Digital pathology for reporting histopathology samples, including cancer screening samples - definitive evidence from a multisite study.

AIMS: To conduct a definitive multicentre comparison of digital pathology (DP) with light microscopy (LM) for reporting histopathology slides including breast and bowel cancer screening samples. METHODS: A total of 2024 cases (608 breast, 607 GI, 609 skin, 200 renal) were studied, including 207 breast and 250 bowel cancer screening samples. Cases were examined by four pathologists (16 study pathologists across the four speciality groups), using both LM and DP, with the order randomly assigned and 6 weeks between viewings. Reports were compared for clinical management concordance (CMC), meaning identical diagnoses plus differences which do not affect patient management. Percentage CMCs were computed using logistic regression models with crossed random-effects terms for case and pathologist. The obtained percentage CMCs were referenced to 98.3% calculated from previous studies. RESULTS: For all cases LM versus DP comparisons showed the CMC rates were 99.95% [95% confidence interval (CI) = 99.90-99.97] and 98.96 (95% CI = 98.42-99.32) for cancer screening samples. In speciality groups CMC for LM versus DP showed: breast 99.40% (99.06-99.62) overall and 96.27% (94.63-97.43) for cancer screening samples; [gastrointestinal (GI) = 99.96% (99.89-99.99)] overall and 99.93% (99.68-99.98) for bowel cancer screening samples; skin 99.99% (99.92-100.0); renal 99.99% (99.57-100.0). Analysis of clinically significant differences revealed discrepancies in areas where interobserver variability is known to be high, in reads performed with both modalities and without apparent trends to either. CONCLUSIONS: Comparing LM and DP CMC, overall rates exceed the reference 98.3%, providing compelling evidence that pathologists provide equivalent results for both routine and cancer screening samples irrespective of the modality used.

Automated scoring methods for quantitative interpretation of Tumour infiltrating lymphocytes (TILs) in breast cancer: a systematic review.

Tumour microenvironment (TME) of breast cancer mainly comprises malignant, stromal, immune, and tumour infiltrating lymphocyte (TILs). Assessment of TILs is crucial for determining the disease's prognosis. Manual TIL assessments are hampered by multiple limitations, including low precision, poor inter-observer reproducibility, and time consumption. In response to these challenges, automated scoring emerges as a promising approach. The aim of this systematic review is to assess the evidence on the approaches and performance of automated scoring methods for TILs assessment in breast cancer. This review presents a comprehensive compilation of studies related to automated scoring of TILs, sourced from four databases (Web of Science, Scopus, Science Direct, and PubMed), employing three primary keywords (artificial intelligence, breast cancer, and tumor-infiltrating lymphocytes). The PICOS framework was employed for study eligibility, and reporting adhered to the PRISMA guidelines. The initial search yielded a total of 1910 articles. Following screening and examination, 27 studies met the inclusion criteria and data were extracted for the review. The findings indicate a concentration of studies on automated TILs assessment in developed countries, specifically the United States and the United Kingdom. From the analysis, a combination of sematic segmentation and object detection (n = 10, 37%) and convolutional neural network (CNN) (n = 11, 41%), become the most frequent automated task and ML approaches applied for model development respectively. All models developed their own ground truth datasets for training and validation, and 59% of the studies assessed the prognostic value of TILs. In conclusion, this analysis contends that automated scoring methods for TILs assessment of breast cancer show significant promise for commodification and application within clinical settings.

A digital score of peri-epithelial lymphocytic activity predicts malignant transformation in oral epithelial dysplasia.

Oral squamous cell carcinoma (OSCC) is amongst the most common cancers, with more than 377,000 new cases worldwide each year. OSCC prognosis remains poor, related to cancer presentation at a late stage, indicating the need for early detection to improve patient prognosis. OSCC is often preceded by a premalignant state known as oral epithelial dysplasia (OED), which is diagnosed and graded using subjective histological criteria leading to variability and prognostic unreliability. In this work, we propose a deep learning approach for the development of prognostic models for malignant transformation and their association with clinical outcomes in histology whole slide images (WSIs) of OED tissue sections. We train a weakly supervised method on OED cases (n = 137) with malignant transformation (n = 50) and mean malignant transformation time of 6.51 years (±5.35 SD). Stratified five-fold cross-validation achieved an average area under the receiver-operator characteristic curve (AUROC) of 0.78 for predicting malignant transformation in OED. Hotspot analysis revealed various features of nuclei in the epithelium and peri-epithelial tissue to be significant prognostic factors for malignant transformation, including the count of peri-epithelial lymphocytes (PELs) (p < 0.05), epithelial layer nuclei count (NC) (p < 0.05), and basal layer NC (p < 0.05). Progression-free survival (PFS) using the epithelial layer NC (p < 0.05, C-index = 0.73), basal layer NC (p < 0.05, C-index = 0.70), and PELs count (p < 0.05, C-index = 0.73) all showed association of these features with a high risk of malignant transformation in our univariate analysis. Our work shows the application of deep learning for the prognostication and prediction of PFS of OED for the first time and offers potential to aid patient management. Further evaluation and testing on multi-centre data is required for validation and translation to clinical practice. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

A review on titanium oxide nanoparticles modified metal-organic frameworks for effective CO2 conversion and efficient wastewater remediation.

Environmental pollution has been increasing since last decade due to increasing industrialisation and urbanisation. Various kinds ofenvironmental pollutants including carbon dioxide (CO2), dyes, pharmaceuticals, phenols, heavy metals along with many organic and inorganic species have been discovered in the various environmental compartments which possess harmful impacts tox human health, wildlife, and ecosystems. Thus, various efforts have been made through regulations, technological advancements, and public awareness campaigns to reduce the impact of the pollution. However, finding suitable alternatives to mitigate their impacts remained a challenge. Metal-organic frameworks (MOFs) are one of the advanced materials with unique features such as high porosity and stability which exhibit versatile applications in environmental remediation. Their composites with titanium oxide nanoparticles (TiO2) have been discovered to offer potential feature such as light harvesting capacity and catalytic activity. The composite integration and properties have been confirmed through characterization using surface area analysis, scanning electron/transmission electron microscopy, atomic force microscopy, fourier transformed infrared spectroscopy, X-ray diffraction analysis, X-ray photoelectron spectroscopy, thermogravimetric analysis, and others. Thus, this work rigorously discussed potential applications of the MOF@TiO2 nanomaterials for the CO2 capture and effective utilization in methanol, ethanol, acetone, acetaldehyde, and other useful products that served as fuel to various industrial processes. Additionally, the work highlights the effective performance of the materials towards photocatalytic degradation of both organic and inorganic pollutants with indepth mechanistic insights. The article will offer significant contribution for the development of sustainable and efficient technologies for the environmental monitoring and pollution mitigation.

Comparison of pharmacokinetics of two tylvalosin oral formulations in broiler chickens.

The objective of the study was to compare the relative bioavailability and pharmacokinetics of two commercially available oral formulations of tylvalosin prepared for use in broiler chickens (ProviLosinR and AviLosinR ). A total of 36 healthy, broiler chickens were administered a single oral dose (25 mg/kg b.w.) of each formulation in a parallel randomized design. The relative bioavailability of ProviLosinR was 108% compared to AviLosinR . There were no significant differences between ProviLosinR and AviLosinR tylvalosin formulations in the average means of the area under the plasma concentration-time curve, maximum plasma concentrations and time to maximum plasma concentrations. In conclusion, tylvalosin was rapidly absorbed and relatively slowly eliminated after oral administration of a single dose for both formulations. ProviLosinR and AviLosinR can be used interchangeably as therapeutic agents in broiler chickens.

A Federated Learning Approach to Tumor Detection in Colon Histology Images.

Federated learning (FL), a relatively new area of research in medical image analysis, enables collaborative learning of a federated deep learning model without sharing the data of participating clients. In this paper, we propose FedDropoutAvg, a new federated learning approach for detection of tumor in images of colon tissue slides. The proposed method leverages the power of dropout, a commonly employed scheme to avoid overfitting in neural networks, in both client selection and federated averaging processes. We examine FedDropoutAvg against other FL benchmark algorithms for two different image classification tasks using a publicly available multi-site histopathology image dataset. We train and test the proposed model on a large dataset consisting of 1.2 million image tiles from 21 different sites. For testing the generalization of all models, we select held-out test sets from sites that were not used during training. We show that the proposed approach outperforms other FL methods and reduces the performance gap (to less than 3% in terms of AUC on independent test sites) between FL and a central deep learning model that requires all data to be shared for centralized training, demonstrating the potential of the proposed FedDropoutAvg model to be more generalizable than other state-of-the-art federated models. To the best of our knowledge, ours is the first study to effectively utilize the dropout strategy in a federated setting for tumor detection in histology images.

Pharmacokinetics and bioavailability of tildipirosin following intravenous and subcutaneous administration in sheep.

Tildipirosin is a semi-synthetic macrolide antibiotic commonly used in cattle and swine to treat bacterial pneumonia. The objective of this study was to investigate the pharmacokinetic profile of tildipirosin after a single intravenous (i.v.) and subcutaneous (s.c.) administration in healthy lambs. Eighteen lambs were randomly divided into three groups (n = 6 each). Lambs received a single s.c. dose of tildipirosin at 4 and 6 mg/kg b.w. in group 1 and 2, respectively. Lambs in group 3 received a single i.v. dose of tildipirosin at 4 mg/kg b.w. Blood samples were collected at 0, 0.5, 0.75, 1.5, 2, 3, 4, 6, 8, 10, 24, 36, 48 hr, and every 24 hr to day 21, and thereafter at day 28 posttildipirosin administration. The plasma concentrations of tildipirosin were determined using high-performance liquid chromatography with tandem mass spectrometry detection (LC/MS/MS). All lambs appeared to tolerate both the intravenous and subcutaneous injection of tildipirosin. Following i.v. administration, the elimination half-life (T1/2 ), mean residence time (MRT), volume of distribution (Vd/F), and total body clearance (Cl/F) were 119.6 ± 9.0 hr, 281.9 ± 25.7 hr, 521.1 ± 107.2 L, and 2.9 ± 0.5 L/hr, respectively. No significant differences in Cmax (657.0 ± 142.8 and 754.6 ± 227.1 ng/ml), Tmax (1.21 ± 0.38 and 1.35 ± 0.44 hr), T1/2 (144 ± 17.5, 156.5 ± 33.4 hr), and MRT (262.0 ± 30.2 and 250.6 ± 54.5 hr) were found in tildipirosin after s.c. dosing at 4 and 6 mg/kg b.w., respectively. The absolute bioavailability (F) of tildipirosin was 71.5% and 75.3% after s.c. administration of 4 and 6 mg/kg b.w., respectively. In conclusion, tildipirosin was rapidly absorbed and slowly eliminated after a single s.c. administration in healthy lambs. Tildipirosin could be used for the treatment and prevention of respiratory bacterial infections in sheep. However, further in vitro and in vivo studies to determine the efficacy and safety are warranted. To our knowledge, this is the first study to determine the tildipirosin pharmacokinetic parameters in sheep plasma.

Magnetic nanoparticles in microfluidic and sensing: From transport to detection.

Superparamagnetic nanoparticles are attracting significant attention. Therefore, being explored in microsystems for a wide range of applications. Typical examples include lab-on-a-chip and microfluidics for synthesis, detection, separation, and transportation of different bioanalytes, such as biomolecules, cells, and viruses to develop portable, sensitive, and cost-effective biosensing systems. Particularly, microfluidic systems incorporated with magnetic nanoparticles and, in combination with magnetoresistive sensors, shift diagnostic and analytical methods to a microscale level. In this context, nanotechnology enables the miniaturization and integration of a variety of analytical functions in a single chip for manipulation, detection, and recognition of bioanalytes reliably and flexibly. In consideration of the above, recent development and benefits are elaborated herein to discuss the role of magnetic nanoparticles inside the microchannels to design highly efficient disposable point-of-care applications from transportation to the detection of bioanalytes.

Visual histological assessment of morphological features reflects the underlying molecular profile in invasive breast cancer: a morphomolecular study.

AIMS: Tumour genotype and phenotype are related and can predict outcome. In this study, we hypothesised that the visual assessment of breast cancer (BC) morphological features can provide valuable insight into underlying molecular profiles. METHODS AND RESULTS: The Cancer Genome Atlas (TCGA) BC cohort was used (n = 743) and morphological features, including Nottingham grade and its components and nucleolar prominence, were assessed utilising whole-slide images (WSIs). Two independent scores were assigned, and discordant cases were utilised to represent cases with intermediate morphological features. Differentially expressed genes (DEGs) were identified for each feature, compared among concordant/discordant cases and tested for specific pathways. Concordant grading was observed in 467 of 743 (63%) of cases. Among concordant case groups, eight common DEGs (UGT8, DDC, RGR, RLBP1, SPRR1B, CXorf49B, PSAPL1 and SPRR2G) were associated with overall tumour grade and its components. These genes are related mainly to cellular proliferation, differentiation and metabolism. The number of DEGs in cases with discordant grading was larger than those identified in concordant cases. The largest number of DEGs was observed in discordant grade 1:3 cases (n = 1185). DEGs were identified for each discordant component. Some DEGs were uniquely associated with well-defined specific morphological features, whereas expression/co-expression of other genes was identified across multiple features and underlined intermediate morphological features. CONCLUSION: Morphological features are probably related to distinct underlying molecular profiles that drive both morphology and behaviour. This study provides further evidence to support the use of image-based analysis of WSIs, including artificial intelligence algorithms, to predict tumour molecular profiles and outcome.

Development, optimisation, and evaluation of nanoencapsulated diacerein emulgel for potential use in osteoarthritis.

AIM: This study aimed to utilise the proficient function of diacerein (DCR) and anti-inflammatory polymers to develop sustained release nanoencapsulated emulgel for potential use in osteoarthritis (OA). METHODS: Chitosan (CHS) and chondroitin sulphate (CS) were employed as natural anti-inflammatory polymers to encapsulate nanoformulation of DCR. Optimised nanoformulation was prepared and characterised by investigating impact of polymers and surfactant on particle size, PDI, and encapsulation efficiency (EE). Afterwards, nanoemulgel of optimised DCR-NPs was formulated and evaluated for transdermal application. RESULTS: Optimised nanoformulation depicted spherical shape with particle size of 320 nm having PDI and EE of 0.3 ± 0.07 and 82 ± 4% (w/w), respectively. DCR-nanoemulgel depicts sustained action of drug up to 96 h with enhanced permeation activity and non-irritancy index. CONCLUSIONS: The elaborated nanoemulgel sustained release of drug having superior penetration properties with provision of enhanced therapeutic effect owing to the presence of CHS, CS, and Argan oil possessing indelible anti-inflammatory attributes.

Pharmacokinetics of toltrazuril and its metabolites in pregnant and nonpregnant ewes and determination of their concentrations in milk, allantoic fluid, and newborn plasma.

The objectives of this study were to determine the pharmacokinetics of toltrazuril and its metabolites in pregnant and nonpregnant ewes following a single oral dose and to determine the plasma concentrations of these compounds in milk, allantoic fluid, and newborn plasma. Eighteen healthy ewes were randomly divided into three groups (n = 6 each): pregnant ewes at 12-13 weeks of gestation (group A), nonpregnant ewes (group B), and pregnant ewes at 1-2 weeks before expected lambing date (group C). Ewes in all groups received a single oral dose of toltrazuril at 20 mg/kg body weight. In groups A and B, blood samples were collected at 1, 3, 5, 7, 9, 12, 15, 18 hr, every 6 hr to day 3, every 12 hr to day 7 and thereafter every 24 hr to day 14 post-toltrazuril administration. In group C, parturition was induced 24-36 hr after toltrazuril administration then milk, allantoic fluid, and newborn plasma samples were collected immediately after birth. Drug metabolites were assayed using ultra high-performance liquid chromatography-ultraviolet detection method (UHPLC-UV). The maximum concentration (Cmax ), area under the plasma concentration-time curve (AUC0-t) , AUC to 24 and 48 hr (AUC0-24 ), and (AUC0-48 ) were significantly higher in pregnant ewes. Longer apparent half-life (T1/2 ), significantly higher apparent volume of distribution (Vd/F) and total clearance (Cl/F) were observed in nonpregnant ewes. The time to maximum plasma concentration (Tmax ), mean residence time (MRT) and elimination rate constant (Kel ) were similar in both groups. The AUC0-24 and AUC0-48 were significantly higher in nonpregnant ewes. The AUC0-t was significantly higher in pregnant ones. The ratio of plasma toltrazuril concentrations in ewes and toltrazuril concentrations in newborn lambs' plasma, allantoic fluid, and milk were 68%, 2.3%, and 5.3%, respectively. Results of this study showed that toltrazuril is well absorbed after a single oral dose in ewes with widespread distribution in different body tissues.

Systematic review on current antiviral therapy in COVID-19 pandemic.

INTRODUCTION: Currently, there are several attempts to find an effective antiviral drugs against the COVID-19. Although majority of the COVID-19 patients have mild to moderate clinical events, up to 5-10% may have severe, life threatening events that urgently require effective drugs. The purpose of this systematic review is to evaluate the effectiveness of antiviral therapies in the treatment of COVID-19. METHODS: An extensive search was performed in PubMed, EMBASE, Cochrane Library for randomised controlled trials (RCTs), prospective case series studies that evaluated therapies COVID-19. The outcomes searched for were mortality, recovery rate, length of hospital stay and clinical improvement from January to May 15, 2020. Independent reviewers searched, identified, screened, and related studies were included. RESULTS: Total of five RCTs on 439 patients and seventeen case series involving 1656 patients were found in the specified review period that reported the use of Lopinavir, Ritonavir, Remdesivir. Oseltamivir, Ribavirin in patients with COVID-19; but none of which showed efficacy of antiviral therapy. Such current findings impede researchers from recommending an appropriate and effective antiviral therapy against COVID-19, making it a serious concern for the global community. DISCUSSION: In the present pandemic and any future epidemics, all the related authorities should pursue many more RCTs, cohort and case series for a prospective outcome in the management and treatment guidelines.

Ventriculoperitoneal shunt-associated abdominal cerebrospinal fluid pseudocysts and the role of laparoscopy and a proposed management algorithm in its treatment. A report of 2 cases.

Abdominal cerebrospinal fluid pseudocyst (APC) is a rare complication associated with a ventriculoperitoneal shunt (VPS) placement. Abdominal cerebrospinal fluid pseudocyst is defined as a cyst surrounded by a non-epithelial lining and filled with the cerebrospinal fluid (CSF). In general, 1% - 4.5% of all patients treated with a VPS develop CSF pseudocysts. Here, we have presented 2 cases of APC complicating VPS placement and a proposed treatment management algorithm. The cases pertained to 7-year-old and 5-year-old children who had undergone VPS placement during infancy and presented with progressive abdominal distention and vomiting and fever, respectively. Both cases were assessed using similar investigations and imaging modalities and diagnosed with APC. However, the treatments were individually tailored based on the algorithm; successful outcomes were achieved in both patients. Abdominal cerebrospinal fluid pseudocyst treatment is difficult considering the presence of adhesions and infection and is associated with a high recurrence rate.

Osteomyelitis post acromioclavicular joint reconstruction.

Acromioclavicular joint (ACJ) injury is a common shoulder injury. There are various techniques of ACJ reconstruction. Superficial infection after ACJ reconstruction is not an uncommon complication. However, osteomyelitis post ACJ reconstruction has never been highlighted as a possible complication. Our patient is a 31-year-old male who sustained a Rockwood 5 ACJ dislocation and had anatomical ACJ reconstruction with autogenous gracilis and semitendinosus graft. Our technique involved the anatomical reconstruction of the ACJ and the coracoclavicular ligament with the usage of two bioscrews and the temporary stabilisation of the ACJ with two k-wires. As in any orthopaedic surgery, infection is often disastrous especially when the surgery involves implants. It can be disastrous with high morbidity to the patient as well as a costly complication to treat. Therefore, we wish to highlight this case as despite its rarity, osteomyelitis can be devastating to the patient and should be prevented if possible.

Circular dichroism enhancement in plasmonic nanorod metamaterials.

Optical activity is a fundamental phenomenon originating from the chiral nature of crystals and molecules. While intrinsic chiroptical responses of ordinary chiral materials to circularly polarized light are relatively weak, they can be enhanced by specially tailored nanostructures. Here, nanorod metamaterials, comprising a dense array of vertically aligned gold nanorods, is shown to provide a significant enhancement of the circular dichroism response of an embedded material. A nanorod composite, acting as an artificial uniaxial crystal, is filled with chiral mercury sulfide nanocrystals embedded in a transparent polymer. The metamaterial, being inherently achiral, enables optical activity enhancement or suppression. Unique properties of inherently achiral structures to tailor optical activities pave a way for flexible characterization of optical activity of molecules and nanocrystal-based compounds.

Alpha-lipoic acid: An inimitable feed supplement for poultry nutrition.

Alpha-lipoic acid (ALA) is a multifunction antioxidant that is produced in small amount by cells as well as its dietary provision facilitates fatty acid mobilization, energy expenditure as well as can scavenge free radicals in poultry birds. It exists in oxidized as well as reduced form, characterized by growth promoting, anti-inflammatory, antioxidative, immunostimulatory, and hypocholesterolemic properties when fed as dietary supplement to farm animals particularly chicken birds. Recently, several studies reported that dietary supplementation of ALA can influence growth performance indicators, immunological, biochemical characteristics, lipid metabolism, and oxidative stress as well as increase antioxidant potential and storability of poultry meat and meat products. Accordingly, this paper adds the reviews and discusses the outcomes of studies documenting the effect of lipoic acid dietary fortification on growth performance, biochemical, and immunological characteristics as well as the effects on lipid peroxidation of fresh meat and meat-based products. Furthermore, this paper also describes the possibilities of utilization of ALA as a feed additive in poultry nutrition to improve the growth performance of poultry as well as meat quality of resultant chicken birds.

Paternal personality and social status influence offspring activity in zebrafish.

BACKGROUND: Evidence for the transmission of non-genetic information from father to offspring is rapidly accumulating. While the impact of chemical and physical factors such as toxins or diet on the fitness of the parents and their offspring have been studied extensively, the importance of behavioural and social circumstances has only recently been recognised. Behavioural traits such as personality characteristics can be relatively stable, and partly comprise a genetic component but we know little about the non-genetic transmission of plastic behavioural traits from parents to offspring. We investigated the relative effect of personality and of social dominance as indicators at the opposite ends of the plasticity range on offspring behaviour in the zebrafish (Danio rerio). We assessed male boldness, a behavioural trait that has previously been shown previously to possess genetic underpinnings, and experimentally manipulated male social status to assess the association between the two types of behaviour and their correlation with offspring activity. RESULTS: We found a clear interaction between the relatively stable and putative genetic effects based on inherited differences in personality and the experimentally induced epigenetic effects from changes in the social status of the father on offspring activity. CONCLUSIONS: Our study shows that offspring behaviour is determined by a combination of paternal personality traits and on-genetic effects derived from the social status of the father.

Validity of self-reported weight and height: a cross-sectional study among Malaysian adolescents.

BACKGROUND: Self-reported weight and height are commonly used in lieu of direct measurements of weight and height in large epidemiological surveys due to inevitable constraints such as budget and human resource. However, the validity of self-reported weight and height, particularly among adolescents, needs to be verified as misreporting could lead to misclassification of body mass index and therefore overestimation or underestimation of the burden of BMI-related diseases. The objective of this study was to determine the validity of self-reported weight and height among Malaysian secondary school children. METHODS: Both self-reported and directly measured weight and height of a subgroup of 663 apparently healthy schoolchildren from the Malaysian Adolescent Health Risk Behaviour (MyAHRB) survey 2013/2014 were analysed. Respondents were required to report their current body weight and height via a self-administrative questionnaire before they were measured by investigators. The validity of self-reported against directly measured weight and height was examined using intraclass correlation coefficient (ICC), the Bland-Altman plot and weighted Kappa statistics. RESULTS: There was very good intraclass correlation between self-reported and directly measured weight [r = 0.96, 95% confidence interval (CI): 0.93, 0.97] and height (r = 0.94, 95% CI: 0.90, 0.96). In addition the Bland-Altman plots indicated that the mean difference between self-reported and direct measurement was relatively small. The mean difference (self-reported minus direct measurements) was, for boys: weight, -2.1 kg; height, -1.6 cm; BMI, -0.44 kg/m2 and girls: weight, -1.2 kg; height, -0.9 cm; BMI, -0.3 kg/m2. However, 95% limits of agreement were wide which indicated substantial discrepancies between self-reported and direct measurements method at the individual level. Nonetheless, the weighted Kappa statistics demonstrated a substantial agreement between BMI status categorised based on self-reported weight and height and the direct measurements (kappa = 0.76, 95% CI: 0.67, 0.84). CONCLUSION: Our results show that the self-reported weight and height were consistent with direct measurements and therefore can be used in assessing the nutritional status of Malaysian school children from the age of 13 to 17 years old in epidemiological studies and for surveillance purposes when direct measurements are not feasible, but not for assessing nutritional status at the individual level.

Comparative assessment of saliva and plasma for drug bioavailability and bioequivalence studies in humans.

Aims: To study the pharmacokinetics of selected drugs in plasma and saliva matrixes in healthy human volunteers, and to suggest using non-invasive saliva sampling instead of plasma as a surrogate in bioavailability and bioequivalence (BA/BE) studies. Methods: Four different pilot BA/BE studies were done in 12-18 healthy humans. Saliva and plasma samples were collected for 3-5 half life values of metformin, tolterodine, rosuvastatin, and paracetamol after oral dosing. Saliva and plasma samples were assayed using LC-MSMS, and then pharmacokinetic parameters were calculated by non-compartmental analysis using Kinetica program. Effective intestinal permeability (Peff) values were also optimized to predict the actual average plasma profile of each drug by Nelder-Mead algorithm of the Parameter Estimation module using SimCYP program. Results: All studied drugs showed salivary excretion with strong correlation coefficients between saliva and plasma concentrations. The optimized Peff ranged 1.44-68.3 × 10-4 cm/s for the drugs under investigation. Saliva/plasma concentrations ratios ranged 0.17-1.5. Inter and intra individual variability of primary pharmacokinetic parameters in saliva matrix was either close to or higher than plasma matrix. This requires larger sample size in saliva studies for some drugs. Conclusion: Our results suggest that there is a potential in BA/BE studies for saliva to be considered as a surrogate for plasma concentration, which goes along with drug regulations. The use of saliva instead of plasma in such studies makes them non-invasive, easy and with a lower clinical burden.

Effectiveness of physical activity intervention among government employees with metabolic syndrome.

BACKGROUND/OBJECTIVE: Our study aimed to assess the effects of physical activity interventions via standing banners (point-of-decision prompt) and aerobics classes to promote physical activity among individuals with metabolic syndrome. METHODS: We conducted a cluster randomized controlled intervention trial (16-week intervention and 8-week follow-up). Malaysian government employees in Putrajaya, Malaysia, with metabolic syndrome were randomly assigned by cluster to a point-of-decision prompt group (n = 44), an aerobics group (n = 42) or a control group (n = 103) based on sample size calculation formula. Step counts were evaluated by Lifecorder e-STEP accelerometers for all participants. Metabolic syndrome was defined according to the 'harmonizing' definition, in which individuals who have at least three of the five metabolic risk factors (waist circumference, high-density lipoprotein cholesterol, triglycerides, fasting glucose levels, systolic and diastolic blood pressure) will be classified as having metabolic syndrome. A total of 80% of the enrolled government employees with metabolic syndrome completed the programme. Data were analyzed using SPSS for Windows (version 20, SPSS, Chicago, IL). RESULTS: There were significantly higher step counts on average in the aerobics group compared to the control group over assessments. Assessments at baseline, post-intervention and follow-up showed a significant difference in step counts between the intervention and control groups. The greatest reductions in the proportions of individuals with metabolic syndrome were observed in the aerobics group with a reduction of 79.4% in the post-intervention assessment compared to the assessment at baseline. CONCLUSION: The findings of this study suggest that physical activity intervention via aerobics classes is an effective strategy for improving step counts and reducing the prevalence of metabolic syndrome.