Therapeutic applications of lysostaphin against Staphylococcus aureus.

Staphylococcus aureus, an opportunistic pathogen, causes diverse community and nosocomial-acquired human infections, including folliculitis, impetigo, sepsis, septic arthritis, endocarditis, osteomyelitis, implant-associated biofilm infections and contagious mastitis in cattle. In recent days, both methicillin-sensitive and methicillin-resistant S. aureus infections have increased. Highly effective anti-staphylococcal agents are urgently required. Lysostaphin is a 27 kDa zinc metallo antimicrobial lytic enzyme that is produced by Staphylococcus simulans biovar staphylolyticus and was first discovered in the 1960s. Lysostaphin is highly active against S. aureus strains irrespective of their drug-resistant patterns with a minimum inhibitory concentration of ranges between 0·001 and 0·064 µg ml-1 . Lysostaphin has activity against both dividing and non-dividing S. aureus cells; and can seep through the extracellular matrix to kill the biofilm embedded S. aureus. In spite of having excellent anti-staphylococcal activity, its clinical application is hindered because of its immunogenicity and reduced bio-availability. Extensive research with lysostaphin lead to the development of several engineered lysostaphin derivatives with reduced immunogenicity and increased serum half-life. Therapeutic efficacy of both native and engineered lysostaphin derivatives was studied by several research groups. This review provides an overview of the therapeutic applications of native and engineered lysostaphin derivatives developed to eradicate S. aureus infections.

Unified approach to stochastic thermodynamics: Application to a quantum heat engine.

In the present study we have developed an alternative formulation for the quantum stochastic thermodynamics based on the c-number Langevin equation for the system-reservoir model. This is analogous to the classical one. Here we have considered both Markovian and non-Markovian dynamics (NMD). Consideration of the NMD is an important issue at the current state of the stochastic thermodynamics. Applying the present formalism, we have carried out a comparative study on the heat absorbed and the change of entropy with time for a linear quantum system and its classical analog for both Markovian and NMD. Here the strength of the thermal noise and its correlation time for the respective cases are the leading quantities to explain any distinguishable feature which may appear with the equilibration kinetics. For another application, we have proposed a formulation with classical look for a quantum stochastic heat engine. Using it we have presented a comparative study on the efficiency and its value at maximum power for a quantum stochastic heat engine and its classical analog. The engines are Carnot like which are coupled with their respective Markovian thermal baths. Here also the noise strength as well as the diffusion constant are the leading quantities to explain any noticeable feature.

Colistin resistance due to insertional inactivation of the mgrB in Klebsiella pneumoniae of clinical origin: First report from India.

OBJECTIVE: Mutations in mgrB, phoP/phoQ, pmrA, pmrB, pmrC, and crrABC regulatory systems have been found responsible for colistin resistance. The aim of our study was to investigate the role of alteration in mgrB gene and plasmid mediate mcr-1 and mcr-2 genes as a source of colistin resistance in 17 non duplicate Klebsiella pneumoniae clinical isolates. METHODS: All isolates classified as resistant to colistin by VITEK 2 system (BioMerieux, Marcy I' Etoile, France) were included. Susceptibility to colistin was also determined by broth microdilution using breakpoints recommended by EUCAST (>2mg/L resistant; and ≤2mg/L susceptible). PCR amplification of mgrB gene was performed and sequenced using specific primers. Presence of mcr-1 and mcr-2 was also investigated using PCR. RESULTS: PCR amplification of the mgrB gene of the 17 K.pneumoniae isolates revealed a larger (~1000bp) amplicon in three isolates when compared with the wild type mgrB ampiclon (250 bp). Sequencing of these amplicons showed that mgrB was disrupted by the insertion of ISKpn14, a IS element belonging to the IS1 family. Sequencing, of the 250 bp mgrB gene in the remaining 14 isolates revealed frame shift mutation after the second codon leading to a premature stop codon in only one isolate. CONCLUSIONS: The study showed that colistin resistance in 20% of the K. pneumoniae isolates was due to loss of function of mgrB. We describe for the first-time from India, insertional inactivation of mgrB by ISKpn14 inserted at different sites, responsible for colistin resistance.

Spin-history artifact during functional MRI: potential for adaptive correction.

PURPOSE: Functional magnetic resonance imaging (fMRI) is limited by sensitivity to millimetre-scale head motion. Adaptive correction is a strategy to adjust the imaging plane in response to measured head motion, thereby suppressing motion artifacts. This strategy should correct for motion in all six degrees of freedom and also holds promise for through-plane motion that creates "spin-history" artifact that cannot easily be removed by postprocessing methods. Improved quantitative understanding of the MRI signal behavior associated with spin-history artifact would be useful for implementing adaptive correction robustly. METHODS: A numerical simulation was developed to predict MRI artifact signal amplitude in a single-slice for simple motions, implemented with and without adaptive correction, and compared with experiment by imaging a phantom at 3.0 T. Functional MRI was also performed of a human volunteer to illustrate adaptive correction in the presence of spin-history artifact. RESULTS: Good agreement was achieved between simulation and experimental results. Although time-averaged artifact signal amplitude was observed to correlate linearly with motion speed, artifact time-courses were nonlinearly related to motion waveforms. In addition, experimental results demonstrated effective adaptive correction of spin-history artifact when the phantom underwent complex motions. Adaptive correction during human fMRI suppressed spin-history artifacts and spurious activations associated with task-correlated motion. CONCLUSIONS: Overall, this work suggests that adaptive correction, especially when implemented with minimal lag between motion measurement and scan plane update, may help to expand the populations for which fMRI can be performed robustly.

Sexual risk factors for cervical cancer among rural Indian women: a case-control study.

BACKGROUND: The association between sexual behaviour and cervical cancer is well established. Despite a high incidence of cervical cancer in India, its role has not been widely investigated in Indian women among whom the rate of sexual promiscuity is known to be very low. A hospital-based case-control study was carried out to investigate the role of sexual risk factors in cervical cancer among rural Indian women. METHODS: A case-control design was used in which a total of 268 subjects, comprising 134 women with invasive cervical cancer as cases and 134 control women were studied. A multiple logistic regression model was used to analyse the data. RESULTS: The risk factors found to be associated with cervical cancer were early age at first coitus, extramarital sex partners of women and the time interval since first exposure. In a multiple logistic regression model, independent effects were observed for early age at first coitus, showing maximum risk in women who reported their first intercourse at < 12 years of age, compared to that of women at > or = 18 years (odds ratio [OR] = 3.5. 95% confidence interval [CI]: 1.1-10.9). Increased risk was also seen for women who had extramarital sex relationships (OR = 5.5, 95% CI: 1.5-19.5). The significant effect of early age at first coitus persisted after adjustment for latency period which also showed its independent risk association with cervical cancer in the multivariate analysis. CONCLUSION: These findings confirm the association between early age at first coitus and cervical cancer in women with a low rate of sexual promiscuity and define the role of these risk factors in cervical carcinogenesis among rural Indian women.

PIP: The association between sex behavior and cervical cancer was investigated among rural Indian women known to have very low levels of promiscuity. 134 women with invasive cervical cancer were matched with 134 controls and analysis performed using a multiple logistic regression model. Risk factors associated with cervical cancer were early age at first coitus, extramarital sex partners of women, and the time interval since first exposure. Independent effects were observed for early age at first coitus, with maximum risk among women who reported their first intercourse at younger than age 12 years compared to that of women at age 18 years or older. Increased risk was also seen for women who had extramarital sex relationships. The significant effect of early age at first coitus persisted after adjustment for a latency period which also showed its independent risk association with cervical cancer in the multivariate analysis.

A case-control study of reproductive risk factors associated with cervical cancer.

Using the logistic-regression technique, a hospital-based case-control study of 177 married women with invasive squamous-cell cervical cancer and 149 hospital-visiting controls enabled evaluation of selected reproductive factors as risks. Early age at marriage was found to be the single best predictor of the disease status. However, those who married late but gave birth to a large number of children were generally found to be suffering from cervical cancer. The results support the hypothesis that it is not so much parity per se that enhances the risk, but the rapidity of multiple pregnancies that matters. Logistic analysis also revealed the independent influence of birth interval on the risk of cervical cancer. These findings warrant serious consideration in future studies, given the obvious implications for prevention. Other implications for the prevention of cervical cancer are briefly discussed.

The possible mode of action of iproniazid. I. Differential luteolytic effect of iproniazid before and after the establishment of placental adolescence.

Iproniazid, a very specific monoamine oxidase inhibitor, at a dose level of 200 mg/kg body weight induced luteolysis and caused lysis of deciduomata as well as resorption of the established embryos. Exogenous replacement of prolactin, a most consistent stimulant of the endocrine functioning of corpus luteum, or progesterone absolutely reversed the adversity developed following iproniazid injection. Moreover, failure of iproniazid even at a higher dose level in the deviation of the normal sequence of pregnancy after the establishment of placental adolescence strongly tempting to suggest that iproniazid could only show its luteolytic effect when the hypothalamic-pituitary complex is exclusively involved in the maintennance of pregnancy.

PIP: The luteolytic effect of iproniazid, a potent monoamine oxidase inhibitor, during pseudopregnancy and pregnancy was studied in rats. A single injection (200 mg/kg) of iproniazid induced luteolysis and caused lysis of deciduomata. Resorption of viable embryos was also observed. The administration of prolactin or progesterone countered the antifertility effects of the drug. Neither a single or double injection of iproiazid on Days 12 and 14 of pregnancy produced deleterious effects on the growth of fetuses, placentas, ovaries and corpus luteum. This suggests that iproniazid exerts its luteolytic effect only when the hypothalamic-pituitary complex is involved in the maintenance of pregnancy.