Inflammation,a significant player of Ataxia–Telangiectasia pathogenesis?

Introduction

Ataxia–Telangiectasia (A-T) syndrome is an autosomal recessive neurodegenerative disorder characterized by cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, chromosome instability, radiosensitivity, and predisposition to malignancy. There is growing evidence that A–T patients suffer from pathologic inflammation that is responsible for many symptoms of this syndrome, including neurodegeneration, autoimmunity, cardiovascular disease, accelerated aging, and insulin resistance. In addition, epidemiological studies have shown A–T heterozygotes, somewhat like deficient patients, are susceptible to ionizing irradiation and have a higher risk of cancers and metabolic disorders.

Area covered

This review summarizes clinical and molecular findings of inflammation in A–T syndrome.

Conclusion

Ataxia–Telangiectasia Mutated (ATM), a master regulator of the DNA damage response is the protein known to be associated with A–T and has a complex nuclear and cytoplasmic role. Loss of ATM function may induce immune deregulation and systemic inflammation.

     

The Perception of Trauma Patients from Social Support in Adjustment to Lower-Limb Amputation: A Qualitative Study

Introduction:

The effect of amputation on an individual''s psychological condition as well as family and social relationships is undeniable because physical disability not just affects the psycho-social adjustment, but also the mental health. When compared to normal people, such people are mostly experiencing social isolation. On the other hand, social support is known as the most powerful force to cope with stressful situations and it allows patients to withstand problems. The present study aims to explain understanding the trauma of patients and the experience of support sources during the process of adaptation to a lower limb amputation.

Materials and Methods:

The present study was conducted using qualitative content analysis. Participants included 20 patients with lower limb amputation due to trauma. Sampling was purposive initially and continued until data saturation. Unstructured interviews were used as the main method of data collection. Collected data were analyzed using qualitative content analysis and constant comparison methods.

Results:

The main theme extracted from the data was support sources. The classes include “supportive family”, “gaining friends’ support”, “gaining morale from peers”, and “assurance and satisfaction with the workplace.”

Conclusion:

Given the high number of physical, mental and social problems in trauma patients, identifying and strengthening support sources can be effective in their adaptation with the disease and improvement of the quality of their life.     

Converging neuronal activity in inferior temporal cortex during the classification of morphed stimuli

How does the brain dynamically convert incoming sensory data into a representation useful for classification? Neurons in inferior temporal (IT) cortex are selective for complex visual stimuli, but their response dynamics during perceptual classification is not well understood. We studied IT dynamics in monkeys performing a classification task. The monkeys were shown visual stimuli that were morphed (interpolated) between pairs of familiar images. Their ability to classify the morphed images depended systematically on the degree of morph. IT neurons were selected that responded more strongly to one of the 2 familiar images (the effective image). The responses tended to peak approximately 120 ms following stimulus onset with an amplitude that depended almost linearly on the degree of morph. The responses then declined, but remained above baseline for several hundred ms. This sustained component remained linearly dependent on morph level for stimuli more similar to the ineffective image but progressively converged to a single response profile, independent of morph level, for stimuli more similar to the effective image. Thus, these neurons represented the dynamic conversion of graded sensory information into a task-relevant classification. Computational models suggest that these dynamics could be produced by attractor states and firing rate adaptation within the population of IT neurons.     

Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans

The vanilloid receptor TRPV1 has been identified as a molecular target for the treatment of pain associated with inflammatory diseases and cancer. Hence, TRPV1 antagonists have been considered for therapeutic evaluation in such diseases. During Phase I clinical trials with AMG 517, a highly selective TRPV1 antagonist, we found that TRPV1 blockade elicited marked, but reversible, and generally plasma concentration-dependent hyperthermia. Similar to what was observed in rats, dogs, and monkeys, hyperthermia was attenuated after repeated dosing of AMG 517 (at the highest dose tested) in humans during a second Phase I trial. However, AMG 517 administered after molar extraction (a surgical cause of acute pain) elicited long-lasting hyperthermia with maximal body temperature surpassing 40 °C, suggesting that TRPV1 blockade elicits undesirable hyperthermia in susceptible individuals. Mechanisms of AMG 517-induced hyperthermia were then studied in rats. AMG 517 caused hyperthermia by inducing tail skin vasoconstriction and increasing thermogenesis, which suggests that TRPV1 regulates vasomotor tone and metabolic heat production. In conclusion, these results demonstrate that: (a) TRPV1-selective antagonists like AMG 517 cannot be developed for systemic use as stand alone agents for treatment of pain and other diseases, (b) individual susceptibility influences magnitude of hyperthermia observed after TRPV1 blockade, and (c) TRPV1 plays a pivotal role as a molecular regulator for body temperature in humans.     

National differences in gender–science stereotypes predict national sex differences in science and math achievement

About 70% of more than half a million Implicit Association Tests completed by citizens of 34 countries revealed expected implicit stereotypes associating science with males more than with females. We discovered that nation-level implicit stereotypes predicted nation-level sex differences in 8th-grade science and mathematics achievement. Self-reported stereotypes did not provide additional predictive validity of the achievement gap. We suggest that implicit stereotypes and sex differences in science participation and performance are mutually reinforcing, contributing to the persistent gender gap in science engagement.     

Adipose tissue derived mesenchymal stem cell (AD-MSC) promotes skin wound healing in diabetic rats

Aims

Stem cells are a new hope to ameliorate impaired diabetic wound healing. The purpose of this study was to evaluate the effect of adipose tissue derived mesenchymal stem cells (AD-MSCs) on wound healing in a diabetic rat model.

Methods

Twenty-six rats became diabetic by a single intraperitoneal injection of streptozotocin. Six rats served as non-diabetic (non-DM). Diabetic rats were divided into two equal groups randomly; control and treatment. Six weeks later, a full-thickness circular excisional wound was created on the dorsum of each rat. AD-MSCs were injected intra-dermally around the wounds of treatment group. PBS was applied to control and non-DM groups. The wound area was measured every other day. After wound healing completion, full thickness skin samples were taken from the wound sites for evaluation of volume density of collagen fibers, length and volume density of vessels, and numerical density of fibroblasts by stereological methods.

Results

AD-MSCs accelerated wound healing rate in diabetic rats, but did not increase length and volume density of the vessels and volume density of the collagen fibers. AD-MSCs decreased the numerical density of fibroblasts.

Conclusions

We concluded that AD-MSCs enhances diabetic wound healing rate probably by other mechanisms rather than enhancing angiogenesis or accumulating collagen fibers.     

Distinguishing between global and dental self-esteem in evaluating malocclusions

Objective: When dealing with the impact of malocclusion on self-esteem, the terms global and dental self-esteem are sometimes used. Although these terms are related to one another, they do not depict the same concept. The aims of this paper were to explore if the two forms of self-esteem are distinguishable, to find out if they represent different factors, and to investigate how they are related to malocclusion.

Materials and methods: A sample consisting of 150 adolescents, aged 13 years, completed self-assessed measures of Dental and Global Self-Esteem. Orthodontic treatment need for each individual was assessed by the Dental Health Component of the Index of Orthodontic Treatment Need (IOTN-DHC). Data were analysed by factor analyses and a 5 (IOTN-DHC grades) by 2 (global vs. dental self-esteem) ANOVA, with the IOTN-DHC grades as the independent and self-esteem (repeated measure) as the dependent variables.

Results: The factor analyses showed that the two forms of self-esteem, based on the measures, are distinguishable. More importantly, the results of the ANOVA revealed that Dental and Global Self-Esteem are differentially related to IOTN-DHC. Specifically, Dental Self-Esteem varied across IOTN-DHC scale while Global Self-Esteem did not. There was no effect of gender.

Conclusions: Dental self-esteem is related to malocclusion while global self-esteem is not. These findings have implications in areas where the predictive power of dental self-esteem needs to be considered.     

A metabolomic study on the effect of intravascular laser blood irradiation on type 2 diabetic patients

Intravenous laser blood irradiation (ILBI) is widely applied in the treatment of different pathologies including diabetes mellitus. The aim of this study is to evaluate the effects of ILBI on the metabolites of blood in diabetic type 2 patients using metabolomics. We compared blood samples of nine diabetic type 2 patients, using metabolomics, before and after ILBI with blue light laser. The results showed significant decrease in glucose, glucose 6 phosphate, dehydroascorbic acid, R-3-hydroxybutyric acid, l-histidine, and l-alanine and significant increase in l-arginine level in blood and blood sugar in the patients have reduced significantly (p?<?0.05). This study clearly demonstrated a significant positive effect of ILBI on metabolites of blood in diabetic type 2 patients. These findings support the therapeutic potential of ILBI in diabetic patients.     

Antibacterial activity of a new mineral trioxide aggregate-based root canal sealer

Objectives: To compare the antibacterial effect of AH‐26, white‐coloured mineral trioxide aggregate (WMTA) and CPM sealer against Staphylococcus aureus and Streptococcus mutans after 24 h and 1 week. Materials and methods: All materials were prepared according to the manufacturers’ directions immediately before testing. The antibacterial effect of each agent was determined by measuring the diameter of the zone of inhibition in millimetres after incubation at 37 °C for 24 h and 7 days in a humid atmosphere. Each test was repeated three times. Results: In the 24‐h and 7‐day samples, the antibacterial activity of AH‐26 was significantly greater than that of the two other materials tested against both bacteria (P < 0.05). The antibacterial activities of CPM sealer and WMTA against S. aureus were not significantly different (P > 0.05) in 24‐h or 7‐day samples, but CPM sealer demonstrated a significantly greater effect than WMTA against S. mutans (P < 0.05). Conclusion: All products studied exhibited antibacterial activity. However, in 24‐h and 7‐day samples, AH‐26 exerted the greatest activity against both organisms tested.