The Validity of Peer Review in a General Medicine Journal

All the opinions in this article are those of the authors and should not be construed to reflect, in any way, those of the Department of Veterans Affairs

EVALUATION OF A METHOD FOR DETECTION OF BOTH METALLO BETALACTAMASE (MBL) AND EFFLUX PRODUCTION USING CARBONYL CYANIDE 3-CHLOROPHENYLHYDRAZONE (CCCP)±COMBINATION METHOD AMONG PSEUDOMONAS AERUGINOSA ISOLATED FROM CLINICAL SPECIMENS

Objective: To standardize a method for the differential detection of Metallo Betalactamase (MBL) production and efflux pump mechanism using Carbonyl Cyanide 3-ChloroPhenylhydrazone (CCCP) among the clinical isolates of Pseudomonas aeruginosa recovered from ocular specimens.Methods: A total of 110 clinical isolates of Pseudomonas aeruginosa were plated onto Muller-Hinton agar (MHA) plate with CCCP and without CCCP. Carbapenems-Ethylenediaminetetraacetic acid (EDTA) combination disk method was performed on CCCP± plates for individual isolates and the results were compared.Results: Out of 110 clinical isolates of P aeruginosa studied, 11(10%) were tested positive for MBL Production by carbapenem-EDTA combination test/CCCP-test. In which, six isolates showed positive for both efflux and MBL production using CCCP+plate and 5 isolates showed positive only for MBL production.Conclusion: The current study standardized a method for detecting both MBL and efflux mechanism in a single plate consists of CCCP± plate containing antibiotic disk with and without EDTA. Implication of this method in routine diagnostics will help the clinicians to treat the patient with appropriate drug choice and dosage.Â

Artificial Intelligence-Driven Drug Discovery: Identifying Novel Compounds for Targeted Cancer Therapies

This study delves into the potential of artificial intelligence (AI) in revolutionizing drug discovery, specifically focusing on the identification of new compounds for targeted cancer therapies. Through the application of advanced machine learning algorithms, our methodology achieved impressive predictive accuracy, with an accuracy rate of 92.5%, an AUC-ROC of 0.94, and an AUC-PR of 0.91. The AI models successfully pinpointed 35 novel compounds predicted to demonstrate high efficacy against specific cancer targets, indicating promising prospects for advancements in cancer treatment. Examination of the molecular structures of these identified compounds unveiled positive characteristics, with 90% adhering to Lipinski's Rule of Five, indicating their suitability as potential drug candidates. Additionally, the average predicted half-life of 12 hours suggests advantageous pharmacokinetic properties, bolstering their potential viability. A comparative assessment highlighted the efficiency advantages of the AI-driven approach, revealing an 80% reduction in time and a 65% reduction in costs compared to traditional methods. Beyond its application in targeted cancer therapies, the success of our approach implies broader implications for the pharmaceutical research landscape, offering a more streamlined and accurate methodology. While these outcomes are promising, it is crucial to recognize limitations and stress the importance of sustained collaboration between computational and experimental researchers. Future directions encompass the refinement of models, incorporation of diverse datasets, and rigorous experimental validation. In summary, our study underscores the efficacy of AI-driven drug discovery in identifying new compounds for targeted cancer therapies. The identified compounds, characterized by favorable structural and pharmacokinetic attributes, present a promising avenue for overcoming challenges in current cancer treatments. These findings set the stage for ongoing exploration, collaborative initiatives, and advancements at the intersection of artificial intelligence and drug discover

In vitro anti-inflammatory, anti-diabetic and antioxidant potential of Cissus quadrangularis along with its orexigenic activity in Drosophila melanogaster

Plants with diverse pharmacological activities are actively being explored for human health. Cissus quadrangularis (L) has been reported to possess numerous phytochemicals and is used to relieve various disorders. This article aims at providing evidence of the diverse pharmacological activities in terms of orexigenic, anti-inflammatory, anti-diabetic and antioxidant activities of C. quadrangularis for further application in clinical development. The results revealed that inhibition of hemolysis was within the range of 8-9-25.6% at concentrations of 12.5-200 µg/ml. Methanol extract of C. quadrangularis stems exhibited porcine pancreatic ?-amylase (PPA) inhibition (p?0.05) at concentrations of 0.25 and 0.30 mg/ml. The glucose adsorption capacity of the C. quadrangularis was observed to be inversely proportional to the molar concentration of glucose. The higher food intake by Drosophila in food medium with plant extract is presumably related to orexigenic property of C. quadrangularis. Protease activity of C. quadrangularis stem extract revealed total activity 975 U/ml and specific activity as 3768 U/mg. The absorbance of C. quadrangularis in reducing power assay were between 0.91and 1.85. Highest total antioxidant activity of 67.2 µg TE/g was observed and the hydroxyl radicals scavenging activity was observed in a dose dependent manner. The results provide supporting data that C. quadrangularis may contain active compounds useful in treating anti-inflammatory, anti-diabetic disorders

Variation in How Cognitive Control Modulates Sentence Processing

Prior research suggests that cognitive control can assist the comprehension of sentences that create conflict between interpretations, at least under some circumstances. However, the mixed pattern of results suggests that cognitive control may not always be necessary for accurate comprehension. We tested whether cognitive control recruitment for language processing is systematically variable, depending on the type of sentential ambiguity or conflict, individual differences in cognitive control, and task demands. Participants completed two sessions in a web-based experiment. The first session tested conflict modulation using interleaved Stroop and sentence comprehension trials. Critical sentences contained syntax-semantics or phrase-attachment conflict. In the second session, participants completed three cognitive control and three working memory tasks. Exploratory factor analysis was used to index individual differences in a cognitive control factor and a working memory factor. At the group level, there were no significant conflict modulation effects for either syntax-semantics or phrase-attachment conflict. At the individual differences level, the cognitive control factor correlated with offline comprehension accuracy but not online processing measures for both types of conflict. Together, the results suggest that the role of cognitive control in sentence processing may vary according to task demands. When overt decisions are required, individual differences in cognitive control may matter such that better cognitive control results in better language comprehension performance. The results add to the mixed evidence on conflict modulation and raise questions about the situations under which cognitive control influences online processing

Identification of a Novel Gammaretrovirus in Prostate Tumors of Patients Homozygous for R462Q RNASEL Variant

Ribonuclease L (RNase L) is an important effector of the innate antiviral response. Mutations or variants that impair function of RNase L, particularly R462Q, have been proposed as susceptibility factors for prostate cancer. Given the role of this gene in viral defense, we sought to explore the possibility that a viral infection might contribute to prostate cancer in individuals harboring the R462Q variant. A viral detection DNA microarray composed of oligonucleotides corresponding to the most conserved sequences of all known viruses identified the presence of gammaretroviral sequences in cDNA samples from seven of 11 R462Q-homozygous (QQ) cases, and in one of eight heterozygous (RQ) and homozygous wild-type (RR) cases. An expanded survey of 86 tumors by specific RT-PCR detected the virus in eight of 20 QQ cases (40%), compared with only one sample (1.5%) among 66 RQ and RR cases. The full-length viral genome was cloned and sequenced independently from three positive QQ cases. The virus, named XMRV, is closely related to xenotropic murine leukemia viruses (MuLVs), but its sequence is clearly distinct from all known members of this group. Comparison of gag and pol sequences from different tumor isolates suggested infection with the same virus in all cases, yet sequence variation was consistent with the infections being independently acquired. Analysis of prostate tissues from XMRV-positive cases by in situ hybridization and immunohistochemistry showed that XMRV nucleic acid and protein can be detected in about 1% of stromal cells, predominantly fibroblasts and hematopoietic elements in regions adjacent to the carcinoma. These data provide to our knowledge the first demonstration that xenotropic MuLV-related viruses can produce an authentic human infection, and strongly implicate RNase L activity in the prevention or clearance of infection in vivo. These findings also raise questions about the possible relationship between exogenous infection and cancer development in genetically susceptible individuals

Perifosine plus lenalidomide and dexamethasone in relapsed and relapsed/refractory multiple myeloma: a Phase I Multiple Myeloma Research Consortium study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92443/1/bjh9173.pd

A One Health Approach to Defining Animal and Human Helminth Exposure Risks in a Tribal Village in Southern India.

The high burden of soil-transmitted helminth infections has been studied in India; however, little data exist on zoonotic helminths, and on animal-associated exposure to soil-transmitted helminths. Our study took place in the Jawadhu Hills, which is a tribal region in Tamil Nadu, India. Using a One Health approach, we included animal and environmental samples and human risk factors to answer questions about the associations among infected household soil, domestic animals, and human risk factors. Helminth eggs were identified by microscopy in animal and soil samples, and a survey about risk factors was administered to the head of the household. Contact with animals was reported in 71% of households. High levels of helminth infections were found across domestic animal species, especially in goats, chickens, and dogs. Helminth eggs were recorded in 44% of household soil (n = 43/97) and separately in 88% of soil near a water source (n = 28/32). Animal contact was associated with 4.05 higher odds of having helminth eggs in the household soil (P = 0.01), and also having a water source at the household was associated with a 0.33 lower odds of having helminth eggs in the household soil (P = 0.04). Soil moisture was a mediator of this association with a significant indirect effect (P < 0.001). The proportion mediated was 0.50. While our work does not examine transmission, these results support consideration of animal-associated exposure to STH and potentially zoonotic helminths in future interventions to reduce helminth burden. Our study provides support for further investigation of the effects of animals and animal fecal matter on human health