Prefrontal and parietal regions are involved in naming of objects seen from unusual viewpoints

Object naming is commonly used for demonstrating semantic memory abilities, known to be affected in normal aging. Yet, neuropsychological assessments of older people do not reflect irregularities. The authors used a test with 2 levels of naming complexity by 2 kinds of stimuli: common objects pictured from a conventional viewpoint (usual condition) or from an unconventional viewpoint (unusual condition). The authors studied naming performance with 129 healthy participants, aged 20-85 years. For the usual stimuli, the success rate was high (90.9%), with no reduction in performance until 65 years of age. However, for the unusual stimuli, there was a marked reduction in performance with age. Brain activity was studied on 11 healthy young participants (20-30 years of age) using functional magnetic resonance imaging. The usual condition activated brain regions associated with visual perception, language, and memory. Additional brain regions associated with semantic searching and decision making were obtained in the unusual condition in the prefrontal cortex (Brodmann's area [BA] 9 and BA 47) and anterior cingulate (BA 32). The results suggest that the poor naming performance for unusual-viewed objects in older people might be related to the shrinkage of frontal gray matter with age.     

The economic burden of preventable adverse drug reactions: a systematic review of observational studies

Introduction: Adverse drug reactions (ADRs) are an important cause of morbidity and mortality worldwide. They are associated with healthcare costs due to hospital admissions or prolonged length of stay, as well as additional interventions. The aim of this study was to conduct a systematic review of observational studies to evaluate the economic impact of preventable ADRs.

Areas covered: Published observational research investigating the cost of preventable ADRs in Western countries (limited to the USA and European countries).

Expert opinion: Several reviews have been carried out in the field of the ADR epidemiology but fewer reviews have investigated the economic impact of ADRs, and at the time of writing, none has focused on preventable ADRs. The reason why future research should focus on the costs of preventable ADRs is that both the costs and the negative clinical outcomes are preventable, and as such, are a key point of public health policy action. Nevertheless, the present review highlights an important and sobering limitation of published research on the cost of preventable ADRs, of which the major limitation is the heterogeneity in methods and in reporting which limit what can be known through the summarizing work of a systematic review.     

In Vivo Pelvic and Hip Joint Kinematics in Patients With Cam Femoroacetabular Impingement Syndrome: A Dual Fluoroscopy Study

Femoroacetabular impingement syndrome (FAIS) may alter the kinematic function of the hip, resulting in pain and tissue damage. Previous motion analysis studies of FAIS have employed skin markers, which are prone to soft tissue artifact and inaccurate calculation of the hip joint center. This may explain why the evidence linking FAIS with deleterious kinematics is contradictory. The purpose of this study was to employ dual fluoroscopy (DF) to quantify in vivo kinematics of patients with cam FAIS relative to asymptomatic, morphologically normal control participants during various activities. Eleven asymptomatic, morphologically normal controls and seven patients with cam FAIS were imaged with DF during standing, level walking, incline walking, and functional range of motion activities. Model-based tracking calculated the kinematic position of the hip by registering projections of three-dimensional computed tomography models with DF images. Patients with FAIS stood with their hip extended (mean [95% confidence interval], −2.2 [−7.4, 3.1]°, flexion positive), whereas controls were flexed (5.3 [2.6, 8.0]°; p = 0.013). Male patients with cam FAIS had less peak internal rotation than the male control participants during self-selected speed level-walking (−0.2 [−6.5, 6.1]° vs. −9.8 [−12.2, −7.3]°; p = 0.007) and less anterior pelvic tilt at heel-strike of incline (5°) walking (3.4 [−1.0, −7.9]° vs. 9.8 [6.4, 13.2]°; p = 0.032). Even during submaximal range of motion activities, such as incline walking, patients may alter pelvic motion to avoid positions that approximate the cam lesion and the acetabular labrum. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:823-833, 2020     

SaOS2 Osteosarcoma Cells as an In Vitro Model for Studying the Transition of Human Osteoblasts to Osteocytes

The central importance of osteocytes in regulating bone homeostasis is becoming increasingly apparent. However, the study of these cells has been restricted by the relative paucity of cell line models, especially those of human origin. Therefore, we investigated the extent to which SaOS2 human osteosarcoma cells can differentiate into osteocyte-like cells. During culture under the appropriate mineralising conditions, SaOS2 cells reproducibly synthesised a bone-like mineralised matrix and temporally expressed the mature osteocyte marker genes SOST, DMP1, PHEX and MEPE and down-regulated expression of RUNX2 and COL1A1. SaOS2 cells cultured in 3D collagen gels acquired a dendritic morphology, characteristic of osteocytes, with multiple interconnecting cell processes. These findings suggest that SaOS2 cells have the capacity to differentiate into mature osteocyte-like cells under mineralising conditions. PTH treatment of SaOS2 cells resulted in strong down-regulation of SOST mRNA expression at all time points tested. Interestingly, PTH treatment resulted in the up-regulation of RANKL mRNA expression only at earlier stages of differentiation. These findings suggest that the response to PTH is dependent on the differentiation stage of the osteoblast/osteocyte. Together, our results demonstrate that SaOS2 cells can be used as a human model to investigate responses to osteotropic stimuli throughout differentiation to a mature osteocyte-like stage.     

Twenty-four-hour ambulatory blood pressure in men and women aged 17 to 80 years: the Allied Irish Bank Study.

In order to determine reference values for ambulatory blood pressure, a sample of 815 healthy bank employees (399 men and 416 women), aged 17-79 years, were investigated. Ambulatory blood pressure was recorded over 24 h, taking measurements at 30-min intervals. Blood pressure was also measured by trained observers in the clinic. Ambulatory blood pressure in the 815 subjects averaged 118/72 mmHg over 24 h, 124/78 mmHg during the day (1000-2259 h) and 106/61 mmHg at night (0100-0659 h). Office blood pressure, measured by an observer, was 4/2 mmHg lower (p less than 0.0001) than daytime ambulatory pressure. The 95th centiles for the daytime ambulatory pressure in men were: 114/88 mmHg for the age group 17-29 years (n = 107); 143/91 mmHg from 30-39 years (n = 123); 150/98 mmHg from 40-49 years (n = 109); and 155/103 mmHg in 50-79 year old men (n = 60); for the corresponding age groups in women, the 95th centiles of the daytime pressure were: 131/83 mmHg (n = 174); 132/85 mmHg (n = 149); 150/94 mmHg (n = 55); and 177/97 mmHg (n = 38).     

The effects of recombinant-DNA-derived interferons on the growth of myeloid progenitor cells

Interferons (IFNs) have been shown to have significant effects on hematopoietic cell growth. Previous studies defining these effects have utilized mouse and human alpha-, beta-, and gamma-IFN isolated from supernatants of stimulated cells. Despite purification, the possible presence of other lymphokines and soluble factors remains a concern. In this study, the effects of gene-cloned alpha- and gamma-IFN on colony- forming units of granulocyte/macrophage (CFU-GM) progenitors cultured from the peripheral blood of normal volunteers were examined. In addition, blast cell colonies from one patient with acute myelogenous leukemia (AML) were studied. The growth of normal CFU-GM and AML blast cell colonies was inhibited in a dose-dependent manner by gamma- and alpha-IFN. gamma-IFN was ten to 100 times more potent than alpha-IFN in that this species of IFN reduced colony formation by greater than 50% at concentrations of less than 15 antiviral U/mL. The effects of gamma- IFN were neutralized by a monoclonal antibody specific for gamma-IFN. These in vitro studies indicate that human gamma-IFN may be an important modulator of myelopoiesis. Although these data indicate a possible efficacy of gamma-IFN in the treatment of AML, the in vitro results should be considered for their in vivo significance.     

Twenty-four-hour ambulatory blood pressure in community-dwelling elderly men and women,aged 60-102 years

OBJECTIVE: To investigate ambulatory blood pressure in elderly people, including 'old elderly' subjects, aged over 80 years. DESIGN: Cross-sectional study of community-dwelling, elderly subjects. METHODS: Subjects were healthy, self-caring, and living independently. Those who were taking medication affecting blood pressure were excluded. Conventional blood pressure was the mean of two measurements. Ambulatory blood pressure monitoring was performed using the SpaceLabs 90207 device. Daytime and night-time blood pressure were defined by fixed clock intervals. RESULTS: Seventy-five 'young elderly', aged 60-79 years, (39 men, 36 women) and 81 'old elderly' aged 80 years and older (37 men, 44 women) underwent 24-h ambulatory blood pressure monitoring. Systolic blood pressure (SBP) was related to age, correlation coefficients between age and SBP were 0.31, 0.25 and 0.31, respectively, for conventional SBP, daytime SBP and night-time SBP (P < 0.01 for all). There was no correlation between age and diastolic blood pressure. Blood pressure levels were similar in men and women. Mean conventional blood pressure, daytime blood pressure and night-time blood pressure were found to be 149/81, 138/82 and 119/69 mmHg, respectively, in the 'young elderly' and 162/82, 147/83, and 133/71 mmHg, respectively, in the 'old elderly (P < 0.01 for SBP). The night : day SBP ratio was significantly higher in the 'old' elderly compared with the 'young' elderly (0.90 versus 0.86, respectively; P < 0.01). CONCLUSIONS: Ambulatory blood pressure levels in healthy, community-dwelling 'old elderly' are higher than those reported for younger adults and reflect the prominent age-related rise in SBP associated with advanced old age. Advanced old age is associated with a diminished nocturnal dip in blood pressure.