Roles of Cytokines in Pathological and Physiological Gastroesophageal Reflux Exposure.

Background/Aims: Gastroesophageal reflux disease is frequently observed and has no definitive treatment. There are 2 main views on the pathogenesis of gastroesophageal reflux disease. The first is that epithelial damage starts from the mucosa by acidic-peptic damage and the inflammatory response of granulocytes. The other view is that T-lymphocytes attract chemoattractants from the basal layer to the mucosa, and granulocytes do not migrate until damage occurs. We aim to investigate the inflammatory processes occurring in the esophageal epithelium of the phenotypes at the molecular level. We also examined the effects of these changes on tissue integrity. Methods: Patients with mild and severe erosive reflux, nonerosive reflux, reflux hypersensitivity, and functional heartburn were included. Inflammatory gene expressions (JAK/STAT Signaling and NFKappaB Primer Libraries), chemokine protein levels, and tissue integrity were examined in the esophageal biopsies. Results: There was chronic inflammation in the severe erosion group, the acute response was also triggered. In the mild erosion group, these 2 processes worked together, but homeostatic cytokines were also secreted. In nonerosive groups, T-lymphocytes were more dominant. In addition, the inflammatory response was highly triggered in the reflux hypersensitivity and functional heartburn groups, and it was associated with physiological reflux exposure and sensitivity. Conclusions: "Microinflammation" in physiological acid exposure groups indicate that even a mild trigger is sufficient for the initiation and progression of inflammatory activity. Additionally, the anti-inflammatory cytokines were highly increased. The results may have a potential role in the treatment of heartburn symptoms and healing of the mucosa.

Optimization of agarose-alginate hydrogel bead components for encapsulation and transportation of stem cells.

Hydrogels have potential uses in various biological applications because of their unique characteristics. Fine-tuning of agarose-alginate (Ag-Al) hydrogel components improves the mechanical characteristics of the final construct for cell encapsulation and transportation. Formulation of suitable dissolving agents may enable the release of encapsulated cells for further applications in laboratory or clinical settings. Objectives: This study aimed at optimizing the composition of Ag-Al hydrogel beads and their dissolving agents for potential use in the transportation of stem cells. Methods: Various agarose, alginate, and CaCl2 concentrations were tested to construct hydrogel beads. The degradation rate and swelling ratio of each hydrogel sample were recorded. The optimized Ag-Al hydrogels were used for encapsulation of stem cells from human exfoliated deciduous teeth (SHED). Optimization of dissolving agents was performed and tested with the hydrogel-encapsulated cells. Data were statistically analyzed in SPSS. Results: The selected concentration of Ag-Al hydrogels components was successfully demonstrated to encapsulate SHED, which remained viable until day 10. An average of 2 min was required for degradation of the hydrogel with encapsulated SHED by a dissolving agent consisting of 100 mM sodium citrate and 100 mM EDTA. The cell viability of SHED released after day 10 of encapsulation was 29.1%. Conclusion: Alteration of Ag-Al components has considerable influence on the mechanical properties of the constructed hydrogel. The feasibility of performing the optimized cell encapsulation protocol, as well as the dissolving step, may provide a useful guide for the transportation of viable cells between countries, for medical research.

Lifetime spirometry patterns of obstruction and restriction, and their risk factors and outcomes: a prospective cohort study.

BACKGROUND: Interest in lifetime lung function trajectories has increased in the context of emerging evidence that chronic obstructive pulmonary disease (COPD) can arise from multiple disadvantaged lung function pathways, including those that stem from poor lung function in childhood. To our knowledge, no previous study has investigated both obstructive and restrictive lifetime patterns concurrently, while accounting for potential overlaps between them. We aimed to investigate lifetime trajectories of the FEV1/forced vital capacity (FVC) ratio, FVC, and their combinations, relate these combined trajectory groups to static lung volume and gas transfer measurements, and investigate both risk factors for and consequences of these combined trajectory groups. METHODS: Using z scores from spirometry measured at ages 7, 13, 18, 45, 50, and 53 years in the Tasmanian Longitudinal Health Study (n=2422), we identified six FEV1/FVC ratio trajectories and five FVC trajectories via group-based trajectory modelling. Based on whether trajectories of the FEV1/FVC ratio and FVC were low (ie, low from childhood or adulthood) or normal, four patterns of lifetime spirometry obstruction or restriction were identified and compared against static lung volumes and gas transfer. Childhood and adulthood characteristics and morbidities of these patterns were investigated. FINDINGS: The prevalence of the four lifetime spirometry patterns was as follows: low FEV1/FVC ratio only, labelled as obstructive-only, 25·8%; low FVC only, labelled as restrictive-only, 10·5%; both low FEV1/FVC ratio and low FVC, labelled as mixed, 3·5%; and neither low FEV1/FVC ratio nor low FVC, labelled as reference, 60·2%. The prevalence of COPD at age 53 years was highest in the mixed pattern (31 [37%] of 84 individuals) followed by the obstructive-only pattern (135 [22%] of 626 individuals). Individuals with the mixed pattern also had the highest prevalence of parental asthma, childhood respiratory illnesses, adult asthma, and depression. Individuals with the restrictive-only pattern had lower total lung capacity and residual volume, and had the highest prevalence of childhood underweight, adult obesity, diabetes, cardiovascular conditions, hypertension, and obstructive sleep apnoea. INTERPRETATION: To our knowledge, this is the first study to characterise lifetime phenotypes of obstruction and restriction simultaneously using objective data-driven techniques and unique life course spirometry measures of FEV1/FVC ratio and FVC from childhood to middle age. Mixed and obstructive-only patterns indicate those who might benefit from early COPD interventions. Those with the restrictive-only pattern had evidence of true lung restriction and were at increased risk of multimorbidity by middle age. FUNDING: National Health and Medical Research Council of Australia, The University of Melbourne, Clifford Craig Medical Research Trust of Tasmania, The Victorian, Queensland & Tasmanian Asthma Foundations, The Royal Hobart Hospital, Helen MacPherson Smith Trust, and GlaxoSmithKline.

AN EVALUATION OF THE OCCUPATIONAL EXTERNAL RADIATION EXPOSURE OF PERSONNEL IN NUCLEAR MEDICINE PRACTICES (2010-2020).

The aim of this study was to examine the radiation doses received by personnel working in the Nuclear Medicine Department between 2010 and 2020. The data obtained were compared with the dosages recommended by international authorities. The UNSCEAR 2008 report stated that the worldwide annual average effective dose to which personnel were exposed when monitored between 2000 and 2002 was 0.70 and 1.40 mSv, respectively. In this report, 0.7 mSv refers to the dose of all monitored personnel, and 1.4 mSv refers to the dose above the detection limit. In this study, the annual average effective dose value for personnel exposed to radiation was calculated as 1.65 mSv. This value represents the dose above the detection limit. Although the individual dose results are below the recommended annual dose limit, it should not be forgotten that more effort should be made to reduce radiation doses using the as low as reasonable achievable principles.

When paediatric facial nerve paralysis is not a Bell's palsy: A case of cerebellopontine angle tumour.

Facial nerve paralysis in children is a rare clinical condition that can lead to serious complications. Due to their rare occurrence, tumours, especially in the cerebellopontine angle, may be overlooked. We report a case of cerebellopontine angle tumour in an 8-year-old boy who presented with a right-sided lower motor neuron type of facial nerve palsy. Further examination showed a mild bilateral nystagmus. However, misled by the initial diagnosis of Bell's palsy, there was a delay in performing diagnostic magnetic resonance imaging of the brain, which showed a large mass in the cerebellopontine. Subsequently, six weeks after his initial presentation, the boy succumbed to the disease. This case illustrates that careful clinical examination, even in a seemingly simple case, is imperative to avoid diagnostic errors.

Risk factors for chronic cough in adults: A systematic review and meta-analysis.

Despite the challenges of diagnosing and managing adult patients with chronic cough, a systematic synthesis of evidence on aetiological risk factor is lacking. We systematically searched PubMed and EMBASE to synthesize the current evidence for longitudinal associations between a wide range of risk factors and chronic cough in the general adult population, following the meta-analysis of observational studies in epidemiology (MOOSE) guidelines. The Newcastle-Ottawa scale was used to assess the quality of the included studies. Fixed-effect meta-analysis was conducted where appropriate. Of 26 eligible articles, 16 domains of risk factors were assessed. There was consistent evidence that asthma (pooled adjusted OR [aOR] = 3.01; 95% CI: 2.33-3.70; I2  = 0%; number of articles [N] = 3) and low education levels/socioeconomic status (SES) (pooled aOR = 1.46; 95% CI: 1.20-1.72; I2  = 0%; N = 3) were associated with an increased risk of chronic cough after adjusting for smoking and other confounders. While continuous smoking was associated with chronic cough (aOR = 1.81; 95% CI: 1.36-2.26; I2  = 57%; N = 3), there was too little evidence to draw conclusions for occupational exposures, outdoor air pollution, early-life exposures, diet, snoring and other chronic conditions, including obesity, chronic obstructive pulmonary disease, gastro-oesophageal reflux disease and chronic pain. Asthma, persistent smoking and lower education/SES were associated with an increased risk of chronic cough. Longitudinal associations between other factors frequently mentioned empirically (i.e., occupational exposures, air pollution and chronic respiratory conditions) need further investigation, ideally with objective and standardized measurement.

Critical COVID-19 is associated with distinct leukocyte phenotypes and transcriptome patterns.

BACKGROUND: Prognostic markers for disease severity and identification of therapeutic targets in COVID-19 are urgently needed. We have studied innate and adaptive immunity on protein and transcriptomic level in COVID-19 patients with different disease severity at admission and longitudinally during hospitalization. METHODS: Peripheral blood mononuclear cells (PBMCs) were collected at three time points from 31 patients included in the Norwegian SARS-CoV-2 cohort study and analysed by flow cytometry and RNA sequencing. Patients were grouped as either mild/moderate (n = 14), severe (n = 11) or critical (n = 6) disease in accordance with WHO guidelines and compared with patients with SARS-CoV-2-negative bacterial sepsis (n = 5) and healthy controls (n = 10). RESULTS: COVID-19 severity was characterized by decreased interleukin 7 receptor alpha chain (CD127) expression in naïve CD4 and CD8 T cells. Activation (CD25 and HLA-DR) and exhaustion (PD-1) markers on T cells were increased compared with controls, but comparable between COVID-19 severity groups. Non-classical monocytes and monocytic HLA-DR expression decreased whereas monocytic PD-L1 and CD142 expression increased with COVID-19 severity. RNA sequencing exhibited increased plasma B-cell activity in critical COVID-19 and yet predominantly reduced transcripts related to immune response pathways compared with milder disease. CONCLUSION: Critical COVID-19 seems to be characterized by an immune profile of activated and exhausted T cells and monocytes. This immune phenotype may influence the capacity to mount an efficient T-cell immune response. Plasma B-cell activity and calprotectin were higher in critical COVID-19 while most transcripts related to immune functions were reduced, in particular affecting B cells. The potential of these cells as therapeutic targets in COVID-19 should be further explored.

Effect of Dasatinib on Genes Related to Mitotic Catastrophe Pathway in Chronic Myeloid Leukemia Cells.

BACKGROUND: Chronic Myeloid Leukemia (CML) is characterized by a reciprocal translocation t(9;22) and forms BCR/ABL1 fusion gene called the Philadelphia chromosome. The therapeutic targets for CML patients mediated with BCR/ABL1 oncogenic are tyrosine kinase inhibitors such as imatinib, dasatinib, and nilotinib. The latter two of which have been approved for the treatment of imatinib-resistant or intolerance CML patients. Mitotic Catastrophe (MC) is one of the non-apoptotic mechanisms initiated in types of cancer cells in response to anti-cancer therapies. Pharmacological inhibitors of G2 checkpoint members or genetic suppression of PLK1, PLK2, ATR, ATM, CHK1, and CHK2 can trigger DNA-damage-stimulated mitotic catastrophe. PLK1 and AURKA/B are anomalously expressed in CML cells, where phosphorylation and activation of PLK1 occur by AURKB at centromeres and kinetochores. OBJECTIVE: The purpose of this study is to investigate the effect of dasatinib on the expression of genes in MC and apoptosis pathways in K562 cells. METHODS: Total RNA was isolated from K-562 cells treated with the IC50 value of dasatinib and untreated cells as a control group. The expression of MC and apoptosis-related genes, was analyzed by the qRT-PCR system. RESULTS: The array-data demonstrated that dasatinib-treated K562 cells significantly caused the decrease of several genes (AURKA, AURKB, PLK, CHEK1, MYC, XPC, BCL2, and XRCC2). CONCLUSION: The evidence supplies a basis to support clinical researches for the suppression of oncogenes such as PLKs with AURKs in the treatment of types of cancer, especially chronic myeloid leukemia.

Home-Initiated-Programme-to-Prepare-for-Operation: evaluating the effect of an animation video on peri-operative anxiety in children: A randomised controlled trial.

BACKGROUND: Hospital admissions and surgical operations commonly trigger anxiety in young children. Despite employing numerous support measures in our hospital, such as a pre-operative play room, the encouragement of parental companionship during induction of anaesthesia and distraction therapy, allaying the anxiety of our young surgical patients remains a challenge. OBJECTIVES: To evaluate the effectiveness of a Home-Initiated-Programme-to-Prepare-for-Operation (HIPPO) on emotional manifestation and anxiety in children undergoing surgery. DESIGN, SETTING AND PATIENTS: One hundred and thirty children were randomly assigned to either control or intervention group between February 2018 and April 2019 in a tertiary paediatric hospital in Singapore. INTERVENTION: In addition to our standard pre-operative workflow, the intervention group received an additional home preparation kit consisting of an animated video on preoperative preparation and age-specific preoperative preparation activity sheets. MAIN OUTCOME MEASURES: The primary outcome was the Children's Emotional Manifestation Scale score to evaluate behaviour and emotion in the children before and during induction of anaesthesia. Secondary outcomes evaluated anxiety levels in parents and children, the child's behaviour and degree of co-operation using the State-Trait Anxiety Inventory scores, State-Trait Anxiety Inventory Children scores, the Induction Compliance Checklist scores, the Visual Analogue Scale scores for anxiety and the feedback questionnaire. RESULTS: The difference between the Children's Emotional Manifestation Scale score in control and intervention groups was not statistically significant. A promising difference was however observed in one of the secondary outcomes where the state-State-Trait Anxiety Inventory Children scores of 7 to 10-year olds in the intervention group almost reached significance; P = 0.067. CONCLUSION: Despite being a child-friendly, easily accessible and affordable tool for patient education, HIPPO did not reduce anxiety experienced by children in the pre-operative waiting area or during induction of anaesthesia. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT04271553.

Application of Phenotype Microarray for Profiling Carbon Sources Utilization between Biofilm and Non-Biofilm of Pseudomonas aeruginosa from Clinical Isolates.

BACKGROUND: This is the fastest work in obtaining the metabolic profiles of Pseudomonas aeruginosa in order to combat the infection diseases which leads to high morbidity and mortality rates. Pseudomonas aeruginosa is a high versatility of gram-negative bacteria that can undergo aerobic and anaerobic respiration. Capabilities in deploying different carbon sources, energy metabolism and regulatory system, ensure the survival of this microorganism in the diverse environment condition. Determination of differences in carbon sources utilization among biofilm and non-biofilm of Pseudomonas aeruginosa provides a platform in understanding the metabolic activity of the microorganism. METHODS: The study was carried out from September 2017 to February 2019. Four archive isolates forming strong and intermediate biofilm and non-biofilms producer were subcultured from archive isolates. ATCC 27853 P. aeruginosa was used as a negative control or non-biofilm producing microorganism. Biofilm formation was confirmed by Crystal Violet Assay (CVA) and Congo Red Agar (CRA). Metabolic profiles of the biofilm and non-biofilms isolates were determined by phenotype microarrays (Biolog Omnilog). RESULTS AND DISCUSSION: In this study, Pseudomonas aeruginosa biofilm isolates utilized uridine, L-threonine and L-serine while non-biofilm utilized adenosine, inosine, monomethyl, sorbic acid and succinamic acid. CONCLUSION: The outcome of this result will be used for future studies to improve detection or inhibit the growth of P. aeruginosa biofilm and non-biofilm respectively.

Importance of Stem Cell Migration and Angiogenesis Study for Regenerative Cell-based Therapy: A Review.

Stem cells play an essential role in maintaining homeostasis, as well as participating in new tissue regeneration. Over the past 20 years, a great deal of effort has been made to investigate the behaviour of stem cells to enable their potential use in regenerative medicine. However, a variety of biological characteristics are known to exist among the different types of stem cells due to variations in the methodological approach, formulation of cell culture medium, isolation protocol and cellular niches, as well as species variation. In recent years, cell-based therapy has emerged as one of the advanced techniques applied in both medical and clinical settings. Cell therapies aim to treat and repair the injury sites and replace the loss of tissues by stimulating the repair and regeneration process. In order to enable the use of stem cells in regenerative therapies, further characterisation of cell behaviour, in terms of their proliferation and differentiation capacity, mainly during the quiescent and inductive state is regarded as highly necessary. The central focus of regenerative medicine revolves around the use of human cells, including adult stem cells and induced pluripotent stem cells for cell-based therapy. The purpose of this review was to examine the existing body of literature on stem cell research conducted on cellular angiogenesis and migration, to investigate the validity of different strategies and variations of the cell type used. The information gathered within this review may then be shared with fellow researchers to assist in future research work, engaging in stem cell homing for cell-based therapy to enhance wound healing and tissue regeneration process.

A systematic review of the role of grass pollen and fungi in thunderstorm asthma.

BACKGROUND: Thunderstorm asthma is defined as epidemics of asthma occurring shortly after a thunderstorm. While grass pollen has been implicated in thunderstorm asthma events, little is known about the role of fungi and studies have not been synthesised. OBJECTIVE: This systematic review aims to evaluate whether grass pollen is necessary in thunderstorm asthma events and whether fungi also play a part in these associations. METHODS: We conducted a systematic search using six electronic databases (i.e. CINAHL, Medline (Ovid), Web of Science, ProQuest Central, EMBASE and Google Scholar) and checked reference lists. The search terms used were pollen AND thunderstorm* AND asthma. The inclusion criteria were studies published in English with original human data relating to outdoor pollen and thunderstorm asthma. RESULTS: Twenty of 2198 studies were eligible. Reported findings differed due to variation in methodological approaches and a meta-analysis was not possible. Nonetheless, of the 20 studies included, 15 demonstrated some relationship with nine demonstrating lagged effects up to four days for increasing grass pollen counts associated with increased risk of thunderstorm asthma. Of the 10 studies that examined fungi, nine demonstrated a positive relationship with thunderstorm asthma. The fungal taxa involved varied, depending on whether measurements were recorded before, during or after the thunderstorm. Nevertheless, none of the studies considered fungi as a potential effect modifier for the pollen-thunderstorm asthma association. CONCLUSION: We found evidence to suggest that grass pollen was a necessary factor for thunderstorm asthma but there are other as yet unrecognised environmental factors that may also be important. Further research is required to examine the role of fungi and other environmental factors such as air quality as potential effect modifiers of the association.

Tualang honey and DHA-rich fish oil reduce the production of pro-inflammatory cytokines in the rat brain following exposure to chronic stress.

OBJECTIVES: The aim of the present study was to investigate the effects of Tualang honey (TH), DHA-rich fish oil, and their combination on the concentrations of selected pro-inflammatory cytokines in rat brains following exposure to chronic stress. METHODS: Fifty male Sprague-Dawley rats were divided into (i) control, (ii) stress-exposed, (iii) stress-exposed and treated with TH (1 g/kg body weight twice daily via oral gavage), (iv) stress-exposed and treated with DHA-rich fish oil (450 mg/kg body weight twice daily via oral gavage), and (v) stress-exposed and treated with a combination of TH and DHA-rich fish oil. The chronic stress regimen consisted of a combination of restraint stress and a swim stress test for 28 days. The concentrations of selected pro-inflammatory cytokines in brain homogenates (TNF-α, IL6, and IFN-γ) were measured by ELISA. RESULTS: The concentrations of TNF-α, IL6, and IFN-γ in brain homogenates from the DHA, TH, and TH + DHA-treated groups were significantly lower compared to the control and stress-only-exposed groups (p < 0.05), but no difference was observed between treatment groups. CONCLUSION: Consumption of DHA-rich fish oil and TH can be effective in lowering pro-inflammatory cytokine levels in the brains of rats under chronic stress conditions. However, consuming these agents together does not provide additional benefits compared to taking them separately.

Short-acting bronchodilators for the management of acute exacerbations of chronic obstructive pulmonary disease in the hospital setting: systematic review.

BACKGROUND: Currently, there is a lack of guidelines for the use of short-acting bronchodilators (SABD) in people admitted to hospital for acute exacerbation of chronic obstructive pulmonary disease (AECOPD), despite routine use in practice and risk of cardiac adverse events. AIM: To review the evidence that underpins use and optimal dose, in terms of risk versus benefit, of SABD for inpatient management of AECOPD and collate the results for future guidelines. METHODS: Medline, Embase, the Cochrane Central Register of Controlled Trials, clinicaltrials.gov and International Clinical Trials Registry Platform were searched (inception to November 2017) for published and ongoing studies. Included studies were randomised controlled trials or controlled clinical trials investigating the effect of SABD (ß2-agonist and/or ipratropium) on inpatients with a diagnosis of AECOPD. This review was undertaken in accordance with PRISMA guidelines and a pre-defined protocol. Due to heterogeneous methodologies, meta-analysis was not possible so the results were synthesised qualitatively. RESULTS: Of 1378 studies identified, 10 met inclusion criteria. Narrative synthesis of 10 studies revealed no significant differences in most outcomes of interest relative to dose, delivery via inhaler or nebuliser, and type of ß2-agonist used. However, some evidence demonstrated significantly increased cardiac side effects with increased dosage of ß2-agonist (45% versus 24%), P<0.05). CONCLUSION: This review identified a paucity of methodologically rigorous evidence evaluating use of SABD among AECOPD. The available evidence did not identify any additional benefits for participants receiving higher doses of short-acting ß2-agonists compared to lower doses, or based on type of delivery method or ß2-agonists used. However, there was a small increase in some adverse events for participants using higher doses of ß2-agonists.

Effects of probiotics supplementation and circuit training on immune responses among sedentary young males.

BACKGROUND: Growing evidence suggests that probiotics may have positive benefits on immune responses following endurance exercise. However, little attention has been given to its possible beneficial effects on immune responses following resistance exercise. METHODS: Forty-one healthy sedentary males were recruited and randomised into four groups: sedentary control with placebo (C), probiotics (P), circuit training with placebo (Ex), and circuit training with probiotics (PEx) groups. Participants in the Ex and PEx groups performed a progressive load of circuit training at 3 times/week for 12 weeks. Each circuit comprised 10 exercises with work to rest ratio of 1:2. Participants consumed either multi-strain probiotics or placebo twice daily for 12 weeks. Body height and weight, blood pressure, resting heart rate, saliva and blood samples were collected at pre- and post-tests. RESULTS: Saliva flow rate and salivary IgA, α-amylase, lactoferrin and lysozyme responses were not significantly different (P>0.05) between groups and also between pre- and post-test within each group. Similarly, total leukocytes, total lymphocytes, T lymphocytes, T-helper, T-cytotoxic, B lymphocytes, and natural killer cells counts were not significantly affected (P>0.05) by the probiotics and/or circuit training. However, circuit training significantly increased (P<0.05) immune cells count at post-test as compared to pre-test. Yet, a combination of circuit training and probiotics showed no significant (P>0.05) effects on immune cells count. CONCLUSIONS: This study did not provide enough support for the positive effects of probiotics on immune responses among sedentary young males following resistance exercise. However, 12 weeks of circuit training enhanced immune cells count.

A Missed Late Presentation of a Congenital Pulmonary Airway Malformation as a Large Infected Bulla.

A congenital pulmonary airway malformation (CPAM) is a rare cystic anomaly that may occur during development of the fetal airways. The vast majority of CPAMs are detected in neonates; as such, it is unusual for diagnosis to occur in adulthood. We report a 21-year-old male patient who presented to the emergency department of the Hospital Ampang, Kuala Lumpur, Malaysia, in 2015 with chest pain, breathlessness and tachypnoea. Based on an initial chest X-ray, the patient was misdiagnosed with pneumothorax and underwent urgent chest tube insertion; however, his condition deteriorated over the course of the next three days. Further imaging was suggestive of infected bullae or an undiagnosed CPAM. The patient therefore underwent video-assisted thoracoscopic surgery, during which a large infected bulla was resected. A diagnosis of an infected CPAM was confirmed by histopathological examination. Following the surgery, the patient recovered quickly and no bullae remnants were found at a one-month follow-up.

Effects of prolonged running in the heat and cool environments on selected physiological parameters and salivary lysozyme responses.

INTRODUCTION: Lysozyme is one of the salivary antimicrobial proteins which act as the "first line of defence" at the mucosal surface. The effects of prolonged exercise in the hot and cool environments among recreational athletes on salivary lysozyme responses are very limited in the literature, especially in the Asian countries. OBJECTIVE: To determine the effects of prolonged running in the hot and cool environments on selected physiological parameters and salivary lysozyme responses among recreational athletes. METHODS: Randomised and cross-over study design. Thirteen male recreational athletes (age: 20.9 ± 1.3 years old) from Universiti Sains Malaysia participated in this study. They performed two separate running trials; 90 min running at 60% of their respective maximum oxygen uptake [Formula: see text] One running trial was performed in the hot (31ºC) while the other was in the cool (18ºC) environment and this sequence was randomised. Each running trial was started with a 5 min warm-up at 50% of participant's respective [Formula: see text] Recovery period between these two trials was one week. In the both trials, saliva samples, blood samples, heart rate, ratings of perceived exertion, skin and tympanic temperatures, oxygen consumption, nude body weight, room temperature, and relative humidity were collected. RESULTS: Participants' skin temperature, tympanic temperature, body weight changes, heart rate, ratings of perceived exertion, and plasma volume changes were significantly higher (p < 0.05) in the hot trial compared to the cool trial. Saliva flow rate was not significantly (p = 0.949) different between the hot (0.32 ± 0.08 ml/min) and cool (0.27 ± 0.05 ml/min) trials. However, in each trial, it significantly decreased (p < 0.05) at post-exercise as compared to pre-exercise but it returned to baseline value at 1 h post-exercise. In addition, there were no significant differences between and within hot and cool trials in salivary lysozyme concentration (p = 0.925; 4.79 ± 1.37 and 4.44 ± 1.11 µg/ml respectively) and secretion rate (p = 0.843; 1.67 ± 1.1 and 1.17 ± 1.0 µg/min respectively). CONCLUSION: This study found similar lysozyme responses between both hot and cool trials. Thus, room/ambient temperature did not affect lysozyme responses among recreational athletes. Nevertheless, the selected physiological parameters were significantly affected by room temperature.

A novel regulatory relationship between RIPK4 and ELF3 in keratinocytes.

Keratinocytes are central to the barrier functions of surface epithelia, such as the gingiva and epidermis. RIPK4 is a key regulator of keratinocyte differentiation; however, the signalling pathways in which it functions remain poorly defined. In this study, we identified a regulatory relationship between RIPK4 and ELF3, an ETS family transcription factor. RIPK4 was shown to be important for the upregulation of ELF3 gene expression by the PKC agonist PMA in both oral and epidermal keratinocytes. RIPK4 promotes keratinocyte differentiation in part by phosphorylating and thereby activating the IRF6 transcription factor. Significantly, silencing of IRF6 inhibited the PMA-inducible expression of ELF3. A role for the GRHL3 transcription factor, a downstream target gene of IRF6, in the regulation of ELF3 expression was similarly demonstrated. ELF3 has previously been shown to regulate the expression of SPPR1A and SPRR1B, small proline-rich proteins that contribute to the cornification of keratinocytes. Consistently, RIPK4 and IRF6 were important for the PMA-inducible expression of SPRR1A and SPRR1B. They were also important for the upregulation of TGM1, a transglutaminase that catalyses the cross-linking of proteins, including small proline-rich proteins, during keratinocyte cornification. RIPK4 was also shown to upregulate the expression of TGM2 independently of IRF6. Collectively, our findings position RIPK4 upstream of a hierarchal IRF6-GRHL3-ELF3 transcription factor pathway in keratinocytes, as well as provide insight into a potential role for RIPK4 in the regulation of keratinocyte cornification.