Medical Comorbidities of Dementia: Links to Caregivers’ Emotional Difficulties and Gains

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154268/1/jgs16244_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154268/2/jgs16244.pd

Classification of fracture and non-fracture groups by analysis of coherent X-ray scatter

Osteoporotic fractures present a significant social and economic burden, which is set to rise commensurately with the aging population. Greater understanding of the physicochemical differences between osteoporotic and normal conditions will facilitate the development of diagnostic technologies with increased performance and treatments with increased efficacy. Using coherent X-ray scattering we have evaluated a population of 108 ex vivo human bone samples comprised of non-fracture and fracture groups. Principal component fed linear discriminant analysis was used to develop a classification model to discern each condition resulting in a sensitivity and specificity of 93% and 91%, respectively. Evaluating the coherent X-ray scatter differences from each condition supports the hypothesis that a causal physicochemical change has occurred in the fracture group. This work is a critical step along the path towards developing an in vivo diagnostic tool for fracture risk prediction

Systemic corticosteroids in dermatological practice. Part I: Main adverse effects

Systemic corticosteroids have been used in dermatological practice for approximately 60 years due to their anti-inflammatory and immunosuppressive effects. The challenge of corticosteroid therapy is to counterbalance the desirable actions and undesirable pharmacological effects. Unfortunately, advanced understanding of the mechanisms of action of corticosteroids has not resulted in the development of minimal toxicity regimens. In this article, we report the main pharmacological properties of systemic corticosteroids, their major indications in clinical practice and the adverse effects of high doses and/or prolonged administration.Há quase 60 anos os corticosteróides sistêmicos têm sido amplamente utilizados na área de dermatologia, trazendo benefícios para muitas doenças em decorrência de suas ações antiinflamatórias e imunossupressoras. O desafio de seu uso consiste em contrabalançar os efeitos benéficos e as atividades farmacológicas indesejáveis. Infelizmente, os avanços no conhecimento sobre os mecanismos de ação dos corticosteróides não resultaram no desenvolvimento de regimes com mínima toxicidade. Dessa maneira, este artigo de revisão discorre sobre os aspectos farmacológicos dos corticosteróides sistêmicos, bem como suas principais indicações de uso e efeitos colaterais da administração em altas doses e/ou por longos períodos de tempo.UNIFESPHospital Central da Santa Casa de São Paulo Departamento de Clínica Médica Serviço de DermatologiaHospital Central da Santa Casa de São Paulo Clínica de DermatologiaUNIFESPSciEL

Early changes in biochemical markers of bone turnover and their relationship with bone mineral density changes after 24 months of treatment with teriparatide

Summary We report the changes in biochemical markers of bone formation during the first 6 months of teriparatide therapy in postmenopausal women with osteoporosis according to previous antiresorptive treatment. Prior therapy does not adversely affect the response to teriparatide treatment. Similar bone markers levels are reached after 6 months of treatment. Introduction The response of biochemical markers of bone turnover with teriparatide therapy in subjects who have previously received osteoporosis drugs is not fully elucidated. We examined biochemical markers of bone formation in women with osteoporosis treated with teriparatide and determined: (1) whether the response is associated with prior osteoporosis therapy, (2) which marker shows the best performance for detecting a response to therapy, and (3) the correlations between early changes in bone markers and subsequent bone mineral density (BMD) changes after 24 months of teriparatide. Methods We conducted a prospective, open-label, 24-month study at 95 centers in 10 countries in 758 postmenopausal women with established osteoporosis (n = 181 treatment-naïve) who had at least one post-baseline bone marker determination. Teriparatide (20 μg/day) was administered for up to 24 months. We measured procollagen type I N-terminal propeptide (PINP), bone-specific alkaline phosphatase (b-ALP), and total alkaline phosphatase (t-ALP) at baseline, 1 and 6 months, and change in BMD at the lumbar spine, total hip and femoral neck from baseline to 24 months. Results Significant increases in formation markers occurred after 1 month of teriparatide regardless of prior osteoporosis therapy. The absolute increase at 1 month was lower in previously treated versus treatment-naïve patients, but after 6 months all groups reached similar levels. PINP showed the best signal-to-noise ratio. Baseline PINP correlated positively and significantly with BMD response at 24 months. Conclusions This study suggests that the long-term responsiveness of bone formation markers to teriparatide is not affected in subjects previously treated with antiresorptive drugs

Anti-tumour activity of bisphosphonates in preclinical models of breast cancer

There is increasing evidence of anti-tumour effects of bisphosphonates from pre-clinical studies, supporting a role for these drugs beyond their traditional use in treatment of cancer-induced bone disease. A range of model systems have been used to investigate the effects of different bisphosphonates on tumour growth, both in bone and at peripheral sites. Most of these studies conclude that bisphosphonates cause a reduction in tumour burden, but that early intervention and the use of high and/or repeated dosing is required. Successful eradication of cancer may only be achievable by targeting the tumour cells directly whilst also modifying the tumour microenvironment. In line with this, bisphosphonates are demonstrated to be particularly effective at reducing breast tumour growth when used in combination with agents that directly target cancer cells. Recent studies have shown that the effects of bisphosphonates on breast tumours are not limited to bone, and that prolonged anti-tumour effects may be achieved following their inclusion in combination therapy. This has opened the field to a new strand of bisphosphonate research, focussed on elucidating their effects on cells and components of the local, regional and distal tumour microenvironment. This review highlights the recent developments in relation to proposed anti-tumour effects of bisphosphonates reported from in vitro and in vivo models, and summarises the data from key breast cancer studies. Evidence for effects on different processes and cell types involved in cancer development and progression is discussed, and the main outstanding issues identified

Novel application and validation of in vivo micro‐CT to study bone modelling in 3D

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149362/1/ocr12265.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149362/2/ocr12265_am.pd

History of clinical transplantation

The emergence of transplantation has seen the development of increasingly potent immunosuppressive agents, progressively better methods of tissue and organ preservation, refinements in histocompatibility matching, and numerous innovations is surgical techniques. Such efforts in combination ultimately made it possible to successfully engraft all of the organs and bone marrow cells in humans. At a more fundamental level, however, the transplantation enterprise hinged on two seminal turning points. The first was the recognition by Billingham, Brent, and Medawar in 1953 that it was possible to induce chimerism-associated neonatal tolerance deliberately. This discovery escalated over the next 15 years to the first successful bone marrow transplantations in humans in 1968. The second turning point was the demonstration during the early 1960s that canine and human organ allografts could self-induce tolerance with the aid of immunosuppression. By the end of 1962, however, it had been incorrectly concluded that turning points one and two involved different immune mechanisms. The error was not corrected until well into the 1990s. In this historical account, the vast literature that sprang up during the intervening 30 years has been summarized. Although admirably documenting empiric progress in clinical transplantation, its failure to explain organ allograft acceptance predestined organ recipients to lifetime immunosuppression and precluded fundamental changes in the treatment policies. After it was discovered in 1992 that long-surviving organ transplant recipient had persistent microchimerism, it was possible to see the mechanistic commonality of organ and bone marrow transplantation. A clarifying central principle of immunology could then be synthesized with which to guide efforts to induce tolerance systematically to human tissues and perhaps ultimately to xenografts

Biochar: pyrogenic carbon for agricultural use: a critical review.

O biocarvão (biomassa carbonizada para uso agrícola) tem sido usado como condicionador do solo em todo o mundo, e essa tecnologia é de especial interesse para o Brasil, uma vez que tanto a ?inspiração?, que veio das Terras Pretas de Índios da Amazônia, como o fato de o Brasil ser o maior produtor mundial de carvão vegetal, com a geração de importante quantidade de resíduos na forma de finos de carvão e diversas biomassas residuais, principalmente da agroindústria, como bagaço de cana, resíduos das indústrias de madeira, papel e celulose, biocombustíveis, lodo de esgoto etc. Na última década, diversos estudos com biocarvão têm sido realizados e atualmente uma vasta literatura e excelentes revisões estão disponíveis. Objetivou-se aqui não fazer uma revisão bibliográfica exaustiva, mas sim uma revisão crítica para apontar alguns destaques na pesquisa sobre biochar. Para isso, foram selecionados alguns temaschave considerados críticos e relevantes e fez-se um ?condensado? da literatura pertinente, mais para orientar as pesquisas e tendências do que um mero olhar para o passad

"Single nucleotide polymorphisms of the OPG/RANKL system genes in primary hyperparathyroidism and their relationship with bone mineral density"

<p>Abstract</p> <p>Background</p> <p>Primary hyperparathyroidism (PHPT) affects mainly cortical bone. It is thought that parathyroid hormone (PTH) indirectly regulates the activity of osteoclasts by means of the osteoprotegerin/ligand of the receptor activator of nuclear factor-κβ (OPG/RANKL) system. Several studies have confirmed that <it>OPG </it>(osteoprotegerin) and <it>RANKL </it>(ligand of the receptor activator of nuclear factor-κβ) loci are determinants of bone mineral density (BMD) in the general population. The aim of this study is to analyze the relationship between fractures and BMD and the rs3102735 (163 A/G), rs3134070 (245 T/G) and rs2073618 (1181 G/C) SNPs of the <it>OPG </it>and the rs2277438 SNP of the <it>RANKL</it>, in patients with sporadic PHPT.</p> <p>Methods</p> <p>We enrolled 298 Caucasian patients with PHPT and 328 healthy volunteers in a cross-sectional study. We analyzed anthropometric data, history of fractures or renal lithiasis, biochemical determinants including markers for bone remodelling, BMD measurements in the lumbar spine, total hip, femoral neck and distal radius, and genotyping for the SNPs to be studied.</p> <p>Results</p> <p>Regarding the age of diagnosis, BMI, menopause status, frequency of fractures or renal lithiasis, we found no differences between genotypes in any of the SNPs studied in the PHPT group. Significant lower BMD in the distal radius with similar PTH levels was found in the minor allele homozygotes (GG) compared to heterozygotes and major allele homozygotes in both <it>OPG </it>rs3102735 (163 A/G) and <it>OPG </it>rs3134070 (245 T/G) SNPs in those with PHPT compared to control subjects. We found no differences between genotypes of the <it>OPG </it>rs2073618 (1181 G/C) SNP with regard to BMD in the PHPT subjects. In the evaluation of rs2277438 SNP of the <it>RANKL </it>in PHPT patients, we found a non significant trend towards lower BMD in the 1/3 distal radius and at total hip in the minor allele homocygotes (GG) genotype group versus heterocygotes and major allele homocygotes (AA).</p> <p>Conclusions</p> <p>Our study provides the first evaluation of the relationship between SNPs of the <it>OPG/RANK </it>system and sporadic PHPT. Subjects with PHPT and minor homocygote genotype (GG) for the <it>OPG </it>rs3102735 (163 A/G) and <it>OPG </it>rs3134070 (245 T/G) SNPs have lower BMD in the distal radius, and this association does not appear to be mediated by differences in PTH serum levels.</p

Comparison of air displacement plethysmography to hydrostatic weighing for estimating total body density in children

BACKGROUND: The purpose of this study was to examine the accuracy of total body density and percent body fat (% fat) using air displacement plethysmography (ADP) and hydrostatic weighing (HW) in children. METHODS: Sixty-six male and female subjects (40 males: 12.4 ± 1.3 yrs, 47.4 ± 14.8 kg, 155.4 ± 11.9 cm, 19.3 ± 4.1 kg/m(2); 26 females: 12.0 ± 1.9 yrs, 41.4 ± 7.7 kg, 152.1 ± 8.9 cm, 17.7 ± 1.7 kg/m(2)) were tested using ADP and HW with ADP always preceding HW. Accuracy, precision, and bias were examined in ADP with HW serving as the criterion method. Lohman's equations that are child specific for age and gender were used to convert body density to % fat. Regression analysis determined the accuracy of ADP and potential bias between ADP and HW using Bland-Altman analysis. RESULTS: For the entire group (Y = 0.835x + 0.171, R(2 )= 0.84, SEE = 0.007 g/cm(3)) and for the males (Y = 0.837x + 0.174, R(2 )= 0.90, SEE = 0.006 g/cm(3)) the regression between total body density by HW and by ADP significantly deviated from the line of identity. However in females, the regression between total body density by HW and ADP did not significantly deviate from the line of identity (Y = 0.750x + 0.258, R(2 )= 0.55, SEE = 0.008 g/cm(3)). The regression between % fat by HW and ADP for the group (Y = 0.84x + 3.81, R(2 )= 0.83, SEE = 3.35 % fat) and for the males (Y = 0.84x + 3.25, R(2 )= 0.90, SEE = 3.00 % fat) significantly deviated from the line of identity. However, in females the regression between % fat by HW and ADP did not significantly deviate from the line of identity (Y = 0.81x + 5.17, R(2 )= 0.56, SEE = 3.80 % fat). Bland-Altman analysis revealed no bias between HW total body density and ADP total body density for the entire group (R = 0.-22; P = 0.08) or for females (R = 0.02; P = 0.92), however bias existed in males (R = -0.37; P ≤ 0.05). Bland-Altman analysis revealed no bias between HW and ADP % fat for the entire group (R = 0.21; P = 0.10) or in females (R = 0.10; P = 0.57), however bias was indicated for males by a significant correlation (R = 0.36; P ≤ 0.05), with ADP underestimating % fat at lower fat values and overestimating at the higher % fat values. CONCLUSION: A significant difference in total body density and % fat was observed between ADP and HW in children 10–15 years old with a potential gender difference being detected. Upon further investigation it was revealed that the study was inadequately powered, thus we recommend that larger studies that are appropriately powered be conducted to better understand this potential gender difference