Evaluation of Habenaria aitchisonii Reichb. for antioxidant, anti-inflammatory, and antinociceptive effects with in vivo and in silico approaches.

Habenaria aitchisonii Reichb was analyzed in this research, including its chemical composition and its in vitro antioxidant, anti-inflammatory, acute oral toxicity, and antinociceptive activity. The chloroform and ethyl acetate fractions were found to be the most powerful based on in vitro antioxidant, anti-inflammatory, and analgesic assays. The acute oral toxicity of the crude methanolic extract was determined before in vivo studies. The acetic acid and formalin tests were used to measure the antinociceptive effect, and the potential mechanisms involved in antinociception were explored. The carrageenan-induced paw edema test was used to examine the immediate anti-inflammatory effect, and many phlogistic agents were used to determine the specific mechanism. Furthermore, for ex vivo activities, the mice were sacrificed, the forebrain was isolated, and the antioxidant levels of glutathione (GSH), superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS) and catalase (CAT) were estimated using a UV spectrophotometer. No toxicity was seen at oral dosages up to 3,000 mg/kg. The antinociceptive impact was much higher than the standard drug. Both the inflammatory and neurogenic phases of the formalin experiment revealed an analgesic effect in the chloroform and ethyl acetate fractions. In carrageenan anti-inflammatory assays, the chloroform fraction (Ha.Chf) was the most potent fraction. We further studied the GC-MS of crude plant extract and found a total of 18 compounds. In the anti-inflammatory mechanism, it was observed that the Ha.Chf inhibits the COX-2 as well as 5-LOX pathways. The results exhibited that this species is a good source of phytocomponents like germacrone, which can be employed as a sustainable and natural therapeutic agent, supporting its traditional use in folk medicine for inflammatory conditions and pain.

Isolation, invitro, invivo anti-inflammatory, analgesic and antioxidant potential of Habenaria plantegania Lindl.

Habenaira plantaginea belong to orchid family which is native to Asia. Members of this family are commonly famous for the cure of pain and inflammation. To date, no research was found on isolation of compounds from this plant for the treatment of inflammation and analgesia nor has been published to our knowledge. The purpose of this study was to evaluate an analgesic, anti-inflammatory and anti-oxidant activity of the isolated compound from the most potent chloroform sub-fraction and the isolated compounds form the habenaria plantaginea. Anti-inflammatory analgesic and antioxidant potential of the various chloroform sub-fractions and isolated compounds from the most potent sub-fraction (HP-1 & HP-1) were screened for their in vitro enzymatic assays. Furthermore, prior to in-vivo investigation, the isolated compounds were subjected for their toxicity study. The potent compound was then examined for acetic acid-induced writhing, hot plate test, carrageenan-induced inflammation assays. Further various phlogistic agents were used for the evaluation of mechanism. In the COX-2 inhibitory assay the chloroform sub fraction Cf-4 demonstrated excellent activity as compared to the other sub-fraction with 92.15% inhibition. The COX-2 enzyme make prostaglandins which are directly involved in inflammation. Likewise against 5-LOX the Cf-4 was the most potent sub-fraction with IC50 3.77 µg/mL. The 5-LOX catalyzes the biosynthesis of leukotrienes which is a group of lipid mediators of inflammation derived from arachidonic acid. Free radicals can induce inflammation through cellular damage while chronic inflammation generates a large number of free radicals, whose eventually lead to inflammation. In antioxidant assays the Cf-4 fraction was displayed excellent results against ABTS, DPPH and H2O2 free radical with 88.88, 77.44, and 65.52% inhibition at highest concentration. Likewise, the compound HP-1 demonstrated 88.81, 89.34 and 80.43% inhibition while compound HP-2 displayed 84.34, 91.52 and 82.34% inhibition against ABTS, DPPH and H2O2 free radical which were comparable to the standard drug ascorbic acid respectively. This study's findings validate the use of this species as traditional use.

Investigation of anti-nociceptive, anti-inflammatory potential and ADMET studies of pure compounds isolated from Isodon rugosus Wall. ex Benth.

The strong ethnopharmacological utilization of Isodon rugosus Wall. Ex. Benth is evident in the treatment of several types of pain and inflammation, including toothache, earache, abdominal pain, gastric pain, and generalized body pain and inflammation. Based on this background, the antinociceptive effects of the crude extract, various fractions, and essential oil have been reported previously. In this research work, we isolate and characterize pure bioactive compounds from I. rugosus and evaluate possible mechanisms using various in vivo and in vitro models. The pure compounds were analyzed for analgesic and anti-inflammatory activities through various assays. The column chromatography of the chloroform fraction of I. rugosus led to the identification of two pure compounds, i.e., 1 and 2. Compound 1 demonstrated notable inhibition (62% writhing inhibition, 72.77% COX-2 inhibition, and 76.97% 5-LOX inhibition) and anti-inflammatory potential (>50% paw edema inhibition at various intervals). The possible mechanism involved in antinociception was considered primarily, a concept that has already been elucidated through the application of naloxone (an antagonist of opioid receptors). The involvement of adrenergic receptors was investigated using a hot plate model (an adrenergic receptor antagonist). The strong ethnomedicinal analgesic background of I. rugosus, supported by previous reports and current observations, leads to the conclusion that I. rugosus is a potential source of antinociceptive and anti-inflammatory bioactive compounds. It may be concluded from the results that the isolated analgesic compounds of I. rugosus may be a possible alternative remedy for pain and inflammation management with admirable efficacy and safety profiles.

Thermoelectric Hydrogel Electronic Skin for Passive Multimodal Physiological Perception.

Electronic skins (e-skins) are being extensively researched for their ability to recognize physiological data and deliver feedback via electrical signals. However, their wide range of applications is frequently restricted by the indispensableness of external power supplies and single sensory function. Here, we report a passive multimodal e-skin for real-time human health assessment based on a thermoelectric hydrogel. The hydrogel network consists of poly(vinyl alcohol)/low acyl gellan gum with [Fe(CN)6]4-/3- as the redox couple. The introduction of glycerol and Li+ furnishes the gel-based e-skin with antidrying and antifreezing properties, a thermopower of 2.04 mV K-1, fast self-healing in less than 10 min, and high conductivity of 2.56 S m-1. As a prospective application, the e-skin can actively perceive multimodal physiological signals without the need for decoupling, including body temperature, pulse rate, and sweat content, in real time by synergistically coupling sensing and transduction. This work offers a scientific basis and designs an approach to develop passive multimodal e-skins and promotes the application of wearable electronics in advanced intelligent medicine.

One-pot synthesis of novel chitosan-salicylaldehyde polymer composites for ammonia sensing.

Chitosan (Chs)-salicylaldehyde (Sal) polymer derivatives were formed via the reaction of Chs-Sal with zinc oxide nanoparticles (ZnO NPs) and beta-cyclodextrin (ß-CD). These polymers were synthesized through inclusion with ß-CD and doping with ZnO NPs to give pseudopolyrotaxane and Chs-Sal/ZnO NPs composite, respectively, for low-temperature detection and sensing of NH3 vapors as great significance in environmental control and human health. Additionally, the polymer (Chs-Sal/ß-CD/ZnO NPs) was prepared via the insertion of generated composite (Chs-Sal/ZnO NPs) through ß-cyclodextrin ring. The structural and morphological characterizations of the synthesized derivatives were confirmed by utilizing FTIR, XRD and, SEM, respectively. Also, the optical properties and thermal gravimetric analysis (TGA) of the synthesized polymers were explored. The obtained results confirmed that using ß-CD or ZnO NPs for modification of polymer (Chs-Sal) dramatically enhanced thermal stability and optical features of the synthesized polymers. Investigations on the NH3-sensing properties of Chs-Sal/ß-CD/ZnO NPs composite were carried out at concentrations down to 10 ppm and good response and recovery times (650 s and 350 s, respectively) at room temperature (RT) and indicated that modification by ß-CD and doping with ZnO NPs effectively improves the NH3-sensing response of Chs-Sal from 712 to 6192 using Chs-Sal/ß-CD/ZnO NPs, respectively, with low LOD and LOQ of 0.12 and 0.4 ppb, respectively.

Nylon fiber waste as a prominent adsorbent for Congo red dye removal.

In this research nylon fibers wastes (NF) were fabricated into porous sheet using a phase inversion technique to be utilized as an adsorbent materials for Congo red dye (CR). The fabricated sheet denoted as NS was characterized using FTIR and XRD. The surface studies of the adsorbent materials using SEM and BET analysis reveals a highly pores structure with an average pore volume 0.61 cc/g and BET surface area of 767 m2/g. The adsorption studies of fabricated NS were employed into CR at different parameters as pH, effect of time and dye concentration. The adsorption isotherm and kinetic studies were more fit to Langmuir and pseudo second order models. The maximum adsorption capacity qmax reached 188 mg/g with removal percentage of 95 for CR concentration of 400 mg/L at pH 6 and 0.025 g NS dose for 10 ml CR solution. The regeneration study reveals a prominent adsorption behavior of NS with removal % of 88.6 for CR (300 mg/L) after four adsorption desorption cycles. Effect of incorporation of NaonFil Clay to NS was studied using Response Surface Methodology (RSM) modeling and reveals that 98.4% removal of CR could be achieved by using 19.35% wt. of fiber with 8.2 g/L dose and zero clay, thus at a predetermined parameters studies of NanoFil clay embedded into NS, there are no significant effect for %R for CR.

Repurposing immune boosting and anti-viral efficacy of Parkia bioactive entities as multi-target directed therapeutic approach for SARS-CoV-2: exploration of lead drugs by drug likeness, molecular docking and molecular dynamics simulation methods.

The COVID-19 pandemic has caused adverse health (severe respiratory, enteric and systemic infections) and environmental impacts that have threatened public health and the economy worldwide. Drug repurposing and small molecule multi-target directed herbal medicine therapeutic approaches are the most appropriate exploration strategies for SARS-CoV-2 drug discovery. This study identified potential multi-target-directed Parkia bioactive entities against SARS-CoV-2 receptors (S-protein, ACE2, TMPRSS2, RBD/ACE2, RdRp, MPro, and PLPro) using ADMET, drug-likeness, molecular docking (AutoDock, FireDock and HDOCK), molecular dynamics simulation and MM-PBSA tools. One thousand Parkia bioactive entities were screened out by virtual screening and forty-five bioactive phytomolecules were selected based on favorable binding affinity and acceptable pharmacokinetic and pharmacodynamics properties. The binding affinity values of Parkia phyto-ligands (AutoDock: -6.00--10.40 kcal/mol; FireDock: -31.00--62.02 kcal/mol; and HDOCK: -150.0--294.93 kcal/mol) were observed to be higher than the reference antiviral drugs (AutoDock: -5.90--9.10 kcal/mol; FireDock: -35.64--59.35 kcal/mol; and HDOCK: -132.82--211.87 kcal/mol), suggesting a potent modulatory action of Parkia bioactive entities against the SARS-CoV-2. Didymin, rutin, epigallocatechin gallate, epicatechin-3-0-gallate, hyperin, ursolic acid, lupeol, stigmasta-5,24(28)-diene-3-ol, ellagic acid, apigenin, stigmasterol, and campesterol strongly bound with the multiple targets of the SARS-CoV-2 receptors, inhibiting viral entry, attachment, binding, replication, transcription, maturation, packaging and spread. Furthermore, ACE2, TMPRSS2, and MPro receptors possess significant molecular dynamic properties, including stability, compactness, flexibility and total binding energy. Residues GLU-589, and LEU-95 of ACE2, GLN-350, HIS-186, and ASP-257 of TMPRSS2, and GLU-14, MET-49, and GLN-189 of MPro receptors contributed to the formation of hydrogen bonds and binding interactions, playing vital roles in inhibiting the activity of the receptors. Promising results were achieved by developing multi-targeted antiviral Parkia bioactive entities as lead and prospective candidates under a small molecule strategy against SARS-CoV-2 pathogenesis. The antiviral activity of Parkia bioactive entities needs to be further validated by pre-clinical and clinical trials.

Low delayed bleeding and high complete closure rate of mucosal defects with the novel through-the-scope dual-action tissue clip after endoscopic resection of large nonpedunculated colorectal lesions (with video).

BACKGROUND AND AIMS: Complete closure after endoscopic resection of large nonpedunculated colorectal lesions (LNPCLs) can reduce delayed bleeding but is challenging with conventional through-the-scope (TTS) clips alone. The novel dual-action tissue (DAT) clip has clip arms that open and close independently of each other, facilitating tissue approximation. We aimed to evaluate the rate of complete closure and delayed bleeding with the DAT clip after endoscopic resection of LNPCLs. METHODS: This was a multicenter prospective cohort study of all patients who underwent defect closure with the DAT clip after EMR or endoscopic submucosal dissection (ESD) of LNPCLs ≥20 mm from July 2022 to May 2023. Delayed bleeding was defined as a bleeding event requiring hospitalization, blood transfusion, or any intervention within 30 days after the procedure. Complete closure was defined as apposition of mucosal defect margins without visible submucosal areas <3 mm along the closure line. RESULTS: One hundred seven patients (median age, 64 years; 42.5% women) underwent EMR (n = 63) or ESD (n = 44) of LNPCLs (median size, 40 mm; 74.8% right-sided colon) followed by defect closure. Complete closure was achieved in 96.3% (n = 103) with a mean of 1.4 ± .6 DAT clips and 2.9 ± 1.8 TTS clips. Delayed bleeding occurred in 1 patient (.9%) without requiring additional interventions. CONCLUSIONS: The use of the DAT clip in conjunction with TTS clips achieved high complete defect closure after endoscopic resection of large LNPCLs and was associated with a .9% delayed bleeding rate. Future comparative trials and formal cost-analyses are needed to validate these findings. (Clinical trial registration number: NCT05852457.).

Outcomes of Cold Snare Endoscopic Mucosal Resection of Nonampullary Duodenal Adenomas ≥1 cm: A Multicenter Study.

BACKGROUND AND AIMS: Endoscopic mucosal resection (EMR) with use of electrocautery (conventional EMR) has historically been used to remove large duodenal adenomas, however, use of electrocautery can predispose to adverse events including delayed bleeding and perforation. Cold snare EMR (cs-EMR) has been shown to be safe and effective for removal of colon polyps, but data regarding its use in the duodenum is limited. The aim of this study is to evaluate the efficacy and safety of cs-EMR for nonampullary duodenal adenomas ≥1 cm. METHODS: This was a multicenter retrospective study of patients with nonampullary duodenal adenomas ≥1 cm who underwent cs-EMR between October 2014 and May 2023. Patients who received any form of thermal therapy were excluded. Primary outcomes were technical success and rate of recurrent adenoma. Secondary outcomes were adverse events and predictors of recurrence. RESULTS: A total of 125 patients underwent resection of 127 nonampullary duodenal adenomas with cs-EMR. Follow up data was available in 89 cases (70.1%). The recurrent adenoma rate was 31.5% (n=28). Adverse events occurred in 3.9% (n=5) with four cases of immediate bleeding (3.1%) and one case of delayed bleeding (0.8%). There were no cases of perforation. The presence of high-grade dysplasia was found to be an independent predictor of recurrence (OR: 10.9 [95% CI: 1.1-102.1], p=0.036). CONCLUSION: This retrospective multicenter study demonstrates that cs-EMR for nonampullary duodenal adenomas is safe and technically feasible with an acceptable recurrence rate. Future prospective studies are needed to directly compare outcomes of cs-EMR with conventional and underwater EMR.

Age-Related Macular Degeneration in Patients with Androgenetic Alopecia: Could the Monocyte/HDL Ratio Be the Link?

INTRODUCTION: Both Androgenetic alopecia (AGA) and age-related macular degeneration (AMD) shared the microinflammatory milieu and increased oxidative stress as important criteria in their pathogenesis. The monocyte/high density lipoprotein (HDL) ratio (MHR) seems to be an easy-to-calculate prognostic marker of microinflammation. OBJECTIVES: To assess MHR in patients with AGA and its correlation to AMD in these patients, if any. METHODS: Forty patients with AGA aged 40 years or more of both sexes and 40 control subjects participated in this case-control study. General, dermatological, and ophthalmologic examination, MHR evaluation and optical coherence tomography (OCT) were performed. RESULTS: The mean MHR was significantly higher in AGA patients (6.98 ± 2.21) than in controls (3.82 ± 0.68) (P < 0.001). AMD was significantly higher in patients than controls (P < 0.001). Eighty percent of AGA patients were diagnosed with AMD versus 20% of control subjects. The presence of AMD in AGA was significantly related to the degree of severity of AGA in male patients (P = 0.02). The MHR was significantly higher in AGA patients found to have AMD (9.37 ± 1.1 and 7.01 ± 1.42 in the wet and dry type respectively) than those without AMD (P < 0.001). CONCLUSIONS: AMD may develop more frequently in those with AGA. The MHR seems to be a missing link between both conditions, and could be utilized as a potential biomarker for predicting AMD in AGA patients.

Multitargeted inhibitory effect of Mitoxantrone 2HCl on cervical cancer cell cycle regulatory proteins: a multitargeted docking-based MM\GBSA and MD simulation study.

Cervical cancer remains a significant global health concern that starts in the cervix, the lower part of the uterus that connects to the vagina and is caused by the human papillomavirus (HPV), necessitating the development of effective multitargeted effective and resistance-proof therapies. In early-stage cervical cancer may not show any symptoms, however, as the cancer progresses, some people may experience- abnormal vaginal bleeding, watery or bloody vaginal discharge, pain in the pelvis or lower back, pain during sex, and frequent and painful urination. In this study, we screened the complete FDA-approved drug library using a multitargeted inhibitory approach against four cervical cancer proteins, namely mitotic arrest deficient -2, DNA polymerase epsilon B-subunit, benzimidazole-related -1, and threonine-protein kinase-1 which crucially plays its role for the in its development process. We employed the HTVS, SP and XP algorithms for efficient filtering and screening that helped to identify Mitoxantrone 2HCl against all of them with docking and MM\GBSA scores ranging from - 11.63 to - 7.802 kcal/mol and - 74.38 to - 47.73 kcal/mol, respectively. We also evaluated the interaction patterns of each complex and the pharmacokinetics properties that helped gain insight into interactions. Subsequently, we performed multiscale MD simulations for 100 ns to understand the dynamic behaviour and stability of the Mitoxantrone 2HCl -protein complexes that revealed the formation of stable drug-protein complexes and provided insights into the molecular interactions that contribute to Mitoxantrone's inhibitory effects on these proteins and can be a better drug for cervical cancer. However, experimental studies of these findings could pave the way for therapies to combat cervical cancer effectively.

A new promising approach to urodynamic stress urinary incontinence care can help menopausal women.

Introduction: The goal of this study is to evaluate the effectiveness of single-incision mini-sling in the surgical treatment of postmenopausal urodynamic stress urinary incontinence (SUI) compared to the standard trans-obturator mid-urethral sling. Material and methods: This prospective study was carried out in two tertiary centres; Al-Azhar University Maternity & Urology Hospitals. A total of 120 postmenopausal women with urodynamic SUI were randomized to undergo either single-incision mini-sling (n = 60) or standard trans-obturator mid-urethral sling procedure (n = 60) from May 2019 until Oct 2021. Main outcome measures: efficacy was evaluated utilizing objective cure rate (cough stress test) and subjective cure rate (Sandvik incontinence severity index and International Consultations on Incontinence Questionnaire - Short Form), intraoperative and postoperative complications, and postoperative pain (using a visual analogue scale). Results: The single-incision mini-sling (SIMS) and transobturator tape (TOT) groups had no statistically significant difference in subjective and objective cure rates (p > 0.05). Compared with the transvaginal tape O group, patients in the SIMS group had significantly less postoperative pain, shorter operative duration, and less intraoperative blood loss (all p-values < 0.05). No significant difference in perioperative complications was observed between both groups. Conclusions: Single-incision mini-sling was superior to TOT in postmenopausal as SIMS is of similar effectiveness, more safe and minimally invasive with earlier ambulance.

A paradigm of higher success rate of intracytoplasmic sperm injection - preovulatory human chorionic gonadotropin-day serum oestradiol.

Introduction: The aim of the study is to evaluate the correlation between the level of serum oestradiol (E2) on the day of human chorionic gonadotropin (hCG-day) administration and successful intracytoplasmic sperm injection (ICSI) outcome. Material and methods: This prospective study was performed during the period from January 2019 to September 2021, at Zagazig Obstetrics and Gynecology Department, and Al-Azhar Obstetrics and Gynecology Department, and private ART centers. One hundred and fifty women attending the infertility clinic for ICSI cycles. All women were divided into 5 groups according to the serum E2 level on the day of hCG administration: Group A - serum E2 < 1000 pg/ml; Group B - serum E2 1000 to < 2000 pg/ml; Group C - serum E2 2000 to < 3000 pg/ml;Group D - serum E2 3000 to < 4000 pg/ml; Group E - serum E2 ≥ 4000 pg/ml. Results: The highest fertilization rate (58.1%) was among women with E2 ≥ 4000 pg/ml, while the lowest (37%) was in women with E2 1000 to < 2000 pg/ml. Also, the highest pregnancy rate (21.5%) was among women with E2 > 4000 pg/ml, while the lowest (5.3%) was in women with E2 < 1000 pg/ml. In the current study the median serum E2 level on the day of hCG administration was highly significant in women who became pregnant when compared to women who did not. The best cut-off value of serum E2 at hCG administration was ≥ 3682.3 pg/ml. Conclusions: this study suggests that the optimal range of E2 level for achieving a successful pregnancy is > 4000 pg/ml.

Mometasone Furoate Use for Recurrent Adenoid Hypertrophy: Randomized Controlled Clinical Trial.

Background& Objective: Adenoid hypertrophy (AH) in children is one of the most causes of nasal obstruction and is associated with many nasal and respiratory symptoms. Till now, surgery is the main option for managing the associated symptom of AH. The intranasal steroid has an effective role in the control of allergic rhinitis and associated AH. This work aimed to assess the effects of local mometasone on recurrent AH in children. Patients& Methods: A randomized controlled trial enrolled 39 patients aged between 2 and 15 years with recurrent AH. Those patients were randomly subdivided into three groups; group (A) received topical mometasone furoate (MF), group (B) did not receive any medication, and group (C) received topical normal saline. All groups were followed up for 8 weeks. Results: Patients who received Mometasone furoate had temporary relief of adenoid hypertrophy-related symptoms (84.6%) in comparison to the control group and placebo group during the duration of treatment. After cessation of treatment with local steroids, all cases experienced symptoms caused by adenoid hypertrophy, and by the end of the third month of follow up all cases underwent adenoidectomy. Conclusion: Mometasone furoate can temporarily reduce the adenoid size, reducing symptoms related to adenoid hypertrophy.

A Comprehensive Review on Cancer Vaccines and Vaccine Strategies in Hepatocellular Carcinoma.

HCC, the most prevalent form of primary liver cancer, presents a substantial global health challenge due to its high mortality and limited therapeutic options. This review delves into the potential of cancer vaccines as a novel therapeutic avenue for HCC. We examine the various categories of cancer vaccines, including peptide-based, dendritic cell-based, viral vector-based, DNA, and mRNA vaccines, and their potential application in HCC management. This review also addresses the inherent challenges in vaccine development, such as tumor heterogeneity and the need for identifying tumor-specific antigens. We underscore the role of cancer vaccines in reshaping the immune environment within HCC, fostering durable immune memory, and their potential in combination therapies. The review also evaluates clinical trials and emphasizes the necessity for more extensive research to optimize vaccine design and patient selection criteria. We conclude with future perspectives, highlighting the significance of personalized therapies, innovative antigen delivery platforms, immune modulatory agents, and predictive biomarkers in revolutionizing HCC treatment. Simple Summary: This review explores the potential of cancer vaccines as a promising therapeutic strategy for hepatocellular carcinoma (HCC), a prevalent and deadly liver cancer. The authors discuss various types of cancer vaccines, their challenges, and their role in modulating the immune response within HCC. They also highlight clinical trials and future perspectives, emphasizing the importance of personalized therapies, novel antigen delivery platforms, and predictive biomarkers. The findings from this research could significantly impact the research community by providing a comprehensive understanding of the current state of cancer vaccines for HCC, thereby guiding future research and potentially transforming HCC treatment strategies.

Pharmacological evaluations of amide carboxylates as potential anti-Alzheimer agents: anti-radicals, enzyme inhibition, simulation and behavioral studies in animal models.

Alzheimer's disease (AD) is a neurological disorder that progresses gradually but irreversibly leading to dementia and is difficult to prevent and treat. There is a considerable time window in which the progression of the disease can be intervened. Scientific advances were required to help the researchers to identify the effective methods for the prevention and treatment of disease. This research was designed to investigate potential mediators for the remedy of AD, five new carboxylate amide zinc complexes (AAZ9-AAZ13) were synthesized and characterized by spectroscopic and physicochemical techniques. The biological evaluation was carried out based on the cholinesterase inhibitory mechanism. The preparation methodology provided the effective synthesis of targeted moieties. The in vitro pharmacological activities were evaluated involving AChE/BChE inhibition and antioxidant potential. All synthesized compounds displayed activity against both enzymes in higher or comparable to the standard drug Galantamine, a reversible inhibitor but the results displayed by compound AAZ10 indicated IC50 of 0.0013 µM (AChE) and 0.061 µM (BChE) as high values for dual AChE/BChE inhibition with potent anti-oxidant results. Structure activity relationship (SAR) indicated that the potent activity of compound AAZ10 appeared due to the presence of nitro clusters at the ortho position of an aromatic ring. The potent synthesized compound AAZ10 was also explored for the in-vivo Anti-Alzheimer activity and anti-oxidant activity. Binding approaches of all synthesized compounds were revealed through molecular docking studies concerning binding pockets of enzymes that analyzed the best posture interaction with amino acid (AA) residues providing an appreciable understanding of enzyme inhibitory mechanisms. Results indicate that synthesized zinc (II) amide carboxylates can behave as an effective remedy in the treatment of Alzheimer's disease.Communicated by Ramaswamy H. Sarma.

Public sector rehabilitation services for physical disabilities in tertiary care hospitals of Karachi, Pakistan: A qualitative study.

BACKGROUND: Around the globe there are 2.4 billion people in need of rehabilitation. Disability and rehabilitation have not gained much importance in the public health arena, possibly due to limited research and awareness regarding the significance of rehabilitation. This study aimed to provide an in-depth understanding of the barriers and facilitators to the provision and utilization of rehabilitation services in public sector tertiary care hospitals of Karachi, Pakistan. METHODOLOGY: This qualitative exploratory study was conducted from August to September 2015 in two tertiary care hospitals of Karachi. The criterion for hospital selection included the availability of functional rehabilitation services. Twenty-four key informant interviews were conducted with health professionals, including doctors, physiotherapists, occupational therapists, prosthetists, orthotists, as well as patients and caregivers. Qualitative content analysis was performed using a consensual qualitative research approach. Responses from key informant interviews were coded into free nodes and then categorized into themes. RESULTS: Two themes emerged from the data: constraints to the provision of rehabilitation services, and barriers to the utilization of rehabilitation services. Basic infrastructure was available at both study sites; however, a lack of structured guidelines for referring patients to these services, a lack of information-sharing and guidance to the patients, and a limited supply of equipment (treatment modalities) hampered the provision of services. The barriers to rehabilitation services included cost pertaining to transport, environmental barriers, lack of support from the employer, and strain on and lack of support from caregivers. CONCLUSION: Rehabilitation services require attention and investment in research and allocation of funds to strengthen the service delivery system. Hospitals, alongside the department of health, need to develop a strategic plan to set future directions and standards of available rehabilitation services.

Polyelectrolyte membranes based on phosphorylated-PVA/cellulose acetate for direct methanol fuel cell applications: synthesis, instrumental characterization, and performance testing.

Designing and synthesis of cost-effective and improved methanol permeable and proton conductive membranes are the main challenges for preparation of polymeric electrolyte membrane (PEM). Herein, a cost-effective PEM membrane based on phosphorylated polyvinyl alcohol (PVA)-grafted-cellulose acetate (CA) was prepared by a solution-casting technique. Water and methanol uptakes of phosphorylated PVA/CA membranes were characterized as function with the molar ratio of CA. Additionally, structure and morphology of phosphorylated PVA/CA (Ph-PVA/CA) membranes were verified by FT-IR analysis, SEM investigation. Furthermore, ion exchange capacity (IEC), proton conductivity and methanol permeation of Ph-PVA/CA membranes were examined based on the concentration of OPA basically. The results manifested a perceptible improvement in proton conductivity from 0.035 to 0.05 S/cm at 25 and 70 °C, respectively using 600 µL of OPA, and IEC of 2.1 meq/g using 400 µL of OPA at ambient temperature. On the other hand, methanol permeability (P = 1.08 × 10-10 cm2/s) was lower than Nafion 117 admirably. The optimum OPA concentration was 200 µL according to conductivity measurements (at 10% PVA, 150 µL GA, and CA 7%). Finally, prepared Ph-PVA/CA membranes exhibited enhancement in critical natures such as proton conductivity and IEC combined with its low-cost materials, which make them excellent candidate as PEM for DMFCs application.

Optimal sampling and statistical inferences for Kumaraswamy distribution under progressive Type-II censoring schemes.

In this paper, we study non-Bayesian and Bayesian estimation of parameters for the Kumaraswamy distribution based on progressive Type-II censoring. First, the maximum likelihood estimates and maximum product spacings are derived. In addition, we derive the asymptotic distribution of the parameters and the asymptotic confidence intervals. Second, Bayesian estimators under symmetric and asymmetric loss functions (Squared error, linear exponential, and general entropy loss functions) are also obtained. The Lindley approximation and the Markov chain Monte Carlo method are used to derive the Bayesian estimates. Furthermore, we derive the highest posterior density credible intervals of the parameters. We further present an optimal progressive censoring scheme among different competing censoring scheme using three optimality criteria. Simulation studies are conducted to evaluate the performance of the point and interval estimators. Finally, one application of real data sets is provided to illustrate the proposed procedures.

Potential of a Miniature Spectral Analyzer for District-Scale Monitoring of Multiple Gaseous Air Pollutants.

Gas sensors that can measure multiple pollutants simultaneously are highly desirable for on-site air pollution monitoring at various scales, both indoor and outdoor. Herein, we introduce a low-cost multi-parameter gas analyzer capable of monitoring multiple gaseous pollutants simultaneously, thus allowing for true analytical measurement. It is a spectral sensor consisting of a Fourier-transform infrared (FTIR) gas analyzer based on a mid-infrared (MIR) spectrometer. The sensor is as small as 7 × 5 × 2.5 cm3. It was deployed in an open-path configuration within a district-scale climatic chamber (Sense City, Marne-la-Vallée, France) with a volume of 20 × 20 × 8 m3. The setup included a transmitter and a receiver separated by 38 m to enable representative measurements of the entire district domain. We used a car inside the climatic chamber, turning the engine on and off to create time sequences of a pollution source. The results showed that carbon dioxide (CO2) and water vapor (H2O) were accurately monitored using the spectral sensor, with agreement with the reference analyzers used to record the pollution levels near the car exhaust. Furthermore, the lower detection limits of CO, NO2 and NO were assessed, demonstrating the capability of the sensor to detect these pollutants. Additionally, a preliminary evaluation of the potential of the spectral sensor to screen multiple volatile organic compounds (VOCs) was conducted at the laboratory scale. Overall, the results demonstrated the potential of the proposed multi-parameter spectral gas sensor in on-site gaseous pollution monitoring.