Fragmentation of care as a barrier to optimal ESKD management

Caring for patients with end-stage kidney disease (ESKD) in the United States is challenging, due in part to the complex epidemiology of the disease's progression as well as the ways in which care is delivered. As CKD progresses toward ESKD, the number of comorbidities increases and care involves multiple healthcare providers from multiple subspecialties. This occurs in the context of a fragmented US healthcare delivery system that is traditionally siloed by provider specialty, organization, as well as systems of payment and administration. This article describes the role of care fragmentation in the delivery of optimal ESKD care and identifies research gaps in the evidence across the continuum of care. We then consider the impact of care fragmentation on ESKD care from the patient and health system perspectives and explore opportunities for system-level interventions aimed at improving care for patients with ESKD.     

The 21-aminosteroid antioxidant, U74389F, prevents estradiol-induced depletion of hypothalamic β-endorphin in adult female rats

A single intramuscular injection of 2 mg estradiol valerate (EV) results in neuronal degeneration and β-endorphin depletion in the hypothalamic arcuate nucleus of adult female rats. We have hypothesized that peroxidase-positive astrocytes in this brain region oxidize estrogens and catecholestrogens to semiquinone radicals which mediate oxidative neuronal injury. In the present study, dietary administration of the potent antioxidant 21-aminosteroid, U-74389F, completely blocked EV-induced β-endorphin depletion in the hypothalami of adult female rats. Neither EV nor 21-aminosteroid treatment had any effect on hypothalamic concentrations of neuropeptide Y and Met-enkephalin, confirming that the estradiol lesion is fairly selective for the β-endorphin cell population. The present findings support the hypothesis that the toxic effect of estradiol on hypothalamic β-endorphin neurons is mediated by free radicals.     

Distinct Leishmania braziliensis isolates induce different paces of chemokine expression patterns

Inflammatory events during Leishmania braziliensis infection in mice were investigated. Large lesions were directly correlated with the inflammatory reaction but not with parasite burden. Different L. braziliensis strains induce different paces of chemokine expression patterns, leading to diverse cell recruitment and differential inflammatory responses.     

Microinvasive ductal carcinoma (T1mic) of the breast. The clinicopathological profile and immunohistochemical features of 28 cases

Microinvasive ductal carcinoma of the breast, namely ductal carcinoma in situ with microinvasion (T1mic) as defined by the American Joint Committee on Cancer (AJCC) Staging Manual, is a rare disease, although it is increasing because of widespread use of mammography. The aim of the present study was to describe the clinicopathological and immunohistochemical features of this entity. Twenty-eight patients who were diagnosed as T1mic from January 1997 to August 2002 were studied by using 3-5 mm-thick serial sections with hematoxylin-eosin staining. Immunohistochemical staining for the estrogen receptor (ER), progesterone receptor (PR), p53, Ki-67, and HER-2 were performed. All 28 patients were female, with a mean age of 48.8 years. Twenty-six patients (93%) revealed mammographic abnormalities on routine examination. All foci of the invasions were measured using an ocular micrometer. Invasive foci consisted of isolated cells or cell clusters, or appeared as a tongue-like projection of tumor through the basement membrane of the duct of ductal carcinoma in situ (DCIS). The mean number of invasive foci was 3, and the mean size was 0.6 mm. We found that high nuclear grade and predominant comedo subtype of DCIS components were 57.1% and 46.4%, respectively. Twenty-four cases (86%) demonstrated necrosis of DCIS components. Microinvasion was often associated with periductal stromal reaction (71.5%) and/or a lymphocytic infiltration (78.6%). All patients, excluding two, received axillary resection (the mean number of lymph nodes examined per case was 12), and none had lymph node metastasis. The positive expression of ER and PR strongly related to low grade nuclei and non-comedo subtype; however, the positive expression of HER-2 and P53 related to high grade nuclei and comedo subtype (P<0.01). Ki-67 expression was significantly higher in the high grade nuclei group than in the low grade group (P<0.01). Our study suggested that high nuclear grade and comedo DCIS were more aggressive and more common with microinvasion, and that microinvasion is more likely to be multifocal.     

Behavior Problems in Children With Diabetes: Disentangling Possible Scoring Confounds on the Child Behavior Checklist

Objective: The Child Behavior Checklist (CBCL; T. M. Achenbach,1991), when used to assess the behavior of children with diabetes,may contain confounds because some behavioral items can havea physiologic etiology, and may skew reports of behavioral disturbance. Methods: Two techniques were used to disentangle possible scoringconfounds in the behavioral ratings of children with and withoutdiabetes: (1) the Somatic Complaints scale was deleted, or (2)Diabetes Items, identified a priori with 89% agreement by ninemedical personnel, were deleted. Results: As expected, with traditionally scored protocols, childrenwith diabetes obtained higher Internalizing and Total BehaviorProblem scores than controls. This group difference persistedwhether the Somatic Complaints scale or the Diabetes Items weredeleted. Conclusions: Compared to controls, children with diabetes obtainedmildly elevated scores on six of the eight CBCL scales, regardlessof scoring method, suggesting that their mildly elevated behavioralprofile is not confounded by physiologic symptomatology.     

Domestic Violence Research: Methodological Issues Related to a Community‐Based Intervention With a Vulnerable Population1

Presently, in our society, thousands of children, adolescents, and adults are physically, mentally, and emotionally traumatized from exposure to domestic violence (DV). Exposure to DV, defined here as male violence against their female partners, occurs among all ethnic, cultural, socioeconomic, geographical, and racial groups. DV can lead to depression, negative self‐esteem, and general psychological distress in women. Children exposed to DV have an increased risk of behavioral, emotional, and social problems. DV shelters often provide group counseling and support services for battered women, children, and adolescents residing there, but the programs do not reach the majority of women living in the broader community. Furthermore, few studies have examined the effectiveness and efficacy of support group treatment intervention programs for battered women and children. This is due, in part, to the methodological difficulties inherent in this design. As a way to meet the needs of families that have experienced DV, academic researchers from a Midwestern university and a director of counseling services from a local domestic violence agency have partnered to offer a psycho‐educational intervention designed to     

Cyclosporin A inhibits vaccinia virus replication in vitro

Summary The effect of the immune modulator, Cyclosporin A (CsA) on vaccinia virus replication has been examined in cell cultures. In the present study we report that CsA is anti-viral towards vaccinia virus. Viral yield was inhibited by more than 97% after 24 h postinfection in the presence of 16 µM to 40 µM CsA. An analysis of the infectious cycle in greater detail revealed that CsA did not effect the total level of [³⁵S] methionine incorporation into vaccinia infected cells. However, both early and late viral gene expression were inhibited by CsA. Late viral protein synthesis appeared to be more sensitive to the drug. At least one late viral polypeptide of approximately Mr 38 000 was virtually undetected up to 8 h postinfection in the presence of 40 µM CsA. Host protein synthesis which is normally inhibited by the virus was not turned off until very late in infection. Viral DNA replication was also inhibited by the addition of CsA at levels comparable to those observed for late protein synthesis.     

Family-based and case-control studies reveal no association of lipocalin-type prostaglandin D2 synthase with schizophrenia.

Several observations point to the involvement of disturbed lipid biology in schizophrenia. Reduced response to niacin flushing test, which involves vasodilatation induced by prostaglandin D2 (PGD2), is among the evidences, together with decreased CSF levels of lipocalin-type prostaglandin D2 synthase (PTGDS), the enzyme responsible for the synthesis of PGD2 in the brain. Since PTGDS is also a carrier for lipophilic molecules such as retinoids and thyroid hormones, altered PTGDS levels might influence both PGD2-mediated signaling, and vitamin A and thyroid hormone availability. To test whether genetic variants of PTGDS are involved in the etiology of schizophrenia, we searched for variants in the coding and regulatory regions of the gene. We identified four previously described polymorphisms. Using two case-control samples from Portugal and Brazil, none of the polymorphisms tested was associated with the disease. In addition, no transmission distortion was observed in an independent parents-offspring sample from the Azorean Islands. Our data do not support the involvement of the PTGDS gene in the etiology of schizophrenia.