A 36‐year‐old woman who presented with upper limb distal weakness since the age of 15 years, with gradual progression to the lower limbs, is reported. Hereditary motor neuropathy was initially ...suspected based on distal weakness and hyporeflexia; however, whole exome sequencing accidentally revealed a compound heterozygous variant in the GNE gene, and ultrasound revealed increased homogeneous echogenicity in the involved muscles, which is characteristic of myopathic changes. Muscle magnetic resonance imaging revealed fatty infiltration in all limb muscles, sparing the triceps brachii, vastus lateralis and vastus medialis. Muscle biopsy revealed intracytoplasmic rimmed vacuole, supporting the diagnosis of GNE myopathy.
Our previous study reported that Epstein-Barr virus(EBV)-encoded latent membrane protein 1 (LMP1) could induce development of CD44(+/High) stem-like cells in nasopharyngeal carcinoma (NPC). However, ...the molecular mechanisms that underlie modulation of cancer stem cells (CSCs) in NPC remain unclear. Here, we show that LMP1 induced CSC-like properties through promotion of the expression of epithelial-mesenchymal transition-like cellular markers and through alterations in differentiation markers. Furthermore, LMP1 activated and triggered phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, which subsequently stimulated expression of CSC markers, development of side population and tumor sphere formation. This suggests that PI3K/AKT pathway has an important role in the induction and maintenance of CSC properties in NPC. Similarly, PI3K/AKT pathway was also activated by phosphorylase in LMP1-induced CD44(+/High) cells. In addition, LMP1 greatly increased expression of miR-21 and downregulated expression of the miR-21 target, PTEN. Overexpression of miR-21 by transfection of miR-21 mimics into LMP1-transformed cells led to phosphorylase-mediated activation of the PI3K/AKT pathway and induction of CSCs. On the contrary, phosphorylation of the PI3K/AKT pathway and the expression of CSC were reversed by an miR-21 inhibitor. The specific inhibitor (Ly294002) of PI3K/AKT pathway significantly decreased expression of miR-21 and CSC markers and upregulated the expression of PTEN, which indicates that miR-21 and PTEN are the downstream effectors of PI3K/AKT and that expression of these two effectors are related to the development of NPC CSCs. Taken together, our novel findings indicate that LMP1, PI3K/AKT, miR-21 and PTEN constitute a positive feedback loop and have a key role in LMP1-induced CSCs in NPC.
The strong spectral dependence of light absorption of brown carbon (BrC) aerosol is regarded to influence aerosol's radiative forcing significantly. The Absorption Angstrom Exponent (AAE) method has ...been widely used in previous studies to attribute light absorption of BrC at shorter wavelengths for ambient aerosols, with a theoretical assumption that the AAE of "pure" black carbon (BC) aerosol equals to 1.0. In this study, the AAE method was applied to both urban and rural environments in the Pearl River Delta (PRD) region of China, with an improvement of constraining the realistic AAE of "pure" BC through statistical analysis of on-line measurement data. A three-wavelength photo-acoustic soot spectrometer (PASS-3) and aerosol mass spectrometers (AMS) were used to explore the relationship between the measured AAE and the relative abundance of organic aerosol to BC. The regression and extrapolation analysis revealed that more realistic AAE values for "pure" BC aerosol (AAEBC) were 0.86, 0.82, and 1.02 between 405 and 781 nm, and 0.70, 0.71, and 0.86 between 532 and 781 nm, in the campaigns of urbanwinter, urbanfall, and ruralfall, respectively. Roadway tunnel experiments were conducted and the results further confirmed the representativeness of the obtained AAEBC values for the urban environment. Finally, the average light absorption contributions of BrC ( relative uncertainties) at 405 nm were quantified to be 11.7 % ( 5 %), 6.3 % ( 4 %), and 12.1 % ( 7 %) in the campaigns of urbanwinter, urbanfall, and ruralfall, respectively, and those at 532 nm were 10.0 % ( 2 %), 4.1 % ( 3 %), and 5.5 % ( 5 %), respectively. The relatively higher BrC absorption contribution at 405 nm in the ruralfall campaign could be reasonably attributed to the biomass burning events nearby, which was then directly supported by the biomass burning simulation experiments performed in this study. This paper indicates that the BrC contribution to total aerosol light absorption at shorter wavelengths is not negligible in the highly urbanized and industrialized PRD region.
The addition of palbociclib to fulvestrant prolonged overall survival among women with hormone receptor–positive, HER2-negative advanced breast cancer who had sensitivity to previous hormonal ...therapy. In the entire trial group, survival differences were not significant.
Background and purpose
Elevated plasma total homocysteine level (tHcy) is associated with increased risk of dementia via increased white matter changes or reduction in cortical volume. Whether tHcy ...has an independent impact on regional perfusion and if it can predict a more rapid cognitive decline in mild Alzheimer dementia (AD) warrants investigation.
Methods
Eighty AD patients with a clinical dementia rating of 1 were enrolled. Their Cognitive Ability Screening Instrument (CASI) scores on enrolment and after 1 year of follow‐up as well as their perfusion index (PI) from single photon emission computed tomography upon enrolment were analyzed.
Results
In cross‐sectional analysis, elevated tHcy was associated with lower frontal PI independent of cerebrovascular risk factors (β = −0.35, P = 0.009). The CASI scores correlated with temporo‐parietal PI (Pearson r range 0.3–0.39, P < 0.01) but not with tHcy or frontal PI. By longitudinal analysis, only tHcy level was related to a more rapid cognitive decline (odds ratio for executive function score 1.82; odds ratio for total CASI score 1.74).
Conclusions
Cognitive performance in mild AD can be reflected by hypo‐perfusion of the temporo‐parietal region while frontal hypo‐perfusion may be mediated by tHcy. tHcy level is an independent risk factor for rapid cognitive decline, especially in the executive function.
We present new observational determinations of the evolution of the 2–10 keV X-ray luminosity function (XLF) of active galactic nuclei (AGN). We utilize data from a number of surveys including both ...the 2 Ms Chandra Deep Fields and the AEGIS-X 200 ks survey, enabling accurate measurements of the evolution of the faint end of the XLF. We combine direct, hard X-ray selection and spectroscopic follow-up or photometric redshift estimates at z < 1.2 with a rest-frame UV colour pre-selection approach at higher redshifts to avoid biases associated with catastrophic failure of the photometric redshifts. Only robust optical counterparts to X-ray sources are considered using a likelihood ratio matching technique. A Bayesian methodology is developed that considers redshift probability distributions, incorporates selection functions for our high-redshift samples and allows robust comparison of different evolutionary models. We statistically account for X-ray sources without optical counterparts to correct for incompleteness in our samples. We also account for Poissonian effects on the X-ray flux estimates and sensitivities and thus correct for the Eddington bias. We find that the XLF retains the same shape at all redshifts, but undergoes strong luminosity evolution out to z∼ 1, and an overall negative density evolution with increasing redshift, which thus dominates the evolution at earlier times. We do not find evidence that a luminosity-dependent density evolution, and the associated flattening of the faint-end slope, is required to describe the evolution of the XLF. We find significantly higher space densities of low-luminosity, high-redshift AGN than in prior studies, and a smaller shift in the peak of the number density to lower redshifts with decreasing luminosity. The total luminosity density of AGN peaks at z= 1.2 ± 0.1, but there is a mild decline to higher redshifts. We find that >50 per cent of black hole growth takes place at z > 1, with around half in LX < 1044 erg s−1 AGN.
Summary
Sarcopenia was reported to be significantly associated with osteoporosis. In this study, we reported for the first time that sarcopenia was an independent risk predictor of osteoporotic ...vertebral compression refractures (OVCRFs). Other risk factors of OVCRFs are low bone mass density T-scores, female sex, and advanced age.
Introduction
The purpose of this study was to investigate the association between osteoporotic vertebral compression refractures (OVCRFs) and sarcopenia, and to identify other risk factors of OVCRFs.
Methods
We evaluated 237 patients with osteoporotic vertebral compression fracture who underwent percutaneous kyphoplasty (PKP) in our hospital from August 2016 to December 2017. To diagnose sarcopenia, a cross-sectional computed tomography (CT) image at the inferior aspect of the third lumbar vertebra (L3) was selected for estimating muscle mass. Grip strength was used to assess muscle strength. Possible risk factors, such as age, sex, body mass index (BMI), bone mineral density (BMD), location of the treated vertebra, anterior-posterior ratio (AP ratio) of the fractured vertebra, cement leakage, and vacuum clefts, were assessed. The multivariable analysis was used to determine the risk factors of OVCRFs.
Results
During the follow-up period, OVCRFs occurred in 64 (27.0%) patients. Sarcopenia was present in 48 patients (20.3%), including 21 OVCRFs and 27 non-OVCRFs patients. Sarcopenia was significantly correlated with advanced age, lower BMI, lower BMD, and hypoalbuminemia. Compared with non-sarcopenic patients, sarcopenic patients had higher OVCRFs risk. In univariate analysis, sarcopenia (
p
= 0.003), female (
p
= 0.024), advanced age (≥ 75 years;
p
< 0.001), lower BMD (
p
< 0.001), lower BMI (
p
= 0.01), TL junction (vertebral levels at the thoracolumbar junction) (
p
= 0.01), cardiopulmonary comorbidity (
p
= 0.042), and hypoalbuminemia (
p
= 0.003) were associated with OVCRFs. Multivariable analysis revealed that sarcopenia (OR 2.271; 95% CI 1.069–4.824,
p
= 0.033), lower BMD (OR 1.968; 95% CI 1.350–2.868,
p
< 0.001), advanced age (≥ 75 years; OR 2.431; 95% CI 1.246–4.744,
p
= 0.009), and female sex (OR 4.666; 95% CI 1.400–15.552,
p
= 0.012) were independent risk predictors of OVCRFs.
Conclusions
Sarcopenia is an independent risk predictor of osteoporotic vertebral compression refractures. Other factors affecting OVCRFs are low BMD T-scores, female sex, and advanced age.
. Huang C‐N, Huang S‐P, Pao J‐B, Hour T‐C, Chang T‐Y, Lan Y‐H, Lu T‐L, Lee H‐Z, Juang S‐H, Wu P‐P, Huang C‐Y, Hsieh C‐J, Bao B‐Y (Kaohsiung Medical University Hospital, Kaohsiung; Kaohsiung Medical ...University, Kaohsiung; Taipei City Hospital, Taipei; Kaohsiung Medical University, Kaohsiung; China Medical University, Taichung; National Taiwan University Hospital; Oriental Institute of Technology; National Taiwan University, Taipei; China Medical University Hospital, Taichung, Taiwan). Genetic polymorphisms in oestrogen receptor‐binding sites affect clinical outcomes in patients with prostate cancer receiving androgen‐deprivation therapy. J Intern Med 2012; 271: 499–509.
Background. Accumulating evidence indicates that oestrogens have significant direct effects on normal prostate development and carcinogenesis. The majority of the biological activities of oestrogens are mediated through the oestrogen receptor (ER), which functions as a hormone‐inducible transcription factor to regulate target gene expression by binding to oestrogen response elements (EREs) in the regulatory regions of target genes. Sequence variants in EREs might affect the ER–ERE interaction and subsequent physiological activities. Therefore, we tested whether common single‐nucleotide polymorphisms (SNPs) inside EREs are related to the clinical outcomes of androgen‐deprivation therapy (ADT) in men with prostate cancer.
Methods. We systematically evaluated 49 ERE SNPs predicted using a genome‐wide database in a cohort of 601 men with advanced prostate cancer treated with ADT. The prognostic significance of these SNPs on disease progression, prostate cancer‐specific mortality (PCSM) and all‐cause mortality (ACM) after ADT was assessed using Kaplan–Meier analysis and a Cox regression model.
Results. Based on multiple hypothesis testing, BNC2 rs16934641 was found to be associated with disease progression; in addition, TACC2 rs3763763 was associated with PCSM, and ALPK1 rs2051778 and TACC2 rs3763763 were associated with ACM. These SNPs remained significant in multivariate analyses that included known clinicopathological predictors. Moreover, a combined genotype effect on ACM was observed when ALPK1 rs2051778 and TACC2 rs3763763 were analysed in combination. Patients with a greater number of unfavourable genotypes had a shorter time to ACM during ADT (P for trend <0.001).
Conclusion. The incorporation of ERE SNPs into models with known predictors might improve outcome prediction in patients with prostate cancer receiving ADT.
The purpose of this study was to summarize the effects of physical activity and exercise on peripheral brain‐derived neurotrophic factor (BDNF) in healthy humans. Experimental and observational ...studies were identified from PubMed, Web of Knowledge, Scopus, and SPORT Discus. A total of 32 articles met the inclusion criteria. Evidence from experimental studies suggested that peripheral BDNF concentrations were elevated by acute and chronic aerobic exercise. The majority of the studies suggested that strength training had no influence on peripheral BDNF. The results from most observational studies suggested an inverse relationship between the peripheral BDNF level and habitual physical activity or cardiorespiratory fitness. More research is needed to confirm the findings from the observational studies.
Huanglongbing (HLB) is a devastating disease of citrus, caused by the phloem-colonizing bacterium Candidatus Liberibacter asiaticus (CLas). Here, we present evidence that HLB is an immune-mediated ...disease. We show that CLas infection of Citrus sinensis stimulates systemic and chronic immune responses in phloem tissue, including callose deposition, production of reactive oxygen species (ROS) such as H
O
, and induction of immunity-related genes. The infection also upregulates genes encoding ROS-producing NADPH oxidases, and downregulates antioxidant enzyme genes, supporting that CLas causes oxidative stress. CLas-triggered ROS production localizes in phloem-enriched bark tissue and is followed by systemic cell death of companion and sieve element cells. Inhibition of ROS levels in CLas-positive stems by NADPH oxidase inhibitor diphenyleneiodonium (DPI) indicates that NADPH oxidases contribute to CLas-triggered ROS production. To investigate potential treatments, we show that addition of the growth hormone gibberellin (known to have immunoregulatory activities) upregulates genes encoding H
O
-scavenging enzymes and downregulates NADPH oxidases. Furthermore, foliar spray of HLB-affected citrus with gibberellin or antioxidants (uric acid, rutin) reduces H
O
concentrations and cell death in phloem tissues and reduces HLB symptoms. Thus, our results indicate that HLB is an immune-mediated disease that can be mitigated with antioxidants and gibberellin.
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