Multiporphyrin coordination arrays based on complexation of magnesium(II) porphyrins with porphyrinylphosphine oxides

Di- and triporphyrin arrays consisting of 5,15-diphenylporphyrinatomagnesium(II) (MgDPP) coordinated to free- base and Ni( II) porphyrinyl mono- and bis-phosphine oxides, as well as the self-coordinating diphenyl[10,20-diphenylporphyrinatomagnesium(II)-5-yl]phosphine oxide [MgDPP(Ph2PO)], were synthesised in excellent yields and characterised by various spectroscopic techniques. Phosphine oxides stabilise Mg(II) coordination to porphyrins and the resulting complexes have convenient solubilities, while the Ni(II) complexes exhibit interesting intramolecular fluorescence quenching behaviour. The binding constant of MgDPP to triphenylphosphine oxide (5.3 +/- 0.1 x 10(5) M-1) and the very high self- association constant of [MgDPP(Ph2PO)] (5.5 +/- 0.5 x 10(8) M-1) demonstrate the strong affinity of phosphine oxides towards Mg(II) porphyrins. These complexes are the first strongly bound synthetic Mg(II) multiporphyrin complexes and could potentially mimic the "special pair" in the photosynthetic reaction centre

Measuring equity in household's health care payments (Tehran-Iran 2013): Technical points for health policy decision makers

Background: Households' financial protection against health payments and expenditures and equity in utilization of health care services are of the most important tasks of governments. This study aims to measuring equity in household's health care payments according to fairness in financial contribution (FFC) and Kakwani indices in Tehran-Iran, 2013. Methods: This cross-sectional study was conducted in 2014.The study sample size was estimated to be 2200 households. Households were selected using stratified-cluster sampling including typical families who reside in the city of Tehran. The data were analyzed through Excel and Stata v.11software. Recall period for the inpatient care was 1 year and for outpatient1 month. Results: The indicator of FFC for households in health financing was estimated to be 0.68 and the trend of the indicator was ascending by the rise in the ranking of households' financial level. The Kakwani index was estimated to be a negative number (-0.00125) which indicated the descending trend of health financing system. By redistribution of incomes or the exempt of the poorest quintiles from health payments, Kakwani index was estimated to be a positive number (0.090555) which indicated the ascending trend of health financing system. Conclusion: According to this study, the equity indices in health care financing denote injustice and a descending trend in the health care financing system. This finding clearly shows that deliberate policy making in health financing by national health authorities and protecting low-income households against health expenditures are required to improve the equity in health

Serration pattern analysis for differentiating epidermolysis bullosa acquisita from other pemphigoid diseases

Background: Direct immunofluorescence (DIF) microscopy of a skin biopsy specimen is the reference standard for the diagnosis of pemphigoid diseases (PDs). Serration pattern analysis enables the differentiation of epidermolysis bullosa acquisita (EBA) from other PDs using DIF microscopy alone. However, practice gaps need to be addressed in order to implement this technique in the routine diagnostic procedure. Objective: We sought to determine and optimize the technical requirements for serration pattern analysis of DIF microscopy and determine interrater conformity of serration pattern analysis. Methods: We compared serration pattern analysis of routine DIF microscopy from laboratories in Groningen, The Netherlands and Lubeck, Germany with 4 blinded observers. Skin biopsy specimens from 20 patients with EBA and other PDs were exchanged and analyzed. Various factors were evaluated, including section thickness, transport medium, and biopsy specimen processing. Results: The interrater conformity of our 4 observers was 95.7%. Recognition of serration patterns was comparable in samples transported in saline and in Michel's medium and with section thicknesses of 4, 6, and 8 mu m. Limitations: Limitations include our small sample size and the availability of 20 samples that were compared retrospectively. Conclusion: DIF serration pattern analysis is not restricted by variation in laboratory procedures, transport medium, or experience of observers. This learnable technique can be implemented as a routine diagnostic method as an extension of DIF microscopy for subtyping PD. (J Am Acad Dermatol 2018;78:754-9.

Negative feedback regulation of the ERK1/2 MAPK pathway

The extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) signalling pathway regulates many cellular functions, including proliferation, differentiation, and transformation. To reliably convert external stimuli into specific cellular responses and to adapt to environmental circumstances, the pathway must be integrated into the overall signalling activity of the cell. Multiple mechanisms have evolved to perform this role. In this review, we will focus on negative feedback mechanisms and examine how they shape ERK1/2 MAPK signalling. We will first discuss the extensive number of negative feedback loops targeting the different components of the ERK1/2 MAPK cascade, specifically the direct posttranslational modification of pathway components by downstream protein kinases and the induction of de novo gene synthesis of specific pathway inhibitors. We will then evaluate how negative feedback modulates the spatiotemporal signalling dynamics of the ERK1/2 pathway regarding signalling amplitude and duration as well as subcellular localisation. Aberrant ERK1/2 activation results in deregulated proliferation and malignant transformation in model systems and is commonly observed in human tumours. Inhibition of the ERK1/2 pathway thus represents an attractive target for the treatment of malignant tumours with increased ERK1/2 activity. We will, therefore, discuss the effect of ERK1/2 MAPK feedback regulation on cancer treatment and how it contributes to reduced clinical efficacy of therapeutic agents and the development of drug resistance

Targeted agents and immunotherapies: optimizing outcomes in melanoma

Treatment options for patients with metastatic melanoma, and especially BRAF-mutant melanoma, have changed dramatically in the past 5 years, with the FDA approval of eight new therapeutic agents. During this period, the treatment paradigm for BRAF-mutant disease has evolved rapidly: the standard-of-care BRAF-targeted approach has shifted from single-agent BRAF inhibition to combination therapy with a BRAF and a MEK inhibitor. Concurrently, immunotherapy has transitioned from cytokine-based treatment to antibody-mediated blockade of the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and, now, the programmed cell-death protein 1 (PD-1) immune checkpoints. These changes in the treatment landscape have dramatically improved patient outcomes, with the median overall survival of patients with advanced-stage melanoma increasing from approximately 9 months before 2011 to at least 2 years - and probably longer for those with BRAF-V600-mutant disease. Herein, we review the clinical trial data that established the standard-of-care treatment approaches for advanced-stage melanoma. Mechanisms of resistance and biomarkers of response to BRAF-targeted treatments and immunotherapies are discussed, and the contrasting clinical benefits and limitations of these therapies are explored. We summarize the state of the field and outline a rational approach to frontline-treatment selection for each individual patient with BRAF-mutant melanoma

Investigating the Relative Frequency of Infection with Herpes Simplex Virus Types 1 and 2 in the Serum of Patients with Multiple Sclerosis via Using Loop-mediated Isothermal Amplification (LAMP)

Introduction: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). It is an Auto immune disease whose cause is still unknown though some factors can be named as its cause such as genetics, geographic element and viral agents. HSV is among the infection agents that may be involved in pathogenesis of MS. The aim of this study was to use a new technique called loop-mediated isothermal amplification to detect presence of Herpes Simplex Virus in patients harboring Multiple Sclerosis as well as in healthy individuals in the control group. Methods: This study is a cross-sectional analytical study in which 50 multiple sclerosis patients and 50 healthy controls were included. The infection with herpes simplex virus types 1 and 2 was investigated by the new technique of LAMP. Results: The sensitivity of this technique was 5 particle viruses and its specificity for HSV was 100%. Within the 50 patients with multiple sclerosis, 11 samples revealed positive results for HSV (22%), while in the control group no infection with herpes simplex virus was found (0%). Conclusion: This study indicates that the LAMP technique owns high sensitivity and specificity for detection of herpes simplex virus types 1 and 2 in serum of patients with multiple sclerosis as well as the control group

Look Different: Effect of Radiation Hormesis on the Survival Rate of Immunosuppressed Mice

Background: Hormesis is defined as the bio-positive response of something which is bio-negative in high doses. In the present study, the effect of radiation hormesis was evaluated on the survival rate of immunosuppressed BALB/c mice by Cyclosporine A. Material and Methods: We used 75 consanguine, male, BALB/c mice in this experiment. The first group received Technetium-99m (3700Bq) and the second group was placed on a sample radioactive soil of Ramsar region (800Bq) for 20 days. The third group was exposed to X-rays (3600Bq) and the fourth group was placed on the radioactive soil and then injected Technetium-99m. The last group was the sham irradiated control group. Finally, 30mg Cyclosporine A as the immunosuppressive agent was orally administered to all mice 48 hours after receiving X-rays and Technetium99m. The mean survival rate of mice in each group was estimated during time. Results: A log rank test was run to determine if there were differences in the survival distribution for different groups and related treatments. According to the results, the survival rate of all pre-irradiated groups was more than the sham irradiated control group (p < .05). The highest survival time was related to the mice which were placed on the radioactive soil of Ramsar region for 20 days and then injected Technetium99m. Conclusion: This study confirmed the presence of hormetic models and the enhancement of survival rate in immunosuppressed BALB/c mice as a consequence of low-dose irradiation. It is also revealed the positive synergetic radioadaptive response on survival rate of immunosuppressed animals

Can technology impact loneliness in dementia? A scoping review on the role of assistive technologies in delivering psychosocial interventions in long-term care

Purpose We aimed to identify assistive technologies that are promising for addressing loneliness in people living with dementia in long-term care. Materials and methods A scoping review was conducted. EBSCO, PubMed, Cochrane Library, and ProQuest were searched from 2000 to 2020. The included studies were selected by three independent researchers and summarised, compared, and categorized according to technology type. Publications were eligible for inclusion when they reported on psychosocial interventions aiming to reduce loneliness and/or social isolation in people with dementia in long-term care settings. Results Twenty-four papers were included (20 original research papers and four reviews). Most studies were conducted in Australia and Europe. The studies aimed to investigate two different types of assistive technology: social robots, and multimedia computer systems. Most studies focussed on behaviour, engagement, and mood as primary outcomes. Only one study directly aimed to alleviate loneliness. Conclusions Even though only one study addressed loneliness directly, it became clear that assistive technologies used to apply psychosocial interventions have the potential to impact loneliness in people with dementia in long-term care. However, it remains unclear why loneliness was not included as an outcome and how loneliness could become a key outcome in evaluating assistive technologies

Can technology impact loneliness in dementia? A scoping review on the role of assistive technologies in delivering psychosocial interventions in long-term care

Purpose: We aimed to identify assistive technologies that are promising for addressing loneliness in people living with dementia in long-term care. Materials and methods: A scoping review was conducted. EBSCO, PubMed, Cochrane Library, and ProQuest were searched from 2000 to 2020. The included studies were selected by three independent researchers and summarised, compared, and categorized according to technology type. Publications were eligible for inclusion when they reported on psychosocial interventions aiming to reduce loneliness and/or social isolation in people with dementia in long-term care settings. Results: Twenty-four papers were included (20 original research papers and four reviews). Most studies were conducted in Australia and Europe. The studies aimed to investigate two different types of assistive technology: social robots, and multimedia computer systems. Most studies focussed on behaviour, engagement, and mood as primary outcomes. Only one study directly aimed to alleviate loneliness. Conclusions: Even though only one study addressed loneliness directly, it became clear that assistive technologies used to apply psychosocial interventions have the potential to impact loneliness in people with dementia in long-term care. However, it remains unclear why loneliness was not included as an outcome and how loneliness could become a key outcome in evaluating assistive technologies.IMPLICATIONS FOR REHABILITATION Loneliness among older adults is associated with health risks, such as the development of dementia, depression, and increased mortality. Ambient Assisted Living (AAL) technologies have been studied to address loneliness for older adults; however people with dementia are often excluded from such studies. This diverse group of technologies is shown to have a promising impact on outcomes, such as social engagement, quality of life, and mood, but loneliness was studied less often. More research is needed to discover the potential of assistive technologies for people with dementia living in long-term care