Workplace wellbeing in community pharmacy practice: A cross-sectional study in Can Tho, Vietnam.

Background: Among pharmacy workers, low workplace wellbeing can lead to reduced effectiveness. However, to date, studies on this issue are limited within the community pharmacy setting in Vietnam. Objectives: This study was conducted to identify the component aspects of workplace wellbeing and their associations with demographic characteristics. Methods: The cross-sectional descriptive study was conducted in Can Tho, Vietnam. Self-administered questionnaires were hand-delivered to all pharmacy workers working at selected community pharmacies. The workplace wellbeing scale comprised 18 items. Results: In total, 382 pharmacy workers participated in this study. Factor analysis revealed three fundamental aspects to workplace wellbeing: Factor 1 - perceived self-worth and job satisfaction, Factor 2 - positive emotions with work, and Factor 3 - negative emotions with work. Factor 1 showed a positive correlation with Factor 2, with a correlation coefficient (ρ) of 0.509, while both Factor 1 (ρ = -0.399) and Factor 2 (ρ = -0.416) demonstrated negative correlations with Factor 3. Higher income was associated with higher positive emotions with work (P = 0.008), higher perceived self-worth and job satisfaction (P = 0.013), and lower negative emotions with work (P < 0.001). Conclusion: Workplace wellbeing of pharmacy workers in their professional environments was associated with financial aspects. These findings suggest that policies aimed at improving income for pharmacy workers could bring benefits to enhancing job satisfaction and workplace wellbeing.

SMCHD1 has separable roles in chromatin architecture and gene silencing that could be targeted in disease.

The interplay between 3D chromatin architecture and gene silencing is incompletely understood. Here, we report a novel point mutation in the non-canonical SMC protein SMCHD1 that enhances its silencing capacity at endogenous developmental targets. Moreover, it also results in enhanced silencing at the facioscapulohumeral muscular dystrophy associated macrosatellite-array, D4Z4, resulting in enhanced repression of DUX4 encoded by this repeat. Heightened SMCHD1 silencing perturbs developmental Hox gene activation, causing a homeotic transformation in mice. Paradoxically, the mutant SMCHD1 appears to enhance insulation against other epigenetic regulators, including PRC2 and CTCF, while depleting long range chromatin interactions akin to what is observed in the absence of SMCHD1. These data suggest that SMCHD1's role in long range chromatin interactions is not directly linked to gene silencing or insulating the chromatin, refining the model for how the different levels of SMCHD1-mediated chromatin regulation interact to bring about gene silencing in normal development and disease.

Magnetic resonance imaging as a first-choice imaging modality in carpal tunnel syndrome: new evidence.

BACKGROUND: Carpal tunnel syndrome (CTS) is the most common type of peripheral nerve compression. Magnetic resonance imaging (MRI) is becoming more popular in practice in the evaluation of CTS. PURPOSE: To evaluate the diagnostic value of MRI in CTS. MATERIAL AND METHODS: A cross-sectional study of 39 wrists was conducted. Clinical and nerve conduction study findings were evaluated and graded according to the Boston Carpal Tunnel Questionnaire (BCTQ) and the American Association of Neuromuscular and Electrodiagnostic Medicine. MRI was performed using a 1.5-T scanner. MRI parameters included cross-sectional area (CSA) of the median nerve and the ratio change in CSA at four levels: distal radioulnar joint (DRUJ-CSA); pisiform (p-CSA); middle of the carpal tunnel (i-CSA); and hook of hamate. The ratio change in CSA was expressed as p-CSA/DRUJ-CSA and ΔCSA (difference between iCSA and DRUJ-CSA), the flattening ratio of the median nerve, the thickness of the flexor retinaculum, flexor retinaculum bowing ratio, signal intensity ratio of the median, nerve and hypothenar muscle signal intensity. RESULTS: With a cutoff point of 10.9 mm2 of the p-CSA, MRI had a sensitivity and specificity of 97.4% and 80% for diagnosis of CTS, respectively. There was a significant association between the clinical and electrophysiological stage with MRI findings (P < 0.001). There was a positive correlation between the BCTQ score and MRI parameters (0.5 < r < 0.7, P < 0.01). CONCLUSION: MRI has good diagnostic value in evaluating CTS. We recommend using p-CSA ≥10.9 mm2 and ΔCSA ≥2.3 mm2 as MRI diagnostic criteria of CTS.

Erratum to "Generalized lymphangiomatosis-A rare manifestation of lymphatic malformation" [Radiology Case Reports 16 (2021) 66-71].

[This corrects the article DOI: 10.1016/j.radcr.2020.10.044.].

HOX epimutations driven by maternal SMCHD1/LRIF1 haploinsufficiency trigger homeotic transformations in genetically wildtype offspring.

The body plan of animals is laid out by an evolutionary-conserved HOX code which is colinearly transcribed after zygotic genome activation (ZGA). Here we report that SMCHD1, a chromatin-modifying enzyme needed for X-inactivation in mammals, is maternally required for timely HOX expression. Using zebrafish and mouse Smchd1 knockout animals, we demonstrate that Smchd1 haplo-insufficiency brings about precocious and ectopic HOX transcription during oogenesis and embryogenesis. Unexpectedly, wild-type offspring born to heterozygous knockout zebrafish smchd1 mothers exhibited patent vertebrate patterning defects. The loss of maternal Smchd1 was accompanied by HOX epi-mutations driven by aberrant DNA methylation. We further show that this regulation is mediated by Lrif1, a direct interacting partner of Smchd1, whose knockout in zebrafish phenocopies that of Smchd1. Rather than being a short-lived maternal effect, HOX mis-regulation is stably inherited through cell divisions and persists in cultured fibroblasts derived from FSHD2 patients haploinsufficient for SMCHD1. We conclude that maternal SMCHD1/LRIF1 sets up an epigenetic state in the HOX loci that can only be reset in the germline. Such an unusual inter-generational inheritance, whereby a phenotype can be one generation removed from its genotype, casts a new light on how unresolved Mendelian diseases may be interpreted.

Loss of C2orf69 defines a fatal autoinflammatory syndrome in humans and zebrafish that evokes a glycogen-storage-associated mitochondriopathy.

Human C2orf69 is an evolutionarily conserved gene whose function is unknown. Here, we report eight unrelated families from which 20 children presented with a fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants. C2ORF69 bears homology to esterase enzymes, and orthologs can be found in most eukaryotic genomes, including that of unicellular phytoplankton. We found that endogenous C2ORF69 (1) is loosely bound to mitochondria, (2) affects mitochondrial membrane potential and oxidative respiration in cultured neurons, and (3) controls the levels of the glycogen branching enzyme 1 (GBE1) consistent with a glycogen-storage-associated mitochondriopathy. We show that CRISPR-Cas9-mediated inactivation of zebrafish C2orf69 results in lethality by 8 months of age due to spontaneous epileptic seizures, which is preceded by persistent brain inflammation. Collectively, our results delineate an autoinflammatory Mendelian disorder of C2orf69 deficiency that disrupts the development/homeostasis of the immune and central nervous systems.

A comparative study of isothermal nucleic acid amplification methods for SARS-CoV-2 detection at point of care

COVID-19, caused by the novel coronavirus SARS-CoV-2, has spread worldwide and put most of the world under lockdown. Despite that there have been emergently approved vaccines for SARS-CoV-2, COVID-19 cases, hospitalizations, and deaths have remained rising. Thus, rapid diagnosis and necessary public health measures are still key parts to contain the pandemic. In this study, the colorimetric isothermal nucleic acid amplification tests (iNAATs) for SARS-CoV-2 detection based on loop-mediated isothermal amplification (LAMP), cross-priming amplification (CPA), and polymerase spiral reaction (PSR) were designed and evaluated. The three methods showed the same limit of detection (LOD) value of 1 copy of the targeted gene per reaction. However, for the direct detection of SARS-CoV-2 genomic-RNA, LAMP outperformed both CPA and PSR, exhibiting the LOD value of roughly 43.14 genome copies/reaction. The results can be read with the naked eye within 45 minutes, without cross-reactivity to closely related coronaviruses. Moreover, the direct detection of SARS-CoV-2 RNA in simulated patient specimens by iNAATs was also successful. Finally, the ready-to-use lyophilized reagents for LAMP reactions were shown to maintain the sensitivity and LOD value of the liquid assays. The results indicate that the colorimetric lyophilized LAMP kit developed herein is highly suitable for detecting SARS-CoV-2 nucleic acids at point-of-care.

FSHD2- and BAMS-associated mutations confer opposing effects on SMCHD1 function.

Structural maintenance of chromosomes flexible hinge domain-containing 1 (Smchd1) plays important roles in epigenetic silencing and normal mammalian development. Recently, heterozygous mutations in SMCHD1 have been reported in two disparate disorders: facioscapulohumeral muscular dystrophy type 2 (FSHD2) and Bosma arhinia microphthalmia syndrome (BAMS). FSHD2-associated mutations lead to loss of function; however, whether BAMS is associated with loss- or gain-of-function mutations in SMCHD1 is unclear. Here, we have assessed the effect of SMCHD1 missense mutations from FSHD2 and BAMS patients on ATP hydrolysis activity and protein conformation and the effect of BAMS mutations on craniofacial development in a Xenopus model. These data demonstrated that FSHD2 mutations only result in decreased ATP hydrolysis, whereas many BAMS mutations can result in elevated ATPase activity and decreased eye size in Xenopus Interestingly, a mutation reported in both an FSHD2 patient and a BAMS patient results in increased ATPase activity and a smaller Xenopus eye size. Mutations in the extended ATPase domain increased catalytic activity, suggesting critical regulatory intramolecular interactions and the possibility of targeting this region therapeutically to boost SMCHD1's activity to counter FSHD.

The Protective Effect of Eupatilin against Hydrogen Peroxide-Induced Injury Involving 5-Lipoxygenase in Feline Esophageal Epithelial Cells

In this study, we focused to identify whether eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone), an extract from Artemisia argyi folium, prevents H2O2-induced injury of cultured feline esophageal epithelial cells. Cell viability was measured by the conventional MTT reduction assay. Western blot analysis was performed to investigate the expression of 5-lipoxygenase by H2O2 treatment in the absence and presence of inhibitors. When cells were exposed to 600 microM H2O2 for 24 hours, cell viability was decreased to 40%. However, when cells were pretreated with 25~150 microM eupatilin for 12 hours, viability was significantly restored in a concentration-dependent manner. H2O2-treated cells were shown to express 5-lipoxygenase, whereas the cells pretreated with eupatilin exhibited reduction in the expression of 5-lipoxygenase. The H2O2-induced increase of 5-lipoxygenase expression was prevented by SB202190, SP600125, or NAC. We further demonstrated that the level of leukotriene B4 (LTB4) was also reduced by eupatilin, SB202190, SP600125, NAC, or nordihydroguaiaretic acid (a lipoxygenase inhibitor) pretreatment. H2O2 induced the activation of p38MAPK and JNK, this activation was inhibited by eupatilin. These results indicate that eupatilin may reduce H2O2-induced cytotoxicity, and 5-lipoxygenase expression and LTB4 production by controlling the p38 MAPK and JNK signaling pathways through antioxidative action in feline esophageal epithelial cells.

A comparison of different automated methods for the detection of white matter lesions in MRI data.

White matter hyperintensities (WMH) are the focus of intensive research and have been linked to cognitive impairment and depression in the elderly. Cumbersome manual outlining procedures make research on WMH labour intensive and prone to subjective bias. This study compares fully automated supervised detection methods that learn to identify WMH from manual examples against unsupervised approaches on the combination of FLAIR and T1 weighted images. Data were collected from ten subjects with mild cognitive impairment and another set of ten individuals who fulfilled diagnostic criteria for dementia. Data were split into balanced groups to create a training set used to optimize the different methods. Manual outlining served as gold standard to evaluate performance of the automated methods that identified each voxel either as intact or as part of a WMH. Otsu's approach for multiple thresholds which is based only on voxel intensities of the FLAIR image produced a high number of false positives at grey matter boundaries. Performance on an independent test set was similarly disappointing when simply applying a threshold to the FLAIR that was found from training data. Among the supervised methods, precision-recall curves of support vector machines (SVM) indicated advantages over the performance achieved by K-nearest-neighbor classifiers (KNN). The curves indicated a clear benefit from optimizing the threshold of the SVM decision value and the voting rule of the KNN. Best performance was reached by selecting training voxels according to their distance to the lesion boundary and repeated training after replacing the feature vectors from those voxels that did not form support vectors of the SVM. The study demonstrates advantages of SVM for the problem of detecting WMH at least for studies that include only FLAIR and T1 weighted images. Various optimization strategies are discussed and compared against each other.