An ESIPT solvatochromic fluorescent and colorimetric probe for sensitive and selective detection of copper ions in environmental samples and cell lines.

Copper is one of the most important transition metals in our body for various physiological functions. An imbalance in the homeostasis of copper in our body can lead to various neurological disorders such as Alzheimer's disease, Parkinson's, and Menkes disease. As a result, there is a need for the detection of excess copper present in the environment and the human system. In this work, we have designed a quinoline-based fluorescent/colorimetric probe (QHS) for rapid and selective detection of copper ions via quenching of fluorescence/color change from yellow to peach which is visible to the naked eye. The probe displayed high selectivity towards copper(II), i.e., Cu(II) in the presence of different metal analytes in water samples. The sensing mechanism of the probe was confirmed by NMR, HRMS, IR spectroscopy, and SEM. The detection limit of Cu(II) ions was found to be 0.493 µM which is lower than the tolerable limit of copper (20 µM) in drinking water as per the EPA. The probe was also utilized for the visualization of Cu(II) in cell lines. The probe was also demonstrated for its application in real-time detection of aqueous samples using portable paper strips.

Synthesis and evaluation of small organic molecule as reactivator of organophosphorus inhibited acetylcholinesterase.

A series of uncharged salicylaldehyde oximes were synthesized and evaluated for the reactivation of organophosphorus (OP) nerve agents simulants Diethylchlorophosphonate (DCP) & Diethylcyanophosphonate (DCNP) and pesticides (paraoxon & malaoxon) inhibited electric eel Acetylcholinesterase (AChE). The computational software Swiss ADME and molinspiration were used to unfold the probability of drug-likeness properties of the oximes derivatives. Substituted aromatic oximes with diethylamino or bromo group with free hydroxyl group ortho to oxime moiety were found efficient to regenerate the enzymatic activity in in-vitro AChE assay. The alkylation of the ortho hydroxyl group of derivatives led to the loss of reactivation potential. The derivatives with a hydroxyl group and without oxime group and vice versa did not show significant reactivation potency against tested OP toxicants. Further, we also evaluated the reactivation potential of these selected molecules on the rat brain homogenate against different OPs inhibited ChE and found maximum reactivation potency of oxime 2e. The in-vitro results were further validated by molecular docking and dynamic studies which showed that the hydroxyl group interacted with serine amino acids in the catalytic anionic site of AChE enzyme and was stable up to 200 ns consequently providing proper orientation to oxime moiety for reactivating the OP inhibited enzyme. It has thus been proved by the structure-activity relationship of oximes derivatives that hydroxyl group ortho to oxime is essential for reactivating OP inhibited electric eel AChE. Amongst the twenty-one oximes derivatives, 2e was found to be most active in regenerating the paraoxon, malaoxon, DCP and DCNP inhibited AChE enzyme.

Natural products and their derivatives as multifunctional ligands against Alzheimer's disease.

Alzheimer's disease (AD), a complex neurodegenerative disorder causing multiple cellular changes including impaired cholinergic system, beta-amyloid (ßA) aggregation, tau hyperphosphorylation, metal dyshomeostasis, neuroinflammation, and many other pathways are involved in the pathogenesis of the disease. However, the exact cause of the disease is not known. Natural products such as flavonoids, alkaloids, resveratrol, and curcumin have multifunctional properties, and have drawn the attention of the researchers because these molecules are capable of interacting concurrently with the multiple targets of AD. Therefore, natural products and their derivatives with proven efficacy could be used in the management of the neurodegenerative disorders. This review focuses on the natural product based multitarget directed ligands like tacrine-coumarin, tacrine-huperzine A, harmine-isoxazoline, berberine-thiophenyl, galantamine-indole, pyridoxine-resveratrol, donepezil-curcumin and their mode of action.

Potential of in situ SSF laccase produced from Ganoderma lucidum RCK 2011 in biobleaching of paper pulp.

Production of laccase from Ganoderma lucidum RCK 2011 under solid-state fermentation (SSF) conditions was optimized using response surface methodology, resulting in an approximate eightfold increase compared to that in the unoptimized media. Further, the enzyme produced under SSF as whole fermented substrate (in situ SSF laccase) was found to be more stable than the in vitro enzyme (harvested by downstreaming processing of fermented wheat bran). Interestingly, the biobleaching potentials of both in situ and in vitro SSF laccases were comparable, saving 25% chlorine dioxide for achieving similar pulp brightness as obtained in the pulp treated chemically. The reduction in the demand of chlorine dioxide in the pulp bleaching sequence subsequently decreased the levels of adsorbable organic halogen (AOX) in the resulting effluents of the process by 20% compared to the effluents obtained from chemical bleaching sequence. Therefore, direct application of in situ SSF laccase in pulp biobleaching will be environmentally friendly as well as economical and viable for implementation in paper mills.

Application of advanced oxidation processes and toxicity assessment of transformation products.

Advanced Oxidation Processes (AOPs) are the techniques employed for oxidation of various organic contaminants in polluted water with the objective of making it suitable for human consumption like household and drinking purpose. AOPs use potent chemical oxidants to bring down the contaminant level in the water. In addition to this function, these processes are also capable to kills microbes (as disinfectant) and remove odor as well as improve taste of the drinking water. The non-photochemical AOPs methods include generation of hydroxyl radical in absence of light either by ozonation or through Fenton reaction. The photochemical AOPs methods use UV light along with H2O2, O3 and/or Fe+2 to generate reactive hydroxyl radical. Non-photochemical method is the commonly used whereas, photochemical method is used when conventional O3 and H2O2 cannot completely oxidize organic pollutants. However, the choice of AOPs methods is depended upon the type of contaminant to be removed. AOPs cause loss of biological activity of the pollutant present in drinking water without generation of any toxicity. Conventional ozonation and AOPs can inactivate estrogenic compounds, antiviral compounds, antibiotics, and herbicides. However, the study of different AOPs methods for the treatment of drinking water has shown that oxidation of parent compound can also lead to the generation of a degradation/transformation product having biological activity/chemical toxicity similar to or different from the parent compound. Furthermore, an increased toxicity can also occur in AOPs treated drinking water. This review discusses various methods of AOPs, their merits, its application in drinking water treatment, the related issue of the evolution of toxicity in AOPs treated drinking water, biocatalyst, and analytical methods for identification of pollutants /transformed products and provides future directions to address such an issue.

Bifunctional in vivo role of laccase exploited in multiple biotechnological applications.

Laccases are multicopper enzymes present in plants, fungi, bacteria, and insects, which catalyze oxidation reactions together with four electron reduction of oxygen to water. Plant, bacterial, and insect laccases have a polymerizing role in nature, implicated in biosynthesis of lignin, melanin formation, and cuticle hardening, respectively. On the other hand, fungal laccases carry out both polymerizing (melanin synthesis and fruit body formation) as well as depolymerizing roles (lignin degradation). This bifunctionality of fungal laccases can be attributed to the presence of multiple isoforms within the same as well as different genus and species. Interestingly, by manipulating culture conditions, these isoforms with their different induction patterns and unique biochemical characteristics can be expressed or over-expressed for a targeted biotechnological application. Consequently, laccases can be considered as one of the most important biocatalyst which can be exploited for divergent industrial applications viz. paper pulp bleaching, fiber modification, dye decolorization, bioremediation as well as organic synthesis. The present review spotlights the role of fungal laccases in various antagonistic applications, i.e., polymerizing and depolymerizing, and co-relating this dual role with potential industrial significance.

Triaging HPV-positive women with p16/Ki-67 dual-stained cytology: Results from a sub-study nested into the ATHENA trial.

OBJECTIVES: In addition to genotyping for HPV16/18, dual-immunostaining for p16/Ki-67 has shown promise as a triage of HPV-positive women. We assessed the performance of p16/Ki-67 dual-stained cytology for triaging HPV-positive women undergoing primary HPV screening. METHODS: All women ≥25years with valid cervical biopsy and cobas® HPV Test results from the cross-sectional phase of ATHENA who were referred to colposcopy (n=7727) were eligible for enrolment. p16/Ki-67 dual-stained cytology was retrospectively performed on residual cytologic material collected into a second liquid-based cytology vial during the ATHENA enrolment visit. The diagnostic performance of dual-stained cytology, with or without HPV16/18 genotyping, for the detection of biopsy-confirmed cervical intraepithelial neoplasia grade 3 or worse (CIN3+) was determined and compared to Pap cytology. Furthermore, the number of colposcopies required per CIN3+ detected was determined. RESULTS: Dual-stained cytology was significantly more sensitive than Pap cytology (74.9% vs. 51.9%; p<0.0001) for triaging HPV-positive women, whereas specificity was comparable (74.1% vs. 75.0%; p=0.3198). Referral of all HPV16/18 positive women combined with dual-stained cytology triage of women positive for 12 "other" HPV genotypes provided the highest sensitivity for CIN3+ (86.8%; 95% CI: 81.9-90.8). A similar strategy but using Pap cytology for the triage of women positive for 12 "other" HPV genotypes was less sensitive (78.2%; 95% CI: 72.5-83.2; p=0.0003), but required a similar number of colposcopies per CIN3+ detected. CONCLUSIONS: p16/Ki-67 dual-stained cytology, either alone or combined with HPV16/18 genotyping, represents a promising approach as a sensitive and efficient triage for colposcopy of HPV-positive women when primary HPV screening is utilized.

Primary cervical cancer screening with human papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening test.

OBJECTIVES: ATHENA evaluated the cobas HPV Test as the primary screen for cervical cancer in women ≥25years. This reports the 3-year end-of-study results comparing the performance of HPV primary screening to different screening and triage combinations. METHODS: 42,209 women ≥25years were enrolled and had cytology and hrHPV testing. Women with abnormal cytology (≥atypical squamous cells of undetermined significance) and those HPV positive were referred to colposcopy. Women not reaching the study endpoint of CIN2+ entered the 3-year follow-up phase. RESULTS: 3-year CIR of CIN3+ in cytology-negative women was 0.8% (95% CI; 0.5-1.1%), 0.3% (95% CI 0.1-0.7%) in HPV-negative women, and 0.3% (95% CI; 0.1-0.6%) in cytology and HPV negative women. The sensitivity for CIN3+ of cytology was 47.8% (95% CI; 41.6-54.1%) compared to 61.7% (95% CI; 56.0-67.5%) for the hybrid strategy (cytology if 25-29years and cotesting with cytology and HPV if ≥30years) and 76.1% (95% CI; 70.3-81.8%) for HPV primary. The specificity for CIN3+ was 97.1% (95% CI; 96.9-97.2%), 94.6% (95% CI; 94.4-94.8%), and 93.5% (95% CI; 93.3-93.8%) for cytology, hybrid strategy, and HPV primary, respectively. Although HPV primary detects significantly more cases of CIN3+ in women ≥25years than either cytology or hybrid strategy, it requires significantly more colposcopies. However, the number of colposcopies required to detect a single CIN3+ is the same as for the hybrid strategy. CONCLUSIONS: HPV primary screening in women ≥25years is as effective as a hybrid screening strategy that uses cytology if 25-29years and cotesting if ≥30years. However, HPV primary screening requires less screening tests.

Interlaboratory variation in the performance of liquid-based cytology: insights from the ATHENA trial.

Although it is recognized that cervical cytology is highly subjective, and that there is considerable interlaboratory variation in how slides are evaluated, little is known as to how this impacts the performance of cytology. In the ATHENA trial, liquid-based cytology specimens from 46,887 eligible women ≥21 years of age were evaluated at four large regional US laboratories, providing a unique opportunity to evaluate the impact of interlaboratory variations on the performance of cervical cytology. All women with abnormal cytology (atypical squamous cells of undetermined significance or higher) were referred to colposcopy, as were all high-risk human papillomavirus (hrHPV)-positive women ≥25 years of age and a random subset of those ≥25 years of age who were negative by both hrHPV testing and cytology. Sociodemographics, risk factors for cervical disease, and prevalence of cervical intraepithelial neoplasia (CIN) were similar across the laboratories. There were considerable differences among the laboratories both in overall cytological abnormal rates, ranging from 3.8 to 9.9%, and in sensitivity of cytology to detect CIN grade 2 or worse (CIN2+), from 42.0 to 73.0%. In contrast, the hrHPV positivity rate varied only from 10.9 to 13.4%, and the sensitivity of hrHPV testing from 88.2 to 90.1%. These observations suggest that hrHPV testing without cytology should be considered as the initial method for cervical cancer screening.

Comparison of cervical cancer screening strategies incorporating different combinations of cytology, HPV testing, and genotyping for HPV 16/18: results from the ATHENA HPV study.

OBJECTIVE: The objective of the study was to compare 9 cervical cancer screening strategies to the current screening standard (cytology with human papillomavirus [HPV] triage of atypical squamous cells of undetermined significance) for the detection of high-grade cervical disease. STUDY DESIGN: Women (n = 34,254) aged 30 years or older from the Addressing the Need for Advanced HPV Diagnostics (ATHENA) study underwent screening with cytology and HPV testing with simultaneous HPV16/18 genotyping; those with atypical squamous cells of undetermined significance cytology or greater or HPV-positive status were referred for colposcopy. RESULTS: In general, screening strategies that offered greater sensitivity also required more referral to colposcopy. HPV testing was more sensitive than cytology for detection of cervical intraepithelial neoplasia grade 2 or greater, but strategies that depended on cytology for triage of HPV-positive women decreased this sensitivity. Various strategies of cotesting with cytology increased sensitivity but did so by increasing testing. Strategies that included integrated HPV16/18 testing provided more efficient referral to colposcopy. CONCLUSION: Strategies that maximize detection of women at greatest risk of cervical intraepithelial neoplasia grade 3 or greater by immediate referral to colposcopy, with follow-up testing of women at intermediate risk, maximize the benefits of cervical cancer screening while decreasing the potential harm. Incorporating screening with HPV and triage of HPV-positive women by a combination of genotyping for HPV16/18 and cytology provided a good balance between maximizing sensitivity (benefit) and specificity by limiting the number of colposcopies (potential harm).

Simple and efficient PET and AIEE mechanism-based fluorescent probes for sensing Tabun mimic DCNP.

The highly sensitive, selective, easy-to-prepare, aqueous media based on two novel probes 2-(pyren-1-yl)imidazo[1,2-a]pyridine (IMP-Py) and (2-(pyren-1-yl)imidazo[1,2-a]pyridin-3-yl)methanol (IMP-Py-OH) are synthesized for the detection of toxic chemical warfare nerve agent mimic diethylcyanochlorophosphonate (DCNP). Both probes are found effective in the detection of DCNP but comparatively, IMP-Py shows better properties in terms of instantaneous response, specificity, selectivity and a low detection limit of 16.9 nM. A significant enhancement of fluorescence intensity of IMP-Py due to aggregation-induced emission enhancement (AIEE) and photoinduced electron transfer (PET) phenomenon was inhibited due to phosphorylation of the hydroxy group of IMP-Py-OH in presence of DCNP has been observed. Taking the advantages of good sensitivity and fast response, probe IMP-Py has been fabricated into a viable paper strips portable product, tested for its potential for the detection of DCNP in tap water as well as with its vapor and response is visible under a UV lamp of 365 nm wavelength.

Chemical Modifications of Pyridoxine for Biological Applications: An Overview.

Pyridoxine and its derivatives, pyridoxamine, and pyridoxal have been recognized for more than 70 years and are known for regulating cellular biology and metabolism. During the past few decades, the anti-oxidant and anti-inflammatory properties of pyridoxine and its vitamers were explored. However, an interesting turnabout was observed in pyridoxine chemical modification in the last two decades. The various important pathophysiological aspects of pyridoxine and its derivatives on several cellular systems have been discovered by researchers. Recent findings have shown that many diseases, like cancer, diabetes, hypertension, tuberculosis, epilepsy, and neurodegenerative diseases are linked to the alteration of pyridoxine. Herein, our main focus is to review the importance of pyridoxine and its derivatives obtained by various chemical modifications, in various disease areas and to recognize important directions for future research.

A Combination of Novel HIV-1 Protease Inhibitor and Cytochrome P450 (CYP) Enzyme Inhibitor to Explore the Future Prospective of Antiviral Agents: Evotaz.

Viruses belong to the class of micro-organisms that are well known for causing infections in the human body. Antiviral medications are given out to prevent the spread of disease-causing viruses. When the viruses are actively reproducing, these agents have their greatest impact. It is particularly challenging to develop virus-specific medications since viruses share the majority of the metabolic functions of the host cell. In the continuous search for better antiviral agents, the United States Food and Drug Administration (USFDA) approved a new drug named Evotaz on January 29, 2015 for the treatment of human immunodeficiency virus (HIV). Evotaz is a combined once-daily fixed drug, containing Atazanavir, an HIV protease inhibitor, and cobicistat, an inhibitor of the human liver cytochrome P450 (CYP) enzyme. The medication is created such that it can kill viruses by concurrently inhibiting protease and CYP enzymes. The medicine is still being studied for a number of criteria, but its usefulness in children under the age of 12 is currently unknown. The preclinical and clinical characteristics of Evotaz, as well as its safety and efficacy profiles and a comparison of the novel drug with antiviral medications presently available in the market, are the main topics of this review paper.

Antimicrobial efficacy of sodium hypochlorite, saline, and Er, Cr:YSGG laser-assisted disinfection in root canal treatment of primary molars: An in vivo study.

Aim: The aim of the study was to compare the antimicrobial efficacy of sodium hypochlorite (NaOCl), Saline, and Er, Cr:YSGG laser-assisted disinfection through microbiological analysis in root canal treatment of primary molars. Materials and Methods: Forty-five primary teeth were selected for this study as per the inclusion and exclusion criteria in the age group of 4-8 years and then randomly allocated to Three Groups A, B, and C. In Group A, during root canal treatment, irrigation was done using NaOCl, in Group B, laser-assisted disinfection was done using Er, Cr:YSGG laser, and in Group C, saline was used as an irrigating agent. This was followed by obtaining pre- and postirrigation samples from the canals for microbiological investigation in all the groups. Data analysis was performed using Statistical Package for the Social Science-21 (SPSS-21). Results: NaOCl was more effective against aerobic bacteria while Er, Cr:YSGG laser was more effective against anaerobic bacteria when used for disinfection in root canal treatment. There was a significant difference among the three groups (P > 0.05). Conclusion: The study showed that NaOCl and Er, Cr:YSGG laser have antimicrobial effects when used for disinfection in root canal treatment of primary teeth. Moreover, the study also shows that Er, Cr:YSGG laser may be used as a valuable tool for laser-assisted disinfection in root canal treatment of primary teeth.

Production of ethanol, lipid and lactic acid from mixed agrowastes hydrolysate.

To combat the shortage of single agro-residue and overcome the problem of seasonal availability, it is beneficial to use mixture of lignocellulosic biomasses. In the present study, efforts were made to use mixed lignocellulosic biomass for production of bioethanol, along with microbial lipids and lactic acid. Upon enzymatic hydrolysis of mixed biomass at varied proportions it was observed that mixture of paddy straw and jute in the ratio 3:1 resulted in best sugar yield (41.50 g/L) at 10% substrate loading. Ethanolic fermentation of mixed substrate hydrolysate by thermotolerant yeast, Saccharomyces cerevisiae JRC6 resulted in 8.39 g/L of ethanol. To maintain sustainability and economic impact, oleaginous yeast (Trichosporon mycotoxinivorans S2) and lactic acid bacteria (Lactobacillus plantarum LP-9) were used for lipid production (14.5 g/L) and lactic acid production (11.08 g/L), respectively. Therefore, this study explored the potential of mixed lignocellulosic biomass to be exploited for production of various value-added products.

Psychological morbidities among Nepalese migrant workers to Gulf and Malaysia.

BACKGROUND: One of the important aftereffects of rapid global development is international mobility, which has placed the health of migrant workers as a key public health issue. A less-developed country, Nepal, with political instability and a significant lack of employment, could not remain untouched by this phenomenon of migration. Our goal was to identify and determine the predictors of anxiety, depression, and psychological wellbeing among Nepalese migrant workers in Gulf countries (United Arab Emirates, Saudi Arabia, Qatar, Oman, Kuwait, Bahrain) and Malaysia. METHODS: A descriptive cross-sectional study was used to collect information from 502 Nepalese migrant workers in the arrival section of Tribhuvan International Airport from May to June 2019 using purposive sampling. Workers with a minimum work experience of 6 months and above were included in the study. A structured questionnaire with socio-demographic items was used along with the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and WHO (five) wellbeing scale for measuring the subjective psychological wellbeing and screening for depression. RESULTS: The mean age of the respondents was 32.97 years. Majority (41.8%) of the respondents had work experience in Qatar and 63.7% had work experience of 1-5 years. The results suggested that 14.4% had mild to severe depression while 4.4% had a moderate level of anxiety. The WHO5 wellbeing index score suggested that 14.1% of the respondents had a score below 13, which is suggestive of poor psychological wellbeing. Further, the country of work (p = 0.043), sleeping hours (p = 0.001), occupation (p = 0.044), working hours (p = 0.000), water intake (p = 0.010) and anxiety level (p = 0.000) were found to be significantly associated with depression score. Similarly, sleeping hours (p = 0.022), occupation (p = 0.016), working hours (p = 0.000), water intake (p = 0.010), and anxiety level (0.000) were significantly associated with the WHO5 wellbeing score. CONCLUSIONS: Nepalese migrant workers in the Gulf countries (United Arab Emirates, Saudi Arabia, Qatar, Oman, Kuwait, Bahrain) and Malaysia bear an important burden of psychological morbidities. This highlights the need to prioritize the migrant worker's mental health by Nepal as well as Gulf countries and Malaysia.

Ecofriendly approach for detection of phenols in water using laccase from different fungi.

Laccase-initiated oxidative coupling reactions of phenol and its derivatives with 4-aminoantipyrene using air as an oxidant has been investigated. The oxidation reaction of phenols and 4-aminoantipyrene is getting a lot of attention due to environmental concerns. Oxidation of simple phenol and 4-aminoantipyrene as a benchmark reaction enabled us to rank the relative oxidation ability of various laccases. Among the laccases tested, laccase from Pycnoporus cinnabarinus successfully yielded 72% antipyrilquinoneimine dye. The present method can also be used to determine p-substituted phenols and chlorophenols. In this work, the influence of mediators on laccase activity has also been studied.

Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: a subanalysis of the ATHENA study.

BACKGROUND: The ATHENA study was designed to assess the performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping compared with liquid-based cytology for cervical cancer screening in a large US population aged 21 years and older. We did a subanalysis of this population to compare the screening performance of the cobas HPV test versus liquid-based cytology in women aged 25 years and older, and assess management strategies for HPV-positive women. METHODS: Women aged 25 years or older who were attending routine cervical screening were enrolled from 61 clinical centres in 23 US states. Cervical specimens were obtained for liquid-based cytology and HPV DNA testing with two first-generation assays (Amplicor HPV test and Linear Array HPV genotyping test) and the second-generation cobas HPV test (with individual HPV16 and HPV18 detection). Colposcopy and diagnostic biopsies were done on women with atypical squamous cells of undetermined significance (ASC-US) or worse cytology, those who tested positive with either first-generation HPV test, and a random sample of women who tested negative for HPV and cytology. All women not selected for colposcopy received their results and exited the study. Participants and colposcopists were masked to cytology and HPV test results until the colposcopy visit was completed. The primary endpoint for this substudy was histologically confirmed cervical intraepithelial neoplasia grade 3 (CIN3) or worse. This study is registered with ClinicalTrials.gov, number NCT00709891; the study is in the follow-up phase, which is due to be completed in December, 2012. FINDINGS: From May 27, 2008, to Aug 27, 2009, 47,208 women were enrolled, of whom 41,955 met our eligibility criteria. Valid cobas HPV and liquid-based cytology test results were available for 40,901 women (97%), who were included in this analysis. Of these, 4275 women (10%) tested cobas HPV positive and 2617 (6%) had abnormal cytology. 431 women were diagnosed with CIN2 or worse and 274 with CIN3 or worse. In women who had colposcopy, the cobas HPV test was more sensitive than liquid-based cytology for detection of CIN3 or worse (252/274 [92·0%, 95% CI 88·1-94·6] vs 146/274 [53·3%, 95% CI 47·4-59·1]; difference 38·7%, 95% CI 31·9-45·5; p<0·0001). Addition of liquid-based cytology to HPV testing increased sensitivity for CIN3 or worse to 96·7% (265/274, 95% CI 93·9-98·3), but increased the number of screen positives by 35·2% (5783/40,901 vs 4275/40,901) compared with HPV testing alone. As a triage test to identify CIN3 or worse in HPV-positive women, detection of HPV16, HPV18, or both alone was equivalent to detection of ASC-US or worse alone in terms of sensitivity (150/252 [59·5%] vs 133/252 [52·8%]; p=0·11) and positive predictive value (PPV) (150/966 [15·5%] vs 133/940 [14·1%]; p=0·20). Among HPV-positive women, detection of HPV16, HPV18, or both or low-grade squamous intraepithelial lesion or worse cytology had better sensitivity (182/252 [72·2%]; p<0·0001) and similar PPV (182/1314 [13·9%]; p=0·70) for detection of CIN3 or worse than ASC-US or worse cytology alone. Furthermore, detection of HPV16, HPV18, or both or high-grade squamous intraepithelial lesion or worse cytology had higher sensitivity (165/252 [65·5%]; p=0·0011) and PPV (165/1013 [16·3%]; p=0·031) for detection of CIN3 or worse than ASC-US or worse cytology alone. INTERPRETATION: HPV testing with separate HPV16 and HPV18 detection could provide an alternative, more sensitive, and efficient strategy for cervical cancer screening than do methods based solely on cytology. FUNDING: Roche Molecular Systems.

Imidazo[1,2-a]pyridine based small organic fluorescent molecules for selective detection of nerve agents simulants.

A fused heterocyclic ESIPT imidazo[1,2-a]pyridine-based probes for colorimetric and fluorometric detection of nerve agents simulant sarin (DCP) and tabun (DCNP) are reported. The probes (5b, 6a & 6b) were found to be highly sensitive and selective for the detection of DCNP and DCP at a micromolar concentration within seconds with no observed interference from other various types of analytes. The LOD for 6b towards DCP was found to be 0.6 µM with a linear range from 0 to 8 µM. The low-cost portable cellulose paper strip fabricated with probe 6b for real-time detection of DCP in the gas phase and spiked water has been developed. The paper strip product was found effective in detecting the presence of DCP in water and vapor state with substantial color changes which could be easily observed by the naked eye and under a handheld UV lamp at a wavelength of 365 nm.

Progress in the Development of Imidazopyridine-Based Fluorescent Probes for Diverse Applications.

Different classes of Imidazopyridine i.e., Imidazo[1,2-a]pyridine, Imidazo[1,5-a] pyridine, Imidazo[4,5-b]pyridine, have shown versatile applications in various fields. In this review, we have concisely presented the usefulness of the fluorescent property of imidazopyridine in different fields such as imaging tools, optoelectronics, metal ion detection, etc. Fluorescence mechanisms such as excited state intramolecular proton transfer, photoinduced electron transfer, fluorescence resonance energy transfer, intramolecular charge transfer, etc. are incorporated in the designed fluorophore to make it for fluorescent applications. It has been widely employed for metal ion detection, where selective metal ion detection is possible with triazole-attached imidazopyridine, ß-carboline imidazopyridine hybrid, quinoline conjugated imidazopyridine, and many more. Also, other popular applications involve organic light emitting diodes and cell imaging. This review shed a light on recent development in this area especially focusing on the optical properties of the molecules with their usage which would be helpful in designing application-based new imidazopyridine derivatives.