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Journal of Human Genetics Jul 2024Heterozygous transmembrane protein 63A (TMEM63A) variants cause transient infantile hypomyelinating leukodystrophy-19, which features remarkable natural resolution of...
Heterozygous transmembrane protein 63A (TMEM63A) variants cause transient infantile hypomyelinating leukodystrophy-19, which features remarkable natural resolution of clinical and imaging findings during childhood. Previous reports have mainly described de novo variants lacking detailed familial cases. Herein, we describe the clinical course of familial cases with a TMEM63A variant. A 5-month-old girl presented with nystagmus, global hypotonia, and difficulty swallowing since birth. Brain magnetic resonance imaging at 1.5 and 5 months revealed diffuse hypomyelination. Her mother, maternal aunt, and grandfather had nystagmus and motor developmental delays in infancy, which resolved spontaneously during childhood. Compared with these cases, the proband's motor developmental delay was profound, and she was the only one with feeding difficulties, necessitating nasogastric tube feeding. Genetic testing revealed a heterozygous TMEM63A variant (NM_014698.3:c.1658G>A, p.(Gly553Asp)) in the proband and her family. This is the first three-generation familial report of a TMEM63A variant that provides insight into its history and heterogeneity.
PubMed: 38951194
DOI: 10.1038/s10038-024-01268-z -
NPJ Parkinson's Disease Jun 2024In Parkinson's disease (PD), GBA1- and LRRK2-mutations are associated with different clinical phenotypes which might be related to differential involvement of the...
In Parkinson's disease (PD), GBA1- and LRRK2-mutations are associated with different clinical phenotypes which might be related to differential involvement of the cholinergic system. We investigated cholinergic integrity in 149 asymptomatic GBA1 and 169 asymptomatic LRRK2 mutation carriers, 112 LRRK2 and 60 GBA1 carriers with PD, 492 idiopathic PD, and 180 controls from the PPMI cohort. Basal forebrain volumes were extracted and white matter pathways from nucleus basalis of Meynert (NBM) to cortex and from pedunculopontine nucleus (PPN) to thalamus were assessed with a free water-corrected DTI model. Bayesian ANCOVAs were conducted for group comparisons and Bayesian linear mixed models to assess associations with cognitive decline. Basal forebrain volumes were increased in asymptomatic GBA1 (Bayes Factor against the null hypothesis (BF) = 75.2) and asymptomatic LRRK2 (BF = 57.0) compared to controls. Basal forebrain volumes were increased in LRRK2- compared to GBA1-PD (BF = 14.5) and idiopathic PD (BF = 3.6*10), with no difference between idiopathic PD and PD-GBA1 (BF = 0.25). Mean diffusivity along the medial NBM pathway was decreased in asymptomatic GBA1 compared to controls (BF = 30.3). Over 5 years, idiopathic PD and PD-GBA1 declined across all cognitive domains whereas PD-LRRK2 patients only declined in processing speed. We found an interaction between basal forebrain volume and time in predicting multiple cognitive domains in idiopathic PD and PD-GBA1, but not in PD-LRRK2. While LRRK2 and GBA1 mutations are both associated with increased basal forebrain volume at asymptomatic stages, this increase persists at the symptomatic PD stage only in LRRK2 and might be related to slower cognitive decline in these patients.
PubMed: 38951174
DOI: 10.1038/s41531-024-00743-w -
Scientific Reports Jul 2024Diffusion tensor imaging (DTI) metrics and tractography can be biased due to low signal-to-noise ratio (SNR) and systematic errors resulting from image artifacts and...
Diffusion tensor imaging (DTI) metrics and tractography can be biased due to low signal-to-noise ratio (SNR) and systematic errors resulting from image artifacts and imperfections in magnetic field gradients. The imperfections include non-uniformity and nonlinearity, effects caused by eddy currents, and the influence of background and imaging gradients. We investigated the impact of systematic errors on DTI metrics of an isotropic phantom and DTI metrics and tractography of a rat brain measured at high resolution. We tested denoising and Gibbs ringing removal methods combined with the B matrix spatial distribution (BSD) method for magnetic field gradient calibration. The results showed that the performance of the BSD method depends on whether Gibbs ringing is removed and the effectiveness of stochastic error removal. Region of interest (ROI)-based analysis of the DTI metrics showed that, depending on the size of the ROI and its location in space, correction methods can remove systematic bias to varying degrees. The preprocessing pipeline proposed and dedicated to this type of data together with the BSD method resulted in an even - 90% decrease in fractional anisotropy (FA) (globally and locally) in the isotropic phantom and - 45% in the rat brain. The largest global changes in the rat brain tractogram compared to the standard method without preprocessing (sDTI) were noticed after denoising. The direction of the first eigenvector obtained from DTI after denoising, Gibbs ringing removal and BSD differed by an average of 56 and 10 degrees in the ROI from sDTI and from sDTI after denoising and Gibbs ringing removal, respectively. The latter can be identified with the amount of improvement in tractography due to the elimination of systematic errors related to imperfect magnetic field gradients. Based on the results, the systematic bias for high resolution data mainly depended on SNR, but the influence of non-uniform gradients could also be seen. After denoising, the BSD method was able to further correct both the metrics and tractography of the diffusion tensor in the rat brain by taking into account the actual distribution of magnetic field gradients independent of the examined object and uniquely dependent on the scanner and sequence. This means that in vivo studies are also subject to this type of errors, which should be taken into account when processing such data.
Topics: Animals; Diffusion Tensor Imaging; Rats; Brain; Signal-To-Noise Ratio; Phantoms, Imaging; Artifacts; Image Processing, Computer-Assisted; Anisotropy; Male
PubMed: 38951163
DOI: 10.1038/s41598-024-66076-z -
Scientific Reports Jul 2024Plant growth and high yields are secured by intensive use of nitrogen (N) fertilizer, which, however, pollutes the environment, especially when N is in the form of...
Plant growth and high yields are secured by intensive use of nitrogen (N) fertilizer, which, however, pollutes the environment, especially when N is in the form of nitrate. Ammonium is oxidized to nitrate by nitrifiers, but roots can release biological nitrification inhibitors (BNIs). Under what conditions does root-exudation of BNIs facilitate nitrogen N uptake and reduce pollution by N loss to the environment? We modeled the spatial-temporal dynamics of nitrifiers, ammonium, nitrate, and BNIs around a root and simulated root N uptake and net rhizosphere N loss over the plant's life cycle. We determined the sensitivity of N uptake and loss to variations in the parameter values, testing a broad range of soil-plant-microbial conditions, including concentrations, diffusion, sorption, nitrification, population growth, and uptake kinetics. An increase in BNI exudation reduces net N loss and, under most conditions, increases plant N uptake. BNIs decrease uptake in the case of (1) low ammonium concentrations, (2) high ammonium adsorption to the soil, (3) rapid nitrate- or slow ammonium uptake by the plant, and (4) a slowly growing or (5) fast-declining nitrifier population. Bactericidal inhibitors facilitate uptake more than bacteriostatic ones. Some nitrification, however, is necessary to maximize uptake by both ammonium and nitrate transporter systems. An increase in BNI exudation should be co-selected with improved ammonium uptake. BNIs can reduce N uptake, which may explain why not all species exude BNIs but have a generally positive effect on the environment by increasing rhizosphere N retention.
Topics: Nitrification; Nitrogen; Plant Roots; Soil Microbiology; Nitrates; Plants; Ammonium Compounds; Soil; Rhizosphere; Fertilizers
PubMed: 38951138
DOI: 10.1038/s41598-024-65247-2 -
Langmuir : the ACS Journal of Surfaces... Jul 2024A critical constraint impeding the utilization of Mn-based oxide catalysts in NH selective catalytic reduction (NH-SCR) is their inadequate resistance to water and...
A critical constraint impeding the utilization of Mn-based oxide catalysts in NH selective catalytic reduction (NH-SCR) is their inadequate resistance to water and sulfur. This vulnerability primarily arises from the propensity of SO to bind to the acidic site in manganese oxide, resulting in the formation of metal sulfate and leading to the irreversible deactivation of the catalyst. Therefore, gaining a comprehensive understanding of the detrimental impact of SO on the acidic sites and elucidating the underlying mechanism of this toxicity are of paramount importance for the effective application of Mn-based catalysts in NH-SCR. Herein, we strategically modulate the acidity of the manganese oxide catalyst surface through the incorporation of Ce and Nb. Comprehensive analyses, including thermogravimetry, NH temperature-programmed desorption, diffused reflectance infrared Fourier transform spectroscopy, and density functional theory calculations, reveal that SO exhibits a propensity for adsorption at strongly acidic sites. This mechanistic understanding underscores the pivotal role of surface acidity in governing the sulfur resistance of manganese oxide.
PubMed: 38951117
DOI: 10.1021/acs.langmuir.4c01289 -
Zhonghua Xue Ye Xue Za Zhi = Zhonghua... Apr 2024The aim of this study was to investigate the effects of polyphyllin Ⅶ (PP Ⅶ) on proliferation, apoptosis, and cell cycle of diffuse large B-cell lymphoma (PLBCL)...
The aim of this study was to investigate the effects of polyphyllin Ⅶ (PP Ⅶ) on proliferation, apoptosis, and cell cycle of diffuse large B-cell lymphoma (PLBCL) cell lines U2932 and SUDHL-4. The DLBCL cell lines were divided into a control group and a PPⅦ group, and experiments were conducted using MTT assay, flow cytometry, and Western blotting.Results showed that compared with the control group, PPⅦ significantly inhibited the proliferation of U2932 and SUDHL-4 cells (<0.05). Apoptosis assays demonstrated that treatment with 0.50 and 1.00 µmol/L PP Ⅶ significantly increased the apoptosis rates of both cell lines (<0.05), upregulated apoptosis-related proteins, and downregulated Bcl-2 protein level (<0.05). Cell cycle analysis revealed that PPⅦ treatment led to an increase in G0/G1-phase cells (<0.05) and a decrease in G2/M-phase cells (<0.05), significantly downregulated cyclin D1, CDK4, CDK6, and survivin protein expression (<0.05). In conclusion, PPⅦ exerted anti-lymphoma effects by inhibiting proliferation, promoting apoptosis, and inducing G0/G1 phase arrest in DLBCL cells.
Topics: Humans; Lymphoma, Large B-Cell, Diffuse; Apoptosis; Cell Proliferation; Cell Line, Tumor; Cell Cycle; Proto-Oncogene Proteins c-bcl-2; Diosgenin; Cyclin D1; Cyclin-Dependent Kinase 4
PubMed: 38951069
DOI: 10.3760/cma.j.cn121090-20230831-00099 -
Zhonghua Xue Ye Xue Za Zhi = Zhonghua... Apr 2024The general population in China is aging, and thus the number of older patients with diffuse large B-cell lymphoma (DLBCL) will continue to increase. Individualized...
The general population in China is aging, and thus the number of older patients with diffuse large B-cell lymphoma (DLBCL) will continue to increase. Individualized treatment is required to maximize therapeutic potential while minimizing the risk of toxicity. To improve the diagnosis and treatment of DLBCL in older people in China, the Lymphocyte Disease Group of the Hematology Division of the Chinese Medical Association and Lymphoma Expert Commitee of Chinese Society of Clinical Oncology (CSCO) have organized relevant experts to formulate this consensus.
Topics: Humans; Lymphoma, Large B-Cell, Diffuse; Aged; China; Consensus
PubMed: 38951058
DOI: 10.3760/cma.j.cn121090-20231228-00343 -
The Journal of Rheumatology Jul 2024Systemic sclerosis sine scleroderma (ssSSc), formally described in 1962, is a subset of SSc which, unlike limited (lcSSc) and diffuse cutaneous (dcSSc) forms, lacks skin...
OBJECTIVE
Systemic sclerosis sine scleroderma (ssSSc), formally described in 1962, is a subset of SSc which, unlike limited (lcSSc) and diffuse cutaneous (dcSSc) forms, lacks skin fibrosis. According to the 2013 ACR/EULAR criteria, SSc can be diagnosed in the absence of skin thickening, even if this is expected to develop later in disease course. Driven by a fatal case of ssSSc with cardiac involvement, we analysed published data on ssSSc prevalence and severity.
METHODS
A systematic literature review and qualitative synthesis of SSc cohorts with data on ssSSc was performed.
RESULTS
Thirty-five studies on a total of 25,455 SSc patients published between 1976 and 2023 were identified. The mean prevalence of ssSSc, albeit using different definitions, was almost 10% (range 0-23%), with the largest study reporting a cross-sectional prevalence of 13%. In 5 studies with a follow-up period of up to 9 years, reclassification of ssSSc into lcSSc or dcSSc ranged from 0% to 28%. Interstitial lung disease, pulmonary arterial hypertension, scleroderma renal crisis, and cardiac diastolic dysfunction were present in 46% (range 9.3-59.1%), 15% (range 5.9-24.6%), 5% (range 1.6-24.6%), and 26.5% (range 1.8-40.7%) of ssSSc patients, respectively. Survival across studies was comparable to lcSSc and better than dcSSc.
CONCLUSION
Published data on ssSSc vary widely regarding prevalence, clinical expression and prognosis partly due to underdiagnosis and misclassification. Although classification criteria should not impact appropriate management of patients, updated ssSSc subclassification criteria, which will take into account time from disease onset, should be considered.
PubMed: 38950948
DOI: 10.3899/jrheum.2023-1113 -
Regional Anesthesia and Pain Medicine Jun 2024The erector spinae plane block (ESP block) is frequently employed for thoracic, abdominal, and spinal surgeries, yet its precise mechanism of action remains a subject of...
BACKGROUND
The erector spinae plane block (ESP block) is frequently employed for thoracic, abdominal, and spinal surgeries, yet its precise mechanism of action remains a subject of debate. While initially postulated to influence both ventral and dorsal rami of the spinal nerve, recent studies indicate a predominant impact on the dorsal rami with limited involvement of the ventral rami. To elucidate this mechanism, we conducted an observational study to assess the distribution of ESP infiltration to the ventral rami.
METHODS
We performed 20 ESP infiltrations bilaterally in 10 unembalmed cadavers, targering the T9 transverse process level. A volume of 20 mL of ropivacaine 0.2% and methylene blue 0.01% was used. Dissection was carried out to assess dye distribution, with a focus on involvement of the ventral and dorsal rami, as well as lateral and longitudinal spread within the spinal muscular plane.
RESULTS
No evidence of dye staining was observed in the ventral rami in any of the cadavers; however, the dorsal rami consistently displayed staining. The dye exhibited extensive longitudinal diffusion across the paravertebral musculature, spanning a median of 10 vertebral spaces (T5-L2). The range extended from 3 to 18 spaces, with an IQR of 11 levels (T4-L2), predominantly affecting the longissimus and iliocostalis muscles.
CONCLUSIONS
The infiltration of injectate into the ESP does not contact the ventral rami of segmental spinal nerves. The inference that an in vivo ESP block is a paravertebral "by-proxy" is, therefore, unlikely.
PubMed: 38950933
DOI: 10.1136/rapm-2024-105691 -
International Journal of Gynecological... Jul 2024To assess the diagnostic performance of ultrasonography in pre-operative assessment of lymph nodes in patients with cervical cancer, to compare the outcomes for pelvic...
OBJECTIVES
To assess the diagnostic performance of ultrasonography in pre-operative assessment of lymph nodes in patients with cervical cancer, to compare the outcomes for pelvic and para-aortic regions, and to detect macrometastases and micrometastases separately.
METHODS
Patients were retrospectively included if they met the following inclusion criteria: pathologically verified cervical cancer; ultrasonography performed by one of four experienced sonographers; surgical lymph node staging, at least in the pelvic region-sentinel lymph node biopsy or systematic pelvic lymphadenectomy or debulking. The final pathological examination was the reference standard.
RESULTS
390 patients met the inclusion criteria between 2009 and 2019. Pelvic node macrometastases (≥2 mm) were confirmed in 54 patients (13.8%), and micrometastases (≥0.2 mm and <2 mm) in another 21 patients (5.4%). Ultrasonography had sensitivity 72.2%, specificity 94.0%, and area under the curve (AUC) 0.831 to detect pelvic macrometastases, while sensitivity 53.3%, specificity 94.0%, and AUC 0.737 to detect both pelvic macrometastases and micrometastases (pN1). Ultrasonography failed to detect pelvic micrometastases, with sensitivity 19.2%, specificity 85.2%, and AUC 0.522. There was no significant impact of body mass index on diagnostic accuracy. Metastases in para-aortic nodes (macrometastases only) were confirmed in 16 of 71 patients who underwent para-aortic lymphadenectomy. Ultrasonography yielded sensitivity 56.3%, specificity 98.2%, and AUC 0.772 to identify para-aortic node macrometastases.
CONCLUSION
Ultrasonography performed by an experienced sonographer can be considered a sufficient diagnostic tool for pre-operative assessment of lymph nodes in patients with cervical cancer, showing similar diagnostic accuracy in detection of pelvic macrometastases as reported for other imaging methods (18F-fluorodeoxyglucose positron emission tomography/CT or diffusion-weighted imaging/MRI). It had low sensitivity for detection of small-volume macrometastases (largest diameter <5 mm) and micrometastases. The accuracy of para-aortic assessment was comparable to that for pelvic lymph nodes, and assessment of the para-aortic region should be an inseparable part of the examination protocol.
Topics: Humans; Female; Uterine Cervical Neoplasms; Middle Aged; Lymph Nodes; Retrospective Studies; Ultrasonography; Adult; Lymphatic Metastasis; Aged; Sensitivity and Specificity; Lymph Node Excision; Preoperative Care; Neoplasm Micrometastasis
PubMed: 38950926
DOI: 10.1136/ijgc-2024-005341