Multidisciplinary Consensus for Rationalizing the Use of Acid Suppressants in Children and Adults: CONFOR.

The use of acid suppression therapy (AST) is a common approach for managing a wide spectrum of acid peptic disorders. Histamine type 2-receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) are the most widely prescribed AST in routine clinical practice. However, an exponential surge in the prescriptions of PPIs, such as Omeprazole, Esomeprazole, Pantoprazole, Lansoprazole in recent years and their associated adverse effects have raised concern about their inappropriate and overuse, both in children and adults. To address these issues, a three-step modified Delphi polling process was employed to establish best practice consensus statements for rationalizing the use of acid suppressants. A multidisciplinary expert panel of 13 health professionals across medical specialties, including gastroenterologists, hepatologists, pediatric gastroenterologists, pediatricians, otolaryngologists, cardiologists, nephrologists, gynecologist and orthopedists actively contributed to this collaborative process of consensus development. The expert panel proposed 21 consensus statements providing best practice points on the general use and safety of acid suppressants based on a comprehensive review of scientific literature and clinical expertise. The panel also collaboratively developed a PPI deprescribing algorithm. Altogether, this consensus paper offers evidence-based recommendations and guidance for the rational use of acid suppressants with a blueprint for deprescribing PPIs. This consensus paper contributes to aiding primary care practitioners in improving patient outcomes and minimizing healthcare costs. Additionally, it enhances patient safety and curtail inappropriate usage. How to cite this article: Prabhoo RY, Pai UA, Wadhwa A, et al. Multidisciplinary Consensus for Rationalizing the Use of Acid Suppressants in Children and Adults: CONFOR. Euroasian J Hepato-Gastroenterol 2024;14(1):99-119.

Glaucarubinone from Simarouba glauca DC. as a potential biocontrol agent for mosquito vector management.

The study explored Simarouba glauca DC. for mosquito larvicidal potential by performing bioactivity-guided chemical investigation of its root extract resulting in isolation of the known bioactive metabolite glaucarubinone (1). Mosquito larvicidal activity of glaucarubinone (1) against the three vector species viz. Anopheles stephensi, Aedes aegypti, and Culex quinquefasciatus was determined using a modified WHO 2005 protocol. It was observed that Culex quinquefasciatus larvae were the most susceptible species with LC50 13.88 ppm and LC90 70.01 ppm followed by Aedes aegypti and Anopheles stephensi at 24 h of exposure. The mode of action as observed microscopically is the lysis of midgut and thorax cells of the third instar larvae. The crystal structure of the glaucarubinone (1) is reported for the first time using X-ray crystallography. This phytochemical product has the potential to act as a green alternative to existing chemical-based insecticides for integrated vector management.

Summertime oxidative potential of atmospheric PM2.5 over New Delhi: Effect of aerosol ageing.

Exposure to elevated particulate matter (PM) concentrations in ambient air has become a major health concern over urban areas worldwide. Reactive oxygen species (ROS) generation due to ambient PM (termed as their oxidative potential, OP) is shown to play a major role in PM-induced health effects. In the present study, the OP of the ambient PM2.5 samples, collected during summer 2019 from New Delhi, were measured using the dithiothreitol (DTT) assay. Average volume-normalized OP (OPV) was 2.9 ± 1.1 nmol DTT min-1 m-3, and mass-normalized OP (OPm) was 61 ± 29 pmol DTT min-1 µg-1. The regression statistics of OPv vs chemical species show the maximum slope of OPV with the elemental carbon (EC, r2 = 0.72) followed by water-soluble organic carbon (WSOC, r2 = 0.72), and organic carbon (OC, r2 = 0.64). A strong positive correlation between OPm and secondary inorganic aerosols (SIA, such as NH4+ and NO3- mass fractions) was also observed, indicating that the sources emitting NO2 and NH3, precursors of NO3- and NH4+, also emit DTT-active species. Interestingly, the slope value of OPv vs OC for aged aerosols (OM/OC > 1.7, f44 > 0.12 and f43 < 0.04) was 1.7 times higher than relatively fresh organic aerosols (OA, OM/OC < 1.7, f44 < 0.12, f43 > 0.04). An increase in OPv and OPoc with f44 indicates the formation of more DTT active species with the ageing of OA. A linear increase in OPoc with increasing Nitrogen/Carbon (N/C) ratio suggests that nitrogenous OA have higher OP.

Dual carbon isotope-based brown carbon aerosol characteristics at a high-altitude site in the northeastern Himalayas: Role of biomass burning.

PM2.5 samples (n = 34) were collected from January to April 2017 over Shillong (25.7°N, 91.9°E; 1064 m amsl), a high-altitude site situated in the northeastern Himalaya. The main aim was to understand the sources, characteristics, and optical properties of local vs long-range transported carbonaceous aerosols (CA) using chemical species and dual carbon isotopes (13C and 14C). Percentage biomass burning (BB)/biogenic fraction (fbio, calculated from 14C) varied from 67 to 92 % (78 ± 7) and correlated well with primary BB tracers like f60, and K+, suggesting BB as a considerable source. Rain events are shown to reduce the fbio fraction, indicating majority of BB-derived CA are transported. Further, δ13C (-26.6 ± 0.4) variability was very low over Shillong, suggesting it's limitations in source apportionment over the study region, if used alone. Average ratio of absorption coefficient of methanol-soluble BrC (BrCMS) to water-soluble BrC (BrCWS) at 365 nm was 1.8, indicating a significant part of BrC was water-insoluble. A good positive correlation between fbio and mass absorption efficiency of BrCWS and BrCMS at 365 nm with the higher slope for BrCMS suggests BB derived water-insoluble BrC was more absorbing. Relative radiative forcing (RRF, 300 to 2500 nm) of BrCWS and BrCMS with respect to EC were 11 ± 5 % and 23 ± 16 %, respectively. Further, the RRF of BrCMS was up to 60 %, and that of BrCWS was up to 22 % with respect to EC for the samples with fbio ≥ 0.85 (i.e., dominated by BB), reflecting the importance of BB in BrC RRF estimation.

Intensified seed spices-based cropping systems for higher productivity, resource-use efficiency, soil fertility and profitability in arid and semi-arid regions of India.

Coriander, fenugreek, nigella etc. are collectively known as seed spices. They are "High value and low volume crops" and considered cash crops for the growers of arid and semi-arid regions of India. Coriander, fenugreek and nigella are grown during the rabi season and take hardly 130-140 days to attain full maturity. In this context, farmers are not able to develop income from available arable land round the year, even though they have sufficient resources as well as manpower. Therefore, coriander, fenugreek and nigella-based cropping systems, four of each (total 12) were evaluated during 3 consecutive years (2019-20 to 2021-22) for their productivity, resource-use efficiency, economics and soil fertility. The results showed that among the seed spices-based cropping systems, maximum system productivity (5193 kg ha-1), production efficiency (18.81 kg ha-1 day-1), water-use efficiency (2.31 kg ha-1 mm-1), economic efficiency (11.85 US $ ha-1 day-1), net return (3270 US $ ha-1), benefit:cost ratio (3.27) and available N (165.6 kg ha-1) were observed under nigella-green coriander-mungbean cropping system. Hence, seed spices growers are recommended to adopt nigella-green coriander-mungbean cropping system in order to realize better productivity, resource-use efficiency, soil fertility and profitability.

Intriguing physicochemical properties and impact of co-dopants on N-doped graphene oxide based ZnS nanowires for photocatalytic application.

Superparamagnetic N-doped graphene oxide (GO)- with ZnS nanowires was synthesized by a one-step hydrothermal method by doping dilute amounts of Ga, Cr, In, and Al ions for water treatment and biomedical applications. In these experiments, to enhance their properties, 2% of Ga3+, In3+, and or Al3+ were codoped along with 2% Cr ions in these ZnS nanowires. The nanocomposite with the composition, In0.02Cr0.02Zn0.96S, has better photocatalytic efficiency than other co-doped nanocomposites. The In (metalloids) and Cr (transition metal ion) are the best combinations to increase the magnetic properties which are beneficial for photocatalytic activity. Synthesized nanocomposite materials were characterized by several techniques such as X-ray diffraction, Field emission-scanning electron microscope (FESEM) with EDAX, vibrating sample magnetometer (VSM), UV-Vis, X-ray photoelectron spectroscopy (XPS), and fluorescence spectroscopy. The correlation of intriguing magnetic properties with their photocatalytic properties is also discussed. XPS was employed for the detection of surface defects, phase transformation, and the nature of chemical components present in the nanocomposites. The Frankel and substitutional defects have a direct impact on photocatalytic activity that was determined from the fluorescence (FL) spectroscopy. FL and XPS reveal that the Cr and In codoped composite has a higher percentage of defects hence its photocatalytic efficiency reaches 94.21%.

A review on the pollution assessment of hazardous materials and the resultant biorefinery products in Palm oil mill effluent.

The voluminous nature of palm oil mill effluent (POME) is directly associated with environmental hazards and could be turned into biorefinery products. The POME, rich in BOD, COD, and oil and grease, with few hazardous materials such as siloxanes, fatty acid methyl ester, and phenolic compounds that may significantly increase the risk of violating the effluent quality standards. Recently, the application of chemical and biological risk assessment that can use electrochemical sensors and microalgae-like species has gained paramount attention towards its remediation. This review describes the existing risk assessment for POME and recommends a novel assessment approach using fish species including invasive ones as suitable for identifying the toxicants. Various physico-chemical and biological treatments such as adsorption, coagulation-flocculation, photo-oxidation, solar-assisted extraction, anaerobic digestion, integrated anaerobic-aerobic, and microalgae cultivation has been investigated. This paper offers an overview of anaerobic technologies, with particular emphasis on advanced bioreactors and their prospects for industrial-level applications. To illustrate, palmitic acid and oleic acid, the precursors of fatty acid methyl ester found in POME pave the way to produce biodiesel with 91.45%. Although there are some challenges in attaining production at an economic scale, this review offers some opportunities that could help in overcoming these challenges.

Production of polyclonal antibodies against leek yellow stripe virus (LYSV) coat protein expressed in Escherichia coli and its application in serological diagnostics.

Leek yellow stripe virus (LYSV) is one of the most important potyviruses, associated with garlic throughout the world, including India. LYSV causes stunting and yellow streaks in garlic and leek leaves and with other coinfecting viruses leading to severe symptom expression and yield reduction. In this study, we have made the first reported attempt to produce specific polyclonal antibodies to LYSV using expressed recombinant coat protein (CP), which would be useful for screening and routine indexing of the garlic germplasm. The CP gene was cloned, sequenced, and further subcloned in pET-28a(+) expression vector, which yielded ∼35 kDa fusion protein. The fusion protein was obtained in insoluble fraction after purification and its identity was confirmed by SDS-PAGE and western blotting. The purified protein was used as immunogen for production of polyclonal antisera in New Zealand white rabbit. Antisera raised, was able to recognize the corresponding recombinant proteins in western blotting, immunosorbent electron microscopy and dot immunobinding assay (DIBA). Developed antisera to LYSV (titer 1:2000) was used for screening of 21 garlic accessions in antigen coated plate enzyme-linked immunosorbent assay (ACP-ELISA) and 16 accessions were found positive for LYSV, indicating its widespread presence within the collection tested. To the best of our knowledge, this is the first report of a polyclonal antiserum against the in-vitro expressed CP of LYSV and its successful application in diagnosis of LYSV in garlic accessions in India.

Characterization of paddy-residue burning derived carbonaceous aerosols using dual carbon isotopes.

A large scale paddy-residue burning (PRB) happens every year in the northwest Indo-Gangetic Plain (IGP) during the post-monsoon season, and winds transport pollutants from the source region up to the northern Indian Ocean affecting air quality of the IGP and marine region. In this study, day-night pairs of fine aerosol samples (n = 69) were collected during October-November over Patiala (30.2°N, 76.3°E, 250 m amsl), a site located in the source region of PRB. Carbonaceous aerosols (CA) were characterised using chemical species and dual carbon isotopes (13C and 14C) to estimate bio vs non-bio contributions and understand their characteristics. Percentage of bio fraction (fbio, estimated using 14C) in CA varied from 74 % to 87 % (avg: 80 ± 3) during days and 71 % to 96 % (avg: 85 ± 7 %) during nights. Further, the fbio was found to be better correlated with aerosol mass spectrometer derived f60 compare to levoglucosan (LG) or nssK+, suggesting f60 a useful proxy for PRB. The δ13C varied from -27.7 ‰ to -26.0 ‰ (avg: -27.0 ± 0.4 ‰) and - 28.7 ‰ to -26.4 ‰ (avg: -27.5 ± 0.7 ‰) during day and night, respectively. Measured δ13C of the samples was found to be more enriched than expected by 0.3 to 2.0 ‰, indicating the presence of aged CA also in Patiala even during PRB period. From fbio versus δ13C correlation, and from Miller-Trans plot, δ13C of PRB is found to be -28.9 ± 1.1 ‰, which also infers that Miller-Trans plot can be used to understand source isotopic signature in the absence of radiocarbon measurements in aerosols. Further, the characteristics ratios of organic carbon (OC) to elemental carbon (EC) (11.9 ± 4.1), LG to potassium (K+) (0.84 ± 0.15), OC/LG (19.7 ± 2.0) and K+/EC (0.75 ± 0.27) were calculated by considering samples with fbio higher than 0.90, which can be used for source apportionment studies. Such studies are crucial in assessing the effects of PRB on regional air quality and climate.

Challenges and opportunities in productivity and sustainability of rice cultivation system: a critical review in Indian perspective.

Abstract: Rice-wheat cropping system, intensively followed in Indo-Gangetic plains (IGP), played a prominent role in fulfilling the food grains demand of the increasing population of South Asia. In northern Indian plains, some practices such as intensive rice cultivation with traditional method for long-term have been associated with severe deterioration of natural resources, declining factor productivity, multiple nutrients deficiencies, depleting groundwater, labour scarcity and higher cost of cultivation, putting the agricultural sustainability in question. Varietal development, soil and water management, and adoption of resource conservation technologies in rice cultivation are the key interventions areas to address these challenges. The cultivation of lesser water requiring crops, replacing rice in light-textured soil and rainfed condition, should be encouraged through policy interventions. Direct seeding of short duration, high-yielding and stress tolerant rice varieties with water conservation technologies can be a successful approach to improve the input use efficiency in rice cultivation under medium-heavy-textured soils. Moreover, integrated approach of suitable cultivars for conservation agriculture, mechanized transplanting on zero-tilled/unpuddled field and need-based application of water, fertilizer and chemicals might be a successful approach for sustainable rice production system in the current scenario. In this review study, various challenges in productivity and sustainability of rice cultivation system and possible alternatives and solutions to overcome such challenges are discussed in details.

Female gender is associated with increased late luminal narrowing within the stent graft after thoracic endovascular aortic repair.

BACKGROUND: Luminal narrowing, suspected secondary to thrombus, occurs within stent grafts at an unclear incidence after thoracic endovascular aortic repair (TEVAR). The significance of this phenomenon has not been determined, nor have the risk factors for development of intragraft luminal narrowing. Small graft diameter is hypothesized to be a risk factor for the development of ingraft stenosis. METHODS: A retrospective analysis was performed of a multicenter healthcare system including all patients who underwent TEVAR between July 2011 and July 2019 with at least 1 year of subsequently available surveillance contrast-enhanced computed tomography imaging. Standard demographic, preoperative, intraoperative, and postoperative variables were collected. Measurements were obtained via direct off-line images from computed tomography scans. Patent intragraft diameters were compared with baseline and interval change values were normalized to time to follow-up. The primary outcome measure was annual rate of intragraft luminal narrowing. RESULTS: There were 208 patients who met the inclusion criteria (94 women, 114 men) with a median follow-up of 822 days. The mean annual rate of percent intragraft diameter reduction was 10.5 ± 7.7% for women and 7.6 ± 5.6% for men (P = .0026). Multivariate analysis demonstrated female gender (P = .0283), preoperative diagnosis of hypertension (P = .0449), and need for coverage of the left subclavian artery (P = .0328) were all significant predictors of intragraft luminal narrowing. Small aortic diameters were not found to be associated independently with ingraft luminal narrowing nor was the concomitant use of antiplatelet or anticoagulation medications. Significant amounts of ingraft luminal narrowing, defined as a greater than 20% intragraft diameter decrease, were associated with an increased need for any reintervention, including for malperfusion, endoleak, and symptomatic aneurysm (P = .0249). Kaplan-Meier estimates demonstrated a significant gender-associated difference in high rates of intragraft luminal narrowing (P = .00189). CONCLUSIONS: In this analysis, female gender is shown to be a significant nonmodifiable risk factor for intragraft luminal narrowing after TEVAR. The development of this phenomenon is not benign; as such, these findings were associated with an increased need for reintervention. This finding may be attributable to differences in aortic compliance or gender-associated differences in coagulation pathways and merits further investigation. Surveillance after thoracic stent grafting must account for patient-specific variations in complication risk.

A Clinical Study Determining Pulp Vitality in Oropharyngeal Cancer Patients Undergoing Radiotherapy Using Diagnostic Tool-Pulse Oximetry.

Pulse oximetry is an equipment that evaluates pulp vitality for concrete endodontic diagnosis and treatment plan. One of the treatment methods of oropharyngeal cancer is radiotherapy. Radiotherapy has some harmful effects on dental pulp that affects pulp vitality. The objective of study was to assess pulp vitality before, at the end of radiotherapy and six months after radiotherapy (RT) in oropharyngeal cancer patients undergoing radiotherapy. 25 patients who were diagnosed with oropharyngeal cancer having asymptomatic intact crowns were selected for the study. Pulp vitality was checked before the commencement of radiotherapy (PV1), immediately after radiotherapy (PV 2) and six months post radiotherapy (PV 3). Pulp vitality of first posterior tooth was selected of each patient and was checked with pulse oximetry. Paired t-test was used as statistical analysis. Statistically significant difference was observed when PV 1 and PV 2, PV 1 and PV 3 and PV 2 and PV 3 were compared amongst each other. There was reduction noted in mean SpO2 value when groups PV 2 and PV1 were compared. This was statistically significant. Statistically significant increase in mean SpO2 value was observed six months post radiotherapy (PV 3). Thus, it can be concluded that statistically significant reduction in mean SpO2 level post radiotherapy recovers after six months.

Evidence-based traditional Siddha formulations for prophylaxis and management of respiratory symptoms in COVID-19 pandemic-a review.

The recent outbreak of COVID-19 is attributed to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This viral disease is rapidly spreading across the globe, including India. The mainstay in managing the disease is supportive care, nutrition, and preventing further progression in the absence of proven antiviral drugs. Currently two vaccines Covishield and Covaxin are administered in India. Long-term plans of developing most reliable mRNA-based vaccines are also underway for the future method of prophylaxis. The Siddha system of medicine's holistic approach emphasizes lifestyle modification, prophylactic interventions, and dietary management to boost the host immunity and treatment with herbal medicines and higher-order medicines as the case may be. In this review, a brief outline of the disease COVID-19, Coronavirus, evidence-based traditional Siddha interventions for respiratory ailments and immune boosters highlighting the relevant published research on individual herbs are dealt, which pave way for further research on drug repurposing for COVID-19. Historical evidence on the prevention and treatment of infections especially antivirals in Siddha classics is studied.

Siddha Varmam and Thokkanam therapy in the treatment of adhesive capsulitis-A case report.

A 60 year married female from Chennai presented with pain and restricted abduction, adduction, external rotation and flexion of right shoulder both in active and passive movements for 2 months. She was diagnosed to be affected by adhesive capsulitis which is equated to Kumbavatham, one of the vatha diseases mentioned in Siddha system of medicine. She was treated with Siddha Varmam therapy and thokkanam with Vathakesari thylam. After 15 days of hospital stay the patient was discharged and was followed for 6 months. There were no adverse reactions/events observed during the course of treatment. The combination therapy has provided the reduction in pain and restricted movements which was measured using goniometer and SPADI index.

Development and characterization of genic SSR-FDM for stem gall disease resistance in coriander (Coriandrum sativum L.) and its cross species transferability.

Coriander (Coriandrum sativum L.) is well known vegetable and spice crop grown globally for its leaves and seeds. Stem gall (Protomyces macrosporus L.) is a fungal disease affecting its quality and yield. However, no information is available on SSR markers linked to disease resistance in coriander. Hence, development of co-dominant genetic markers is prerequisite for disease investigations in coriander. In-house stem gall resistance and susceptible cultivars transcriptome data were utilized. Totally, 59,933 and 56,861 transcripts were examined, 9141 and 8346 Simple Sequence Repeats (SSR) were identified and the most abundant type was the tri, followed by di, tetra, penta and hexa nucleotide repeats. A total of ten selected SSR-Functional Domain Markers (FDM) were developed based on functional annotation terms associated with pathogen response and validated among ten coriander cultivars and their transferability was examined in five fennel (Foeniculum vulgare L.) cultivars. Nine primer pairs resulted from amplified bands. Marker ACorSGD-1 shown monomorphic bands among coriander genotypes except Acr-1 showed heterologouse and multiple bands in fennel cultivars. Markers ACorSGD-4, 5, 7 and 9 shown presence in resistant cultivars and absence of bands among susceptible cultivars of coriander and thus, considered to be the candidate markers for disease screening. Marker ACorSGD-6 shown monomorphic bands among coriander. Markers ACorSGD-1, 2, 3, and 5 shown transferability among fennel cultivars. A total of 136 alleles in coriander and fennel were produced. Using UPGMA clustering method a dendrogram was generated and cultivars were grouped into two separate clusters with coriander and fennel. Identified and developed SSR-FDM markers are useful for linkage mapping for disease resistant in coriander.

Stent Graft Oversizing is Associated with an Increased Risk of Long-Term Left Ventricular Wall Thickening in Young Patients Following Thoracic Endovascular Aortic Repair.

BACKGROUND: Left ventricular (LV) wall thickening occurs in patients following thoracic endovascular aortic repair (TEVAR). Clinical consequences of cardiovascular (CV) remodeling may be more significant younger patients with longer anticipated life spans. Risk factors for CV remodeling following TEVAR are unknown but may be related to graft size. METHODS: A retrospective analysis was performed of a multicenter healthcare system including patients aged ≤60 who underwent TEVAR between 2011 and 2019 with at least 1 year follow-up computed tomography angiography imaging available. Standard perioperative variables, native aortic diameter, and stent graft specifications were collected. Graft oversizing was calculated by dividing proximal graft diameter by proximal aortic diameter on preoperative imaging. Posterior LV wall thickness was measured at baseline and interval increases were normalized to time-to-follow-up. Primary outcome was annual rate of posterior LV wall thickening. RESULTS: One hundred one patients met inclusion criteria with a mean (SD) follow-up time of 1270 (693) days. Overall mean (SD) rate of LV wall thickness change was 0.534 (0.750) mm per year. Mean (SD) absolute LV wall thickness at most recent follow-up was 10.97 (2.85) mm for men, 9.69 (2.03) mm for women. Multivariate analysis demonstrated that higher rates of LV wall thickening were associated with narrower graft diameters (P = 0.0311). Greater absolute LV wall thickness at follow-up was associated with narrower grafts (P= 0.0155) and greater graft oversizing (P= 0.0376). Logistic regression demonstrated individuals who met criteria for LV hypertrophy were more likely to have narrower stent-grafts (P= 0.00798) and greater graft oversizing (P= 0.0315). CONCLUSIONS: LV wall thickening occurred to a greater degree in individuals with narrower stent-grafts and higher rates of graft oversizing. This has significant implications for long-term cardiovascular health in younger patients may undergo TEVAR for atypical indications. Particular attention should be paid to long-term effects of stent-graft oversizing when selecting grafts in such populations.

Tubercular Tenosynovitis of Extensor Tendons of Ankle : A Case Report.

Introduction: India being an endemic region for Tuberculosis (TB) has a high incidence of musculoskeletal TB with various presentations. Tenosynovitis is a rare presentation and few cases have been reported involving the hand and wrist but isolated involvement of extensor tendons at the ankle is even rarer and unreported. Case Report: Thirty-five-year-old female patient presenting with a dumbbell-shaped swelling over the anterolateral aspect of right ankle with mild dull aching pain. MRI revealed altered signal intensities surrounding the extensor tendons at the ankle without the involvement of the joint. Surgical debridement was done and six-month ATT was given. Gross specimen revealed rice bodies and histopathological examination showed caseous necrosis and epitheloid cell granulomas. Conclusion: Tuberculosis TB being endemic can have varied presentations, early diagnosis can be made if clinical suspicion for TB is considered. ATT is the mainstay of treatment, but surgical debridement is necessary for extensive lesions with compressive symptoms.

Effect of TNFα blockade on UVB-induced inflammatory cell migration and collagen loss in mice.

UVB irradiation induces pro-inflammatory cytokines including interleukin-1 (IL-1) and tumor necrosis factor-α (TNFα) in the skin. TNFα stimulates the chemotaxis of inflammatory cells to the skin. These cells secrete metalloproteinases (MMPs) and other enzymes that damage the cutaneous matrix. Therefore, blocking TNFα activity could be effective in preventing the influx of inflammatory cells and subsequent collagen degradation in the skin. In addition, TNFα downregulates procollagen mRNA, and thus blockade may be beneficial to production of type I collagen. Female C57BL/6 J mice were treated with etanercept (TNFα blocker, 4 mg/kg/day) for 4 days 1 h prior to UVB irradiation (100 mJ/cm2/day for 5 days). On the 5th day mice were sacrificed 3 h after UVB exposure. Blocking TNFα significantly inhibited UVB-induced recruitment of macrophages, mast cells, and neutrophils. UVB-irradiated mice skin contained more mature collagen compared to etanercept and UVB + etanercept-treated mice. Skin from UVB + etanercept-treated mice had more collagen fragments relative to UVB-irradiated mice. Procollagen protein was lower in UVB-irradiated and UVB + etanercept-treated mice. TNFα blockade decreased decorin and TGF-ß1 in UVB-irradiated mice compared to UVB alone. MMP13 was inhibited by etanercept in UVB-irradiated mice (p < 0.01). In conclusion, blockade of TNFα significantly decreased mature collagen in UVB-irradiated mice, while increasing collagen fragmentation and decreasing procollagen.

Functional characterization of Candida glabrata ORF, CAGL0M02233g for its role in stress tolerance and virulence.

Present investigation is aimed to analyze the role of an uncharacterized ORF of Candida glabrata (CBS138), CAGL0M02233g (an ortholog of RAD53, a key DNA checkpoint effector in Saccharomyces cerevisiae) in tolerance of various stresses and in biofilm formation. The CAGL0M02233g was cloned in p416TEF shuttle vector for constitutive expression under TEF1 promoter in BG14 strain (ura3 auxotrophic C. glabrata), and upregulated expression of the cloned ORF was confirmed by immunoblotting. The constitutive expression of CAGL0M02233g rendered cells resistant to the DNA damage stressor (MMS), replication stressor (HU) and hypoxia mimetic (CoCl2) in plate spot and growth curve assays. Hypoxia (a low oxygen condition) is an imperative host factor that influences Candida pathogenesis. Biofilm formation by the BG14 cells transformed with p416TEF-CAGL0M02233g (REX cell) was reduced to approximately 50% under hypoxia. It is notable that biofilm formation by the REX cells was significantly lower than that of BG14 cells transformed with p416TEF vector (VC cell) under hypoxia. The biofilm of the REX cells has shown higher susceptibility to fluconazole than that of VC cells under hypoxia and REX cells at normoxia. This is the first report on the function of CAGL0M02233g in tolerance of various stressors and in modulation of the biofilm under hypoxia.