Activation of the IKK2/NF-κB pathway in VSMCs inhibits calcified vascular stiffness in CKD

IKK2/NF-κB pathway–mediated inflammation in vascular smooth muscle cells (VSMCs) has been proposed to be an etiologic factor in medial calcification and stiffness. However, the role of the IKK2/NF-κB pathway in medial calcification remains to be elucidated. In this study, we found that chronic kidney disease (CKD) induces inflammatory pathways through the local activation of the IKK2/NF-κB pathway in VMSCs associated with calcified vascular stiffness. Despite reducing the expression of inflammatory mediators, complete inhibition of the IKK2/NF-κB pathway in vitro and in vivo unexpectedly exacerbated vascular mineralization and stiffness. In contrast, activation of NF-κB by SMC-specific IκBα deficiency attenuated calcified vascular stiffness in CKD. Inhibition of the IKK2/NF-κB pathway induced cell death of VSMCs by reducing anti–cell death gene expression, whereas activation of NF-κB reduced CKD-dependent vascular cell death. In addition, increased calcification of extracellular vesicles through the inhibition of the IKK2/NF-κB pathway induced mineralization of VSMCs, which was significantly reduced by blocking cell death in vitro and in vivo. This study reveals that activation of the IKK2/NF-κB pathway in VSMCs plays a protective role in CKD-dependent calcified vascular stiffness by reducing the release of apoptotic calcifying extracellular vesicles

Differing deregulation of HER2 in primary gastric cancer and synchronous related metastatic lymph nodes

 Sorbtional properties of carbonic sorbents on the base of pine sawdust in the processes of purification of water mediums and complicated technological solution from petroleum products and phosphorus compounds are investigated. The possibility of carbonic sorbents modification by halogen organic compounds to increase the degree of purification of water ecosystems is analyzed. Исследованы сорбционные свойства углеродных сорбентов на основе опилок сосны в процессе очистки водных сред и сложных технологических растворов от нефтепродуктов и соединений фосфора. Рассмотрена возможность модифицирования углеродных сорбентов галогенсодержащих органическими соединениями с целью повыше-ния степени очистки водных экосистем. Досліджено сорбційні властивості вуглецевих сорбентів на основі обпилювань сосни у процесі очищення водних середовищ і складних технологічних розчинів від нафтопродуктів і з’єднань фосфору. Розглянуто можливість модифікування вуглецевих сорбентів галогеновмісними органічними з’єднаннями з метою підвищення ступеня очищення водних екосистем

Ectopic adrenal adenoma causing gross hematuria: Steroidogenic enzyme profiling and literature review

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149375/1/iju512068.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149375/2/iju512068_am.pd

Activating transcription factor-4 promotes mineralization in vascular smooth muscle cells

Emerging evidence indicates that upregulation of the ER stress–induced pro-osteogenic transcription factor ATF4 plays an important role in vascular calcification, a common complication in patients with aging, diabetes, and chronic kidney disease (CKD). In this study, we demonstrated the pathophysiological role of ATF4 in vascular calcification using global Atf4 KO, smooth muscle cell–specific (SMC-specific) Atf4 KO, and transgenic (TG) mouse models. Reduced expression of ATF4 in global ATF4-haplodeficient and SMC-specific Atf4 KO mice reduced medial and atherosclerotic calcification under normal kidney and CKD conditions. In contrast, increased expression of ATF4 in SMC-specific Atf4 TG mice caused severe medial and atherosclerotic calcification. We further demonstrated that ATF4 transcriptionally upregulates the expression of type III sodium-dependent phosphate cotransporters (PiT1 and PiT2) by interacting with C/EBPβ. These results demonstrate that the ER stress effector ATF4 plays a critical role in the pathogenesis of vascular calcification through increased phosphate uptake in vascular SMCs

A Proposed Set of Metrics to Reduce Patient Safety Risk From Within the Anatomic Pathology Laboratory

Background: Anatomic pathology laboratory workflow consists of 3 major specimen handling processes. Among the workflow are preanalytic, analytic, and postanalytic phases that contain multistep subprocesses with great impact on patient care. A worldwide representation of experts came together to create a system of metrics, as a basis for laboratories worldwide, to help them evaluate and improve specimen handling to reduce patient safety risk. Method: Members of the Initiative for Anatomic Pathology Laboratory Patient Safety (IAPLPS) pooled their extensive expertise to generate a list of metrics highlighting processes with high and low risk for adverse patient outcomes. Results: Our group developed a universal, comprehensive list of 47 metrics for patient specimen handling in the anatomic pathology laboratory. Steps within the specimen workflow sequence are categorized as high or low risk. In general, steps associated with the potential for specimen misidentification correspond to the high-risk grouping and merit greater focus within quality management systems. Primarily workflow measures related to operational efficiency can be considered low risk. Conclusion: Our group intends to advance the widespread use of these metrics in anatomic pathology laboratories to reduce patient safety risk and improve patient care with development of best practices and interlaboratory error reporting programs

A prospective study of the psychobehavioral factors responsible for a change from non-patient irritable bowel syndrome to IBS patient status

<p>Abstract</p> <p>Background</p> <p>To investigate non-patient irritable bowel syndrome (IBS) change to IBS and to determine factors predictive of the onset of IBS, individual biological factors, psychological factors, behavioral factors, and environmental factors were examined.</p> <p>Methods</p> <p>The subjects were 105 non-patient IBS (male = 59, female = 46, average age:21.49 ± 2.37), including 68 of the diarrhea-predominant type and 37 of the constipation-predominant type selected from 1,409 university and technical college students by use of a questionnaire based on the Rome II diagnostic criteria. The subjects were followed for three years, and various characteristics and IBS symptoms were serially observed (12 times). The IBS incidence rate was calculated.</p> <p>Results</p> <p>During the three years, 37 non-patient IBS (35.24%) changed to IBS: 28 diarrhea-predominant type and 9 constipation-predominant type. All IBS symptoms disappeared in 26 non-patient IBS subjects (24.76%). According to quantification method II (discriminant analysis), seven factors (stressor, two kinds of stress coping styles, cognitive appraisal, eating habits, sleeping time, and psychologically abuse) were adopted as a predictive model for IBS incidence and were confirmed as predictive of IBS.</p> <p>Conclusion</p> <p>The results of this research show that non-patient IBS is a changeable state that can change into IBS or persons without symptoms. Most of the non-patient IBS subjects who became asymptomatic had had symptoms for six months or less. Furthermore, the longer a non-patient IBS subject had symptoms, the higher the risk of a change to IBS became. The findings suggest the usefulness of identifying and approaching non-patient IBS as early as possible to prevent the onset of IBS. It must be noted that the persons surveyed in the present study had only the diarrhea-predominant and constipation-predominant types. Therefore, the findings of the present study are limited only these two types. Further study including the mixed type is needed.</p

Impact of Chronic Kidney Disease on the Presence and Severity of Aortic Stenosis in Patients at High Risk for Coronary Artery Disease

<p>Abstract</p> <p>Objective</p> <p>We evaluated the impact of chronic kidney disease (CKD) on the presence and severity of aortic stenosis (AS) in patients at high risk for coronary artery disease (CAD).</p> <p>Methods</p> <p>One hundred and twenty consecutive patients who underwent invasive coronary angiography were enrolled. Aortic valve area (AVA) was calculated by the continuity equation using transthoracic echocardiography, and was normalized by body surface area (AVA index).</p> <p>Results</p> <p>Among all 120 patients, 78% had CAD, 55% had CKD (stage 3: 81%; stage 4: 19%), and 34% had AS (AVA < 2.0cm²). Patients with AS were older, more often female, and had a higher frequency of CKD than those without AS, but the prevalence of CAD and most other coexisting conventional risk factors was similar between patients with and without AS. Multivariate linear regression analysis indicated that only CKD and CAD were independent determinants of AVA index with standardized coefficients of -0.37 and -0.28, respectively. When patients were divided into 3 groups (group 1: absence of CKD and CAD, n = 16; group 2: presence of either CKD or CAD, n = 51; and group 3: presence of both CKD and CAD, n = 53), group 3 had the smallest AVA index (1.19 ± 0.30*# cm²/m², *p < 0.05 vs. group 1: 1.65 ± 0.32 cm²/m², and #p < 0.05 vs. group 2: 1.43 ± 0.29* cm²/m²) and the highest peak velocity across the aortic valve (1.53 ± 0.41*# m/sec; *p < 0.05 vs. group 1: 1.28 ± 0.29 m/sec, and #p < 0.05 vs. group 2: 1.35 ± 0.27 m/sec).</p> <p>Conclusion</p> <p>CKD, even pre-stage 5 CKD, has a more powerful impact on the presence and severity of AS than other conventional risk factors for atherosclerosis in patients at high risk for CAD.</p