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Fatin Hannani Zakarial Ansar,1 Saiful Yazan Latifah,1,2 Wan Hamirul Bahrin Wan Kamal,3 Khei Choong Khong,3 Yen Ng,3 Jia Ning Foong,1 Banulata Gopalsamy,2 Wei Keat Ng,1 Chee Wun How,4 Yong Sze Ong,1 Rasedee Abdullah,2,5 Mohd Yusmaidie Aziz6 1Laboratory of Molecular Medicine, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 3Laboratory of Preclinical Study, Block 24, Medical Technology Division, Malaysian Nuclear Agency, Kajang, Selangor, Malaysia; 4Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 5Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 6Advanced Medical and Dental Institute, University of Science Malaysia, Kepala Batas, Pulau Pinang, MalaysiaCorrespondence: Saiful Yazan Latifah; Wan Hamirul Bahrin Wan Kamal Tel +60 3 89472308Fax +60 3 89436178Email latifahsy@upm.edu.my; mirul@nuclearmalaysia.gov.myBackground: Thymoquinone (TQ), an active compound isolated from Nigella sativa, has been proven to exhibit various biological properties such as antioxidant. Although oral delivery of TQ is valuable, it is limited by poor oral bioavailability and low solubility. Recently, TQ-loaded nanostructured lipid carrier (TQ-NLC) was formulated with the aim of overcoming the limitations. TQ-NLC was successfully synthesized by the high-pressure homogenization method with remarkable physiochemical properties whereby the particle size is less than 100 nm, improved encapsulation efficiency and is stable up to 24 months of storage. Nevertheless, the pharmacokinetics and biodistribution of TQ-NLC have not been studied. This study determined the bioavailability of oral and intravenous administration of thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) in rats and its distribution to organs.Materials and Methods: TQ-NLC was radiolabeled with technetium-99m before the administration to the rats. The biodistribution and pharmacokinetics parameters were then evaluated at various time points. The rats were imaged at time intervals and the percentage of the injected dose/gram (%ID/g) in blood and each organ was analyzed.Results: Oral administration of TQ-NLC exhibited greater relative bioavailability compared to intravenous administration. It is postulated that the movement of TQ-NLC through the intestinal lymphatic system bypasses the first metabolism and therefore enhances the relative bioavailability. However, oral administration has a slower absorption rate compared to intravenous administration where the AUC0-∞ was 4.539 times lower than the latter.Conclusion: TQ-NLC had better absorption when administered intravenously compared to oral administration. However, oral administration showed greater bioavailability compared to the intravenous route. This study provides the pharmacokinetics and biodistribution profile of TQ-NLC in vivo which is useful to assist researchers in clinical use.Keywords: thymoquinone, nanostructured lipid carrier, bioavailability, biodistribution, pharmacokinetics

Yong Sze Ong,1 Latifah Saiful Yazan,1,2 Wei Keat Ng,1 Mustapha M Noordin,3 Sarah Sapuan,1 Jhi Biau Foo,1 Yin Sim Tor1 1Laboratory of Molecular Biomedicine, Institute of Bioscience, 2Department of Biomedical Science, Faculty of Medicine and Health Sciences, 3Department of Pathology and Veterinary Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia Background: Thymoquinone (TQ), the predominant active lipophilic component in Nigella sativa seed oil, has a variety of pharmacological properties such as anticancer activities. However, translation of TQ to clinical phase is still not possible due to its hydrophobic properties. This problem can be solved by encapsulating it in nanoformulations to enhance its pharmacological properties. In our previous study, TQ has been successfully encapsulated in a nanostructured lipid carrier (hereinafter referred to as TQNLC) with excellent physiochemical properties such as high encapsulation efficiency, high drug-loading capacity, particle diameter less than 100 nm, and stability up to 2 years. In vitro studies also proved that TQNLC exhibited antiproliferative activity toward breast and cervical cancer cell lines. However, no toxicity profile related to this formulation has been reported. In this study, we determine and compare the in vivo toxicity of both TQNLC and TQ. Materials and methods: The in vivo toxicity (acute and subacute toxicity) study was carried out by oral administration of TQNLC and TQ to BALB/c mice. Animal survival, body weight, organ weight-to-body weight ratio, hematological profile, biochemistry profile, and histopathological changes were analyzed. Results: In acute toxicity, TQ that is loaded in nanostructured lipid carrier (NLC) was found to be less toxic than pure TQ. It can be concluded that encapsulation of TQ in lipid carrier minimizes the toxicity of the compound. In the subacute toxicity study, oral administration of 100 mg/kg of TQNLC and TQ did not cause mortality to either male or female but resulted in toxicity to the liver. It is postulated that long-term consumption of TQNLC and TQ may cause toxicity to the liver but not to the extent of altering the functions of the organ. For both treatments, the no observed adverse effect level (NOAEL) was found to be 10 mg/kg/d for mice in both sexes. Conclusion: For long-term oral consumption, TQ and TQNLC at a dose of 10 mg/kg is safe in mice and does not exert any toxic effect. The results provide safety information of TQNLC, which would further help researchers in clinical use. Keywords: thymoquinone, nanostructured lipid carrier, toxicity

States of severely impaired consciousness (SIC) are characterized by cognitive and motor limitations.This case report describes a 45-year-old female with impaired consciousness who began to `walk'. Sheinitially presented to the hospital unresponsive and was subsequently diagnosed with metabolic encephalopathydue to severe hypoglycaemia. Traditional indices of consciousness indicated a low level ofresponsiveness; however, during physical therapy, she displayed reciprocal walking movements whenlifted to a standing position by two therapists. Despite her ability to walk increased distances during andafter neurorehabilitation, she was unable to consistently demonstrate responses indicative of higherlevels of consciousness. This case illustrates the challenge of rating patients with limited behaviouralrepertoire using established measures of impaired consciousness. [ABSTRACT FROM AUTHOR]

Background: There is sustained interest in understanding the perspectives of liver transplant recipients and living donors, with several qualitative studies shedding light on this emotionally charged subject. However, these studies have relied primarily on traditional semi-structured interviews, which, while valuable, come with inherent limitations. Consequently, there remains a gap in our comprehension of the broader public discourse surrounding living liver donation. This study aims to bridge this gap by delving into public conversations related to living liver donation through a qualitative analysis of Twitter (now X) posts, offering a fresh perspective on this critical issue., Methods: To compile a comprehensive dataset, we extracted original tweets containing the hashtags "#donateliver" OR "#liverdonor", all posted in English from January 1, 2012, to December 31, 2022. We then selected tweets from individual users whose Twitter (X) accounts featured authentic human names, ensuring the credibility of our data. Employing Braun and Clarke's reflexive thematic analysis approach, the study investigators read and analysed the included tweets, identifying two main themes and six subthemes. The Health Policy Triangle framework was applied to understand the roles of different stakeholders involved in the discourse and suggest areas for policy improvement., Results: A total of 361 unique tweets from individual users were analysed. The major theme that emerged was the persistent shortage of liver donors, underscoring the desperation faced by individuals in need of life-saving liver transplants and the urgency of addressing the organ shortage problem. The second theme delved into the experiences of liver donors post-surgery, shedding light on a variety of aspects related to the transplantation process, including the visibility of surgical scars, and the significance of returning to physical activity and exercise post-surgery., Conclusion: The multifaceted experiences of individuals involved in the transplantation process, both recipients and donors, should be further studied in our efforts to improve the critical shortage of liver donors., (© 2024. The Author(s).)

Background: Hepatectomy is an established treatment for colorectal liver metastasis (CLM) or neuroendocrine liver metastasis. However, its role in non-colorectal non-neuroendocrine liver metastasis (NCNNLM) is controversial. This study aims to compare long-term survival outcomes after hepatectomy between NCNNLM and CLM in a population-based cohort., Methods: From 2009 to 2018, curative hepatectomy were performed in 964 patients with NCNNLM (n ​= ​133) or CLM (n ​= ​831). Propensity score (PS) matching was performed. Short-term and long-term outcomes were compared between PS-matched groups. Univariate and multivariate analyses were performed to identify prognostic factors affecting survival., Results: There were 133 patients in the NCNNLM group and 266 patients in the CLM group. The mortality (1.5 ​% vs 1.5 ​%) and morbidity (19.5 ​% vs 20.3 ​%) rates were comparable between the two groups. There was no statistically significant difference in 5-year overall (48.9 ​% vs 39.8 ​%) and recurrence-free (25.1 ​% vs 23.4 ​%) survival rates between NCNNLM and CLM groups. A high pre-operative serum bilirubin level, severe postoperative complications and multiple tumors were independent prognostic factors for poor survival., Conclusion: Hepatectomy for selected patients with NCNNLM can achieve similar long-term oncological outcomes as those with CLM. High serum bilirubin, severe postoperative complication and multiple tumors are poor prognostic factors for survival., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: None

Introduction: In managing hypertension, monotherapy and sometimes a combination of more than one agent are used to achieve blood pressure (BP) control. The objective of this prospective, observational, multi-centre study was to assess the level of BP control in patients receiving one or more anti-hypertensive drugs in private medical centres in Malaysia according to the treatment regimens (monotherapy, free drug combinations and single pill combinations)., Materials and Methods: Data were collected through medical records and interview sessions with patients on current pharmacotherapy for hypertension management at baseline and 2-3 months later. Results are expressed as mean ± SD for continuous data and as frequencies and percentages for categorical data., Results: Among 182 recruited patients, 89 (49%) achieved BP control by the end of the study. Majority (62/89) patients were on single-pill (monotherapy or SPC) antihypertensives. Majority (63/89) required more than two antihypertensives to achieve BP control., Conclusion: Both SPC and free drug combination antihypertensives reduced BPs, but physicians preferred SPC to improve BP control and increase treatment compliance.

Cancer is one of the leading causes of mortality worldwide; nearly 10 million people died from it in 2020. The high mortality rate results from the lack of effective screening approaches where early detection cannot be achieved, reducing the chance of early intervention to prevent cancer development. Non-invasive and deep-tissue imaging is useful in cancer diagnosis, contributing to a visual presentation of anatomy and physiology in a rapid and safe manner. Its sensitivity and specificity can be enhanced with the application of targeting ligands with the conjugation of imaging probes. Phage display is a powerful technology to identify antibody- or peptide-based ligands with effective binding specificity against their target receptor. Tumour-targeting peptides exhibit promising results in molecular imaging, but the application is limited to animals only. Modern nanotechnology facilitates the combination of peptides with various nanoparticles due to their superior characteristics, rendering novel strategies in designing more potent imaging probes for cancer diagnosis and targeting therapy. In the end, a myriad of peptide candidates that aimed for different cancers diagnosis and imaging in various forms of research were reviewed., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Irritable bowel syndrome is a prototypical disorder of the brain-gut-microbiome axis, although the underlying pathogenesis and mechanisms remain incompletely understood. With the recent advances in 'omics' technologies, studies have attempted to uncover IBS-specific variations in the host-microbiome profile and function. However, no biomarker has been identified to date. Given the high inter-individual and day-to-day variability of the gut microbiota, and a lack of agreement across the large number of microbiome studies, this review focused on omics studies that had sampling at more than one time point. A systematic literature search was performed using various combinations of the search terms "Irritable Bowel Syndrome" and "Omics" in the Medline, EMBASE, and Cochrane Library up to 1 December 2022. A total of 16 original studies were reviewed. These multi-omics studies have implicated Bacteroides , Faecalibacterium prausnitzii , Ruminococcus spp., and Bifidobacteria in IBS and treatment response, found altered metabolite profiles in serum, faecal, or urinary samples taken from IBS patients compared to the healthy controls, and revealed enrichment in the immune and inflammation-related pathways. They also demonstrated the possible therapeutic mechanisms of diet interventions, for example, synbiotics and low fermentable oligosaccharides, disaccharides, monosaccharides, and polyol (FODMAP) diets on microbial metabolites. However, there was significant heterogeneity among the studies and no uniform characteristics of IBS-related gut microbiota. There is a need to further study these putative mechanisms and also ensure that they can be translated to therapeutic benefits for patients with IBS.

There is accumulating evidence on the beneficial effects of probiotic supplementation for patients with depressive disorders. However, prior reviews on the topic have largely focused on clinical effectiveness with limited emphasis on the underlying mechanisms of action and effects of probiotics on gut microbiota. In accordance with PRISMA guidelines, a systematic literature search of Medline, EMBASE and the Cochrane Library using combinations of the key words, ("depress*" OR "MDD" OR "suicide"), ("probiotic" OR "Lactobacillus" OR "Bifidobacterium") AND ("gut" OR "gut micr*" OR "microbiota"), as well as grey literature was performed. We found seven clinical trials involving patients with major depressive disorder (MDD). The small number of studies and heterogeneous sources of data precluded meta-analysis. Most trials (other than one open-label trial) had a low-to-moderate risk of bias, which was largely due to a lack of control for the effects of diet on gut microbiota. Probiotic supplementation yielded only modest effects on depressive symptoms and there were no consistent effects on gut microbiota diversity, and in most instances, no significant alterations in gut microbiota composition were observed after four to eight weeks of probiotic intervention. There is also a lack of systematic reporting on adverse events and no good longer-term data. Patients with MDD may require a longer time to show clinical improvement and the microbial host environment may also need longer than eight weeks to produce significant microbiota alterations. To advance this field, further larger-scale and longer-term studies are required.

Background: Progressive supranuclear palsy (PSP) is a rare, disabling, neurodegenerative disease, with few studies done in Asian populations., Methods: We prospectively characterized the clinical features and disease burden in a consecutively-recruited multi-ethnic Asian PSP cohort. Patients were extensively phenotyped using the Movement Disorder Society (MDS-PSP) clinical diagnostic criteria and the PSP-Clinical Deficits Scale (PSP-CDS). Caregiver burden was measured using the modified Zarit Burden Interview (ZBI). Investigations (neuroimaging and genetic tests) were reviewed., Results: There were 104 patients (64.4% male; 67.3% Chinese, 21.2% Indians, 9.6% Malays), consisting of 48.1% Richardson syndrome (PSP-RS), 37.5% parkinsonian phenotype (PSP-P), and 10.6% progressive gait freezing phenotype (PSP-PGF). Mean age at motor onset was 66.3 ± 7.7 years, with no significant differences between the PSP phenotypes. Interestingly, REM-sleep behaviour disorder (RBD) symptoms and visual hallucinations (considered rare in PSP) were reported in 23.5% and 22.8% of patients, respectively, and a family history of possible neurodegenerative or movement disorder in 20.4%. PSP-CDS scores were highest (worst) in PSP-RS; and correlated moderately with disease duration (r s  = 0.45, P < 0.001) and weakly with caregiver burden (r s  = 0.22, P = 0.029) in the overall cohort. Three of 48 (6.3%) patients who had whole-exome sequencing harboured pathogenic/likely pathogenic GBA variants., Conclusions: Significant heterogeneity in clinical features and disease burden, and high rates of RBD symptoms, visual hallucinations, and familial involvement were observed in this relatively large cohort. Our findings highlight important considerations when assessing Asian patients, and provide further support for the notion of overlapping neurobiology between PSP and Lewy body disorders., Competing Interests: Declaration of competing interest The authors have no financial conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Due to the fast dynamics and re-equilibration of supramolecular self-assembly, bottom-up molecular strategies to fabricate well-defined and controllable multiblock structures are rare. Herein, we propose a new concept for fabrication of fluorescent multiblock microcolumns containing 1 to 7 blocks via hierarchical supramolecular self-assembly based on cucurbit[8]uril (CB[8]), NaBr and an AIEgen guest. Through the complexation between CB[8] and different numbers of AIEgen guests (2, 1, 0), the competitive displacement caused by the binding of the sodium cation to the CB[8] portal, and the reversible assembly of positively charged guests in salt solutions, one-pot hierarchical supramolecular self-assembly is realized. The molecular structure of each block is analyzed by single-crystal X-ray diffraction. The AIEgen enables the self-assembly of multiblocks to be visualized, understood, and regulated., (© 2022 Wiley-VCH GmbH.)

Competing Interests: The authors declare that they have no conflict of interest.

Purpose: Trauma remains a major cause of morbidity and disability worldwide; however, reliable data on the health status of an urban Asian population after injury are scarce. The aim was to evaluate 1-year post-trauma return to work (RTW) status in Hong Kong., Methods: This was a prospective, multi-center cohort study involving four regional trauma centers from 2017 to 2019 in Hong Kong. Participants included adult patients entered into the trauma registry who were working or seeking employment at the time of injury. The primary outcome was the RTW status up to 1 year. The Extended Glasgow Outcome Scale, 12-item Short Form (SF-12) survey and EQ5D were also obtained during 1-, 3-, 6-, 9-, and 12-month follow-ups. Multivariable Cox proportional hazards regression analysis was used for analysis., Results: Six hundred and seven of the 1115 (54%) recruited patients had RTW during the first year after injury. Lower physical requirements (p = 0.003, HR 1.51) in pre-injury job nature, higher educational levels (p < 0.001, HR 1.95), non-work-related injuries (p < 0.001, HR 1.85), shorter hospital length of stay (p = 0.007, HR 0.98), no requirement for surgery (p = 0.006, HR 1.34), and patients who could be discharged home (p = 0.006, HR 1.43) were associated with RTW within 12 months post-injury. In addition, 1-month outcomes including extended Glasgow Outcome Scale ≥ 6 (p = 0.001, HR 7.34), higher mean SF-12 physical component summary (p = 0.002, HR 1.02) and mental component summary (p < 0.001, HR 1.03), and higher EQ5D health index (p = 0.018, HR 2.14) were strongly associated with RTW., Conclusions: We have identified factors associated with failure to RTW during the first year following in Hong Kong including socioeconomic factors, injury factors and treatment-related factors and 1-month outcomes. Future studies should focus on the interventions that can impact on RTW outcomes., Trial Registration: ClinicalTrials.gov Identifier NCT03219424., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Polyhydroxyalkanoates (PHAs) are bio-based polymers produced in bacterial cells to replace some petrochemical plastics. It has always been a challenge to commercialise PHA due in part to the costly recovery processes of the PHA granules from the bacterial cells. The biological approach of using mealworms, Tenebrio molitor, for the recovery of PHA from the bacterial cells is a newly established method that is at the scale-up stage. On the other hand, the aquaculture feed industry needs a low-cost mealworm meal as a protein source. We aimed at studying the nutritional value of the mealworms (which are by-products) used for the poly(3-hydroxybutyrate) (PHB) (the most common type of PHA) recovery from the bacterial and examining the effect of the mealworms on the growth performance, and feed utilization efficiency of red hybrid tilapia (Oreochromis sp.). The cells were fed to the mealworms to digest the proteinaceous cellular materials and excrete the PHB granules in the form of fecal pellets. The resulting mealworms were used as fishmeal replacement to formulate five isonitrogenous (35% crude protein) and isolipidic (8% lipid) diets at mealworm meal (MwM) inclusion levels of 0% (MwM0/control diet), 25% (MwM25), 50% (MwM50), 75% (MwM75) or 100% (MwM100). The results showed good nutritive value mealworms [high protein (75%), low-lipid (10%)] and up to 75% MwM inclusion diet was good in supplying satisfactory nutrients and energy to the red hybrid tilapia. This approach is beneficial in a way that minimal cost was involved in recovering kilograms of PHB and the proteins, lipids, and minerals from the bacterial cells do not end up as wastes but in turn, are used as nutrition by the larvae., (© 2022. The Author(s).)

Background and Aim: Irritable bowel syndrome (IBS) is a prevalent and complex gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits. Observational studies have suggested a relationship between serum vitamin D levels and IBS symptoms. This systematic review and meta-analysis aimed to investigate the clinical effects of vitamin D supplementation on IBS symptom severity and quality of life (QoL) measures., Methods: Medline, Embase, Scopus, Web of Science, and The Cochrane Library databases were systematically searched. Data abstraction and quality assessment were conducted by four authors independently, and discrepancies were resolved through consensus from the senior author. Continuous data were pooled with standardized mean difference (SMD) using the DerSimonian and Laird's random-effects model. Sensitivity analysis by risk of bias and potentially "predatory" publication were performed as well., Results: A total of 685 patients across eight studies were included in the meta-analysis. Vitamin D supplementation significantly improved IBS symptom severity scale scores, with a SMD of -0.77 (95% confidence interval [CI] -1.47 to -0.07, P = 0.04, I 2  = 91%). Improvements in IBS-QoL scores were also observed, albeit not statistically significant (SMD 0.54; 95% CI -0.34 to 1.41, P = 0.15, I 2  = 87%). However, small sample sizes, a relatively young study population, limited ethnicities, and varied vitamin D dosing strategies across the studies were notable limitations., Conclusions: Vitamin D supplementation could be part of our clinical armamentarium when managing IBS patients due to the potential efficacy and good safety profile. Further randomized, controlled trials are required to confirm the therapeutic effects., (© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Dermal delivery of bioactive molecules remains an attractive route of administration in osteoarthritis (OA) due to the local accumulation of drugs while avoiding their systemic side effects. In this study we propose a proniosome gel comprising non-ionic surfactants that self-assemble into de-hydrated vesicles for the delivery of the natural anti-inflammatory compound berberine. By modulating the hydrating ability of the proniosome gel, berberine can be efficiently released with minimal mechanical force. A combination of sorbitan oleate (S80) and polyethlene glycol sorbitan monolaurate (T20) in a sorbitan stearate (S60)-based proniosome enables a readily hydrated gel to deliver berberine into the skin, as confirmed by ex vivo skin permeation studies. Concurrently, an in vitro model of OA using primary mouse chondrocytes demonstrated that the release of berberine at a concentration as low as 1 μg mL -1 is sufficient to restore the production of sulphated glycosaminoglycans (sGAG) to levels comparable to healthy chondrocytes while avoiding the cytotoxic concentrations (IC 50 = 33 μg mL -1 ) on skin keratinocytes. In a mouse model of OA, the optimized formulation is able to attenuate inflammation and pain and minimize cartilage degeneration. Taken together, these data demonstrate the feasibility of adopting proniosome gels as a suitable platform to deliver active molecules for the management of osteoarthritis.

Introduction: In Singapore, non-anaesthesiologists generally administer sedation during gastrointestinal endoscopy. The drugs used for sedation in hospital endoscopy centres now include propofol in addition to benzodiazepines and opiates. The requirements for peri-procedural monitoring and discharge protocols have also evolved. There is a need to develop an evidence-based clinical guideline on the safe and effective use of sedation by non-anaesthesiologists during gastrointestinal endoscopy in the hospital setting., Methods: The Academy of Medicine, Singapore appointed an expert workgroup comprising 18 gastroenterologists, general surgeons and anaesthesiologists to develop guidelines on the use of sedation during gastrointestinal endoscopy. The workgroup formulated clinical questions related to different aspects of endoscopic sedation, conducted a relevant literature search, adopted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology and developed recommendations by consensus using a modified Delphi process., Results: The workgroup made 16 recommendations encompassing 7 areas: (1) purpose of sedation, benefits and disadvantages of sedation during gastrointestinal endoscopy; (2) pre-procedural assessment, preparation and consent taking for sedation; (3) Efficacy and safety of drugs used in sedation; (4) the role of anaesthesiologist administered sedation during gastrointestinal endoscopy; (5) performance of sedation; (6) post-sedation care and discharge after sedation; and (7) training in sedation for gastrointestinal endoscopy for non-anaesthesiologists., Conclusion: These recommendations serve to guide clinical practice during sedation for gastrointestinal endoscopy by non-anaesthesiologists in the hospital setting.

The deployment of photonic integrated circuits (PICs) necessitates an integration platform that is scalable, high-throughput, cost-effective, and power-efficient. Here we present a monolithic InP on SOI platform to synergize the advantages of two mainstream photonic integration platforms: Si photonics and InP photonics. This monolithic InP/SOI platform is realized through the selective growth of both InP sub-micron wires and large dimension InP membranes on industry-standard (001)-oriented silicon-on-insulator (SOI) wafers. The epitaxial InP is in-plane, dislocation-free, site-controlled, intimately positioned with the Si device layer, and placed right on top of the buried oxide layer to form "InP-on-insulator". These attributes allow for the realization of various photonic functionalities using the epitaxial InP, with efficient light interfacing between the III-V devices and the Si-based waveguides. We exemplify the potential of this InP/SOI platform for integrated photonics through the demonstration of lasers with different cavity designs including subwavelength wires, square cavities, and micro-disks. Our results here mark a critical step forward towards fully-integrated Si-based PICs., (© 2021. The Author(s).)

Considering that the periodic photonic nanostructures are commonly realized by expensive nanofabrication processes and the tunability of structure parameters is limited and complicated, we demonstrate a solution-processed upside-down molding method to fabricate photonic resonators on perovskites with a pattern geometry controllable to a certain extent. This upside-down approach not only reveals the effect of capillary force during the imprinting but also can control the waveguide layer thickness due to the inversion of the perovskite membranes.

The present study investigated the influence of berberine (BBR) supplementation in normal and high-lipid (HL) diets on lipid metabolism and accumulation in black sea bream (Acanthopagrus schlegelii). BBR was supplemented at 50 mg/kg to control (Con, 11·1 % crude lipid) and high-lipid (HL, 20·2 % crude lipid) diets and named as ConB and HLB, respectively. After the 8-week feeding trial, fish body length and specific growth rate were significantly reduced by HL diets (P < 0·05). Muscle and whole-body crude lipid contents were significantly influenced by both BBR supplementation and dietary lipid level. Fish fed the HLB diet had significantly lower serum TAG, LDL-cholesterol contents and alanine aminotransferase activity compared with the HL group. The HL group presented vast lipid accumulation in the liver, and hypertrophied hepatocytes along with large lipid droplets, and translocation of nuclear to the cell periphery. These abnormalities in black sea bream were alleviated in the HLB group. BBR supplementation in the HL diet significantly down-regulated the hepatic expression levels of acetyl-CoA carboxylase α, sterol regulatory element-binding protein-1, 6-phosphogluconate dehydrogenase, glucose 6-phosphate dehydrogenase and pparγ, whereas the lipoprotein lipase, hormone-sensitive lipase and carnitine palmitoyltransferase 1a expression levels were significantly up-regulated. However, the expression levels of these genes showed opposite trends in muscle (except for pparγ). In conclusion, dietary BBR supplementation in the HL diet reduced hepatic lipid accumulation by down-regulating lipogenesis gene expression and up-regulating lipolysis gene expression, and it increased muscle lipid contents with opposite trends of the mechanism observed in the liver.

Artemether, an artemisinin derivative, is used in the management of life-threatening severe malaria. This study aimed to develop an intravenous dosage form of artemether using nanotechnology. Artemether-loaded zein nanoparticles were prepared by modified antisolvent precipitation using sodium caseinate as a stabilizer. Subsequently, the physicochemical properties of the nanoparticles were characterized; the in vitro hemolytic property was examined with red blood cells, while the pharmacokinetic profile was evaluated in Sprague-Dawley rats after intravenous administration. The artemether-loaded zein nanoparticles were found to display good encapsulation efficiency, excellent physical stability and offer an in vitro extended-release property. Interestingly, encapsulation of artemether into zein nanoparticles substantially suppressed hemolysis, a common clinical phenomenon occurring after artemisinin-based antimalarial therapy. Upon intravenous administration, artemether-loaded zein nanoparticles extended the mean residence time of artemether by ~80% in comparison to the free artemether formulation (82.9 ± 15.2 versus 45.6 ± 16.4 min, p < 0.01), suggesting that the nanoparticles may prolong the therapeutic duration and reduce the dosing frequency in a clinical setting. In conclusion, intravenous delivery of artemether by artemether-loaded zein nanoparticles appears to be a promising therapeutic option for severe malaria.

This paper reports on the long-term effectiveness of a non-formal co-curricular educational program based on a campus ecogarden at a Hong Kong university in developing pro-sustainability awareness, attitudes and behavior among undergraduate students. This service-based, nature-based experiential learning program, termed the Ecogarden Farmer and Biodiversity Surveyor, has been running at the university since 2015. The program is divided into two consecutive phases: a training phase comprising various learning activities and a successive internship phase consisting of the all-round practical tasks involved in managing the garden. A retrospective evaluation of the program using phenomenographic approach and content analysis was adopted to reveal the diversity of students' learning experience, as the indicators of the success of the program. Of 112 participants from 4 cohorts, 32 completed online questionnaires, and semi-structured interviews were successfully conducted with twelve participants, three from each of the four cohorts. The results indicated that the program's outcomes could be categorized into five themes. Most outcomes fit into the theme 'an increase in knowledge and skill level,' followed by 'rise in environmental awareness,''facilitation of personal growth,' and 'enhancement of career development.' Many structural experiences revealed may suggest the success of the program. The longer the participants had participated in the program, the more in-depth and diversified reflection of the senior participants relating to personal development were mentioned. This study provides critical insights into the validity of retrospective program evaluation for assessing the long-term impact of EfS programs by introducing a cross-sectional study of different cohorts as a serial time-point sampling strategy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cheang, Ng, Wong, Li and Tsoi.)

Composite hemangioendothelioma is a rare vascular tumor morphologically comprising several distinct vascular components and exhibits a borderline malignant potential. We described the case of a 53-year-old female who presented with an infiltrative mass in the paravertebral soft tissue. The tumor showed discrete nests of synaptophysin-expressing epithelioid cells accompanied by rich vasculature, features highly reminiscent of sympathetic paraganglioma. Further analysis revealed areas resembling spindle cell hemangioma, retiform hemangioendothelioma, cavernous hemangioma/lymphangioma, and epithelioid hemangioendothelioma without the myxohyaline matrix in the tumor, and a final diagnosis of composite hemangioendothelioma with synaptophysin expression was made. Critical appraisal of this recently described entity and its possible pathogenic relationship with retiform hemangioendothelioma were discussed.

This study aimed to explore changes in psychological responses (perceived stress, traumatic stress, stigma, coping) over time in residents, as well as their predictors. The level of perceived stress, traumatic stress, stigma, and coping responses were assessed using the Perceived Stress Scale, Impact of Event-Revised, Healthcare Workers Stigma Scale, and Brief Coping Orientation to Problems Experienced (COPE) Inventory, respectively. We collected responses from 274 residents at baseline and 221 residents at 3 months follow-up (timepoint 2) from the National Healthcare Group (NHG) residency programs in Singapore. All residents reported lower perceived stress and lower perceived stigma compared to baseline. Use of avoidance coping was associated with all three psychological responses (perceived stress, traumatic stress, and stigma) across the two timepoints. Compared to baseline, specific factors associated with perceived stress and traumatic stress at timepoint 2 were living alone, less problem solving, and seeking social support. Residency programs should encourage active coping strategies (e.g., seeking social support, positive thinking, problem solving) among residents, and proactively identify residents who may be at higher risk of psychological sequelae due to circumstances that contribute to isolation.

Background: Behavioural theories are crucial to the development and success of effective hand hygiene interventions. Research demonstrates that hand hygiene behaviours can also be influenced by religious and cultural beliefs. In this paper we detail the processes undertaken to develop a valid and reliable questionnaire to examine healthcare workers' beliefs and behaviours related to the use of alcoholbased hand rub (ABHR), with particular emphasis on associated religious and cultural factors., Methods: Using the Theory of Planned Behaviour, an existing questionnaire was modified and pilot-tested on 35 staff in the Quality Department. Cronbach's alpha values and mean inter-item correlations of the scale items were the main outcome measures. A Pearson correlation was conducted to assess for social desirability response bias., Results: The questionnaire demonstrated high content and face validity and satisfactory internal consistency in most scales, except for the religious beliefs, cultural beliefs and perceived behavioural control scales, where the inter-item correlations were 0.10, 0.13, and 0.14, respectively. There was a significant correlation between scores on the social desirability scale and the attitude scale. Partial correlation should be used to control the effect of social desirability responding when analysing data from the attitudes scale., Conclusions: A validation process allowed the introduction and subsequent modification of religious and cultural belief scales to an existing questionnaire examining behavioural and attitudinal influences on hand hygiene using ABHR. Such processes should be considered for questionnaire development and modification when considering religious and cultural factors as drivers of behaviour., (Copyright © 2019 Australasian College for Infection Prevention and Control. Published by Elsevier B.V. All rights reserved.)

Background: Hand hygiene with ABHR is more effective, time-saving and skin-friendly than traditional handwashing. However, alcohol-based hand rub (ABHR) use can be an obstacle for specific religions. The study aimed to test the effect of a modified hand hygiene program featuring religion-relevant, culturally-specific interventions on compliance and beliefs about ABHR use., Methods: A cohort study design was employed between August and November 2017 at a large tertiary hospital in the United Arab Emirates. Hand hygiene audit data and a cross-sectional survey were used to measure the impact of the modified hand hygiene program on compliance with, and beliefs about, ABHR use., Results: The intervention group had higher mean compliance with overt (p = 0.002) and covert (p = 0.04) ABHR use post-intervention, and higher mean compliance with overt ABHR use (p = 0.002) than the control group. The intervention group had more positive religious beliefs (p = 0.01) about ABHR use than the control group., Conclusion: Implementing a hand hygiene program featuring tailored religion-relevant interventions in a culturally appropriate way had a positive effect on compliance with, and beliefs about, ABHR use., (Copyright © 2019 Australasian College for Infection Prevention and Control. Published by Elsevier B.V. All rights reserved.)

Competing Interests: The authors have no conflicts of interest to disclose.

A compact, efficient, and monolithically grown III-V laser source provides an attractive alternative to bonding off-chip lasers for Si photonics research. Although recent demonstrations of microlasers on (001) Si wafers using thick metamorphic buffers are encouraging, scaling down the laser footprint to nanoscale and operating the nanolasers at telecom wavelengths remain significant challenges. Here, we report a monolithically integrated in-plane InP/InGaAs nanolaser array on (001) silicon-on-insulator (SOI) platforms with emission wavelengths covering the entire C band (1.55 μm). Multiple InGaAs quantum wells are embedded in high-quality InP nanoridges by selective-area growth on patterned (001) SOI. Combined with air-cladded InP/Si optical cavities, room-temperature operation at multiple telecom bands is obtained by defining different cavity lengths with lithography. The demonstration of telecom-wavelength monolithic nanolasers on (001) SOI platforms presents an important step towards fully integrated Si photonics circuits.