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Purpose: Antimicrobial resistance (AMR) phenomenon is a global health issue. The surging of resistant infections is pushing up costs of treatment, leading to difficulty in treating infections, worse clinical outcomes f and severe economic loss. AMR is not limited to human health. The problem also has impacts on animal husbandry practices resulting in similarly higher costs for treatment and animal-origin food production. Effort to address this requires a One Health-holistic and multisectoral approach, as resistant bacteria arising in humans, animals or the environment may spread from one to another leading to bigger threat.One-health approach pilot project was established as integrated surveillance system to monitor ESBL E.coli in three main areas of concern; human (hospital and community), food, and the environment based on a global protocol. The use of ESBL producing E coli as a single indicator for Gram-negative resistance was adopted from European Antimicrobial Resistance Surveillance Network. Methods & Materials: Ninety- eight ESBL producing E.coli were selected for whole genome analysis using Nextera® XT DNA Library Preparation kit (Illumina®, USA).Twenty-five isolated were derived from hospitalized patients, seven from community Health Clinics, 46 isolates were from chicken ceca samples representing food chain and 20 were from water samples. Results were analyze using Resfinder 3.2, Multi-Locus Sequence Typing 2.0 and CSI phylogeny 1.4. Results: The strains isolated were diverse with 51 different ST identified. ST45 (5/98 5%) was the predominant type, however ST3 was more widely distributed, detected among hospital strains and food chain sector. Nineteen new clones were identified. Single nucleotide polymorphism phylogenetic analysis of core genomes revealed that all organisms were interrelated. Majority of the isolates harbored ESBL blaCTX-M-33 gene (n=76)(76%). In addition, some isolates also harbored carbapenemases resistant gene; blaOXA1 (n=5)(5%), blaOXA2 (n=10)(10%) and colistin resistant gene; blaMCR1(n=40)(40%) and blaMCR3(n=4)(4%). Conclusion: Isolates derived from all three sources were interrelated. The concept of one-health approach is very important in understanding the spread as well as combating antimicrobial resistance.

Knee osteoarthritis (OA) is a common condition with a prevalence of 365 million individuals globally, and it is an independent risk factor for falls and fractures, notably asymptomatic morphometric vertebral fractures (AMVF). The high prevalence of knee OA, the severity of AMVF, and their combined impacts on quality of life underscore the need for early detection, appropriate treatment and management. To address this, our cross-sectional study aims to identify potential predictive factors associated with AMVF in knee OA patients. Our cohort consisted of 76 patients diagnosed with knee OA, predominantly female (84.2%), of Malay ethnicity (84.2%), and obese (55.3%). In univariable analysis, significant association was found between occupation (moderate or heavy work) and AMVF (p<0.001). Diabetes mellitus comorbidity (p = 0.016) and fat mass percentage (p = 0.027) also demonstrated a significant association with AMVF in knee OA patients. Multivariable logistic regression analysis revealed that an increase in fat mass percentage resulted in decreased AMVF incidence (HR: 0.83, 95% CI: 0.70-0.97; p = 0.018), while occupation (moderate or heavy work) remained a highly significant predictor (HR: 57.76, 95% CI: 4.23-788.57; p = 0.002). These findings support the potential importance of considering occupational activities and body fat composition in managing AMVF among knee OA patients, but further research is required to establish causal relationships., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2024 Zolkiply et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: This study aimed to perform a systematic review and meta-analysis to investigate the relationship between wood dust exposure and leukemia. The objectives included synthesizing available evidence, assessing its quality, identifying potential sources of heterogeneity, and drawing conclusions regarding the association between wood dust and leukemia., Methods: A systematic literature search was conducted to identify studies meeting that report on the association between wood dust and leukemia. The Joanna Briggs Institute Critical Appraisal tools were employed to ensure robust quality assessment. Meta-analysis, using random-effects models, synthesized evidence from studies with low risk of bias. Overall odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses explored potential sources of heterogeneity., Results: The meta-analysis included a comprehensive review of various study types, encompassing 7 studies that examined the association between wood dust exposure and leukemia risk. The analysis revealed a statistically significant positive association, with an overall odds ratio (OR) of 1.56 (95% CI: 1.15-2.12). This indicates that individuals exposed to wood dust are 1.56 times more likely to develop leukemia compared to those not exposed, with the 95% confidence interval ranging from 1.15 to 2.12, highlighting a substantial risk elevation across different study designs. Quality assessment using The Joanna Briggs Institute Critical Appraisal tools demonstrated a low risk of bias across all included studies, enhancing the credibility of the observed association. Subgroup analyses were conducted to explore potential sources of heterogeneity within the studies. Notably, subgroup analysis based on the year of the study revealed significant differences, as indicated by an I^2 value of 87%. The robustness of these results underscores the importance of addressing wood dust exposure as an occupational hazard, particularly in industries related to woodworking and forestry., Conclusion: This meta-analysis provides robust evidence supporting an increased risk of leukemia associated with wood dust exposure implying proactive measures in people exposed to dust., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Soleimani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The umbilicus, an essential embryonic organ, connects the foetus to the placenta. Postnatally, its remnants can lead to both benign and malignant lesions. Tumour metastasis to the umbilicus, though rare, poses significant diagnostic and therapeutic challenges due to overlapping clinical and radiological features with benign conditions. In this case series, we present three cases of elderly women with similar presentations of umbilical or infraumbilical lesions, investigated using standard imaging protocols, which subsequently led to different diagnoses and management plans. Case 1 involves a 64-year-old postmenopausal woman, who presented with an enlarging umbilical mass and serous discharge. Imaging revealed a vascularized lesion in the umbilicus and a suspicious adnexal mass, which was confirmed to be a Sister Mary Joseph nodule secondary to high-grade serous carcinoma of the right ovary. Case 2 involves an 80-year-old diabetic woman, who presented with a painful umbilical mass. Imaging revealed an aggressive-looking umbilical lesion, which was confirmed to be liposarcoma. Case 3 involves an 80-year-old woman, who presented with infraumbilical abdominal swelling and fever. Imaging revealed an infected urachal cyst. Histopathology confirmed an abscess associated with Actinomycetes infection. An umbilical lesion in an adult, particularly an elderly patient, that does not respond to typical treatment should raise the suspicion of a more sinister diagnosis. Integration of clinical, radiological, and pathological data is crucial for accurate diagnosis and effective management., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Soo et al.)

Introduction: Diffusion-weighted imaging (DWI) in magnetic resonance imaging (MRI) has been proposed as the first line of neuroimaging for acute ischaemic stroke. The reliability of DWI in detecting intracranial haemorrhage, however, is still unproven, compared with susceptibility-weighted imaging (SWI) and CT scan which being considered the gold standard. This study seeks to establish the reliability of DWI as a first-line imaging modality to detect the intracranial haemorrhage in the patients present within the thrombolysis window., Materials and Methods: A retrospective cross-sectional analysis was performed on patients who presented to our institution from April 2020 until July 2021 for acute stroke and had MRI brain as first-line neuroimaging. A total of 31 subjects were included in this study. Two radiologists assessed the signal patterns in DWI sequence and compared them with SWI and CT Brain, whenever available, as the gold standard for observing the presence of intracranial haemorrhage., Results: The majority of patients with hyperacute bleed proven to be revealed on SWI or CT, thus showed characteristics of central hyperintensity and peripheral hypointense rim, on DWI. Slightly more than half (51.6%) presented with mild to moderate NIHSS scores (1-15). The sensitivity, specificity, positive predictive value and negative predictive value of DWI in detecting intracranial intra-axial haemorrhages were exceptionally high. There is strong interobserver level of agreement in identifying central haemorrhagic signal intensity [kappa = 0.94 (0.06), p < 0.05]., Conclusion: This study supported the DWI sequence as a reliable sequence in MRI, to detect intracranial haemorrhage in hyperacute stroke.

Violence against healthcare workers recently became a growing public health concern and has been intensively investigated, particularly in the tertiary setting. Nevertheless, little is known of workplace violence against healthcare workers in the primary setting. Given the nature of primary healthcare, which delivers essential healthcare services to the community, many primary healthcare workers are vulnerable to violent events. Since the Alma-Ata Declaration of 1978, the number of epidemiological studies on workplace violence against primary healthcare workers has increased globally. Nevertheless, a comprehensive review summarising the significant results from previous studies has not been published. Thus, this systematic review was conducted to collect and analyse recent evidence from previous workplace violence studies in primary healthcare settings. Eligible articles published in 2013-2023 were searched from the Web of Science, Scopus, and PubMed literature databases. Of 23 included studies, 16 were quantitative, four were qualitative, and three were mixed method. The extracted information was analysed and grouped into four main themes: prevalence and typology, predisposing factors, implications, and coping mechanisms or preventive measures. The prevalence of violence ranged from 45.6% to 90%. The most commonly reported form of violence was verbal abuse (46.9-90.3%), while the least commonly reported was sexual assault (2-17%). Most primary healthcare workers were at higher risk of patient- and family-perpetrated violence (Type II). Three sub-themes of predisposing factors were identified: individual factors (victims' and perpetrators' characteristics), community or geographical factors, and workplace factors. There were considerable negative consequences of violence on both the victims and organisations. Under-reporting remained the key issue, which was mainly due to the negative perception of the effectiveness of existing workplace policies for managing violence. Workplace violence is a complex issue that indicates a need for more serious consideration of a resolution on par with that in other healthcare settings. Several research gaps and limitations require additional rigorous analytical and interventional research. Information pertaining to violent events must be comprehensively collected to delineate the complete scope of the issue and formulate prevention strategies based on potentially modifiable risk factors to minimise the negative implications caused by workplace violence., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The use of natural reducing and capping agents has gained importance as a way to synthesize nanoparticles (NPs) in an environmentally sustainable manner. Increasing numbers of studies have been published on the green synthesis of NPs using natural sources such as bacteria, fungi, and plants. In recent years, the use of honey in the synthesis of metal and metal oxide NPs has become a new and promising area of research. Honey acts as both a stabilizing and reducing agent in the NP synthesis process and serves as a precursor. This review focuses on the use of honey in the synthesis of silver NPs (Ag-NPs) and zinc oxide NPs (ZnO-NPs), emphasizing its role as a reducing and capping agent. Additionally, a comprehensive examination of the bio-based reducing and capping/stabilizing agents used in the honey-mediated biosynthesis mechanism is provided. Finally, the review looks forward to environmentally friendly methods for NP synthesis.

Abstract: Recent advances in technology, particularly in the field of magnetic resonance imaging, have brought forth new sequences, including vessel wall imaging (VWI). Traditionally, the workup for intracranial vascular pathology has always turned to luminal imaging using computed tomography angiography, magnetic resonance angiography, or digital subtraction angiography. Since its introduction, VWI has enabled researchers and practicing clinicians to better understand disease processes and manage patients to the best standard of care possible. Spontaneous recanalization in acute ischemic stroke (AIS) is a known but understudied phenomenon. Available literature has looked at this phenomenon and postulated the occurrence based on conventional cross-sectional imaging and angiography; however, objective evidence pointing to the occurrence of this phenomenon is scarce. We would like to share our experience using VWI in a patient who was clinically suspected to have a middle cerebral artery syndrome at onset, with resolution of the symptoms 3 hours after initial presentation. VWI showed vessel wall enhancement at the suspected vessel involved, with evidence of acute infarcts at the vascular territory supplied. A presumptive diagnosis of AIS with spontaneous recanalization was made. Our experience could potentially aid in the understanding of spontaneous recanalization in patients with AIS, particularly in the postulation of the pathophysiology., Competing Interests: The authors declare no conflicts of interest., (Copyright © Wolters Kluwer Health, Inc. All rights reserved.)

Wounds with impaired healing, including delayed acute injuries and chronic injuries, generally fail to progress through normal healing stages. A deeper understanding of the biochemical processes involved in chronic wound cures is necessary to correct the microenvironmental imbalances in the wound treatment designs of products. The therapeutic benefits of honey, particularly its antimicrobial activity, make it a viable option for wound treatment in a variety of situations. Integration with nanotechnology has opened up new possibilities not only for wound healing but also for other medicinal applications. In this review, recent advances in honey-based nanoparticles for wound healing are discussed. This also covers the mechanism of the action of nanoparticles in the wound healing process and perspectives on the challenges and future trends of using honey-based nanoparticles. The underlying mechanisms of wound healing using honey are believed to be attributed to hydrogen peroxide, high osmolality, acidity, non-peroxide components, and phenols. Therefore, incorporating honey into various wound dressings has become a major trend due to the increasing demand for combination dressings in the global wound dressing market because these dressings contain two or more types of chemical and physical properties to ensure optimal functionality. At the same time, their multiple features (low cost, biocompatibility, and swelling index) and diverse fabrication methods (electrospun fibres, hydrogels, etc.) make them a popular choice among researchers.

Background: The practice of wet nursing or breastfeeding another woman's child in Malaysia, especially among Muslim mothers, is on the rise. This is due to the emergence of public awareness of the benefits of breast milk to children. However, it is claimed that some mothers do not have a clear understanding of the Islamic rulings concerning wet nursing, especially those related to mahram (prohibition to marry), nasab (lineage) and inheritance. Hence, the purpose of this study is to examine the level of understanding of the legal implications of wet nursing and the factors influencing the practice among Muslim mothers who have practiced breastfeeding., Methods: This was a cross-sectional descriptive study that was conducted between January and July 2019. This study was conducted with 100 Muslim mothers who had breastfed others' child(ren) in Selangor. Data were obtained using a validated questionnaire (Cronbach's alpha = 0.8) and processed using the Statistical Package for the Social Sciences (SPSS) software., Results: The results show that the majority of the respondents understand the basic Islamic rulings on wet nursing, especially on the persons prohibited to marry, conditions and feeding method. However, the respondents need to further understand the rulings related to nasab (lineage), guardianship and inheritance involving the milk child. Various factors that have influenced wet nursing in society were also found., Conclusions: This study has significant implications for the need to have more activities to create awareness and enhance the understanding related to wet nursing among Muslim women in society. Therefore, more research studies related to wet nursing and the impact of the practice should be conducted to offer better solutions to society., Competing Interests: The authors have declared that no competing interests exist.

Aims: Coagulase-negative Staphylococci (CoNS) are frequently isolated in peritoneal dialysis (PD)-related peritonitis with a high rate of relapse and repeat peritonitis after initial response to antimicrobials. The optimal treatment regimen for CoNS peritonitis remains debatable. Hence, this study aimed to describe the clinical and microbiologic characteristics of CoNS peritonitis in a PD center and determine predictive factors influencing the outcomes., Methods: All cases of CoNS peritonitis in Selayang Hospital between 2011 and 2019 were reviewed retrospectively., Results: A total of 906 episodes of peritonitis were recorded; 140 episodes (15%) in 98 patients were caused by CoNS. The oxacillin and gentamicin resistance rates were 47% and 46%, respectively. The overall primary response rate was 90%, and the complete cure rate was 79%. Patients with concomitant exit-site infection (odds ratio (OR) 0.06, 95% confidence interval (CI) 0.01 to 0.40, P < 0.01) and history of recent systemic antibiotic use (OR 0.04, 95% CI 0.01 to 0.82, P =0.04) were less likely to achieve primary response. CoNS episodes that were treated with beta-lactam-based or vancomycin-based therapy had a similar primary response rate and complete cure rate. The rates of relapse and repeat were 12% and 16%, respectively. Relapsed episodes (OR 0.35, 95% CI 0.13 to 0.97, P =0.04) had a significantly lower complete cure rate than the first episodes., Conclusion: Relapsed CoNS peritonitis was common and was associated with worse outcomes than the first episode of CoNS peritonitis. Oxacillin resistance was common, but the treatment outcome remained favourable when a beta-lactam-based regimen was used as empirical therapy., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Siew Yan Lau et al.)

Acute transverse myelitis is an inflammatory disorder of the spinal cord in which there is no evidence of spinal cord compression. Longitudinally extensive transverse myelitis (LETM) is a specific subtype of acute transverse myelitis that usually affects three or more vertebral levels and produces marked neurological deficits. While the most-common cause of LETM is neuromyelitis optica or neuromyelitis optica spectrum disorder, there are rare cases of other causes mimicking this condition, including tuberculosis (TB). We sought to review the clinicoradiological features of TB myelopathy associated with longitudinally extensive lesion, which may mimic LETM, in the English literature. We searched the PubMed, Google Scholar, Web of Science, and Scopus databases for relevant articles using search terms including "longitudinally extensive transverse myelitis," "tuberculosis," "TB spinal cord," and various combinations of these expressions. Full-text papers were selected without limiting the publication year. We also examined the reference lists of key papers to identify further articles that are potentially relevant. We found 10 cases in 7 papers describing TB myelopathy associated with longitudinally extensive lesion. The demographics, clinical features, relevant cerebrospinal fluid findings, and radiological findings were compiled and summarized. TB myelopathy associated with longitudinally extensive lesion is very rare, with no documented prevalence. Early and accurate diagnosis is important since the condition is potentially treatable., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2020 Korean Neurological Association.)

Uncontrolled distribution of nanoparticles (NPs) within the body can significantly decrease the efficiency of drug therapy and is considered among the main restrictions of NPs application. The aim of this study was to develop a depot combination delivery system (CDS) containing fingolimod loaded poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) NPs dispersed into a matrix of oleic acid-grafted-aminated alginate (OA-g-AAlg) to minimize the nonspecific biodistribution (BD) of PHBV NPs. OA-g-AAlg was synthesized in two step; First, Alg was aminated by using adipic dihydrazide (ADH). The degree of hyrazide group substitution of Alg was determined by trinitro-benzene-sulfonic acid (TNBS) assay. Second, OA was attached to AAlg through formation of an amide bond. Chemical structure of OA-g-AAlg was confirmed with FTIR and HNMR spectroscopy. Furthermore, rheological properties of OA-g-AAlg with different grafting ratios were evaluated. In-vitro release studies indicated that 47% of fingolimod was released from the CDS within 28 days. Blood and tissue samples were analyzed using liquid chromatography/tandem mass spectrometry following subcutaneous (SC) injection of fingolimod-CDS into Wistar rats. The elimination phase half-life of CDS-fingolimod was significantly higher than that of fingolimod (∼32 d vs. ∼20 h). To investigate the therapeutic efficacy, lymphocyte count was assessed over a 40 day period in Wistar rats. Peripheral blood lymphocyte count decreased from baseline by 27 ± 8% in 2 days after injection. Overall, the designed CDS represented promising results in improving the pharmacokinetic properties of fingolimod. Therefore, we believe that this sustained release formulation has a great potential to be applied to delivery of various therapeutics.

Objective: The aim of this study was to explore parents' awareness and usage of CRS, incentives and challenges in CRS use, as well as their perception about potential CRS legislation in Malaysia. Methods: This was a cross-sectional study conducted in a public tertiary care center in Northern Malaysia. A self-developed researcher-assisted questionnaire was developed in English and translated into Malay language, to explore parents' awareness ad CRS usage, as well as the incentives and barriers in CRS use. Parents of a newborn were conveniently sampled, excluding parents with pre-term newborn or those without a car. Upon obtaining written informed consent, the parents were allowed to answer the questionnaire within 20 minutes, assisted by the researchers. Parents who were found not using CRS for their newborn were given a digital pamphlet with CRS-related information via mobile devices. Results: A total of 200 parents were approached and 193 of them consented to participate in this study. The majority of the parents (87.6%) were aware of CRS, but only half of them (57.0%) provided a CRS for their current newborn. From 100 CRS users, most of them used a CRS for "child's safety" purposes (84.5%). Among 83 CRS nonuser, nearly half of them (45.8%) perceived that it is adequate to carry their child during traveling without using a CRS. When exploring previous experience in using CRS among all parents (n = 193), more than half of them (63.9%) faced difficulty as their child refused to use the CRS. More than half (54.9%) of all parents were not aware about the possible CRS legislation in Malaysia. However, the majority of them (90.7%) agreed with the implementation of CRS law. Conclusions: Although majority of the parents were aware about CRS, but only half had a CRS for their current newborn. Most of the parents supported CRS legislation in Malaysia, but assistance will be required to help them through challenges related to CRS use.

Competing Interests: None.

A combined system including sonocatalysis and photocatalysis was applied for catalytic degradation of tetracycline (TC) antibiotic using TiO 2 decorated on magnetic activated carbon (MAC@T) in coupling with ultraviolet (UV) and ultrasound (US) irradiations. MAC was fabricated via magnetization of AC using Fe 3 O 4 nanoparticles. FESEM, EDS, TEM, BET, XRD, PL, VSM and UV-visible DRS techniques were used to characterize the catalyst features. The performance of MAC@T/UV/US system was examined under impact of different input variable such as catalyst loading, solution pH, initial TC concentration, US power, scavenging agents, chemical oxidants and co-exiting anions. The degradation rate was enhanced substantially when MAC@T coupled with US and UV irradiations. At optimal conditions, over 93% TC and 50% TOC were removed under 180 min reaction. Whereas, the complete removal of TC was obtained after 60 min treatment, when MAC@T/UV/US coupled with oxidants. Decreasing sequence of the inhibitory effect of anions was chloride > bicarbonate > phosphate > nitrate > sulfate. Both Fe leaching and loss of the decontamination were slight with reused times, indicating MAC@T has a high stability and reusability. According to trapping tests, holes, OH and 1 O 2 were contributed in the degradation process. In conclusion, integration of MAC@T composite and US/UV for enhancing catalytic degradation efficiency can be introduced as a successful and promising technique, owing to excellent catalytic activity, easy recovery, good adsorption capacity and high durability and recycling potential., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Despite years of experience and rigorous research, injectable insulin is the sole trusted treatment method to control the blood glucose level in diabetes type 1 patients, but injection of insulin is painful and poses a lot of stress to the patients, especially children, therefore, development of a non-injectable formulation of insulin is a major breakthrough in the history of medicine and pharmaceutical sciences., Methods: In this study, a novel peptide grafted derivative of chitosan (CPP-g- chitosan) is synthesized and its potential for oral delivery of proteins and peptides is evaluated. Drug-loaded nanoparticles were developed from this derivative using ionic gelation method with application of sodium tripolyphosphate (TPP) as a cross-linking agent. Human insulin was used as the model protein drug and release kinetic was studied at gastrointestinal pH. Finally the developed nanoparticles were filled into very tiny enteric protective capsules and its effects on blood glucose level are evaluated in laboratory animals., Results: Presence of the positively charged cell-penetrating peptide moiety in the structure of chitosan polymer had slight inhibitory effects on the release of insulin from the nanoparticles in simulated gastric fluid (pH 1.2) comparing to native chitosan. The nanoparticles were positively charged in gastrointestinal pH with size ranging from 180 nm to 326 nm. The polypeptide grafted to chitosan is a novel analog of Penetratin, presenting both the hydrophilic and hydrophobic characteristics altering the release behavior of the nanoparticles and significantly increase the absorption of insulin into the rat epithelium comparing to nanoparticles from simple chitosan. In-vivo results in diabetic rat proved that this nanoparticulate system can significantly lower the blood glucose levels in diabetic rats and remain effective for a duration of 9-11 hours., Conclusion: The results indicate that nanoparticles developed from this new peptide conjugated derivative of chitosan are very promising for oral delivery of proteins and peptides., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

The principal purpose of the present study was to prepare and characterize a complex drug delivery system consisting of Nafarelin-poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles (NPs) in combination with sodium alginate/poloxamer 407 in situ gel. Nafarelin-loaded PHBV NPs were prepared via double emulsion solvent evaporation technique. Box-Behnken Response Surface Methodology was utilized to optimize NPs. Mean particle size, polydispersity index (PDI), entrapment efficiency (EE), and drug loading (DL) of the optimized NPs were measured. Incorporation of Nafarelin within NPs was proven by differential scanning calorimetry (DSC). The combination delivery system (CDS) was prepared by adding Nafarelin-loaded PHBV NPs to sodium alginate/poloxamer 407 solution followed by physical mixing. Morphological properties of Nafarelin-loaded PHBV NPs and CDS were evaluated by SEM. Rheological properties were employed to investigate the effects of alginate concentration on sol-gel transition temperature. The release profile of Nafarelin from both PHBV NPs and CDS were individually assessed. The cumulative release percentage from CDS was significantly lower than Nafarelin released from PHBV NPs. Based on the favorable results in this study, the CDS consisting of sodium alginate/poloxamer 407 loaded with PHBV NPs could be a promising candidate for designing a long-lasting formulation of Nafarelin.

Purpose: The aim of this research work was to explore the possibility of providing multifunctional oral insulin delivery system by conjugating several types of dipeptides on chitosan and trimethyl chitosan to be used as drug carriers., Method: Conjugates of Glycyl-glycine and alanyl-alanine of chitosan and trimethyl chitosan (on primary alcohol group of polymer located on carbon 6) were synthesized and nanoparticles containing insulin were prepared for oral delivery. Preparation conditions of nanoparticles were optimized and their performance to enhance the permeability of insulin as well as cytotoxicity of nanoparticles in Caco-2 cell line was evaluated. To evaluate the efficacy of orally administered nanoparticles, nanoparticles with the most permeability enhancing ability were studied in male Wistar rats as animal model by measuring insulin and glucose Serum levels., Result: Structural study of all the conjugates by infrared spectroscopy and nuclear magnetic resonance confirmed the successful formation of the conjugates with the desirable substitution degree. By optimizing preparation conditions, nanoparticles with expected size (157.3-197.7 nm), Zeta potential (24.35-34.37 mV), polydispersity index (0.365-0.512), entrapment efficiency (70.60-86.52%) and loading capacity (30.92-56.81%), proper morphology and desirable release pattern were obtained. Glycyl-glycine and alanyl-alanine conjugate nanoparticles of trimethyl chitosan showed 2.5-3.3 folds more effective insulin permeability in Caco-2 cell line than their chitosan counterparts. In animal model, oral administration of glycyl-glycine and alanyl-alanine conjugate nanoparticles of trimethyl chitosan demonstrated reasonable increase in Serum insulin level with relative bioavailability of 17.19% and 15.46% for glycyl-glycine and alanyl-alanine conjugate nanoparticles, respectively, and reduction in Serum glucose level compared with trimethyl chitosan nanoparticles (p < 0.05)., Conclusion: It seems that glycyl-glycine and alanyl-alanine conjugate nanoparticles of trimethyl chitosan have met the aim of this research work and have been able to orally deliver insulin with more than one mechanism in animal model. Hence, they are promising candidates for further research studies., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This study was focused on the fabrication, statistical optimization and in vitro characterization of poly (hydroxybutyrate-co-hydroxyvalerate) (PHBV) nanoparticles loaded with fingolimod. PHBV-based fingolimod nanoparticles were prepared by single and double evaporation methods; the incorporation efficiency of fingolimod was higher with the single emulsion evaporation method in the nanosize range particles. Fingolimod HCL was neutralized with NaOH in order to slow down the release of the highly soluble fingolimod. The encapsulation efficiency of neutralized fingolimod was much higher (53-73%) due to the insoluble form of the drug used in encapsulation. It was found that the amount of fingolimod, concentration of PHBV and polyvinyl alcohol (PVA) would influence the encapsulation efficiency significantly. The effect of these parameters on the Particle size, PdI, loading capacity and loading efficacy was studied. The optimum conditions were 1.32% PHBV, 0.42% PVA and 5 mg fingolimod. The average size of optimized nanoparticles which measured with the aid of the Box-Behnken experimental design was 250 nm and entrapment efficiency of 73(%). Drug-release from the nanospheres over a four-week period has shown a characteristic triphasic release pattern with an initial burst effect.

In the current study, biodegradable PHBV/PLGA blend nanoparticles (NPs) containing Teriparatide were loaded in hyaluronic acid/jeffamine (HA-JEF ED-600) hydrogel to prepare a combination delivery system (CDS) for prolonged delivery of Teriparatide. The principal purpose of the present study was to formulate an effective and prolonged Teriparatide delivery system in order to reduce the frequency of injection and thus enhance patient's compliance. Morphological properties, swelling behaviour, crosslinking efficiency and rheological characterization of HA-JEF ED-600 hydrogel were evaluated. The CDS was acquired by adding PHBV/PLGA NPs to HA-JEF ED-600 hydrogel simultaneously with crosslinking reaction. The percentage of NPs incorporation within the hydrogel as well as the loading capacity and morphology of Teriparatide loaded CDS were examined. Intrinsic fluorescence and circular dichroism spectroscopy proved that Teriparatide remains stable after processing. The release profile represented 63% Teriparatide release from CDS within 50days with lower burst release compared to NPs and hydrogel. MTT assay was conducted by using NIH3T3 cell line and no sign of reduction in cell viability was observed. Based on Miller and Tainter method, LD 50 of Teriparatide loaded CDS was 131.8mg/kg. In vivo studies demonstrated that Teriparatide loaded CDS could effectively increase serum calcium level after subcutaneous injection in mice. Favourable results in the current study introduced CDS as a promising candidate for controlled delivery of Teriparatide and pave the way for future investigations in the field of designing prolonged delivery systems for other peptides and proteins., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The purpose of this study was the preparation, optimisation and in vitro characterisation of PHBV and PLGA blend nanoparticles (NPs) for prolonged delivery of Teriparatide. Double emulsion solvent evaporation technique was employed for the fabrication of NPs. The nanoformulation was optimised using the Box-Behnken methodology. The morphological properties of NPs were assessed by both SEM and transmission electron microscopy (TEM). Encapsulation of Teriparatide within the NPs and lacking of chemical bonds between drug and copolymers were proved by XRPD, FTIR and DSC. The structural stability of Teriparatide after processing was confirmed by fluorescence spectrometry. The average size of optimised NPs was 250.0 nm with entrapment efficiency (EE) of 89.5% and drug loading (DL) of 5.0%. Teriparatide release from optimised NPs led to 64.4% release over 30 days and it showed a diffusion-based mechanism. Based on the favourable results, PHBV/PLGA blend NPs could be a promising candidate for designing a controlled release formulation of Teriparatide.

Background: Precore stop codon (G1896A) mutation is one of the commonest mutations found in patients with chronic hepatitis B. However, over the years, this mutation was not reported much in Malaysia., Objectives: We therefore investigated the presence of G1896A mutation in Malaysian population and its association with HBeAg status, clinical stage, hepatitis B virus (HBV) genotype and e-seroconversion rate., Patients and Methods: Serum samples from 93 patients confirmed as hepatitis B carriers were collected for molecular assay. The whole genome of HBV was amplified by polymerase chain reaction and directly sequenced. The precore and basal core promoter regions were analyzed for presence of mutations., Results: The most commonly observed mutation in the precore region was C1858T with 64.5% prevalence. The precore mutation of interest (G1896A) was identified in 25.8% of isolates. The basal core promoter mutations detected were A1762T-G1764A (26.9%), C1653T (8.6%), A1752G (10.8%) and C1766T (2.2%). No significant association was observed between G1896A mutation and HBeAg-negativity. Nonetheless, G1896A was highly prevalent among HBV genotype B. Clinical association revealed that subjects with G1896A mutations were mainly detected in asymptomatic chronic hepatitis B (58.3%) and liver cirrhosis (41.7%). One subject was diagnosed with fulminant hepatitis (4.2%) and 8.3% had hepatocellular carcinoma (HCC)., Conclusions: Our data suggested an intermediate prevalence of G1896A mutation among Malaysian hepatitis B carriers. The stop codon mutation has a significant association with genotype B and patients with chronic hepatitis B and liver cirrhosis.

In this paper, we propose an easy-to-implement passive liquid valve (PLV) for the microfluidic compact-disc (CD). This valve can be implemented by introducing venting chambers to control the air flow of the source and destination chambers. The PLV mechanism is based on equalizing the main forces acting on the microfluidic CD (i.e., the centrifugal and capillary forces) to control the burst frequency of the source chamber liquid. For a better understanding of the physics behind the proposed PLV, an analytical model is described. Moreover, three parameters that control the effectiveness of the proposed valve, i.e., the liquid height, liquid density, and venting chamber position with respect to the CD center, are tested experimentally. To demonstrate the ability of the proposed PLV valve, microfluidic liquid switching and liquid metering are performed. In addition, a Bradford assay is performed to measure the protein concentration and evaluated in comparison to the benchtop procedure. The result shows that the proposed valve can be implemented in any microfluidic process that requires simplicity and accuracy. Moreover, the developed valve increases the flexibility of the centrifugal CD platform for passive control of the liquid flow without the need for an external force or trigger.

Background: The S gene region of the hepatitis B virus (HBV) codes for surface antigen (HBs Ag) and is responsible for classification of HBV strains., Objectives: The current study aimed to identify important mutations in the S gene in Hepatitis B virus (HBV) isolated from Malaysian HBV carriers., Materials and Methods: Isolated HBV DNAs were subjected for PCR amplification and sequencing of HBV full genome., Results: A total of 76 HBV full genome and 17 partial genome sequences were obtained from the 93 sequenced sera samples Genotyping of the full genome sequences by HEPSEQ software revealed a distribution of 49.46%, 48.39% and 2.15% of genotypes C, B, and D, respectively; whereas phylogenetic and jumping profile Hidden Markov Model (jpHMM) analysis identified six (7.89%) recombinant B/C strains. The distribution of sub-genotypes were B2 (78.79%) and B3 (21.21%) for genotype B, sub genotype D2 (100%) for genotype D and sub genotype C1 (75.76%), C2 (15.15%), C3 (6.06%) and C5 (3.13%) for genotype C. Mutation analysis in the S gene demonstrated two significant mutations which were W182 stop codon and deletion at open reading frame (ORF) of pre-S1 with the frequency occurrence of 2.2% (2/93) and 5.4% (5/93), respectively. The two patients with W182 stop codon were both male, infected with HBV genotype C and one showed progression of liver disease to hepatocellular carcinoma (HCC)., Conclusions: Association with sex, genotype and clinical symptoms revealed that the pre-S1 ORF deletion occurred in 40% , 40%,and 20% of genotypes B,C, and D respectively, and 80% of the female population, of which all but one were diagnosed with chronic hepatitis B. Additionally, several mutations were found in the BCP region with the following incidence rate; C1653 T (8.6%), A1752 G (10.8%),1762 AGG--TGA 1764 (26.9%), C1766T(2.2%),T1768 A (10.8%), C1858 T (64.5%), G1896 A (25.8%).

Background: Mutations in the polymerase (P) gene of hepatitis B virus are often associated with drug resistance. The pattern of mutations varies geographically, thus giving rise to genotypes diversity., Objectives: This study was carried out to detect mutations in P gene of hepatitis B virus isolated from Malaysian HBV carriers., Materials and Methods: A total of 58 sera samples were analyzed by PCR and sequencing, of which the P gene of isolated HBV was successfully amplified and sequenced from 40 samples., Results: Genotyping of these samples revealed that the predominant genotype was genotype C (22/40, 55.0%), followed by genotype B (17/40, 42.5%), and only 1 sample showed genotype D (2.5%). A number of significant drug resistant mutations were found in five patients including S202I, N236T, M250L, L180M/V, M204I, A181T, T184G, M250V, and V173L. Of these, L180M/V and M204I were most frequently detected (80%) and associated with lamivudine in combination with emtricitabine and telbivudine drug resistance. Association with age, sex, and clinical symptoms revealed that these patients were all male, mid to elderly age and almost all hadcirrhotic liver disease., Conclusions: Detection and surveillance of the significant sites of mutations in HBV is crucial for clinicians to decide on the choice of antiviral treatment and further management of hepatitis B carriers.

Abstract. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is a pathogen recognized to be distinct in both phenotype and genotype from hospital-acquired MRSA. We have identified CA-MRSA cases in Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia, including their antibiotic susceptibility patterns and genotypic characteristics. Cases were identified during January to December 2009 from routine clinical specimens, where culture and antibiotic susceptibility results yielded pauci-resistant MRSA isolates suspected as being CA-MRSA. The patients' clinical data were collected and their specimens were sent for molecular confirmation and analysis. Five cases of CA-MRSA were identified, which had a multi-sensitive pattern on antibiotic susceptibility tests and were resistant to only penicillin and oxacillin. All cases were skin and soft-tissue infections, including diabetic foot with gangrene, infected scalp hematoma, philtrum abscess in a healthcare worker, thrombophlebitis complicated with abscess and infected bedsore. All five cases were confirmed MRSA by detection of mecA. SCCmec typing (ccr and mec complex) revealed SCCmec type IV for all cases except the infected bedsore case. Panton-Valentine leukocidin gene was positive in all isolates. As clinical features among methicillin-sensitive Staphylococcus aureus, CA-MRSA and "nosocomial CA-MRSA" are indistinct, early recognition is necessary in order to initiate appropriate antibiotics and infection control measures. Continual surveillance of pauci-resistant MRSA and molecular analysis are necessary in order to identify emerging strains as well as their epidemiology and transmission, both in the community and in healthcare setting.