A collection of potent antimicrobials consisting of novel 1,3-bis-benzoic acid and trifluoromethyl phenyl derived pyrazoles has been synthesized and tested for antibacterial activity. The majority of ...trifluoromethyl phenyl derivatives are highly potent growth inhibitors of Gram-positive bacteria and showed low toxicity to human cultured cells. In particular, two compounds (59 and 74) were selected for additional studies. These compounds are highly effective against Staphylococcus aureus as shown by a low minimum inhibitory concentration (MIC), a bactericidal effect in time-kill assays, moderate inhibition of biofilm formation as well as biofilm destruction, and a bactericidal effect against stationary phase cells representing non-growing persister cells. Multistep resistance assays showed a very low tendency for S. aureus and Enterococcus faecalis to develop resistance through mutation. Additionally, in vivo mouse model studies showed no harmful effects at doses up to 50 mg/kg using 14 blood plasma organ toxicity markers or TUNEL assay in liver and kidney. Investigations into the mode of action by performing macromolecular synthesis inhibition studies showed a broad range of inhibitory effects, suggesting targets that have a global effect on bacterial cell function.
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•Drug resistance bacteria is a worldwide problem.•Potent anti-bacterial pyrazoles.•Anti-MRSA and anti-VRE agents.•Novel compounds are non-toxic in vivo.
The current research explores the outcome of europium doping on the structure, morphology, electrical conductivity and optoelectronic characteristics of SnS
2
thin films deposited on glass substrates ...by nebulizer spray technique. X-ray diffraction analysis substantiates the presence of hexagonal structure in both pure and Eu-doped SnS
2
thin films with the highly preferred orientation diffracted from the plane (002). It shows the intensity of the predominant peak is highest for 2% Eu-doped SnS
2
thin film. From the XRD data, the crystallite size was found to be highest for 2% SnS
2
:Eu, and same sample showed a less dislocation density of 0.97 × 10
15
lines/m
2
and microstrain of 0.081 × 10
–3
/lines
2
m
4
. The crystallite size first increases with increasing doping concentration of Eu (0–2%), then decreases for higher concentrations. The SEM and AFM micro images reveal the agglomeration of grains at higher Eu concentration. The compositional analysis through EDAX studies supports the presence of Eu, Sn and S. The SnS
2
optical band gap value is found to vary from 2.70 to 2.91 eV as the Eu doping is increased from 2 to 6%. All the SnS
2
thin film samples manifest a n-type conductivity as authenticated from Hall studies and a low resistivity of 4.34 × 10
−1
cm with an elevated carrier concentration of 5.43 × 10
17
cm
−3
, respectively, was observed for SnS
2
:Eu (2 wt%). The same sample established a higher responsivity (41.64 × 10
−3
AW
−1
), competent external quantum efficiency (97.24%), and a better detectivity (40.88 × 10
8
Jones). Hence, the 2% Eu-doped SnS
2
film is recognized to be best suited for the fabrication of high-speed optoelectronic devices. This paper also discusses a putative mechanism for photo-detector performance under air and UV radiation.
In this long-term follow-up study, men with hemophilia B had steady production of functional factor IX after gene transfer with an adeno-associated viral vector. Patients had a marked reduction in ...bleeding episodes and factor IX replacement with minimal toxicity.
Hemophilia B, an X-linked recessive bleeding disorder, results from a defect in the gene encoding coagulation factor IX, a serine protease that is critical for blood clotting. Patients with functional plasma levels of factor IX that are less than 1% of the normal value (1 IU per deciliter) have a severe phenotype characterized by frequent spontaneous bleeding episodes that result in chronic, debilitating arthropathy and occasionally death.
1
Current treatment to prevent these bleeding episodes entails lifelong intravenous injections of factor IX every 2 or 3 days. Although this treatment is effective in preventing spontaneous bleeding episodes, it is not curative . . .
Biofilms are formed by the attachment of single or mixed microbial communities to a variety of biological and/or synthetic surfaces. Biofilm micro-organisms benefit from many advantages of the ...polymicrobial environment including increased resistance against antimicrobials and protection against the host organism's defence mechanisms. These benefits stem from a number of structural and physiological differences between planktonic and biofilm-resident microbes, but two main factors are the presence of extracellular polymeric substances (EPS) and quorum sensing communication. Once formed, biofilms begin to synthesise EPS, a complex viscous matrix composed of a variety of macromolecules including proteins, lipids and polysaccharides. In terms of drug delivery strategies, it is the EPS that presents the greatest barrier to diffusion for drug delivery systems and free antimicrobial agents alike. In addition to EPS synthesis, biofilm-based micro-organisms can also produce small, diffusible signalling molecules involved in cell density-dependent intercellular communication, or quorum sensing. Not only does quorum sensing allow microbes to detect critical cell density numbers, but it also permits co-ordinated behaviour within the biofilm, such as iron chelation and defensive antibiotic activities. Against this backdrop of microbial defence and cell density-specific communication, a variety of drug delivery systems have been developed to deliver antimicrobial agents and antibiotics to extracellular and/or intracellular targets, or more recently, to interfere with the specific mechanisms of quorum sensing. Successful delivery strategies have employed lipidic and polymeric-based formulations such as liposomes and cyclodextrins respectively, in addition to inorganic carriers e.g. metal nanoparticles. This review will examine a range of drug delivery systems and their application to biofilm delivery, as well as pharmaceutical formulations with innate antimicrobial properties such as silver nanoparticles and microemulsions.
A study on the effect of swift Heavy Ions Ti
7+
@ (100 MeV) irradiated on TGS single crystal has been performed at various ion fluencies. UV–Vis-NIR absorption measurements suggest the tuning of ...energy gap upon irradiation and
E
g
values linearly decreased with respect to increase in ion fluences. From the Dielectric study, it has been identified that Curie temperature (
T
c
) of 〈011〉 TGS decreases to 322 K from 325 K upon irradiation, and peak boarding due to induced strain was also notified therein. Strikingly, upon irradiation the piezoelectric coefficient of the irradiated sample of 〈011〉 TGS got increased from 41 pC/N to a maximum of 52 pC/N for an ion fluencies of 10
13
ions/cm
2
. The other significant results have been discussed in detail.
Abstract
We studied the incidence of HPV genotypes in mostly Black women with cervical carcinoma and correlated histopathologic tumor characteristics, immune markers and clinical data with survival. ...Disease-free survival (DFS) and overall survival (OS) were recorded for 60 months post-diagnosis. Fifty four of the 60 (90%) patients were Black and 36 (60%) were < 55 years of age. Of the 40 patients with typeable HPV genotypes, 10 (25%) had 16/18 HPV genotypes, 30 (75%) had one of the non-16/18 HPV genotypes, and 20 (50%) had one of the 7 genotypes (35, 39, 51, 53, 56, 59 and 68) that are not included in the nonavalent vaccine. Mixed HPV infections (≥ 2 types) were found in 11/40 (27.5%) patients. Patients infected with non-16/18 genotypes, including the most common genotype, HPV 35, had significantly shorter DFS and OS. PD-L1 (p = 0.003), MMR expression (p = 0.01), clinical stage (p = 0.048), histologic grade (p = 0.015) and mixed HPV infection (p = 0.026) were independent predictors of DFS. A remarkably high proportion of cervical cancer cells in our patients expressed PD-L1 which opens the possibility of the use of immune checkpoint inhibitors to treat these cancers. Exclusion of the common HPV genotypes from the vaccine exacerbates mortality from cervical cancer in underserved Black patients.
Middle East respiratory syndrome coronavirus (MERS-CoV) is not efficiently transmitted between humans, but it is highly prevalent in dromedary camels. Here we report that the MERS-CoV ...receptor--dipeptidyl peptidase 4 (DPP4)--is expressed in the upper respiratory tract epithelium of camels but not in that of humans. Lack of DPP4 expression may be the primary cause of limited MERS-CoV replication in the human upper respiratory tract and hence restrict transmission.
Summary Background A quarter of the world's neonatal deaths and 15% of maternal deaths happen in India. Few community-based strategies to improve maternal and newborn health have been tested through ...the country's government-approved Accredited Social Health Activists (ASHAs). We aimed to test the effect of participatory women's groups facilitated by ASHAs on birth outcomes, including neonatal mortality. Methods In this cluster-randomised controlled trial of a community intervention to improve maternal and newborn health, we randomly assigned (1:1) geographical clusters in rural Jharkhand and Odisha, eastern India to intervention (participatory women's groups) or control (no women's groups). Study participants were women of reproductive age (15–49 years) who gave birth between Sept 1, 2009, and Dec 31, 2012. In the intervention group, ASHAs supported women's groups through a participatory learning and action meeting cycle. Groups discussed and prioritised maternal and newborn health problems, identified strategies to address them, implemented the strategies, and assessed their progress. We identified births, stillbirths, and neonatal deaths, and interviewed mothers 6 weeks after delivery. The primary outcome was neonatal mortality over a 2 year follow up. Analyses were by intention to treat. This trial is registered with ISRCTN, number ISRCTN31567106. Findings Between September, 2009, and December, 2012, we randomly assigned 30 clusters (estimated population 156 519) to intervention (15 clusters, estimated population n=82 702) or control (15 clusters, n=73 817). During the follow-up period (Jan 1, 2011, to Dec 31, 2012), we identified 3700 births in the intervention group and 3519 in the control group. One intervention cluster was lost to follow up. The neonatal mortality rate during this period was 30 per 1000 livebirths in the intervention group and 44 per 1000 livebirths in the control group (odds ratio OR 0.69, 95% CI 0·53–0·89). Interpretation ASHAs can successfully reduce neonatal mortality through participatory meetings with women's groups. This is a scalable community-based approach to improving neonatal survival in rural, underserved areas of India. Funding Big Lottery Fund (UK).
Antibodies to Middle East respiratory syndrome coronavirus (MERS-CoV) were detected in serum and milk collected according to local customs from 33 camels in Qatar, April 2014. At one location, ...evidence for active virus shedding in nasal secretions and/or faeces was observed for 7/12 camels; viral RNA was detected in milk of five of these seven camels. The presence of MERS-CoV RNA in milk of camels actively shedding the virus warrants measures to prevent putative food-borne transmission of MERS-CoV.
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