Search

The Extended Screening for Inborn Errors of Metabolism is done for aminoacidopathies, fatty acid oxidation disorders and organic acid disorders. In a single dried blood spot, the tandem mass spectrometry is capable of measuring multiple analytes like amino acids, acylcarnitines, nucleosides, succinylacetone and lysophosphatidylcholines. This study was proposed to establish age specific reference internal for aminoacids and acylcartinitine in dried blood spot by tandem mass spectrometry. A total of 480 apparently healthy children were enrolled for the study and sub classified into four groups as follows: Group A: 0-1 month, Group B: 1 month-1 year, Group C: 1-5 year and Group D: 5-12 years each having 120 participants. Sample size were calculated as per CLSI approved guidelines. Tables 1 and 2 presents the age-specific percentile distribution of aminoacids and acylcarnitines established from healthy subjects as per rank-based method recommended by the IFCC and CLSI. Tables 3, 4 and 5 presents the cut-off values of primary and secondary marker/ratios for screening of aminoacidopathies, fatty acid oxidation disorders and organic acid disorders respectively. As a general principle, the interpretation of extended newborn screening results should be based on age specific cut-off established by the laboratory for primary analyte concentration and secondary analyte concentration/ ratios. This study was useful in establishing age specific cut-off values for various amino acids and acylcarnitines in South Indian population. [Table: see text] [Table: see text] [Table: see text] [Table: see text] [Table: see text]., Competing Interests: Conflict of interestNo potential conflict of interest relevant to this article was reported., (© The Author(s), under exclusive licence to Association of Clinical Biochemists of India 2023, corrected publication 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

We have designed and developed novel and selective TLR7 agonists that exhibited potent receptor activity in a cell-based reporter assay. In vitro , these agonists significantly induced secretion of cytokines IL-6, IL-1β, IL-10, TNFa, IFNa, and IP-10 in human and mouse whole blood. Pharmacokinetic and pharmacodynamic studies in mice showed a significant secretion of IFNα and TNFα cytokines. When combined with aPD1 in a CT-26 tumor model, the lead compound showed strong synergistic antitumor activity with complete tumor regression in 8/10 mice dosed using the intravenous route. Structure-activity relationship studies enabled by structure-based designs of TLR7 agonists are disclosed., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Background: Patients with symptomatic calcified coronary lesions have poor outcomes. Such lesions require additional atherectomy devices for bed preparation., Aim: To assess the safety and efficacy of OPN balloon in patients with calcified coronary lesions., Methods: This is an investigator-initiated, prospective, observational study. The primary outcome of the study was a procedural success., Results: We studied 71 patients (133 lesions). Maximum lesions were located in LAD [46.6 %]. The OPN balloon was used for pre-dilatation alone in 28.6 % (Pre-stent OPN group), post-dilatation alone in 63.2 % of lesions (Post-stent OPN group), and in both situations in 8.3 % of lesions with procedural success in 98.5 % of patients. Further dilatation with different NC balloons was required in both groups (30 %). The median (IQR) OPN balloon diameter in the pre- and post-stent OPN group were 2.5 (2.5, 3.0) and 3.0 (3.0,3.0) mm (p = 0.001), respectively. The difference between the diameter of the stent and OPN balloon used in pre-stent OPN group was 0.5 (0.2, 0.5) mm while it was 0.0 (0.0,0.2) mm in the post-stent OPN group (p < 0.001). Eight complications and two deaths occured. Distal shaft rupture was also noticed., Conclusion: OPN balloon is safe, and effective in treating calcified coronary lesions. We propose to undersize the balloon by 0.5 mm for pre-dilatation followed by 0.25 mm larger NC balloon if needed. In the post-dilatation group, use a 1:1 size balloon in a non-tortuous straight segment. Use imaging especially when (1) the pressure taken more than the rated burst pressure, (2) an OPN balloon size is ≥3 mm (3) using 1:1 size OPN balloon in a tortuous segment., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Hydrogels are 3D crosslinking networks of hydrophilic biopolymers which can able to absorb and retain large amount of water. In this present study, the Sodium alginate (SA)- Galactoxyloglucan (GXG) blended hydrogel beads were prepared and optimized through two level optimization steps. Alginate and xyloglucan are the cell wall polysaccharides biopolymers obtained from the plant sources, Sargassum sp. and Tamarindus indica L. respectively. The extracted biopolymers were confirmed and characterized by UV-Spectroscopy, FT-IR, NMR and TGA analysis. Based on the hydrophilicity, non-toxicity and biocompatibility, SA-GXG hydrogel were prepared and optimized through two-level optimization steps. The optimized hydrogel bead formulation was characterized through FT-IR, TGA and SEM analysis. From the obtained result, it is found that the polymeric formulation GXG (2 % w/v)-SA (1.5 % w/v), cross-linker (CaCl 2 ) concentration at 0.1 M and the cross-linking time at 15 Min showed significant swelling index. The optimized hydrogel beads are porous and show good swelling capacity and thermal stability. The optimized protocol of hydrogel beads may be useful in designing hydrogel beads for specific applications in agricultural, Biomedical and remediation sectors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The intention of this work is to study a mathematical model for fractal-fractional tuberculosis and COVID-19 co-infection under the Atangana-Baleanu fractal-fractional operator. Firstly, we formulate the tuberculosis and COVID-19 co-infection model by considering the tuberculosis recovery individuals, the COVID-19 recovery individuals, and both disease recovery compartment in the proposed model. The fixed point approach is utilized to explore the existence and uniqueness of the solution in the suggested model. The stability analysis related to solve the Ulam-Hyers stability is also investigated. This paper is based on Lagrange's interpolation polynomial in the numerical scheme, which is validated through a specific case with a comparative numerical analysis for different values of the fractional and fractal orders., (© 2023. The Author(s).)

The cadmium tungstate rods have been given much attention due to their potential for usage in numerous luminescent applications. We have prepared single crystalline Sn-doped Cd 1-x Sn x WO 4 (where x = 0, 1, 3, and 5%) nanorods (NRDs) and characterized them using refined X-ray diffraction and TEM analysis, revealing a monoclinic phase and a crystallite size that decreased from 62 to 38 nm as Sn concentration increased. Precise Sn doping modulation in CdWO 4 NRDs causes surface recombination of electrons and holes, which causes the PL intensity to decrease as the Sn content rises. The chromaticity diagram shows that an increase in the Sn content caused a change in the emission color from sky blue to light green, which was attributed to the increased defect density. The photoluminescence time decay curve of all samples fit well with double-order exponential decay, and the average decay lifetime was found to be 1.11, 0.93, and 1.16 ns for Cd 1-x Sn x WO 4 , x = 0, 1, and 5%, respectively. This work provides an understanding of the behavior of Sn-doped CdWO 4 NRDs during electron transitions and the physical nature of emission that could be used in bio-imaging, light sources, displays, and other applications.

Bismuth ion (Bi 3+ ) sensitized, europium ion (Eu 3+ ) activated La 2 Zr 2 O 7 nanophosphors are prepared successfully by simple wet chemical method. Strong blue emission of singly doped La 2 Zr 2 O 7 with Bi 3+ was observed at 310 nm excitation, its wide emission spectrum has a peak maximum at 465 nm ascribed to electronic transition 3 P 1  →  1 S 0 of Bi 3+ . The recorded photoluminescence spectra of y at% Eu 3+ codoped La 2 Zr 2 O 7 , when excited at 285 nm, the emission spectrum exhibits maximum peaks at wavelength values 615 nm, 646 nm and 665 nm which are ascribed to 5 D 0  →  7 F 2 , 5 D 0  →  7 F 3 and 5 D 0  →  7 F 4 transitions of Eu 3+ respectively. The chromaticity coordinates for the optimized sample were found to be (0.519, 0.329). Sensitizing with Bi 3+ can affect the luminescence properties of La 2 Zr 2 O 7 :Eu 3+ phosphors. With reference to the change in Eu 3+ concentration from Y  = 1, 2, 3, 4 and 5%, color tunable luminescence from blue to orange, red of La 2 Zr 2 O 7 :Bi 3+ ,Eu 3+ phosphors are observed. The lifetime decay values, energy level description and CIE chromatic color coordinates for Bi 3+ , Eu 3+ in La 2 Zr 2 O 7 :Bi 3+ ,Eu 3+ codoped sample was discussed. The spectral overlap between sensitizer, activator ions confirms the efficient energy transfer from Bi 3+ to Eu 3+ in La 2 Zr 2 O 7 :Bi 3+ ,Eu 3+ codoped sample and is via a dipole-quadruple mechanism., (© 2022 John Wiley & Sons Ltd.)

Background: As dental lasers are becoming more popular in the branch of oral medicine for its various advantages and applications, this study was carried out to evaluate better mode of obtaining oral biopsies which is a common and inevitable procedure for providing final diagnosis in majority of conditions., Methodology: In this study, a total of 60 patients who required biopsy for final diagnosis of oral mucosal lesions as part of diagnosis in department of Oral Medicine were selected, out of which 30 were subjected to scalpel biopsies and 30 patients were subjected to diode laser biopsies. A 980 nm Zolar plus diode laser was used for the study. Out of 30 patients who were subjected to laser biopsies, 3W continuous mode settings were used for 15 patients and 3W pulsed mode was used for 15 patients. The specimens were sent to Department of Oral Pathology for histopathological evaluation to provide the final diagnosis. The time taken for each patient, volume of local anesthesia, during operative, postoperative pain scale, and co-relation of provisional and final diagnosis was noted for comparison purpose and the pathologist comments, peripheral tissue damage and artifact's for each slide were noted., Results: The study results showed the postoperative pain was comparatively less in diodlaser than scalpel, the lasers were patient friendly as the heammorage was negligible when compared to scalpel and suturing was not required. The pulsed mode in diode laser was advantageous over continuous mode when amount of thermal damage and postoperative pain score was compared., Conclusion: The results showed that oral biopsies can be made better using diode lasers, by having thorough knowledge on the device., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Pharmacy and Bioallied Sciences.)

Data science has been an invaluable part of the COVID-19 pandemic response with multiple applications, ranging from tracking viral evolution to understanding the vaccine effectiveness. Asymptomatic breakthrough infections have been a major problem in assessing vaccine effectiveness in populations globally. Serological discrimination of vaccine response from infection has so far been limited to Spike protein vaccines since whole virion vaccines generate antibodies against all the viral proteins. Here, we show how a statistical and machine learning (ML) based approach can be used to discriminate between SARS-CoV-2 infection and immune response to an inactivated whole virion vaccine (BBV152, Covaxin). For this, we assessed serial data on antibodies against Spike and Nucleocapsid antigens, along with age, sex, number of doses taken, and days since last dose, for 1823 Covaxin recipients. An ensemble ML model, incorporating a consensus clustering approach alongside the support vector machine model, was built on 1063 samples where reliable qualifying data existed, and then applied to the entire dataset. Of 1448 self-reported negative subjects, our ensemble ML model classified 724 to be infected. For method validation, we determined the relative ability of a random subset of samples to neutralize Delta versus wild-type strain using a surrogate neutralization assay. We worked on the premise that antibodies generated by a whole virion vaccine would neutralize wild type more efficiently than delta strain. In 100 of 156 samples, where ML prediction differed from self-reported uninfected status, neutralization against Delta strain was more effective, indicating infection. We found 71.8% subjects predicted to be infected during the surge, which is concordant with the percentage of sequences classified as Delta (75.6%-80.2%) over the same period. Our approach will help in real-world vaccine effectiveness assessments where whole virion vaccines are commonly used., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Pars plana vitrectomy with implantation of an Ahmed glaucoma valve in the vitreous cavity has been reported with a success rate in the management of refractory and neovascular glaucoma. This study aimed to present the outcomes of pars plana Ahmed glaucoma valve (PPAV) surgical implantation in cases with refractory glaucoma., Methods: In this single-center, retrospective, comparative study, 87 consecutive patients diagnosed with refractory glaucoma who underwent PPAV surgical implantation between October 2015 and October 2019 were evaluated. A successful postoperative outcome was defined as intraocular pressure (IOP) ≤ 21 mmHg upon examination and a reduction in the number of anti-glaucoma agents used at the latest follow-up., Results: Finally, 81 eyes of 78 patients with refractory glaucoma were included; 54 (66.66%) of the eyes had neovascular glaucoma. The mean follow-up was 20.65 ± 12.17 months (range: 2-52 months). The mean preoperative IOP was 40.01 ± 1.19 mmHg and reduced significantly to 16.73 ± 0.82 mmHg at the latest follow-up ( P < 0.001); a successful IOP outcome was achieved in 88.89% of eyes. The mean number of anti-glaucoma agents decreased significantly from 2.86 ± 0.09 preoperatively to 1.46 ± 0.11 at the latest follow-up (P < 0.001); while 61 (75.31%) of eyes had a reduction in the number of IOP lowering eye drops, and 14 (17.28%) had no need for IOP lowering eye drops., Conclusions: PPAV surgery is a successful procedure for IOP reduction in patients with refractory glaucoma. Our study demonstrated either reduction or elimination of IOP lowering eye drops postoperatively. Large scale studies with a comparison group, a longer follow-up, and having various subtypes of glaucoma are required as future research to confirm these outcomes., Competing Interests: None., (© Author(s).)

In the field of photocatalysis, the suppression of electron-hole recombination through various defects has been an emerging trend to enhance photocatalytic activity. The separation efficiency of electron-hole recombination of well-explored wolframite structured monoclinic CdWO 4 , prepared using the one-pot hydrothermal method, was further improved by Bi 3+ doping in CdWO 4 . Studies using the partial density of states illustrated that Bi 6s and 6p orbitals altered the electronic band structure to the extent of lowering the band gap, resulting in more photon absorption. The positron annihilation lifetime studies unveiled the formation of cluster defects such as oxygen (V0o, V o 1+ , V o 2+ ) along with cadmium vacancies () in Bi-doped CdWO 4 . The coexistence and synergy of more adsorption sites of V0o, V o 1+ , V o 2+ , V Cd for dye and O 2 molecules, suitable oxide/redox band potentials, the modified electronic band structure especially owing to W-O1-Bi-O2-W linkages, together with high surface area endowed Bi-doped CdWO 4 to form ˙O 2 - radicals played a predominant role in the methyl orange degradation. All the experimental findings demonstrated conclusively that Bi 3+ doping at Cd 2+ facilitated CdWO 4 to exhibit superior photocatalytic activity.

Background: Immune-mediated protection is mediated by T cells expressing pathogen-specific T cell antigen receptors (TCR) that are maintained at diverse sites of infection as tissue-resident memory T cells (TRM) or that disseminate as circulating effector-memory (TEM), central memory (TCM), or terminal effector (TEMRA) subsets in blood and tissues. The relationship between circulating and tissue resident T cell subsets in humans remains elusive, and is important for promoting site-specific protective immunity., Methods: We analyzed the TCR repertoire of the major memory CD4 + and CD8 + T cell subsets (TEM, TCM, TEMRA, and TRM) isolated from blood and/or lymphoid organs (spleen, lymph nodes, bone marrow) and lungs of nine organ donors, and blood of three living individuals spanning five decades of life. High-throughput sequencing of the variable (V) portion of individual TCR genes for each subset, tissue, and individual were analyzed for clonal diversity, expansion and overlap between lineage, T cell subsets, and anatomic sites. TCR repertoires were further analyzed for TRBV gene usage and CDR3 edit distance., Results: Across blood, lymphoid organs, and lungs, human memory, and effector CD8 + T cells exhibit greater clonal expansion and distinct TRBV usage compared to CD4 + T cell subsets. Extensive sharing of clones between tissues was observed for CD8 + T cells; large clones specific to TEMRA cells were present in all sites, while TEM cells contained clones shared between sites and with TRM. For CD4 + T cells, TEM clones exhibited the most sharing between sites, followed by TRM, while TCM clones were diverse with minimal sharing between sites and subsets. Within sites, TRM clones exhibited tissue-specific expansions, and maintained clonal diversity with age, compared to age-associated clonal expansions in circulating memory subsets. Edit distance analysis revealed tissue-specific biases in clonal similarity., Conclusions: Our results show that the human memory T cell repertoire comprises clones which persist across sites and subsets, along with clones that are more restricted to certain subsets and/or tissue sites. We also provide evidence that the tissue plays a key role in maintaining memory T cells over age, bolstering the rationale for site-specific targeting of memory reservoirs in vaccines and immunotherapies.

Background: Strategic, operational and tactical superiority of Navy hinges on extremely efficient warships which in turn depend on professionally competent sailors ready to undertake tasks to deliver timely, structured and metered response. Ships and their potentialities are tools to achieve the required strategic advantage which is dependent on the proficiency of sailors. Sailors who are fit ashore may be debilitated on board because of sea sickness., Aims: To study the incidence and severity of sea sickness among 500 naval personnel from various ships. Setting and design: An observational study conducted from May 2019 to March 2020 among 500 naval personnel from various ships of the fleet., Materials and Methods: Motion Sickness Assessment Questionnaire (MSAQ) was used to collect data from personnel of different departments working in different part of ship aged between 20 to 50 years., Results: The majority suffered mild symptoms (78.78%) and did not require any medication. Their symptoms were selflimiting and settled on rest within 24 hours. Moderately severe symptoms were observed among 19.31 % personnel and had to be administered medication and rest for 24 hours. Only 1.91% had severe symptoms and had to be excused from duties along with medication and rest., Conclusion: Sea sickness is unpleasant and has an adverse effect on employability of the sailors. It is mild and self limiting in majority of the personnel not requiring active intervention. Some personnel may require desensitisation along with pharmacotherapy., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Indian Journal of Occupational and Environmental Medicine.)

Acute pulmonary thromboembolism is associated with high mortality, similar to that of myocardial infarction and stroke. We studied the clinical presentation and management of pulmonary thromboembolism in the Indian population. An analysis of 140 patients who presented with acute pulmonary thromboembolism at a large volume center in India from June 2015 through December 2018 was performed. The mean age of our study population was 50 years with 59% being male. Comorbidities including deep vein thrombosis, diabetes mellitus, hypertension, and chronic obstructive pulmonary disease were present in 52.9%, 40%, 35.7% and 7.14% of patients, respectively. Out of 140 patients, 40 (28.6%) patients had massive pulmonary thromboembolism, 36 (25.7%) sub-massive pulmonary thromboembolism, and 64 (45.7%) had low-risk pulmonary thromboembolism. Overall, in-hospital mortality was 25.7%. Multivariate regression analysis found chronic kidney disease and pulmonary thromboembolism severity to be the only independent risk factors. Thrombolysis was performed in 62.5% of patients with a massive pulmonary thromboembolism and 63.9% of patients with a sub-massive pulmonary thromboembolism. In the massive pulmonary thromboembolism group, patients receiving thrombolytic therapy had lower mortality compared with patients who did not receive therapy ( p =0.022), whereas this difference was not observed in patients in the sub-massive pulmonary thromboembolism group. We conclude that patients with acute pulmonary thromboembolism in India presented more than a decade earlier than our western counterparts, and it was associated with poor clinical outcomes. Thrombolysis was associated with significantly reduced in-hospital mortality in patients with massive pulmonary thromboembolism., (© The Author(s) 2021.)

The Fe-doped NiO nanoparticles that were synthesized using a co-precipitation method are characterized by enhanced room-temperature ferromagnetic property evident from magnetic measurements. Neutron powder diffraction experiments suggested an increment of the magnetic moment of 3 d ions in the nanoparticles as a function of Fe-concentration. The temperature, time, and field-dependent magnetization measurements show that the effect of Fe-doping in NiO has enhanced the intraparticle interactions due to formed defect clusters. The intraparticle interactions are proposed to bring additional magnetic anisotropy energy barriers that affect the overall magnetic moment relaxation process and emerging as room temperature magnetic memory. The outcome of this study is attractive for the future development of the room temperature ferromagnetic oxide system to facilitate the integration of spintronic devices and understanding of their fundamental physics., Competing Interests: The authors declare no conflict of interest.

This study depicts the use of a fiber-optic coupled Fourier transform infrared spectroscopy-attenuated total reflection (FTIR-ATR) probe for the in-depth study of arene diazonium salt formation and their utilization in the Heck-Matsuda reaction. The combination of these chemical reactions and in situ IR spectroscopy enabled us to recognize the optimum parameters for arene diazonium salt formation and to track the concentrations of reactants, products and intermediates under actual reaction conditions without time consuming HPLC analysis and the necessity of collecting the sample amid the reaction. Overall advantages of the proposed methodology include precise reaction times as well as identification of keto enol tautomerization in allylic alcohols supporting the 'path a' elimination mechanism in the Heck-Matsuda reaction., Competing Interests: The authors declare no conflict of interest.

Monitoring of acute phase proteins such as serum amyloid A at gene expression level may provide quick information about immune status of the host and its susceptibility towards common infections. Present study was carried out to evaluate and compare the mRNA expression of SAA gene in Rhode Island Red chicken (RIR) and Japanese quails using real time PCR analysis in response to inactivated Salmonella gallinarum culture. The results showed that expression of SAA gene was approximately 17-33 folds higher in case of birds administered with bacterial culture when compared to un-inoculated controls and expression was higher and quicker in case of quails than RIR chicken. The SAA genes from chicken and quail were cloned and upon sequence analysis it was observed that deduced amino acid sequence of SAA from chicken and quails were having approximately seven percent variation which might have significance in function of this protein in these species., Competing Interests: Declaration of Competing Interest None of the authors have any conflict of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: Management of a trauma patient aims at stabilization or resuscitation and revival from critical condition resulting from various sequences of systemic pathophysiological responses in the body. Hematological changes are the first signs reflecting the homeostasis mechanisms starting in the body after injury. The aim of the current study is to evaluate the physiological changes following maxillofacial trauma and extrapolate the findings to understand the posttrauma responses., Patients and Method: This is a retrospective study involving 192 subjects divided into two groups, trauma group and control group. In both the groups, baseline vitals and complete blood picture were recorded for comparison. In trauma group, the recordings were made within 24 h after maxillofacial injury., Results: All the parameters were analyzed using SPSS version 18. Independent sample t -test was used to assess the nature of data distribution and statistical significance was considered only at P value < 0.05. On comparison of complete blood picture mean values of hemoglobin (13.63 vs 12.18), RBC count (4.51 vs 4.10), WBC count (8835.48 vs 8336.56) were seen to be higher in trauma patients compared to control subjects. The mean bleeding times are almost equal (2.35 vs 2.47) but the clotting times (5.42 vs 5.26), random blood glucose (94.78 vs 90.13), and blood urea (27.14 vs 26.30) were marginally higher in trauma group but were statistically insignificant. The mean value of serum creatinine (0.84 vs 0.80) was comparatively higher in trauma patients and was statistically significant. Study of vitals revealed that mean systolic blood pressures were almost equal (120.65 vs 121.08) in both the groups. The mean diastolic blood pressures (79.46 vs 88.49) and oxygen saturation (93.73 vs 98.86) in trauma patients are comparatively reduced. The mean values of temperature (99.30 vs 98.50) and pulse rate (102.38 vs 97.14) were on relatively higher side in trauma group compared with control group., Summary and Conclusion: Using basic blood parameters and vitals in the present study, the compensatory mechanisms happening in the body after maxillofacial trauma can be seen. These changes although significant on side by side comparison can still fall within the normal physiological range provided by various diagnostic setups. Hence, the need for maxillofacial surgeon to be sensitive to minor variations in these aspects to ensure safety of the patient cannot be overemphasized., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Journal of Family Medicine and Primary Care.)

Lysyl oxidase (LOX) is an extracellular metalloenzyme which mediates crosslinking of collagen and elastin. It has been reported to play a pivotal role in cancer metastasis especially in women suffering from breast cancer. The present study is the first to evaluate the gene expression levels of LOX by Real time-polymerase chain reaction (Real time-PCR) in dogs with mammary tumor besides molecular cloning and expression of canine lysyl oxidase gene (lox). Real time-PCR studies showed a significant upregulation (threefold higher) of lox in mammary tumor cases as compared to healthy dogs indicating its possible diagnostic and prognostic role in canine mammary tumors (CMTs). Cloning and sequencing of lox gene revealed 1230 bp CDS which is mostly conserved in C-terminal region. Sequence analysis of canine lox showed that it shares 99% homology with the predicted sequence available on NCBI and had greatest identity with the lox gene from cat. Protein structure predicted with homology modelling was validated by Ramachandran plot analysis which revealed most (approximately 95%) of the amino acids in favoured region. Additionally, recombinant lysyl oxidase expressed as His-tagged fusion protein in prokaryotic expression vector (pPROExHTa) was used in an ELISA for detection of circulating protein LOX in serum of CMT subjects. Receiver operating characteristics analysis of the ELISA revealed high sensitivity (90%) and specificity (85%) with histopathology as reference standard. Taken together, we propose LOX as a diagnostic biomarker and a putative prognostic candidate in CMT cases.

The present study was aimed to evaluate the immuno-modulatory effect of Brucella -specific recombinant HSP40 (rDnaJ) when co-immunized with Brucella rOmp22 in mice. For this, dnaJ of Brucella abortus was cloned, expressed in E. coli, and purified to homogeneity using Ni-NTA agarose columns. Three groups of mice ( n  = 6 in each group) were used in the study. The control group was immunized with rOmp22 alone, while group 1 mice were injected subcutaneously with rOmp22 along with conventional adjuvants (FCA, FIA), and group 2 mice with rOmp22 mixed with rDnaJ. IgG isotype (IgG1 and IgG2a) response to rOmp22 immunization was evaluated by enzyme-linked immunosorbent assay which was found to be directed towards the cell-mediated arm of immune system (CMI) in group 2 mice in which rOmp22 was co-immunized with rDnaJ. Expression profiling of IL-4 and IL-12 was checked in all the groups by qRT PCR. IL12 mRNA was up-regulated to a greater extent in group2 mice, suggesting that the CMI arm of immune system was stimulated. Hence, it was concluded that CMI response against rOmp22 is stimulated to a greater extent in mice when co-immunized with Brucella rDnaJ., Competing Interests: Conflict of interestAll the authors of this paper declare that they have no conflict of interest., (© King Abdulaziz City for Science and Technology 2019.)

In this work, a human ventricular model (ten Tusscher and Panfilov model) coupled with the tissue level monodomain model is used to analyze the influence of multiple myocardial ischemia on the human cardiac tissue. The existence and uniqueness of the ischemic model comprising the monodomain model with a discontinuous ionic model for the human cardiac tissue is discussed. The coupled system of partial differential equation and ordinary differential equations are solved numerically using [Formula: see text] finite elements in space and Backward Euler finite difference scheme in time. The apriori finite element error estimate for the numerical scheme has been shown to be of [Formula: see text]. Essentially, we evaluate the impact of the increasing size of the ischemic region and the presence of the multiple ischemic regions having equal or different intensities on the neighboring healthy part of the cardiac tissue. We examine both the individual and the combined influence of two types of ischemia, Hyperkalemia (with the variation of the extracellular potassium ion concentration, [Formula: see text]) and Hypoxia (with the variation of intracellular Adenosine triphosphate (ATP) concentration via parameter [Formula: see text]) on the cardiac electrical activity of cardiac tissue. We observe that with the increase in the ischemic region size by a factor five times, there is an additional almost 10% drop in the action potential duration (APD) in the neighboring healthy regions. The combined effect of Hyperkalemia and Hypoxia brings an additional 12% drop in APD in the ischemic subregions and an additional 5% drop in APD in the neighboring healthy part of the cardic tissue in comparison to the only Hyperkalemic ischemia. When the Hyperkalemic and/or Hypoxic degeneracy of a ischemic zone is non-uniform then innercore degeneracy has greater influence on resting potential and APD of outercore of variable intensity ischemic zone than the other way. Also, increasing the number of ischemic subregions from 2 to 4 leads to a 4% drop in APD.

Targeted degrading Aspergillus niger-derived prolyl endopeptidase (AN-PEP) is promising in gluten hydrolysis because it specifically cleaves the proline-rich sites in gluten. The current study aims to understand the safety aspects of AN-PEP hydrolysed low immunoreactive wheat flours by testing immune responses using cell line and animal models. In the AN-PEP hydrolysed wheat flour (AN-PEP HWF) gliadin extract, there was no increase in the levels of zonulin-1 (Zo-1) and pro-inflammatory cytokines (IL-6 and IL-8) but a significant increase was noted in the control wheat flour (CWF) gliadin-treated Caco-2 cells. The Zo-1 localization in Caco-2 cells was significantly noted in the reacted positive fluorescence cells that were treated with the control wheat flour. Further, a safety evaluation of HWF was carried out in gluten-sensitized BALB/c mice. Mouse anti-gliadin (IgG, IgA and IgE) antibodies were significantly generated in the CWF treated animals rather than the AN-PEP HWF groups. The serum pro-inflammatory (IL-1β, IL-4, IL-6, IL-15, TNF-α and IFN-γ) markers were observed in significant levels in CWF challenged mice and a similar trend was observed in ex-vivo splenocyte cells. A small intestine histopathological sectioning revealed that there are no abnormalities or structural changes in AN-PEP HWF challenged mice., (Copyright © 2019. Published by Elsevier Ltd.)

Background: There is an increased incidence of allergic contact dermatitis (ACD) over the lower extremities due to over-the-counter topical preparations, occupational risk, and usage of several chemicals in the manufacture of designer footwear., Aims and Objectives: The aim of the study was to identify the common allergens and polysensitization pattern involved in ACD over the lower extremities., Materials and Methods: It is a cross-sectional study, wherein a total of 80 patients were recruited over a period of 18 months. Demographic and clinical characteristics were noted. Patch test was done with the Indian standard series. Interpretation of patch test readings was read according to the International Contact Dermatitis Research Group criteria at 48 and 96 h., Results: There were 45 males and 35 females (M:F= 1.3:1). Mean age was 41.65 years. Most of the patients belonged to 21-40 years age group. Farmers, homemakers, and students were commonly affected. Most common presentation was itching, hyperpigmentation, and scaly plaques over the feet. Patch test was performed in 75% of the patients. One or more positive results were observed in 57% of the patients. Common allergens noted were potassium dichromate (35%), followed by nickel sulfate (23.5%), mercapto mix, and mercaptobenzothiazole. Potassium dichromate and nickel were the common allergens reported in males and females, respectively. Neomycin was the common medication responsible for dermatitis medicamentosa. Polysensitization was seen with mercapto mix, mercaptobenzothiazole, potassium dichromate, and fragrance mix., Conclusion: Potassium dichromate and nickel were the common allergens responsible for ACD over the lower extremities. Polysensitization was seen commonly with mercapto mix, mercaptobenzothiazole, and fragrance mix., Recommendation: Screening for usage of topical preparations and late patch test readings (96 h or more) is recommended., Competing Interests: There are no conflicts of interest.

Tissue-resident memory T cells (TRMs) accelerate pathogen clearance through rapid and enhanced functional responses in situ. TRMs are prevalent in diverse anatomic sites throughout the human lifespan, yet their phenotypic and functional diversity has not been fully described. Here, we identify subpopulations of human TRMs based on the ability to efflux fluorescent dyes [efflux(+) TRMs] located within mucosal and lymphoid sites with distinct transcriptional profiles, turnover, and functional capacities. Compared with efflux(-) TRMs, efflux(+) TRMs showed transcriptional and phenotypic features of quiescence including reduced turnover, decreased expression of exhaustion markers, and increased proliferative capacity and signaling in response to homeostatic cytokines. Moreover, upon activation, efflux(+) TRMs secreted lower levels of inflammatory cytokines such as IFN-γ and IL-2 and underwent reduced degranulation. Interestingly, analysis of TRM subsets following activation revealed that both efflux(+) and efflux(-) TRMs undergo extensive transcriptional changes following TCR ligation but retain core TRM transcriptional properties including retention markers, suggesting that TRMs carry out effector function in situ. Overall, our results suggest a model for tissue-resident immunity wherein heterogeneous subsets have differential capacities for longevity and effector function.

Translating studies on T cell function and modulation from mouse models to humans requires extrapolating in vivo results on mouse T cell responses in lymphoid organs (spleen and lymph nodes [LN]) to human peripheral blood T cells. However, our understanding of T cell responses in human lymphoid sites and their relation to peripheral blood remains sparse. In this study, we used a unique human tissue resource to study human T cells in different anatomical compartments within individual donors and identify a subset of memory CD8 + T cells in LN, which maintain a distinct differentiation and functional profile compared with memory CD8 + T cells in blood, spleen, bone marrow, and lungs. Whole-transcriptome and high-dimensional cytometry by time-of-flight profiling reveals that LN memory CD8 + T cells express signatures of quiescence and self-renewal compared with corresponding populations in blood, spleen, bone marrow, and lung. LN memory T cells exhibit a distinct transcriptional signature, including expression of stem cell-associated transcription factors TCF-1 and LEF-1, T follicular helper cell markers CXCR5 and CXCR4, and reduced expression of effector molecules. LN memory T cells display high homology to a subset of mouse CD8 + T cells identified in chronic infection models that respond to checkpoint blockade immunotherapy. Functionally, human LN memory T cells exhibit increased proliferation to TCR-mediated stimulation and maintain higher TCR clonal diversity compared with memory T cells from blood and other sites. These findings establish human LN as reservoirs for memory T cells with high capacities for expansion and diverse recognition and important targets for immunotherapies., (Copyright © 2018 by The American Association of Immunologists, Inc.)

Context: Salivary analytes may be used as biomarkers for translational and clinical applications. Heat shock proteins (Hsps) are ubiquitous, highly conserved proteins found in all prokaryotic and eukaryotic species. Hsp27, a low molecular weight protein, may act as a salivary biomarker. Leukoplakia is the most common oral potentially malignant disorder and various salivary biomarkers such as interleukin-6, 8, tumor necrosis factor-α and MMPs have been detected in it. Oral leukoplakia presents clinically as homogenous and nonhomogenous forms; the microscopic pattern ranges from simple epithelial hyperplasia to carcinoma in situ ., Aims: This study aims to detect salivary Hsp27 in oral leukoplakia by enzyme-linked immunosorbent assay (ELISA) and to correlate its expression pattern with histopathology., Materials and Methods: A total of 45 cases had constituted the study group. Salivary Hsp27 levels were assessed by ELISA in histopathologically confirmed cases of oral leukoplakia and were compared with that of healthy volunteers., Statistical Analysis: Mann-Whitney U-test and Spearman's correlation coefficient were used for the detection of Hsp27 and its correlation with mean absorbance levels., Results: The mean absorbance values had shown elevated expression of Hsp27 in oral leukoplakia when compared to that in healthy volunteers., Conclusions: The present study had shown elevated expression of salivary Hsp27 in oral leukoplakia which could be attributed to altered redox potential., Competing Interests: There are no conflicts of interest.