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Fulltext Plasma Cell Leukemia with Successful Upfront Venetoclax in Combination with Allogeneic Transplantation

Tang ASO, Ahmad Asnawi AW, Koh AZY, Chong SL, Liew PK, Selvaratnam V, et al.

Am J Case Rep, 2023 Mar 08;24:e938868.
PMID: 36882990 DOI: 10.12659/AJCR.938868

BACKGROUND Plasma cell leukemia (PCL) is an aggressive form of plasma cell neoplasm. We report the first case of primary PCL successfully treated with upfront novel agents consisting of Venetoclax and daratumumab in combination with intensive chemotherapy and allogeneic transplantation. CASE REPORT A 59-year-old woman presented with epistaxis, gum bleeding, and blurred vision. On examination, she appeared pale, with multiple petechiae and hepatomegaly. Fundoscopy revealed retinal hemorrhages. Laboratory investigations revealed bicytopenia and leukocytosis, with mild coagulopathy and hypofibrinogenemia. Elevated globulin and calcium levels were also observed. Serum protein electrophoresis demonstrated IgG lambda paraproteinemia, with a serum-free light chain kappa-to-lambda ratio of 0.074. A skeletal survey revealed the presence of lytic lesions. Bone marrow investigations confirmed the presence of lambda-light-chain-restricted clonal plasma cells. FISH detected t(11;14) and 17p13.1 deletion. Therefore, a final diagnosis of primary PCL was made. The patient received 1 cycle of bortezomib, cyclophosphamide, and dexamethasone (VCD) and 5 cycles of Venetoclax-VCD, followed by an unsuccessful stem cell mobilization. One cycle of daratumumab in combination with bortezomib, lenalidomide, and dexamethasone (VRD) was then given. The patient achieved complete remission. She underwent allogeneic stem cell transplantation of an HLA-matched sibling donor. Post-transplant marrow assessment showed disease remission and absence of t(11;14) and 17p deletions. She was administered pamidronate and lenalidomide maintenance. She remained clinically well with a good performance status and no active graft-versus-host disease 18 months after transplant. CONCLUSIONS The success of our patient in achieving complete remission has highlighted the efficacy and safety of this novel therapy in the front-line management of PCL.
Fulltext Evolution of structural and electronic properties standardized description in rhenium disulfide at the bulk-monolayer transition

Baglov A, Khoroshko L, Zhoidzik A, Dong M, Weng Q, Kazi M, et al.

Heliyon, 2024 Apr 15;10(7):e28646.
PMID: 38586325 DOI: 10.1016/j.heliyon.2024.e28646

The structural and electronic properties of ReS2 different forms - three-dimensional bulk and two-dimensional monolayer - were studied within density functional theory and pseudopotentials. A method for standardizing the description of bulk unit cells and "artificial" slab unit cells for DFT research has been proposed. The preference of this method for studying zone dispersion has been shown. The influence of the vacuum layer thickness on specified special high-symmetry points is discussed. Electron band dispersion in both classical 3D Brillouin zones and transition to 2D Brillouin zones in the proposed two-dimensional approach using the Niggli form of the unit cell was compared. The proposed two-dimensional approach is preferable for low-symmetry layered crystals such as ReS2. It was established that the bulk ReS2 is a direct gap semiconductor (band gap of 1.20 eV), with the direct transition lying in the X point of the first Brillouin zone, and it is in good agreement with published experimental data. The reduction in material dimension from bulk to monolayer was conducted with an increasing band gap up to 1.45 eV, with a moving direct transition towards the Brillouin zone center. The monolayer of ReS2 is a direct-gap semiconductor in a wide range of temperatures, excluding only a narrow range at low temperatures, where it comes as a quasi-direct gap semiconductor. The transition, situated directly in the Γ-point, lies 3.3 meV below the first direct transition located near this point. The electronic density of states of ReS2 in the bulk and monolayer cases of ReS2 were analyzed. The molecular orbitals were built for both types of ReS2 structures as well as the electron difference density maps. For all types of ReS2 structures, an analysis of populations according to Mulliken and Voronoi was carried out. All calculated data is discussed in the context of weak quantum confinement in the 2D case.
Fulltext Physicochemical characteristics of grease-trap wastewater with different potential mechanisms of FOG solid formation, separation, and accumulation inside grease traps

Tang LY, Wong NH, Chieng TA, Kiu AKJ, Choo CS, Li Y, et al.

Water Res, 2024 Jun 01;256:121607.
PMID: 38640568 DOI: 10.1016/j.watres.2024.121607

This work investigates the physicochemical characteristics of grease-trap wastewater discharged from a large community market. It proposes potential mechanisms of fat, oil, and grease (FOG) solid formation, separation, and accumulation inside grease traps. Sixty-four samples, i.e., the floated scum, suspended solid-liquid wastewater, and settled sludge, were collected from the grease-trap inlet and outlet chambers. A lower pH of 5-6 at 25-29 °C inside the grease trap than those reported under the sewer conditions (pH 6-7) was revealed. A significant difference in solid and dissolved constituents was also discovered between the inlet and outlet chambers, indicating that the baffle wall could affect the separation mechanism. The sludge samples had 1.5 times higher total solids (TS) than the scum samples, i.e., 0.225 vs. 0.149 g g-1 TS, revealing that the sludge amount impacted more significantly the grease trap capacity and operation and maintenance. In contrast, the scum samples had 1.4 times higher volatile solids (VS) than the sludge samples, i.e., 0.134 vs. 0.096 g g-1 VS, matching with the 64.2 vs. 29.7% of carbon content from CHN analysis. About 2/3 of the free fatty acids (FFAs) with palmitic acids were the primary saturated FFAs, while the remaining 1/3 of unsaturated FFAs were found in the solid and liquid samples. Although up to 0.511 g g-1 FOG can be extracted from the scum samples, none from the sludge samples. More diverse minerals/metals other than Na, Cl, and Ca were found in the sludge samples than in the scum samples. Grease-trap FOG solids and open drain samples exhibited similar physicochemical properties to those reported in the literature. Four potential mechanisms (crystallization, emulsification, saponification, and baffling) were presented. This work offers insights into the physicochemical properties of grease-trap wastewater that can help explore its FOG solid formation, separation, and accumulation mechanisms inside a grease trap.
Fulltext Predominance and emergence of clones of hospital-acquired methicillin-resistant Staphylococcus aureus in Malaysia

Ghaznavi-Rad E, Nor Shamsudin M, Sekawi Z, Khoon LY, Aziz MN, Hamat RA, et al.

J Clin Microbiol, 2010 Mar;48(3):867-72.
PMID: 20089756 DOI: 10.1128/JCM.01112-09

We define the epidemiology of predominant and sporadic methicillin-resistant Staphylococcus aureus (MRSA) strains in a central teaching and referral hospital in Kuala Lumpur, Malaysia. This is done on the basis of spa sequencing, multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) typing, and virulence gene profiling. During the period of study, the MRSA prevalence was 44.1%, and 389 MRSA strains were included. The prevalence of MRSA was found to be significantly higher in the patients of Indian ethnicity (P < 0.001). The majority (92.5%) of the isolates belonged to ST-239, spa type t037, and possessed the type III or IIIA SCCmec. The arginine catabolic mobile element (ACME) arcA gene was detected in three (1.05%) ST-239 isolates. We report the first identification of ACME arcA gene-positive ST-239. Apart from this predominant clone, six (1.5%) isolates of ST-22, with two related spa types (t032 and t4184) and a singleton (t3213), carrying type IVh SCCmec, were detected for the first time in Asia. A limited number of community-acquired (CA) MRSA strains were also detected. These included ST-188/t189 (2.1%), ST-1/t127 (2.3%), and ST-7/t091 (1%). Panton-Valentin leukocidin (PVL) was detected in all ST-1 and ST-188 strains and in 0.7% of the ST-239 isolates. The majority of the isolates carried agr I, except that ST-1 strains were agr III positive. Virulence genes seg and sei were seen only among ST-22 isolates. In conclusion, current results revealed the predominance of ST-239-SCCmec III/IIIA and the penetration of ST-22 with different virulence gene profiles. The emergence in Malaysia of novel clones of known epidemic and pathogenic potential should be taken seriously.
Fulltext Bioactive 2-(Methyldithio)Pyridine-3-Carbonitrile from Persian Shallot (Allium stipitatum Regel.) Exerts Broad-Spectrum Antimicrobial Activity

Karunanidhi A, Ghaznavi-Rad E, Jeevajothi Nathan J, Joseph N, Chigurupati S, Mohd Fauzi F, et al.

Molecules, 2019 Mar 13;24(6).
PMID: 30871159 DOI: 10.3390/molecules24061003

Antibiotic resistance is a problem that continues to challenge the healthcare sector, especially in clinically significant pathogens like methicillin-resistant Staphylococcus aureus (MRSA). Herein is described the isolation and structure elucidation of a bioactive compound from Allium stipitatum with antimicrobial activity. Crude Allium stipitatum dichloromethane extract (ASDE) was subjected to systematic purification by chromatographic procedures to afford various bioactive fractions. A fraction that exhibited anti-MRSA activity (4 µg·mL-1) was further characterized to determine the structure. The structure of the compound was elucidated as 2-(methyldithio)pyridine-3-carbonitrile (2-Medpy-3-CN). The 2-Medpy-3-CN compound, which was screened for antimicrobial activity, exhibited minimum inhibitory concentrations (MICs) in the range of 0.5 to >64 µg·mL-1 for tested bacterial species and 0.25 to 2 µg·mL-1 for Candida spp. Further studies are important to confirm the drug target and mechanism of action.
The development of a novel, multilingual IBD knowledge questionnaire for Asian patients with inflammatory bowel disease

Razima Wan Ibrahim N, Danaee M, Khoo XH, Sithambaram S, Shahrani S, Hwong-Ruey Leow A, et al.

BMC Gastroenterol, 2023 May 25;23(1):185.
PMID: 37231353 DOI: 10.1186/s12876-023-02817-0

BACKGROUND: Inflammatory bowel disease is an uncommon disease in developing nations whereby patient's knowledge on the disease may be limited. The CCKNOW questionnaire, a widely known questionnaire to assess patient's knowledge on the disease, may be too complex to comprehend for patients in developing countries. The aim of this study is to develop a new tool known as AIBDKQ questionnaire to evaluate the local inflammatory bowel disease patient's knowledge.
METHODS: This was a prospective study carried out in four phases. In phase 1, three gastroenterologists with expertise in IBD generated a total of 21 questions related to the general knowledge of the disease in the English language. Phase 2 involved content and face validity whereby the questions were further validated by other gastroenterologists. In phase 3, the validated questions were translated into three languages namely Malay, Mandarin and Tamil which are commonly used in Malaysia. In phase 4 (statistical validity), administration of the questionnaires to patients and hospital staff were conducted to assess the construct validity, discriminative ability, predictive validity and reliability of the questionnaires.
RESULTS: A total of 21 questions were generated initially. Further evaluation indicated that 20 items had adequate kappa and content validity index for relevance (CVI: 0.714 to 1, Kapp: 0.645 to 1) and clarity (CVI: 0.714 to 1, Kapp: 0.645 to 1). The questionnaires in four languages were administered to 213 patients to assess the construct validity. Six items were removed (three for low communality, one for small loading factors, two for cross loading), resulting in 16 final questions. Assessment with 34 hospital staff involving nurses, doctors and clerks showed significant differences in knowledge between the groups (F = 14.007, p
Fulltext Estimating direct and spill-over impacts of political elections on COVID-19 transmission using synthetic control methods

Lim JT, Maung K, Tan ST, Ong SE, Lim JM, Koo JR, et al.

PLoS Comput Biol, 2021 May;17(5):e1008959.
PMID: 34043622 DOI: 10.1371/journal.pcbi.1008959

Mass gathering events have been identified as high-risk environments for community transmission of coronavirus disease 2019 (COVID-19). Empirical estimates of their direct and spill-over effects however remain challenging to identify. In this study, we propose the use of a novel synthetic control framework to obtain causal estimates for direct and spill-over impacts of these events. The Sabah state elections in Malaysia were used as an example for our proposed methodology and we investigate the event's spatial and temporal impacts on COVID-19 transmission. Results indicate an estimated (i) 70.0% of COVID-19 case counts within Sabah post-state election were attributable to the election's direct effect; (ii) 64.4% of COVID-19 cases in the rest of Malaysia post-state election were attributable to the election's spill-over effects. Sensitivity analysis was further conducted by examining epidemiological pre-trends, surveillance efforts, varying synthetic control matching characteristics and spill-over specifications. We demonstrate that our estimates are not due to pre-existing epidemiological trends, surveillance efforts, and/or preventive policies. These estimates highlight the potential of mass gatherings in one region to spill-over into an outbreak of national scale. Relaxations of mass gathering restrictions must therefore be carefully considered, even in the context of low community transmission and enforcement of safe distancing guidelines.
Fulltext Investigation of the association between foot-and-mouth disease clinical signs and abattoir serological data in large ruminants in northern Lao People's Democratic Republic

Gee E, Young JR, Khounsy S, Phommachanh P, Christensen P, Theppangna W, et al.

Front Vet Sci, 2024;11:1392885.
PMID: 39135894 DOI: 10.3389/fvets.2024.1392885

Foot-and-mouth disease (FMD) is a highly infectious and endemic disease in Lao PDR. However, surveillance is weak, and outbreaks are not routinely reported. To address this, serum samples were routinely collected from cattle and buffalo from provincial abattoirs between November 2021 and December 2022. A total of 2,663 serum samples were collected from large ruminants (n = 1,625 cattle; n = 1,038 buffalo) from 17 provinces. Samples were tested for specific antibodies directed against FMD non-structural protein (NSP) to determine the proportion of animals exposed to FMD virus. In addition to sampling from abattoirs, further independent data was collected to report clinical signs and outcomes from 94 districts in 12 northern provinces. These incident reports were recorded by district staff using a Google Form and summarised monthly in the National Animal Disease Reporting System. Information was collected on species, incident date, herd size, location and which clinical signs the animals presented. Overall, 46% of the tested animals returned a positive result using ID Screen® FMD NSP Competition ELISA. Results from serological testing were then compared with reported clinical signs from the same district. In districts reporting 'mouth problems' (regardless of other clinical signs) the median FMD seroprevalence was 49.7%, compared to 31.6% in districts not reporting mouth problems (p = 0.021). This finding suggests that reporting clinical cases of 'mouth problems' could be a potential predictor of FMD infection at a district level in cattle and buffalo in Lao PDR. Furthermore, in districts reporting 'fever', 'mouth problems', and 'nose/mouth secretions' together, the median FMD seroprevalence was 46.2%, compared to 24.4% in districts not reporting these signs (p = 0.033). In districts reporting 'mouth problems' and 'nose/mouth secretions' the median FMD seroprevalence was 49.4%, compared to 25.5% in districts not reporting these signs (p = 0.037). In districts reporting both 'fever' and 'mouth problems,' the median FMD seroprevalence was 46.4% compared to 25% in districts not reporting these signs (p = 0.017). Based on serological data generated by abattoir surveillance, this study identified clinical signs most predictive of FMD seroprevalence. These novel findings can be used to guide passive surveillance efforts in the future specifically in northern Laos and help support improved FMD surveillance more broadly in FMD endemic countries in Southeast Asia.
Feral cats and risk for Nipah virus transmission

Epstein JH, Abdul Rahman S, Zambriski JA, Halpin K, Meehan G, Jamaluddin AA, et al.

Emerg Infect Dis, 2006 Jul;12(7):1178-9.
PMID: 16848051
Fulltext Growing crystals and studying structure and electronic properties of Cu2ZnGe(SхSe1-x)4 compositions

Bodnar IV, Khoroshko VV, Yashchuk VA, Gremenok VF, Kazi M, Khandaker MU, et al.

Heliyon, 2023 Nov;9(11):e22533.
PMID: 38074888 DOI: 10.1016/j.heliyon.2023.e22533

Single crystals of Cu2ZnGeSe4 and Cu2ZnGeS4 solid solutions were developed and successfully obtained using the chemical vapor transfer method, with iodine acting as a transporter. The structure, compositional dependences of lattice parameters, pycnometric and X-ray densities and microhardness were determined. The chemical composition determined by the X-ray microanalysis satisfactorily corresponds to the nominal one with a tolerance of ±5 %. The XRD analysis showed that all the obtained compounds and their solid solutions have unit cell described by tetragonal symmetry. The attice parameters were found to be а = 5.342 ± 0.005 Å, с = 10.51 ± 0.01 Å for the Сu2ZnGeS4 compound and а = 5.607 ± 0.005 Å, с = 11.04 ± 0.01 Å for the Cu2ZnGeSe4, respectively. Structural studies confirmed the validity of the Vegard's law in relation to the obtained samples. The pycnometric densities of ∼4.28 g/cm3 for the Cu2ZnGeS4 and ∼5.46 g/cm3 for the Cu2ZnGeSe4 were found to be slightly less than their X-ray densities of ∼4.32 g/cm3 and ∼5.52 g/cm3, respectively. The maximum microhardness of ∼398 kg/mm2 for these solid solutions corresponds to x = 0.60. The melt point of the solid solutions increases from ∼1180 °C for the Сu2ZnGeSe4 up to ∼1400 °C for the Сu2ZnGeS4. Based on X-ray fluorescence analysis and DTA data, the phase diagram of the Cu2ZnGeSe4-Cu2ZnGeS4 system was constructed. Analysis of the obtained diagram indicates its first type according to Rozbom's classification.
Fulltext Measuring population health and quality of life: Developing and testing of the significant quality of life measure (SigQOLM)

Bujang MA, Lai WH, Hon YK, Yap EPP, Tiong XT, Ratnasingam S, et al.

Heliyon, 2023 Dec;9(12):e22668.
PMID: 38149205 DOI: 10.1016/j.heliyon.2023.e22668

Quality of life (QOL) should ideally be determined by a broader spectrum of measurable parameters. This study aims to develop and validate a study instrument that is designed to determine a holistic measure of health and non-health aspects of QOL, and it is called the 'Significant Quality of Life Measure' (SigQOLM). This study involves five phases which aim to (i) explore and understand the subject matter content, (ii) develop a questionnaire, (iii) assess its content validity and face validity, (iv) conduct a pilot study, and lastly (v) perform a field-test by using the questionnaire. For the field-testing phase, a cross-sectional study was conducted which elicited responses from healthcare workers via a self-administered survey for all the SigQOLM items. Based on the results, the overall framework of the SigQOLM consists of four elements, 18 domains with 69 items. The element of "Health" is measured by nine domains, while "Relationships", "Functional activities, and "Survival" are measured by three domains respectively. The SigQOLM has been developed successfully and then validated with a high level of reliability, validity, and overall model fit. Therefore, the SigQOLM will provide researchers and policymakers another viable option to elicit a more comprehensive outcome measure of QOL which shall then enable them to implement specific interventions for improving the QOL of all the people, both healthy or otherwise.
Fulltext Routine blood parameters of dengue infected children and adults. A meta-analysis

Low GK, Jiee SF, Masilamani R, Shanmuganathan S, Rai P, Manda M, et al.

Pathog Glob Health, 2023 Sep;117(6):565-589.
PMID: 36593636 DOI: 10.1080/20477724.2022.2161864

The World Health Organization (WHO) has revised dengue case classification in 2009 to better reflect the severity of the disease. However, there was no comprehensive meta-analysis of pooled routine blood parameters according to the age or the categories of the 2009 WHO classification. This study aimed to meta-analyze the routine blood parameters of dengue infected children and adults. Electronic search was performed with eligible articles included for review. Meta-analysis was conducted for six blood parameters stratified into children, adults and all ages, which were further grouped into the three 2009 WHO case classifications (dengue without warning signs, DwoWS; dengue with warning signs, DwWS; severe dengue, SD), non-severe dengue (non-SD) and 'All' cases. A total of 55 articles were included in the meta-analysis. Fifteen studies were conducted in the children's age category, 31 studies in the adult category and nine studies in all ages. The four selected pooled blood parameters for children were white blood cell (WBC) (×103/L) with 5.11 (SD), 5.64 (DwWS), 5.52 (DwoWS) and 4.68 (Non-SD) hematocrit (HCT) (%) with 36.78 (SD), 40.70 (DwWS), 35.00 (DwoWS) and 29.78 (Non-SD) platelet (PLT) (×103/µL) with 78.66 (SD), 108.01 (DwWS), 153.47 (DwoWS) and 108.29 (non-SD); and aspartate aminotransferase (AST) (/µL) with 248.88 (SD), 170.83 (DwWS), 83.24 (DwoWS) and 102.99 (non-SD). For adult, WBC were 4.96 (SD), 6.44 (DwWS), 7.74 (DwoWS) and 3.61 (non-SD); HCT were 39.50 (SD), 39.00 (DwWS), 37.45 (DwoWS) and 41.68 (non-SD); PLT were 49.62 (SD), 96.60 (DwWS), 114.37 (DwoWS) and 71.13 (non-SD); and AST were 399.50 (SD), 141.01 (DwWS), 96.19 (DwoWS) and 118.13 (non-SD). These blood parameters could not differentiate between each dengue severity according to the WHO 2009 classification, SD, DwoWS, DwWS and non-SD, because the timing of blood drawing was not known and there was an overlapping confidence interval among the clinical classification. Hence, these pooled blood parameter values could not be used to guide clinicians in management and did not correlate with severity as in previous scientific literatures and guidelines.
Fulltext Increasing mine waste will induce land cover change that results in ecological degradation and human displacement

Owen JR, Kemp D, Lechner AM, Ang Li Ern M, Lèbre É, Mudd GM, et al.

J Environ Manage, 2024 Feb;351:119691.
PMID: 38064991 DOI: 10.1016/j.jenvman.2023.119691
Fulltext Purification and Characterization of Gum-Derived Polysaccharides of Moringa oleifera and Azadirachta indica and Their Applications as Plant Stimulants and Bio-Pesticidal Agents

Shobana N, Prakash P, Samrot AV, Jane Cypriyana PJ, Kajal P, Sathiyasree M, et al.

Molecules, 2022 Jun 09;27(12).
PMID: 35744846 DOI: 10.3390/molecules27123720

Plant gums are bio-organic substances that are derived from the barks of trees. They are biodegradable and non-adverse complex polysaccharides that have been gaining usage in recent years due to a number of advantages they contribute to various applications. In this study, gum was collected from Moringa oleifera and Azadirachta indica trees, then dried and powdered. Characterizations of gum polysaccharides were performed using TLC, GC-MS, NMR, etc., and sugar molecules such as glucose and xylose were found to be present. Effects of the gums on Abelmoschus esculentus growth were observed through root growth, shoot growth, and biomass content. The exposure of the seeds to the plant gums led to bio stimulation in the growth of the plants. Poor quality soil was exposed to the gum polysaccharide, where the polysaccharide was found to improve soil quality, which was observed through soil analysis and SEM analysis of soil porosity and structure. Furthermore, the plant gums were also found to have bio-pesticidal activity against mealybugs, which showed certain interstitial damage evident through histopathological analysis.
Fulltext Pteropid bats are confirmed as the reservoir hosts of henipaviruses: a comprehensive experimental study of virus transmission

Halpin K, Hyatt AD, Fogarty R, Middleton D, Bingham J, Epstein JH, et al.

Am J Trop Med Hyg, 2011 Nov;85(5):946-51.
PMID: 22049055 DOI: 10.4269/ajtmh.2011.10-0567

Bats of the genus Pteropus have been identified as the reservoir hosts for the henipaviruses Hendra virus (HeV) and Nipah virus (NiV). The aim of these studies was to assess likely mechanisms for henipaviruses transmission from bats. In a series of experiments, Pteropus bats from Malaysia and Australia were inoculated with NiV and HeV, respectively, by natural routes of infection. Despite an intensive sampling strategy, no NiV was recovered from the Malaysian bats and HeV was reisolated from only one Australian bat; no disease was seen. These experiments suggest that opportunities for henipavirus transmission may be limited; therefore, the probability of a spillover event is low. For spillover to occur, a range of conditions and events must coincide. An alternate assessment framework is required if we are to fully understand how this reservoir host maintains and transmits not only these but all viruses with which it has been associated.
The degree of astrocyte activation in multiple system atrophy is inversely proportional to the distance to α-synuclein inclusions

Radford R, Rcom-H'cheo-Gauthier A, Wong MB, Eaton ED, Quilty M, Blizzard C, et al.

Mol. Cell. Neurosci., 2015 Mar;65:68-81.
PMID: 25731829 DOI: 10.1016/j.mcn.2015.02.015

Multiple system atrophy (MSA) exhibits widespread astrogliosis together with α-synuclein (α-syn) glial cytoplasmic inclusions (GCIs) in mature oligodendrocytes. We quantified astrocyte activation by morphometric analysis of MSA cases, and investigated the correlation to GCI proximity. Using Imaris software, we obtained "skinned" three-dimensional models of GFAP-positive astrocytes in MSA and control tissue (n=75) from confocal z-stacks and measured the astrocyte process length and thickness and radial distance to the GCI. Astrocytes proximal to GCI-containing oligodendrocytes (r<25μm) had significantly (p, 0.05) longer and thicker processes characteristic of activation than distal astrocytes (r>25μm), with a reciprocal linear correlation (m, 90μm(2)) between mean process length and radial distance to the nearest GCI (R(2), 0.7). In primary cell culture studies, α-syn addition caused ERK-dependent activation of rat astrocytes and perinuclear α-syn inclusions in mature (MOSP-positive) rat oligodendrocytes. Activated astrocytes were also observed in close proximity to α-syn deposits in a unilateral rotenone-lesion mouse model. Moreover, unilateral injection of MSA tissue-derived α-syn into the mouse medial forebrain bundle resulted in widespread neuroinflammation in the α-syn-injected, but not sham-injected hemisphere. Taken together, our data suggests that the action of localized concentrations of α-syn may underlie both astrocyte and oligodendrocyte MSA pathological features.
Current trend of pneumococcal serotypes distribution and antibiotic susceptibility pattern in Malaysian hospitals

Yasin RM, Zin NM, Hussin A, Nawi SH, Hanapiah SM, Wahab ZA, et al.

Vaccine, 2011 Aug 5;29(34):5688-93.
PMID: 21723357 DOI: 10.1016/j.vaccine.2011.06.004

From January 2008 to December 2009, 433 Streptococcus pneumoniae strains were examined to determine the serotype distribution and susceptibility to selected antibiotics. About 50% of them were invasive isolates. The strains were isolated from patients of all age groups and 33.55% were isolated from children below 5 years. The majority was isolated from blood (48.53%) and other sterile specimens (6.30%). Community acquired pneumonia (41.70%) is the most common diagnosis followed by sepsis (9.54%). Serotyping was done using Pneumotest Plus-Kit and antibiotic susceptibility pattern was determined by modified Kirby-Bauer disk diffusion method and measurement of minimum inhibitory concentration (MIC) using E-test strip. Ten most common serotypes were 19F (15.02%), 6B (10.62%), 19A (6.93%), 14 (6.70%), 1 (5.08%), 6A (5.08%), 23F (4.85%), 18C (3.93%), 3 (2.08%) and 5 (1.85%). Penicillin MIC ranged between ≤ 0.012-4 μg/ml with MIC₉₀ of 1 μg/ml. Penicillin resistant rate is 31.78%. The majority of penicillin less-susceptible strains belonged to serotype 19F followed by 19A and 6B. Based on the serotypes distribution 22 (44.00%), 28 (56.00%) and 39 (78.00%) of the invasive isolates from children ≤ 2 years were belonged to serotypes included in the PCV7, PCV10 and PCV13, respectively.
Fulltext DRD and GRIN2B polymorphisms and their association with the development of impulse control behaviour among Malaysian Parkinson's disease patients

Zainal Abidin S, Tan EL, Chan SC, Jaafar A, Lee AX, Abd Hamid MH, et al.

BMC Neurol, 2015;15:59.
PMID: 25896831 DOI: 10.1186/s12883-015-0316-2

Impulse control disorder (ICD) and behaviours (ICB) represent a group of behavioural disorders that have become increasingly recognised in Parkinson's disease (PD) patients who previously used dopaminergic medications, particularly dopamine agonists and levodopa. It has been suggested that these medications can lead to the development of ICB through the abnormal modulation of dopaminergic transmission and signalling in the mesocorticolimbic dopaminergic system. Several studies have reported an association between polymorphisms in the dopamine receptor (DRD) and N-methyl-D-aspartate 2B (GRIN2B) genes with the development of ICB in PD (PD-ICB) patients. Thus, this study aimed to investigate the association of selected polymorphisms within the DRD and GRIN2B genes with the development of ICB among PD patients using high resolution melt (HRM) analysis.
Fulltext Management of patients with liver derangement during the COVID-19 pandemic: an Asia-Pacific position statement

Wong GL, Wong VW, Thompson A, Jia J, Hou J, Lesmana CRA, et al.

Lancet Gastroenterol Hepatol, 2020 08;5(8):776-787.
PMID: 32585136 DOI: 10.1016/S2468-1253(20)30190-4

The COVID-19 pandemic has spread rapidly worldwide. It is common to encounter patients with COVID-19 with abnormal liver function, either in the form of hepatitis, cholestasis, or both. The clinical implications of liver derangement might be variable in different clinical scenarios. With growing evidence of its clinical significance, it would be clinically helpful to provide practice recommendations for various common clinical scenarios of liver derangement during the COVID-19 pandemic. The Asia-Pacific Working Group for Liver Derangement during the COVID-19 Pandemic was formed to systematically review the literature with special focus on the clinical management of patients who have been or who are at risk of developing liver derangement during this pandemic. Clinical scenarios covering the use of pharmacological treatment for COVID-19 in the case of liver derangement, and assessment and management of patients with chronic hepatitis B or hepatitis C, non-alcoholic fatty liver disease, liver cirrhosis, and liver transplantation during the pandemic are discussed.
Fulltext Two Secreted Proteoglycans, Activators of Urothelial Cell-Cell Adhesion, Negatively Contribute to Bladder Cancer Initiation and Progression

Papadaki V, Asada K, Watson JK, Tamura T, Leung A, Hopkins J, et al.

Cancers (Basel), 2020 Nov 13;12(11).
PMID: 33202923 DOI: 10.3390/cancers12113362

Osteomodulin (OMD) and proline/arginine-rich end leucine repeat protein (PRELP) are secreted extracellular matrix proteins belonging to the small leucine-rich proteoglycans family. We found that OMD and PRELP were specifically expressed in umbrella cells in bladder epithelia, and their expression levels were dramatically downregulated in all bladder cancers from very early stages and various epithelial cancers. Our in vitro studies including gene expression profiling using bladder cancer cell lines revealed that OMD or PRELP application suppressed the cancer progression by inhibiting TGF-β and EGF pathways, which reversed epithelial-mesenchymal transition (EMT), activated cell-cell adhesion, and inhibited various oncogenic pathways. Furthermore, the overexpression of OMD in bladder cancer cells strongly inhibited the anchorage-independent growth and tumorigenicity in mouse xenograft studies. On the other hand, we found that in the bladder epithelia, the knockout mice of OMD and/or PRELP gene caused partial EMT and a loss of tight junctions of the umbrella cells and resulted in formation of a bladder carcinoma in situ-like structure by spontaneous breakdowns of the umbrella cell layer. Furthermore, the ontological analysis of the expression profiling of an OMD knockout mouse bladder demonstrated very high similarity with those obtained from human bladder cancers. Our data indicate that OMD and PRELP are endogenous inhibitors of cancer initiation and progression by controlling EMT. OMD and/or PRELP may have potential for the treatment of bladder cancer.

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