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We establish some coupled coincidence and coupled common fixed point theorems for the mixed g-monotone mappings satisfying [InlineEquation not available: see fulltext.]-contractive conditions in the setting of ordered generalized metric spaces. Presented theorems extend and generalize the very recent results of Choudhury and Maity (Math. Comput. Model. 54(1-2):73-79, 2011). To illustrate our results, an example and an application to integral equations have also been given. MSC: 54H10, 54H25. [ABSTRACT FROM AUTHOR]

The aim of this paper is to extend the notions of E.A. property and CLRg property for coupled mappings and use these notions to generalize the recent results of Xin-Qi Hu (2011). The main result is supported by a suitable example. [ABSTRACT FROM AUTHOR]

Diagnosing extra-pulmonary tuberculosis is a challenge that can confound even the most practiced clinicians as clinical manifestations are vague, non-specific and typical chest radiograph findings may not be evident till late in the disease. Conventional methods for mycobacteriological culture and drug susceptibility testing are slow and cumbersome. Novel technologies for rapid detection of Mycobacterium tuberculosis and its anti-TB drug resistance have therefore become a priority hence with the development of molecular line probe assays are most advanced. Herewith we are reporting a case of splenic tuberculosis in an immunocompromised patient for its rarity and to emphasis the fact that such patients can be diagnosed early for better treatment outcome to enhance the longevity if a health setup possesses all the modern diagnostic services. [ABSTRACT FROM AUTHOR]

Background: Chromoblastomycosis is a non-contagious, chronic localized fungal infection of cutaneous and sub-cutaneous tissues caused by several species of phaeoid (ie. Dematiaceous) fungi. It usually known to occur following trauma with wood splinters and usually occurs on the hands, feet and legs. Diagnosis can be made by direct microscopic demonstration of pathognomic brown sclerotic cells in skin scrapings and a positive fungal culture, confirms the same. Case Presentation: A 40-years old male presented with complaints of slowly spreading raised hyperpigmented lesions, three in number over right side of face and solitary plaque over lip with mild scaling from last six months and it was not associated with itching. Patient did not have any history of injury over the face with wooden splinters. The patient was initially suspected to have Lichen planus and was treated accordingly. But condition of the patients did not improve. He was then sent for Microbiological diagnosis. Laboratory Diagnosis: The diagnosis of Chromoblastomycosis was made by demonstration of sclerotic bodies with transverse septa arranged in cluster on KOH examination. Isolation of Fonsecaea pedrosii on SDA confirmed Chromoblastomycosis. Conclusion: Although Chromoblastomycosis is very rare on the face, our case demonstrates the need for consideration of Chromoblastomycosis in the differential diagnosis of resistant verrucous plaques of the face. We report an unusual case of Chromoblastomycosis for the first time from the state of Maharashtra and probably second case from India. [ABSTRACT FROM AUTHOR]

Background and Objectives: Methicillin resistance is acquired by the bacterium due to mecA gene which codes for penicillin-binding protein (PBP2a) having low affinity for ß-lactam antibiotics. mecA gene is located on a mobile genetic element called staphylococcal cassette chromosome mec (SCCmec). SCCmec genomic island comprises two site-specific recombinase genes namely ccrA and ccrB [cassette chromosome recombinase] accountable for mobility. Currently, SCCmec elements are classified into types I, II, III, IV and V based on the nature of the mec and ccr gene complexes and are further classified into subtypes according to variances in their J region DNA. SSCmec type IV has been found in community-acquired isolates with various genetic backgrounds. The present study was undertaken to categorize the types of SCCmec types and subtypes I, II, III, IVa, b, c, d, and V and PVL genes among clinical MRSA isolates from COVID-19 confirmed cases. Materials and Methods: Based on the Microbiological and Molecular (mecA gene PCR amplification) confirmation of MRSA isolated from 500 MRSA SCCmec clinical samples, 144 cultures were selected for multiplex analysis. The multiplex PCR method developed by Zhang et al. was adapted with some experimental alterations to determine the specific type of these isolates. Results: Of the total 500 MRSA, 144 MRSA (60 were CA-MRSA and 84 were HA-MRSA) were selected for characterization of novel multiplex PCR assay for SSCmec Types I to V in MRSA. Molecular characterization of multiplex PCR analysis revealed results compare to the phenotypic results. Of the 60 CA-MRSA; in 56 MRSA strains type IVa was found and significantly defined as CA-MRSA while 4 strains showed mixed gens subtypes. Type II, III, IA, and V were present in overall 84 HA-MRSA. Molecular subtyping was significantly correlated to define molecularly as CA-MRSA and HA-MRSA however 15 (10%) strains showed mixed genes which indicates the alarming finding of changing epidemiology of CA-MRSA and HA-MRSA as well. Conclusion: We have all witnessed of COVID-19 pandemic, and its mortality was mostly associated with co-morbid conditions and secondary infections of MDR pathogens. Rapid detections of causative agents of these superbugs with their changing epidemiology by investing in typing and subtyping clones are obligatory. We have described an assay designed for targeting SSCmec types and subtypes I, II, III, IVa, V according to the current updated SCCmec typing system. Changing patterns of molecular epidemiology has been observed by this newly described assay. [ABSTRACT FROM AUTHOR]

Introduction: Ultrasound measurement of Inferior Vena Cava (IVC) diameter and collapsibility is increasingly used for volume status assessment and fluid responsiveness in paediatric and adult population. There is a wide variation in the age specific IVC diameters in paediatric population, whereas age specific variation in IVC collapsibility in euvolaemic children is not much known. Aim: To analyse the correlation of baseline IVC diameter and collapsibility with age and sex in euvolaemic children. Materials and Methods: This cross-sectional study was conducted at Kerala Institute of Medical Sciences, a tertiary care hospital in south Kerala, India, over a study period from June 2014 to May 2016. A total of 80 children in the age group of one month to 15 years, who presented without evidence of volume depletion were enrolled. The IVC was assessed approximately 2 cm distal to IVC-hepatic vein junction, Motion mode (M-mode) measurement of maximum (expiratory) and minimum (inspiratory) width of IVC diameter was measured. Collapsibility Index was also calculated for each subject by measuring difference between the maximum and minimum IVC diameters divided by the maximum diameter. The statistical data was analysed using the statistical software Statistical Package for Social Sciences (SPSS) version 16. All the numerical data was expressed as mean±Standard Deviation (SD). Quantitative analysis was performed using Analysis of Variance (ANOVA) and t-test. The correlation of IVC parameters were assessed using Karl Pearson correlation coefficient. The p-value less than 0.05 was considered as significant. Results: Eighty euvolaemic children between the age one month and 15 years were enrolled in the study. The mean age of study group was 5±4 years. Males 41 (51.3%) and females 39 (48.8%) were almost equally distributed. A significant strong positive correlation was found between IVC expiratory and inspiratory diameter with age using Karl Pearson correlation, r= 0.912, p<0.001; r=0.876, p<0.001, respectively. No significant correlation was found between IVC collapsibility and age, Karl Pearson correlation, r=0.079, p=0.485. No correlation was found between sex and the IVC parameters. Conclusion: According to the present study results, IVC diameter showed a positive correlation with age but not with sex. The IVC collapsibility had no correlation with either age or sex. [ABSTRACT FROM AUTHOR]

Introduction: Modalities like Bispectral Index Monitoring (BIS) and End Tidal Anaesthetic Gas (ETAG) concentration guided anaesthesia have been used to study the intraoperative awareness but their efficacy for achieving early tracheal extubation has not been established. Aim: To compare the effect of BIS monitoring and ETAG concentration guided anaesthesia on time to tracheal extubation and haemodynamics for isoflurane based general anaesthesia. Materials and Methods: This prospective observational cohort study was conducted in the Department of Anaesthesiology at Mahatma Gandhi Memorial Government Medical College and MY Hospital, Indore, Madhya Pradesh, India, from June 2020 to June 2021. Total 60 patients with American Society of Anesthesiologists (ASA) status I and II who received isoflurane based general anaesthesia were included in study. Depending upon the modality being used by the anaesthesiologist to monitor and maintain the depth of anaesthesia, the patients were allocated in equal numbers into two group. Group B received BIS guided anaesthesia, where BIS value was kept between 40 and 60 and group E received ETAG concentration guided anaesthesia, where Minimum Alveolar Concentration (MAC) was kept between 0.7 to 1.3. Tracheal extubation time was recorded from stopping all anaesthetic agents upto the time of extubation. Unpaired t-test was applied for analysis of data. Results: The mean tracheal extubation time was significantly longer in the BIS group (21.14±2.23 minutes) as compared to ETAG group (15.20±1.27 minutes). All hemodynamic parameters i.e., pulse rate, mean arterial pressure and saturation remained within normal limits and were comparable between the two groups at all the time intervals. Conclusion: The tracheal extubation time is significantly longer in BIS guided anaesthesia as compared to ETAG guided anaesthesia. The ETAG monitoring promotes earlier extubation of patients as compared to BIS monitoring in isoflurane based general anaesthesia. [ABSTRACT FROM AUTHOR]

Introduction: Tobacco smoking is a worldwide accepted health hazard and its effect on cardiopulmonary system is a wellknown fact. In a long run, it results in to gross derangements in haemodynamics and arterial blood gases which can lead to further complications during general anaesthesia. Aim: To evaluate the effect of smoking on cardiopulmonary system, and also to compare its effects on haemodynamics and arterial blood gases during general anaesthesia for abdominal surgeries in smokers and non smokers. Materials and Methods: This analytical study was conducted in the Department of Anaesthesiology, Mahatma Gandhi Memorial Medical Colledge, Indore, Madhya Pradesh, India, from May 2020 to April 2021. The study included 74 male patients of American Society of Anaesthesiologist (ASA) grade I and II, aged 20-70 years, undergoing elective abdominal surgeries. The patients were divided into two groups, smokers and non smokers, depending on their smoking status. Haemodynamic monitoring was done from preinduction time till 48 hours after extubation, and arterial blood gas analysis was also done before induction and 2 hours after extubation in both the groups. T-test and Mann-whitney test were applied according to the requirement. A p-value < 0.05 was taken as statistically significant. The statistical software Statistical Package for Social Sciences (SPSS) version 20.0 and Medcalc 19.5 were used for the analysis. Results: Significant increase in Heart Rate (HR) and Mean Arterial Pressure (MAP) was observed in smokers as compared to non smokers at all time intervals (p-value<0.001). End-tidal carbon dioxide concentration (EtCO2) values were found to be significantly higher in smokers (37.77±2.63 mmHg) than non smokers (32.99±2.83 mmHg) (p-value<0.001). Regarding arterial blood gas analysis significant difference was observed in preoperative and postoperative arterial carbon dioxide concentration (PaCO2) (p-value<0.0001), and pH levels (p-value<0.0001) in both the groups. A significant difference was also seen in preoperative and postoperative PaCO2 levels of the smokers (p-value= 0.0004) with a corresponding change in their pH levels also (p-value=0.0012). Peak Expiratory Flow Rate (PEFR) was lower in smokers in comparison to non smokers (p-value<0.0001). Conclusion: Smoking has significant effects on haemodynamic status and arterial blood gases of smokers which can be aggravated during general anaesthesia. [ABSTRACT FROM AUTHOR]

Among intensive care unit patients, lower respiratory tract infections (LRTI) are one of the most common infections to occur. The aim of this study was to determine the microbiological profile and antibiogram of pathogens isolated from tracheal secretions. Place of study. Dr. D. Y. Patil Medical college; Type of study - Retrospective study and cross-sectional study; Study period-April 2020 to September 2020 (6 months).152 isolates from non-repeated samples received for culture and sensitivity were considered for the study. Sample -Tracheal secretions. The sample was processed on blood and MacConkey's agar, identification done by standard biochemical tests, and antibiotic sensitivity was performed by disk diffusion (Kirby-Bauer test) method on Muller Hinton agar According to CLSI 2020 guidelines. Total-152 tracheal aspirates; Positive samples-148. The most commonly reported among the isolates was Klebsiella pneumoniae 51, (64.7%) followed by Acinetobacter Spp 45(30.40%) and Pseudomonas 37(25%). Alarming rate of resistance was seen in gram-negative isolates in tracheal secretions to carbapenems but good sensitivity was seen in tigecycline and colistin both. So, with a lack of new antibiotics, the current scenario presents a major threat in dealing with these pathogens in the future. [ABSTRACT FROM AUTHOR]

We investigated the function of the newly discovered myosin family protein myosin 18A (Myo18A) in Ab-mediated immunity by generating B cell-conditional Myo18Adeficient mice. Myo18A deficiency led to expansion of bone marrow progenitor B cells and mature B cells in secondary lymphoid organs. Myo18A-deficient mice displayed serum IgM hyperglobulinemia and increased splenic IgM-secreting cells, with older mice switching to IgG1 hyperglobulinemia and autoantibody development. Immunization of Myo18A-deficient mice with inactivated influenza virus led to development of more potent neutralizing Abs against the major Ag hemagglutinin, associated with persistent accumulation of Ag-specific germinal center B cells and more Ag-specific bone marrow plasma cells. In vitro stimulation with TLR7 and BCR ligands revealed a greater ability of Myo18A-deficient B cells to differentiate into Ab-secreting cells, associated with higher AID and Blimp-1 expression. Overall, our study demonstrates that Myo18A is a novel negative regulator of B cell homeostasis, differentiation, and humoral immunity. [ABSTRACT FROM AUTHOR]

Intermediate and high-risk rhabdomyosarcoma (RMS) patients have poor prognosis with available treatment options, highlighting a clear unmet need for identification of novel therapeutic strategies. Ezrin-radixin-moesin (ERM) family members are membrane-cytoskeleton linker proteins with well-defined roles in tumor metastasis, growth, and survival. ERM protein activity is regulated by dynamic changes in the phosphorylation at a conserved threonine residue in their C-terminal actin-binding domain. Interestingly, ERM family member, ezrin, has elevated expression in the RMS tissue. Despite this, the translational scope of targeting ERM family proteins in these tumors through pharmacological inhibition has never been considered. This study investigates the inhibition of ERM phosphorylation using a small molecule pharmacophore NSC668394 as a potential strategy against RMS. Upon in vitro treatment with NSC668394, RMS cells exhibit a dose-dependent decrease in cell viability and proliferation, with induction of caspase-3 cleavage and apoptosis. siRNA-mediated knockdown of individual ERM protein expression revealed that each regulates RMS survival to a different degree. In vivo administration of NSC668394 in RMS xenografts causes significant decrease in tumor growth, with no adverse effect on body weight. Collectively, this study highlights the importance of the active conformation of ERM proteins in RMS progression and survival and supports pharmacologic inhibition of these proteins as a novel therapeutic approach. [ABSTRACT FROM AUTHOR]

Intestinal ischemia/reperfusion (I/R) injury is a relatively common pathological condition that can lead to multi-organ failure and mortality. Regulatory mechanism for this disease is poorly understood, although it is established that circulating pathogenic natural IgM, which is primarily produced by B1a cells outside of the peritoneal cavity, are integrally involved. CD6 was originally identified as a marker for T cells and was later found to be present on some subsets of B cells in humans; however, whether CD6 plays any role in intestinal I/R-induced injury and, if so, the underlying mechanisms, remain unknown. Here we report that CD6-/- mice were significantly protected from intestinal inflammation and mucosal damage compared with WT mice in a model of intestinal I/R-induced injury. Mechanistically, we found that CD6 was selectively expressed on B1 cells outside of the bone marrow and peritoneal cavity and that pathogenic natural IgM titers were reduced in the CD6-/- mice in association with significantly decreased B1a cell population. Our results reveal an unexpected role of CD6 in the pathogenesis of intestinal IR-induced injury by regulating the self-renewal of B1a cells. [ABSTRACT FROM AUTHOR]

Ezrin, an actin-binding protein, orchestrates the organization of the cortical cytoskeleton and plasma membrane during cell migration, adhesion, and proliferation. Its role in monocytes/macrophages (MΦs) is less understood. Here, we used a monocyte/MΦ-specific ezrin knock-out mouse model to investigate the contribution of ezrin to monocyte recruitment and adaptation to the lung extracellular matrix (ECM) in response to lipopolysaccharide (LPS). Our study revealed that LPS induces ezrin expression in monocytes/MΦs and is essential for monocytes to adhere to lung ECM, proliferate, and differentiate into tissue-resident interstitial MΦs. Mechanistically, the loss of ezrin in monocytes disrupts activation of focal adhesion kinase and AKT serine-threonine protein kinase signaling, essential for lung-recruited monocytes and monocyte-derived MΦs to adhere to the ECM, proliferate, and survive. In summary, our data show that ezrin plays a role beyond structural cellular support, influencing diverse monocytes/MΦ processes and signaling pathways during inflammation, facilitating their differentiation into tissue-resident macrophages., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval: The ethical approval for animal study was obtained from the Yale University Institutional Animal Care and Use Committee (IACUC protocol number to EMB 10680.3). The institution has an approved Animal Welfare Assurance (D16-00146) on file with the Office of Laboratory Animal Welfare. All methods were performed in accordance with relevant guidelines and regulations. Inclusion and diversity: We support inclusive, diverse, and equitable conduct of research., (© 2024. The Author(s).)

Acinetobacter baumannii and Enterococcus faecalis are opportunistic bacteria frequently associated with hospital-acquired infections. A. baumannii nosocomial infections in intensive care units are a worldwide problem, with high mortality rates. It may also develop rapidly multidrug resistance (MDR), extensive drug resistance (XDR), and even pan-drug resistance (PDR). Colistin resistance which is an example of pan-drug resistance, is highly alarming as it's used as a last-line antibiotic. Microbes capable of crossing epithelial barriers such as E. faecalis have developed novel strategies to counter antimicrobial agents and cause bacteremia in immunocompromised patients. However, the coinfection of these bacteria in the same patient is unusual. Here, we report a genomic investigation of the extensively drug-resistant E. faecalis and A. baumannii isolated from the blood sample of a patient diagnosed with pauci-immune crescentic glomerulonephritis (PICGN). Identification of cultures isolated from blood sample was carried out using whole-genome sequencing and resistome profiles were mapped. Whole genome sequencing revealed that E. faecalis SVJ-EF01 had a genome size of 2,935,226 bp and GC content of 37.4%, whereas A. baumannii SVJ-AC01 had a genome size of 3,730,857 bp and GC content of 39%. Draft genomes were functionally annotated demonstrating that the organism harbors multiple virulence factors and antimicrobial-resistant mechanisms including MDR efflux pumps. A. baumannii genome possessed a CRISPR-Cas system which might contribute to antimicrobial resistance. This highlights the significance of polymicrobial nature in ESKAPE pathogenesis research. This genomic investigation helps to gain insights into the virulence, resistance profile, and functional potential of these pathogens., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest. Ethical Approval: This article did not require any ethical approval., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To describe the utility of film array meningoencephalitis (FAME) panel in the management of children with acute encephalitis syndrome (AES)., Methods: A retrospective audit was conducted between January 2017 to July 2022. We included children aged < 18 years with a diagnosis of AES for whom a CSF analysis study including FAME panel testing performed within 48 hours of admission was available. Electronic medical records were reviewed for details including demographic profile, clinical presentation, investigations and outcome., Results: Out of 157 CSF samples sent for FAME panel testing, 49 were positive (31.4%.) Viral pathogens were identified in 42 (Enterovirus: 31, Human herpes virus 6: 9, Varicella zoster virus: 1, and Cytomegalovirus: 1) Bacterial pathogens were identified in 6 (Streptococcus pneumoniae: 2, Streptococcus agalactiae: 2, Hemophilus influenzae: 1, and Escherischia coli: 1). Fungal etiology (Cryptococcus neoformans) was detected in one child. Antibiotics could be stopped within 72 hours of initiation in 42 children in whom a viral etiology was established. Acyclovir could be stopped in 21 out of 32 children within 72 hours after the FAME panel testing. FAME panel was presumed to be false positive in 4 children., Conclusion: Etiology of AES could be established in nearly a third of children with AES using the rapid diagnostic FAME panel testing in CSF and it was found to be effective in reducing empirical antibiotic/antiviral therapy.

Follicular regulatory T cells (Tfr) can play opposite roles in the regulation of germinal center (GC) responses. Depending on the studies, Tfr suppress or support GC and B cell affinity maturation. However, which factors determine positive vs. negative effects of Tfr on the GC B cell is unclear. In this study, we show that GC centrocytes that express MYC up-regulate expression of CCL3 chemokine that is needed for both the positive and negative regulation of GC B cells by Tfr. B cell-intrinsic expression of CCL3 contributes to Tfr-dependent positive selection of foreign Ag-specific GC B cells. At the same time, expression of CCL3 is critical for direct Tfr-mediated suppression of GC B cells that acquire cognate to Tfr nuclear proteins. Our study suggests that CCR5 and CCR1 receptors promote Tfr migration to CCL3 and highlights Ccr5 expression on the Tfr subset that expresses Il10 . Based on our findings and previous studies, we suggest a model of chemotactically targeted checkpoint control of B cells undergoing positive selection in GCs by Tfr, where Tfr directly probe and license foreign antigen-specific B cells to complete their positive selection in GCs but, at the same time, suppress GC B cells that present self-antigens cognate to Tfr., Competing Interests: Competing interests statement:The authors declare no competing interest.

Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is a highly effective treatment option for patients with relapsed/refractory large B-cell lymphoma. However, widespread use is deterred by the development of clinically significant acute inflammatory toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), that induce significant morbidity and require close monitoring. Identification of host biochemical signatures that predict the severity and time-to-onset of CRS and ICANS may assist patient stratification to enable timely mitigation strategies. Here, we report pretreatment host metabolites that are associated with CRS and ICANS induced by axicabtagene ciloleucel or tisagenlecleucel therapy. Both untargeted metabolomics analysis and validation using targeted assays revealed a significant association between the abundance of specific pretreatment biochemical entities and an increased risk and/or onset of clinically significant CRS (q < .1) and ICANS (q < .25). Higher pretreatment levels of plasma glucose and lower levels of cholesterol and glutamate were associated with a faster onset of CRS. In contrast, low baseline levels of the amino acids proline and glycine and the secondary bile acid isoursodeoxycholate were significantly correlated with clinically significant CRS. Lower concentration of the amino acid hydroxyproline was associated with higher grade and faster onset of ICANS, whereas low glutamine was negatively correlated with faster development of ICANS. Overall, our data indicate that the pretreatment host metabolome has biomarker potential in determining the risk of clinically significant CRS and ICANS, and may be useful in risk stratification of patients before anti-CD19 CAR T-cell therapy., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background and Objectives: Methicillin resistance is acquired by the bacterium due to mecA gene which codes for penicillin-binding protein (PBP2a) having low affinity for β-lactam antibiotics. mecA gene is located on a mobile genetic element called staphylococcal cassette chromosome mec (SCC mec ). SCC mec genomic island comprises two site-specific recombinase genes namely ccrA and ccrB [cassette chromosome recombinase] accountable for mobility. Currently, SCC mec elements are classified into types I, II, III, IV and V based on the nature of the mec and ccr gene complexes and are further classified into subtypes according to variances in their J region DNA. SSC mec type IV has been found in community-acquired isolates with various genetic backgrounds. The present study was undertaken to categorize the types of SCC mec types and subtypes I, II, III, IVa, b, c, d, and V and PVL genes among clinical MRSA isolates from COVID-19 confirmed cases., Materials and Methods: Based on the Microbiological and Molecular ( mecA gene PCR amplification) confirmation of MRSA isolated from 500 MRSA SCC mec clinical samples, 144 cultures were selected for multiplex analysis. The multiplex PCR method developed by Zhang et al. was adapted with some experimental alterations to determine the specific type of these isolates., Results: Of the total 500 MRSA, 144 MRSA (60 were CA-MRSA and 84 were HA-MRSA) were selected for characterization of novel multiplex PCR assay for SSC mec Types I to V in MRSA. Molecular characterization of multiplex PCR analysis revealed results compare to the phenotypic results. Of the 60 CA-MRSA; in 56 MRSA strains type IVa was found and significantly defined as CA-MRSA while 4 strains showed mixed gens subtypes. Type II, III, IA, and V were present in overall 84 HA-MRSA. Molecular subtyping was significantly correlated to define molecularly as CA-MRSA and HA-MRSA however 15 (10%) strains showed mixed genes which indicates the alarming finding of changing epidemiology of CA-MRSA and HA-MRSA as well., Conclusion: We have all witnessed of COVID-19 pandemic, and its mortality was mostly associated with co-morbid conditions and secondary infections of MDR pathogens. Rapid detections of causative agents of these superbugs with their changing epidemiology by investing in typing and subtyping clones are obligatory. We have described an assay designed for targeting SSC mec types and subtypes I, II, III, IVa,V according to the current updated SCC mec typing system. Changing patterns of molecular epidemiology has been observed by this newly described assay., (Copyright © 2023 The Authors. Published by Tehran University of Medical Sciences.)

Carbapenemases are β-lactamase enzymes that hydrolyze a variety of β-lactams including carbapenem and belong to different Ambler classes (A, B, D). These enzymes can be encoded by plasmid or chromosomal-mediated genes. The major issues associated with carbapenemases-producing organisms are compromising the activity and increasing the resistance to carbapenems which are the last resort antibiotics used in treating serious infections. The global increase of pathogen, carbapenem-resistant A. baumannii has significantly threatened public health. Thus, there is a pressing need for a better understanding of this pathogen, to know the various carbapenem resistance encoding genes and dissemination of resistance genes from A. baumannii which help in developing strategies to overcome this problem. The horizontal transfer of resistant determinants through mobile genetic elements increases the incidence of multidrug, extensive drug, and Pan-drug resistant A. baumannii . Therefore, the current review aims to know the various mechanisms of carbapenem resistance, categorize and discuss carbapenemases encoding genes and various mobile genetic elements, and the prevalence of carbapenemase genes in recent years in A. baumannii from various geographical regions., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Gupta et al.)

Genome-level rearrangements of Ig genes during B cell development are critical for generation of a diverse repertoire of BCRs that bind to a multitude of foreign Ags and some self Ags. Bone marrow B cell development involves a variety of cell-cell interactions, cell migration, and receptor signaling that likely benefit from the activity of membrane-cytoskeletal reorganizing proteins. However, the specific contribution of such proteins toward BCR repertoire diversification is poorly understood. Ezrin is a membrane-cytoskeletal linker protein that regulates mature B cell activation through spatial organization of the BCR. We employed next-generation sequencing to investigate whether Ezrin plays a role in IgH rearrangements and generation of BCR diversity in developing bone marrow B cells. BCR repertoire development occurred stochastically in B cell progenitors from both control and B cell conditional Ezrin-deficient mice. However, the loss of Ezrin resulted in fewer unique CDRs (CDR3s) in the BCRs and reduced Shannon entropy. Ezrin-deficient pre-B cells revealed similar utilization of joining (J) genes but significantly fewer variable (V) genes, thereby decreasing V-J combinatorial diversity. V-J junctional diversity, measured by CDR3 length and nucleotide additions and deletions, was not altered in Ezrin-deficient pre-B cells. Mechanistically, Ezrin-deficient cells showed a marked decrease in RAG1 gene expression, indicating a less efficient DNA recombination machinery. Overall, our results demonstrate that Ezrin shapes the BCR repertoire through combinatorial diversification., (Copyright © 2022 The Authors.)

In response to microbes and other danger signals, the NLRP3 inflammasome in immune cells triggers the activation of the protease caspase-1, which mediates the maturation of the inflammatory cytokine IL-1β. Here, we investigated how the NLRP3 inflammasome is regulated. We found that its activation in primary mouse macrophages induced the Src family kinase Lyn to phosphorylate NLRP3 at Tyr 918 , which correlated with a subsequent increase in its ubiquitination that facilitated its proteasome-mediated degradation. NLRP3 tyrosine phosphorylation and ubiquitination was abrogated in Lyn-deficient macrophages, which produced increased amounts of IL-1β. Furthermore, mice lacking Lyn were more susceptible to LPS-induced septic shock in an NLRP3-dependent manner. Our data demonstrate that Lyn-mediated tyrosine phosphorylation is a prerequisite for the ubiquitination that dampens NLRP3 inflammasome activity.

Background  Evaluating the expression pattern of oxacillinases (OXA) carbapenemases is essential to understand the prevalence and spread of carbapenem resistance Acinetobacter baumannii . Objectives  The aim of the study is to evaluate the presence of OXA carbapenemase genes and IS Aba1 upstream to these genes in carbapenem-resistant A. baumannii clinical isolates. Materials and Methods   A. baumannii isolated from clinical samples were phenotypically identified and antibiotics sensitivity was performed. Multiplex polymerase chain reaction (PCR) was used to detect OXA51-like gene, OXA carbapenemases genes (OXA-23-like, OXA-24-like, and OXA-58-like), and IS Aba1 in carbapenem-resistant isolates. Results  Out of 55 Acinetobacter isolates, 54 were confirmed as A. baumannii by PCR. Bla OXA-23 -like gene was observed in 51 isolates of A. baumannii and none of the isolates showed the presence of bla OXA-24 -like and bla OXA-58 -like genes. Presence of IS Aba1 upstream to OXA-23-like gene, OXA-51-like gene, and both OXA-51-like/OXA-23-like genes was observed in 51, 7, and 4 A. baumannii isolates, respectively. Conclusion  The genetic pattern of carbapenem-resistant A. baumannii isolated in this study was unique, which should be factored for clinical protocols to manage infections caused by emerging resistant strains of A. baumannii ., Competing Interests: Conflict of Interest None declared., (The Indian Association of Laboratory Physicians. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Medical countermeasures to treat biothreat agent infections require broad-spectrum therapeutics that do not induce agent resistance. A cell-based high-throughput screen (HTS) against ricin toxin combined with hit optimization allowed selection of a family of compounds that meet these requirements. The hit compound Retro-2 and its derivatives have been demonstrated to be safe in vivo in mice even at high doses. Moreover, Retro-2 is an inhibitor of retrograde transport that affects syntaxin-5-dependent toxins and pathogens. As a consequence, it has a broad-spectrum activity that has been demonstrated both in vitro and in vivo against ricin, Shiga toxin-producing O104:H4 entero-hemorrhagic E. coli and Leishmania sp. and in vitro against Ebola, Marburg and poxviruses and Chlamydiales. An effect is anticipated on other toxins or pathogens that use retrograde trafficking and syntaxin-5. Since Retro-2 targets cell components of the host and not directly the pathogen, no selection of resistant pathogens is expected. These lead compounds need now to be developed as drugs for human use., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Lymphocyte activation and migration involve large-scale actin cytoskeletal remodeling. The Ezrin-Radixin-Moesin (ERM) family proteins reversibly link the plasma membrane and cortical actin meshwork and mediate the dynamic nature of the membrane-cytoskeletal interface to facilitate remodeling. The reversibility of this linkage is controlled by the conformation of ERM proteins and depends on the phosphorylation of a conserved threonine residue in the actin-binding domain. Disruption of the phospho-cycling nature of ERM proteins through dominant negative and constitutively active mutants results in impaired lymphocyte migration and activation. In recent years, a novel role has emerged for ERM proteins as signaling scaffolds that can modulate B and T-cell activation through additional posttranslational modifications at tyrosine residues. Here, we highlight recent studies that have redefined the role of ERM proteins in lymphocyte activation and migration. We discuss how lymphocyte-specific knockouts of ERM proteins and high resolution imaging techniques have identified a novel function for them as rheostats that modulate the strength of antigen receptor signaling in B cells. Finally, we describe scenarios in which ERM protein function is coopted by pathogens for their own transmission and speculate on the potential of ERM proteins for regulating undesirable lymphocyte behaviors such as autoimmunity and malignancy., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Pterostilbene, a dimethyl ester derivative of resveratrol, may act as an cytotoxic and hence as an anti-cancer agent. The present study was conducted to test the anti-cancer activity of pterostilbene purified from Pterocarpus marsupium on breast (MCF-7) and prostate (PC3) cancer cell lines. The purified pterostilbene was found to cause apoptosis in both the cell lines, which was marked by DNA fragmentation, formation of apoptotic bodies and membrane distortions. Apoptosis probably was due to the production of reactive oxygen species in MCF-7 and nitric oxide over production in PC3 cells. Even the drug detoxifying anti-oxidant enzymes could not nullify the effect of pterostilbene as required by the cancer cells for survival. Pterostilbene was found to inhibit the cell proliferating factors like Akt, Bcl-2 and induced the mitochondrial apoptotic signals like Bax, and the series of caspases. It also inhibited Matrix metalloproteinase 9 (MMP9) and alpha-methylacyl-CoA recemase (AMACR), two very well known metastasis inducers. In conclusion, pterostilbene has multiple target sites to induce apoptosis. Hence, after proper validation it can be used as a potential agent for the cure of breast and prostate cancer., (Copyright 2010 Elsevier Ltd. All rights reserved.)

B cells comprise an essential component of the humoral immune system. They are equipped with the unique ability to synthesize and secrete pathogen-neutralizing antibodies, and share with professional antigen presenting cells the ability to internalize foreign antigens, and process them for presentation to helper T cells. Recent evidence indicates that specialized cholesterol- and glycosphingolipid-rich microdomains in the plasma membrane commonly referred to as lipid rafts, serve to compartmentalize key signaling molecules during the different stages of B cell activation including B cell antigen receptor (BCR)-initiated signal transduction, endocytosis of BCR-antigen complexes, loading of antigenic peptides onto MHC class II molecules, MHC-II associated antigen presentation to helper T cells, and receipt of helper signals via the CD40 receptor. Here we review the recent literature arguing for a role of lipid rafts in the spatial organization of B cell function.

Bone marrow abnormalities are frequently observed in HIV infected individuals at all stages of the disease. The most common abnormal finding is dysplasia affecting one or more cell lines. Erythroid dysplasia is the most common type of dysplasia and is recognized in over 50% of HIV infected patients, abnormal granulocytic and megakaryocytic development is encountered in one-third of patients. Plasma cells are strikingly increased in bone marrow of HIV infected patients. It may represent a physiological response to antigenic stimulation by viruses, other infective agents or secondary to dysregulated B-cell proliferation due to HIV. Herein we present a review discussing the various bone marrow abnormalities associated with the HIV disease.

Aim: Present work was carried out to study the bone marrow abnormalities in patients with HIV/AIDS and to find their association with peripheral hematological abnormalities., Methods: Seventy four patients of HIV/AIDS were included in the study. The patients had anemia, leucopenia, thrombocytopenia or pyrexia of unknown origin (PUO) as indications for bone marrow examination. A complete blood count, relevant biochemical investigations, HIV RNA load and CD4 positive lymphocyte counts were done, besides a thorough history and clinical examination. HIV positive patients were classified as those having AIDS and those without AIDS according to NACO criteria., Results: Majority of patients (72.9%) had AIDS. Bone marrow was normocellular in 78.95% of non-AIDS and 74.55% of AIDS, hypocellular in 5.26% of non-AIDS and 7.27% of AIDS, hypercellular in 15.79% of non-AIDS and 18.18 % of AIDS patients. Myelodysplasia was present in 21.05% of non AIDS and 36.46% of AIDS and the most common series affected was granulocytic (15.79% of total in non-AIDS and 30.9% in AIDS). Dysplasia was statistically significantly associated with lower CD4 count (p = 0.031) and anemia (p = 0.013). Myelodysplasia was apparent even before patients developed anemia (16.67%). Increased plasma cells in bone marrow were observed in 57.89% of non-AIDS and 65.45% of AIDS, whereas decreased lymphoid cells were seen in 36.84% of non AIDS and 60.00% of AIDS patients., Conclusions: Myelodysplasia is found in 32.43% of cases of HIV/AIDS and is more common in AIDS than in non AIDS patients. Granulocytic series is most commonly associated with evidence of dysplasia. Myelodysplasia is more common in patients with CD4 count < 200/microl and in patients with anemia. 54.05% of patients had decreased lymphoid cells in bone marrow and it was more commonly seen in AIDS than in non AIDS.

Diffuse infiltrative lymphocytic syndrome (DILS), is a rare manifestation of human immunodeficiency virus (HIV) disease which is characterized by a diffuse visceral CD8 lymphocytic infiltration, a persistent CD8 lymphocytosis, bilateral parotid swelling and cervical lymphadenopathy. We describe a case of a HIV positive female, who had bilateral parotid swelling and CD8 lymphocytosis, to illustrate this rare clinical entity.