The Impact of multimorbidity burden, frailty risk scoring, and 3-directional morphological indices vs. testing for CSF responsiveness in normal pressure hydrocephalus

Objective: Multimorbidity burden across disease cohorts and variations in clinico-radiographic presentations within normal pressure hydrocephalus (NPH) confound its diagnosis, and the assessment of its amenability to interventions. We hypothesized that novel imaging techniques such as 3-directional linear morphological indices could help in distinguishing between hydrocephalus vs. non-hydrocephalus and correlate with responsiveness to external lumbar drainage (CSF responsiveness) within NPH subtypes.Methodology: Twenty-one participants with NPH were recruited and age-matched to 21 patients with Alzheimer’s Disease (AD) and 21 healthy controls (HC) selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Patients with NPH underwent testing via the NPH programme with external lumbar drainage (ELD); pre- and post-ELD MRI scans were obtained. The modified Frailty Index (mFI-11) was used to stratify the NPH cohort, including Classic and Complex subtypes, by their comorbidity and frailty risks. The quantitative imaging network tool 3D Slicer was used to derive traditional 2-dimensional (2d) linear measures; Evans Index (EI), Bicaudate Index (BCI) and Callosal Angle (CA), along with novel 3-directional (3d) linear measures; z-Evans Index and Brain per Ventricle Ratio (BVR). 3-Dimensional (3D) ventricular volumetry was performed as an independent correlate of ventriculomegaly to CSF responsiveness.Results: Mean age for study participants was 71.14 ± 6.3 years (18, 85.7% males). The majority (15/21, 71.4%) of participants with NPH comprised the Complex subtype (overlay from vascular risk burden and AD); 12/21 (57.1%) were Non-Responders to ELD. Frailty alone was insufficient in distinguishing between NPH subtypes. By contrast, 3d linear measures distinguished NPH from both AD and HC cohorts, but also correlated to CSF responsiveness. The z-Evans Index was the most sensitive volumetric measure of CSF responsiveness (p = 0.012). Changes in 3d morphological indices across timepoints distinguished between Responders vs. Non-Responders to lumbar testing. There was a significant reduction of indices, only in Non-Responders and across multiple measures (z-Evans Index; p = 0.001, BVR at PC; p = 0.024). This was due to a significant decrease in ventricular measurement (p = 0.005) that correlated to independent 3D volumetry (p = 0.008).Conclusion. In the context of multimorbidity burden, frailty risks and overlay from neurodegenerative disease, 3d morphological indices demonstrated utility in distinguishing hydrocephalus vs. non-hydrocephalus and degree of CSF responsiveness. Further work may support the characterization of patients with Complex NPH who would best benefit from the risks of interventions

Reliability model for helicopter main gearbox lubrication system using influence diagrams

This paper presents the development of a model to assess the reliability of helicopter main gearbox (MGB) lubricating systems. The loss of oil from a helicopter MGB will lead to increased friction between components, a rise in component surface temperatures, and subsequent mechanical failure of gearbox components. A number of significant helicopter accidents have been caused due to such loss of lubrication. Current certification requirements for Category A helicopters require that gearboxes which use pressurized lubrication systems must show a capability to continue operation for a period of 30 minutes after suffering a loss of oil. This paper reports on methods for assessing reliability of pressurized MGB lubrication systems. Safety risk modeling was conducted for MGB oil system related accidents and incidents in order to analyse the key failure mechanisms and the contributory factors. As such, the dominant failure modes for lubrication systems and key contributing components were identified. The Influence Diagram (ID) approach was then employed to investigate reliability issues of the MGB lubrication systems at the level of primary causal factors. Early indications show significant benefits from this approach where multiple influences would render alternative approaches overly complex. The ID tool can systematically investigate complex context of events, conditions, and influences that are direct triggers of failures. Within this study, an ID model was introduced to describe the interrelationships between MGB lubrication system failure types. In this way the influence of each of these factors on the overall MGB lubrication system reliability may be assessed

Immunomodulatory effects of damnacanthal isolated from roots of Morinda elliptica

Morinda elliptica Ridley (Rubiaceae) has been used traditionally as a medicine to treat various diseases in Malaysia and Southeast Asia. In the present study we investigated the immunomodulatory effects of damnacanthal isolated from the roots of Morinda elliptica. The immunomodulatory effect of this compound was evaluated by using the lymphocyte proliferation assay with mouse thymocytes and human peripheral blood mononuclear cells (PBMC). In addition, the effect of the compound on PBMC cell cycle progression was studied by using flow cytometry. The production of human interleukin-2 and human inteleukin-12 cytokines was also assessed using the enzyme linked immunosorbent assay (ELISA) technique. The lymphocyte proliferation assay showed that damnacanthal was able to activate mouse thymocytes and PBMC at a low concentration (0.468 μg/mL). Moreover, the production of human interleukin-2 and human interleukin-12 cytokines in the culture supernatant from damnacanthal activated lymphocytes was markedly up-regulated at 24 h and sustained until 72 h with a slight decrease with time. A positive correlation was found between the level of these two cytokines and the MTT-based proliferation assay. Based on the above results, damnacanthal can act as an immunomodulatory agent which may be very useful for maintaining a healthy immune system

Genetic characterization of Porcine Circovirus 2 found in Malaysia

Background: Porcine circovirus type 2 is the primary etiological agent associated with a group of complex multi-factorial diseases classified as Porcine Circovirus Associated Diseases (PCVAD). Sporadic cases reported in Malaysia in 2007 caused major economic losses to the 2.2 billion Malaysian ringgit (MYR) (approximately 0.7 billion US dollar) swine industry. The objective of the present study was to determine the association between the presence of PCV2 and occurrences of PCVAD. Results: This study showed that 37 out of 42 farms sampled were positive for PCV2 using PCR screening. Thirteen whole genome of PCV2 isolates from pigs with typical PCVAD symptoms were successfully sequenced. These isolates shared 98.3-99.2% similarities with sequences of isolates from the Netherlands. All thirteen isolates fell into the same clade as PCV2b isolates from other countries. Amino acid sequence analysis of the putative capsid protein (ORF2) of the PCV2 revealed that there are three clusters found in Malaysia, namely cluster 1C and 1A/1B. Of interest, three of the isolates (isolates Mal 005, Mal 006 and Mal 010) had a proline substitution for arginine or isoleucine encoded at nt. position 88-89. Eight of the isolates had mutations at the C terminus of the putative capsid protein suggestive of higher pathogenicity which may account for the high reports of PCVAD clinical symptoms in 2007. Conclusion: Phylogenetic study suggests that there may be a link between movements of animals by import of breeders into the country being the route of entry of the virus. While it is not possible to eradicate the virus from commercial pigs, the swine industry in Malaysia can be safeguarded by control measures implemented throughout the country. These measures should include improved biosecurity, disease surveillance; vaccination as well as enforcement of regulations formulated to control and prevent the spread of this disease on a national scale

Structure of BRCA1-BRCT/Abraxas Complex Reveals Phosphorylation-Dependent BRCT Dimerization at DNA Damage Sites.

BRCA1 accumulation at DNA damage sites is an important step for its function in the DNA damage response and in DNA repair. BRCA1-BRCT domains bind to proteins containing the phosphorylated serine-proline-x-phenylalanine (pSPxF) motif including Abraxas, Bach1/FancJ, and CtIP. In this study, we demonstrate that ionizing radiation (IR)-induces ATM-dependent phosphorylation of serine 404 (S404) next to the pSPxF motif. Crystal structures of BRCT/Abraxas show that phosphorylation of S404 is important for extensive interactions through the N-terminal sequence outside the pSPxF motif and leads to formation of a stable dimer. Mutation of S404 leads to deficiency in BRCA1 accumulation at DNA damage sites and cellular sensitivity to IR. In addition, two germline mutations of BRCA1 are found to disrupt the dimer interface and dimer formation. Thus, we demonstrate a mechanism involving IR-induced phosphorylation and dimerization of the BRCT/Abraxas complex for regulating Abraxas-mediated recruitment of BRCA1 in response to IR.We thank beamline scientists at Diamond Light Source for help during data collection of crystal and SAXS. The crystallization experiments were performed in the Crystallographic X-ray facility at the Department of Biochemistry, University of Cambridge. We are grateful to the Facility Manager, Dr. Dimitri Chirgadze, for his assistance in using these facilities and advice during crystal structure determination. We also thank Dr. Yanfen Hu (University of Texas Health Science Center at San Antonia) for the pFlag-BRCA1 plasmid and Dr. Angela Pacitto (University of Cambridge) for reading the manuscript. We thank Dr. Adriana Paulucci-Holthanuzen (Department of Genetics-MD Anderson Microscopy Core Facility) for assistance with images and analysis. Q.W., T.O. and T.L.B. are funded by the Wellcome Trust (Grant 093167/Z/10/Z). A.P. is an awardee of the Schissler Foundation Fellowship, the Center for Cancer Epigenetics Scholarship and the Andrew Sowell-Wade Huggins Scholarship. This work is supported by the National Institutes of Health grant (CA155025 to B.W) with funds from the University of Texas MD Anderson Cancer Center (IRG, Center for Cancer Epigenetics, Center for Genetics and Genomics Pilot Award). S.M. is funded by the Medical Research Council (grant 98101 to C.V.R.) and C.V.R. is a Royal Society Research Professor. T.K.F and B.X. are supported by National Institutes of Health grant (R01CA138804 to B.X).This is the final version of the article. It first appeared from Cell Press via http://dx.doi.org/10.1016/j.molcel.2015.12.01

Patient-reported adverse drug reactions and drug-drug interactions: a cross-sectional study on Malaysian HIV/AIDS patients

Objective: This study aimed to explore the adverse drug reactions (ADRs) reported by patients and to identify drug-drug interactions (DDIs) among human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients. Subjects and Methods: This cross-sectional study was conducted at the Medication Therapy Adherence Clinic, Hospital Sungai Buloh, an HIV/AIDS referral centre. The patients were randomly selected and were encouraged to describe ADRs caused specifically by any of the prescribed antiretroviral drugs (ARDs). Sociodemographic characteristics were recorded from the patients’ medical records. In addition data on antiretroviral treatment (ART), DDIs and other conventional medication were also documented. Results: A total of 325 randomly selected HIV/AIDS patients with a mean age of 22.94 years participated in the study. The most frequently prescribed ARDs were lamivudine (64.6%), zidovudine (40.6%) and efavirenz (42.5%). Commonly reported ADRs were fatigue (54.8%), allergic reactions (41.5%), weight loss (41.5%), dry mouth (35.1%) and memory loss (35.1%). Female (87.8%), non-complementary and alternative medicine (CAM) users (87.3%) and participants below 50 years old (81.1%) were identified as having a higher prevalence of ADRs compared to males (79.6%), CAM users (78.7%) and participants aged 50 years or more (77.5%). Patient age was found to be significantly associated (p = 0.048) with the ADRs. In addition, a total of 44 cases of DDIs belonging to category D were also found in this study. Conclusions: This study enabled us to identify the most common ADRs and DDIs associated with the use of ART. Safe and effective treatment depends on the healthcare providers’ knowledge of the same

Green drying: continuous dehumidified-air dryer

Non-thermal drying, such as dehumidified-air drying has been introduced to overcome the drawbacks of conventional thermal and direct contact adsorption drying. However, existing approach of this method is not so user friendly as the dehumidified-air cannot be supplied continuously due to the depletion of desiccants. The desiccants also need a high temperature for the regeneration. Therefore, a continuous dehumidified-air dryer is focused in this study. The dehumidified-air was produced alternately by adsorbents, which located in two chambers. The adsorbents were then regenerated at ambient temperature by pressure-swing concepts. This continuous dehumidified-dryer was commissioned by drying A. paniculata, at the dehumidified-air 10 to 30 L/min and 30 to 50°C. The sample was dried at less than 10 hours, and about 75 % of andrographolide had been maintained. The Page model was well describing the drying behaviour, and the diffusivity coefficient was determined as 1.88 x 10-13 m2/s

Quantifying HIV-1 Viral Load with Fluorescence Correlation Spectroscopy

The DVD team is working to develop a cost-effective technique for measuring HIV load in resource-restricted regions. Our client is Dr Phil Thuma and the Macha Research Centre in Zambia. Our design utilizes a fluorescence correlation spectroscopy (FCS) approach, including a protein-engineered probe, custom optics, a field programmable gate array (FPGA), and a graphical display to assess viral load in a patient blood sample. In this talk we will present on the design and testing of our optical FCS system, the method of processing and analyzing the signal, and creation of the user interface display. Our team is currently finalizing the design of each device component and looking towards device integration and prototyping in the Fall of 2020.https://mosaic.messiah.edu/engr2020/1015/thumbnail.jp

Hubungan antara Pembangunan Penerapan Nilai dalam Pendidikan Abad Ke-21 dengan Pembentukan Sahsiah Murid Sekolah Kurang Murid (SKM) Luar Bandar di Sabah

Penerapan nilai dalam pendidikan abad ke-21 amat penting bagi membentuk sahsiah murid yang mapan dalam pelbagai aspek seperti yang digariskan dalam Falsafah pendidikan Kebangsaan (FPK). Kajian korelasi ini dijalankan bagi mengkaji hubungan pembangunan penerapan nilai dalam pendidikan abad ke-21 dengan pembentukan sahsiah murid Sekolah Kurang Murid (SKM) luar bandar di Sabah. Kajian ini menggunakan reka bentuk bukan eksperimen dan kaedah kuantitatif. Seramai 209 orang guru SKM dijadikan sampel dalam kajian ini yang dipilih menggunakan kaedah pensamplean rawak mudah. Instrumen soal selidik pula digunakan bagi mengukur variabel-variabel kajian. Data mentah dianalisis menggunakan perisian Statistical Package for Social Sciences (SPSS) dengan menggunakan analisis statistik inferensi yang melibatkan ujian Korelasi Pearson. Hasil analisis menunjukkan terdapat hubungan positif signifikan yang kuat antara pembangunan penerapan nilai dalam pendidikan abad ke-21 dengan pembentukan sahsiah murid Sekolah Kurang Murid (SKM) luar bandar di Sabah (r=0.88, P<0.05). Dapatan kajian ini memberi maklumat berguna berkaitan dengan penerapan nilai dalam pendidikan abad ke-21 dan pembentukan sahsiah murid yang diharap dapat memberikan sumbangan ke arah memperkasakan sistem pendidikan kebangsaan