Unstable os odontoideum contributing to cervical myelopathy and obstructive sleep apnea

Background: Sleep apnea is characterized by repetitive cessation of breathing during sleep. It may be attributed to obstructive, central, or mixed pathologies close to the upper airway resulting in a decreased diameter of the oropharyngeal tract. Case Description: A 36-year-old male with progressive cervicomedullary myelopathy/quadriparesis exhibited obstructive sleep apnea (OSA) attributed to an anteriorly displaced os odontoideum (OO). Atlantoaxial screw-rod stabilization resulted in improvement of both neurological function and OSA. Conclusion: A symptomatic unstable OO may contribute to suboccipital pain, progressive quadriparesis, vertebrobasilar insufficiency, and OSA. Appropriate operative intervention utilizing atlantoaxial screw-rod stabilization may help to resolve these deficits. © 2019 Published by Scientific Scholar on behalf of Surgical Neurology Internationa

Dual inhibition of histone deacetylases and phosphoinositide 3-kinase enhances therapeutic activity against B cell lymphoma

Phosphoinositide 3-kinase (PI3K) and Myc are known to cooperate in promoting the survival and growth of a variety of B-cell lymphomas. While currently there are no small molecule inhibitors of Myc protein, histone deacetylase (HDAC) inhibitors have been shown to reduce levels of Myc protein by suppressing its transcription. We assessed the efficacy of CUDC-907, a new rationally designed dual inhibitor of PI3K and HDACs, in a panel of lymphoma cell lines. CUDC-907 treatment resulted in a dose- and time-dependent growth inhibition and cell death of DLBCL cell lines, irrespective of the cell of origin. CUDC-907 treatment down-regulated the phosphorylation of PI3K downstream targets, including AKT, PRAS40, S6, and 4EBP1, increased histone 3 acetylation, and decreased Myc protein levels. SILAC-based quantitative mass spectrometry demonstrated that CUDC-907 treatment decreased the protein levels of several components of the B cell receptor (BCR) and Toll like receptor (TLR) pathways, including BTK, SYK, and MyD88 proteins. These cellular changes were associated with an inhibition of NF-kB activation. CUDC-907 demonstrated in vivo efficacy with no significant toxicity in a human DLBCL xenograft mouse model. Collectively, these data provide a mechanistic rationale for evaluating CUDC-907 for the treatment of patients with Myc and PI3K-dependent lymphomas

ALDH1 in combination with CD44 as putative cancer stem cell markers are correlated with poor prognosis in urothelial carcinoma of the urinary bladder

Background: The aldehyde dehydrogenase 1 family member A1 (ALDH1A1) is one of the promising markers for identifying cancer stem cells in many cancer types, along with other markers including CD44. The aim of the present study was to evaluate the expression and clinical significance of putative cancer stem cell markers, CD44 and ALDH1A1, in a series of urothelial carcinomas of urinary bladder (UCUB) by tissue microarray (TMA). Materials and Methods: A total of 159 Urothelial Carcinomas (UC) including 96 (60) low grade and 63 (40) high grade carcinomas were immunohistochemically examined for the expression of CD44 and ALDH1A1. Correlations of the relative expression of these markers with clinicopathological parameters were also assessed. Results: High level expression of ALDH1A1 was found in 16 (25/159) of bladder UC which was significantly correlated with increased tumor size (p value=0.002), high grade (p value<0.001), pathologic stage (T1, p value=0.007 and T2, p value<0.001) and increased rate of recurrence (p value=0.013). A high level of CD44 expression was found in 43 (68/159) of cases, being positively correlated with histologic grade (p value=0.032) and recurrence (p value=0.039). Conclusions: Taken together, our results showed that ALDH1 was concurrently expressed in a fraction of CD44+ tumors and its expression correlated with poor prognosis in UCs. ALDH1A1 could be an ideal marker for targeted therapy of UCs in combination with conventional therapies, particularly in patients with high grade carcinomas. These findings indicate that cells expressing ALDH1A1 along with CD44 can be a potential therapeutic target in bladder carcinomas

Co-expression of Cancer Stem Cell Markers OCT4 and NANOG Predicts Poor Prognosis in Renal Cell Carcinomas

Many renal cancer patients experience disease recurrence after combined treatments or immunotherapy due to permanence of cancer stem cells (CSCs). This study was conducted to evaluate the expression patterns and clinical significance of octamer-binding transcription factor 4 (OCT4) and NANOG as the key stem cell factors in renal cell carcinoma (RCC). A total of 186 RCC tissues were immunostained on a tissue microarray (TMA) for the putative CSC markers OCT4 and NANOG. Subsequently, the correlation among the expression of these markers, the clinicopathological variables and survival outcomes were determined. OCT4 and NANOG were expressed in both the nucleus and the cytoplasm of RCC cells. Coexpression of OCT4 and NANOG in renal cancer was significantly associated with RCC subtypes. A significant association was found among nuclear coexpression of OCT4 and NANOG, worse PFS in RCC, and the clear cell renal cell carcinomas (ccRCC) subtype. The OCT4-nuclear high/NANOG-nuclear high phenotype in RCC and ccRCC subtype indicated aggressive tumor behavior and predicted a worse clinical outcome, which may be a useful biomarker to identify patients at high risk of postoperative recurrence and metastasis. Cytoplasmic expression of NANOG could be considered as a novel independent prognostic predictor in patients with renal cancer. © 2018, The Author(s)

Correlation energy of a two-dimensional electron gas from static and dynamic exchange-correlation kernels

We calculate the correlation energy of a two-dimensional homogeneous electron gas using several available approximations for the exchange-correlation kernel $f_{\rm xc}(q,\omega)$ entering the linear dielectric response of the system. As in the previous work of Lein {\it et al.} [Phys. Rev. B {\bf 67}, 13431 (2000)] on the three-dimensional electron gas, we give attention to the relative roles of the wave number and frequency dependence of the kernel and analyze the correlation energy in terms of contributions from the $(q, i\omega)$ plane. We find that consistency of the kernel with the electron-pair distribution function is important and in this case the nonlocality of the kernel in time is of minor importance, as far as the correlation energy is concerned. We also show that, and explain why, the popular Adiabatic Local Density Approximation performs much better in the two-dimensional case than in the three-dimensional one.Comment: 9 Pages, 4 Figure

Experimental wound healing using microamperage electrical stimulation in rabbits

We investigated the effects of microamperage electrical stimulation (MES) on the healing of skin incision in rabbits. Thirty male adult rabbits were randomly divided into sham-treated and experimental groups. Each group was divided into three subgroups, based on the duration of experiment (4, 7, and 15 days). A full-thickness incision was made on the skin of each rabbit. The experimental group received an MES of 200 microamperes current intensity for 2 h/day. Morphometrical and biomechanical evaluations were carried out. The mean number of fibroblasts at day 7 and the mean of tensile strength at day 15 were found to be significantly higher for the experimental group than for those in the sham-treated group (p < 0.01 and p < 0.05, respectively). Daily application of MES significantly accelerated the wound-healing process of full-thickness incision in the rabbits' skin

SMAD4 Expression in Renal Cell Carcinomas Correlates With a Stem-Cell Phenotype and Poor Clinical Outcomes

Renal cell carcinoma (RCC) is the most lethal neoplasm of common urologic cancers with poor prognoses. SMAD4 has a principal role in TGF-β (Transformis growth factorβ)-induced epithelial to mesenchymal transition (EMT) as a key factor in gaining cancer stem cell (CSC) features and tumor aggressiveness. This study aimed to evaluate the expression patterns and clinical significance of SMAD4 in RCC and the impact of its targeting on stem cell/mesenchymal cells and EMT characteristics in renal spheroid derived cells (SDCs) compared to parental cells (PCs) in RCC. The expression pattern and clinical significance of SMAD4 was evaluated in RCC. SDCs were enriched using a sphere culture system. Then SDCs and their PCs were compared with respect to their sphere and colony formation, expression of putative CSC markers, invasiveness as well as expression of genes, including stemness/mesenchymal, SMAD4 and TGFβ1genes. Finally, the effect of SMAD4 knockdown on SDCs was analyzed. We demonstrated that SMAD4 is positively correlated with decreased disease specific survival (DSS) in RCC patients and clear cell RCC (ccRCC) subtype and associates with poor DSS in patients with RCC, especially in ccRCC as the most metastatic RCC subtype. SDCs exhibited higher stem cell/mesenchymal properties. Inhibition of SMAD4 in PCs accelerated the dissociation of SDCs and decreased their clonogenicity, invasiveness, expression of mesenchymal markers and expression of SMAD4 and TGFβ1 genes compared to SDCs before transfection. We suggest that targeting SMAD4 may be useful against renal CSCs and may improve RCC prognosis. © Copyright © 2021 Rasti, Madjd, Saeednejad Zanjani, Babashah, Abolhasani, Asgari and Mehrazma

KiDS-1000: Cross-correlation with Planck cosmic microwave background lensing and intrinsic alignment removal with self-calibration

CONTEXT: Galaxy shear and cosmic microwave background (CMB) lensing convergence cross-correlations contain additional information on cosmology with respect to auto-correlations. While remaining immune to certain systemic effects, these cross-correlations are nonetheless affected by the galaxy's intrinsic alignments (IA). These effects may, in fact, be responsible for the reported low lensing amplitude of the galaxy shear × CMB convergence cross-correlations, compared to the standard Planck ACDM (cosmological constant and cold dark matter) cosmology predictions. AIMS: In this work, we investigate how IA affects the Kilo-Degree Survey (KiDS) galaxy lensing shear and Planck CMB lensing convergence cross-correlation and we compare it to previous treatments, both with and without IA taken into consideration. METHODS: We compared the marginalization over IA parameters and the IA self-calibration (SC) method (with additional observables defined only from the source galaxies) to demonstrate that SC can efficiently break the degeneracy between the CMB lensing amplitude, Alens, and the IA amplitude, AIA. We further investigated how different systematics affect the resulting AIA and Alens and we validated our results with the MICE2 simulation. RESULTS: We find that by including the SC method to constrain IA, the information loss due to the degeneracy between CMB lensing and IA is strongly reduced. The best-fit values are Alens = 0.84-0.22+0.22 and AIA = 0.60-1.03+1.03, while different angular scale cuts can affect Alens by ~10%. We show that an appropriate treatment of the boost factor, cosmic magnification, and photometric redshift modeling is important for obtaining the correct IA and cosmological results

Joint constraints on cosmology and the impact of baryon feedback: Combining KiDS-1000 lensing with the thermal Sunyaeva- Zeldovich effect from Planck and ACT

We conduct a pseudo-analysis of the tomographic cross-correlation between 1000 deg2 of weak-lensing data from the Kilo-Degree Survey (KiDS-1000) and the thermal Sunyaeva- Zeldovich (tSZ) effect measured by Planck and the Atacama Cosmology Telescope (ACT). Using HMX, a halo-model-based approach that consistently models the gas, star, and dark matter components, we are able to derive constraints on both cosmology and baryon feedback for the first time from these data, marginalising over redshift uncertainties, intrinsic alignment of galaxies, and contamination by the cosmic infrared background (CIB). We find our results to be insensitive to the CIB, while intrinsic alignment provides a small but significant contribution to the lensinga- tSZ cross-correlation. The cosmological constraints are consistent with those of other low-redshift probes and prefer strong baryon feedback. The inferred amplitude of the lensinga- tSZ cross-correlation signal, which scales as I8(Om/0.3)0.2, is low by compared to the primary cosmic microwave background constraints by Planck. The lensinga- tSZ measurements are then combined with pseudo-CAmeasurements of KiDS-1000 cosmic shear into a novel joint analysis, accounting for the full cross-covariance between the probes, providing tight cosmological constraints by breaking parameter degeneracies inherent to both probes. The joint analysis gives an improvement of 40% on the constraint of S8 = I8Om/0.3 over cosmic shear alone, while providing constraints on baryon feedback consistent with hydrodynamical simulations, demonstrating the potential of such joint analyses with baryonic tracers such as the tSZ effect. We discuss remaining modelling challenges that need to be addressed if these baryonic probes are to be included in future precision-cosmology analyses