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CD4+ Foxp3+ Regulatory T-cells in Modulating Inflammatory Microenvironment in Chronic Rhinosinusitis with Nasal Polyps: Progress and Future Prospect

M Yusoff NNF, Ahmad S, Wan Abdul Rahman WF, Mohamud R, C Boer J, Plebanski M, et al.

Cytokine, 2024 Jun;178:156557.
PMID: 38452440 DOI: 10.1016/j.cyto.2024.156557

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a subtype of chronic rhinosinusitis (CRS) characterized by the presence of nasal polyps (NP) in the paranasal mucosa. Despite the complex etiology, NP is believed to result from chronic inflammation. The long-term aftermath of the type 2 response is responsible for symptoms seen in NP patients, i.e. rhinorrhea, hyposmia, and nasal obstruction. Immune cellular tolerogenic mechanisms, particularly CD4 + Foxp3 + regulatory T cells (Tregs), are crucial to curtail inflammatory responses. Current evidence suggests impaired Treg activity is the main reason underlying the compromise of self-tolerance, contributing to the onset of CRSwNP. There is compelling evidence that tumor necrosis factor 2 (TNFR2) is preferentially expressed by Tregs, and TNFR2 is able to identify the most potent suppressive subset of Tregs. Tumor necrosis factor (TNF)-TNFR2 interaction plays a decisive role in the activation and expansion of Tregs. This review summarizes current understanding of Tregs biology, focusing on the discussion of the recent advances in the study of TNF-TNFR2 axis in the upregulation of Treg function as a negative feedback mechanism in the control of chronic inflammation. The role of dysregulation of Tregs in the immunopathogenesis of CRSwNP will be analyzed. The future perspective on the harnessing Tregs-mediated self-tolerant mechanism in the management of CRSwNP will be introduced.
Photonics-powered augmented reality skin electronics for proactive healthcare: multifaceted opportunities

Taha BA, Addie AJ, Kadhim AC, Azzahran AS, Haider AJ, Chaudhary V, et al.

Mikrochim Acta, 2024 Apr 08;191(5):250.
PMID: 38587660 DOI: 10.1007/s00604-024-06314-3

Rapid technological advancements have created opportunities for new solutions in various industries, including healthcare. One exciting new direction in this field of innovation is the combination of skin-based technologies and augmented reality (AR). These dermatological devices allow for the continuous and non-invasive measurement of vital signs and biomarkers, enabling the real-time diagnosis of anomalies, which have applications in telemedicine, oncology, dermatology, and early diagnostics. Despite its many potential benefits, there is a substantial information vacuum regarding using flexible photonics in conjunction with augmented reality for medical purposes. This review explores the current state of dermal augmented reality and flexible optics in skin-conforming sensing platforms by examining the obstacles faced thus far, including technical hurdles, demanding clinical validation standards, and problems with user acceptance. Our main areas of interest are skills, chiroptical properties, and health platform applications, such as optogenetic pixels, spectroscopic imagers, and optical biosensors. My skin-enhanced spherical dichroism and powerful spherically polarized light enable thorough physical inspection with these augmented reality devices: diabetic tracking, skin cancer diagnosis, and cardiovascular illness: preventative medicine, namely blood pressure screening. We demonstrate how to accomplish early prevention using case studies and emergency detection. Finally, it addresses real-world obstacles that hinder fully realizing these materials' extraordinary potential in advancing proactive and preventative personalized medicine, including technical constraints, clinical validation gaps, and barriers to widespread adoption.
Exploring the synergistic effect of carboxymethyl cellulose and chitosan in enhancing thermal stability of polyurethanes through statistical mixture design approach

Javaid MA, Cheema SA, Nasir N, Ahmad S, Hussain MT, Tanveer Z, et al.

Int J Biol Macromol, 2024 Apr 05.
PMID: 38583848 DOI: 10.1016/j.ijbiomac.2024.131441

The thermal stability of polyurethanes, known for its limitations, was addressed in this research by seeking improvement through the introduction of carbohydrate-based chain extenders. In this research paper, we systematically sought to improve the thermal resistance of polyurethanes by incorporating carboxymethyl cellulose and chitosan, representing a pioneering application of the mixture design approach in their preparation. In this synthesis, hydroxyl-terminated polybutadiene and isophorone diisocyanate (IPDI) were reacted to prepare -NCO terminated prepolymer, which was subsequently reacted with varying mole ratios of CMC and CSN to develop a series of five PU samples. The prepared PU samples were characterized using the Fourier-transformed infrared spectroscopic technique. Thermal pyrolysis of PU samples was examined using thermal gravimetric analysis (TGA). It was observed that, among all the samples, PUS-3 showed remarkable thermal stability over a wide temperature range. A comprehensive statistical analysis was conducted to substantiate the experimental findings. It was estimated that CMC and CSN significantly enhance the thermal stability of the samples when involved in an interaction fashion. The ANOVA Table for the mixture design demonstrates that over 90 % of the total variation in thermal stability is explained by the mixture model across a wide temperature range. Moreover, PSU-3 exhibited 4 % more thermal stability over a wide range of temperatures on average, as compared to contemporary samples.
Development of a zebrafish model for toxicity evaluation of adulterated Apis mellifera honey

Fakhlaei R, Selamat J, Abdull Razis AF, Sukor R, Ahmad S, Khatib A, et al.

Chemosphere, 2024 Mar 28;356:141736.
PMID: 38554873 DOI: 10.1016/j.chemosphere.2024.141736

Since ancient times, honey has been used for medical purposes and the treatment of various disorders. As a high-quality food product, the honey industry is prone to fraud and adulteration. Moreover, limited experimental studies have investigated the impact of adulterated honey consumption using zebrafish as the animal model. The aims of this study were: (1) to calculate the lethal concentration (LC50) of acid-adulterated Apis mellifera honey on embryos, (2) to investigate the effect of pure and acid-adulterated A. mellifera honey on hatching rate (%) and heart rate of zebrafish (embryos and larvae), (3) to elucidate toxicology of selected adulterated honey based on lethal dose (LD50) using adult zebrafish and (4) to screen the metabolites profile of adulterated honey from blood serum of adult zebrafish. The result indicated the LC50 of 31.10 ± 1.63 (mg/ml) for pure A. mellifera honey, while acetic acid demonstrates the lowest LC50 (4.98 ± 0.06 mg/ml) among acid adulterants with the highest mortality rate at 96 hpf. The treatment of zebrafish embryos with adulterated A. mellifera honey significantly (p ≤ 0.05) increased the hatching rate (%) and decreased the heartbeat rate. Acute, prolong-acute, and sub-acute toxicology tests on adult zebrafish were conducted at a concentration of 7% w/w of acid adulterants. Furthermore, the blood serum metabolite profile of adulterated-honey-treated zebrafish was screened by LC-MS/MS analysis and three endogenous metabolites have been revealed: (1) Xanthotoxol or 8-Hydroxypsoralen, (2) 16-Oxoandrostenediol, and (3) 3,5-Dicaffeoyl-4-succinoylquinic acid. These results prove that employed honey adulterants cause mortality that contributes to higher toxicity. Moreover, this study introduces the zebrafish toxicity test as a new promising standard technique for the potential toxicity assessment of acid-adulterated honey in this study and hazardous food adulterants for future studies.
Second twin outcome at birth: retrospective analysis in a single tertiary centre in Malaysia

Rahman RA, Mohammed Nawi A, Ishak S, Balaraman K, Abu MA, Abd Azman SH, et al.

J Perinat Med, 2024 Mar 22.
PMID: 38511669 DOI: 10.1515/jpm-2023-0449

OBJECTIVES: To investigate factors associated with outcome of second twin during labour.
METHODS: The study was a retrospective cohort study in a single tertiary centre in Malaysia from 2014 until 2018 involving all twin pregnancies delivered at or more than 24 weeks of gestation.
RESULTS: Total of 409 twin pregnancies were included. Dichorionic twin comprises of 54.5 % (n=223) and 45.5 % (n=186) are monochorionic. Women with dichorionic pregnancies are significantly older (p<0.001), have more pre-existing medical disorders (p=0.011) and fetal structural anomalies (p=0.009). Monochorionic pregnancies are significantly more amongst Malay (p=0.01) and conceived spontaneously (p<0.001). There are significantly more fetuses both in cephalic presentation (p=0.026), birthweight discrepancy more than 20 % (p=0.038) and shorter mean inter-twin delivery duration (p=0.048) in monochorionic pregnancies. Second twin delivered with Apgar score <7 is significantly more in dichorionic pregnancies (p=0.006). The second twin is associated with lower birthweight, small for gestational age and arterial cord pH<7.25. Within the group of women who delivered both fetuses vaginally, there was significantly more second twins with intertwin delivery duration less than 30 min who were delivered vaginally without instrumentation (p=0.018). There was significantly more second twin with intertwin delivery duration of 30 min and more with arterial cord pH<7.25 (p=0.045). Those who delivered spontaneously had inter-twin delivery duration within 15-29 min. The outcome of second twin is not influenced by type of twin, gestational age at delivery, inter-twin delivery duration, mode of delivery and presentation at birth.
CONCLUSIONS: The neonatal outcome for the second twin at birth is not influenced by type of twin, gestational age at delivery, inter-twin delivery duration, mode of delivery and presentation at birth in a cohort managed with non-active management of the second twin in Malaysia.
Fulltext Effectiveness of stingless bee (Kelulut) honey versus conventional gel dressing in diabetic wound bed preparation: A randomized controlled trial

Rosli MA, Mohd Nasir NA, Mustafa MZ, Othman MA, Zakaria Z, Halim AS

J Taibah Univ Med Sci, 2024 Feb;19(1):209-219.
PMID: 38124990 DOI: 10.1016/j.jtumed.2023.11.003

PURPOSE: Kelulut honey contains trehalulose and has high antioxidant content, such as phenolic and flavonoid substances, which can promote wound healing. This study evaluated the effectiveness of Kelulut honey in diabetic wound healing compared to a commercially available conventional gel dressing (Intrasite gel).
METHODS: A prospective, randomized, single-blinded control trial was performed on eligible diabetic patients with full-thickness cavity wounds. Patients' demographics, size and site of wounds, and baseline routine blood investigations were recorded. The wounds were dressed every other day with Kelulut honey for the intervention group or gel for the control group. The wound size reduction and granulation tissue formation percentage were calculated every 6 days for 1 month.
RESULTS: Seventy-one patients were randomized. After 30 days of follow-up, 62 participants were available for analysis: 30 from the control group and 32 from the treatment group. The control group had increased granulation tissue at baseline and more wounds on the lower limb and posterior trunk. Both groups showed an increasing mean and median percentage of wound epithelialization and granulation tissue over time, with significantly higher values at every timepoint in the honey group (p
Optimization of operational parameters using RSM, ANN, and SVM in membrane integrated with rotating biological contactor

Waqas S, Harun NY, Arshad U, Laziz AM, Sow Mun SL, Bilad MR, et al.

Chemosphere, 2024 Feb;349:140830.
PMID: 38056711 DOI: 10.1016/j.chemosphere.2023.140830

Membrane fouling is a critical bottleneck to the widespread adoption of membrane separation processes. It diminishes the membrane permeability and results in high operational energy costs. The current study presents optimizing the operating parameters of a novel rotating biological contactor (RBC) integrated with an external membrane (RBC + ME) that combines membrane technology with an RBC. In the RBC + ME, the membrane panel is placed external to the bioreactor. Response surface methodology (RSM) is applied to optimize the membrane permeability through three operating parameters (hydraulic retention time (HRT), rotational disk speed, and sludge retention time (SRT)). The artificial neural networks (ANN) and support vector machine (SVM) are implemented to depict the statistical modelling approach using experimental data sets. The results showed that all three operating parameters contribute significantly to the performance of the bioreactor. RSM revealed an optimum value of 40.7 rpm disk rotational speed, 18 h HRT and 12.4 d SRT, respectively. An ANN model with ten hidden layers provides the highest R2 value, while the SVM model with the Bayesian optimizer provides the highest R2. RSM, ANN, and SVM models reveal the highest R-square values of 0.97, 0.99, and 0.99, respectively. Machine learning techniques help predict the model based on the experimental results and training data sets.
Author Correction: Physico- and phytochemical properties of Brassica juncea as affected by agroclimatic conditions

Batool U, Nawaz R, Ahmad S, Irshad MA, Irfan A, Gaafar AZ, et al.

Sci Rep, 2024 Jan 25;14(1):2185.
PMID: 38272994 DOI: 10.1038/s41598-024-52693-1
Physico- and phytochemical properties of Brassica juncea as affected by agroclimatic conditions

Batool U, Nawaz R, Ahmad S, Irshad MA, Irfan A, Gaafar AZ, et al.

Sci Rep, 2024 Jan 08;14(1):797.
PMID: 38191635 DOI: 10.1038/s41598-023-48808-9

Physicochemical and phytochemical assessment of leaf mustard (Brassica juncea L.) grown in different agroclimatic conditions is essential to highlight their compositional variability and evaluate the most suitable bunch of agroclimatic and agronomic practices. B. juncea is one of the important leafy vegetables that serve as source of vitamin A and C and iron, and plenty of antioxidants. This in situ research was executed to assess the quality variability of B. juncea grown in different agroecosystems. Leaves' samples of B. juncea were procured from 15 farmers' fields exhibiting different agroclimatic conditions i.e., elevation, nutrient management, temperature, irrigation, and tillage practices. Leaves' samples were subjected to physicochemical and phytochemical analysis, i.e., moisture, pH, TSS, ascorbic acid, carotenoids, phenolics, flavonoids, and antioxidant potential. In the leaves' samples of B. juncea, the target properties were found to vary significantly (P ≤ 0.05) in different agroclimatic conditions. The moisture content, ascorbic acid, phenolic content, carotenoids, and antioxidants were found in the range of 62.7-79.3%, 74-91 mg/100 g, 49.2-49.2 mg GAE/100 g, 436.3-480 mg β carotene/100 g, 32.7-46.67%, respectively. This study elaborates the significant variation of physicochemical and phytochemical attributes of B. juncea due to the prevailing agroclimatic conditions. This necessitates the appropriate choice of B. juncea concerning its composition and ecological conditions of its cultivation in the prospective health benefits.
Clinical characteristics and outcomes of patients with mpox during the 2022 mpox outbreak compared with those before the outbreak: A systematic review and meta-analysis

Cho W, Park S, Kim HJ, Lee M, Choi YS, Yeo SG, et al.

Rev Med Virol, 2024 Jan;34(1):e2508.
PMID: 38282393 DOI: 10.1002/rmv.2508

On 23 July 2022, the World Health Organization declared the global mpox outbreak as a public health emergency of international significance. The mpox virus (MPXV) that caused the outbreak was classified as clade IIb, which belongs to the West African clade. However, the relationship between MPXV clades and symptoms, as well as the severity of mpox outcomes, is not fully understood. Thus, we aimed to investigate the global mpox prevalence and the differences in clinical manifestations and outcomes among patients with mpox between pre-outbreak (2003-2021) and the current mpox outbreak. In this systematic review and meta-analysis, PubMed/MEDLINE, Web of Science, Embase, Cumulative Index to Nursing and Allied Health Literature, and Google Scholar were searched using the keyword "monkeypox" and "mpox" up to 13 October 2022. A random effects model was used to obtain the pooled prevalence and 95% confidence intervals. This study included 27 articles, and 5698 patients with mpox with 19 distinctive features from 19 countries across five continents were assessed. Patients with mpox during the 2022 mpox outbreak showed mild clinical manifestations and outcomes compared with those before the 2022 mpox outbreak: mild rash (relative ratio [RR]: 5.09, 95% confidence interval [CI]: 1.52-17.08), fever (0.68, 0.49-0.94), pruritus (0.25, 0.19-0.32), myalgia (0.50, 0.31-0.81), headache (0.56, 0.35-0.88), skin ulcer (0.32, 0.17-0.59), abdominal symptom (0.29, 0.20-0.42), pharyngitis (0.32, 0.18-0.58), nausea or vomiting (0.15, 0.02-0.93), conjunctivitis (0.11, 0.03-0.38), concomitant infection with HIV (1.70, 0.95-3 0.04), and death (0.02, 0.001-0.31). MPXV clade IIb exhibited higher infectivity but may cause mild disease symptoms and low mortality rate. It is important to consider MPXV infection in patients with mpox-related features and/or a history of sexual transmission to prevent the spread of the disease and recognise the current pandemic threat.
Influence of fly ash on thermo-mechanical and mechanical behavior of injection molded polypropylene matrix composites

Meena R, Hashmi AW, Ahmad S, Iqbal F, Soni H, Meena A, et al.

Chemosphere, 2023 Dec;343:140225.
PMID: 37742771 DOI: 10.1016/j.chemosphere.2023.140225

Polypropylene composites find widespread application in industries, including packaging, plastic parts, automotive, textiles, and specialized devices like living hinges known for their remarkable flexibility. This study focuses on the manufacturing of polypropylene composite specimens by incorporating varying weight percentages of fly ash particles with polypropylene using a twin-screw extruder and injection molding machine. The composites were comprehensively tested, evaluating tensile, compressive, and flexural strength, solid-state and polymer melt properties, modulus, damping, and thermal response. The findings reveal that the compressive strength of polypropylene increases up to 2 wt% of added fly ash particles and subsequently exhibits a slight decline. Tensile strength demonstrates an increase up to 1 wt% of fly ash, followed by a decrease with a 2 wt% addition, and then a subsequent increase. Flexural strength shows improvement up to 3 wt% fly ash addition before declining. The storage modulus curve is categorized into three regions: the glassy region (up to 0 °C), the glass transition region (0-50 °C), and the glass transition region of polypropylene (>50 °C), each corresponding to different molecular motions. Weight loss curves exhibit similar trends, indicating uniform pyrolysis behavior attributed to consistent chemical bonds. Plastic degradation commences around 440 °C and concludes near 550 °C. Additionally, elemental mapping of fly ash composition identified various elements such as O, Si, K, Mg, Ca, Cl, Na, P, Al, Fe, S, Cu, Ti, and Ni. These findings offer valuable insights into the mechanical and thermal properties of polypropylene composites reinforced with fly ash, rendering them suitable for a wide range of industrial applications necessitating strength and durability across temperature variations.
Whole genome sequencing analysis demonstrates therapy-induced echinocandin resistance in Candida auris isolates

Spruijtenburg B, Ahmad S, Asadzadeh M, Alfouzan W, Al-Obaid I, Mokaddas E, et al.

Mycoses, 2023 Dec;66(12):1079-1086.
PMID: 37712885 DOI: 10.1111/myc.13655

Candida auris is an emerging, multidrug-resistant yeast, causing outbreaks in healthcare facilities. Echinocandins are the antifungal drugs of choice to treat candidiasis, as they cause few side effects and resistance is rarely found. Previously, immunocompromised patients from Kuwait with C. auris colonisation or infection were treated with echinocandins, and within days to months, resistance was reported in urine isolates. To determine whether the development of echinocandin resistance was due to independent introductions of resistant strains or resulted from intra-patient resistance development, whole genome sequencing (WGS) single-nucleotide polymorphism (SNP) analysis was performed on susceptible (n = 26) and echinocandin-resistant (n = 6) isolates from seven patients. WGS SNP analysis identified three distinct clusters differing 17-127 SNPs from two patients, and the remaining isolates from five patients, respectively. Sequential isolates within patients had a maximum of 11 SNP differences over a time period of 1-10 months. The majority of isolates with reduced susceptibility displayed unique FKS1 substitutions including a novel FKS1M690V substitution, and nearly all were genetically related, ranging from only three to six SNP differences compared to susceptible isolates from the same patient. Resistant isolates from three patients shared the common FKS1S639F substitution; however, WGS analysis did not suggest a common source. These findings strongly indicate that echinocandin resistance is induced during antifungal treatment. Future studies should determine whether such echinocandin-resistant strains are capable of long-term colonisation, cause subsequent breakthrough candidiasis, have a propensity to cross-infect other patients, or remain viable for longer time periods in the hospital environment.
First Report of Fruit Rot Caused by Fusarium incarnatum-equiseti species complex on Greenhouse Bell Pepper in Malaysia

Ishak NF, Wan Azhar WMA, Ahmad S, Khairuddin AU, Laboh R

Plant Dis, 2023 Oct 19.
PMID: 37858968 DOI: 10.1094/PDIS-06-23-1076-PDN

In Malaysia, bell pepper (Capsicum annuum var. grossum), also known as sweet pepper or paprika, is one of the highly imported vegetable crops. In 2021 alone, Malaysia imported nearly 74 thousand metric tons of its chilies, including bell peppers, from other countries (DOSM, 2022). Often, farmers grow the bell peppers in moderate to cool conditions within highland regions for local commercial purposes. In June 2022, the Malaysian Agricultural Research and Development Institute (MARDI) in Serdang, Selangor, conducted a research study to grow lowland bell peppers under a glasshouse rain protection system. A disease inspection carried out found fruit rot on approximately 30% of mature bell pepper fruits in the greenhouse. Symptoms appeared as firm and sunken black lesions covered with white to light pink spore masses on the outer surface, which eventually fell off. Infected fruit parts were disinfected with 10% hypochlorite (NaOCl) for 2 min, followed by double washing with sterile distilled water, air-dried, and placed onto potato dextrose agar (PDA). After 3 days of incubation, the fungal colonies that grew from the symptomatic tissue pieces were transferred onto new PDA to obtain pure cultures. The pure fungal colony appeared dense, whitish aerial mycelium that slowly became cream to pinkish-orange after 7 days of incubation at room temperature (25±2 °C). To examine the morphology features, the pure cultures were subbed onto carnation leaf agar (CLA) and incubated at 25±2°C for 14 days. Macroconidia were abundant, slightly curved with tapered apical cells, 3- to 5-septate, and ranged between 21.8 and 34.0 x 3.0 and 5.1 μm. Microconidia were single-celled, often 1-septate, and ranged between 10.0 and 12.6 x 2.1 and 3.4 μm. Chlamydospores were globose and in chains. The fungus was identified as Fusarium sp. according to Fusarium key by Leslie and Summerell (2006). PCR amplification and DNA sequencing were performed using primers EF1F/EF2R and ITS1/ITS4 (O'Donnell et al., 1998; White et al., 1990) to amplify the partial elongation factor 1-alpha (TEF1-α) gene and internal transcribed spacer region (ITS), respectively. The TEF1-α and ITS sequences of this isolate were deposited in GenBank as OQ672911 and OR349657. BLAST analysis with TEF1-α gene sequences revealed 99.74% and 99.33% sequence identity with F. pernambucanum (accession no. ON330424) and Fusarium isolate NRRL 25134 (accession no. JF740755), respectively; both belonged to the Fusarium incarnatum-equiseti species complex (FIESC). BLAST search of the TEF1-α sequence in the database of the International Mycological Association (www.mycobank.org) showed 99.18% identity with FIESC (NRRL 36548). The ITS sequences were 100% identical to those of F. incarnatum (MT563420, MT563419, and MT563418). Pathogenicity test was conducted on three unwounded and three wounded mature red bell pepper fruits (SP299 Red Masta variety). Two healthy bell peppers were used as controls for each treatment. Prior to inoculation, the fruits were surface-sterilized by dipping in 70% ethanol and rinsed twice with sterile distilled water. Unwounded fruits were inoculated with fungal mycelium disks (5 mm diameter), whereas control fruits were inoculated with sterile PDA agar disks. For wound method, 6 µl of spore suspension (1x106 spores/ml) was obtained from 7-day-old cultures and injected (1 mm depth) into the fruit wall using a sterile syringe needle. Control fruits were inoculated with sterile distilled water only. Each fruit was inoculated with the inoculum at three distinct spots and kept in a humid chamber at a temperature of 25±2 °C. The pathogenicity test was done twice. Five days post-inoculation, the control fruits showed no symptoms, whereas all inoculated wounded and non-wounded fruits developed necrotic lesions with white mycelium growing on the inoculation points. The pathogen was successfully re-isolated from the infected fruits and morphologically identified as FIESC, fulfilling Kochs postulates. It has been reported previously that the members of FIESC are responsible for the fruit rot of bell peppers under greenhouse conditions (Ramdial et al., 2016). To the best of our knowledge, this is the first report of FIESC causing fruit rot on greenhouse bell peppers in Malaysia. This fruit rot disease may impose significant constraints on bell pepper production in Malaysia; hence, effective strategies to control the pathogen and prevent disease dispersal should be implemented.
Evaluation of the Impact of Orthodontic Treatment on Patients' Self-Esteem: A Systematic Review

Shaadouh RI, Hajeer MY, Burhan AS, Ajaj MA, Jaber ST, Zakaria AS, et al.

Cureus, 2023 Oct;15(10):e48064.
PMID: 37920628 DOI: 10.7759/cureus.48064

Malocclusion may affect interpersonal relationships, self-esteem (SE), and psychological well-being, weakening patients' psychological and social activities. Several studies investigated the effect of orthodontic treatment on these social and psychological aspects, such as SE. However, the direct relationship between SE and orthodontic treatment has not yet been confirmed. This systematic review aimed to evaluate the existing evidence in the literature concerning the influences of orthodontic treatment on patients' SE systematically and critically. An electronic search in the following databases was done in September 2022: PubMed®, Web of Science™, Scopus®, Embase®, GoogleTM Scholar, Cochrane Library databases, Trip, and OpenGrey. Then, the reference list of each candidate study was checked for any potentially linked papers that the electronic search might not have turned up. Inclusion criteria were set according to the population/intervention/comparison/outcome/study design (PICOS) framework. For the data collection and analysis, two reviewers extracted data separately. The risk of bias 2 (RoB-2) and the risk of bias in non-randomized studies (ROBINS-I) tools were used to assess the risk of bias for randomized controlled trials (RCTs) and non-RCTs, respectively. The grading of recommendations assessment, development and evaluation (GRADE) approach was employed to evaluate the quality of the evidence for each finding. Sixteen studies (five RCTs, seven cohorts, and four cross-sectional) were included in this review. Unfortunately, the results could not be pooled into a meta-analysis. Only six studies have reported an increase in SE after orthodontic treatment (P<0.05 in these studies). No agreement between the included studies was observed regarding the influence of fixed orthodontic treatment, gender, or age on SE. The quality of evidence supporting these findings ranged from very low to low. There is low evidence indicating that fixed orthodontic treatment can improve patients' SE. In addition, unclear data are available about the influence of patients' gender and age on SE after orthodontic treatment. Therefore, high-quality RCTs are required to develop stronger evidence about this issue.
Efficacy and safety of nab-paclitaxel in metastatic gastric cancer: a meta-analysis

Ahmad S, Lambuk L, Ahmed N, Mussa A, Tee V, Mohd Idris RA, et al.

Nanomedicine (Lond), 2023 Oct;18(24):1733-1744.
PMID: 37982749 DOI: 10.2217/nnm-2022-0300

Background: Nab-paclitaxel is formulated to address several limitations of paclitaxel. Methods: A systematic review was done of several databases and a meta-analysis with a random-effects model was conducted to assess the efficacy and safety of nab-paclitaxel in metastatic gastric cancer (MGC). Results: Included studies revealed that nab-paclitaxel provides a 30.4% overall response rate and 65.7% disease control rate in MGC patients. The overall survival was 9.65 months and progression-free survival was 4.48 months, associated with the treatment line and regimen. The highest incidence of grade 3 and higher treatment-related adverse events was for neutropenia (29.9%). Conclusion: Nab-paclitaxel provides better disease response and longer survival with manageable side effects in MGC compared with paclitaxel.
Fulltext The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories: A Systematic Analysis for the Global Burden of Disease Study 2019

GBD 2019 Lip, Oral, and Pharyngeal Cancer Collaborators, Cunha ARD, Compton K, Xu R, Mishra R, Drangsholt MT, et al.

JAMA Oncol, 2023 Oct 01;9(10):1401-1416.
PMID: 37676656 DOI: 10.1001/jamaoncol.2023.2960

IMPORTANCE: Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning.
OBJECTIVE: To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates.
EVIDENCE REVIEW: The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019.
FINDINGS: In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia.
CONCLUSIONS AND RELEVANCE: In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.
Fulltext Gene coexpression network analysis reveals perirenal adipose tissue as an important target of prenatal malnutrition in sheep

Ahmad S, Drag MH, Mohamad Salleh S, Cai Z, Nielsen MO

Physiol Genomics, 2023 Sep 01;55(9):392-413.
PMID: 37458462 DOI: 10.1152/physiolgenomics.00128.2022

We have previously demonstrated that pre- and early postnatal malnutrition in sheep induced depot- and sex-specific changes in adipose morphological features, metabolic outcomes, and transcriptome in adulthood, with perirenal (PER) as the major target followed by subcutaneous (SUB) adipose tissue. We aimed to identify coexpressed and hub genes in SUB and PER to identify the underlying molecular mechanisms contributing to the early nutritional programming of adipose-related phenotypic outcomes. Transcriptomes of SUB and PER of male and female adult sheep with different pre- and early postnatal nutrition histories were used to construct networks of coexpressed genes likely to be functionally associated with pre- and early postnatal nutrition histories and phenotypic traits using weighted gene coexpression network analysis. The modules from PER showed enrichment of cell cycle regulation, gene expression, transmembrane transport, and metabolic processes associated with both sexes' prenatal nutrition. In SUB (only males), a module of enriched adenosine diphosphate metabolism and development correlated with prenatal nutrition. Sex-specific module enrichments were found in PER, such as chromatin modification in the male network but histone modification and mitochondria- and oxidative phosphorylation-related functions in the female network. These sex-specific modules correlated with prenatal nutrition and adipocyte size distribution patterns. Our results point to PER as a primary target of prenatal malnutrition compared to SUB, which played only a minor role. The prenatal programming of gene expression and cell cycle, potentially through epigenetic modifications, might be underlying mechanisms responsible for observed changes in PER expandability and adipocyte-size distribution patterns in adulthood in both sexes.
Acetylsalicylic acid-sulfa drugs conjugates as potential urease inhibitors and anti-inflammatory agents: bio-oriented drug synthesis, molecular docking, and dynamics simulation studies

Ahmad S, Abdul Qadir M, Ahmed M, Imran M, Yousaf N, Asari A, et al.

J Biomol Struct Dyn, 2023 Aug 29.
PMID: 37643014 DOI: 10.1080/07391102.2023.2252083

To explore the new mode of action and reduce side effects, making conjugates of existing drugs is becoming an attractive tool in the realm of medicinal chemistry. In this work, we exploited this approach and synthesized new conjugates to assess their activities against the enzymes involved in different pathological conditions. Specifically, we design and synthesized conjugates involving acetylsalicylic acid and sulfa drugs, validating the newly crafted conjugates using techniques like IR, 1HNMR, 13CNMR, and elemental analysis. These conjugates underwent assessment for their ability to inhibit cyclooxygenase-2 (COX-2), urease enzymes, and their anti-inflammatory potential. A competitive mode of urease inhibition was observed for acetylsalicylic acid conjugated with sulfanilamide, sulfacetamide, and sulfadiazine with IC50 of 2.49 ± 0.35 µM, 6.21 ± 0.28 µM, and 6.57 ± 0.44 µM, respectively. Remarkably, the acetylsalicylic acid-sulfamethoxazole conjugate exhibited exceptional anti-inflammatory activity, effectively curtailing induced edema by 83.7%, a result akin to the reference anti-inflammatory drug indomethacin's performance (86.8%). Additionally, it demonstrated comparable COX-2 inhibition (75.8%) to the reference selective COX-2 inhibitor celecoxib that exhibited 77.1% inhibition at 10 µM concentration. To deepen our understanding, we employed molecular docking techniques to predict the binding interactions of competitive inhibitors with COX-2 and urease receptors. Additionally, MD simulations were carried out, confirming the stability of inhibitor-target complexes throughout the simulation period, devoid of significant conformational changes. Collectively, our research underscores the potential of coupling approved medicinal compounds to usher in novel categories of pharmacological agents, holding promise for addressing a wide spectrum of pathological disorders involving COX-2 and urease enzymes.Communicated by Ramaswamy H. Sarma.
Strategies for strengthening toughened poly(lactic acid) blend via natural reinforcement with enhanced biodegradability: A review

Shahdan D, Rosli NA, Chen RS, Ahmad S, Gan S

Int J Biol Macromol, 2023 Aug 11;251:126214.
PMID: 37572810 DOI: 10.1016/j.ijbiomac.2023.126214

The growing popularity of poly(lactic acid) (PLA) can be attributed to its favorable attributes, such as excellent compostability and robust mechanical properties. Two notable limitations of PLA are its high brittleness and slow biodegradation rate. Both of blending and copolymerization strategies work well to improve PLA's toughness while sacrificing the good tensile strength and modulus properties of PLA. One of the most effective and economical approaches to address this challenge is to incorporate natural reinforcing agents into the toughened PLA system, thereby simultaneously promoting the biodegradation rate of PLA. Nevertheless, the enhancement of tensile strength and modulus is accompanied by a notable decrease in elongation. Therefore, this review provides comprehensive information on the literature works related to the tensile strength, modulus, elongation at break and impact strength of the toughened PLA and its natural fiber reinforced composites. The impact of natural reinforcing agent on the tensile fracture mechanism as well as the synergistic effect on strengthening and toughening performance will be discussed. This review also focuses on the factors boosting the biodegradability of toughened PLA blend by using natural reinforcing fiber. Review presents potential future insights into the development of biodegradable and balanced strengthened-toughened PLA based advanced materials.
Fulltext The Impact of Temporomandibular Disorders on Orthodontic Management: A Systematic Review and Meta-Analysis

Alam MK, Abutayyem H, Alzabni KMD, Almuhyi NHS, Alsabilah KAS, Alkubaydan FST, et al.

Cureus, 2023 Aug;15(8):e44243.
PMID: 37645665 DOI: 10.7759/cureus.44243

The literature on the impact of temporomandibular disorders (TMDs) on orthodontic management or vice versa lacks clarity. This study presents a review that aims to evaluate the influence of TMDs on orthodontic management and explore the association between TMDs and various aspects of orthodontic treatment. A systematic search was conducted across multiple databases to identify relevant articles documenting the correlation between TMD incidence and orthodontic treatment to achieve the objectives. The selection process followed predefined criteria, and the selected studies underwent bias assessment using the AXIS tool and Cochrane risk of bias (RoB) tool. Among the articles identified, nine studies were deemed suitable for inclusion in the review. The findings from the subsequent meta-analysis indicated a significant overall effect, suggesting that orthodontic treatment may increase the risk of developing TMD. Furthermore, the analysis revealed that patients with TMD had higher odds of experiencing orthodontic issues than those without TMD. Subgroup analysis further demonstrated that orthodontic treatment could have a negative impact on the psychological well-being of TMD patients, while its effect on TMD incidence was found to be negligible. The results highlight the need for additional research to gain a better understanding of the underlying mechanisms and develop appropriate interventions aimed at minimizing the risk of TMD in patients undergoing orthodontic treatment. Clinicians should be aware of TMD as a potential complication of orthodontic treatment and implement appropriate monitoring strategies.

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