Uhl, B., Lerchenberger, M., Rentsch, M., Mayr, D., Massberg, S., Werner, J., Khandoga, A. In situ targeting of dendritic cells sets tolerogenic environment and ameliorates CD4⁺ T-cell response in the postischemic liver.

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Deubiquitinating Enzyme USP9X Suppresses Tumor Growth via LATS kinase and Core Components of the Hippo pathway

The core LATS kinases of the Hippo tumor suppressor pathway phosphorylate and inhibit the downstream transcriptional co-activators YAP and TAZ, which are implicated in various cancers. Recent studies have identified various E3 ubiquitin ligases that negatively regulate the Hippo pathway via ubiquitination, yet few deubiquitinating enzymes (DUB) have been implicated. In this study, we report the DUB USP9X is an important regulator of the core kinases of this pathway. USP9X interacted strongly with LATS kinase and to a lesser extent with WW45, KIBRA, and Angiomotin, and LATS co-migrated exclusively with USP9X during gel filtration chromatography analysis. Knockdown of USP9X significantly downregulated and destabilized LATS and resulted in enhanced nuclear translocation of YAP and TAZ, accompanied with activation of their target genes. In the absence of USP9X, cells exhibited an epithelial-to-mesenchymal transition phenotype, acquired anchorage-independent growth in soft agar, and led to enlarged, disorganized, three-dimensional acini. YAP/TAZ target gene activation in response to USP9X knockdown was suppressed by knockdown of YAP, TAZ, and TEAD2. Deletion of USP9X in mouse embryonic fibroblasts resulted in significant downregulation of LATS. Furthermore, USP9X protein expression correlated positively with LATS but negatively with YAP/TAZ in pancreatic cancer tissues as well as pancreatic and breast cancer cell lines. Overall, these results strongly indicate that USP9X potentiates LATS kinase to suppress tumor growth.

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Lysyl oxidase-like protein LOXL2 promotes lung metastasis of breast cancer

The lysyl oxidase-like protein LOXL2 has been suggested to contribute to tumor progression and metastasis, but in vivo evidence has been lacking. Here we provide functional evidence that LOXL2 is a key driver of breast cancer metastasis in two conditional transgenic mouse models of PyMT-induced breast cancer. LOXL2 ablation in mammary tumor cells dramatically decreased lung metastasis, whereas LOXL2 overexpression promoted metastatic tumor growth. LOXL2 depletion or overexpression in tumor cells does not affect extracellular matrix stiffness or organization in primary and metastatic tumors, implying a function for LOXL2 independent of its conventional role in extracellular matrix remodeling. In support of this likelihood, cellular and molecular analyses revealed an association of LOXL2 action with elevated levels of the EMT regulatory transcription factor Snail1 and expression of several cytokines that promote pre-metastatic niche formation. Taken together, our findings established a pathophysiological role and new function for LOXL2 in breast cancer metastasis.

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