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Kjeldsen Nicolaisen posted an update 1 week, 5 days ago
Mycobacterium abscessus, an emerging pathogen responsible for severe lung infections in cystic fibrosis patients, displays either smooth (S) or rough (R) morphotypes. The S-to-R transition is associated with reduced levels of glycopeptidolipid (GPL) production and is correlated with increased pathogenicity in animal and human hosts. While the structure of GPL is well established, its biosynthetic pathway is incomplete. In addition, the biological functions of the distinct structural parts of this complex lipid remain elusive. Herein, the fmt gene encoding a putative O-methyltransferase was deleted in the M. abscessus S variant. Subsequent biochemical and structural analyses demonstrated that methoxylation of the fatty acyl chain of GPL was abrogated in the Δfmt mutant, and this defect was rescued upon complementation with a functional fmt gene. In contrast, the introduction of fmt derivatives mutated at residues essential for methyltransferase activity failed to complement GPL defects, indicating that fmt encodes an O-methyltransferase. Unexpectedly, phenotypic analyses showed that Δfmt was more hydrophilic than its parental progenitor, as demonstrated by hexadecane-aqueous buffer partitioning and atomic force microscopy experiments with hydrophobic probes. Importantly, the invasion rate of THP-1 macrophages by Δfmt was reduced by 50% when compared to the wild-type strain. Together, these results indicate that Fmt O-methylates the lipid moiety of GPL and plays a substantial role in conditioning the surface hydrophobicity of M. abscessus as well as in the early steps of the interaction between the bacilli and macrophages.
The early recognition and management of the behavioral and psychological symptoms of dementia (BPSD) are important to inform treatment decisions. Current BPSD screening tools are time-consuming and require advanced skills, limiting their application in routine clinical practice. An easier and quicker tool for use by nonphysician healthcare personnel is needed.
A 14-item, Thai-language, BPSD scoring system for dementia (BPSD-T) was developed, based on clinical surveys and modifications after a pilot study. The Neuropsychiatric Inventory (NPI), BPSD-T, Thai Mental State Examination (TMSE), Clinical Dementia Rating Scale (CDR), and Barthel Index were performed. BPSD-T and NPI scores were compared, and test validity and reliability were analyzed.
A total of 168 people with dementia (mean age, 80.7±6.7years) and their primary caregivers were recruited. A total of 105 (62.5%) subjects were diagnosed with Alzheimer’s disease (AD), and 31 (18.5%) with AD with small-vessel disease. The Global CDR was 0.5-1 for 7e will enable earlier recognition, targeted intervention, improved quality of care, and reduced caregiver burden.
BPSD-T is a quick, reliable, and valid test to evaluate BPSD from the common dementia subtypes and severity, with a good correlation with the NPI. Its application in routine clinical practice will enable earlier recognition, targeted intervention, improved quality of care, and reduced caregiver burden.
PWS is challenging to diagnose prenatally due to a lack of precise and well-characterized fetal phenotypes and noninvasive markers. Here we present the case of prenatal diagnosis of Prader-Willi syndrome, which was suspected with whole-genome NIPS.
Whole-genome noninvasive prenatal screening showed a high risk for trisomy 15. Amniocentesis followed by FISH analysis and SNP-based chromosomal microarray was performed.
Simultaneous analysis of maternal and fetal samples with SNP microarrays demonstrated maternal uniparental disomy (UPD).
The presented case is the first case of PWS described in detail, which was suspected by NIPS results. It demonstrates that the choice of confirmation methods concerning the time needed is crucial for the right diagnosis. We suppose that prenatal testing of UPD is essential for chromosome regions, which play a key role in the appearance of various gene-imprinting failure syndromes like PWS or AS.
The presented case is the first case of PWS described in detail, which was suspected by NIPS results. Antineoplastic and Immunosuppressive Antibiotics inhibitor It demonstrates that the choice of confirmation methods concerning the time needed is crucial for the right diagnosis. We suppose that prenatal testing of UPD is essential for chromosome regions, which play a key role in the appearance of various gene-imprinting failure syndromes like PWS or AS.
The objective of this study was to assess the relationship between white matter hyperintensities (WMH) and the occurrence and progression of apathy in Parkinson’s disease (PD).
We recruited patients with PD who underwent baseline evaluation, which included apathy assessment and magnetic resonance imaging (MRI) head scans. After 2.5years of follow-up, we re-evaluated patient apathy symptoms. The severity and location of WMH were assessed with fluid-attenuated inversion recovery (FLAIR) sequences using the Fazekas visual rating scale. Logistic regression and linear regression analyses of baseline WMH characteristics were conducted to explore the potential association between apathy and WMH.
A total of 141 PD patients were recruited. The apathy group had a higher proportion of male patients, advanced disease, and depression, which was coupled with a lower quality of life. Morever, higher WMH severity was significantly associated with apathy. Logistic regression analyses demonstrated that WMH severity was a risk factor for apathy. In addition, linear regression analysis also suggests that apathy severity is positively correlated with baseline WMH Fazekas scales (ϐ=0.959, P<0.001). Baseline WMH severity was also a risk factor for apathy progression.
WMH is associated with apathy and could be a promising marker to predict apathy progression in PD.
WMH is associated with apathy and could be a promising marker to predict apathy progression in PD.We address existing controversies regarding neuroanatomical substrates of reading-aloud processes according to the dual-route processing models, in this particular instance in a series of 49 individuals with brain tumors who performed several reading tasks of real-time neuropsychological testing during surgery (low- to high-grade cerebral neoplasms involving the left hemisphere). We explored how reading abilities in individuals with brain tumors evolve during and after surgery for a brain tumor, and we studied the reading performance in a sample of 33 individuals in a 4-month follow-up after surgery. Impaired reading performance was seen pre-surgery in 7 individuals with brain tumors, intra-surgery in 18 individuals, at immediate post-surgery testing in 26 individuals, and at follow-up in 5 individuals. We classified their reading disorders according to operational criteria for either phonological or surface dyslexia. Neuroimaging results are discussed within the theoretical framework of the dual-route model of reading. Lesion-mask subtraction analyses revealed that areas selectively related with phonological dyslexia were located-along with the left hemisphere dorsal stream-in the Rolandic operculum, the inferior frontal gyrus, the precentral gyrus, the supramarginal gyrus, the insula (and/or the underlying external capsule), and parts of the superior longitudinal fasciculus, whereas lesions related to surface dyslexia involved the ventral stream, that is, the left middle and inferior temporal gyrus and parts of the left inferior longitudinal fasciculus.
HealthLinks Chronic Care is a state-wide public hospital initiative designed to improve care for cohorts at-risk of potentially preventable hospitalizations at no extra cost. MonashWatch (MW) is an hospital outreach service designed to optimize admissions in an at-risk cohort. Telehealth operators make regular phone calls (≥weekly) using the Patient Journey Record System (PaJR). PaJR generates flags based on patient self-report, alerting to a risk of admission or emergency department attendance. ‘Total flags’ of global health represent concerns about self-reported general health, medication, and wellness. ‘Red flags’ represent significant disease/symptoms concerns, likely to lead to hospitalization.
A time series analysis of PaJR phone calls to MW patients with ≥1 acute non-surgical admissions in a 20-day time window (10 days pre-admission and 10 days post-discharge) between 23 December 2016 and 11 October 2017. Pettitt’s hypothesis-testing homogeneity measure was deployed to analyse Victorian Admitted Epspital syndrome’. There is evidence of a 10-day ‘pre-hospital’ window for interventions to possibly prevent or shorten an acute admission in this MW cohort. Further validation in a larger diverse sample is needed.
Estrogen may inhibit cell senescence that contributes to age-related disorders. This study determined the effects of menopausal hormone treatments on circulating levels of markers of cell senescence.
Growth differentiation factor 15 (GDF15), tumor necrosis factor receptor 1 (TNFR1), FAS, and macrophage inflammatory protein 1α (MIP1α) were measured in serum using multiplexed bead-based assays and compared among menopausal women participating in the Kronos Early Estrogen Prevention Study randomized to either placebo (n=38), oral conjugated equine estrogen (oCEE, n=37), or transdermal 17β-estradiol (tE2, n=34). Serum levels of the senescent markers for each treatment were compared to placebo 36months after randomization using the Wilcoxon rank sum test.
Serum levels of GDF15, TNFR1, and FAS, but not MIP1α, were lower in both the oCEE and tE2 groups compared to placebo. The difference in levels between treatment and placebo for GDF15, TNFR1, and FAS were greater for oCEE [-108pg/mL (p=.008), -234pg/mL (p=.0to the effects of menopause on the biology of aging.Myocardial infarction (MI) is the most common cause of a heart failure, which occurs due to myocardial ischemia leading to left ventricular (LV) remodeling. LV remodeling particularly occurs at the ischemic area and the region surrounds it, known as the border zone. The role of the border zone in initiating LV remodeling process urges the investigation on the correlation between early border zone changes and remodeling outcome. Thus, this study aims to simulate a preliminary conceptual work of the border zone formation and evolution during onset of MI and its effect towards early LV remodeling processes by incorporating the oxygen concentration effect on the electrophysiology of an idealized three-dimensional LV through electro-chemical coupled mathematical model. The simulation result shows that the region of border zone, represented by the distribution of electrical conductivities, keeps expanding over time. Based on this result, the border zone is also proposed to consist of three sub-regions, namely mildly, moderately, and seriously impaired conductivity regions, which each region categorized depending on its electrical conductivities. This division could be used as a biomarker for classification of reversible and irreversible myocardial injury and will help to identify the different risks for the survival of patient. Larger ischemic size and complete occlusion of the coronary artery can be associated with an increased risk of developing irreversible injury, in particular if the reperfusion treatment is delayed. Increased irreversible injury area can be related with cardiovascular events and will further deteriorate the LV function over time.