Monosynaptic Rabies Tracing Reveals Sex- and Age-Dependent Dorsal Subiculum Connectivity Alterations in an Alzheimer's Disease Mouse Model.

The subiculum (SUB), a hippocampal formation structure, is among the earliest brain regions impacted in Alzheimer's disease (AD). Toward a better understanding of AD circuit-based mechanisms, we mapped synaptic circuit inputs to dorsal SUB using monosynaptic rabies tracing in the 5xFAD mouse model by quantitatively comparing the circuit connectivity of SUB excitatory neurons in age-matched controls and 5xFAD mice at different ages for both sexes. Input-mapped brain regions include the hippocampal subregions (CA1, CA2, CA3), medial septum and diagonal band, retrosplenial cortex, SUB, postsubiculum (postSUB), visual cortex, auditory cortex, somatosensory cortex, entorhinal cortex, thalamus, perirhinal cortex (Prh), ectorhinal cortex, and temporal association cortex.

Hippocampal neural circuit connectivity alterations in an Alzheimer's disease mouse model revealed by monosynaptic rabies virus tracing.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with growing major health impacts, particularly in countries with aging populations. The examination of neural circuit mechanisms in AD mouse models is a recent focus for identifying new AD treatment strategies. We hypothesize that age-progressive changes of both long-range and local hippocampal neural circuit connectivity occur in AD.

CT-morphologic and CT-textural patterns of response in inoperable soft tissue sarcomas treated with pazopanib-a preliminary retrospective cohort study.

Objective: To analyze patterns of response in soft tissue sarcomas exposed to pazopanib using CT-morphologic and textural features and their suitability for evaluating therapeutic response.

Methods: Retrospective evaluation of CT response and texture patterns in 33 patients (23 female; mean age: 61.2 years, range, 30-85 years) with soft tissue sarcomas treated with pazopanib from October 2008 to July 2017.

Redox Non-Innocent Behavior of a Terminal Iridium Hydrazido(2-) Triple Bond.

The synthesis of the first terminal Group 9 hydrazido(2-) complex, Cp*IrN(TMP) (6) (TMP=2,2,6,6-tetramethylpiperidine) is reported. Electronic structure and X-ray diffraction analysis indicate that this complex contains an Ir-N triple bond, similar to Bergman's seminal Cp*Ir(N Bu) imido complex. However, in sharp contrast to Bergman's imido, 6 displays remarkable redox non-innocent reactivity owing to the presence of the N lone pair.

Five-year changes in biologic risk factors and risk of type 2 diabetes: are attained but not initial risk factor levels of importance?

Independent effects of changes in biologic risk factors on type 2 diabetes incidence remain unclear. The authors examined whether associations between changes in biologic risk factors and diabetes risk are driven by initial or attained risk factor levels. Biologic risk factors were measured at baseline and at each 5-year interval follow-up (rounds 2, 3, and 4) among 4,204 initially healthy men and women, aged 20-59 years, participating in the Dutch Doetinchem Cohort Study (1987-2007).

Radio frequency ablation combined with interleukin-2 induces an antitumor immune response to renal cell carcinoma in a murine model.

Purpose: Immune based therapy has gained renewed interest in the search for treatment strategies for metastasized renal cell carcinoma. We determined whether radio frequency ablation combined with interleukin-2 would induce a tumor specific immune response and serve as an in situ vaccine against renal cell carcinoma.

Materials And Methods: Mice with orthotopic renal tumors were treated with radio frequency ablation combined with interleukin-2, radio frequency ablation only, interleukin-2 only or no treatment as the control.

Hormone therapy and coronary heart disease risk by vasomotor menopausal symptoms.

Objectives: We examined whether the association between hormone therapy (HT) use and coronary heart disease (CHD) risk differed between women with and without vasomotor symptoms (VMS).

Study Design: We used data from a Dutch (EPOS) and Swedish (WHILA) population-based sample of 8865 women, aged 46-64 years, and free of CHD, stroke, venous thrombosis/pulmonary embolism or cancer at baseline. Data on HT use, VMS and potential confounders were collected by questionnaires.

Vasomotor menopausal symptoms are associated with increased risk of coronary heart disease.

Objective: Emerging evidence suggests that women with vasomotor menopausal symptoms (VMS) may have an adverse cardiovascular disease (CVD) risk profile. We investigated whether VMS are related to an increased risk of future coronary heart disease (CHD) and whether possible associations can be explained by CVD risk factors.

Methods: Data used were from a Dutch and Swedish population-based sample of 10,787 women enrolled between 1995 and 2000, aged 46 to 64 years, and free of CVD at baseline.

Lack of anti-tumour reactivity despite enhanced numbers of circulating natural killer T cells in two patients with metastatic renal cell carcinoma.

Natural killer T (NK T) cells play a central role as intermediates between innate and adaptive immune responses important to induce anti-tumour reactivity in cancer patients. In two of 14 renal cell carcinoma (RCC) patients, treated with interferon (IFN)-α, we detected significantly enhanced numbers of circulating NK T cells which were typed phenotypically and analysed for anti-tumour reactivity. These NK T cells were T cell receptor (TCR) Vα24/Vβ11(+), 6B11(+) and bound CD1d tetramers.

Menstrual cycle characteristics and risk of coronary heart disease and type 2 diabetes.

In a prospective cohort study, we observed that women with a history of irregular cycles have a 28% increased coronary heart disease risk and tended to have a higher type 2 diabetes risk as compared with women who had a regular cycle length of 27 to 29 days. This association could not be explained by metabolic risk factors or altered hormone levels.

Vasomotor symptoms, estradiol levels and cardiovascular risk profile in women.

Objectives: We investigated whether menopausal vasomotor symptoms (VMS) are related to an adverse cardiovascular risk profile. Furthermore, we examined the association between estradiol levels and VMS, and whether an association between VMS and cardiovascular risk factors can be explained by estradiol levels.

Study Design: We used data from a Swedish population-based sample of 5857 women, aged 50-64 years.

Gender differences in risk factors for coronary heart disease.

Coronary heart disease (CHD), traditionally considered a male disease, is also a major threat to women. This review article addresses independent risk factors for CHD that are specific for women as well as non-gender-specific risk factors and how their effects differ between men and women. Although polycystic ovary syndrome (PCOS) in women is associated with an adverse metabolic risk profile, current evidence regarding future risk of CHD is conflicting.

A high menaquinone intake reduces the incidence of coronary heart disease.

Background And Aim: Vitamin K dependent proteins have been demonstrated to inhibit vascular calcification. Data on the effect of vitamin K intake on coronary heart disease (CHD) risk, however, are scarce. To examine the relationship between dietary vitamins K(1) and K(2) intake, and its subtypes, and the incidence of CHD.

Vasomotor symptoms are associated with a lower bone mineral density.

Objective: The severity of vasomotor symptoms has been hypothesized to be linked to a lower bone mineral density (BMD). We examined whether women with vasomotor symptoms are different from women without symptoms with regard to BMD.

Methods: We used data from a population-based sample of 5,600 women, aged 46 to 57 years and free from bone diseases, who participated in the first cross-sectional part of the Eindhoven Perimenopausal Osteoporosis Study between 1994 and 1995.

Do differences in childhood diet explain the reduced overweight risk in breastfed children?

Breastfeeding has been associated with a reduced risk of overweight later in life. This study investigates whether differences in diet and lifestyle at 7 years of age between breastfed and formula-fed children can explain the difference in overweight prevalence at 8 years of age. We studied 2,043 Dutch children born in 1996-1997 who participated in the Prevention and Incidence of Asthma and Mite Allergy birth cohort study.

Value of serum S-100B for prediction of distant relapse and survival in stage III B/C melanoma.

Background: The biochemical marker serum S-100B has been proven to reflect the stage of melanoma and to be useful for disease monitoring and prediction of survival, mainly in stage IV disease. For stage III melanoma, limited data are available and its predictive value for relapse is unknown. Serum S-100B was evaluated prospectively for monitoring response and its predictive value for relapse and overall survival in stage IIIB/C melanoma patients.

Predictive factors for severe toxicity of sunitinib in unselected patients with advanced renal cell cancer.

Sunitinib has been registered for the treatment of advanced renal cell cancer (RCC). As patient inclusion was highly selective in previous studies, experience with sunitinib in general oncological practice remains to be reported. We determined the efficacy and safety of sunitinib in patients with advanced RCC included in an expanded access programme.

Cytokine therapy response as a selection criterion for cytoreductive nephrectomy in metastatic renal clear-cell carcinoma of intermediate prognosis. Results and conclusions from a combined analysis.

Aims: To assess the strategy of using an absence of progression at metastatic sites following initial cytokine therapy outcome as a selection criterion for nephrectomy in patients with synchronous metastatic renal carcinoma and an intermediate prognosis according to the Memorial Sloan Kettering prognostic index classification.

Materials And Methods: A combined retrospective analysis of patients with clear-cell subtype from studies of initial cytokine treatment response to assist with selection of patients for nephrectomy. We analyzed survival times, UCLA integrated staging system scores, number of nephrectomies and risk of progression to unresectability of the primary tumor during treatment.

Lack of elevation of serum S100B in patients with metastatic melanoma as a predictor of outcome after induction with an autologous vaccine of proliferating tumor cells and dendritic cells.

Serum levels of S100B and/or lactate dehydrogenase (LDH) are putative tumor markers in melanoma. Early changes in such markers may correlate with a positive immune response to vaccine therapy. In patients with metastatic melanoma, S100B and LDH serum levels were measured at baseline, and 1 week after 3 weekly subcutaneous injections of investigational, patient-specific vaccines consisting of autologous dendritic cells loaded with antigens from irradiated proliferating autologous tumor cells, and suspended in granulocyte macrophage colony-stimulating factor.

Sunitinib for treatment of advanced renal cell cancer: primary tumor response.

Purpose: Nephrectomy before immunotherapy in patients with metastatic renal cell cancer (RCC) will improve patient outcome. In addition, the primary tumor is known to be refractory to cytokines. Sunitinib is now approved for treatment of advanced RCC, but its effect on the primary tumor has yet to be reported.

Menopausal complaints are associated with cardiovascular risk factors.

It has been hypothesized that women with vasomotor symptoms differ from those without with respect to cardiovascular risk factors or responses to exogenous hormone therapy. We studied whether the presence and extent of menopausal complaints are associated with cardiovascular risk profile. Data were used from a population-based sample of 5523 women, aged 46 to 57 years, enrolled between 1994 and 1995.

Phase I clinical study with multiple peptide vaccines in combination with tetanus toxoid and GM-CSF in advanced-stage HLA-A*0201-positive melanoma patients.

Successful induction of functional tumor-specific T cells by peptide vaccination in animal models has resulted in many clinical trials to test this approach in advanced-stage melanoma patients. In this phase I clinical trial, 11 end-stage melanoma patients were vaccinated intradermally with 3 peptides: MART-1(26-35) E27L (ELAGIGILTV), tyrosinase(368-376) N375Q (YMDGTMSQV), and gp100(209-217) T210M (IMQVPFSV), admixed with tetanus toxoid and granulocyte-monocyte colony stimulating factor. The peptide vaccine was well tolerated at all tested doses, and led to grade 1-2 toxicity only.

Temozolomide in advanced malignant melanoma with small brain metastases: can we withhold cranial irradiation?

Background: The efficacy of radiotherapy (RT) in patients who have brain metastases from melanoma is limited. In this study, the authors evaluated the efficacy of treatment with temozolomide in patients with metastatic melanoma, including small brain metastases, who did not require immediate RT and investigated the feasibility of deferring RT.

Methods: Patients with brain metastasis were identified from 3 prospective studies of temozolomide (with or without immunotherapy) for metastatic melanoma.

Intra-national variation in trends in overweight and leisure time physical activities in The Netherlands since 1980: stratification according to sex, age and urbanisation degree.

Objective: To investigate time trends in overweight and Leisure Time Physical Activities (LTPA) in The Netherlands since 1980. Intra-national differences were examined stratified for sex, age and urbanisation degree.

Subjects And Methods: We used a random sample of about 140,000 respondents aged 20-69 years from the Health Interview Survey (Nethhis) and subsequent Permanent Survey on Living Conditions (POLS).

Extended continuous oral temozolomide in patients with progressive metastatic renal cell carcinoma not responding to interferon alpha 2b.

The aim of the study was to evaluate the toxicity and efficacy of oral extended continuous temozolomide in patients with progressive metastatic renal cell carcinoma (RCC) not responding to immunotherapy after removal of the primary tumor. Patients with progressive metastatic RCC received protracted temozolomide 100 mg/m2 orally on days 1-21 every 28 days. Response was assessed after 2 cycles to be followed by another 2 cycles in the absence of progression.