Regulation of STAT3 signaling in IFNγ and IL10 pathways and in their cross-talk.

The pro-inflammatory IFNγ-STAT1 pathway and anti-inflammatory IL10-STAT3 pathway elicit cellular responses primarily utilizing their canonical STATs. However IL10 mediated STAT1 and IFNγ mediated STAT3 activation is also observed, suggesting crosstalk of these functionally opposing signaling pathways can potentially reshape the canonical dynamics both STATs and alter the expression of their target genes. Herein, we measured the dynamics of STATs in response to different doses of IL10 or IFNγ and in their co-stimulation and employed quantitative modeling to understand the regulatory mechanisms controlling signal responses in individual and co-simulation scenarios. Our experiments show, STAT3 in particular, exhibits a bell-shaped dose-response while treated with IFNγ or IL10 and our model quantiatively captured the dose-dependent dynamics of both the STATs in both pathways. The model next predicted and subsequent experiments validated that STAT3 dynamics would robustly remain IL10 specific when subjected to a co-stimulation of both IFNγ and IL10. Genes common to both pathways also exhibited IL10 specific expression during the co-stimulation. The findings thus uncover anovel feature of the IL10-STAT3 signaling axis during pathway crosstalk. Finally, parameter sampling coupled to information theory based analysis showed that bell-shaped signal-response of STAT3 in both pathways is primarily dependent on receptor concentration whereas robustness of IL10-STAT3 signaling axis in co-stimulation results from the negative regulation of the IFNγ pathway.

Antibiofilm and anti-quorum sensing activities of eugenol and linalool from Ocimum tenuiflorum against Pseudomonas aeruginosa biofilm.

AIMS: The aim of this study is to determine the ability of two bioactive compounds, namely, eugenol and linalool, purified from leaves of Ocimum tenuiflorum for eradication of biofilm produced by Pseudomonas aeruginosa. METHODS AND RESULTS: The phytoextract of O. tenuiflorum (KT), a common ethno-botanical plant of India, was purified through high-performance liquid chromatography and was analysed using ultraviolet (UV) spectroscopy and gas chromatography-mass spectrometry (GC-MS). Eugenol and linalool were found to be the most active amongst all phytocompounds present in phytoextract and showed a significant reduction in the viability of sessile cells of P. aeruginosa and the minimum revival after withdrawal of phyto-challenge. They could bring about notable reduction in the protein and carbohydrate content of exopolysaccharide of biofilm. Eugenol and linalool could affect the synthesis of quorum sensing (QS) proteins like LasA and LasB as well as virulence factors such as pyocyanin, and rhamnolipids, which seriously hamper the formation of biofilm. The biofilm framework was extremely affected by the phytocompounds through the reduction of protein and carbohydrate content of extracellular polymeric substance (EPS). Another interesting found out was that they brought about maximum inhibition to the genomic DNA and RNA content. The studies were supported by in silico interaction between eugenol and linalool with the QS proteins. The antibiofilm efficacies of eugenol, linalool and phytoextract (KT) were further confirmed by microscopic studies with scanning electron microscopy (SEM), atomic force microscopy and fluorescence confocal microscopy microscopic studies. CONCLUSIONS: The phytocompounds are proved to be more effective than conventional antibiotics in inhibiting the biofilm forming sessile cells and can be used as a replacement for antibiotic. SIGNIFICANCE AND IMPACT OF THE STUDY: Pure eugenol extracted from common basil leaves can be used as a safe substitute for common antibiotic for treatment of chronic infections caused by P. aeruginosa. It will be cost effective, devoid of notable side effects and will not generate antibiotic resistance in host body.

Use of immunoadsorption columns in ABO-incompatible renal transplantation: A prospective study at a tertiary care center in India.

BACKGROUND: We present our experience of ABO-incompatible renal transplant using immunoadsorption (IA) columns. We have compared efficacy of two commercially available columns. METHODS: This single-center prospective study was conducted at Army Hospital Research and Referral, Delhi. All consecutive ABO-incompatible renal transplants from January 2014 to February 2018 were analyzed. Of 30 patients who underwent transplantations, 28 underwent antibody depletion with immunoadsorption columns. Of them, 14 cases were in the "Glycosorb group," while 14 in the "Adsopak group." RESULTS: The donors in the Adsopak group were older than those in the Glycosorb group (p < 0.05). Both groups had spousal donors in majority. The cutoff for the antibody titer was 1:8. The median titer in the Adsopak group was 128 (range, 1:4 to 1:2048), while that in the Glycosorb group was 24 (range, 1:8 to 1:128). All patients in the Glycosorb group had baseline titers ≤1:128, while 13 patients in the Adsopak group had baseline titers ≤1:512. Nil titer was achievable with Glycosorb® (50%,7/14) but not with Adsopak® (P < 0.01). Around 4 sessions were required for the Glycosorb group, while around 8 sessions were required for the Adsopak group before transplantation (p < 0.001). The Glycosorb group was advantageous in terms of graft failure because no rejection was noticed in these patients in their follow-up period. Three patients in the Adsopak group developed rejection (two had mixed rejection, and one had antibody-mediated rejection). Four patients died of sepsis (three in the Glycosorb and one in the Adsopak group). Lower baseline serum creatinine level was achieved in the Glycosorb group. CONCLUSIONS: Results of ABO-incompatible renal transplantation were satisfactory, and the use of immunoadsorption columns could effectively deplete antibody titers. Glycosorb columns were more efficient than Adsopak columns. Graft survival was better with Glycosorb. Posttransplant infections were a major cause of mortality.

In vitro activity of a novel antibacterial agent, levonadifloxacin, against clinical isolates collected in a prospective, multicentre surveillance study in India during 2016-18.

BACKGROUND: Levonadifloxacin is a novel antibiotic belonging to the benzoquinolizine subclass of fluoroquinolones with potent activity against MRSA and quinolone-resistant Staphylococcus aureus. IV levonadifloxacin and its oral prodrug alalevonadifloxacin have recently been approved in India for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) including diabetic foot infections. OBJECTIVES: To investigate the in vitro activity of levonadifloxacin against contemporary clinical isolates collected from multiple tertiary care hospitals across India in the Antimicrobial Susceptibility Profiling of Indian Resistotypes (ASPIRE) surveillance study. METHODS: A total of 1376 clinical isolates, consisting of staphylococci (n = 677), streptococci (n = 178), Enterobacterales (n = 320), Pseudomonas aeruginosa (n = 140) and Acinetobacter baumannii (n = 61), collected (2016-18) from 16 tertiary hospitals located across 12 states in India, were included in the study. The MICs of levonadifloxacin and comparator antibiotics were determined using the reference agar dilution method and broth microdilution method. RESULTS: Levonadifloxacin exhibited potent activity against MSSA (MIC50/90: 0.5/1 mg/L), MRSA (MIC50/90: 0.5/1 mg/L) and levofloxacin-resistant S. aureus (MIC50/90: 1/1 mg/L) isolates. Similarly, potent activity of levonadifloxacin was also observed against CoNS including MDR isolates (MIC50/90: 1/2 mg/L). Against Streptococcus pneumoniae, levonadifloxacin (MIC50/90: 0.5/0.5 mg/L) showed superior activity compared with levofloxacin (MIC50/90: 1/2 mg/L). Among levofloxacin-susceptible Enterobacterales, 80.6% of isolates were inhibited at ≤2 mg/L levonadifloxacin. CONCLUSIONS: Levonadifloxacin displayed potent activity against contemporary MRSA and fluoroquinolone-resistant staphylococcal isolates, thus offering a valuable IV as well as an oral therapeutic option for the treatment of ABSSSIs. Furthermore, levonadifloxacin exhibited a broad-spectrum activity profile as evident from its activity against streptococci and levofloxacin-susceptible Gram-negative isolates.

Participation of Phosphatidylinositol-3 Kinase Signalling in Human Chorionic Gonadotropin, Bovine Insulin (B-Insulin) and Human-Insulin-Like Growth Factor-I Induced Oocyte Maturation and Steroidogenesis in the Grey Mullet, Mugil Cephalus.

CONTEXT: The grey mullet, Mugil cephalus, is an edible fish of high economic importance. Breeding biology with reference to hormonal/growth factor regulation of oocyte maturation needs to be known for its commercial production. OBJECTIVE: The present study was conducted to examine the potency of maturation inducing hormones, chorionic gonadotropin (hCG), bovine-insulin, and insulin like growth factor1 (h-IGF-1) I on ovarian steroidogenesis and oocyte maturation. DESIGN: The role of hormones and growth factors on steroidogenesis and oocyte maturation was investigated using specific inhibitors, Wortmannin for phosphatidylinositol-3 (PI3) kinase, trilostane for 3ß-hydroxysteroid dehydrogenase, 1-octanol and 1-heptanol for gap junctions, actinomycin D for transcription and cycloheximide for translation of signal molecules. METHODS: Actions of hormonal and growth factors were examined for steroidogenesis, by radioimmunoassay and oocyte maturation by germinal vesicle breakdown (GVBD). Specific inhibitors were used to determine the cell signaling pathways, PI3 kinase. RESULTS: All the inhibitors attenuated the hCG-induced oocyte maturation (GVBD%), steroidogenesis including transcription, translation, gap junctions and PI3 kinase signaling. These inhibitors failed to inhibit h-IGF-I and b-insulin-induced oocyte maturation, steroidogenesis, translation and PI3 kinase signaling. CONCLUSION: hCG induces oocyte maturation via steroid dependent pathway involving gap junctions, transcription, translation and PI3 kinase signaling, unlike h-IGF-I and b-insulin in the mullet.

Correspondence analysis to evaluate the transmission of Staphylococcus aureus strains in two New York State maximum-security prisons.

Prisons/jails are thought to amplify the transmission of Staphylococcus aureus (SA) particularly methicillin-resistant SA infection and colonisation. Two independently pooled cross-sectional samples of detainees being admitted or discharged from two New York State maximum-security prisons were used to explore this concept. Private interviews of participants were conducted, during which the anterior nares and oropharynx were sampled and assessed for SA colonisation. Log-binomial regression and correspondence analysis (CA) were used to evaluate the prevalence of colonisation at entry as compared with discharge. Approximately 51% of admitted (N = 404) and 41% of discharged (N = 439) female detainees were colonised with SA. Among males, 59% of those admitted (N = 427) and 49% of those discharged (N = 393) were colonised. Females had a statistically significant higher prevalence (1·26: P = 0·003) whereas males showed no significant difference (1·06; P = 0·003) in SA prevalence between entry and discharge. CA demonstrated that some strains, such as spa types t571 and t002, might have an affinity for certain mucosal sites. Contrary to our hypothesis, the prison setting did not amplify SA transmission, and CA proved to be a useful tool in describing the population structure of strains according to time and/or mucosal site.

PiSZ alpha-1 antitrypsin deficiency (AATD): pulmonary phenotype and prognosis relative to PiZZ AATD and PiMM COPD.

INTRODUCTION: The PiSZ genotype results in less severe deficiency of alpha-1 antitrypsin (AAT) than PiZZ. Less is known about phenotypic and prognostic features. METHODS: We studied 699 PiZZ, 126 PiSZ and 316 PiMM patients. All AAT deficiency (AATD) patients were augmentation naive. PiSZ were compared with PiZZ patients for clinical phenotype at baseline including CT findings, smoke exposure, progression of lung disease and survival. Similarly, PiSZ patients diagnosed as a result of investigation for possible lung disease (lung index cases) were compared with PiMM. Multivariable analytical techniques and matching (PiSZ to PiZZ) were employed to account for demographic differences. RESULTS: Pack-years smoked and FEV1 exhibited a negative correlation in PiSZ and ZZ patients (both r=-0.43), with emphysema and COPD occurring more commonly in PiZZ patients at <20 pack-year exposure. In multivariable analyses, PiSZ patients were less likely to have emphysema (p<0.01) and had better survival than PiZZ (p=0.017), but lung function decline did not differ significantly. 42% of PiSZ patients had upper-zone-dominant emphysema on CT scan. Analyses of AAT level confirmed a critical threshold at 11 µM, particularly with regard to phenotypes classical of PiZZ AATD.Significant baseline differences suggested that PiSZ had presented earlier to health services than PiMM. Once this was accounted for, risk of emphysema did not differ between PiSZ and PiMM although survival was lower in PiMM patients (p<0.01). CONCLUSIONS: PiSZ patients are less susceptible to cigarette smoke than PiZZ. The pattern of emphysema may be similar at diagnosis to usual COPD.

Prevalence and risk factors for Staphylococcus aureus colonization in individuals entering maximum-security prisons.

To assess the prevalence and risk factors for colonization with Staphylococcus aureus in inmates entering two maximum-security prisons in New York State, USA, inmates (N=830) were interviewed and anterior nares and oropharyngeal samples collected. Isolates were characterized using spa typing. Overall, 50·5% of women and 58·3% of men were colonized with S. aureus and 10·6% of women and 5·9% of men were colonized with MRSA at either or both body sites. Of MSSA isolates, the major subtypes were spa type 008 and 002. Overall, risk factors for S. aureus colonization varied by gender and were only found in women and included younger age, fair/poor self-reported general health, and longer length of prior incarceration. Prevalence of MRSA colonization was 8·2%, nearly 10 times greater than in the general population. Control of epidemic S. aureus in prisons should consider the constant introduction of strains by new inmates.

Chloroplast pigments, proteins, lipid peroxidation and activities of antioxidative enzymes during maturation and senescence of leaves and reproductive organs of Cajanus cajan L.

A comparative investigation was undertaken with pigeon pea leaves and attached flower buds/flowers/pods during their developmental stages including senescence in a natural system in experimental plots. Alterations in chloroplast pigments, total soluble proteins, lipid peroxidation, malondialdehyde (MDA) content and activities of guaiacol peroxidase (POD, EC 1.11.1.7) and superoxide dismutase (SOD, EC 1.15.1.1) were studied at 5-day interval from initial to 40-day stage. Chloroplast pigments and proteins of leaves increased upto 15 and 20-day stages respectively followed by a steady decline. Reproductive parts, however, exhibited rise in chloroplast pigments upto 25-day and protein till last stage as developing pods gain the amount from the senescing leaves which are nearest to them. Senescing leaves show very high POD activity than the developing and senescing pods and POD appears to be associated with chlorophyll degradation. Considerably higher activity and amount of LOX and MDA respectively have been noticed in senescing leaves than in flowers and pods. Increase in SOD activity during early stage of leaf growth and maturation indicates protective role that declined at senescent stages. Pods are unique in having very high SOD activity, only last stage of senescence does show a decline.

Modelling system dynamics and phytoplankton diversity at Ranchi lake using the carbon and nutrient mass balance equations.

Modelling system dynamics in a hyper-eutrophic lake is quite complex especially with a constant influx of detergents and sewage material which continually changes the state variables and interferes with the assessment of the chemical rhythm occurring in polluted conditions as compared to unpolluted systems. In this paper, a carbon and nutrient mass balance model for predicting system dynamics in a complex environment was studied. Studies were conducted at Ranchi lake to understand the altered environmental dynamics in hyper-eutrophic conditions, and its impact on the plankton community. The lake was monitored regularly for five years (2007 - 2011) and the data collected on the carbon flux, nitrates, phosphates and silicates was used to design a mass balance model for evaluating and predicting the system. The model was then used to correlate the chemical rhythm with that of the phytoplankton dynamics and diversity. Nitrates and phosphates were not limiting (mean nitrate and phosphate concentrations were 1.74 and 0.83 mgl⁻¹ respectively). Free carbon dioxide was found to control the system and, interacting with other parameters determined the diversity and dynamics of the plankton community. N/P ratio determined which group of phytoplankton dominated the community, above 5 it favoured the growth of chlorophyceae while below 5 cyanobacteria dominates. TOC/TIC ratio determined the abundance. The overall system was controlled by the availability of free carbon dioxide which served as a limiting factor.

Improving outcomes in patients with vestibular schwannomas: microsurgery versus radiosurgery.

Vestibular schwannomas (VSs) account for 6% of all intracranial tumors. Historically, VSs have been treated with microsurgery (MS); however, stereotactic radiosurgery (SRS) has emerged as a viable alternative. This review seeks to compare the tumor control rates, functional outcomes, and costs associated with these two modalities. A focused review of the published literature (1966-2012) was conducted comparing outcomes between MS and SRS in those with VS. Outcomes of interest included hearing preservation, facial nerve preservation, tumor control, and cost-effectiveness. Three level 2 studies, eight level 3 studies, and several level 4 studies were reviewed and assessed. Evidence from level 2 studies show that SRS (40-68%) results in higher rates of serviceable hearing compared to MS (0-5%), and higher rates of facial nerve preservation are likewise seen after SRS (98-100%) compared to MS (66-83%) in patients with tumors <3 cm in size. Complications vary as expected by treatment modality, with CSF leak, tinnitus, and trigeminal symptoms being among the most common complications following MS. Hydrocephalus, tinnitus, and trigeminal symptoms were reported in a small percentage of patients after SRS. Tumor control is comparable between MS and SRS for tumors <3cm in size. Total costs for MS can reach over two times higher than for SRS, although long-term follow-up data is needed. SRS has been shown to be efficacious and have a lower morbidity in most patients with tumors that are <3cm. SRS can be considered as the primary modality of choice for treatment of most VS that are <3cm.

India-discovered levonadifloxacin & alalevonadifloxacin: A review on susceptibility testing methods, CLSI quality control and breakpoints along with a brief account of their emerging therapeutic profile as a novel standard-of-care.

BACKGROUND: Levonadifloxacin (intravenous) and alalevonadifloxacin (oral prodrug) are novel antibiotics based on benzoquinolizine subclass of fluoroquinolone, licensed for clinical use in India in 2019. The active moiety, levonadifloxacin, is a broad-spectrum antibiotic with a high potency against methicillin-resistant Staphylococcus. aureus, multi-drug resistant pneumococci and anaerobes. OBJECTIVE: This review, for the first time, critically analyses the antimicrobial susceptibility testing methods, Clinical Laboratory & Standards Institute (CLSI)-quality control of susceptibility testing and breakpoints of levonadifloxacin. Further, the genesis, discovery and developmental aspects as well as therapeutic profile of levonadifloxacin and alalevonadifloxacin are briefly described. CONTENTS: In order to aid the scientific and clinician communities with a single comprehensive overview on all the key aspects of levonadifloxacin and alalevonadifloxacin, the present article covers the reference MIC and disk diffusion methods for levonadifloxacin susceptibility testing that were approved by CLSI and the reference ranges for quality control strains published in the CLSI M100 document. The breakpoints of levonadifloxacin were derived in concordance to US FDA, European Committee on Antibiotic Susceptibility Testing (EUCAST) and CLSI approaches. Further, the article provides a brief account of challenges encountered during the discovery stages of levonadifloxacin and alalevonadifloxacin, activity spectrum and safety benefits accruing from structural novelty-linked mechanism of action. Further, the review also covers in vitro and in vivo activities, registrational clinical studies and patient-friendly features of levonadifloxacin/alalevonadifloxacin. Cumulatively, levonadifloxacin has a potential to offer a long awaited new standard-of-care treatment for the resistant Gram-positive bacterial infections.

Association of Baseline Patient-reported Health-related Quality of Life Metrics with Outcome in Localised Prostate Cancer.

AIMS: Although health-related quality of life (HR-QoL) outcomes are pivotal in oncology, the prognostic significance of patient-reported HR-QoL metrics is largely undefined in localised prostate cancer. We report the association of baseline HR-QoL metrics with overall survival and toxicity in localised prostate cancer. MATERIALS AND METHODS: This was a secondary analysis of a phase III randomised controlled study conducted in a single-payer health system. Patients with Gleason score ≤7, clinical stage T1b-T3a and prostate-specific antigen <30 ng/ml were randomised to neoadjuvant and concurrent androgen deprivation therapy (ADT) for 6 months starting 4 months before prostate radiotherapy or concurrent and adjuvant ADT for 6 months starting simultaneously with prostate radiotherapy. HR-QoL scores were estimated using the European Organisation for Research and Treatment of Cancer QoL questionnaire. A multistate Markov model was used to determine the association of baseline HR-QoL metrics with overall survival and a multilevel multivariable Cox regression was used to determine the association with the incidence of delayed-onset grade ≥3 radiotherapy-related toxicities. To adjust for multiple analyses, P < 0.025 was considered as statistically significant. RESULTS: Overall, 393 patients with baseline HR-QoL data were included in this analysis: 194 in the neoadjuvant arm and 199 in the adjuvant arm. Baseline financial difficulty (hazard ratio 1.020, 95% confidence interval 1.010-1.030, P = 0.02) and dyspnoea (hazard ratio 1.020, 95% confidence interval 1.003-1.030, P = 0.01) were associated with inferior overall survival. Baseline dyspnoea was associated with a higher incidence of grade ≥3 toxicity (hazard ratio 1.020, 95% confidence interval 1.010-1.030, P = 0.023). CONCLUSION: In a cohort of localised prostate cancer patients treated with radiotherapy and short-term ADT, a 10-point higher baseline financial difficulty or dyspnoea was associated with a 20% increased risk of death. With each 10-point increase in baseline dyspnoea, we noted a 20% increase in the associated risk of grade ≥3 delayed-onset radiotherapy-related toxicity.

Reappraisal of the electric dipole moment enhancement factor for thallium.

The electric dipole moment (EDM) enhancement factor of atomic Tl is of considerable interest as it has been used in determining the most accurate limit on the electron EDM to date. However, its value varies from -179 to -1041 in different approximations. In view of the large uncertainties associated with many of these calculations, we perform an accurate calculation employing the relativistic coupled-cluster theory and obtain -466, which in combination with the most accurate measurement of Tl EDM [Phys. Rev. Lett. 88, 071805 (2002)] yields a new limit for the electron EDM: |d(e)| < 2.0 × 10⁻²7e cm.

Multiplexed bio-imaging using cadmium telluride quantum dots synthesized by mathematically derived process parameters in a continuous flow active microreactor.

Quantum dots (QDs) are semiconductor nanocrystals with unique size-tunable emissions. To obtain a precise emission spectrum, monodispersity in size is imperative, which is achieved by controlling the reaction kinetics in a continuous flow of active microreactors. Further, a multivariate approach (dimensional analysis) is employed to impose stringent control on the reaction process resulting in monodispersed preparation of cadmium telluride (CdTe) quantum dots. Dimensional analysis knits multiple variables into a dimensionless mathematical form which not only predicts parameters precisely to obtain narrow size tunability but also guarantees reproducibility in synthesis. Analytical, structural, and optical characterization of the microreactor synthesized polydimethylsiloxane (PDMS) coated CdTe QDs reveal quantum efficient (61.5%), photostable (44%), and biocompatible nanocrystals of 5-15 nm. Further, PDMS-coated QDs (P-QDs) are conjugated with organelle-specific antibodies/biomarkers for in-vitro imaging in NIH 3T3 cells. Likewise, proliferating cell nuclear antigen (PCNA) and anti-myosin (MF20), cardiomyocytes antibodies are conjugated with P-QDs (red and green, respectively) to image the zebrafish's cardiac tissue. Antibodies tagged with quantum dots are imaged simultaneously using confocal microscopy. Thus, multiplexed bio-imaging of in-vitro and zebrafish tissue is demonstrated successfully. The results indicate the suitability of continuous flow active microreactor in conjunction with the mathematical prediction of process parameters to synthesize reproducibly monodispersed and quantum efficient QDs.

Radiation induced effects on viability and antioxidant enzymes of crustaceans from different habitats.

The paper describes differential tolerance of two fresh water crustaceans Mesocyclops hyalinus and Allodiaptomus satanus to 60Co gamma radiation. Mesocyclops hyalinus is dominant species at site 1, near a Thermal Power Plant at Kolaghat East Midnapore where fly ash deposition is a regular phenomenon. Allodiaptomus satanus is dominant species at site 2 at Kolkata, Ballygung where anthroponotic activities are more pronounced. M. hyalinus is naturally exposed to more stressful situation than A. satanus as revealed by comparing the hydrological parameters of the two habitats. Experimental exposure to ionizing radiation resulted in differential changes in viability morphology and antioxidant enzyme activities in the two selected species. Survival experiments showed greater tolerance of M. hyalinus compared to A. satanus up to 8Gy (absorbed dose) after which if showed drastic fail in survival. More pronounced morphological changes were observed in A. satanus as compared to that in M. hyalinus. The pattern of changes in antioxidant enzyme activity is distinctly opposite in the two radiation exposed species. While in M. hyalinus stimulation in activity of both CAT (excepting at 10Gy absorbed dose) and SOD was observed A. satanus showed decrease in activity of both the enzymes when compared to their unirradiated counterparts.

Fulminant Neisseria meningitidis septicaemia with purpura fulminans requiring limb amputation.

Despite the isolation of Neisseria meningitidis over 200 years ago, meningococcal disease remains a feared cause of bacterial sepsis, with significant morbidity and mortality, despite prompt antibiotic use and modern critical care support. Neisseria meningitides is a Gram-negative encapsulated diplococcus, which exists only in the human host (Kvalsvig and Unsworth, 2003). The bacterium can cause life-threatening septic shock and coagulopathy, which may rapidly manifest within a matter of hours from preceding mild symptoms (Kvalsvig and Unsworth, 2003). Whilst N. meningitidis is recognised as a common commensal organism in the nasopharynx, associated with asymptomatic carriage in up to 10 %, manifestation of life-threatening disease is rare (Rappuoli and Pizza, 2015). We report the case of 31-year-old male presenting with devastating meningococcal septicaemia with disseminated intravascular coagulopathy (DIC) and purpura fulminans, requiring surgical debridement and a right above-knee amputation for sepsis-driven skin necrosis. The patient suffered extensive tissue loss secondary to a type 3 immune hypersensitivity reaction involving immune-complex mediated inflammation and tissue necrosis. Due to a strong immune component driving the patient's failure to convalesce pulsed intravenous methylprednisolone was used alongside antimicrobial therapy. The use of steroids was associated with fever subsidence and significant clinical improvement, highlighting the benefit of corticosteroid use in immune-complex mediated pathology.

Assessment of antibacterial activity of levonadifloxacin against contemporary gram-positive clinical isolates collected from various Indian hospitals using disk-diffusion assay.

Objectives: Levonadifloxacin is a novel benzoquinolizine subclass of quinolone with broad-spectrum activities against problematic pathogens such as methicillin-resistant Staphylococcus aureus, quinolone-resistant S. aureus, vancomycin intermediate S. aureus, and vancomycin-resistant S. aureus. Levonadifloxacin and its oral prodrug, alalevonadifloxacin, have been recently approved in India for the treatment of acute bacterial skin and skin structure infections, including concurrent bacteraemia and diabetic foot infections. The aim of the study is to assess the activity of levonadifloxacin against Gram-positive clinical isolates collected from various Indian hospitals using the disc-diffusion method. Materials and Methods: Nonduplicate isolates of S. aureus and other Gram-positive isolates collected from June 2019 to March 2020 were subjected to levonadifloxacin susceptibility testing (disk diffusion method) as per the Clinical and Laboratory Standards Institute guidelines (Year 2019). Levonadifloxacin 10 µg impregnated disks were used during the testing. Results: A total of 664 diverse Gram-positive clinical isolates collected from six different hospitals in India were analyzed. Majority (65.5%) of the isolates were S. aureus. All the S. aureus and other Gram-positive isolates were found to be susceptible to levonadifloxacin as per the prespecified interpretive criteria identified based on population pharmacokinetic model and Monte Carlo simulation enabled probability of pharmacodynamic target attainment analysis. Conclusions: The present study showed that levonadifloxacin was highly active against contemporary Gram-positive pathogens and furthermore demonstrated that levonadifloxacin susceptibilities can be reliably determined using the disc-diffusion method.

Suppression of epididymal sperm antigenicity in the rabbit by uteroglobin and transglutaminase in vitro.

There is evidence that the mammalian female genital tract is capable of responding immunologically when challenged with alloantigens. The antigenic properties of male gametes have been well delineated. However, it is only rarely that a female mammal ever responds immunologically to the male gametic antigens as a result of coitus. When a proposed mechanism of suppression of antigenicity of epididymal spermatozoa was tested experimentally, the results indicated that two proteins (uteroglobin and transglutaminase) present in the prostate may be responsible for suppressing sperm antigenicity in the rabbit.

Chikungunya in west bengal, India.

Fever of unknown origin broke out in several districts of West Bengal, from August 2007 to December 2007. The cases were suffering from high fever, severe joint pain lasting for several weeks after clinical cure and appearance of skin rashes. Patients' sera were collected at least five days after fever and were analyzed to detect specific IgM antibodies. A total of 800 patients were investigated and 321 (40.13%) were found to be reactive for Chikungunya antibodies. Of the patients, 66% were male. Predominant signs and symptoms observed in the sero-positive cases were fever (100%), arthralgia (96%) and diffuse erythematous skin rash (94%). Of the patients, 3% had haemorrhagic manifestations. Re-emerging Chikungunya virus spread in epidemic form in several districts of West Bengal after a gap of four decades.