CdTe QD-based inhibition and reactivation assay of acetylcholinesterase for the detection of organophosphorus pesticides

An enzyme immobilized glutathione (GSH)-capped CdTe quantum dot (QD)-based fluorescence assay has been developed for monitoring organophosphate pesticides. In principle, GSH-capped CdTe QDs exhibit higher sensitivity towards H₂O₂ produced from the active enzymatic reaction of acetylcholinesterase (AChE) and choline oxidase (CHOx), which results in the fluorescence (FL) “turn-off” of the GSH-capped CdTe QDs. A “turn-on” FL of the CdTe QDs at 520 nm was recovered in the presence of organophosphate (OP). The FL changes of the GSH-capped CdTe QD/AChE/CHOx biosensor reasonably correspond to the amount of OP pesticides. The detection limit of the CdTe/AChE/CHOx biosensor towards paraoxon, dichlorvos, malathion and triazophos was 1.62 × 10⁻¹⁵ M, 75.3 × 10⁻¹⁵ M, 0.23 × 10⁻⁹ M and 10.6 × 10⁻¹² M, respectively. The GSH-capped CdTe QDs/AChE/CHOx biosensor was applied as a FL nanoprobe for assaying the enzymatic activity of AChE. The inhibited AChE was reactivated up to 94% using pyridine oximate (2-PyOx⁻), and functionalized pyridinium oximates (4-C₁₂PyOx⁻ and 4-C₁₈PyOx⁻) of varying chain lengths. It was found that the reactivation potency of the tested oximes varied with the chain length of the oximes. This biosensing system offers the promising benefit for the determination of the OP pesticides in food, water and environmental samples.

An enzyme immobilized glutathione (GSH)-capped CdTe quantum dot (QD)-based fluorescence assay has been developed for monitoring organophosphate pesticides.     

Prediction of atrial fibrillation in patients with severe mitral stenosis—role of atrial contribution to ventricular filling

Objective—Atrial contribution to ventricular filling was studied to assess its role in predicting the future development of atrial fibrillation (AF) in patients with severe mitral stenosis (MS) and sinus rhythm.

Design—Two hundred and eight patients with severe MS and sinus rhythm were followed up for 1 year. Baseline data were compared between group I (who developed AF at follow‐up) and group II (who maintained sinus rhythm). Left atrial size, severity of MS, velocity time integral (VTI) of mitral valve flow and VTI due to atrial systole (A‐VTI) were noted. Percentage contribution of A‐VTI to the total VTI (A‐%) was calculated. Sensitivity and specificity of A‐% to predict the onset of AF was obtained.

Results—Left atrial size, severity of MS and total VTI were similar in the two groups. Group I patients were older (31.1?±?9.1 and 18.4?±?6.5 years, respectively, p?<?0.03) with smaller A‐VTI (5.3?±?2.2 and 6.7?± 3.4?cm, respectively, p?<?0.01) and A‐% (8.9?±?1.8 and 11.2?±?2.7, respectively, p?<?0.003). A‐% of <9% (mean value of A‐VTI in group I) had high sensitivity (84%, positive predictive value 76%) and specificity (80%, negative predictive value 87%) to predict the development of AF.

Conclusion—Atrial contribution to ventricular filling is reduced in patients prone to develop AF (due to inefficient left atrial contraction, much before its dilatation). It can be used for early identification of patients likely to develop AF with high sensitivity and specificity. It is simple, easily available, cost‐effective and will guide earlier intervention and more frequent follow‐up. There is a preclinical loss in atrial pump function much before the eventual onset of AF.     

Multistage antiplasmodial activity of hydroxyethylamine compounds,in vitro and in vivo evaluations

Malaria, a global threat to the human population, remains a challenge partly due to the fast-growing drug-resistant strains of Plasmodium species. New therapeutics acting against the pathogenic asexual and sexual stages, including liver-stage malarial infection, have now attained more attention in achieving malaria eradication efforts. In this paper, two previously identified potent antiplasmodial hydroxyethylamine (HEA) compounds were investigated for their activity against the malaria parasite''s multiple life stages. The compounds exhibited notable activity against the artemisinin-resistant strain of P. falciparum blood-stage culture with 50% inhibitory concentrations (IC₅₀) in the low micromolar range. The compounds'' cytotoxicity on HEK293, HepG2 and Huh-7 cells exhibited selective killing activity with IC₅₀ values > 170 μM. The in vivo efficacy was studied in mice infected with P. berghei NK65, which showed a significant reduction in the blood parasite load. Notably, the compounds were active against liver-stage infection, mainly compound 1 with an IC₅₀ value of 1.89 μM. Mice infected with P. berghei sporozoites treated with compound 1 at 50 mg kg⁻¹ dose had markedly reduced liver stage infection. Moreover, both compounds prevented ookinete maturation and affected the developmental progression of gametocytes. Further, systematic in silico studies suggested both the compounds have a high affinity towards plasmepsin II with favorable pharmacological properties. Overall, the findings demonstrated that HEA and piperidine possessing compounds have immense potential in treating malarial infection by acting as multistage inhibitors.

Malaria, a global threat to the human population, remains a challenge partly due to the fast-growing drug-resistant strains of Plasmodium species.     

Understanding the underutilization of cervical brachytherapy for locally advanced cervical cancer

PurposeTo understand the reasons behind current low utilization of brachytherapy for locally advanced cervical cancer in the United States.Methods and MaterialsA 17-item survey was e-mailed to the American Brachytherapy Society (ABS) listserv of active members in 2018. Responses of attending physicians in the United States were included in the analysis.ResultsAmong a total of 135 respondents, 81 completed the survey. Eighty-four percent agree/strongly agree that cervical brachytherapy is underutilized, and 46.9% disagree/strongly disagree that residents are receiving adequate training for brachytherapy; 75.3% agree/strongly agree that inadequate maintenance of brachytherapy skills is a major obstacle to brachytherapy use; and 71.6% agree/strongly agree that increased time requirement constitutes a major obstacle. Over 97% will recommend brachytherapy for most patients with cervical cancer if given access/time; 72.8% always perform their own brachytherapy, whereas 29.6% reported some type of barrier exists in performing brachytherapy themselves, with time required to perform brachytherapy (9.9%) being a leading factor. A quarter (24.7%) routinely refer to other radiation oncologists for brachytherapy. Even among ABS members, 37.0% reported that they would perform an intensity-modulated radiation therapy or stereotactic body radiation therapy boost in specific scenarios in potentially curable patients. The most common scenario is inability to place a uterine tandem (56.7%).ConclusionsThe underutilization of brachytherapy in cervical cancer is widely recognized by ABS members with inadequate training during residency and inadequate maintenance of skills being possible major contributing factors. Even among ABS members, there are identifiable barriers. Continued advocacy and future initiatives in enhancing access to brachytherapy training and efficiency are needed.     

Synthesis of primaquine glyco‐conjugates as potential tissue schizontocidal antimalarial agents

Primaquine ( PQ ) is the only drug used to prevent relapse of malaria due to P. vivax and P. ovale, by eradicating the dormant liver form of the parasite (hypnozoites). The side‐effects associated with PQ limits is uses in treatment of malaria. To overcome the premature oxidative deamination and to increase the life span of drug in the biological system, the novel glyco‐conjugates of PQ were synthesized by coupling of primaquine with hexoses in phosphate buffer. The saccharide part of the hybrid molecules thought to direct the drug to the liver, where hypnozoites resides. All the synthesized compounds were fully characterized and evaluated for their radical curative activities. The three compounds viz glucoside ( 15a ), galactoside ( 15b ) and mannoside ( 15c ) with high activity were tested for their activity in rhesus monkeys where the most active compound 15b showed twofold activity (100% radical curative activity at 1.92 mmol/kg) than the standard drug PQ diphosphate (3.861 mmol/kg). It is proposed that results from these studies may be advantageous to develop a new potent tissue schizonticide antimalarial compound.     

Polyacrylamide hydrogel (Bulkamid®) for stress urinary incontinence in women: a systematic review of the literature

Introduction and hypothesis

Polyacrylamide hydrogel (PAHG, Bulkamid®) is one of several injectable agents currently used for the treatment of women with urinary stress incontinence. Although bulking agents appear to have lower efficacy rates compared to other surgical treatments, current evidence based on large prospective or comparative studies as well as systematic reviews is limited. The purpose of this study was to conduct a systematic review on the efficacy of PAHG in the treatment of female patients with stress urinary incontinence with regard to reproducibility, feasibility, safety and clinical outcome.

Methods

We searched MEDLINE (1966–2015), Scopus (2004–2015), POPLINE (1974–2015) and ClinicalTrials.gov (2008–2015) along with reference lists of electronically retrieved studies. Observational studies, prospective, retrospective and randomized controlled studies were included. Two reviewers independently selected studies, assessed the risk of bias and tabulated data to structured forms.

Results

We included 8 studies, which enrolled a total of 767 patients who received treatment with PAHG. We found that 186 of 767 women (24.3 %, range 12–35 %) required reinjection in order to achieve adequate efficacy. The most frequent adverse effects were pain at the site of injection (4–14 %) and urinary tract infections (3–7 %). Both the number of incontinence episodes/24 h and the number of ml/24 h were significantly reduced 1 year following treatment and the quality of life of patients was significantly improved.

Conclusions

PAHG is a safe intervention for treating women with stress urinary incontinence, but repeat injections are often required. Further research is mandated in the field in order to compare its efficacy to other bulking agents.

     

Fertility preservation through gonadal cryopreservation

Fertility preservation is an area of immense interest in today's society. The most effective and established means of fertility preservation is cryopreservation of gametes (sperm and oocytes) and embryos. Gonadal cryopreservation is yet another means for fertility preservation, especially if the gonadal function is threatened by premature menopause, gonadotoxic cancer treatment, surgical castration, or diseases. It can also aid in the preservation of germplasm of animals that die before attaining sexual maturity. This is especially of significance for valuable, rare, and endangered animals whose population is affected by high neonatal/juvenile mortality because of diseases, poor management practices, or inbreeding depression. Establishing genome resource banks to conserve the genetic status of wild animals will provide a critical interface between ex-situ and in-situ conservation strategies. Cryopreservation of gonads effectively lengthens the genetic lifespan of individuals in a breeding program even after their death and contributes towards germplasm conservation of prized animals. Although the studies on domestic animals are quite promising, there are limitations for developing cryopreservation strategies in wild animals. In this review, we discuss different options for gonadal tissue cryopreservation with respect to humans and to laboratory, domestic, and wild animals. This review also covers recent developments in gonadal tissue cryopreservation and transplantation, providing a systematic view and the advances in the field with the possibility for its application in fertility preservation and for the conservation of germplasm in domestic and wild species.     

Penicillium marneffei--an indicator disease of AIDS: a case report

Penicillium marneffei (PM), the only dimorphic species of the genus penicillium is the etiological agent of penicilliosis marneffei. This opportunistic fungal infection occurs among human immunodeficiency virus (HIV) infected and other immunocompromised patient in several regions of South-east Asia, where the infection is considered as an indicator disease of AIDS. A case of penicilliosis marneffei is reported in a patient whose HIV status was unknown and later turned to be in the late stage of AIDS. This demonstrates that it is indeed an indicator disease of AIDS. In India, penicilliosis has been reported among the inhabitants of Manipur state where the prevalence of HIV infection / AIDS is very high. The causative agent was first isolated from a captive bamboo rat. Investigation of the prevalence of the organism among bamboo rats of different countries of South East Asia revealed four species of bamboo rats to be harboring the organism. These four species of bamboo rats are Rhizomys sinensis, R. pruinosus, R. sumatrensis and Cannomys badius. In Manipur, Penicillium marneffei has been isolated from Cannomys badius. Any patient presenting with penicilliosis marneffei should be subjected to HIV counselling and testing if the HIV status is not known and further study regarding the ecology and epidemiology of the fungus is needed.     

Isolation of Aspergillus nidulans from a case of fungal rhinosinusitis: a case report

A rare species i.e. A. nidulans is reported as a causative agent of allergic fungal rhinosinusitis in this study. It is an increasingly recognized type of chronic recurring hypertrophic sinus disease. There are more than 185 species of aspergillus and over 95% of all infections are caused by A. fumigatus, A. flavus and A. niger. A. fumigatus alone accounts for the large majority of cases of both invasive and non invasive aspergillosis. A young immunocompetent lady presented with bilateral nasal obstruction due to multiple polypoid mass at Sheth Vadilal Sarabhai General Hospital, Ahmedabad. Provisional diagnosis of sinonasal polyposis possibly due to fungal cause with infiltration in to nasal cavity was made. Bilateral functional endoscopic sinus surgery with polypectomy was done. The specimen was examined by standard methods and the fungus was identified as A. nidulans by slide culture.