Exposures to Synthetic Estrogens at Different Times During the Life, and Their Effect on Breast Cancer Risk

Women are using estrogens for many purposes, such as to prevent pregnancy or miscarriage, or to treat menopausal symptoms. Estrogens also have been used to treat breast cancer which seems puzzling, since there is convincing evidence to support a link between high lifetime estrogen exposure and increased breast cancer risk. In this review, we discuss the findings that maternal exposure to the synthetic estrogen diethylstilbestrol during pregnancy increases breast cancer risk in both exposed mothers and their daughters. In addition, we review data regarding the use of estrogens in oral contraceptives and as postmenopausal hormone therapy and discuss the opposing effects on breast cancer risk based upon timing of exposure. We place particular emphasis on studies investigating how maternal estrogenic exposures during pregnancy increase breast cancer risk among daughters. New data suggest that these exposures induce epigenetic modifications in the mammary gland and germ cells, thereby causing an inheritable increase in breast cancer risk for multiple generations.     

Cephalometric pharyngeal changes after Le Fort I osteotomy in different types of clefts

Fifty patients with clefts (30 unilateral cleft lip and palate (UCLP), 9 bilateral cleft lip and palate (BCLP), and 11 cleft palate only (CP), mean age 25 years) treated with Le Fort I osteotomy were compared retrospectively from cephalograms taken shortly before operation, and at six months and one year postoperatively. Patients with bimaxillary surgery or previous velopharyngoplasty, or both, were excluded. Maxillary advancement was moderate in all groups. One year postoperatively there was a significant change (73%–90% of the surgical advancement) in the sagittal depth of the nasopharyngeal airway but not in the depth of the oropharyngeal airway, the length of the soft palate or the position of the hyoid bone. The nasopharyngeal airway was largest in the CP group both preoperatively and postoperatively. Eleven patients (7 CP, 4 UCLP) had a velopharyngoplasty after the osteotomy to improve their speech. There was no difference in the nasopharyngeal airway in the patients treated by velopharyngoplasty compared with those not so treated, but they seemed to have the shortest maxillas and the greatest surgical changes vertically.     

Long-term maintenance of novel vocabulary in persons with chronic aphasia

Background: The study of novel word learning in aphasia can shed light on the functionality of patients' learning mechanisms and potentially help in treatment planning. Previous studies have indicated that persons with aphasia are able to learn some new vocabulary. However, these learning outcomes appear short-lived and evidence for the ability to use the newly learned words in the long term is lacking.

Aims: Participants with aphasia and matched controls underwent short training where they were taught to name novel objects with novel names. We studied the participants' word learning and particularly their long-term maintenance. We also examined whether the language and verbal short-term memory impairments of the participants with aphasia related to their ability to acquire and maintain phonological and semantic information on novel words.

Methods & Procedures: Two participants with nonfluent aphasia, LL and AR, and two matched controls took part in the experiment. They were taught to name 20 unfamiliar objects by repeating the names in the presence of the object picture. Half of the items carried a definition that was used to probe incidental semantic learning. There were four training sessions, a post-training test, and follow-up tests up to 6 months post-training. Learning measures included recognition of the trained objects, as well as spontaneous and cued recall in visual confrontation naming. Incidental semantic learning was measured by spontaneous recall of the definitions.

Outcomes & Results: Combining spontaneous and phonologically cued responses, LL acquired 70% and AR 55% of the novel words. With phonological cueing, LL named 50% of the items correctly up to 6 months post-training (vs 95–100% for the controls) and AR 25% up to 8 weeks post-training. AR's lexical-semantic processing, pseudoword repetition and verbal short-term capacity were inferior to those of LL. In line with this, AR learned fewer words and showed more decline in recognition memory for the trained items, and weaker recall of the semantic definitions.

Conclusions: Our results support previous findings that people with aphasia can learn to name novel items. More importantly, the results show for the first time that, with phonological cueing, an individual with aphasia can maintain some of this learning up to 6 months post-training. Moreover the results provide further evidence for the significance of the functional status of lexical-semantic processing on word learning success.     

Quality of Life and Outcomes in African Americans with CKD

Low health-related quality of life (HRQOL) has been associated with increased risk for hospitalization and death in ESRD. However, the relationship of HRQOL with outcomes in predialysis CKD is not well understood. We evaluated the association between HRQOL and renal and cardiovascular (CV) outcomes in 1091 African Americans with hypertensive CKD enrolled in the African American Study of Kidney Disease and Hypertension (AASK) trial and cohort studies. Outcomes included CKD progression (doubling of serum creatinine/ESRD), CV events/CV death, and a composite of CKD progression or death from any cause (CKD progression/death). We assessed HRQOL, including mental health composite (MHC) and physical health composite (PHC), using the Short Form-36 survey. Cox regression analyses were used to assess the relationship between outcomes and five-point decrements in MHC and PHC scores using measurements at baseline, at the most recent annual visit (time-varying), or averaged from baseline to the most recent visit (cumulative). During approximately 10 years of follow-up, lower mean PHC score was associated with increased risk of CV events/CV death and CKD progression/death across all analytic approaches, but only time-varying and cumulative decrements were associated with CKD progression. Similarly, lower mean MHC score was associated with increased risk of CV events/CV death regardless of analytic approach, while only time-varying and cumulative decrements in mean MHC score was associated with CKD progression and CKD progression or death. In conclusion, lower HRQOL is associated with a range of adverse outcomes in African Americans with hypertensive CKD.     

Separate mechanisms for development and performance of compulsive checking in the quinpirole sensitization rat model of obsessive-compulsive disorder (OCD)

Rationale

Acute administration of serotonergic agonist, meta-chlorophenylpiperazine (mCPP), attenuates performance of compulsive checking in an animal model of obsessive-compulsive disorder (OCD). It is not known whether mCPP has a similar effect on development of compulsive checking.

Objectives

The objective of the study was to examine whether similar mechanisms mediate the development versus the performance of compulsive checking in the rat model.

Methods

Four groups of male rats (N?=?14/group) were tested: two experimental groups co-injected with D2/D3 dopamine agonist quinpirole (0.25 mg/kg) and mCPP (0.625 mg/kg or 1.25 mg/kg), and two control groups, one co-injected with quinpirole and saline, the other receiving injections of saline. The time course of development of compulsive checking across injections 1 to 10 in quinpirole-treated rats was compared to rats co-injected with quinpirole and mCPP.

Results

Results showed that during the course of chronic treatment, mCPP (1.25 mg/kg) significantly attenuated performance of checking behavior. However, when these rats were retested for expression of compulsive checking (that is, with an injection of quinpirole only), their profile of compulsive checking was no different from the control rats treated throughout with quinpirole only.

Conclusions

Findings show that mCPP inhibits performance of compulsive checking but does not block quinpirole from inducing the neural substrate underlying this compulsive behavior. Hence, a separate mechanism underlies the induction of compulsive checking and the performance of it. It is suggested that development of the OCD endophenotype reflects neuroplastic changes produced by repeated dopamine D2/D3 receptor stimulation, while stimulation of serotonergic receptors mediates a negative feedback signal that shuts down the motor performance of checking.     

Islet amyloid in type 2 diabetes, and the toxic oligomer hypothesis

Type 2 diabetes (T2DM) is characterized by insulin resistance, defective insulin secretion, loss of beta-cell mass with increased beta-cell apoptosis and islet amyloid. The islet amyloid is derived from islet amyloid polypeptide (IAPP, amylin), a protein coexpressed and cosecreted with insulin by pancreatic beta-cells. In common with other amyloidogenic proteins, IAPP has the propensity to form membrane permeant toxic oligomers. Accumulating evidence suggests that these toxic oligomers, rather than the extracellular amyloid form of these proteins, are responsible for loss of neurons in neurodegenerative diseases. In this review we discuss emerging evidence to suggest that formation of intracellular IAPP oligomers may contribute to beta-cell loss in T2DM. The accumulated evidence permits the amyloid hypothesis originally developed for neurodegenerative diseases to be reformulated as the toxic oligomer hypothesis. However, as in neurodegenerative diseases, it remains unclear exactly why amyloidogenic proteins form oligomers in vivo, what their exact structure is, and to what extent these oligomers play a primary or secondary role in the cytotoxicity in what are now often called unfolded protein diseases.     

Linguistic and pragmatic aspects of narration in Finnish typically developing children and children with specific language impairment

This study investigates narratives of Finnish children with specific language impairment (SLI) from linguistic and pragmatic perspectives, in order to get a comprehensive overview of these children’s narrative abilities. Nineteen children with SLI (mean age 6;1 years) and 19 typically developing age-matched children participated in the study. Their picture-elicited narrations were analysed for linguistic productivity and complexity, grammatical and referential accuracy, event content, the use of mental state expressions and narrative comprehension. Children with SLI showed difficulties in every aspect of narration in comparison to their peers. Only one measure of productivity, the number of communication units, did not reach statistical significance. Not only was linguistic structure fragile but also pragmatic aspects of storytelling (referencing, event content, mental state expressions and inferencing) were demanding for children with SLI. Results suggest that pragmatic aspects of narration should be taken into account more often when assessing narrative abilities of children with SLI.