Serological Prediction of infections in Diabetic Patients with Diabetes Ketoacidosis in Penang, Malaysia

Purpose: To determine the prevalence and predictors of infection in diabetic patients with diabetic ketoacidosis (DKA) who were .18 years.Methods: A retrospective cohort design was adopted for this study. A total of 967 diabetes ketoacidosis patients from Hospital Pulau Pinang for the 3-year period, Jan 2008 - Dec 2010, were identified and enrolled. The data were analysed, as appropriate, by Student t-test and ANOVA for the normally distributed data, Mann-Whitney U rank sum and Kruskall-Wallis tests for continuous, non-nominal data and Chi-square for dichotomous variables. Odd Ratios with 95% confidence interval (CI) were alsopresented where applicable.Results: Of the total diabetes ketoacidosis patients, 112 (11.6 %) were cases without infection, 679 (70.2 %) bacterial infection cases and 176 (18.2 %) presumed viral infection cases. The mean white blood count (WBC) for all the patients was 18,177 } 9,431 while 721 (74.6 %) had leukocytosis, defined by WBC . 15,000/mm3. WBC differential, leukocytosis, as well as sex and body temperature were not significant predictors (p >.05) of bacterial infection. There was, however, a significant difference (p <.05) in terms of age within groups, as those > 57 years showed a higher rate of infection.Conclusion: The infection rate in elderly patients with DKA is high and a majority of them lack clinical evidence. Age has a significant effect on the rate and prediction of infection. Leukocytosis is commonly found but severe ketoacidosis was more likely than the presence of infection.Keywords: Diabetes mellitus, Diabetes ketoacidosis, Infections, Predictors, White blood cell

Curcumin induces chemo/radio-sensitization in ovarian cancer cells and curcumin nanoparticles inhibit ovarian cancer cell growth

<p>Abstract</p> <p>Background</p> <p>Chemo/radio-resistance is a major obstacle in treating advanced ovarian cancer. The efficacy of current treatments may be improved by increasing the sensitivity of cancer cells to chemo/radiation therapies. Curcumin is a naturally occurring compound with anti-cancer activity in multiple cancers; however, its chemo/radio-sensitizing potential is not well studied in ovarian cancer. Herein, we demonstrate the effectiveness of a curcumin pre-treatment strategy for chemo/radio-sensitizing cisplatin resistant ovarian cancer cells. To improve the efficacy and specificity of curcumin induced chemo/radio sensitization, we developed a curcumin nanoparticle formulation conjugated with a monoclonal antibody specific for cancer cells.</p> <p>Methods</p> <p>Cisplatin resistant A2780CP ovarian cancer cells were pre-treated with curcumin followed by exposure to cisplatin or radiation and the effect on cell growth was determined by MTS and colony formation assays. The effect of curcumin pre-treatment on the expression of apoptosis related proteins and β-catenin was determined by Western blotting or Flow Cytometry. A luciferase reporter assay was used to determine the effect of curcumin on β-catenin transcription activity. The poly(lactic acid-<it>co</it>-glycolic acid) (PLGA) nanoparticle formulation of curcumin (Nano-CUR) was developed by a modified nano-precipitation method and physico-chemical characterization was performed by transmission electron microscopy and dynamic light scattering methods.</p> <p>Results</p> <p>Curcumin pre-treatment considerably reduced the dose of cisplatin and radiation required to inhibit the growth of cisplatin resistant ovarian cancer cells. During the 6 hr pre-treatment, curcumin down regulated the expression of Bcl-X_Land Mcl-1 pro-survival proteins. Curcumin pre-treatment followed by exposure to low doses of cisplatin increased apoptosis as indicated by annexin V staining and cleavage of caspase 9 and PARP. Additionally, curcumin pre-treatment lowered β-catenin expression and transcriptional activity. Nano-CUR was successfully generated and physico-chemical characterization of Nano-CUR indicated an average particle size of ~70 nm, steady and prolonged release of curcumin, antibody conjugation capability and effective inhibition of ovarian cancer cell growth.</p> <p>Conclusion</p> <p>Curcumin pre-treatment enhances chemo/radio-sensitization in A2780CP ovarian cancer cells through multiple molecular mechanisms. Therefore, curcumin pre-treatment may effectively improve ovarian cancer therapeutics. A targeted PLGA nanoparticle formulation of curcumin is feasible and may improve the <it>in vivo </it>therapeutic efficacy of curcumin.</p

Sustainable Waste Management in Malaysia: Leveraging Supply Chain Solutions for a Greener Future

Sustainable waste management has become a critical global concern, and Malaysia is no exception. With the country's increasing urbanization and economic growth, waste generation has risen significantly, posing environmental and social challenges. This paper explores the concept of sustainable waste management in Malaysia and proposes leveraging supply chain solutions as a pathway towards a greener future. The study examines the current waste management practices, their limitations, and the potential environmental impacts. It highlights the need for integrated and innovative approaches encompassing the entire waste management supply chain, from collection to disposal. By adopting sustainable supply chain practices, such as waste segregation, recycling, and waste-to-energy conversion, Malaysia can achieve more efficient resource utilization, reduce greenhouse gas emissions, and minimize landfill usage. Furthermore, the paper addresses the role of government policies, private sector engagement, and public awareness in fostering a successful transition towards sustainable waste management. The findings and recommendations presented in this study contribute to the ongoing efforts to develop a comprehensive and eco-friendly waste management system in Malaysia and serve as a model for other developing nations facing similar challenges

The Role of Logispreneurs in Advancing Waste Management in Malaysia: Towards a Sustainable Reverse Logistics and Green Future

Waste management has emerged as a critical challenge in Malaysia, driven by rapid urbanization, industrialization and changing consumption patterns. In response to these challenges, logispreneurs, a new breed of entrepreneurs with expertise in logistics and supply chain management, have emerged as key players in transforming waste management practices in the country. This research explores the vital roles and contributions of logispreneurs in the context of waste management in Malaysia, focusing on their efforts to enhance efficiency, sustainability, and environmental responsibility. Through a simple literature analysis, this study highlights the multifaceted roles that logispreneurs play in shaping the waste management landscape. They pioneer integrated waste collection and transportation systems, leveraging advanced technologies and data analytics to optimize routes and reduce carbon footprints. Moreover, logispreneurs lead the way in establishing reverse logistics networks for recyclable materials, fostering excellent recycling rates and diverting substantial waste from landfills. Logispreneurs specialize in managing hazardous waste materials, and ensuring safe transportation and disposal while complying with environmental regulations. They also contribute to public awareness and education campaigns, raising consciousness about sustainable waste management practices nationwide. This study elucidates the pivotal role logispreneurs play in revolutionizing waste management practices in Malaysia. Their logistics expertise and environmental consciousness amalgam present a promising pathway toward a sustainable future. By optimizing supply chain efficiencies, driving innovation and embracing social and environmental responsibility, logispreneurs are instrumental in building a resilient waste management ecosystem that ensures preservation of Malaysia's natural resources and safeguards the well-being of its citizens for generations to come

Tracking the early depleting transmission dynamics of COVID-19 with a time-varying SIR model

The susceptible-infectious-removed (SIR) model offers the simplest framework to study transmission dynamics of COVID-19, however, it does not factor in its early depleting trend observed during a lockdown. We modified the SIR model to specifically simulate the early depleting transmission dynamics of COVID-19 to better predict its temporal trend in Malaysia. The classical SIR model was fitted to observed total (I total), active (I) and removed (R) cases of COVID-19 before lockdown to estimate the basic reproduction number. Next, the model was modified with a partial time-varying force of infection, given by a proportionally depleting transmission coefficient, βt and a fractional term, z. The modified SIR model was then fitted to observed data over 6 weeks during the lockdown. Model fitting and projection were validated using the mean absolute percent error (MAPE). The transmission dynamics of COVID-19 was interrupted immediately by the lockdown. The modified SIR model projected the depleting temporal trends with lowest MAPE for I total, followed by I, I daily and R. During lockdown, the dynamics of COVID-19 depleted at a rate of 4.7% each day with a decreased capacity of 40%. For 7-day and 14-day projections, the modified SIR model accurately predicted I total, I and R. The depleting transmission dynamics for COVID-19 during lockdown can be accurately captured by time-varying SIR model. Projection generated based on observed data is useful for future planning and control of COVID-19

White matter microstructure in 22q11 deletion syndrome: a pilot diffusion tensor imaging and voxel-based morphometry study of children and adolescents

Young people with 22q11 Deletion Syndrome (22q11DS) are at substantial risk for developing psychosis and have significant differences in white matter (WM) volume. However, there are few in vivo studies of both WM microstructural integrity (as measured using Diffusion Tensor (DT)-MRI) and WM volume in the same individual. We used DT-MRI and structural MRI (sMRI) with voxel based morphometry (VBM) to compare, respectively, the fractional anisotropy (FA) and WM volume of 11 children and adolescents with 22q11DS and 12 controls. Also, within 22q11DS we related differences in WM to severity of schizotypy, and polymorphism of the catechol-O-methyltransferase (COMT) gene. People with 22q11DS had significantly lower FA in inter-hemispheric and brainstem and frontal, parietal and temporal lobe regions after covarying for IQ. Significant WM volumetric increases were found in the internal capsule, anterior brainstem and frontal and occipital lobes. There was a significant negative correlation between increased schizotypy scores and reduced WM FA in the right posterior limb of internal capsule and the right body and left splenium of corpus callosum. Finally, the Val allele of COMT was associated with a significant reduction in both FA and volume of WM in the frontal lobes, cingulum and corpus callosum. Young people with 22q11DS have significant differences in both WM microstructure and volume. Also, there is preliminary evidence that within 22q11DS, some regional differences in FA are associated with allelic variation in COMT and may perhaps also be associated with schizotypy

Alpha-tocotrienol is the most abundant tocotrienol isomer circulated in plasma and lipoproteins after postprandial tocotrienol-rich vitamin E supplementation

<p>Abstract</p> <p>Background</p> <p>Tocotrienols (T3) and tocopherols (T), both members of the natural vitamin E family have unique biological functions in humans. T3 are detected in circulating human plasma and lipoproteins, although at concentrations significantly lower than α-tocopherol (α-T). T3, especially α-T3 is known to be neuropotective at nanomolar concentrations and this study evaluated the postprandial fate of T3 and α-T in plasma and lipoproteins.</p> <p>Methods</p> <p>Ten healthy volunteers (5 males and 5 females) were administered a single dose of vitamin E [526 mg palm tocotrienol-rich fraction (TRF) or 537 mg α-T] after 7-d pre-conditioning on a T3-free diet. Blood was sampled at baseline (fasted) and 2, 4, 5, 6, 8, and 24 h after supplementation. Concentrations of T and T3 isomers in plasma, triacylglycerol-rich particles (TRP), LDL, and HDL were measured at each postprandial interval.</p> <p>Results</p> <p>After TRF supplementation, plasma α-T3 and γ-T3 peaked at 5 h (α-T3: 4.74 ± 1.69 μM; γ-T3: 2.73 ± 1.27 μM). δ-T3 peaked earlier at 4 h (0.53 ± 0.25 μM). In contrast, α-T peaked at 6 h (30.13 ± 2.91 μM) and 8 h (37.80 ± 3.59 μM) following supplementation with TRF and α-T, respectively. α-T was the major vitamin E isomer detected in plasma, TRP, LDL, and HDL even after supplementation with TRF (composed of 70% T3). No T3 were detected during fasted states. T3 are detected postprandially only after TRF supplementation and concentrations were significantly lower than α-T.</p> <p>Conclusions</p> <p>Bio-discrimination between vitamin E isomers in humans reduces the rate of T3 absorption and affects their incorporation into lipoproteins. Although low absorption of T3 into circulation may impact some of their physiological functions in humans, T3 have biological functions well below concentration noted in this study.</p

The association between histamine 2 receptor antagonist use and Clostridium difficile infection: a systematic review and meta-analysis.

Background Clostridium difficile infection (CDI) is a major health problem. Epidemiological evidence suggests that there is an association between acid suppression therapy and development of CDI. Purpose We sought to systematically review the literature that examined the association between histamine 2 receptor antagonists (H2RAs) and CDI. Data source We searched Medline, Current Contents, Embase, ISI Web of Science and Elsevier Scopus from 1990 to 2012 for all analytical studies that examined the association between H2RAs and CDI. Study selection Two authors independently reviewed the studies for eligibility. Data extraction Data about studies characteristics, adjusted effect estimates and quality were extracted. Data synthesis Thirty-five observations from 33 eligible studies that included 201834 participants were analyzed. Studies were performed in 6 countries and nine of them were multicenter. Most studies did not specify the type or duration of H2RAs therapy. The pooled effect estimate was 1.44, 95% CI (1.22–1.7), I2 = 70.5%. This association was consistent across different subgroups (by study design and country) and there was no evidence of publication bias. The pooled effect estimate for high quality studies was 1.39 (1.15–1.68), I2 = 72.3%. Meta-regression analysis of 10 study-level variables did not identify sources of heterogeneity. In a speculative analysis, the number needed to harm (NNH) with H2RAs at 14 days after hospital admission in patients receiving antibiotics or not was 58, 95% CI (37, 115) and 425, 95% CI (267, 848), respectively. For the general population, the NNH at 1 year was 4549, 95% CI (2860, 9097). Conclusion In this rigorous systematic review and meta-analysis, we observed an association between H2RAs and CDI. The absolute risk of CDI associated with H2RAs is highest in hospitalized patients receiving antibiotics

Disrupted white matter integrity in treatment-resistant schizophrenia

Treatment response in schizophrenia is heterogeneous and has been posited to divide into three distinct subcategories: treatment-responsive (first-line responders; FLR), treatment-resistant (TRS, responding to clozapine), and ultra-treatment-resistant schizophrenia (UTRS, requiring augmented antipsychotic therapy). Previous work suggests that white matter abnormalities drive antipsychotic resistance but little work has been carried out to identify differences between those with TRS and those with UTRS. The current study aimed to establish whether differences in white matter structure are present across both treatment-resistant subtypes of schizophrenia or if UTRS is distinct from TRS. Diffusion-weighted images were acquired for 18 individuals with TRS, 14 with UTRS, 18 FLR and 20 healthy controls. Measures of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and parallel diffusivity (PD) were obtained using tract-based spatial statistics. Analysis of variance (ANOVA) and post-hoc between-groups t-tests interrogating differences were conducted for each white matter measure. Those with TRS had lower FA than healthy controls across widespread regions of the brain, including the superior longitudinal fasciculus, corpus callosum, thalamic radiation, corticospinal tract, internal capsule, corona radiata and fronto-occipital fasciculus (p<.05 FWE-corrected). Lower FA was also observed in those with TRS compared with UTRS in the superior longitudinal fasciculus (p<.05 FWE-corrected). However, post-hoc tests failed to survive corrections for multiple comparisons across the 12 post-hoc contrasts. No differences in MD, PD or RD were observed between groups. These data suggest that TRS is distinct from UTRS and that lower FA could act as a biomarker of treatment resistance in people with schizophrenia