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further refined for clinical diagnostic applications.
The DESI-MS system allowed for identification of IDH mutation status, glioma diagnosis, and estimation of tumor cell infiltration intraoperatively in a large human glioma cohort. This methodology should be further refined for clinical diagnostic applications.
This study aimed to determine the effect of pinacidil, a nonselective KATP channel opener, on diabetes-induced retinal gliosis and inflammation.
Primary and immortalized cell lines of retinal microglia and Müller cells were used to set up a coculture model. In the trans-well system, microglia were seeded in the upper chamber and Müller cells in the bottom chamber. Microglia were polarized into proinflammatory (M1, with lipopolysaccharide and INF-γ) with or without different pinacidil concentrations before coculturing with Müller cells. The expression of inflammatory or anti-inflammatory genes and protein in microglia, and the expression of glial fibrillary acidic protein (GFAP), Kir4.1, and AQP4 in Müller cells were examined by real-time polymerase chain reaction and Western blot. Pinacidil was injected intravitreally into streptozotocin-induced diabetic rats. Retinal gliosis and inflammation were examined by immunohistochemistry and Western blot.
Intravitreal injection of pinacidil alleviated diabetes-induced Müller cell gliosis and microglial activation and reduced vascular endothelial growth factor expression. In vitro study demonstrated that pinacidil inhibited tumor necrosis factor and interleukin-1β expression in M1-type microglia and alleviated the M1 microglia-induced GFAP expression in the Müller cells. Furthermore, we found that pinacidil on its own, or in combination with IL-4, can upregulate arginase-1 (Arg-1) and Kir6.1 expression in microglial cells.
Our results suggest that potassium channels are critically involved in diabetes-induced gliosis and microglial activation. The KATP opener, pinacidil, can reduce microglial activation by upregulating Kir6.1 expression.
Our results suggest that potassium channels are critically involved in diabetes-induced gliosis and microglial activation. The KATP opener, pinacidil, can reduce microglial activation by upregulating Kir6.1 expression.
To investigate brain white matter pathways using magnetic resonance diffusion tensor imaging (DTI) and correlate the findings with developmental outcomes at 18 months of corrected age in preterm infants with and without retinopathy of prematurity (ROP).
In this prospective cohort study, probabilistic maps of the 26 white matter pathways associated with motor, cognitive, visual, and limbic/language functions were generated in 84 preterm infants using DTI obtained at term-equivalent age. The mean fractional anisotropy (FA) and mean diffusivity (MD) values were compared between those with and without ROP. Developmental outcomes were assessed using the third edition of Bayley Scales of Infant and Toddler Development (BSID-III) at 18 months of corrected age. Multiple regression analyses were performed to confirm the association among developmental outcomes, white matter pathways, and ROP or severe ROP after adjusting for potential confounders.
The white matter pathways were insignificantly associated with ROP or severe ROP. There were no significant differences in the FA and MD values of the pathways between ROP infants treated with and without bevacizumab therapy. Furthermore, there were no significant differences in BSID-III scores between infants with and without ROP or severe ROP. The BSID-III scores at 18 months of age showed a significant association with FA or MD values in several pathways.
ROP or severe ROP was insignificantly associated with maturation delay of the white matter pathways. Developmental outcomes were similar between preterm infants with and without ROP or severe ROP or between ROP infants with and without intravitreal bevacizumab therapy.
ROP or severe ROP was insignificantly associated with maturation delay of the white matter pathways. Developmental outcomes were similar between preterm infants with and without ROP or severe ROP or between ROP infants with and without intravitreal bevacizumab therapy.
Bis-retinoids are a major component of lipofuscin that accumulates in the retinal pigment epithelium (RPE) in aging and age-related macular degeneration (AMD). Although bis-retinoids are known to originate from retinaldehydes required for the light response of photoreceptor cells, the relative contributions of the chromophore, 11-cis retinal, and photoisomerization product, all-trans retinal, are unknown. In photoreceptor outer segments, all-trans retinal, but not 11-cis retinal, is reduced by retinol dehydrogenase 8 (RDH8). Using Rdh8-/- mice, we evaluated the contribution of increased all-trans retinal to the formation and stability of RPE lipofuscin.
Rdh8-/- mice were reared in cyclic-light or darkness for up to 6 months, with selected light-reared cohorts switched to dark-rearing for the final 1 to 8 weeks. The bis-retinoid A2E was measured from chloroform-methanol extracts of RPE-choroid using HPLC-UV/VIS spectroscopy. Lipofuscin fluorescence was measured from whole flattened eyecups (excitation, 488rmore, decreases in A2E levels occurring after moving cyclic-light-reared Rdh8-/- mice to darkness are consistent with processing of A2E within the RPE and the existence of a mechanism that could be a therapeutic target for controlling A2E cytotoxicity.
Restless legs syndrome is a common neurologic disorder that is more prevalent in women than in men, and it has been suggested that female hormones may be involved in the disorder's pathophysiology.
To determine whether women who underwent premenopausal bilateral oophorectomy were at increased risk of restless legs syndrome.
This cohort study was performed using data from the Mayo Clinic Cohort Study of Oophorectomy and Aging-2 for a population in Olmsted County, Minnesota. There were 1653 women who underwent premenopausal bilateral oophorectomy before the age of 50 years for a benign indication between 1988 and 2007 and 1653 age-matched women (of same age plus or minus 1 year) in a reference group. Follow-up was conducted until the end of the study period (ie, December 31, 2014). Data were analyzed from January to July 2020.
Undergoing bilateral oophorectomy, as shown in medical record documentation.
Diagnosis of restless legs syndrome, as defined using Diagnostic and Statistical Manual of Mental Diio (HR) of 1.44 (95% CI, 1.08-1.92; P = .01). After stratification by indication for the bilateral oophorectomy, there was an increased risk of restless legs syndrome among women without a benign ovarian condition (HR, 1.52; 95% CI, 1.03-2.25; P = .04) but not among women with a benign condition (HR, 1.25; 95% CI, 0.80-1.96; P = .34). Treatment with estrogen therapy through the age of 46 years in women who underwent bilateral oophorectomy at younger ages was not associated with a difference in risk.
This cohort study found that risk of restless legs syndrome was increased among women who underwent bilateral oophorectomy prior to menopause, especially those without a benign ovarian indication.
This cohort study found that risk of restless legs syndrome was increased among women who underwent bilateral oophorectomy prior to menopause, especially those without a benign ovarian indication.
Female community health volunteers (FCHVs) are frontline community health workers who have been a valuable resource in improving public health outcomes in Nepal, but their value is understudied in diabetes care.
To assess whether an FCHV-delivered intervention is associated with reduced blood glucose levels among adults with type 2 diabetes.
This community-based, open-label, 2-group, cluster randomized clinical trial with a 12-month delayed control group design was conducted in 14 clusters of a semiurban setting in Western Nepal. A total of 244 adults with type 2 diabetes were recruited between November 2016 and April 2017. The follow-up assessment was conducted at 12 months after enrollment. Data analysis was performed from January to February 2019.
Seven clusters were randomized to the FCHV-delivered intervention in which 20 FCHVs provided home visits 3 times a year (once every 4 months) for health promotion counseling and blood glucose monitoring. If participants had blood glucose levels of 126 mg/e intervention group and 153.43 [43.39] mg/dL in the control group). At 12-month follow-up, the mean fasting blood glucose decreased by 22.86 mg/dL in the intervention group, whereas it increased by 7.38 mg/dL in the control group. The mean reduction was 27.90 mg/dL greater with the intervention (95% CI, -37.62 to -18.18 mg/dL; P < .001). In secondary outcome analyses, there was a greater decline in mean systolic blood pressure in the intervention group than in the control group (-5.40 mm Hg; 95% CI, -8.88 to -1.92 mm Hg; P = .002). There was detectable difference in the intake of antihyperglycemic medication between the groups (relative risk, 1.35; 95% CI, 1.1 to 1.74; P = .02).
These findings suggest that an FCHV-delivered intervention is associated with reduced blood glucose levels among adults with type 2 diabetes in a low-resource setting in Nepal.
ClinicalTrials.gov Identifier NCT03304158.
ClinicalTrials.gov Identifier NCT03304158.
Glucagonlike peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and dipeptidyl peptidase-4 inhibitors (DPP-4i) are associated with low rates of hypoglycemia, and postmarketing trials of GLP-1RA and SGLT2i demonstrated that these medications improved cardiovascular and kidney outcomes.
To compare trends in initiation of treatment with GLP-1RA, SGLT2i, and DPP-4i by older adults with type 2 diabetes insured by Medicare Advantage vs commercial health plans.
This retrospective cohort study used administrative claims data from a deidentified database of commercially insured and Medicare Advantage beneficiaries. Adults aged 58 to 66 years with type 2 diabetes who filled any medication prescription to lower glucose levels from January 1, 2016, to December 31, 2019, were compared between groups.
Enrollment in a Medicare Advantage or commercial health insurance plan.
The odds of initiating GLP-1RA, SGLT2i, and DPP-4i treatment were examined for Medicare Advantage vs cot decisions and efforts to promote greater equity in diabetes management appear to be needed.
These findings suggest that Medicare Advantage beneficiaries may be less likely than commercially insured beneficiaries to be treated with newer medications to lower glucose levels, with greater disparities among lower-income patients. XMU-MP-1 inhibitor Better understanding of nonclinical factors contributing to treatment decisions and efforts to promote greater equity in diabetes management appear to be needed.Race, ethnicity, and racism (RER) are interconnected with the critical problems tackled in the Grand Challenges for Social Work (GCSW). Yet, the extent to which the GCSW discuss the central role of RER is less clear. This article investigates how the GCSW integrate RER in their discourse. Using content analysis, authors examined all 21 concept papers that comprise the 12 initial GCSW to determine their attention to RER. Authors assessed whether each paper made any reference to race or ethnicity, whether race or ethnicity was considered as a primary theme, and whether racism was mentioned. Nine GCSW had at least one paper that mentioned race or ethnicity; seven had at least one paper that treated race and ethnicity as a major construct. Five GCSW contained at least one paper that discussed racism's impacts on their topical interests. None of the papers analyzed in the study defined or specified their conceptualization of racism. The GCSW are strategically positioned to widen and deepen social work's focus on RER, and the recent adoption of the 13th GCSW to "Eliminate racism" is an important first step.
Homepage: https://www.selleckchem.com/products/xmu-mp-1.html
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