Patients with arterial hypertension have an increased risk of developing tumors, particularly renal cell carcinoma. Arterial hypertension is linked to DNA damage via the generation of oxidative ...stress, in which an upregulated renin–angiotensin–aldosterone system plays a crucial role. The current study investigated surrogates of oxidative stress and DNA damage in a group of hypertensive patients (HypAll, n = 64) and subgroups of well (HypWell, n = 36) and poorly (HypPoor, n = 28) controlled hypertensive patients compared to healthy controls (n = 8). In addition, a longitudinal analysis was performed with some of the hypertensive patients. Markers for oxidative stress in plasma (SHp, D-ROM, and 3-nitrotyrosine) and urine (8-oxodG, 15-F2t-isoprostane, and malondialdehyde) and markers for DNA damage in lymphocytes (γ-H2AX and micronuclei) were measured. In HypAll, all markers of oxidative stress except malondialdehyde were increased compared to the controls. After adjustment for age, this association was maintained for the protein stress markers SHp and 3-nitrotyrosine. With regard to the markers for DNA damage, there was no difference between HypAll and the controls. Further, no significant differences became apparent in the levels of both oxidative stress and DNA damage between HypWell and HypPoor. Finally, a positive correlation between the development of blood pressure and oxidative stress was observed in the longitudinal study based on the changes in D-ROM and systolic blood pressure. In conclusion, we found increased oxidative stress in extensively treated hypertensive patients correlating with the level of blood-pressure control but no association with DNA damage.
Diabetes is a risk factor for the development of cardiovascular diseases associated with impaired angiogenesis or increased endothelial cell apoptosis.
Here it is shown that angiogenic repair of ...ischemic hindlimbs was impaired in Lepr(db/db) mice, a leptin receptor-deficient model of diabetes, compared with wild-type (WT) C57BL/6 mice, as evaluated by laser Doppler flow and capillary density analyses. To identify molecular targets associated with this disease process, hindlimb cDNA expression profiles were created from adductor muscle of Lepr(db/db) and WT mice before and after hindlimb ischemia using Affymetrix GeneChip Mouse Expression Set microarrays. The expression patterns of numerous angiogenesis-related proteins were altered in Lepr(db/db) versus WT mice after ischemic injury. These transcripts included neuropilin-1, vascular endothelial growth factor-A, placental growth factor, elastin, and matrix metalloproteinases implicated in blood vessel growth and maintenance of vessel wall integrity.
These data illustrate that impaired ischemia-induced neovascularization in type 2 diabetes is associated with the dysregulation of a complex angiogenesis-regulatory network.
The promyelocytic zinc finger transcription factor (PLZF) is required for the development of activated phenotypes in NKT and other innate T lymphocytes. Although strong TCR stimulation has been ...implicated in the induction of PLZF, the factors regulating PLZF expression are incompletely understood. We show in this study that costimulation of preselection double-positive thymocytes through the signaling lymphocyte activation molecule family receptor Ly108 markedly enhanced PLZF expression compared with that induced by TCR stimulation alone. Costimulation with Ly108 increased expression of early growth response protein (Egr)-2 and binding of Egr-2 to the promoter of Zbtb16, which encodes PLZF, and resulted in PLZF levels similar to those seen in NKT cells. In contrast, costimulation with anti-CD28 failed to enhance Egr-2 binding and Zbtb16 expression. Moreover, mice lacking Ly108 showed decreased numbers of PLZF-expressing CD4(+) T cells. Together, these results support a potential role for Ly108 in the induction of PLZF.
Aims
This study aimed to evaluate the bidirectional relationship between kidney and cardiovascular (CV) events in trial participants with type 2 diabetes and CV disease.
Methods and results
Post hoc ...analyses of EMPA‐REG OUTCOME using Cox regression models were performed to assess the association of baseline factors with risk of a kidney event and bidirectional associations of incident kidney events and CV events. Among placebo‐treated participants, baseline factors significantly associated with greater kidney event risk included lower baseline estimated glomerular filtration rate, albuminuria, higher uric acid, low‐density lipoprotein cholesterol levels, and prior heart failure (HF). Coronary artery disease was not associated with increased risk. In placebo‐treated participants, occurrence of an incident non‐fatal kidney event increased the subsequent risk of hospitalization for HF (HHF) but not 3‐point major adverse CV events (non‐fatal stroke, non‐fatal myocardial infarction, and CV death). Vice versa, HHF (but not myocardial infarction/stroke) increased the risk of subsequent kidney events. These associations were generally also seen in empagliflozin‐treated participants and in the overall population. Interestingly, the risk of kidney events following HHF was not significantly increased in the relatively small number of placebo‐treated participants already diagnosed with HF at baseline.
Conclusions
These findings demonstrate a bidirectional inter‐relationship between HHF and kidney events. Further exploration of this relationship and strategies to optimize the use of therapies to reduce both kidney and HF outcomes is warranted.
Domestic violence is the most common cause of nonfatal injury to women in the United States. To identify risk factors for such injuries, we examined the socioeconomic and behavioral characteristics ...of women who were victims of domestic violence and the men who injured them.
We conducted a case-control study at eight large, university-affiliated emergency departments. The 256 intentionally injured women had acute injuries resulting from a physical assault by a male partner. The 659 controls were women treated for other conditions in the emergency department. Information was collected with a standardized questionnaire; no information was obtained directly from the male partners.
The 256 intentionally injured women had a total of 434 contusions and abrasions, 89 lacerations, and 41 fractures and dislocations. In a multivariate analysis, the characteristics of the partners that were most closely associated with an increased risk of inflicting injury as a result of domestic violence were alcohol abuse (adjusted relative risk, 3.6; 95 percent confidence interval, 2.2 to 5.9); drug use (adjusted relative risk, 3.5; 95 percent confidence interval, 2.0 to 6.4); intermittent employment (adjusted relative risk, 3.1; 95 percent confidence interval, 1.1 to 8.8); recent unemployment (adjusted relative risk, 2.7; 95 percent confidence interval, 1.2 to 6.5); having less than a high-school-graduate's education (adjusted relative risk, 2.5; 95 percent confidence interval, 1.4 to 4.4); and being a former husband, estranged husband, or former boyfriend (adjusted relative risk, 3.5; 95 percent confidence interval, 1.5 to 8.3).
Women at greatest risk for injury from domestic violence include those with male partners who abuse alcohol or use drugs, are unemployed or intermittently employed, have less than a high-school-graduate's education, and are former husbands, estranged husbands, or former boyfriends of the women.
Treatment with sodium-glucose co-transporter-2 inhibitors induces an initial 3–5 ml/min/1.73 m2 decline in estimated glomerular filtration rate (eGFR). Although considered to be of hemodynamic origin ...and largely reversible, this ‘eGFR dip’ may cause concern in clinical practice, which highlights the need to better understand its incidence and clinical implications. In this post hoc analysis of the EMPA-REG OUTCOME trial, 6,668 participants randomized to empagliflozin 10 mg, 25 mg or placebo with eGFR available at baseline and week four were categorized by initial eGFR change into three groups; over 10% decline (‘eGFR dipper’), over 0 and up to 10% decline (‘eGFR intermediate’), no eGFR decline (‘eGFR non-dipper’). Baseline characteristics of ‘eGFR intermediate’ and ‘eGFR non-dipper’ were generally comparable. An initial ‘eGFR dip’ was observed in 28.3% of empagliflozin versus 13.4% of placebo-treated participants; odds ratio 2.7 95% Confidence Interval 2.3–3.0. In multivariate logistic regression, diuretic use and higher KDIGO risk category at baseline were independently predictive of an ‘eGFR dip’ in empagliflozin versus placebo. Safety and beneficial treatment effects with empagliflozin on cardiovascular and kidney outcomes were consistent across subgroups based on these predictive factors. The initial ‘eGFR dip’ did not have a major impact on the treatment effect of empagliflozin on subsequent cardiovascular death, hospitalization for heart failure, and incident or worsening kidney disease. Thus, patients with type 2 diabetes with more advanced kidney disease and/or on diuretic therapy were more likely to experience an ‘eGFR dip’ of over 10% with empagliflozin, but reduction in cardiovascular and kidney outcomes was not relevantly modified by such ‘eGFR dip.’
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Gliomas are the most common intrinsic brain tumors in adults, and in accordance with their clinical behavior and patients' outcome, they are graded by the World Health Organization (WHO) ...classification of brain tumors. One very interesting candidate for targeted tumor therapy may be epidermal growth factor receptor (
) amplification. Here, we performed an integrated comparative analysis of
amplification in 34 glioma samples using standard fluorescence in situ hybridization (FISH) and Illumina EPIC Infinium Methylation Bead Chip and correlated results with molecular glioma hallmarks. We found that the EPIC analysis showed the same power of detecting
amplification compared with FISH.
amplification was detectable in high-grade gliomas (25%). Moreover,
amplification was found to be present solely in
wildtype gliomas (26%) and
mutated gliomas (27%), occurring independently of MGMT promoter methylation status and being mutually exclusive with 1p/19q codeletion (LOH). In summary, EPIC Bead Chip analysis is a reliable tool for detecting
amplification and is comparable with the standard method FISH.
amplification is a phenomenon of
wildtype
mutated high-grade gliomas.
Women with gynecologic cancers may face geographic barriers to standard-of-care consultation with a gynecologic oncologist. While telemedicine may help overcome these geographic barriers, there are ...no qualitative data exploring gynecologic cancer patients' attitudes towards telemedicine for cancer care. Patients with gynecologic malignancies may have preferences distinct from general oncology populations due to the sensitive nature of the diseases and anatomy involved.
Semi-structured interviews were conducted with 15 patients with gynecologic cancers to identify perceived advantages and disadvantages of telemedicine use for gynecologic cancer care. Past experience with telemedicine was elicited as were suggestions for cancer care encounters most compatible with telemedicine. Interviews were transcribed, coded, and analyzed for emergent themes.
All patients interviewed were open to the use of telemedicine. Emergent themes regarding advantages of telemedicine included convenience, cost savings, reduced travel, avoidance of infectious disease, and availability of care for those too unwell for in-person visits. Themes regarding disadvantages of telemedical care included technical difficulties, perceived need for examination or testing, and potential compromise of therapeutic relationship. Patients were particularly concerned that difficulty in establishing a therapeutic relationship would compromise initial consultations with gynecologic oncologists via telemedicine.
Patients with gynecologic cancer are open to use of telemedicine for their care. Particular attention should be paid to overcoming patients' hesitancy to have initial visits with gynecologic oncologists, as these consultations have the greatest potential to improve access to high-quality gynecologic cancer care.
•Cost, convenience, safety, and comfort were identified as advantages of telemedical care for gynecologic cancers.•Testing, examination, and clinician-patient rapport were perceived as barriers to high-quality care via telemedicine.•Participants were particularly concerned about initial visits and cancer diagnoses delivered remotely.•These themes should be used as patient-reported outcomes for implementation of telemedicine for gynecologic cancer care.
We present algebraic multilevel iteration (AMLI) methods for isogeometric discretization of scalar second order elliptic problems. The construction of coarse grid operators and hierarchical ...complementary operators are given. Moreover, for a uniform mesh on a unit interval, the explicit representation of B-spline basis functions for a fixed mesh size h is given for p=2,3,4 and for C0- and Cp-1-continuity. The presented methods show h- and (almost) p-independent convergence rates. Supporting numerical results for convergence factor and iterations count for AMLI cycles (V-, linear W-, nonlinear W-) are provided. Numerical tests are performed, in two-dimensions on square domain and quarter annulus, and in three-dimensions on quarter thick ring.
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