Obesity is a complex and multifactorial disease that occurs as a result of the interaction between "obesogenic" environmental factors and genetic components. Although the genetic component of obesity is clear from the heritability studies, the genetic basis remains largely elusive. Successes have been achieved in identifying the causal genes for monogenic obesity using animal models and linkage studies, but these approaches are not fruitful for polygenic obesity. The developments of genome-wide association approach have brought breakthrough discovery of genetic variants for polygenic obesity where tens of new susceptibility loci were identified. However, the common SNPs only accounted for a proportion of heritability. The arrival of NGS technologies and completion of 1000 Genomes Project have brought other new methods to dissect the genetic architecture of obesity, for example, the use of exome genotyping arrays and deep sequencing of candidate loci identified from GWAS to study rare variants. In this review, we summarize and discuss the developments of these genetic approaches in human obesity.
MeSH terms: Animals; Genotype; Humans; Models, Genetic; Obesity/genetics*; Genetic Predisposition to Disease; Genomics*; Genome-Wide Association Study
Bone allografts have been used widely to fill up essential void in orthopaedic surgeries. The benefit of using allografts to replace and reconstruct musculoskeletal injuries, fractures or disease has obtained overwhelming acceptance from orthopaedic surgeons worldwide. However, bacterial infection and disease transmission through bone allograft transplantation have always been a significant issue. Sterilization by radiation is an effective method to eliminate unwanted microorganisms thus assist in preventing life threatening allograft associated infections. Femoral heads procured from living donors and long bones (femur and tibia) procured from cadaveric donors were sterilized at 25 kGy in compliance with international standard ISO 11137. According to quality requirements, all records of bone banking were evaluated annually. This retrospective study was carried out on annual evaluation of radiation records from 1998 until 2012. The minimum doses absorbed by the bones were ranging from 25.3 to 38.2 kGy while the absorbed maximum doses were from 25.4 to 42.3 kGy. All the bones supplied by our UMMC Bone Bank were sterile at the required minimum dose of 25 kGy. Our analysis on dose variation showed that the dose uniformity ratios in 37 irradiated boxes of 31 radiation batches were in the range of 1.003-1.251, which indicated the doses were well distributed.
Substandard medicines, whether the result of intentional manipulation or lack of compliance with good manufacturing practice (GMP) or good distribution practice (GDP), pose a significant potential threat to patient safety. Spontaneous adverse drug reaction reporting systems can contribute to identification of quality problems that cause unwanted and/or harmful effects, and to identification of clusters of lack of efficacy. In 2011, the Uppsala Monitoring Centre (UMC) constructed a novel algorithm to identify reporting patterns suggestive of substandard medicines in spontaneous reporting, and applied it to VigiBase(®), the World Health Organization's global individual case safety report database. The algorithm identified some historical clusters related to substandard products, which were later able to be confirmed in the literature or by contact with national centres (NCs). As relevant and detailed information is often lacking in the VigiBase reports but might be available at the reporting NC, further evaluation of the algorithm was undertaken with involvement from NCs.
MeSH terms: Algorithms; Drug Contamination; Drug Industry/standards*; Pharmaceutical Preparations/standards*; Product Surveillance, Postmarketing/methods*; Therapeutic Equivalency; Cluster Analysis; Databases, Factual*
Dual choice bioassays were used to evaluate the antifeedant property of essential oil and methanolic extract of Alpinia galanga (L.) (locally known as lengkuas) against two species of termites, Coptotermes gestroi (Wasmann) and Coptotermes curvignathus (Holmgren) (Isoptera: Rhinotermitidae). A 4-cm-diameter paper disc treated with A. galanga essential oil and another treated with either methanol or hexane as control were placed in a petri dish with 10 termites. Mean consumption of paper discs (miligram) treated with 2,000 ppm of essential oil by C. gestroi was 3.30 ± 0.24 mg and by C. curvignathus was 3.32 ± 0.24 mg. A. galanga essential oil showed significant difference in antifeedant effect, 2,000 ppm of A. galanga essential oil was considered to be the optimum concentration that gave maximum antifeedant effect. The essential oil composition was determined using gas chromatography-mass spectrometry. The major component of the essential oil was 1,8-cineol (61.9%). Antifeedant bioassay using 500 ppm of 1,8-cineol showed significant reduction in paper consumption by both termite species. Thus, the bioactive agent in A. galangal essential oil causing antifeeding activity was identified as 1,8-cineol. Repellent activity shows that 250 ppm of 1,8-cineol caused 50.00 ± 4.47% repellency for C. gestroi, whereas for C. curvignathus 750 ppm of 1,8-cineol was needed to cause similar repellent activity (56.67 ± 3.33%). C. curvignathus is more susceptible compare to C. gestroi in Contact Toxicity study, the lethal dose (LD50) of C. curvignathus was 945 mg/kg, whereas LD50 value for C. gestroi was 1,102 mg/kg. Hence 1,8-cineol may be developed as an alternative control against termite in sustainable agriculture practices.
Patients with cystic fibrosis (CF) show decreased plasma concentrations of antioxidants due to malabsorption of lipid soluble vitamins and consumption by chronic pulmonary inflammation. β-Carotene is a major source of retinol and therefore is of particular significance in CF. The aim of this study was to investigate the effect of daily intake of red palm oil (RPO) containing high amounts of β-carotene on the antioxidant levels in CF patients. Sixteen subjects were recruited and instructed to enrich their food with 2 to 3 tablespoons of RPO (~1.5 mg of β-carotene) daily over 8 weeks. Carotenoids, retinol, and α-tocopherol were measured in plasma at baseline and after intervention. In addition β-carotene, lycopene, α-tocopherol, and vitamin C were measured in buccal mucosa cells (BMC) to determine the influence of RPO on antioxidant tissue levels. Eleven subjects completed the study properly. Plasma β-carotene, retinol, and α-carotene of these patients increased, but plasma concentrations of other carotenoids and α-tocopherol as well as concentrations of β-carotene, lycopene, α-tocopherol, and vitamin C in BMC remained unchanged. Since RPO on a daily basis did not show negative side effects the data suggest that RPO may be used to elevate plasma β-carotene in CF.
Vibrio parahaemolyticus is a marine and estuarine bacterium that has been the leading cause of foodborne outbreaks which leads to a significant threat to human health worldwide. Consumption of seafood contaminated with V. parahaemolyticus causes acute gastroenteritis in individuals. The bacterium poses two main virulence factor including the thermostable direct hemolysin (tdh) which is a pore-forming protein that contributes to the invasiveness of the bacterium in humans and TDH-related hemolysin (trh), which plays a similar role as tdh in the disease pathogenesis. This study aimed to investigate the antimicrobial resistance V. parahaemolyticus strains in shrimps purchased from wetmarkets and supermarkets. The toxR-based PCR assay indicated that a total of 57.8% (185/320) isolates were positive for V. parahaemolyticus. Only 10% (19/185) toxR-positive isolate exhibit the trh gene and none of the isolates were tested positive for tdh. The MAR index was measured for 14 common antimicrobial agents. The results indicated 98% of the isolates were highly susceptible to imipenem, ampicillin sulbactam (96%), chloramphenicol (95%), trimethoprim-sulfamethoxazole (93%), gentamicin (85%), levofloxacin (83%), and tetracycline (82%). The chloramphenicol (catA2) and kanamycin (aphA-3) resistance genes were detected in the resistant V. parahaemolyticus isolates. Our results demonstrate that shrimps are contaminated with V. parahaemolyticus, some of which carry the trh-gene thus being potential to cause food borne illness. The occurrence of multidrug resistance strains in the environment could be an indication of excessive usage of antibiotics in agriculture and aquaculture fields.
The content of 12 elements in Cambodian dried striped snakehead fish was determined using inductively coupled plasma mass spectrometry. The present study compares the level of the trace toxic metals and nutritional trace elements in the fish processed using solar drying system (SDS) and open sun drying (OSD). The skin of SDS fish has lower level of As, Pb, and Cd compared to the OSD sample. As such, the flesh of the fish accumulated higher amount of toxic metals during OSD compared to SDS. However, arsenic was detected in both samples within the safe limit. The nutritional elements (Fe, Mn, Mg, Se, Mo, Cu, Ni, and Cr) were higher in the skin sample SDS fish compared to OSD fish. These beneficial metals were not accumulated in the flesh sample SDS fish demonstrating lower level compared to drying under conventional system. The reddish coloration of the SDS fish was due to the presence of high Cu content in both the skin and flesh samples which possibly account for no mold formation 5 days after packaging. As conclusion, drying of Cambodian C. striata using solar-assisted system has proven higher content of the nutritious elements compared to using the conventional system despite only slight difference in the toxic metals level between the two systems.
Purpose: The mucopolysaccharidoses (MPS) are a group of rare lysosomal storage disorders, characterized by the accumulation of glycosaminoglycans within multiple organ systems including the eye. This study aimed to determine the prevalence of glaucoma in patients with MPS, as well as the characteristics, diagnosis and management of patients with MPS and glaucoma.
Methods: A multicentre retrospective case-note review was carried out by ophthalmologists from four tertiary referral centres to identify patients with MPS who had been treated for glaucoma. Clinical ophthalmological data were collected using standardized data collection forms.
Results: Fourteen patients were identified (27 eyes) of 294 patients with MPS. The prevalence of glaucoma ranged from 2.1% to 12.5%. The median age at diagnosis of glaucoma was 8 years. Diagnostic evaluation of glaucoma was incomplete in many patients: intraocular pressure was documented in all eyes, but optic disc appearance was only assessed in 67%, central corneal thickness in 26%, visual fields in 19% and iridocorneal angle in 15%.
Conclusions: Patients with MPS need regular assessment for possible glaucoma including during childhood. Multiple factors contribute to the challenges of assessment, diagnosis and monitoring of glaucoma in these patients.
Keywords: Hunter; Hurler; Hurler-Scheie; Maroteaux-Lamy; Morquio; Scheie; glaucoma; mucopolysaccharidosis; prevalence.
The staggering growth in smartphone and wearable device use has led to a massive scale generation of personal (user-specific) data. To explore, analyze, and extract useful information and knowledge from the deluge of personal data, one has to leverage these devices as the data-mining platforms in ubiquitous, pervasive, and big data environments. This study presents the personal ecosystem where all computational resources, communication facilities, storage and knowledge management systems are available in user proximity. An extensive review on recent literature has been conducted and a detailed taxonomy is presented. The performance evaluation metrics and their empirical evidences are sorted out in this paper. Finally, we have highlighted some future research directions and potentially emerging application areas for personal data mining using smartphones and wearable devices.
This study investigates the antagonistic effects of the probiotic strains Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 against vulvovaginal candidiasis (VVC)-causing Candida glabrata.
Traditional department-based surgical interest groups in Russian medical schools are useful tools for student-based selection of specialty training. They also form a nucleus for initiating research activities among undergraduate students. In Russia, the Departments of Topographical Anatomy and Operative Surgery play an important role in initiating student-led research and providing learners with advanced, practical surgical skills. In tandem with department-led activities, student surgical interest groups prepare learners through surgical competitions, known as "Surgical Olympiads," which have been conducted in many Russian centers on a regular basis since 1988. Surgical Olympiads stimulate student interest in the development of surgical skills before graduation and encourage students to choose surgery as their postgraduate specialty. Many of the participants in these surgical Olympiads have become highly qualified specialists in general surgery, orthopedic surgery, neurosurgery, urology, gynecology, and emergency medicine. The present article emphasizes the role of student interest groups and surgical Olympiads in clinical anatomical and surgical undergraduate training in Russia.
The crude methanol extracts and fractions of the root and stem barks of Dillenia serrata Thunb. showed 64% to 73% inhibition on the production of prostaglandin E2 (PGE2) in lipopolysaccharide-induced human whole blood using a radioimmunoassay technique. Three triterpenoids isolated from the root bark of the plant, koetjapic (1), 3-oxoolean-12-en-30-oic (2), and betulinic (3) acids, exhibited significant concentration-dependent inhibitory effects on PGE2 production with IC50 values of 1.05, 1.54, and 2.59 μM, respectively, as compared with the positive control, indomethacin (IC50 = 0.45 μM). Quantification of compounds 1 and 3 in the methanol extracts and fractions were carried out by using a validated reversed-phase high performance liquid chromatography (RP-HPLC) method. The ethyl acetate fraction of the stem bark showed the highest content of both compound 1 (15.1%) and compound 3 (52.8%). The strong inhibition of the extracts and fractions on cyclooxygenase-2 (COX-2) enzymatic activity was due to the presence of their major constituents, especially koetjapic and betulinic acids.
Curcumin has poor in vivo absorption and bioavailability, highlighting a need for new curcumin analogues with better characteristics in these aspects. The aim of this study is to determine the anti-cancer properties of four selected curcumin analogues, on the cytotoxicity, proliferative and apoptotic effects on androgen-independent human prostate cancer cells (PC-3 and DU 145). Initial cytotoxicity screening showed MS17 has the highest cell inhibitory effect, with EC50 values of 4.4 ± 0.3 and 4.1 ± 0.8 µM, followed by MS13 (7.5 ± 0.1 and 7.4 ± 2.6 µM), MS49 (14.5 ± 1.2 and 12.3 ± 2.3 µM) and MS40E (28.0 ± 7.8 and 30.3 ± 1.9 µM) for PC-3 and DU 145 cells, respectively. Time-dependent analysis also revealed that MS13 and MS17 displayed a greater anti-proliferative effect than the other compounds. MS17 was chosen based on the high selectivity index value for further analysis on the morphological and biochemical hallmarks of apoptosis. Fluorescence microscopy analysis revealed apoptotic changes in both treated prostate cancer cells. Relative caspase-3 activity increased significantly at 48 h in PC-3 and 12 h in DU 145 cells. Highest enrichment of free nucleosomes was noted at 48 h after treatment with MS17. In conclusion, MS17 demonstrated anti-proliferative effect and induces apoptosis in a time and dose-dependent manner suggesting its potential for development as an anti-cancer agent for androgen-independent prostate cancer.
One of the novel applications of the nanostructures is the modification and development of membranes for hemocompatibility of hemodialysis. The toxicity and hemocompatibility of Ag nanoparticles and arginine-treated multiwalled carbon nanotubes (MWNT-Arg) and possibility of their application in membrane technology are investigated here. MWNT-Arg is prepared by amidation reactions, followed by characterization by FTIR spectroscopy, Raman spectroscopy, and thermogravimetric analysis. The results showed a good hemocompatibility and the hemolytic rates in the presence of both MWNT-Arg and Ag nanoparticles. The hemolytic rate of Ag nanoparticles was lower than that of MWNT-Arg. In vivo study revealed that Ag nanoparticle and MWNT-Arg decreased Hematocrit and mean number of red blood cells (RBC) statistically at concentration of 100 µg mL(-1) . The mean decrease of RBC and Hematocrit for Ag nanoparticles (18% for Hematocrit and 5.8 × 1,000,000/µL) was more than MWNT-Arg (20% for Hematocrit and 6 × 1000000/µL). In addition, MWNT-Arg and Ag nanoparticles had a direct influence on the White Blood Cell (WBC) drop. Regarding both nanostructures, although the number of WBC increased in initial concentration, it decreased significantly at the concentration of 100 µg mL(-1) . It is worth mentioning that the toxicity of Ag nanoparticle on WBC was higher than that of MWNT-Arg. Because of potent antimicrobial activity and relative hemocompatibility, MWNT-Arg could be considered as a new candidate for biomedical applications in the future especially for hemodialysis membranes.
Sea snake envenomation is a serious occupational hazard in tropical waters. In Malaysia, the beaked sea snake (Hydrophis schistosus, formerly known as Enhydrina schistosa) and the spine-bellied sea snake (Hydrophis curtus, formerly known as Lapemis curtus or Lapemis hardwickii) are two commonly encountered species. Australian CSL sea snake antivenom is the definitive treatment for sea snake envenomation; it is unfortunately extremely costly locally and is not widely available or adequately stocked in local hospitals. This study investigated the cross-neutralizing potential of three regionally produced anti-cobra antivenoms against the venoms of Malaysian H. schistosus and H. curtus. All three antivenoms conferred paraspecific protection from sea snake venom lethality in mice, with potency increasing in the following order: Taiwan bivalent antivenom < Thai monocled cobra monovalent antivenom < Thai neuro polyvalent antivenom (NPAV). NPAV demonstrated cross-neutralizing potencies of 0.4 mg/vial for H. schistosus venom and 0.8 mg/vial for H. curtus, which translates to a dose of less than 20 vials of NPAV to neutralize an average amount of sea snake venom per bite (inferred from venom milking). The cross-neutralization activity was supported by ELISA cross-reactivity between NPAV and the venoms of H. schistosus (58.4%) and H. curtus (70.4%). These findings revealed the potential of NPAV as a second-line treatment for sea snake envenomation in the region. Further profiling of the cross-neutralization activity should address the antivenomic basis using purified toxin-based assays.
Probiotics are live microorganisms that confer health benefits through the gastrointestinal microbiota. This nutritional supplement may benefit athletes who undergo rigorous training by maintaining their gastrointestinal functions and overall health. In this study the influence of moderate physical exercise using a graded treadmill exercise, alone or in combination with the consumption of a soy product fermented with Lactobacillus plantarum LAB12 (LAB12), on tumour necrosis factor alpha (TNF-α) responses was investigated in a murine model. Male BALB/c mice were randomly divided into four groups of six mice each (control, exercise alone, LAB12 and LAB12 + exercise). Mice treated with the potential probiotic LAB12 were orally gavaged for 42 days. At autopsy, blood and spleen from the animals were collected. The splenocytes were cultured in the presence of a mitogen, concanavalin A (Con A). The amount of TNF-α produced by the Con A-stimulated splenocytes was quantified using ELISA, while their proliferation was determined using the [(3)H]-thymidine incorporation method. This study shows that LAB12-supplemented and exercise-induced mice showed marked increase (P<0.05) in cell proliferation compared to the control animals. TNF-α production was suppressed (P<0.05) in the LAB12 group compared to the untreated mice. These results demonstrate that supplementation with LAB12 has immunomodulatory effects, under conditions of moderate physical exercise, which may have implications for human athletes. Further investigation in human trials is warranted to confirm and extrapolate these findings.
Most identity-based identification (IBI) schemes proposed in recent literature are built using pairing operations. This decreases efficiency due to the high operation costs of pairings. Furthermore, most of these IBI schemes are proven to be secure against impersonation under active and concurrent attacks using interactive assumptions such as the one-more RSA inversion assumption or the one-more discrete logarithm assumption, translating to weaker security guarantees due to the interactive nature of these assumptions. The Schnorr-IBI scheme was first proposed through the Kurosawa-Heng transformation from the Schnorr signature. It remains one of the fastest yet most secure IBI schemes under impersonation against passive attacks due to its pairing-free design. However, when required to be secure against impersonators under active and concurrent attacks, it deteriorates greatly in terms of efficiency due to the protocol having to be repeated multiple times. In this paper, we upgrade the Schnorr-IBI scheme to be secure against impersonation under active and concurrent attacks using only the classical discrete logarithm assumption. This translates to a higher degree of security guarantee with only some minor increments in operational costs. Furthermore, because the scheme operates without pairings, it still retains its efficiency and superiority when compared to other pairing-based IBI schemes.
The present study aimed to assess the cost-utility analysis of using an adjunctive recombinant activated factor VIIa (rFVIIa) in children for controlling life-threatening bleeding in dengue haemorrhagic fever (DHF)/dengue shock syndrome (DSS). We constructed a decision-tree model, comparing a standard care and the use of an additional adjuvant rFVIIa for controlling life-threatening bleeding in children with DHF/DSS. Cost and utility benefit were estimated from the societal perspective. The outcome measure was cost per quality-adjusted life years (QALYs). Overall, treatment with adjuvant rFVIIa gained QALYs, but the total cost was higher. The incremental cost-utility ratio for the introduction of adjuvant rFVIIa was $4241.27 per additional QALY. Sensitivity analyses showed the utility value assigned for calculation of QALY was the most sensitive parameter. We concluded that despite high cost, there is a role for rFVIIa in the treatment of life-threatening bleeding in patients with DHF/DSS.
MeSH terms: Adolescent; Cost-Benefit Analysis; Decision Trees; Hemorrhage/complications; Hemorrhage/drug therapy*; Hemorrhage/economics*; Humans; Recombinant Proteins/economics; Recombinant Proteins/therapeutic use; Factor VIIa/economics*; Factor VIIa/therapeutic use*; Quality-Adjusted Life Years; Severe Dengue/complications; Severe Dengue/drug therapy*; Severe Dengue/economics*