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Fulltext Exploring the natural products chemical space through a molecular search to discover potential inhibitors that target the hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD)

Sayaf AM, Ullah Khalid S, Hameed JA, Alshammari A, Khan A, Mohammad A, et al.

Front Pharmacol, 2023;14:1202128.
PMID: 37670941 DOI: 10.3389/fphar.2023.1202128

Introduction: Hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD) enzymes are major therapeutic targets of anemia and ischemic/hypoxia diseases. To overcome safety issues, liver failure, and problems associated with on-/off-targets, natural products due to their novel and unique structures offer promising alternatives as drug targets. Methods: In the current study, the Marine Natural Products, North African, South African, East African, and North-East African chemical space was explored for HIF-PHD inhibitors discovery through molecular search, and the final hits were validated using molecular simulation and free energy calculation approaches. Results: Our results revealed that CMNPD13808 with a docking score of -8.690 kcal/mol, CID15081178 with a docking score of -8.027 kcal/mol, CID71496944 with a docking score of -8.48 kcal/mol and CID11821407 with a docking score of -7.78 kcal/mol possess stronger activity than the control N-[(4-hydroxy-8-iodoisoquinolin-3-yl)carbonyl]glycine, 4HG (-6.87 kcal/mol). Interaction analysis revealed that the target compounds interact with Gln239, Tyr310, Tyr329, Arg383 and Trp389 residues, and chelate the active site iron in a bidentate manner in PHD2. Molecular simulation revealed that these target hits robustly block the PHD2 active site by demonstrating stable dynamics. Furthermore, the half-life of the Arg383 hydrogen bond with the target ligands, which is an important factor for PHD2 inhibition, remained almost constant in all the complexes during the simulation. Finally, the total binding free energy of each complex was calculated as CMNPD13808-PHD2 -72.91 kcal/mol, CID15081178-PHD2 -65.55 kcal/mol, CID71496944-PHD2 -68.47 kcal/mol, and CID11821407-PHD2 -62.06 kcal/mol, respectively. Conclusion: The results show the compounds possess good activity in contrast to the control drug (4HG) and need further in vitro and in vivo validation for possible usage as potential drugs against HIF-PHD2-associated diseases.
Fulltext Prevalence and associated factors of burnout among family medicine residents in Al Madina, Saudi Arabia

Aldubai SAR, Aljohani AM, Alghamdi AG, Alghamdi KS, Ganasegeran K, Yenbaawi AM

J Family Med Prim Care, 2019 02;8(2):657-662.
PMID: 30984690 DOI: 10.4103/jfmpc.jfmpc_268_18

Background and Aim: Burnout is a common problem for interns and residents. It has been associated with physical and mental health of health care providers as well as low job satisfaction and medical errors. Few studies have investigated this problem among residents. This study aimed to determine the prevalence of burnout and its associated factors among family residents in Al Madina city, Saudi Arabia.
Materials and Methods: This cross-sectional study was conducted among 75 residents in the family medicine residency programs in Al Madina, Saudi Arabia. A self-administered questionnaire was used that includes questions on sociodemographic characteristics and sources of stress and burnout. T test, analysis of variance (ANOVA) test, and multiple linear regression analysis were employed.
Results: Majority were female (54.7%) and aged 26 to 30 years (84.0%). The significant predictors of burnout in the final model were "tests/examinations" (P = 0.014), "large amount of content to be learnt" (P = 0.016), "unfair assessment from superiors" (P = 0.001), "work demands affect personal/home life" (P = 0.001), and "lack of support from superiors" (P = 0.006).
Conclusion: Burnout is present among family medicine residents at a relatively high percentage. This situation is strongly triggered by work-related stressors, organizational attributes, and system-related attributes, but not socio-demographics of the respondents. Systemic changes to relieve the workload of family medicine residents are recommended to promote effective management of burnout.
Searches for electroweak production of charginos, neutralinos, and sleptons decaying to leptons and W, Z, and Higgs bosons in pp collisions at 8 TeV

CMS Collaboration, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, et al.

Eur Phys J C Part Fields, 2014 09 26;74(9):3036.
PMID: 25814912

Searches for the direct electroweak production of supersymmetric charginos, neutralinos, and sleptons in a variety of signatures with leptons and [Formula: see text], [Formula: see text], and Higgs bosons are presented. Results are based on a sample of proton-proton collision data collected at center-of-mass energy [Formula: see text] with the CMS detector in 2012, corresponding to an integrated luminosity of 19.5 [Formula: see text]. The observed event rates are in agreement with expectations from the standard model. These results probe charginos and neutralinos with masses up to 720 [Formula: see text], and sleptons up to 260 [Formula: see text], depending on the model details.
Fulltext Search for heavy neutrinos and [Formula: see text] bosons with right-handed couplings in proton-proton collisions at [Formula: see text]

CMS Collaboration, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, et al.

Eur Phys J C Part Fields, 2014;74(11):3149.
PMID: 25814876 DOI: 10.1140/epjc/s10052-014-3149-z

A search for heavy, right-handed neutrinos, [Formula: see text] ([Formula: see text]), and right-handed [Formula: see text] bosons, which arise in the left-right symmetric extensions of the standard model, has been performed by the CMS experiment. The search was based on a sample of two lepton plus two jet events collected in proton-proton collisions at a center-of-mass energy of 8[Formula: see text] corresponding to an integrated luminosity of 19.7 [Formula: see text]. For models with strict left-right symmetry, and assuming only one [Formula: see text] flavor contributes significantly to the [Formula: see text] decay width, the region in the two-dimensional [Formula: see text] mass plane excluded at a 95 % confidence level extends to approximately [Formula: see text] and covers a large range of neutrino masses below the [Formula: see text] boson mass, depending on the value of [Formula: see text]. This search significantly extends the [Formula: see text] exclusion region beyond previous results.
Fulltext The gender responsiveness of social entrepreneurship in health - A review of initiatives by Ashoka fellows

Khalid S, Dixon S, Vijayasingham L

Soc Sci Med, 2022 Jan;293:114665.
PMID: 34954676 DOI: 10.1016/j.socscimed.2021.114665

There are vocal calls to act on the gender-related barriers and inequities in global health. Still, there are gaps in implementing programmes that address and counter the relevant dynamics. As an approach that focuses on social problems and public service delivery gaps, social entrepreneurship has the potential to be a closer health sector partner to tackle and transform the influence of gender in health to achieve health systems goals better. Nevertheless, social entrepreneurs' engagement and impact on gender and health remain understudied. Using the Ashoka Fellows database as a sampling frame in November 2020 (n = 3352, health n = 129), we identified and reviewed the work of 21 organizations that implemented gender-responsive health-related programmes between 2000 and 2020. We applied the UNU-IIGH 6-I Analytic Framework to review the gender issues, interventions, included populations, investments, implementation, and impact in each organization. We found that a low proportion of fellows engage in gender-responsive health programming (<1%). Many organizations operate in low-and middle-income countries (16/21). The gender-responsive programmes include established health sector practices, to address gendered-cultural dynamics and deliver people-centred resources and services. Interestingly, most organizations self-identify as NGOs and rely on traditional grant funding. Fewer organizations (6/21) adopt market-based and income-generating solutions - a missed opportunity to actualise the potential of social entrepreneurship as an innovative health financing approach. There were few publicly available impact evaluations-a gap in practice established in social entrepreneurship. All organizations implemented programmes at community levels, with some cross-sectoral, structural, and policy-level initiatives. Most focused on sexual and reproductive health and gender-based violence for predominantly populations of women and girls. Closer partnerships between social entrepreneurs and gender experts in the health sector can provide reciprocally beneficial solutions for cross-sectorally and community designed innovations, health financing, evidence generation and impact tracking that improve the gender-responsiveness of health programmes, policies, and systems.
Fulltext Risks of stillbirth and neonatal death with advancing gestation at term: A systematic review and meta-analysis of cohort studies of 15 million pregnancies

Muglu J, Rather H, Arroyo-Manzano D, Bhattacharya S, Balchin I, Khalil A, et al.

PLoS Med, 2019 07;16(7):e1002838.
PMID: 31265456 DOI: 10.1371/journal.pmed.1002838

BACKGROUND: Despite advances in healthcare, stillbirth rates remain relatively unchanged. We conducted a systematic review to quantify the risks of stillbirth and neonatal death at term (from 37 weeks gestation) according to gestational age.
METHODS AND FINDINGS: We searched the major electronic databases Medline, Embase, and Google Scholar (January 1990-October 2018) without language restrictions. We included cohort studies on term pregnancies that provided estimates of stillbirths or neonatal deaths by gestation week. We estimated the additional weekly risk of stillbirth in term pregnancies that continued versus delivered at various gestational ages. We compared week-specific neonatal mortality rates by gestational age at delivery. We used mixed-effects logistic regression models with random intercepts, and computed risk ratios (RRs), odds ratios (ORs), and 95% confidence intervals (CIs). Thirteen studies (15 million pregnancies, 17,830 stillbirths) were included. All studies were from high-income countries. Four studies provided the risks of stillbirth in mothers of White and Black race, 2 in mothers of White and Asian race, 5 in mothers of White race only, and 2 in mothers of Black race only. The prospective risk of stillbirth increased with gestational age from 0.11 per 1,000 pregnancies at 37 weeks (95% CI 0.07 to 0.15) to 3.18 per 1,000 at 42 weeks (95% CI 1.84 to 4.35). Neonatal mortality increased when pregnancies continued beyond 41 weeks; the risk increased significantly for deliveries at 42 versus 41 weeks gestation (RR 1.87, 95% CI 1.07 to 2.86, p = 0.012). One additional stillbirth occurred for every 1,449 (95% CI 1,237 to 1,747) pregnancies that advanced from 40 to 41 weeks. Limitations include variations in the definition of low-risk pregnancy, the wide time span of the studies, the use of registry-based data, and potential confounders affecting the outcome.
CONCLUSIONS: Our findings suggest there is a significant additional risk of stillbirth, with no corresponding reduction in neonatal mortality, when term pregnancies continue to 41 weeks compared to delivery at 40 weeks.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015013785.
Phytoremediation of bauxite wastewater potentiality by Jatropa curcas

Kristanti RA, Mardarveran P, Almaary KS, Elshikh MS, AbdelGawwad MR, Tang DKH

Bioprocess Biosyst Eng, 2023 Mar;46(3):373-379.
PMID: 35773493 DOI: 10.1007/s00449-022-02745-5

Bauxite wastewater creates soil contamination and produces toxic effects on human health such as respiratory and skin rash problems. In this study, we investigated the phytoremediation ability of Jatropha curcas to remove bauxite wastewater from soil. Pot experiments were conducted to investigate the bauxite wastewater on the phytoremediation potential of J. curcas grown in contaminated soils. J. curcas exhibited a significant increase in plant growth leaf, root activity, plant height, and plant shoot when grown in bauxite contaminated soils compared with J. curcas grown in uncontaminated soils after 30 d treatment. Under bauxite exposure, a higher aluminium removal (88.5%) was observed in soils planted with J. curcas than unplanted soils (39.6%). The bioconcentration factor was also found to be 5.62, indicating that J. curcas have great tolerance and hyperaccumulator of aluminium under high aluminium concentrations and are capable of phytoextraction of soil contaminated with bauxite wastewater.
Fulltext Zerumbone-induced antinociception: involvement of the L-arginine-nitric oxide-cGMP -PKC-K+ ATP channel pathways

Perimal EK, Akhtar MN, Mohamad AS, Khalid MH, Ming OH, Khalid S, et al.

Basic Clin Pharmacol Toxicol, 2011 Mar;108(3):155-62.
PMID: 20955360 DOI: 10.1111/j.1742-7843.2010.00635.x

This study investigated the antinociceptive effects of zerumbone in chemical behavioural models of nociception in mice. Zerumbone given through intraperitoneal route (i.p.) produced dose-related antinociception when assessed on acetic acid-induced abdominal writhing test in mice. In addition, the i.p. administration of zerumbone exhibited significant inhibition of the neurogenic pain induced by intraplantar (i.pl.) injection of capsaicin and bradykinin. Likewise, zerumbone given by i.p. route reduced the nociception produced by i.pl. injection of glutamate and phorbol myristate acetate (PMA). The antinociception caused by zerumbone in the acetic acid test was significantly attenuated by i.p. pre-treatment of mice with l-arginine (nitric oxide precursor) and glibenclamide (ATP-sensitive K(+) channel inhibitor). However, the antinociception of zerumbone was enhanced by methylene blue (non-specific gyanylyl cyclase inhibitor). Together, these results indicate that zerumbone produces pronounced antinociception against chemical models of nociception in mice. It also strongly suggests that the l-arginine-nitric oxide-cGMP-PKC-K(+) ATP channel pathways, the TRPV1 and kinin B2 receptors play an important role in the zerumbone-induced antinociception.
Antinociceptive activity of methanolic extract of Acmella uliginosa (Sw.) Cass

Ong HM, Mohamad AS, Makhtar N', Khalid MH, Khalid S, Perimal EK, et al.

J Ethnopharmacol, 2011 Jan 7;133(1):227-33.
PMID: 20920570 DOI: 10.1016/j.jep.2010.09.030

Acmella uliginosa (Sw.) Cass. is a medicinal herbaceous plant that is commonly used by the Malay community in Malaysia to relieve pain often associated with mouth ulcers, toothache, sore throat, and stomach ache.
Antinociceptive activity of a synthetic chalcone, flavokawin B on chemical and thermal models of nociception in mice

Mohamad AS, Akhtar MN, Zakaria ZA, Perimal EK, Khalid S, Mohd PA, et al.

Eur J Pharmacol, 2010 Nov 25;647(1-3):103-9.
PMID: 20826146 DOI: 10.1016/j.ejphar.2010.08.030

The present study examined the potential antinociceptive activity of flavokawin B (6'-hydroxy-2',4'-dimethoxychalcone), a synthetic chalcone using chemical- and thermal-induced nociception models in mice. It was demonstrated that flavokawin B (FKB; 0.3, 1, 3 and 10 mg/kg) administered via both oral (p.o.) and intraperitoneal (i.p.) routes produced significant and dose-dependent inhibition in the abdominal constrictions induced by acetic acid, with the i.p. route producing antinociception of approximately 7-fold more potent than the p.o. route. It was also demonstrated that FKB produced significant inhibition in the two phases of the formalin-induced paw licking test. In addition, the same treatment of flavokawin B (FKB) exhibited significant inhibition of the neurogenic nociceptive induced by intraplantar injections of glutamate and capsaicin. Likewise, this compound also induced a significant increase in the response latency period to thermal stimuli in the hot plate test and its antinociceptive effect was not related to muscle relaxant or sedative action. Moreover, the antinociception effect of the FKB in the formalin-induced paw licking test and the hot plate test was not affected by pretreatment of non-selective opioid receptor antagonist, naloxone. The present results indicate that FKB produced pronounced antinociception effect against both chemical and thermal models of pain in mice that exhibited both peripheral and central analgesic activity.
Fulltext In vivo analgesic effect of aqueous extract of Tamarindus indica L. fruits

Khalid S, Shaik Mossadeq WM, Israf DA, Hashim P, Rejab S, Shaberi AM, et al.

Med Princ Pract, 2010;19(4):255-9.
PMID: 20516700 DOI: 10.1159/000312710

To study the effects of Tamarindus indica L. aqueous fruit extract on the antinociceptive activities in rodent models.
Fulltext Synthesis of 4-(dimethylamino)pyridine propylthioacetate coated gold nanoparticles and their antibacterial and photophysical activity

Anwar A, Khalid S, Perveen S, Ahmed S, Siddiqui R, Khan NA, et al.

J Nanobiotechnology, 2018 Jan 29;16(1):6.
PMID: 29378569 DOI: 10.1186/s12951-017-0332-z

BACKGROUND: Gold nanoparticles are useful candidate for drug delivery applications and are associated with enhancement in the bioavailability of coated drugs and/or therapeutic agent. Since, heterocyclic compounds are known to exhibit antimicrobial potential against variety of pathogens, we designed this study to evaluate the antibacterial effects of gold nanoparticles conjugation with new synthesized cationic ligand; 4-Dimethyl aminopyridinium propylthioacetate (DMAP-PTA) in comparison with pure compound and antibiotic drug Pefloxacin. Antibacterial activity of DMAP-PTA coated gold nanoparticles was investigated against a fecal strain of E. coli (ATCC 8739).
RESULTS: A new dimethyl aminopyridine based stabilizing agent named as DMAP-PTA was synthesized and used for stabilization of gold nanoparticles. Gold nanoparticles coated with DMAP-PTA abbreviated as DMAP-PTA-AuNPs were thoroughly characterized by UV-visible, FT-IR spectroscopic methods and transmission electron microscope before biological assay. DMAP-PTA, DMAP-PTA-AuNPs and Pefloxacin were examined for their antibacterial potential against E. coli, and the minimum inhibitory concentration (MIC) was determined to be 300, 200 and 50 µg/mL respectively. Gold nanoparticles conjugation was found to significantly enhance the antibacterial activity of DMAP-PTA as compared to pure compound. Moreover, effects of DMAP-PTA-AuNPs on the antibacterial potential of Pefloxacin was also evaluated by combination therapy of 1:1 mixture of DMAP-PTA-AuNPs and Pefloxacin against E. coli in a wide range of concentrations from 5 to 300 µg/mL. The MIC of Pefloxacin + DMAP-PTA-AuNPs mixture was found to be 25 µg/mL as compared to Pefloxacin alone (50 µg/mL), which clearly indicates that DMAP-PTA-AuNPs increased the potency of Pefloxacin. AFM analysis was also carried out to show morphological changes occur in bacteria before and after treatment of test samples. Furthermore, DMAP-PTA-AuNPs showed high selectivity towards Pefloxacin in spectrophotometric drug recognition studies which offers tremendous potential for analytical applications.
CONCLUSIONS: Gold nanoparticles conjugation was shown to enhance the antibacterial efficacy of DMAP-PTA ligand, while DMAP-PTA-AuNPs also induced synergistic effects on the potency of Pefloxacin against E. coli. DMAP-PTA-AuNPs were also developed as Pefloxacin probes in recognizing the drug in blood and water samples in the presence of other drugs.
REPORT- Some ethanobotanically important plants from Cholistan area for anti avian influenza virus (AIV) H9N2 screening

Shahzad MI, Ashraf H, Aslam A, Parveen S, Kamran Z, Naz N, et al.

Pak J Pharm Sci, 2019 Nov;32(6):2751-2756.
PMID: 31969311

Avian influenza or bird flu is a common problem of domestic and wild birds. Some of its strains are able to cross the species barrier and cause infection in various members of class Mammalia. In view of relatively lesser efficacy of vaccines, antiviral therapies remain the only choice for the sustenance of mammals acquiring this highly devastating infection. This study is based on the evaluation of antiviral potential of methanol extracts of eleven selected Cholistani plants. The methanol extracts were prepared by using dried plants material followed by concentrating in a rotary evaporator and finally air dried before dissolving in nanopure water. The suspension was filter sterilized and subjected to in ovo antiviral assays. The allantoic fluids were harvested and haemagglutinin (HA) titers were determined. Among the eleven plants evaluated all methanol extracts were found effective against AIV H9N2 except S. baryosma extract. The medicinal plants O. compressa, N. procumbens, and S. surattense were found to be more effective than others and they retained HA titers at 0 after challenge. The next in order were extracts of O. esculentum, H. salicornicum and S. fruticosa which kept HA titers at 4, 8 and 16 respectively. The extracts of H. recurvum, P. antidotale, S. icolados and A. aspera were found less effective than above mentioned plant extracts and they kept the HA titers at 32, 64, 128 and 256 respectively. These results led us to conclude that the medicinal plants of Cholistan region are a rich source of antiviral agent(s) against AIV H9N2 and could be a source of cost effective alternate therapeutics.
Fulltext Human CD3+ T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells

Munisvaradass R, Kumar S, Govindasamy C, Alnumair KS, Mok PL

Int J Mol Sci, 2017 Sep 08;18(9).
PMID: 28885562 DOI: 10.3390/ijms18091797

Breast cancer is a common malignancy among women. The innate and adaptive immune responses failed to be activated owing to immune modulation in the tumour microenvironment. Decades of scientific study links the overexpression of human epidermal growth factor receptor 2 (ERBB2) antigen with aggressive tumours. The Chimeric Antigen Receptor (CAR) coding for specific tumour-associated antigens could initiate intrinsic T-cell signalling, inducing T-cell activation, and cytotoxic activity without the need for major histocompatibility complex recognition. This renders CAR as a potentially universal immunotherapeutic option. Herein, we aimed to establish CAR in CD3+ T-cells, isolated from human peripheral blood mononucleated cells that could subsequently target and induce apoptosis in the ERBB2 overexpressing human breast cancer cell line, SKBR3. Constructed CAR was inserted into a lentiviral plasmid containing a green fluorescent protein tag and produced as lentiviral particles that were used to transduce activated T-cells. Transduced CAR-T cells were then primed with SKBR3 cells to evaluate their functionality. Results showed increased apoptosis in SKBR3 cells co-cultured with CAR-T cells compared to the control (non-transduced T-cells). This study demonstrates that CAR introduction helps overcome the innate limitations of native T-cells leading to cancer cell apoptosis. We recommend future studies should focus on in vivo cytotoxicity of CAR-T cells against ERBB2 expressing tumours.
Knowledge, attitude and perception regarding antimicrobial resistance and usage among ruminant farmers in Selangor, Malaysia

Sadiq MB, Syed-Hussain SS, Ramanoon SZ, Saharee AA, Ahmad NI, Mohd Zin N, et al.

Prev Vet Med, 2018 Aug 01;156:76-83.
PMID: 29891148 DOI: 10.1016/j.prevetmed.2018.04.013

The increasing public health problem of antimicrobial resistance (AMR) has been linked to the extensive antimicrobial use (AMU) in food animals. We conducted a survey among ruminant farmers in Selangor, Malaysia to assess their level of awareness on AMR, attitudes towards AMU, and determinants that influence their practices. The survey was developed in English and Malay, validated, and administered to ruminant farmers in Selangor. A total of 84 farmers (response rate of 55%) completed the structured questionnaire. They appeared to be little aware of AMR and the impact on animals and public health. Indications of inappropriate AMU include their misconception on conditions requiring antibiotic therapy and easy accessibility to antibiotics. More than 70% (60/84) of the respondents believed that all sick animals need to be given antimicrobials. Half of the farmers especially those involved in the production of small and large ruminants; namely mixed ruminant farmers (MRF) (63%, 31/49) indicated that antimicrobials do not have any side effects in animals. Sixty-four percent (54/84) of the farmers have stored antimicrobials in their farms of which the practice was more common (P = 0.02) among the MRF compared to the single ruminant farmers (SRF). Although most of the farmers felt good farm biosecurity will help reduce AMU, they were indifferent regarding using antimicrobials only when prescribed by a veterinarian and non-storage of antimicrobials for later uses. Farmers with larger herd size (>100 animals/herd) and few years of farming experience agreed more to the suggestions about their role and that of veterinarians respectively in reducing the drivers of AMR. These areas might need to be considered by advisors to inform ruminant farmers on AMR and to encourage them for prudent AMU in food-producing animals.
Fulltext Antinociceptive activity of Melicope ptelefolia ethanolic extract in experimental animals

Sulaiman MR, Mohd Padzil A, Shaari K, Khalid S, Shaik Mossadeq WM, Mohamad AS, et al.

J Biomed Biotechnol, 2010;2010:937642.
PMID: 21274262 DOI: 10.1155/2010/937642

Melicope ptelefolia is a medicinal herb commonly used in Malaysia to treat fever, pain, wounds, and itches. The present study was conducted to evaluate the antinociceptive activity of the Melicope ptelefolia ethanolic extract (MPEE) using animal models of nociception. The antinociceptive activity of the extract was assessed using acetic acid-induced abdominal writhing, hot-plate, and formalin-induced paw licking tests. Oral administration of MPEE produced significant dose-dependent antinociceptive effects when tested in mice and rats using acetic acid-induced abdominal constriction test and on the second phase of the formalin-induced paw licking test, respectively. It was also demonstrated that MPEE had no effect on the response latency time to the heat stimulus in the thermal model of the hot-plate test. In addition, the antinociception produced by MPEE was not blocked by naloxone. Furthermore, oral administration of MPEE did not produce any effect in motor performance of the rota-rod test and in acute toxicity study no abnormal behaviors as well as mortality were observed up to a dose level of the extract of 5 g/kg. These results indicated that MPEE at all doses investigated which did not produce any sedative and toxic effects exerted pronounce antinociceptive activity that acts peripherally in experimental animals.
Fulltext Systematic Review Reporting - Writing concisely and precisely

Chien PF, Khan KS

Pak J Med Sci, 2023;39(2):317-322.
PMID: 36950392 DOI: 10.12669/pjms.39.2.7428

Systematic reviews rank at the top of the evidence hierarchy. Concise writing implies drafting the systematic review article succinctly, i.e. using as few words to express as full an extent of the research effort as possible. Precise writing means drafting the text with accuracy especially with respect to the methodological and statistical aspects. The Abstract ought to be succinct and structured to allow for editors, peer reviewers and readers to get the gist of the key aspects of the systematic review with a quick read. The readership needs to be able to critically appraisal systematic reviews for their internal and external validity rapidly. The Abstract also needs to be standalone, representing an independent summary that can be fully understood without the need for reading the full paper. The standard structure of the main text of a scientific article called IMRaD (Introduction, Methods, Results and Discussion) applies equally to systematic reviews in the same way as it does to any other kinds of research manuscripts whether related to laboratory experiments or clinical trials. Restricting the word count limits to those imposed by journals may at first seem difficult, even unfair, to systematic reviewers. However, with the availability of online appendices to transparently and fully report the details of the methods, results and other aspects of the work undertaken allows for a succinct print or PDF article. Writing a shorter manuscript is more effortful than writing a longer report. This commentary is aimed at novice systematic reviewers to help them learn the written and unwritten writing rules in order to assist them in producing impactful publications to support evidence-based medicine.
Experimental investigation on the use of highly charged nanoparticles to improve the stability of weakly charged colloidal system

Zubir MN, Badarudin A, Kazi SN, Misran M, Amiri A, Sadri R, et al.

J Colloid Interface Sci, 2015 Sep 15;454:245-55.
PMID: 26048724 DOI: 10.1016/j.jcis.2015.05.019

The present work highlighted on the implementation of a unique concept for stabilizing colloids at their incipiently low charge potential. A highly charged nanoparticle was introduced within a coagulated prone colloidal system, serving as stabilizer to resist otherwise rapid flocculation and sedimentation process. A low size asymmetry of nanoparticle/colloid serves as the new topic of investigation in addition to the well-established large size ratio nanoparticle/microparticle study. Highly charged Al2O3 nanoparticles were used within the present research context to stabilize TiO2 and Fe3O4 based colloids via the formation of composite structures. It was believed, based on the experimental evidence, that Al2O3 nanoparticle interact with the weakly charged TiO2 and Fe3O4 colloids within the binary system via absorption and/or haloing modes to increase the overall charge potential of the respective colloids, thus preventing further surface contact via van der Waal's attraction. Series of experimental results strongly suggest the presence of weakly charged colloids in the studied bimodal system where, in the absence of highly charged nanoparticle, experience rapid instability. Absorbance measurement indicated that the colloidal stability drops in accordance to the highly charged nanoparticle sedimentation rate, suggesting the dominant influence of nanoparticles to attain a well-dispersed binary system. Further, it was found that the level of colloidal stability was enhanced with increasing nanoparticle fraction within the mixture. Rheological observation revealed that each hybrid complexes demonstrated behavior reminiscence to water with negligible increase in viscosity which serves as highly favorable condition particularly in thermal transport applications.
Comparative taxonomical, biological and pharmacological potential of healthy and geminivirus infected leaves of Hibiscus rosa-sinensis L.: First report

Shaheen S, Khalid S, Siqqique R, Abbas M, Ifikhar T, Ijaz I, et al.

Microb Pathog, 2023 Dec;185:106428.
PMID: 37977480 DOI: 10.1016/j.micpath.2023.106428

In the present research project, the first report on comparative analysis of the taxonomical, biological and pharmacological potential of healthy and geminivirus infected Hibiscus rosa sinensis (L.) leaves of the family Malvaceae was done by using different micro and macroscopic techniques. First of all, leaves were characterized for Cotton leaf curl Multan virus (CLCuMuV) and its associated betasatellite (Cotton leaf curl Multan Betasatellite; CLCuMB). Different morphological parameters like shape and size of stem, leaves, seeds and roots, presence and absence of ligule, distance between nodes and internodes and type of inflorescence etc. were analyzed. CLCuMuV infected H. rosa-sinensis revealed systematic symptoms of infection like chlorosis of leaves, stunted growth, decrease in size of roots, shoots and distortion etc. Anatomical investigation was performed under light ad scanning electron microscope. Different anatomical features like length and shape of guard cells, subsidiary cells, presence or absence of stomata, secretory ducts and trichomes were examined. In both plant samples anomocytic types of stomata and elongated, non-glandular and pointed tip trichomes were present, but the size (especially length and width) of trichomes and other cells like epidermal, subsidiary, and guard cells were highest in virus infected plants likened to healthy one. In the antibacterial activity, the maximum antibacterial potentail was seen in methanolic extract of K. pneumonea while antifungal activity was shown by methanolic extract of A. solani. Plants interact with different biological entities according to environmental conditions continuously and evolved. These types of interactions induce changes positively and negatively on plant metabolism and metabolites production. Many plant viruses also attacked various host plants consequently alter their secondary metabolism. To overcome such virus infected plants produces many important and different types of secondary plant metabolites as a defense response. Subsequent analysis of this n-hexane plant extract using Gas chromatography mass spectroscopy technique revealed that Hibiscus eluted contained 10 main compounds in Healthy sample and 13 compounds in infected one. Presence of essential secondary metabolites were also analyzed by FTIR analysis. The present study provides a comprehensive and novel review on taxonomy (morphology, anatomy) and antimicrobial potential of both healthy and geminivirus infected H. rosa-sinensis.
Evaluation of golden percentage in natural maxillary anterior teeth width: A systematic review

Ahmed N, Halim MS, Khalid S, Ghani ZA, Jamayet NB

J Prosthet Dent, 2021 Jul 31.
PMID: 34340826 DOI: 10.1016/j.prosdent.2021.06.015

STATEMENT OF PROBLEM: The color and form of teeth are 2 of the 3 main determinants of success in an esthetic restoration; the third is dental proportion. A recent systematic review of the literature devoted to the evaluation of dental proportion is lacking.
PURPOSE: The purpose of this systematic review was to investigate the quality and outcome of studies into maxillary anterior tooth proportion and to determine whether dental proportion ratios based on different geographic regions are appropriate.
MATERIAL AND METHODS: An electronic search was conducted using PubMed, MEDLINE, Google Scholar, Embase, Scopus, Cochrane Library, Web of Science, and Science Direct databases. English-language articles reporting with the specific combination of medical subject heading (MeSH) key words were analyzed by 2 investigators. The titles, full text, and abstracts were scanned by investigators independently to identify articles that fulfilled the inclusion criteria. The general characteristics, outcomes, and quality of each study were reviewed and analyzed systematically.
RESULTS: The search plan resulted in a total of 73 articles until September 2020; of which, 16 articles fulfilling the inclusion criteria were selected. The geographic distribution of the selected article revealed 12 articles from Asia, 2 from Continental Europe, and 2 from the United Kingdom. Golden percentage values of 25%, 15%, and 10% for central, lateral incisor, and canine teeth were not found. The mean predicted dental percentage was either larger or smaller than the successive widths of maxillary natural anterior teeth.
CONCLUSIONS: The golden percentage could not be used to formulate a smile design. Rather, the dental ratios should be set on a racial and ethnic basis for a population.

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