Reinvestigation of diphenylmethylpiperazine analogues of pyrazine as new class of Plasmodial cysteine protease inhibitors for the treatment of malaria.

Malaria eradication is still a global challenge due to the lack of a broadly effective vaccine and the emergence of drug resistance to most of the currently available drugs as part of the mainline artemisinin-based combination therapy. A variety of experimental approaches are quite successful in identifying and synthesizing new promising pharmacophore hybrids with distinct mechanisms of action. Based on our recent findings, the current study demonstrates the reinvestigation of a series of diphenylmethylpiperazine and pyrazine-derived molecular hybrids. Pyrazine-derived molecular hybrids were screened to investigate the antiplasmodial activity on drug-susceptible Pf3D7 and drug-resistant PfW2 strains. The selected compounds were shown to be potent dual inhibitors of cysteine protease PfFP2 and PfFP3. Time-course parasitic development study demonstrated that compounds were able to arrest the growth of the parasite at the early trophozoite stage. The compounds did not show hemolysis of red blood cells and showed selectivity to the parasite compared with the mammalian Vero and A5489 cell lines. The study underlined HR5 and HR15 as a new class of Plasmodial falcipain inhibitors with an IC50 of 6.2 µM and 5.9 µM for PfFP2 and 6.8 µM and 6.4 µM for PfFP3, respectively. Both compounds have antimalarial efficacy with IC50 values of 3.05 µM and 2.80 µM for the Pf3D7 strain, and 4.35 µM and 3.39 µM for the PfW2 strain, respectively. Further structural optimization may turn them into potential Plasmodial falcipain inhibitors for malaria therapeutics.

Can an Enhanced Recovery Protocol Result in a Safe and Effective Outpatient Simultaneous Bilateral Total Knee Arthroplasty?

BACKGROUND: Outpatient total knee arthroplasty (OP TKA) is found to benefit patients as well as the health care system. Studies on OP TKA have been limited to unilateral total knee arthroplasty (TKA). This study aimed to determine if enhanced recovery after surgery (ERAS) protocols can result in performing simultaneous bilateral TKA (SBTKA) safely and effectively in the OP setting. METHODS: This retrospective study compared patients who underwent SBTKA in an OP setting (OP group, n = 100) using an ERAS protocol from April 1, 2021, to June 30, 2022, and a propensity-matched historical group (inpatient group, n = 100) operated in an inpatient setting via conventional protocol from July 1, 2019, to June 30, 2020. The complication rate, readmission rate, visual analog score (VAS), range of motion (ROM), and Knee Society Score (KSS) were compared between the groups in the early postoperative and follow-up periods up to 1 year. RESULTS: We found a comparable complication rate (4 versus 7%, P = .4) and readmission rate (2 versus 3%, P = .7). The VAS score was significantly lower in the OP group on day 1, day 2, day 7, and day 14 postsurgery (P < .001). The KSS and ROM were significantly better in the OP group after 14 days (P < .001). The VAS, KSS, and ROM were comparable between the groups at 1 month and later follow-up periods (P > .05). CONCLUSIONS: An ERAS protocol in SBTKA patients resulted in safe same-day discharge with better early functional outcomes compared with conventional practices. The results from similar future studies can alleviate surgeon and patient concerns about OP TKA.

Exploring geochemical distribution of potentially toxic elements (PTEs) in wetland and agricultural soils and associated health risks.

This study is carried out to understand the degree of soil pollution, transport mechanism, and distribution pattern of potentially toxic elements (PTEs), including the exposure effects on human health. Towards this, topsoil samples were collected from the Saman wetland and surrounding agricultural fields in the Gangetic plain, India. The results show that the mean concentration of Cu, Hg, Zn, Pb, Th, As, U, and Cd of both soil types exceed the natural background values. The multivariate analysis suggests the soils are moderately contaminated with As, Cd, Zn, Pb, and Hg (possibly from anthropogenic sources) and heavily contaminated with Th and U, likely ascended from geogenic sources. The GIS-based geostatistical plots coupled with principal component analysis (PCA) and hierarchical cluster analysis (HCA) apportion the sources of these toxic elements, which vary greatly and are closely correlated to the geogenic processes and local anthropogenic sources like pesticides and agrochemicals. The health risk assessment revealed that the cumulative hazard index (HI) values of PTEs are lower than the safe level, suggesting no significant noncarcinogenic effect for adults and children. However, excess cancer risk (ECR) values exceed the permissible limit (1 × 10-6), signifying that exposure to the toxic element concentration may cause cancer in the exposed population, most probably in the children subpopulation. Thus, this study highlights the importance of local compliance, ensuring the quality checks and management policies in using pesticides and other agrochemicals containing PTEs to control the imposed cancer risks.

Motivating school communities towards behavior change and local ownership: a gamification intervention to prevent trachoma at primary schools in southern Ethiopia.

BACKGROUND: Ethiopia alone carries 49% of the global burden of trachoma, associated with a lack of safe water, sanitation and hygiene (WASH) and poor health practices. The aim of this study was to examine whether gamification among schoolchildren and promotion of local ownership of school WASH is associated with healthy behaviors and WASH infrastructure improvements. METHODS: Application of the Accelerate gamification intervention for elimination of trachoma, with an emphasis on gamification among schoolchildren and community involvement in motivating face-washing, handwashing and functional use of latrines, was undertaken. RESULTS: The study was conducted over 9 mo in 223 rural schools from six districts within the intervention area, reaching 93 518 schoolchildren. At baseline, students were observed washing their hands after using latrines in 23 (10.3%) schools. This increased to 132 (59%) schools (p≤0.001) at follow-up. The number of latrines increased from 585 at baseline to 594 at follow-up (p=0.031). The availability of handwashing stations in schools increased from 31 (13.9%) with water access (8%) and soap (5%) to 155 (69.5%) schools with handwashing stations with water access in 153 (98.7%) (p<0.001) and soap in 121 (78%) (p<0.001). CONCLUSIONS: Motivational strategies such as gamification among schoolchildren and promotion of local ownership of school WASH may be associated with healthy behaviors and WASH infrastructure improvements.

Naphthyl bearing 1,3,4-thiadiazoleacetamides targeting the parasitic folate pathway as anti-infectious agents: in silico, synthesis, and biological approach.

Malaria is still a complex and lethal parasitic infectious disease, despite the availability of effective antimalarial drugs. Resistance of malaria parasites to current treatments necessitates new antimalarials targeting P. falciparum proteins. The present study reported the design and synthesis of a series of a 2-(4-substituted piperazin-1-yl)-N-(5-((naphthalen-2-yloxy)methyl)-1,3,4-thiadiazol-2-yl)acetamide hybrids for the inhibition of Plasmodium falciparum dihydrofolate reductase (PfDHFR) using computational biology tools followed by chemical synthesis, structural characterization, and functional analysis. The synthesized compounds were evaluated for their in vitro antimalarial activity against CQ-sensitive PfNF54 and CQ-resistant PfW2 strain. Compounds T5 and T6 are the most active compounds having anti-plasmodial activity against PfNF54 with IC50 values of 0.94 and 3.46 µM respectively. Compound T8 is the most active against the PfW2 strain having an IC50 of 3.91 µM. Further, these active hybrids (T5, T6, and T8) were also evaluated for enzyme inhibition assay against PfDHFR. All the tested compounds were non-toxic against the Hek293 cell line with good selectivity indices. Hemolysis assay also showed non-toxicity of these compounds on normal uninfected human RBCs. In silico molecular docking studies were carried out in the binding pocket of both the wild-type and quadruple mutant Pf-DHFR-TS to gain further insights into probable modes of action of active compounds. ADME prediction and physiochemical properties support their drug-likeness. Additionally, they were screened for antileishmanial activity against L. donovani promastigotes to explore broader applications. Thus, this study provides molecular frameworks for developing potent antimalarials and antileishmanial agents.

Evolution of Diagnostic and Forensic Microbiology in the Era of Artificial Intelligence.

Diagnostic microbiology plays a vital role in managing infectious diseases, combating antimicrobial resistance, and containment of outbreaks. During the fourth industrial revolution, when artificial intelligence (AI) became an essential part of our day-to-day lives, its integration into healthcare would further revolutionize our knowledge and potential. Although in the budding stage, AI with machine learning is being increasingly utilized in various aspects of diagnostic microbiology. It can handle large datasets that are difficult to analyze manually. Researchers have developed and demonstrated several machine-learning algorithms for interpreting bacterial cultures, conducting image analysis for microbial detection, and predicting antimicrobial susceptibility patterns. Thus, AI may most likely be the ultimate solution to the ever-increasing demand for improved results with shorter turnaround times. AI can also assist forensic microbiologists in crime scene investigations, as it can guide individual identification, cause and time since death, and manner of death. This review summarizes the application of AI in diagnostic microbiology for performing diverse sets of microbial investigations and is an essential aid in forensic microbiology.

Development of diphenylmethylpiperazine hybrids of chloroquinoline and triazolopyrimidine using Petasis reaction as new cysteine proteases inhibitors for malaria therapeutics.

Malaria is a widespread infectious disease, causing nearly 247 million cases in 2021. The absence of a broadly effective vaccine and rapidly decreasing effectiveness of most of the currently used antimalarials are the major challenges to malaria eradication efforts. To design and develop novel antimalarials, we synthesized a series of 4,7-dichloroquinoline and methyltriazolopyrimidine analogues using a multi-component Petasis reaction. The synthesized molecules (11-31) were screened for in-vitro antimalarial activity against drug-sensitive and drug-resistant strains of Plasmodium falciparum with an IC50 value of 0.53 µM. The selected compounds were screened to evaluate in-vitro and in-silico enzyme inhibition efficacy against two cysteine proteases, PfFP2 and PfFP3. The compounds 15 and 17 inhibited PfFP2 with an IC50 = 3.5 and 4.8 µM, respectively and PfFP3 with an IC50 = 4.9 and 4.7 µM, respectively. Compounds 15 and 17 were found equipotent against the Pf3D7 strain with an IC50 value of 0.74 µM, whereas both were displayed IC50 values of 1.05 µM and 1.24 µM for the PfW2 strain, respectively. Investigation of effect of compounds on parasite development demonstrated that compounds were able to arrest the growth of the parasites at trophozoite stage. The selected compounds were screened for in-vitro cytotoxicity against mammalian lines and human red-blood-cell (RBC), which demonstrated no significant cytotoxicity associated with the molecules. In addition, in silico ADME prediction and physiochemical properties supported the drug-likeness of the synthesized molecules. Thus, the results highlighted the diphenylmethylpiperazine group cast on 4,7-dichloroquinoline and methyltriazolopyrimidine using Petasis reaction may serve as models for the development of new antimalarial agents.

A Family of 2D-MXenes: Synthesis, Properties, and Gas Sensing Applications.

Gas sensors, capable of detecting and monitoring trace amounts of gas molecules or volatile organic compounds (VOCs), are in great demand for numerous applications including diagnosing diseases through breath analysis, environmental and personal safety, food and agriculture, and other fields. The continuous emergence of new materials is one of the driving forces for the development of gas sensors. Recently, 2D materials have been gaining huge attention for gas sensing applications, owing to their superior electrical, optical, and mechanical characteristics. Especially for 2D MXenes, high specific area and their rich surface functionalities with tunable electronic structure make them compelling for sensing applications. This Review discusses the latest advancements in the 2D MXenes for gas sensing applications. It starts by briefly explaining the family of MXenes, their synthesis methods, and delamination procedures. Subsequently, it outlines the properties of MXenes. Then it describes the theoretical and experimental aspects of the MXenes-based gas sensors. Discussion is also extended to the relation between sensing performance and the structure, electronic properties, and surface chemistry. Moreover, it highlights the promising potential of these materials in the current gas sensing applications and finally it concludes with the limitations, challenges, and future prospects of 2D MXenes in gas sensing applications.

Slipped Capital Femoral Epiphysis Associated With Vitamin C Deficiency in a 7-year-old Boy.

Scurvy is rare in the present world and is mostly found in children with abnormal dietary habits and physical and mental disabilities. Scurvy can present in various forms, mimicking several common diseases, thus making the diagnosis difficult. Spontaneous epiphyseal separation is known to occur in scurvy, although rarely reported. The usual locations of these epiphyseal separations are distal femur and proximal humerus. Our case is unique in that scurvy in a seemingly normal child resulted in proximal femur epiphyseal separation which was not reported previously. We report a case of a 7-year-old boy presenting with pain and swelling in multiple joints for 6 months and later inability to walk. Pseudoparalytic frog-leg posture, dietary history of selective eating, and typical radiologic features made us consider a diagnosis of scurvy which was confirmed by a low serum vitamin C level. He developed epiphyseal separation of proximal femur and was treated with percutaneous screw fixation. Vitamin C supplementation resulted in prompt improvement clinically and radiologically.

SKINTED: A Rare Complication After Total Knee Arthroplasty.

BACKGROUND: Surgery of the knee, injury to the infrapatellar branch of the saphenous nerve, traumatic eczematous dermatitis is a neuropathic dermatitis specific to total knee arthroplasty (TKA), occurring around the healed surgical scar area. Very few case reports exist in orthopaedic literature regarding this rare skin complication after TKA. We report a series of cases and estimated the incidence of this condition in our institute. METHODS: During the 1-year period from January 2018 to December 2018, patients who have undergone TKA and later presented with skin lesions adjacent to the operated site were identified. Detailed history was taken, and full clinical examination was performed for all the reported cases. RESULTS: A total of 9 lesions in 8 patients were identified out of a total of 203 consecutive TKAs operated during the study period, with an estimated incidence of 4.4%. The mean age was 64 years (range, 58-78 years). The mean time from surgery to diagnosis was 4 months (range, 3-6 months). CONCLUSIONS: This group of dermatitis caused due to surgical transection of the infrapatellar branch of the saphenous nerve during TKA is a rare cutaneous complication, with an estimated incidence of 4.4% from this study. Lesions typically appear lateral to the operative scar within an area of hypoesthesia. Lesions in all patients improved after topical steroid therapy with no recurrences at further follow-up. Arthroplasty surgeons should have awareness of this benign complication, thereby avoiding unwarranted additional workup and alleviating unnecessary psychological stress to the patient.

Design and synthesis of leucine-linked quinazoline-4(3H)-one-sulphonamide molecules distorting malarial reductase activity in the folate pathway.

Optimization of a modified Grimmel's method for N-heterocyclization of a leucine-linked sulfonamide side-arm at position 2 leading to 2,3-disustituted-4-quinazolin-(3H)-ones was accomplished. Further, 22 hybrid quinazolinone motifs (4a-v) were synthesized by N-heterocyclization reaction under microwave irradiation using the ionic liquid [Bmim][BF4 ]-H2 O as green solvent as well as the catalyst. The in vitro screening of the hybrid entities against the malarial species Plasmodium falciparum yielded five potent molecules 4l, 4n, 4o, 4t, and 4u owning antimalarial activity comparable to those of the reference drugs. In continuation, an in silico study was carried out to obtain a pharmacophoric model and quantitative structure-activity relationship. We also built a 3D-QSAR model to procure more information that could be applied to design new molecules with more potent Pf-DHFR inhibitory activity. The designed pharmacophore was recognized to be more potent for the selected molecules, exhibiting five pharmacophoric features. The active scaffolds were further evaluated for enzyme inhibition efficacy against alleged receptor Pf-DHFR computationally and in vitro, proving their candidature as lead dihydrofolate reductase inhibitors, and the selectivity of the test candidates was ascertained by toxicity study against Vero cells. Good oral bioavailability was also proved by studying pharmacokinetic properties.

Column and batch sorption investigations of nickel(II) on extractant-impregnated resin.

Macroporous resin-supported reagents have been identified as potential adsorbents for removal of toxic pollutants. This article presents an experimental designed to evaluate the sorption and desorption of nickel(II) with the help of column and batch procedure using simple extractant-impregnated resin (EIR). Isonitroso-4-methyl-2-pentanone (IMP) as an extractant was impregnated on a solid support like Amberlite XAD-4 to prepare the EIR sorbent. Column experimental conditions such as pH, sample flow rate and volume, eluting solution, and interfering ions were studied to optimize the nickel(II) sorption and recovery from aqueous media. The column results suggest that the quantitative nickel(II) sorption was observed at pH 5-6, and the quantitative recovery (≥ 95%) was achieved by using 1.0 M HNO3. The high concentrations of cations and anions (except EDTA) present in the spiked binary and multi-element mixture solution show no interferences in both quantitative sorption and recovery of nickel(II), whereas the batch experiments were performed to evaluate nickel(II) sorption behavior using the linearized and non-linearized kinetic and isotherm models. By error function analysis, the Freundlich isotherm and the pseudo-first-order kinetic model were found to describe best the experimental data obtained over the studied concentration range and sorption time, respectively. The maximum sorption capacity of nickel(II) onto the EIR sorbent was found to be ~ 81 mg/g. The mean free energy (E = 10.1 kJ/mol) determined using Dubinin-Radushkevich isotherm suggests chemical nature of nickel(II) sorption on EIR. The novelty of the EIR adsorbent lies in its potential for separation and recovery of nickel(II) at trace level in water samples of different origin.

Green synthesis, biological evaluation, molecular docking studies and 3D-QSAR analysis of novel phenylalanine linked quinazoline-4(3H)-one-sulphonamide hybrid entities distorting the malarial reductase activity in folate pathway.

A modified Grimmel's method for N-heterocyclization of phenylalanine linked sulphonamide side arm at position-2 was optimized leading to 2,3-disustituted-4-quinazolin-(3H)-ones. Further, [Bmim][BF4]-H2O (IL) was used as green solvent as well as catalyst for the synthesis of twenty two hybrid quinazolinone motifs (4a-4v) by N-heterocyclization reaction using microwave irradiation technique. The in vitro screening of the hybrid entities against the malarial species Plasmodium falciparum yielded five potent molecules 4l, 4n, 4r, 4t & 4u owing comparable antimalarial activity to the reference drugs. In continuation, anin silicostudy was carried out to obtain a pharmacophoric model and quantitative structure activity relationship. We also built a 3D-QSAR model to procure more information that could be applied to design new molecules with more potent Pf-DHFR inhibitory activity. The designed pharmacophore was recognized to be more potent for the selected molecules, exhibiting five pharmacophoric features. The active scaffolds were further evaluated for enzyme inhibition efficacy against alleged receptor Pf-DHFR computationally and in vitro, proving their candidature as lead dihydrofolate reductase inhibitors as well as the selectivity of the test candidates was ascertained by toxicity study against vero cells. The perception of good oral bioavailability was also proved by study of pharmacokinetic properties.

Sorption and recovery of platinum from simulated spent catalyst solution and refinery wastewater using chemically modified biomass as a novel sorbent.

In this study, Lagerstroemia speciosa biomass modified by polyethylenimine (PEI-LS) was developed as a potential biosorbent for sorption and recovery of platinum(II) from platinum bearing waste solutions. Batch experiments were conducted to study the effect of various parameters on the sorption and recovery of platinum(II) using PEI-LS. The equilibrium time for platinum(II) sorption process was found to be 6 h. Both the sorption kinetics and sorption isotherm data fits pseudo second-order kinetic model and Langmuir isotherm, respectively. The maximum sorption capacity of platinum(II) onto PEI-LS at pH 2 for the studied temperature range (25-45 °C) is in the range of 122-154 mg/g. Evaluation of thermodynamic parameters suggests that the platinum(II) sorption is spontaneous and endothermic in nature. The regeneration of PEI-LS can be achieved using acidic thiourea as an eluent for recovery of platinum from the biosorbent. Fourier transform infrared (FT-IR) analysis suggests many functional groups were involved in platinum(II) sorption onto PEI-LS. Both the scanning electron microscope/energy dispersive spectroscopy (SEM/EDS) and X-ray photoelectron spectroscopy (XPS) analysis suggest a successful modification of raw biomass with PEI. The XPS analysis further concludes that platinum(II) sorption is governed by ion-exchange and co-ordination reaction. Finally, the PEI-LS was shown to recover ≥ 90% of platinum from two simulated solutions: the acid-leached spent catalyst solution and refinery wastewater. The biosorbent developed in this study is a low-cost and eco-friendly media that can be effectively used for platinum recovery from industrial wastewater.

Transitions between lifetime alcohol use, regular use and remission: Results from the 2004 South African Stress and Health Survey.

BACKGROUND: Hazardous alcohol consumption presents a serious threat to the health and wellbeing of all people and is linked to chronic and acute health problems. OBJECTIVES: To: (i) estimate the prevalence of alcohol use disorders and remission from alcohol abuse and dependence in the South African (SA) population; and (ii) determine whether age of onset, education, sex and level of cohort alcohol use are associated with commencement of use, regularity of use, and transitions to and remission from more harmful levels of use. METHODS: The study was a nationally representative sample of 4 315 individuals aged ≥18 years. In a multistage, area probability sample of adults, data were collected from 4 311 alcohol users using the World Mental Health Survey Initiative version of the Composite International Diagnostic Interview version 3.0. All analyses were carried out using SAS version 9.4. RESULTS: Of the respondents, 40.6% indicated lifetime use of alcohol, 35.3% reported regular use, and 8.8% met diagnostic criteria for alcohol abuse and 2.7% for alcohol dependence. The prevalence of remission from lifetime abuse without dependence was 55.9%. The median age of onset of alcohol use was 20 years, with transition from use to regular use occurring within ~1 - 3 years. The results suggest that males, students (compared with those who had completed a high level of education) and greater alcohol use in the respondent's birth cohort were all associated with increased odds of commencing alcohol use. For transitions from use to regular use, increased odds were associated with males, greater birth cohort alcohol use, low education and later (>21 years) onset of first alcohol use. CONCLUSIONS: Our findings suggest that cohort alcohol use is associated with transition to commencement of use and from use to regular use in the general SA population. The study further highlighted the need for interventions among males and university students, given that hazardous alcohol consumption seems to be the most prevalent public health issue encountered by university students and males.

Ionic liquid mediated stereoselective synthesis of alanine linked hybrid quinazoline-4(3H)-one derivatives perturbing the malarial reductase activity in folate pathway.

Grimmel's method was optimized as well as modified leading to the cyclization and incorporation of alanine linked sulphonamide in 4-quinazolin-(3H)-ones. Further, the generation of heterocyclic motif at position-3 of 4-quinazolinones was explored by synthesis of imines, which unfortunately led to an isomeric mixture of stereoisomers. The hurdle of diastereomers encountered on the path was eminently rectified by development of new rapid and reproducible methodology involving the use of imidazolium based ionic liquid as solvents as well as catalyst for cyclization as well as synthesis of imines in situ at position-3 leading to procurement of single E-isomer as the target hybrid heterocyclic molecules. The purity and presence of single isomer was also confirmed by HPLC and spectroscopic techniques. Further, the synthesized sulphonamide linked 4-quinazolin-(3H)-ones hybrids were screened for their antimalarial potency rendering potent entities (4b, 4c, 4 l, 4 t and 4u). The active hybrids were progressively screened for enzyme inhibitory efficacy against presumed receptor Pf-DHFR and h-DHFR computationally as well as in vitro, proving their potency as dihydrofolate reductase inhibitors. The ADME properties of these active molecules were also predicted to enhance the knowhow of the oral bioavailability, indicating good bioavailability of the active entities.

Photocatalytic reduction of organic pollutant under visible light by green route synthesized gold nanoparticles.

We report a rapid method of green chemistry approach for synthesis of gold nanoparticles (AuNPs) using Lagerstroemia speciosa leaf extract (LSE). L. speciosa plant extract is known for its effective treatment of diabetes and kidney related problems. The green synthesis of AuNPs was complete within 30min at 25°C. The same could also be achieved within 2min at a higher reaction temperature (80°C). Both UV-visible spectroscopy and transmission electron microscopy results suggest that the morphology and size distribution of AuNPs are dependent on the pH of gold solution, gold concentration, volume of LSE, and reaction time and temperature. Comparison between Fourier transform infrared spectroscopy (FT-IR) spectra of LSE and the synthesized AuNPs indicate an active role of polyphenolic functional groups (from gallotannins, lagerstroemin, and corosolic acid) in the green synthesis and capping of AuNPs. The green route synthesized AuNPs show strong photocatalytic activity in the reduction of dyes viz., methylene blue, methyl orange, bromophenol blue and bromocresol green, and 4-nitrophenol under visible light in the presence of NaBH4. The non-toxic and cost effective LSE mediated AuNPs synthesis proposed in this study is extremely rapid compared to the other reported methods that require hours to days for complete synthesis of AuNPs using various plant extracts. Strong and stable photocatalytic behavior makes AuNPs attractive in environmental applications, particularly in the reduction of organic pollutants in wastewater.

Reliability of the English version of the painDETECT questionnaire.

BACKGROUND: The painDETECT questionnaire (PD-Q) has been used widely for the identification of neuropathic pain (NeP); however, the reliability of the English version of the PD-Q has never been investigated. OBJECTIVE: This study aimed to determine the reliability of the PD-Q pre- (T0) and immediately post- (T1) clinical consultation and at one-week follow-up (T2). METHODS: We recruited 157 patients attending a Neurosurgery Spinal Clinic and Pain Management Department. Minor changes to PD-Q instructions were made to facilitate patient understanding; however, no changes to individual items or scoring were made. Intraclass correlation coefficients (ICCs) were used to assess the reliability of PD-Q total scores between T0-T1 and T0-T2; weighted kappa (κ) was used to assess the agreement of PD-Q classifications (unlikely NeP, ambiguous, likely NeP) between all time-points. To ensure stability of clinical pain, patients scoring ≤2 or ≥6 on the Patient Global Impression Scale (PGIC) at T2 were excluded from the T0-T2 analysis. RESULTS: Accounting for missing data and exclusions (change in PGIC score), data for 136 individuals (mean [SD] age: 56.8 [15.2]; 54% male) was available, of whom n = 129 were included in the T0-T1 and n = 69 in the T0-T2 comparisons. There was almost perfect agreement between the PD-Q total scores at T0-T1 time-points (ICC 0.911; 95% CI: 0.882-0.941) and substantial agreement at T0-T2 (ICC 0.792; 95% CI: 0.703-0.880). PD-Q classifications demonstrated substantial agreement for T0-T1 (weighted κ: 0.771; 95% CI: 0.683-0.858) and for T0-T2 (weighted κ: 0.691; 95% CI: 0.553-0.830). Missing data was accounted in 13% of our cohort and over 42% of our patients drew multiple pain areas on the PD-Q body chart. CONCLUSION: The English version of the PD-Q is reliable as a screening tool for NeP. The validity of the questionnaire is still in question and has to be investigated in future studies.

Novel 2,3-disubstituted quinazoline-4(3H)-one molecules derived from amino acid linked sulphonamide as a potent malarial antifolates for DHFR inhibition.

An optimization of a modified Grimmel's method for N-heterocyclization of Leucine linked sulphonamide leading to 2,3-disustituted-4-quinazolin-(3H)-ones was accomplished. Further, nineteen hybrid quinazolinone motifs (5a-5s) were synthesized by N-heterocyclization reaction under microwave irradiation using TEAA (IL) as green solvent as well as catalyst. The in vitro screening of the hybrid entities against the plasmodium species P. falciparum yielded five antimalarial potent molecules 5g, 5l, 5m, 5n &5p owing comparable activity to the reference drugs. The active scaffolds were further evaluated for enzyme inhibition efficacy against alleged receptor Pf-DHFR computationally as well as in vitro, proving their candidature as lead dihydrofolate reductase inhibitors. The prediction of the ADMET properties of the potent molecules also indicated their good oral bioavailability.

Formulation and In Vitro Evaluation of Ofloxacin Tablets using Natural Gums as Binders.

Natural gums are economical, easily available, and useful as tablet binders. In the present investigation, an attempt was made to formulate Ofloxacin tablets using three natural binders, namely Acacia arabica, Hibiscus esculentus, and xanthan gum. Such six batches of Ofloxacin tablets were prepared by using different types and amounts of the natural binders by the wet granulation method. The tablets were analyzed for their hardness, friability, and weight variation, and in vitro release was performed in a phosphate buffer at pH 6.8. The prepared tablets were also evaluated for their various release kinetics and similarity factors f2. The physical properties of the tablets containing the natural binders showed sufficient hardness, desirable disintegration time, and low friability. Their better percentage of drug release was observed as compared to the marketed formulation showing more than 85% drug release within 45 minutes. The in vitro release data was well-fitted into zero-order and the values of release exponent 'n' were between 0.303 and 0.514. The high similarity factor f2 of 64.50 was achieved with the best batch in comparison to the marketed tablets. The results obtained indicated that the gum Acacia arabica performed as well as gelatin compared to the other binders for the Ofloxacin tablet formulation.