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Background Urinary tract infection (UTI) is one of the most common causes of fever in the pediatric age group. The study was designed to study the clinical profile, etiologic microorganisms, and antibiogram patterns. Methods The present study is a hospital-based cross-sectional study done over a study period of one and a half years. Results Females comprised a higher proportion of the study subjects. Increased urinary frequency and urgency were the most prevalent presenting symptoms in the study population, seen in 39 (39%) and 20 (20%) of the children, respectively.  Escherichia coli  was found to be the most common causative organism in 45 (45%) children followed by Klebsiella in 22 (22%) children. The organisms showed maximum sensitivity to linezolid (88%) followed by levofloxacin(78%), and piperacillin-tazobactam(76%). Cotrimoxazole(16%) and cefixime(9%) showed the maximum resistance. The outcome was favorable for the majority of the patients treated at par with the antibiogram. Eleven (11%) of the children were found to have anatomical abnormalities in their genitourinary system, and it was found to be significantly associated with recurrence (P value=0.05). Conclusions UTI as one of the leading causes of fever and has to be dealt with a high index of suspicion while evaluating for cases of fever without a focus on children. The antibiogram of the underlying organisms needs to be followed while treating cases of UTI to ensure prompt recovery and avoid the emergence of antimicrobial resistance. This also highlights the need for periodic surveillance of the local prevalence of organisms and their antimicrobial susceptibilities to tailor proper management. Children with anatomical abnormalities in their renal system need to be followed up carefully for chances of recurrence., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Krishna Mandal et al.)

Immunotherapeutic modulation of antigen-specific T-cell responses instead of the whole repertoire helps avoid immune-related adverse events. We have developed an artificial antigen-presenting system (aAPS) where multiple copies of a multimeric peptide-MHC class I complex presenting a murine class I MHC restricted ovalbumin-derived peptide (signal 1), along with a costimulatory ligand (signal 2) are chemically conjugated to a dextran backbone. Cognate naive CD8 + T cells, when treated with this aAPS underwent significant expansion and showed an activated phenotype. Furthermore, elevated expression of effector cytokines led to the differentiation of these cells to cytotoxic T lymphocytes which resulted in target cell lysis, indicative of the functional efficacy of the aAPS. CD8 + T cells with decreased proliferative potential due to repeated antigenic stimulation could also be re-expanded by the developed aAPS. Thus, the developed aAPS warrants further engineering for future application as a rapidly customizable personalized immunotherapeutic agent, incorporating patient-specific MHC-restricted tumor antigens and different costimulatory signals to modulate both naive and antigen-experienced but exhausted tumor-specific T cells in cancer., (© 2023 Wiley-VCH GmbH.)

Background Scrub typhus is a reemerging, acute, undifferentiating febrile illness and one of the most neglected tropical diseases, calling for an in-depth investigation into its clinical diversity, complications, and mortality, which drives us to carry out this research work. Methods Over a year, prospective observational research was carried out after gaining parental consent and institutional ethical clearance, 206 children of either gender aged between one month and 12 years who had been hospitalized with a fever for at least five days and subsequently tested positive for  Orientia ​​​​  tsutsugamushi  were included in the study. Basic demographic information, clinical characteristics, laboratory findings, complications, related coinfections, and results were gathered and analyzed. A P -value of 0.05 was set as the statistical benchmark. Results The current study found that boys outnumbered girls. The ratio of boys to girls was 1.22:1, and the average age was 5.18 years. All had a fever (100%), and the other most frequently occurring clinical signs and symptoms were abdominal pain (16.99%), vomiting (22.33%), hepatosplenomegaly (49.51%), facial puffiness (39.32%), edema (27.18%), lymphadenopathy (19.90%), eschar (19.90%), macular-erythematous rash (17.96%), cough (21.84%), conjunctival congestion (25.24%), and headache (13.59%). Anemia (81.55%), leucocytosis (20.39%), leucopenia (6.8%), thrombocytopenia (49.51%), thrombocytosis (2.43%), and elevated serum levels of alanine aminotransferase (ALT, 57.28%) and aspartate aminotransferase (AST, 63.59%) were characteristic laboratory results. The coinfections were dengue, enteric fever, urinary tract infections, and malaria. Children who also had dengue were more likely to develop thrombocytopenia, which was statistically significant ( P -value = 0.008). With doxycycline medication, early defervescence of fever occurred earlier than with azithromycin, and it was statistically significant ( P -value = 0.000). The complications were hepatitis (63.59%), lower respiratory tract infections (LRTIs, 22.82%),   scrub typhus meningoencephalitis (STME, 3.88%), acute kidney injury (AKI, 2.91%), myocarditis (1.46%), and acute disseminated encephalomyelitis (ADEM, 0.49%). Except for one who had ADEM, everyone was sent back home after receiving the best care possible. The average duration of hospital stay was 6.89 days. Conclusions Even in the absence of eschar, scrub typhus should be suspected in any febrile child who experiences clinical signs of meningoencephalitis syndrome, capillary leakage, skin rash, conjunctival congestion, LRTI, AKI, lymphadenopathy, hepatosplenomegaly, thrombocytopenia, and liver dysfunction in the post-monsoon season. Strong clinical suspicion and prompt anti-scrub drug administration go a long way in preventing or decreasing the morbidity and mortality of the same., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Kumar Jana et al.)

Antigen-specificity of T cells provides important clues to the pathogenesis of T cell-mediated autoimmune diseases and immune-evasion strategies of tumors. Identification of T cell clones involved in autoimmunity or cancer is achieved with soluble peptide-MHC (pMHC) complex multimers. Importantly, these complexes can also be used to manipulate disease-relevant T cells to restore homeostasis of T cell-mediated immune response. While auto-antigen-specific T cells can be deleted or anergized by T cell receptor engagement with cognate pMHC complexes in the absence of costimulation, integration of these complexes in artificial antigen-presenting systems can activate tumor antigen-specific T cells. Here the authors discuss the advancements in pMHC-complex-mediated immunotherapeutic strategies in autoimmunity and cancer and identify the lacunae in these strategies that need to be addressed to facilitate clinical implementation.

T cell costimulation is mediated by the interaction of a number of receptors and ligands present on the surface of the T cell and antigen-presenting cell, respectively. Stimulatory or inhibitory signals from these receptor-ligand interactions work in tandem to preserve immune homeostasis. BTNL2 is a type-1 membrane protein that provides inhibitory signal to T cells and plays an important role in several inflammatory and autoimmune diseases. Therefore, manipulation of the molecular interaction of BTNL2 with its putative receptor could provide strategies to restore immune homeostasis in these diseases. Hence, it is imperative to study the structural characteristics of this molecule, which will provide important insights into its function as well. In this study, the membrane-distal ectodomain of murine BTNL2 was expressed in bacteria as inclusion bodies, refolded in vitro and purified for functional and structural characterization. The domain is monomeric in solution as demonstrated by size-exclusion chromatography and analytical ultracentrifugation, and also binds to its putative receptor on naïve B cells and activated T cell subsets. Importantly, for the first time, we report the structure of BTNL2 as determined by solution NMR spectroscopy and also the picosecond-nanosecond timescale backbone dynamics of this domain. The N-terminal ectodomain of BTNL2, which was able to inhibit T cell function as well, exhibits distinctive structural features. The N-terminal ectodomain of BTNL2 has a significantly reduced surface area in the front sheet due to the non-canonical conformation of the CC' loop, which provides important insights into the recognition of its presently unknown binding partner., Competing Interests: Conflict of Interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Ointments are highly viscous forms intended for external applications either medicated or non-medicated means. Formulation of ointment depends upon the base ingredients to measure the viscosity difference. Several limitations of ointment bases has been encountered timely as agglomeration, oil phase ingredients can form lumps, poor dispersion, poor drug delivery efficiency, make stained, immiscible, and difficult to wash off. Therefore, it is necessary to make a new type of ointment bases that can overcome those limitations. This review summarizes a new type of ointment base preparation from the copolymer of renewable phenolic derivatives. The nanohydrogel preparation from these copolymers are especially effortless and highly efficient in drug delivery, exhibited versatile biological activities such as antioxidant, anti-inflammatory and wound healing in addition to antimicrobial property. Molecular self-assembly mechanisms have been addressed for nanogel formulation. The strategy makes a significant value in health-care application and be supposed to come marketed soon.

Objective: We executed the Social Media Mining for Health (SMM4H) 2017 shared tasks to enable the community-driven development and large-scale evaluation of automatic text processing methods for the classification and normalization of health-related text from social media. An additional objective was to publicly release manually annotated data., Materials and Methods: We organized 3 independent subtasks: automatic classification of self-reports of 1) adverse drug reactions (ADRs) and 2) medication consumption, from medication-mentioning tweets, and 3) normalization of ADR expressions. Training data consisted of 15 717 annotated tweets for (1), 10 260 for (2), and 6650 ADR phrases and identifiers for (3); and exhibited typical properties of social-media-based health-related texts. Systems were evaluated using 9961, 7513, and 2500 instances for the 3 subtasks, respectively. We evaluated performances of classes of methods and ensembles of system combinations following the shared tasks., Results: Among 55 system runs, the best system scores for the 3 subtasks were 0.435 (ADR class F1-score) for subtask-1, 0.693 (micro-averaged F1-score over two classes) for subtask-2, and 88.5% (accuracy) for subtask-3. Ensembles of system combinations obtained best scores of 0.476, 0.702, and 88.7%, outperforming individual systems., Discussion: Among individual systems, support vector machines and convolutional neural networks showed high performance. Performance gains achieved by ensembles of system combinations suggest that such strategies may be suitable for operational systems relying on difficult text classification tasks (eg, subtask-1)., Conclusions: Data imbalance and lack of context remain challenges for natural language processing of social media text. Annotated data from the shared task have been made available as reference standards for future studies (http://dx.doi.org/10.17632/rxwfb3tysd.1).

Green chemistry polymers from renewable resources have recently received much more attention from pharmaceutical researchers. However, the appropriate application of a polymer depends on its chemical nature, biocompatibility and microstructure. Here, tannin polyphenols from the common beverage, tea, are used to develop a novel self-assembled porous capsule as a microstructure of hydrogel for versatile biological applications, such as drug delivery, antioxidant and wound healing activity. Hydrogel has been successfully used for the delivery of both anticancer and antimicrobial drugs. The developed material shows excellent biocompatibility and antioxidant activity in vitro. The scratch assay for in vitro wound healing activity reveals their higher potential to repair the damaged cells in comparison to control.

Amniotic membrane (AM) is frequently used in ophthalmologic surgery for rapid ocular surface reconstruction. Sometimes it may create a major problem with associated infections after biofilm formation over the membrane. To overcome this problem, AM was coated with the antimicrobial peptide clavanin A. The antifungal activity of clavanin A in the native and self-assembled form was determined against the common ocular surface pathogens Candida albicans, Aspergillus fumigatus, Alternaria sp. and Fusarium sp. Biofilm formation over the coated surface was significantly reduced in comparison with the uncoated membrane. The coated membrane revealed effectiveness in terms of biocompatibility, cell attachment colonization when tested in non-cancerous 3T3 and human embryonic kidney (HEK)-293 cell lines. Clavanin A-coated AM also exhibited excellent physical, morphological and antifungal characteristics, indicating potential applicability for ocular surface infection control.

Lignin, one of the most abundant renewable feedstock, is used to develop a biocompatible hydrogel as anti-infective ointment. A hydrophilic polyoxazoline chain is grafted through ring opening polymerization, possess homogeneous spherical nanoparticles of 10-15 nm. The copolymer was covalently modified with triazole moiety to fortify the antimicrobial and antibiofilm activities. The hydrogel was capable of down regulating the expression level of IL-1β in LPS induced macrophage cells, and to cause significant reduction of iNOS production. It supported cellular anti-inflammatory activity which was confirmed with luciferase assay, western blot, and NF-κB analysis. This novel lignin-based hydrogel tested in-vivo has shown the abilities to prevent infection of burn wound, aid healing, and an anti-inflammatory dressing material. The hydrogel reported here provides a new material platform to introduce a cost-effective and efficient ointment option after undertaking further work to look at its use in the area of clinical practice.

Health-care materials associated with infections are very common in hospital admitted patients. There are generally infected by contact with the catheter or other multipurpose devices which are contacted with microbes. The respiratory infections associated with the pathogens having strong biofilm forming ability on catheter surface, causes life-threatening in every year. Therefore, a catheter coating material is of great interest which inhibits the biofilm formation of pathogens on a catheter to prevent respiratory infections. In this study, we synthesized cardanol containing copolymers as antimicrobial healthcare material via radical polymerization of cardanyl methacrylate (CMA) with styrene (St) monomer in presence of free radical initiator. The rate of polymerization was drastically reduced with the increase of feeding CMA monomer in copolymer. The thermal and mechanical properties were found to increase with incorporation of cardanol moiety in brittle and hard polystyrene. This soft copolymer was grafted onto polyvinyl chloride respiratory catheter which showed high antibacterial activity, inhibit the biofilm formation and also prevent bacterial adhesion. Therefore, the developed coating material on respiratory catheter surface is effective way to control the respiratory catheter-associated nosocomial infections.

Amphotericin B and anidulafungin are widely used antifungal drugs for the treatment of systemic and serious mycoses. Amphotericin B is a relatively toxic drug which has long been established. This study is first of its kind to systematically investigate the nature of binding to DNA, and to evaluate intercalation of AMP-B or ANIDULA with the aid of UV-Vis, ITC, and CD spectroscopy. The binding affinity of AMP-B with exclusion sites of 4.68 base pairs (1.2 × 10(5) M(-1)) was found to be higher than that of ANIDULA with exclusion sites of 6.67 base pairs (3.78 × 10(4) M(-1)); consistent with the binding affinity values obtained for AMP-B (10(5) M(-1)) and ANIDULA (10(4) M(-1)). The binding of two drugs with double-stranded DNA was favoured by negative enthalpy as well as negative entropy changes. The intercalation of drugs to duplex polynucleotide induced changes in the intrinsic CD spectra and revealed comparatively higher affinity towards AMP-B than ANIDULA. Molecular docking studies revealed that the negative binding energy was higher in the case of AMP-B reflecting more affinity towards single-stranded DNA. The results of the cytotoxicity, immunoblotting, and gene specific LA-QPCR assay have indicated that ANIDULA is less genotoxic than AMP-B. Hence, the superiority of ANIDULA over AMP-B as a systemic antifungal drug has been established beyond doubt.

A novel antibacterial ointment using bacitracin, specific for Gram-positive bacteria, and gramicidin S, a highly toxic antibacterial peptide, was here developed showing broad-spectrum antibacterial activities against pathogenic strains with less toxicity after self-assembly into nanofiber structures. Such structures were confirmed with scanning electron microscopy and CD analyses. In addition, in silico studies using docking associated with molecular dynamics were carried out to obtain information about fiber structural oligomerization. Thus, the bacitracin and gramicidin S-based self-assembled nanopeptide ribbon may be a successful ointment formulation for bacterial infection control.

Effects of glucose on the susceptibility of antifungal agents were investigated against Candida spp. Increasing the concentration of glucose decreased the activity of antifungal agents; voriconazole was the most affected drugs followed by amphotericin B. No significant change has been observed for anidulafungin. Biophysical interactions between antifungal agents with glucose molecules were investigated using isothermal titration calorimetry, Fourier transform infrared, and (1)H NMR. Glucose has a higher affinity to bind with voriconazole by hydrogen bonding and decrease the susceptibility of antifungal agents during chemotherapy. In addition to confirming the results observed in vitro, theoretical docking studies demonstrated that voriconazole presented three important hydrogen bonds and amphotericin B presented two hydrogen bonds that stabilized the glucose. In vivo results also suggest that the physiologically relevant higher glucose level in the bloodstream of diabetes mellitus mice might interact with the available selective agents during antifungal therapy, thus decreasing glucose activity by complex formation. Thus, proper selection of drugs for diabetes mellitus patients is important to control infectious diseases., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

Cardanol is a non-isoprenoic phenolic lipid-mixture of distilled cashew nut shell liquid obtained from Anacardium occidentale. Herein, cardanol is purified from cashew nut shell liquid (CNSL) and synthesized to new compounds with different azo amphiphiles. These synthesized compounds are allowed to self-assembled in hydrophobic environment and checked antifungal activity against Candida albicans. Self-assembled structure of CABA showed higher antifungal activity (16μg/mL) and chitin-binding ability in comparison to CAP and CANB. Furthermore, the self-assembled azo amphiphiles are immobilized with silver ions to prepare hydrogel which showed eight folds enhanced antifungal activity. Toxicity is reduced by several folds of self-assembled or hydrogel structure in comparison to pure compounds. Thus, the self-assembled structure of amphiphiles and their hydrogels have been found to be new macromolecules of interest with potential use as antifungal drugs., (Copyright © 2014 Elsevier B.V. All rights reserved.)

An antifungal lipopeptide fengycin, producing strain SM1 was isolated from farm land soil sample and identified as Bacillus thuringiensis strain SM1 by using 16S rDNA analysis. Fengycin detected in the culture extract was further purified using HPLC and showed a molecular mass of 1492.8 Da by MALDI-TOF-MS analysis. Purified fengycin was allowed to construct their self-assembled structure onto a hydrophobic surface showing a clear improvement of antibacterial activity. In self-assembly, fengycin adapts a spherical micelle core shell like structure. Self-assembled fengycin may be a successful antimicrobial compound modifying its action from confined antifungal function. Besides it can open up a new area of research in supramolecular lipopeptide based compound making. This can revealed the mode of action of this unique self-assembled structure to fully evaluate its potential for use as an antimicrobial drug to control the emergence of bacterial infection.

Poly (vinyl) alcohol stabilized aqueous ferrofluids (PVA-ff) were used as nanotemplates for the crystallization of calcium hydroxyapatite (HAp). Four sets of PVA-ff-HAp nanocomposites were synthesized using 20, 40, 60 and 80 ml of PVA-ff for the same initial constituents of HAp. Various physico-chemical analyses suggest that the HAp lattice structure accommodates PVA-ff to a certain extent, beyond which the magnetic intra-molecular interactions predominate and PVA-ff starts to be pushed out of the HAp matrix. The in situ incorporation of PVA-ff during HAp synthesis results in a novel magnetic biomaterial with potential applications as targeted delivery vehicles.

A connectionist model along with its state dynamics is developed for detecting corner points in binary and gray images. For a given binary/gray image, each pixel in the image is assigned with some initial cornerity (our measurable quantity) which is a vector representing the direction and strength of the corner. These cornerities are then mapped onto a neural-network model which is essentially designed as a cooperative computational framework. The cornerity at each pixel is updated depending on the neighborhood information. After the network dynamics settles to stable state, the dominant points are obtained by finding out the local maxima in the cornerities. Theoretical investigations are made to ensure the stability and convergence of the network. It is found that the network is able to detect corner points even in the noisy images and for open object boundaries. The dynamics of the network is extended to accept the edge information from gray images also. The effectiveness of the model is experimentally demonstrated in synthetic and real-life binary and gray images.