Objective: Spinal muscular atrophy, lower limb-dominant (SMA-LED), and Charcot-Marie-Tooth type 2O (CMT2O) are two kinds of familial neuromuscular diseases. In this study, we reported two patients with CMT2O caused by DYNC1H1 mutations and further analyzed the genotype-phenotype correlations. Methods: Two CMT2O patients and their parents’ clinical data were collected and genetic analysis was applied. PubMed, Web of Science, CNKI and Wanfang Data were searched, and all publications that met the inclusion criteria were carefully screened. Results: Genetic testing of our two CMT2O patients revealed heterozygous mutations DYNC1H1 c.1792C>T/p.R598C and c.790C>G/p.R264G, respectively. Next, a total of 22 original published articles were included and analyzed. Compared to SMA-LED, CMT2O patients had no proximal-dominant wasting, more distal-dominant weakness of lower limbs and more sensory abnormalities. Genotype-phenotype analysis revealed that mutations in the DYN1 region of DYNC1H1 protein were associated with a more severe phenotype, more complicated symptoms and more involvement of the central nervous system than that in the DHC_N1 region. Conclusion: Our findings of the phenotypic differences between SMA-LED and CMT2O patients provide references for early diagnosis and differentiation of the two diseases. The genotype-phenotype correlation may reflect the pathogenesis underlying dyneinopathy caused by DYNC1H1 mutations.
Soil water holding capacities (SWHCs) is important input factor in hydrological simulation models for sustainable water management. Forests that covered 63% of South Korea are the main source of clean water, and it is essential to estimate SWHCs on a nationwide scale for effective forest water resources management. However, there are a few studies estimating SWHCs on a nationwide scale in the temperate regions especially in South Korea. Fortunately, forest spatial big data have been collected on a national scale, and the nationwide prediction of the SWHC can be possible with this dataset. In this study, spatial prediction of forest SWHCs (saturated water content, water content at pF1.8 and 2.7) was conducted with 953 forest soil samples and forest spatial big dataset. 4 soil properties and 14 environmental covariates were used for predicting SWHCs. Simple linear regression and random forest model were compared for selecting the optimal predictive model. From the variable importance analysis, environmental covariates had as big importance as soil properties had. And prediction performance of the model with environmental covariates as the input data was higher than that of the model with soil properties. Comparing two models, the random forest model could accurately and stably predict SWHCs than the simple linear model. As a result of spatial prediction of SWHCs at the national scale through the random forest model and the forest spatial big dataset, it was confirmed that higher SWHCs were distributed along with the Baekdudaegan, the watershed-crest-line in South Korea.
This study characterizes the dynamics of exchange fluxes between Brazos River Alluvium Aquifer and the Brazos River, TX, USA. Seven alternative conceptual models for the connection between the river and the aquifer were simulated in HYDRUS 2D using small-scale, high-resolution transects across the river. These models assumed varying aquifer lithology and river incision depths and considered processes such as riverbed clogging and seepage face flows. The simulations were forced by observed river stage values and tested against observed hydraulic heads in two nearby monitoring wells. The nearly 1.5 years of sub-hourly measurements spanned both flood and drought periods. The best-fit conceptual model supported a hypothesized hydraulic disconnection between the subsurface near the river and the wider alluvial aquifer. In contrast to the assumptions of previous studies, these data were more consistent with the presence of an abandoned paleochannel rather than riverbed clogging or other low-permeability zones. The implications for groundwater-surface water exchanges, and their modelling, are profound. Across the range of models, the difference in average baseflow predicted was nearly 13 m3/d/m, equivalent to seven times the firm water rights allocated for river users.
Global climate change poses major challenges for current biodiversity conservation efforts. Assessing species’ vulnerability to climate change is a prerequisite for developing effective strategies to reduce emerging climate-related threats. We used the maximum entropy algorithm (MaxEnt model) to assess potential changes in snow leopard (Panthera uncia) suitable habitat in Qinghai Province, China under a mild climate change scenario. Our results showed that the area of snow leopard suitable habitat in Qinghai Province was 302,821 km2 under current conditions and 228,997 km2 under 2050’s climatic scenario, and that its mean elevation would shift upward 90 m. At present, nature reserves protect 38.78% of the currently suitable habitat and will protect 42.56% of future suitable habitat. Current areas climate refugia amounted to 212,341 km2, mainly distributed in Sanjiangyuan, Qilian mountains and surrounding areas. Our results provide valuable information for formulating strategies to meet future conservation challenges brought on by climate stress. We suggest that conservation efforts in Qinghai Province should focus on protecting areas of climate refugia and on maintaining or building corridors when planning for future species management.
Background and aim of the study Guidelines on myocardial revascularization indicate for type V myocardial infarction (MI) that postoperative troponin elevations need not be exclusively ischemic but may also be caused by direct epicardial injury. Additional complexity arises from the introduction of high-sensitive troponin markers. The present study attempts to contribute to the understanding of postoperative high-sensitive cardiac troponin T (hs-cTnT) increase. Methods Type of surgery, potential factors affecting the postoperative hs-cTnT increase, and possible thresholds indicative of type V MI were analyzed. Results Among 400 included patients, 2.8% had intervention-related ischemia analogous to the type V MI definition. Receiver-operating characteristics confirmed good discriminatory power for hs-cTnT and creatine kinase myocardial band (CK-MB), with ischemia indicating thresholds for hs-cTnT (1705.5 ng/l) and for CK-MB (113 U/l). The median postoperative hs-cTnT/CK-MB increase differed significantly depending on the type of surgery, with the highest increase after mitral valve and the lowest after off-pump coronary surgery. Regression analysis confirmed Maze procedure (p<0.001), cardiopulmonary bypass time (p=0.03), emergency indications (p= 0.01) and blood transfusion (p=0.02) as significant factors associated with hs-cTnT increase. In contrast, CK-MB increase was also associated with mortality (p=0.002). Intra-pericardial defibrillation was the only ischemia-independent factor additionally associated with proposed thresholds (p<0.001). Conclusions The present results confirm the influence of the type of surgery and other intervention-related parameters on the postoperative hs-cTnT increase. Type V MI-indicating thresholds may require reassessment, especially using high-sensitive markers.
Veillonella species rarely cause serious infections, but the incidence of infection has been increasing among immunocompromised individuals. This case of an epidural abscess and spondylitis caused by Veillonella parvula in a hemodialysis patient illustrates the importance of performing anaerobic blood culture in immunocompromised patients with signs of infection.
Variable creep load is one of the most important failure modes for hot-component of aero-engine. To accurately predict creep damage and remaining life, a novel nonlinear creep damage accumulation model is proposed based on the Wilshire function and isodamage line, which takes the influence of load history into account and uses ultimate tension strength to compensate the temperature effect. Experimental result of tests on four kinds of material were utilized to verify the accuracy of the proposed model and to compare it with existing models. It was determined that the novel model was better at predicting damage accumulation than all others model. Furthermore, the proposed model elucidates the evolutionary process of creep damage, and four cases of damage evolution process are discussed.
The Pigeon circovirus (PiCV) containing a circular single stranded DNA (approximately 2 kb) genome belongs to the genus Circovirus of the family Circoviridae. PiCV infections in pigeons ( Columba livia) have been reported worldwide. Currently, pigeon racing is becoming increasingly popular and considered to be a national sport in China, and even, the greatest competitions of racing pigeons are taking place in China. However, there are still no epidemiologic data regarding PiCV infections among racing pigeons in China. To trace the prevalence, genetic variation and evolution of PiCV in sick and healthy racing pigeons, 622 samples were collected from 11 provinces or municipalities in China from 2016 to 2019. Samples were tested by polymerase chain reaction. The results showed that the positive rate of PiCV was 19.3% (120/622) at the sample level and 59.0% (23/39) at the club level, thus suggesting that the virus was prevalent in Chinese racing pigeons. A sequence analysis revealed that the cap genes of the PiCV strains identified in our study displayed a high genetic diversity and shared nucleotide homologies of 71.9%–100% and amino acid homologies of 71.7%–100%. 28 and 36 unique amino acid substitutions were observed in the Cap and Rep proteins derived from our PiCV strains, respectively. Furthermore, The ATT and GTG were highly suspected to be the start codons of the Cap protein. A cap-gene-based phylogenetic analysis showed that the strains in this study could be further divided into seven clades (A, B, C, E, G, H, and I) and some of them were closely related to worldwide strains from different types of pigeons. A large number of recombination events (31 events) were also detected in the PiCV genomes from Chinese racing pigeons. These findings indicate that PiCV strains circulating in China exhibit a high genetic diversity.
Primary breast osteosarcoma (PBOS) is an extremely rare and poor prognostic malignancy that has not a definitive treatment guideline. Here we presented a successfully treated case of PBOS and provided a comprehensive review of the literature which revealed the divergence of opinions regarding the histogenesis and management of this malignancy.
A 70-year-old woman was diagnosed poorly differentiated hepatocellular carcinoma (HCC), lymphocyte rich. In this case, programmed cell death 1 expression was observed. Immune checkpoint inhibitor treatment may be effective in such cases, although there have been no reports of their use for poorly differentiated HCC, lymphocyte-rich.
A 69-year-old man suffered from lethal peritoneal carcinomatosis. At autopsy, no primary lesion was identified in the gastrointestinal, pancreatobiliary, respiratory, urinary and male reproductive organs. The tumor consisted of mucin-containing and gland-forming columnar cells with minimal nuclear atypia. The final diagnosis was primary peritoneal mucinous adenocarcinoma in a man.
This case series reports lead poisoning with “Swamp stone” powder in a family. Swamp stone contains heavy metals with poisoning potentials. The chelating agent had more efficiency in parents than their children in lowering the blood level lead. It is important to find sources for lead poisoning and educate population.
Background: Higher anticholinergic burden from medications is associated with increased risk of cardiovascular disease and cognitive function decline. A mechanistic pathway has never been established. We aimed to determine whether chronic inflammation may mediate these associations. Methods: Participants were drawn from the European Prospective Investigation into Cancer, Norfolk cohort (40-79 years at baseline). The anticholinergic cognitive burden score (ACB) was calculated at baseline/first (1HC) (1993/97) and second (2HC) (1998/2000) health checks. Plasma fibrinogen and C-reactive protein (CRP) were measured during 1HC and Tumour Necrosis Factor alpha (TNF-α) and interleukin 6 (IL-6) during 2HC. Cross-sectional associations between ACB and inflammatory markers were examined for 1HC and 2HC, respectively. The prospective association was also examined between 1HC ACB and 2HC inflammatory markers. All models adjusted for age, sex, lifestyle factors, co-morbidities and medications. Results: 17,678 and 22,051 participants were included in cross-sectional analyses for CRP, and fibrinogen, respectively. A total of 5,101 participants with available data for TNF-α and IL-6 were included in the longitudinal analyses. Cross-sectionally, a point increase in the ACB was associated with a significant increase in all inflammatory markers (beta (standard error): fibrinogen – 0.035g/l (0.006), p<0.001; CRP 0.284mg/l (0.044), p<0.001; TNF-α 0.031pg/ml (0.010), p=0.002; and IL-6 0.112pg/ml (0.033), p=0.001. Longitudinally, a unit increase in the ACB was associated with a significant increase in TNF-α 0.028pg/ml (0.011), p=0.013 and IL-6 0.076 pg/ml (0.035), p=0.029. Conclusion: Higher anticholinergic burden was significantly associated with higher inflammatory markers. Inflammation may mediate the relationship between exposure to anticholinergic medications and adverse outcomes
Objectives: A lot of medication risks related to high-dose methotrexate (HDMTX) therapy still remain to be identified and standardized. This study aims to establish an evidence-based practice guideline for individualized medication of HDMTX. Methods: The practice guideline was launched by the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society. The guideline was developed following the WHO handbook for guideline development and the methodology of evidence-based medicine (EBM). The guideline was initially registered in the International Practice Guidelines Registry Platform (IPGRP-2017CN021). Systematic reviews were conducted to synthesis available evidence. A multicenter cross-sectional study was conducted by questionnaires to evaluate patients’ perception and willingness on individualized medication of HDMTX. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the quality of evidence and to grade the strength of recommendations. Results: Multidisciplinary working groups were included in this guideline, including clinicians, pharmacists, methodologists, pharmacologists and pharmacoeconomic specialists. A total of 124 patients were involved to integrate patient values and preferences. Finally, the guideline presents 28 recommendations, regarding evaluation prior to medication (renal function, liver function, pleural effusion, comedications, genetic testing), pre-treatment and routine dosing regimen, therapeutic drug monitoring (necessity, method, timing, target concentration), leucovorin rescue (initial timing, dosage regimen and optimization), management of toxicities. Of them, 12 are strong recommendations. Conclusions: We developed an evidence-based practice guideline with respect to HDMTX medication using a rigorous and multidisciplinary approach. This guideline provides comprehensive and practical recommendations involving the whole process of HDMTX medication to health care providers.
Achieving Cardiac resynchronization therapy (CRT) with Biventricular pacing(BiVP) pacing for patients with moderate-to-severe heart failure (HF), left ventricular (LV) systolic dysfunction and ventricular dyssynchrony is well established and is currently the standard of care. Multiple studies have demonstrated significant improvement in quality of life, functional status, and exercise capacity in patients with New York Heart Association (NYHA) class III and IV heart failure who underwent resynchronization therapy1,2. In addition, resynchronization therapy is associated with survival benefit3. However, one third of patients do not respond to BIVP. New modalities for resynchronization have emerged namely His bundle pacing (HBP) and left ventricular septal pacing (LVSP). In this paper, we will review the benefits and limitations of BiVP and also the role of new pacing modalities such as HBP and LVSP in patients with HF with reduced left ventricular ejection fraction (LVEF) and electrical dysynchrony.
We report a COVID-19 case with unprecedented viral complexity. In the first severe episode, two different SARS-CoV-2 strains (superinfection) were identified within a week. Three months after discharge, patient was readmitted and was infected in a nosocomial outbreak with a different strain, suffering a second milder COVID-19 episode.