Peripheral Nerve Stimulation After Total Knee Arthroplasty and Non-Operable Patella Fracture.

Chronic knee pain, affecting over 25% of adults in the United States, has surged by 65% over the past two decades leading to rising functional deficits, mobility problems, and a diminished quality of life. While conservative management with pharmacologic and minimally invasive injections are pursued early in the disease process, total knee arthroplasty for refractory osteoarthritis of the knee is often considered. This procedure usually improves pain and functionality within the first three months. However, a significant portion of patients often suffer from postoperative pain that can become chronic and debilitating. We detail the case of a patient with a previous TKA as well as a non-operable patella fracture who obtained significant relief with PNS despite prior conservative and minimally invasive management.

A chemoinformatic-biophysics based approach to identify novel anti-virulent compounds against Pseudomonas aeruginosa disulfide-bond protein A1.

The conventional course of drug discovery is a lengthy, expensive and complex process and often experiences a high failure rate. This in-silico based study screened novel drug molecules against Pseudomonas aeruginosa disulfide-bond protein A1 (PaDsbA1; PDB ID of 4ZL7) using a variety of chemoinformatic and biophysics approaches. The structure-based virtual screening identified three antipseudomonal compounds (BDC_30129064, BDC_20699588 and BDC_25329008) that targeted PaDsbA1 enzyme with a binding energy score of -7.8 kcal/mol, -7.7 kcal/mol and -7.7 kcal/mol, respectively. The compounds revealed deep binding at the enzyme active pocket with close distance hydrogen bond interactions with Thr46, Pro55, Val58, Arg62, His88, and Asp180. The co-crystalized hexaethylene glycol revealed a binding energy of -6.02 kcal/mol. The docked compounds were further subjected to molecular dynamics simulation analysis in order to check the dynamic movements of docked complexes. The complexes reported no drastic changes during simulation time. In the simulation, stable compounds binding and docked conformation were accomplished. The docking and simulation results were validated using free binding energies calculation through molecular mechanics with generalized born surface area solvation and molecular mechanics Poisson Boltzmann surface area (MMGBSA/MMPBSA) approaches. The net binding energy estimated by MMGBSA for BDC_30129064, BDC_20699588 and BDC_25329008 was -75.07 kcal/mol, -77.87 kcal/mol and -59.1 kcal/mol, respectively while that of MMPBSA for the compounds was -72.47 kcal/mol, -78.99 kcal/mol and -60.991 kcal/mol, respectively. The physiochemical properties of the selected compounds indicated them to be physiochemically stable with good absorption, distribution, metabolism and elimination properties. From the above observations and predictions, the compounds can be recommended for further experimental validation in order to decipher their anti-virulence capacity in blocking disulfide bond formation in P. aeruginosa.Communicated by Ramaswamy H. Sarma.

Knowledge and awareness of Hepatitis B, Hepatitis C, and HIV among pregnant women in Pakistan.

INTRODUCTION: Hepatitis B, Hepatitis C, and Human Immunodeficiency Virus (HIV) affect a significant proportion of the populace in developing countries. Pregnant women and deprived segments of the population are disproportionately affected. The aim of our study was to assess the awareness regarding the three blood-borne infections amongst pregnant Pakistani women belonging to low socioeconomic classes. METHODOLOGY: A cross-sectional survey was conducted among 297 pregnant women at two antenatal healthcare facilities in Islamabad, Pakistan between September and November 2019. A pretested structured questionnaire was employed for data collection and knowledge levels were classified into three categories i.e. "Good", "Average", and "Poor" according to pre-set criteria. Data were analyzed using Microsoft Excel 2016 and SPSS Version 21. RESULTS: None of the study participants had "Good" knowledge regarding the three blood-borne infections. Around 52% of the women had "Poor" while 47% had "Average" knowledge. None of the study participants were aware that HIV can be transmitted during delivery. Women aged 30-35 years had significantly higher knowledge as compared to other age groups (p < 0.001). The difference in knowledge amongst women in association with education, income status, and previous pregnancies was not significant. CONCLUSIONS: Awareness regarding Hepatitis B, Hepatitis C, and HIV amongst pregnant Pakistani women of low socioeconomic status is insufficient which can lead to an increased risk of acquiring these infections, especially during childbirth. It is vital to impart health education regarding these diseases and monitor hygiene standards in health care facilities.

Comparison of Peer-Assisted Learning with Traditional Faculty-led Teaching in Family Medicine Clerkship: An Experimental Study.

OBJECTIVE: To compare the effects of reciprocal peer-assisted learning (PAL) with traditional faculty-led teaching on the academic performance of fourth-year medical students in Family Medicine clerkship. STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Department of Health Professions Education and Department of Family Medicine, Shifa College of Medicine, Islamabad, Pakistan, from 22nd February 2019 to 25th February 2020. METHODOLOGY: The study was conducted longitudinally in three clerkship rounds of Family Medicine with 77 fourth-year students separated into a control group and an intervention group taught by faculty and peers respectively. All peer tutors were trained prior to their sessions and there were parallel peer-led and faculty-led sessions. Both groups were given a pre-test prior to the intervention and a post-test after the intervention. The data were entered in SPSS version 24 and analysed using chi-square, independent and paired sample t-tests. RESULTS: Participants of both intervention (PAL) and control (non-PAL) groups demonstrated a significant difference in post and pre-test scores with a p-value <0.05. However, the mean difference in the post-and pre-test scores between the two groups was not significant with a p-value >0.05. CONCLUSION: Students taught by peers performed as well as students taught by the faculty in this study, as depicted by their academic scores. Henceforth PAL is comparable to faculty-led teaching in acquisition of knowledge in Family Medicine clerkship. KEY WORDS: Peer-assisted learning, Reciprocal peer-assisted learning, Traditional teaching, Family medicine.

Antimicrobial and antioxidant activities of a new metabolite from Quercus incana.

Phytochemical investigations of Quercus incana led to the isolation of a new catechin derivative quercuschin (1), along with six known compounds: quercetin (2), methyl gallate (3), gallic acid (4), betulinic acid (5), (Z)-9-octadecenoic acid methyl ester (6) and ß-sitosterol glucoside (7) from the ethyl acetate fraction of methanolic extract of the bark. Compound 1 was screened for its antibacterial, antifungal and antioxidant potential. Antibacterial and antifungal activities of the compound were tested against different bacterial and fungal strains, employing the agar well diffusion methods. The antibacterial activity was the highest against Streptococcus pyogenes with 80.0% inhibition, while the antifungal activity of the compound was the highest against Candida glabrata with 80.5% inhibition. The results of the antioxidant activity indicated that the compound exhibited antioxidant activity comparable to that of standard, butylated hydroxyanisole (51.2 µg/10 µl versus 45.9 µg/10 µl).

Scientific investigation of crude alkaloids from medicinal plants for the management of pain.

BACKGROUND: Tissue damage is associated with pain, which is an alarming sign. Aspirin and morphine have been widely used in recent decades for management of pain. Medicinal herbs have been in use for treatment of different diseases for centuries. Many of these herbs possess analgesic activity with relatively less incidences of adverse effects. The strong positive correlation of alkaloids in medicinal plants for analgesic activity persuades an intention to determine possible analgesic activity of total alkaloids extracted from the selected medicinal plants using animal models to answer its possible mechanisms. METHODS: Crude alkaloids from selected medicinal plants (Woodfordia fruticosa, Adhatoda vasica, Chenopodium ambrosioides, Vitex negundo, Peganum harmala and Broussonetia papyrifera) were extracted as per reported literature. The test crude alkaloids were screened foracute toxicity study. Writhings induced by acetic acid, tail immersion method and formalin-induced nociception assay procedures were used for possible analgesic effects of the crude alkaloids. RESULTS: Crude alkaloids were safe up to dose of 1250 mg/kg body weight in mice. The alkaloids significantly reduced the abdominal constrictions, and increased the time for paw licking response in both phases with a significant raise in latency time in nociception models (P ≤ 0.05). Moreover, the antinociceptive response was significantly attenuated by pretreatment with naloxone suggesting involvement of the opioid receptors for possible antinociceptive action. CONCLUSIONS: Crude alkaloids of Woodfordia fruticosa and Peganum harmala showed prominent analgesic potentials through inhibition of peripheral as well as central nervous system mechanisms. Further work is required for isolation of the pharmacologically active constituents.

Pharmacological basis for the use of Hypericum oblongifolium as a medicinal plant in the management of pain, inflammation and pyrexia.

BACKGROUND: The present therapeutic agents for the treatment of pain, inflammation and pyrexia are not very effective and accompanied by various side effects. Therefore, new effective agents are the most wanted. The present study investigates the anti-nociceptive, anti-inflammatory and antipyretic activities of crude methanol extract of Hypericum oblongifolium. METHODS: In vivo acetic acid induced writhing and hot plate tests were used for antinociceptive effects at 100, 200 and 300 mg/kg i.p. The anti-inflammatory and antipyretic potential of methanol extract were tested in carrageenan induced paw edema in mice and yeast induced hyperthermia respectively. RESULTS: The extract doses of 100, 200 and 300 mg/kg i.p. revealed significant inhibitory effect (P < 0.001) in acetic acid induced writhing test. Pretreatment of extract at doses of 100, 200 and 300 mg/kg i.p. produced significant anti-inflammatory effect (P < 0.001) in the carrageenan induced paw edema. The methanol extract also showed significant antipyretic effect in yeast induced hyperthermia in mice during various assessment times. CONCLUSIONS: The methanol extract of H. oblongifolium showed significant anti-nociceptive, anti-inflammatory and antipyretic effects in various animal models and thus validates the traditional uses of the plant in said conditions.

Lipoxygenase and urease inhibition of the aerial parts of the Polygonatum verticillatum.

Over expression of lipoxygenase (LOX) and urease has already contributed to the pathology of different human disease. Targeting the inhibition of these enzymes has proved great clinical utility. The aim of the present study was to scrutinised the inhibitory profile of the aerial parts of the Polygonatum verticillatum enzyme against LOX, urease, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using standard experimental protocols. When checked against lipoxygenase, the extracts revealed significant attenuation. Of the tested extracts, the ethyl acetate fraction was the most potent (half-maximal inhibitory concentration (IC(50)): 97 µg/mL) followed by aqueous fraction IC(50): 109 µg/mL). Regarding urease inhibition, n-butanol was the most potent fraction (IC(50): 97 µg/mL). However, the extracts did not show significant inhibition on AChE and BChE. In the preliminary phytochemical tests, the aerial parts of the plant showed the presence of saponins, alkaloids, flavonoids, phenols, tannins and terpenoids. The current findings could be attributed to these groups of compounds.

Anti-inflammatory activity of Heliotropium strigosum in animal models.

The current project was designed to evaluate the anti-inflammatory activity of crude extract of Heliotropium strigosum and its subsequent solvent fractions in post carrageenan-induced edema and post xylene-induced ear edema at 50, 100, and 200 mg/kg intraperitoneally. The results revealed marked attenuation of edema induced by carrageenan injection in a dose-dependent manner. The ethyl acetate fraction was most dominant with 73.33% inhibition followed by hexane fraction (70.66%). When the extracts were challenged against xylene-induced ear edema, again ethyl acetate and hexane fractions were most impressive with 38.21 and 35.77% inhibition, respectively. It is concluded that various extracts of H. strigosum possessed strong anti-inflammatory activity in animal models.

Evaluation of Viola betonicifolia for its nutrition value.

In the present study, Viola betonicifolia (whole plant) and solvent fractions obtained thereof were evaluated for various micronutrients such as lead, copper, chromium, iron, nickel, zinc, cadmium, cobalt and macronutrients such as sodium, potassium and calcium using atomic absorption spectrophotometer and flame photometry respectively. It was observed that cobalt and cadmium were not detectible in tested samples while remaining nutrients were present in variable concentrations. The concentrations of all metals were compared with the recommended limits for plants and the daily consumption of all the nutrients were calculated on the basis of dose (15 g/70 kg/day or 214 mg/Kg body weight) prescribed by hakims in their practice. The concentration of chromium was far beyond the recommended limits in almost all the samples. Proximate analysis was carried out in the powdered form of the plant. Viola betonicifolia appeared as a good source of life essential nutrients like fats (18.70%), proteins (15.70%), carbohydrates (21.42%), fiber (39.01%) and vitamin C (150 mg/100 g). In conclusion, Viola betonicifolia is an excellent source of various micro and macronutrients for human being and can be used safely as a nutritional supplement.

Analgesic and antiinflammatory activities of taxoids from Taxus wallichiana Zucc.

A study was conducted to identify constituents that might be responsible for analgesic and antiinflammatory conditions. Tasumatrol B, 1,13-diacetyl-10-deacetylbaccatin III (10-DAD) and 4-deacetylbaccatin III (4-DAB) were isolated from the bark extract of Taxus wallichiana Zucc. All the compounds were assessed for analgesic and antiinflammatory activities using an acetic acid-induced writhing model, a hot-plate test, a carrageenan-induced paw oedema model, a cotton-pellet oedema model and in vitro lipoxygenase inhibitory assay. All the compounds, especially tasumatrol B, revealed significant analgesic activity in comparison to a saline group based on an acetic acid-induced model. Similarly all of the test compounds, particularly tasumatrol B, showed significant antiinflammatory activity. However, all the compounds failed to exhibit any considerable activity in of the hot-plate test and the in vitro lipoxygenase inhibitory assay. This study has highlighted the potential of tasumatrol B to be further explored as a new lead compound for the management of pain and inflammation, one that has been discovered by scientific validation of the traditional medicinal use of T. wallichiana Zucc.

Assessment of potential toxicity of a smokeless tobacco product (naswar) available on the Pakistani market.

BACKGROUND: 'Naswar' is a smokeless tobacco product (STP) widely used in Pakistan. It has been correlated with oral and oesophageal cancer in recent clinical studies. The toxic effects associated with STPs have been associated with trace level contaminants present in these products. The toxin levels of Pakistani naswar are reported for the first time in this study. METHODS: A total of 30 Pakistani brands of naswar were tested for a variety of toxic constituents and carcinogens such as cadmium, arsenic, lead and other carcinogenic metals, nitrite and nitrate, and nicotine and pH. RESULTS: The average values of all the toxins studied were well above their allowable limits, making the product a health risk for consumers. Calculated lifetime cancer risk from cadmium and lead was 1 lac (100,000) to 10 lac (1,000,000) times higher than the minimum 10E-4 (0.00001) to 10E-6 (0.000001), which is the 'target range' for potentially hazardous substances, according to the US Environmental Protection Agency. Similarly, the level of arsenic was in the range of 0.15 to 14.04 µg/g, the average being 1.25 µg/g. The estimated average bioavailable concentration of arsenic is 0.125-0.25 µg/g, which is higher than the allowable standard of 0.01 µg/g. Similarly, the average minimum daily intake of chromium and nickel was 126.97 µg and 122.01 µg, as compared to allowable 30-35 µg and 35 µg, respectively; a 4-5 times higher exposure. However, beryllium was not detected in any of the brands studied. The pH was highly basic, averaging 8.56, which favours the formation of tobacco specific amines thus making the product potentially toxic. This study validates clinical studies correlating incidence of cancer with naswar use in Pakistan. CONCLUSIONS: This study shows that the production, packaging, sale and consumption of naswar should be regulated so as to protect the public from the health hazards associated with its consumption.

Anti-inflammatory activities of Taxusabietane A isolated from Taxus wallichiana Zucc.

Current study was conducted to identify constituents of Taxus wallichiana Zucc. that might be responsible for its folk use in anti-inflammatory conditions. Taxusabietane A was isolated from the bark extract of Taxus wallichiana Zucc. Taxusabietane A was analyzed for in-vitro and in-vivo anti-inflammatory activities using Lipoxygenase (LOX) inhibition assay and carrageenan-induced paw edema model. Taxusabietane A revealed considerable LOX inhibitory activity with the IC(50) value being 57 ± 0.31. Standard compound Baicalein showed the IC(50) value being 22.1 ± 0.03 µM. Taxusabietane A also showed significant (5 and 10 mg/kg) anti-inflammatory activity induced by carrageenan. However, this study highlighted the potential of Taxusabietane A to be further explored as a new lead compound for management of conditions associated with inflammation.