Characteristics of patients admitted with heart failure: Insights from the first Malaysian Heart Failure Registry.

AIMS: Heart failure (HF) is a growing health problem, yet there are limited data on patients with HF in Malaysia. The Malaysian Heart Failure (MY-HF) Registry aims to gain insights into the epidemiology, aetiology, management, and outcome of Malaysian patients with HF and identify areas for improvement within the national HF services. METHODS AND RESULTS: The MY-HF Registry is a 3-year prospective, observational study comprising 2717 Malaysian patients admitted for acute HF. We report the description of baseline data at admission and outcomes of index hospitalization of these patients. The mean age was 60.2 ± 13.6 years, 66.8% were male, and 34.3% had de novo HF. Collectively, 55.7% of patients presented with New York Heart Association (NYHA) Class III or IV; ischaemic heart disease was the most frequent aetiology (63.2%). Most admissions (87.3%) occurred via the emergency department, with 13.7% of patients requiring intensive care, and of these, 21.8% needed intubation. The proportion of patients receiving guideline-directed medical therapy increased at discharge (84.2% vs. 93.6%). The median length of stay (LOS) was 5 days, and in-hospital mortality was 2.9%. Predictors of LOS and/or in-hospital mortality were age, NYHA class, estimated glomerular filtration rate, and comorbid anaemia. LOS and in-hospital mortality were similar regardless of ejection fraction. CONCLUSIONS: The MY-HF Registry showed that the HF population in Malaysia is younger, predominantly male, and ischaemic-driven and has good prospects with hospitalization for optimization of treatment. These findings suggest a need to reassess current clinical practice and guide resource allocation to improve patient outcomes.

Application of novel nanobubble-contained electrolyzed catalytic water to cleanup petroleum-hydrocarbon contaminated soils and groundwater: A pilot-scale and performance evaluation study.

Soil and groundwater contamination caused by petroleum hydrocarbons is a severe environmental problem. In this study, a novel electrolyzed catalytic system (ECS) was developed to produce nanobubble-contained electrolyzed catalytic (NEC) water for the remediation of petroleum-hydrocarbon-contaminated soils and groundwater. The developed ECS applied high voltage (220 V) with direct current, and titanium electrodes coated with iridium dioxide were used in the system. The developed ECS prototype contained 21 electrode pairs (with a current density of 20 mA/cm2), which were connected in series to significantly enhance the hydroxyl radical production rate. Iron-copper hybrid oxide catalysts were laid between each electrode pair to improve the radical generation efficiency. The electron paramagnetic resonance (EPR) and Rhodamine B (RhB) methods were applied for the generated radical species and concentration determination. During the operation of the ECS, high concentrations of nanobubbles (nanobubble density = 3.7 × 109 particles/mL) were produced due to the occurrence of the cavitation mechanism. Because of the negative zeta potential and nano-scale characteristics of nanobubbles (mean diameter = 28 nm), the repelling force would prevent the occurrence of bubble aggregations and extend their lifetime in NEC water. The radicals produced after the bursting of the nanobubbles would be beneficial for the increase of the radical concentration and subsequent petroleum hydrocarbon oxidation. The highly oxidized NEC water (oxidation-reduction potential = 887 mV) could be produced with a radical concentration of 9.5 × 10-9 M. In the pilot-scale study, the prototype system was applied to clean up petroleum-hydrocarbon polluted soils at a diesel-oil spill site via an on-site slurry-phase soil washing process. The total petroleum hydrocarbon (TPH)-contaminated soils were excavated and treated with the NEC water in a slurry-phase reactor. Results show that up to 74.4% of TPH (initial concentration = 2846 mg/kg) could be removed from soils after four rounds of NEC water treatment (soil and NEC water ratio for each batch = 10 kg: 40 L and reaction time = 10 min). Within the petroleum-hydrocarbon plume, one remediation well (RW) and two monitor wells (located 1 m and 3 m downgradient of the RW) were installed along the groundwater flow direction. The produced NEC water was injected into the RW and the TPH concentrations in groundwater (initial concentrations = 12.3-15.2 mg/L) were assessed in these three wells. Compared to the control well, TPH concentrations in RW and MW1 dropped to below 0.4 and 2.1 mg/L after 6 m3 of NEC water injection in RW, respectively. Results from the pilot-scale study indicate that the NEC water could effectively remediate TPH-contaminated soils and groundwater without secondary pollution production. The main treatment mechanisms included (1) in situ chemical oxidation via produced radicals, (2) desorption of petroleum hydrocarbons from soil particles due to the dispersion of nanobubbles into soil pores, and (3) enhanced TPH oxidation due to produced radicals and energy after nanobubble bursting.

From Primary to Tertiary Care: Expert Position Statements to Guide Heart Failure with Preserved Ejection Fraction Diagnosis.

Globally, heart failure with preserved ejection fraction (HFpEF) is quickly becoming the dominant form of heart failure (HF) in ageing populations. However, there are still multiple gaps and challenges in making a firm diagnosis of HFpEF in many low-to-middle income Asian countries. In response to this unmet need, the Malaysian HFpEF Working Group (MY-HPWG) gathered and reviewed evidence surrounding the use of different diagnostic modalities indicated for patients with HFpEF to identify diagnostic tools that could be conveniently accessed across different healthcare settings. As a result, five recommendation statements were proposed and an accompanying algorithm was developed, with the aim of improving the diagnostic rate of HFpEF. The MY-HPWG recommends using more easily accessible and non-invasive tools, such as natriuretic peptide (NP) biomarkers and basic echocardiogram (ECHO), to ensure timely HFpEF diagnosis in the primary and secondary care settings, and prompt referral to a tertiary care centre for more comprehensive assessments in uncertain cases.

The Effects of Repetitive Transcranial Magnetic Stimulation Antidepressant Response on Cold Cognition: A Single-Arm Prospective Longitudinal Study.

PURPOSE: The cognitive neuropsychological model of depression suggests that the cognitive deficits observed in depressed subjects are the result of attenuated top-down cognitive control resulting in increased bottom-up emotional processing. Remediation of cognitive impairments in cold cognition has been proposed as a valuable treatment for depression. The study aimed to examine the effects of clinical response to repetitive transcranial magnetic stimulation (rTMS) on cold cognition over the course of 8 weeks in medication-refractory depressed subjects. MATERIALS AND METHODS: Twenty-two medication-refractory depressed subjects received twenty sessions of high-frequency rTMS targeting the left dorsolateral prefrontal cortex, one of the key nodes of the cognitive control network. Cold cognition and antidepressant treatment response were monitored at baseline, week 2, 4 and 8. Clinical response was defined as ≥50% reduction in Montgomery-Åsberg Depression Rating Scale score at week 8. Longitudinal changes in cold cognition were modeled using (generalized) linear mixed models. It was hypothesized that the excitatory effects of rTMS would improve cognition in the domains of executive function, memory, and attention. Additionally, responders were expected to show larger cognitive improvements than nonresponders. RESULTS: A decrease in median latency was observed on a task that measured executive function, irrespective of treatment response status. Further, responders showed significantly larger improvements in A-Prime (the ability to detect target sequences) on a sustained attention task. Post hoc analysis indicated higher levels of rumination in non-responders. CONCLUSION: Our findings suggest that distractions during tasks with low perceptual complexity affected nonresponders disproportionately possibly due to higher rumination levels. Overall, cold cognition in medication-resistant depressed subjects was minimally affected by rTMS, substantiating the safety of rTMS treatment. LIMITATIONS: The sample size was small, and the study did not include a control group.

Diverse and abundant multi-drug resistant E. coli in Matang mangrove estuaries, Malaysia.

E.coli, an important vector distributing antimicrobial resistance in the environment, was found to be multi-drug resistant, abundant, and genetically diverse in the Matang mangrove estuaries, Malaysia. One-third (34%) of the estuarine E. coli was multi-drug resistant. The highest antibiotic resistance prevalence was observed for aminoglycosides (83%) and beta-lactams (37%). Phylogenetic groups A and B1, being the most predominant E. coli, demonstrated the highest antibiotic resistant level and prevalence of integrons (integron I, 21%; integron II, 3%). Detection of phylogenetic group B23 downstream of fishing villages indicates human fecal contamination as a source of E. coli pollution. Enteroaggregative E. coli (1%) were also detected immediately downstream of the fishing village. The results indicated multi-drug resistance among E. coli circulating in Matang estuaries, which could be reflective of anthropogenic activities and aggravated by bacterial and antibiotic discharges from village lack of a sewerage system, aquaculture farms and upstream animal husbandry.

The dnd operon for DNA phosphorothioation modification system in Escherichia coli is located in diverse genomic islands.

BACKGROUND: Strains of Escherichia coli that are non-typeable by pulsed-field gel electrophoresis (PFGE) due to in-gel degradation can influence their molecular epidemiological data. The DNA degradation phenotype (Dnd(+)) is mediated by the dnd operon that encode enzymes catalyzing the phosphorothioation of DNA, rendering the modified DNA susceptible to oxidative cleavage during a PFGE run. In this study, a PCR assay was developed to detect the presence of the dnd operon in Dnd(+) E. coli strains and to improve their typeability. Investigations into the genetic environments of the dnd operon in various E. coli strains led to the discovery that the dnd operon is harboured in various diverse genomic islands. RESULTS: The dndBCDE genes (dnd operon) were detected in all Dnd(+) E. coli strains by PCR. The addition of thiourea improved the typeability of Dnd(+) E. coli strains to 100% using PFGE and the Dnd(+) phenotype can be observed in both clonal and genetically diverse E. coli strains. Genomic analysis of 101 dnd operons from genome sequences of Enterobacteriaceae revealed that the dnd operons of the same bacterial species were generally clustered together in the phylogenetic tree. Further analysis of dnd operons of 52 E. coli genomes together with their respective immediate genetic environments revealed a total of 7 types of genetic organizations, all of which were found to be associated with genomic islands designated dnd-encoding GIs. The dnd-encoding GIs displayed mosaic structure and the genomic context of the 7 islands (with 1 representative genome from each type of genetic organization) were also highly variable, suggesting multiple recombination events. This is also the first report where two dnd operons were found within a strain although the biological implication is unknown. Surprisingly, dnd operons were frequently found in pathogenic E. coli although their link with virulence has not been explored. CONCLUSION: Genomic islands likely play an important role in facilitating the horizontal gene transfer of the dnd operons in E. coli with 7 different types of islands discovered so far.

The Complete Sequence and Comparative Analysis of a Multidrug-Resistance and Virulence Multireplicon IncFII Plasmid pEC302/04 from an Extraintestinal Pathogenic Escherichia coli EC302/04 Indicate Extensive Diversity of IncFII Plasmids.

Extraintestinal pathogenic Escherichia coli (ExPEC) that causes extraintestinal infections often harbor plasmids encoding fitness traits such as resistance and virulence determinants that are of clinical importance. We determined the complete nucleotide sequence of plasmid pEC302/04 from a multidrug-resistant E. coli EC302/04 which was isolated from the tracheal aspirate of a patient in Malaysia. In addition, we also performed comparative sequence analyses of 18 related IncFIIA plasmids to determine the phylogenetic relationship and diversity of these plasmids. The 140,232 bp pEC302/04 is a multireplicon plasmid that bears three replication systems (FII, FIA, and FIB) with subtype of F2:A1:B1. The plasmid is self-transmissible with a complete transfer region. pEC302/04 also carries antibiotic resistance genes such as bla TEM-1 and a class I integron containing sul1, cml and aadA resistance genes, conferring multidrug resistance (MDR) to its host, E. coli EC302/04. Besides, two iron acquisition systems (SitABCD and IutA-IucABCD) which are the conserved virulence determinants of ExPEC-colicin V or B and M (ColV/ColBM)-producing plasmids were identified in pEC302/04. Multiple toxin-antitoxin (TA)-based addiction systems (i.e., PemI/PemK, VagC/VagD, CcdA/CcdB, and Hok/Sok) and a plasmid partitioning system, ParAB, and PsiAB, which are important for plasmid maintenance were also found. Comparative plasmid analysis revealed only one conserved gene, the repA1 as the core genome, showing that there is an extensive diversity among the IncFIIA plasmids. The phylogenetic relationship of 18 IncF plasmids based on the core regions revealed that ColV/ColBM-plasmids and non-ColV/ColBM plasmids were separated into two distinct groups. These plasmids, which carry highly diverse genetic contents, are also mosaic in nature. The atypical combination of genetic materials, i.e., the MDR- and ColV/ColBM-plasmid-virulence encoding regions in a single ExPEC plasmid is rare but of clinical importance. Such phenomenon is bothersome when the plasmids are transmissible, facilitating the spread of virulence and resistance plasmids among pathogenic bacteria. Notably, certain TA systems are more commonly found in particular ExPEC plasmid types, indicating the possible relationships between certain TA systems and ExPEC pathogenesis.

Collaborative regulation of development but independent control of metabolism by two epidermis-specific transcription factors in Caenorhabditis elegans.

Cell fate specification is typically initiated by a master regulator, which is relayed by tissue-specific regulatory proteins (usually transcription factors) for further enforcement of cell identities, but how the factors are coordinated among each other to "finish up" the specification remains poorly understood. Caenorhabditis elegans epidermis specification is initiated by a master regulator, ELT-1, that activates its targets, NHR-25 and ELT-3, two epidermis-specific transcription factors that are important for development but not for initial specification of epidermis, thus providing a unique paradigm for illustrating how the tissue-specific regulatory proteins work together to enforce cell fate specification. Here we addressed the question through contrasting genome-wide in vivo binding targets between NHR-25 and ELT-3. We demonstrate that the two factors bind discrete but conserved DNA motifs, most of which remain in proximity, suggesting formation of a complex between the two. In agreement with this, gene ontology analysis of putative target genes suggested differential regulation of metabolism but coordinated control of epidermal development between the two factors, which is supported by quantitative analysis of expression of their specific or common targets in the presence or absence of either protein. Functional validation of a subset of the target genes showed both activating and inhibitory roles of NHR-25 and ELT-3 in regulating their targets. We further demonstrated differential control of specification of AB and C lineage-derived epidermis. The results allow us to assemble a comprehensive gene network underlying C. elegans epidermis development that is likely to be widely used across species and provides insights into how tissue-specific transcription factors coordinate with one another to enforce cell fate specification initiated by its master regulator.

Prevalence and characterization of verotoxigenic-Escherichia coli isolates from pigs in Malaysia.

BACKGROUND: Postweaning diarrhea caused by pathogenic Escherichia coli, in particular verotoxigenic E. coli (VTEC), has caused significant economic losses in the pig farming industry worldwide. However, there is limited information on VTEC in Malaysia. The objective of this study was to characterize pathogenic E. coli isolated from post-weaning piglets and growers with respect to their antibiograms, carriage of extended-spectrum beta-lactamases, pathotypes, production of hemolysins and fimbrial adhesins, serotypes, and genotypes. RESULTS: PCR detection of virulence factors associated with different E. coli pathotypes (ETEC, EPEC, EHEC, and VTEC) revealed that VTEC was the only pathotype identified from six swine farms located at north-western Peninsular Malaysia. A low prevalence rate of VTEC was found among the swine samples (n = 7/345) and all 7 VTEC isolates were multidrug resistant. Five of these isolates from different hosts raised in the same pen were likely to be of the same clone as they shared identical sero-pathotypes (O139:H1, VT2e/α-hly/F18), resistance profiles and DNA fingerprinting profiles. Two other serotypes, O130: H26 (n = 1) and O168: H21 (n = 1) carrying virulence factors were also identified. O168: H21 is possibly a new serotype as this has not been previously reported. CONCLUSIONS: The occurrence of VTEC with infrequently encountered serotypes that are multidrug resistant and harbouring virulence factors may be of public health concern. The detection of possible clones in this study also showed that the combination of different typing tools including phenotyping and genotyping methods is useful for molecular epidemiologic surveillance and studies.

Genome sequence of multidrug-resistant Escherichia coli EC302/04, isolated from a human tracheal aspirate.

Escherichia coli is an important etiologic agent of lower respiratory tract infections (LRTI). Multidrug-resistant E. coli EC302/04 was isolated from a tracheal aspirate, and its genome sequence is expected to provide insights into antimicrobial resistance as well as adaptive and virulence mechanisms of E. coli involved in LRTI.

Prevalence and characterization of multidrug-resistant and extended-spectrum beta-lactamase-producing Escherichia coli from pediatric wards of a Malaysian hospital.

The emergence of Escherichia coli resistant to extended-spectrum cephalosporins (ESCs) is of concern as ESC is often used to treat infections by Gram-negative bacteria. One-hundred and ten E. coli strains isolated in 2009-2010 from children warded in a Malaysian tertiary hospital were analyzed for their antibiograms, carriage of extended-spectrum beta-lactamase (ESBL) and AmpC genes, possible inclusion of the beta-lactamase genes on an integron platform, and their genetic relatedness. All E. coli strains were sensitive to carbapenems. About 46% of strains were multidrug resistant (MDR; i.e., resistant to ≥3 antibiotic classes) and almost half (45%) were nonsusceptible to ESCs. Among the MDR strains, high resistance rates were observed for ampicillin (98%), tetracycline (75%), and trimethoprim/sulfamethoxazole (73%). Out of 110 strains, bla(TEM-1) (49.1%), bla(CTX-M) (11.8%), and bla(CMY-2) (6.4%) were detected. Twenty-one strains were ESBL producers. CTX-M-15 was the predominant CTX-M variant found and this is the first report of a CTX-M-27-producing E. coli strain from Malaysia. Majority (3.1%) of the strains harbored class 1 integron-encoded integrases with a predominance of aadA and dfr genes within the integron variable region. No gene cassette encoding ESBL genes was found and integrons were not significantly associated with ESBL or non-ESBL producers. Possible clonal expansion was observed for few CTX-M-15-positive strains but the O25-ST131 E. coli clone known to harbor CTX-M-15 was not detected while CMY-2-positive strains were genetically diverse.

Bickerstaff's brainstem encephalitis complicating Salmonella Paratyphi A infection.

Patients with enteric fever frequently develop neurological complications during their illness. Among them, majority has encephalopathy, but focal deficits or peripheral nervous involvements are occasionally encountered. We describe a young woman who developed a neurological syndrome consistent with Bickerstaff's brainstem encephalitis, with symptoms and signs including convulsion, impaired consciousness, external ophthalmoplegia, ataxia, bulbar palsy and pyramidal signs, following Salmonella Paratyphi A infection. This is the first case report of this syndrome after S. Paratyphi A infection, and it is the second case of Bickerstaff's brainstem encephalitis complicating enteric fever reported in the literature. This case also demonstrated, for the first time, a positive anti-GQ1b IgG response in a patient with Bickerstaff's brainstem encephalitis and related disorders that appear as complications during enteric fever.

Differential effects of the antidepressants tranylcypromine and fluoxetine on limbic cannabinoid receptor binding and endocannabinoid contents.

The goal of this study was to determine whether the endocannabinoid system is altered by chronic antidepressant treatment. The effects of 3-week administration of the monoamine oxidase inhibitor, tranylcypromine (10 mg/kg) and the selective serotonin reuptake inhibitor, fluoxetine (5 mg/kg) on cannabinoid CB(1) receptor densities and endocannabinoid contents were determined in limbic brain regions of the rat. Tranylcypromine significantly reduced tissue content of the endocannabinoid N-arachidonylethanolamine (anandamide) in the prefrontal cortex, hippocampus and hypothalamus and increased 2-arachidonoylglycerol content in the prefrontal cortex. Tranylcypromine treatment significantly increased CB(1) receptor binding density in the prefrontal cortex and hippocampus, but not in the hypothalamus. Treatment with fluoxetine increased CB(1) receptor density in the prefrontal cortex, but had no effect on endocannabinoid contents in any brain region examined. These data suggest that monoaminergic neurotransmission can regulate the endocannabinoid system and further indicates a role of the endocannabinoid system in affective illness and its treatment.

Transient resonance Raman and density functional theory investigation of the chlorine atom/carbon disulfide molecular complex involved in selective alkane photochlorination reactions.

The structure and bonding of the chlorine atom/carbon disulfide (CS(2)/Cl) complex involved in selective photochlorination reactions with alkanes was directly probed using transient resonance Raman spectroscopy. The experimental Raman vibrational frequencies were compared to those computed from density functional theory calculations for probable structures of the CS(2)/Cl complex. Our results indicate that the S [double bond] C [double bond] S...Cl complex species is responsible for the approximately 370 nm transient absorption band observed after ultraviolet photolysis of CCl(4) in the presence of CS(2). We discuss the structure and properties of the S [double bond] C [double bond] S...Cl complex and compare them with those for the related benzene/Cl and pyridine/Cl complexes.