Utility of myxedema score as a predictor of mortality in myxedema coma.

OBJECTIVE: Myxedema crisis (MC) is a rare condition. There is a dearth of data regarding the predictors of mortality in MC. Predictive scores for mortality specific to the clinical and biochemical profile of MC are still lacking. DESIGN AND METHODS: All consecutive patients presenting with MC from September 2006 to December 2020 comprised the new cohort. Patients managed between January 1999 and August 2006 comprised the old cohort. Both cohorts were compared for the determination of secular trends. Combined analysis of both the cohorts was done for clinico-demographic profile and predictors of mortality. Myxedema score (MS) and qSOFA (Quick Sequential Organ Failure Assessment) score were evaluated in all the patients. RESULTS: A total of forty-one patients (new cohort; n = 18 and old cohort; n = 23) were enrolled into the study. There was a female predominance (80.5%). Nearly half (51.2%) of the patients were newly diagnosed with hypothyroidism on admission. Overall mortality was 60.9%. On comparative analysis among survivors and non-survivors, female gender (OR 20.4, p value 0.018), need for mechanical ventilation (OR16.4, p value 0.009), in-hospital hypotension (OR 9.1, p value 0.020), and high qSOFA score (OR 7.1, p value 0.023) predicted mortality. MS of > 90 had significantly higher mortality (OR-11.8, p value - 0.026) while MS of > 110 had 100% mortality. There was no change in secular trends over last 20 years. There was no difference in outcome of patients receiving oral or IV levothyroxine. CONCLUSION: Myxedema crisis is associated with high mortality despite improvement in health care services. The current study is first to elucidate the role of the MS in predicting mortality in patients with MC.

Results of ala carte Posteromedial Soft Tissue Release in Idiopathic Clubfoot.

INTRODUCTION: The aim of this study is to assess the outcomes of ala carte posteromedial release in children over two years of age who were not responding to the Ponseti method of treatment of idiopathic clubfoot. MATERIAL AND METHODS: A retrospective observational study from September 2013 to August 2015 was conducted at a tertiary level medical teaching institution. The clubfeet were classified according to the Harold and Walker classification. Radiographic parameters assessed were the talocalcaneal angle (AP, lateral), talus-first metatarsal angle (AP, lateral) and calcaneal-fifth metatarsal angle. The scar and the functional score, according to Laaveg and Ponseti, were evaluated as outcome measures at the final follow-up. RESULTS: Twenty-four children with a mean age of 43.7 ± 24.7 months were enrolled in the study. There was a total of 36 clubfeet: 21 (65.6%) with a poor functional outcome; 12 (37.4%) with excellent to good scar in both horizontal and vertical components. There was a statistical significance between the pre-operative and post-operative radiological parameters (p<0.05). None of the patients presented with any limitation of activities of daily living despite the poor functional outcome in many of the children. There was no significant association between the qualities of scar (horizontal, vertical) and the functional outcome with age at presentation, pre-operative Harold and Walker classification and pre-operative radiographic angles. CONCLUSION: Surgical intervention in terms of ala carte posteromedial soft tissue release could not produce a good outcome over four years in CTEV. The threshold for surgery in CTEV should be high, given the poor results.

Unconventional Transverse Transport above and below the Magnetic Transition Temperature in Weyl Semimetal EuCd_{2}As_{2}.

As exemplified by the growing interest in the quantum anomalous Hall effect, the research on topology as an organizing principle of quantum matter is greatly enriched from the interplay with magnetism. In this vein, we present a combined electrical and thermoelectrical transport study on the magnetic Weyl semimetal EuCd_{2}As_{2}. Unconventional contribution to the anomalous Hall and anomalous Nernst effects were observed both above and below the magnetic transition temperature of EuCd_{2}As_{2}, indicating the existence of significant Berry curvature. EuCd_{2}As_{2} represents a rare case in which this unconventional transverse transport emerges both above and below the magnetic transition temperature in the same material. The transport properties evolve with temperature and field in the antiferromagnetic phase in a different manner than in the paramagnetic phase, suggesting different mechanisms to their origin. Our results indicate EuCd_{2}As_{2} is a fertile playground for investigating the interplay between magnetism and topology, and potentially a plethora of topologically nontrivial phases rooted in this interplay.

Results of ala carte Posteromedial Soft Tissue Release in Idiopathic Clubfoot

@#Introduction: The aim of this study is to assess the outcomes of ala carte posteromedial release in children over two years of age who were not responding to the Ponseti method of treatment of idiopathic clubfoot. Materials and Methods: A retrospective observational study from September 2013 to August 2015 was conducted at a tertiary level medical teaching institution. The clubfeet were classified according to the Harold and Walker classification. Radiographic parameters assessed were the talocalcaneal angle (AP, lateral), talus-first metatarsal angle (AP, lateral) and calcaneal-fifth metatarsal angle. The scar and the functional score, according to Laaveg and Ponseti, were evaluated as outcome measures at the final follow-up. Results: Twenty-four children with a mean age of 43.7 ± 24.7 months were enrolled in the study. There was a total of 36 clubfeet: 21 (65.6%) with a poor functional outcome; 12 (37.4%) with excellent to good scar in both horizontal and vertical components. There was a statistical significance between the pre-operative and post-operative radiological parameters (p<0.05). None of the patients presented with any limitation of activities of daily living despite the poor functional outcome in many of the children. There was no significant association between the qualities of scar (horizontal, vertical) and the functional outcome with age at presentation, pre-operative Harold and Walker classification and pre-operative radiographic angles. Conclusion: Surgical intervention in terms of ala carte posteromedial soft tissue release could not produce a good outcome over four years in CTEV. The threshold for surgery in CTEV should be high, given the poor results.

Assessment of natural regeneration of mangrove with reference to edaphic factors and water in Southern Gulf of Kachchh, Gujarat, India.

The study was carried out to determine the natural regeneration of four species of mangroves along with estimation of physico-chemical characteristics of sediment and water from seven sites of mangroves in the southern Gulf of Kachchh. Spatial variation of different parameters of water and sediment investigated were: water-pH (7.87-8.04); Salinity (37.07-39.42 ppt); Nitrate (1.21-2.71 ppm); Nitrite (0.03-0.08 ppm); Phosphate (0.39-0.95 ppm) and sediment-pH (7.39-7.61); Bulk density (0.36-0.54 g/cc); Particle density (1.19-1.68 g/cc); Organic carbon (0.77-1.05%); and Organic matter (1.06-1.71%). The density (recruit/sq. m) of natural recruitment of four mangrove species was in order of Avicennia marina > Ceriops tagal > Aegiceras corniculatum > Rhizophora mucronata. Cluster analysis grouped seven sites in three major clusters i.e. Group A (Poshitra & Khijadiya - 91% similarity); Group B (Dedeka-Mundeka, Kalubhar & Pirotan- 94% similarity) and Group C (Sikka & Jodiya- 93% similarity) whereas Non-metric multidimensional scaling showed formation of two groups (Coastal and Islands) depending on the environmental conditions and mangrove natural regeneration. Principal component analysis showed the number of parameters such as salinity, texture and organic carbon which affects the natural regeneration of mangrove species in the study area.

Unmasking and aggravation of polycythemia vera by canagliflozin.

BACKGROUND: Sodium-glucose co-transporter-2 inhibitors are novel antidiabetes drugs that act via inhibition of renal glucose reabsorption. This action causes osmotic diuresis, reduces intravascular volume and is associated with various adverse effects. In the present paper, we describe the first report on the unmasking of underlying polycythemia vera by canagliflozin in a person with Type 2 diabetes mellitus, which was temporally related to the use of the drug. CASE REPORT: A 51-year-old obese man with Type 2 diabetes was prescribed canagliflozin 100 mg for control of his glycaemia. He presented 6 months later with asymptomatic elevation of his haemogram measurements (haemoglobin: 16.9 g/dl; haematocrit: 55%; red cell number: 8.1 million/mm3 ; total leukocytes: 23010/mm3 ; platelet count: 9.7 *106 /mm3 ). He had no history of smoking, exposure to high altitude or other drugs. Subsequent investigations revealed myeloproliferative neoplasm (polycythemia vera) on trephine biopsy of bone marrow, normal erythropoietin level and JAK2V617F positivity. Because of the possibility that the underlying condition had been unmasked by canagliflozin, the latter was stopped. This led to a remarkable improvement in the man's haematological profile, with no other significant intervention. The man subsequently restarted the drug of his own accord, causing his haematological profile to worsen again and thereby posing a challenge in monitoring of both polycythemia vera as well as diabetes mellitus. CONCLUSION: This report brings to light unmasking of a new adverse effect of sodium-glucose co-transporter-2 inhibitors in clinical practice caused by volume loss, apart from hypotension and falls.

Direct observation of orbital hybridisation in a cuprate superconductor.

The minimal ingredients to explain the essential physics of layered copper-oxide (cuprates) materials remains heavily debated. Effective low-energy single-band models of the copper-oxygen orbitals are widely used because there exists no strong experimental evidence supporting multi-band structures. Here, we report angle-resolved photoelectron spectroscopy experiments on La-based cuprates that provide direct observation of a two-band structure. This electronic structure, qualitatively consistent with density functional theory, is parametrised by a two-orbital ([Formula: see text] and [Formula: see text]) tight-binding model. We quantify the orbital hybridisation which provides an explanation for the Fermi surface topology and the proximity of the van-Hove singularity to the Fermi level. Our analysis leads to a unification of electronic hopping parameters for single-layer cuprates and we conclude that hybridisation, restraining d-wave pairing, is an important optimisation element for superconductivity.

Membrane-bound ß-catenin degradation is enhanced by ETS2-mediated Siah1 induction in Helicobacter pylori-infected gastric cancer cells.

ß-catenin has two different cellular functions: intercellular adhesion and transcriptional activity. The E3 ubiquitin ligase Siah1 causes ubiquitin-mediated degradation of the cytosolic ß-catenin and therefore, impairs nuclear translocation and oncogenic function of ß-catenin. However, the effect of Siah1 on the cell membrane bound ß-catenin has not been studied. In this study, we identified that the carcinogenic bacterium H. pylori increased ETS2 transcription factor-mediated Siah1 protein expression in gastric cancer cells (GCCs) MKN45, AGS and Kato III. Siah1 protein level was also noticeably higher in gastric adenocarcinoma biopsy samples as compared to non-cancerous gastric epithelia. Siah1 knockdown significantly decreased invasiveness and migration of H. pylori-infected GCCs. Although, Siah1 could not increase degradation of the cytosolic ß-catenin and its nuclear translocation, it enhanced degradation of the membrane-bound ß-catenin in the infected GCCs. This loss of membrane-bound pool of ß-catenin was not associated with the proteasomal degradation of E-cadherin. Thus, this work delineated the role of Siah1 in increasing invasiveness of H. pylori-infected GCCs.

Proteolytic inactivation of nuclear alarmin high-mobility group box 1 by complement protease C1s during apoptosis.

Effective clearance of apoptotic cells by phagocytes prevents the release of intracellular alarmins and manifestation of autoimmunity. This prompt efferocytosis is complemented by intracellular proteolytic degradation that occurs within the apoptotic cells and in the efferosome of the phagocytes. Although the role of extracellular proteases in apoptotic cells clearance is unknown, the strong association of congenital C1s deficiency with Systemic Lupus Erythematosus highlights the protective nature that this extracellular protease has against autoimmunity. The archetypical role of serine protease C1s as the catalytic arm of C1 complex (C1qC1r2C1s2) involve in the propagation of the classical complement pathway could not provide the biological basis for this association. However, a recent observation of the ability of C1 complex to cleave a spectrum of intracellular cryptic targets exposed during apoptosis provides a valuable insight to the underlying protective mechanism. High-mobility group box 1 (HMGB1), an intracellular alarmin that is capable of inducing the formation of antinuclear autoantibodies and causes lupus-like conditions in mice, is identified as a novel potential target by bioinformatics analysis. This is verified experimentally with C1s, both in its purified and physiological form as C1 complex, cleaving HMGB1 into defined fragments of 19 and 12 kDa. This cleavage diminishes HMGB1 ability to enhance lipopolysaccharide mediated pro-inflammatory cytokines production from monocytes, macrophages and dendritic cells. Further mass spectrometric analysis of the C1 complex treated apoptotic cellular proteins demonstrated additional C1s substrates and revealed the complementary role of C1s in apoptotic cells clearance through the proteolytic cleavage of intracellular alarmins and autoantigens. C1 complex may have evolved as, besides the bacteriolytic arm of antibodies in which it activates the complement cascade, a tissue renewal mechanism that reduces the immunogenicity of apoptotic tissue debris and decreases the likelihood of autoimmunity.

Single Versus Multi-visit Endodontic Treatment of Teeth with Apical Periodontitis: An in vivo Study with 1-year Evaluation.

BACKGROUND: Apical periodontitis (AP) is one of the most prevalent diseases of the teeth. Treatment of AP is based on the removal of the cause, i.e., bacteria from the root canals. Achievement of adequate bacterial eradication in one appointment treatment remains a controversy. AIM: This prospective study was conducted with the objective to compare the periapical healing of teeth with AP treated in (a) single visit versus (b) two visits, either with or without Vitapex as an intracanal medicament. SUBJECTS AND METHODS: Patients were selected randomly from the Department of Conservative Dentistry and Endodontics. Forty-three patients (81 teeth) met the inclusion criteria, i.e., AP (both symptomatic and asymptomatic) visible radiographically size ≥2 mm × 2 mm, not suffering from any immune-compromising disease, age between 16 and 65 years and tooth not accessed previously. Patients were randomly divided into three groups, i.e., single-visit group (Group 1), multi-visit group without any intracanal medicament (Group 2), and multi-visit group with Vitapex as interim intracanal medicament (Group 3). Comparison was done radiographically using periapical index (PAI). The primary outcome measure was the change in periapical radiolucency after 1 year assessed by PAI scores. The Mann-Whitney U-test was used to evaluate differences between groups at baseline (immediate postoperative) and at the 12-month follow-up evaluation. Change in PAI score for each group from baseline to 12-month follow-up evaluation was tested with the Wilcoxon signed rank test. The secondary outcome measures, proportion of teeth in each group that could be considered improved (decreased PAI score) or healed (PAI <2), were assessed with the Chi-square test. RESULTS: No statistically significant difference in periapical healing was found between three groups. CONCLUSION: After 1-year evaluation, no difference in periapical healing was found between single-visit treatment and multi-visit treatment groups with the given sample size.

Enhanced efficacy of sequential administration of Albendazole for the clearance of Wuchereria bancrofti infection: Double blind RCT.

Till today, there is no effective treatment protocol for the complete clearance of Wuchereria bancrofti (W.b) infection that causes secondary lymphoedema. In a double blind randomized control trial (RCT), 146 asymptomatic W. b infected individuals were randomly assigned to one of the four regimens for 12 days, DEC 300 mg + Doxycycline 100 mg coadministration or DEC 300 mg + Albendazole 400 mg co-administration or DEC 300 mg + Albendazole 400 mg sequential administration or control regimen DEC 300 mg and were followed up at 13, 26 and 52 weeks post-treatment for the clearance of infection. At intake, there was no significant variation in mf counts (F(3,137)=0.044; P=0.988) and antigen levels (F(3,137)=1.433; P=0.236) between the regimens. Primary outcome analysis showed that DEC + Albendazole sequential administration has an enhanced efficacy over DEC + Albendazole co-administration (80.6 Vs 64.7%), and this regimen is significantly different when compared to DEC + doxycycline co-administration and control (P<0.05), in clearing microfilaria in 13 weeks. Secondary outcome analysis showed that, all the trial regimens were comparable to control regimen in clearing antigen (F(3, 109)=0.405; P=0.750). Therefore, DEC + Albendazole sequential administration appears to be a better option for rapid clearance of W. b microfilariae in 13 weeks time. (Clinical trials.gov identifier - NCT02005653).

Childhood-onset systemic lupus erythematosus in Singapore: clinical phenotypes, disease activity, damage, and autoantibody profiles.

Childhood-onset systemic lupus erythematosus (cSLE) is a multisystem autoimmune disease characterized by immune dysregulation affecting patients less than 18 years old. One-fifth of SLE cases are diagnosed during childhood. cSLE presents differently from adults and has a more severe and aggressive course. We describe the clinical and antibody profiles in our cSLE Singapore cohort. All cSLE patients who satisfied the 1997 American College of Rheumatology diagnostic criteria were captured in our lupus registry from January 2009 to January 2014. Data including demographic, cumulative clinical, serologic data, and damage indices were collected. Adjusted mean SLEDAI-2K (AMS) was used to summarize disease activity over multiple visits. Cluster analysis using non-hierarchical K-means procedure was performed on eight selected antibodies. The 64 patients (female:male ratio 5:1; Chinese 45.3%, Malay 28.1%, Indian 9.4%, and other races 17.2%) had a mean onset age of 11.5 years (range 2.1-16.7) and mean age at diagnosis was 11.9 years (range 2.6-18.0). Our study demonstrated differences in clinical manifestations for which hematologic involvement was the most common manifestation with less renal disease and uncommon neurologic manifestation as compared to other cSLE cohorts reported in our region. Antibody clusters were identified in our cohort but their clinical association/discrimination and outcome prediction required further validation study. Outcomes of our cohort in regard to disease activity after therapy and organ damages were comparable if not better to other cSLE cohorts elsewhere. Steroid-related damage, including symptomatic multifocal avascular necrosis and cataract, were not uncommon locally. Infection remains the major cause of death for the continent. Nevertheless, the five year survival rate of our cohort (98.4%) was high.

Evaluation of various feedstuffs of ruminants in terms of chemical composition and metabolisable energy content.

AIM: The aim was to determine the chemical composition and metabolisable energy (ME) content of feedstuffs used in ruminant animals using in vitro method. MATERIALS AND METHODS: A total of 18 feedstuffs used for ruminant feeding including cultivated non-leguminous fodders like maize, sorghum, pearl millet, and oat; leguminous fodders like cowpea and berseem; agro-industrial by-products such as wheat bran, deoiled rice bran, rice polish, wheat straw, and concentrates such as mustard oil cake, groundnut cake, soybean meal, cotton seed cake, grains like maize, oat, wheat, and barley were taken for this study. Chemical compositions and cell wall constituents of test feeds were determined in triplicate. The crude protein (CP) content was calculated as nitrogen (N) × 6.25. True dry matter digestibility (TDMD), true organic matter digestibility (TOMD), ME, and partitioning factor (PF) values were determined by in vitro gas production technique (IVGPT). RESULTS: The CP content of non-leguminous fodders varied from 7.29% (sorghum) to 9.51% (maize), but leguminous fodders had less variation in CP. Oilseed cakes/meals had high CP and ether extract (EE) content than other feedstuffs except rice polish, which had 12.80% EE. Wheat straw contained highest fiber fractions than the other ingredients. ME content was highest in grains (wheat-12.02 MJ/kg) and lowest in wheat straw (4.65 MJ/kg) and other roughages. TDMD of grains and oilseed cakes/meals were higher than the fodders and agro-industrial by-products. The same trend was observed for TOMD. CONCLUSIONS: It was concluded that the energy feeds showed a great variation in chemical composition and ME content. The results of this study demonstrated that the kinetics of gas production of energy feed sources differed among themselves. Evaluation of various feedstuffs is helpful in balanced ration formulation for field animals and under farm conditions for better utilization of these commonly available feed resources.

Comparison of outcomes of locoregionally advanced oropharyngeal and non-oropharyngeal squamous cell carcinoma over two decades.

BACKGROUND: Human papillomavirus (HPV) has emerged as a causative agent and positive prognostic factor for oropharyngeal (OP) head and neck squamous cell cancer (HNSCC). This prompts inquiry into whether therapy improvements or increasing incidence of HPV drives the apparent improvements in HNSCC outcomes observed in non-randomized clinical trials. PATIENTS AND METHODS: We reviewed all locoregionally advanced HNSCC patients treated with chemotherapy and radiation in prospective institutional trials at a single institution. Patients were divided into three groups (1, 2, 3) according to treatment time period (1993-1998, 1999-2003, 2004-2010, respectively). We reasoned that if a favorable trend was observed over time in OP but not non-OP patients, HPV status may be confounding treatment effects, whereas this would be unlikely if both subgroups improved over time. RESULTS: Four hundred and twenty-two patients were identified with OP (55.7%) and non-OP (44.3%) HNSCC. Five-year OP overall survival (OS) improved from 42.3% (group 1) to 72.5% (group 2), and 78.4% (group 3), adjusted P = 0.0084. Non-OP 5-year OS was 51.0% (group 1), 58.8% (group 2), and 66.3% (group 3), adjusted P = 0.51. Five-year recurrence-free survival (RFS) improved for OP groups from 42.3% to 68.4% to 75.8% (adjusted P = 0.017). Non-OP 5-year RFS was 42.9%, 53.6%, and 61.7% for sequential groups (adjusted P = 0.30). Five-year OP distant failure-free survival (DFFS) improved from 42.3% to 71.1% to 77.8% (adjusted P = 0.011). Five-year non-OP DFFS was 46.9%, 57.1%, and 66.0% for sequential groups (adjusted P = 0.38). CONCLUSIONS: Over the past two decades, OP HNSCC outcomes improved significantly, while non-OP outcomes only trended toward improvement. Although our patients are not stratified by HPV status, improving OP outcomes are likely at least partly due to the increasing HPV incidence. These data further justify trial stratification by HPV status, investigations of novel approaches for carcinogen-related HNSCC, and current de-intensification for HPV-related HNSCC.

Enhanced efficacy of sequential administration of Albendazole for the clearance of Wuchereria bancrofti infection: Double blind RCT

Till today, there is no effective treatment protocol for the complete clearance of Wuchereria bancrofti (W.b) infection that causes secondary lymphoedema. In a double blind randomized control trial (RCT), 146 asymptomatic W. b infected individuals were randomly assigned to one of the four regimens for 12 days, DEC 300 mg + Doxycycline 100 mg coadministration or DEC 300 mg + Albendazole 400 mg co-administration or DEC 300 mg + Albendazole 400 mg sequential administration or control regimen DEC 300 mg and were followed up at 13, 26 and 52 weeks post-treatment for the clearance of infection. At intake, there was no significant variation in mf counts (F(3,137)=0.044; P=0.988) and antigen levels (F(3,137)=1.433; P=0.236) between the regimens. Primary outcome analysis showed that DEC + Albendazole sequential administration has an enhanced efficacy over DEC + Albendazole co-administration (80.6 Vs 64.7%), and this regimen is significantly different when compared to DEC + doxycycline co-administration and control (P<0.05), in clearing microfilaria in 13 weeks. Secondary outcome analysis showed that, all the trial regimens were comparable to control regimen in clearing antigen (F(3, 109)=0.405; P=0.750). Therefore, DEC + Albendazole sequential administration appears to be a better option for rapid clearance of W. b microfilariae in 13 weeks time. (Clinical trials.gov identifier – NCT02005653)

Assessment of salivary total antioxidant levels and oral health status in children with cerebral palsy.

UNLABELLED: Oxidative stress plays a pivotal role in the pathogenesis of neurological disorders. Saliva may constitute a first line of defence, against free radical-modified oxidative stress. The objective of the present study was to evaluate Total Antioxidant Capacity (TAC), levels of Nitric Oxide (NO), and Sialic Acid (SA) in saliva of cerebral palsied children. STUDY DESIGN: Thirty four non-institutionalized children in the age group of 7-12 years having cerebral palsy formed the study group. The control group consisted of thirty three normal, healthy children. The W.H.O. criteria was used for diagnosis and recording of dental caries. Oral hygiene status was assessed using the Simplified Oral Hygiene Index OHI-S. Estimation of Total Antioxidant Capacity, levels of Nitric Oxide and Sialic Acid in saliva was done. Data obtained was subjected to statistical analysis. RESULTS: Children with CP had higher deft scores than that of normal children. Oral hygiene of children with CP was significantly poorer than that of normal children. Total Antioxidant Capacity of saliva was significantly higher in normal children than cerebral palsied children. Levels of Sialic Acid in saliva were significantly higher in cerebral palsy children. CONCLUSIONS: In children with CP, TAC of saliva showed an inverse relation with dental caries.

Effect of Diethylcarbamazine (DEC) on prostaglandin levels in Wuchereria bancrofti infected microfilaraemics.

Diethylcarbamazine (DEC) interferes with arachidonic acid metabolism for the clearance of microfilariae in Wuchereria bancrofti infected individuals. In this study, we have quantified the plasma concentrations of prostaglandin E2 (PGE2) and 6-keto-PGF1α, the end products of arachidonic acid metabolic pathway in microfilaraemics (DEC treated and untreated), and normal healthy individuals at pre- and 3,9,12,36, and 72 h of post-DEC treatment. We have also determined the microfilariae counts at pre and post day 2 (36 h) and day 3 (72 h) of DEC treatment by membrane filtration technique. Significant reduction in PGE2 and 6-keto-PGF1α concentrations was found at 12 h of DEC treatment. Rapid reduction in microfilarial counts was observed at 36 h of post-DEC treatment. Higher levels of prostaglandins were found at pre-treatment hours in microfilaraemics compared to normal healthy individuals (P < 0.05). Our findings indicate that DEC inhibits prostaglandins for the clearance of microfilariae, and increased levels of prostaglandins in microfilaraemics may be contributed by the parasite or host upon stimulation.

TGF-ß conditions intestinal T cells to express increased levels of miR-155, associated with down-regulation of IL-2 and itk mRNA.

Transforming growth factor (TGF)-ß, is an immunosuppressive cytokine that inhibits T-cell activation. We hypothesized that TGF-ß mediates its immunoinhibitory effects by modulation of micro RNA (miRNA)-155 (miR-155). Interleukin (IL)-2 and interferon-γ are down-regulated by TGF-ß in activated CD4 peripheral blood T cells and lamina propria T cells (LPT), but miR-155 is upregulated ninefold specifically in LPT. Consequently, this study focuses on the role of TGF-ß-enhanced miR-155 on LPT immune responses. TGF-ß induces miR-155 in both freshly isolated and LPT lymphoblasts, whereas other inducible miRNAs are not regulated by TGF-ß. Using MAMI bioinformatics database, we determined that inducible T-cell kinase (itk) is a functional target of miR-155 that exhibits an inverse mRNA response to that of miR-155. To determine experimentally that miR-155 regulates itk, transfection experiments were performed that demonstrated miR-155 overexpression decreased itk and IL-2 mRNA, whereas antagonism of miR-155 restored both mRNAs in activated cells. These findings describe a TGF-ß-dependent function for miR-155 in modulating cytokine and T-cell immune responses in the gut.