Search

Spurred by the explosion of information technology and access to information, Internet health sites used to gather information about disease and wellness have become an accepted health education tool (Sciamanna, Clark, Houston & Diaz, 2002). There is growing evidence of concerted efforts to use the Internet to increase the access of health information to underserved populations such as Hispanics, a subpopulation with significant disparity in access to health care and health information (Hartel & Mehling, 2002). Many Hispanics are in danger of being left behind in the process, not because they reside on the wrong side of the 'technology-divide,' but because they reside on the wrong side of the 'quality gap.' Although 36% of Hispanics report having Internet access (Barreto, Ibarra, Macias&Pachon, 2000), the full advantage of the Internet requires that they have access to quality information. And while there has been significant work carried out on the reliability of health material on the Internet, only a few studies have looked at the quality of the health information on the Web written in Spanish (Berland et al., 2001). In this study, 10 health themes were searched using popular search engines to generate fifty health Websites aimed at providing Spanish speakers health information. The sites were then evaluated by two raters using a 16-question assessment tool that was validated in previous research done on Internet health Websites. Summated Kappa coefficients on the reviewer ratings were found to have high inter-rater reliability (r = .78). The results of this evaluation indicated that there is significant variability in the quality of health information on the Web. Furthermore, this lack of consistency in quality in health Websites is more likely to be seen in those developed and managed within Spanish-speaking countries in Latin America, the Caribbean and Europe. The article concludes that a mechanism should be developed to standardize the quality of the health information on the Internet, and to ensure the Internet as a promising vehicle through which to eliminate health disparities in Spanish populations. [ABSTRACT FROM AUTHOR]

Abstract: The use of mobile phones is widespread in health institutions, including areas with defined microbiological risk as clinical laboratories. In this study, the presence of potentially pathogenic bacteria was investigated in mobile phones of laboratory personnel of four hospitals of Maracaibo, Venezuela. Qualitative microbiological culture of swabs from the surface of 200 mobile phones was performed. A questionnaire was applied, to evaluate adherence of staff to standard hygiene practices during the workday. In 83% of phones bacterial contamination was evidenced, and 29% had bacteria with defined pathogenic potential, predominantly Enterococcus spp., strict anaerobes bacteria, Staphylococcus aureus and enterobacteria. Some pathogenic strains showed resistance patterns suggestive of nosocomial bacteria. A high percentage of staff refused to apply minimal hygiene measures to manipulate their phones during the workday. Microbiological results, analyzed together with the low level of adherence of personnel to the standard hygienic practices, allow attributing an important hazard to mobiles phone use in clinical laboratories, which could involve not only owners of such devices and usual manipulators, but also could extend to his occasional manipulators in the community. Resumen: El uso de teléfonos móviles se ha generalizado en las instituciones de salud, inclusive en áreas con riesgos microbiológicos definidos, como los laboratorios clínicos. En el presente estudio, se investigó la presencia de bacterias potencialmente patógenas, en los teléfonos móviles del personal de laboratorio de cuatro instituciones hospitalarias de Maracaibo, Venezuela. Se realizó el cultivo microbiológico cualitativo de hisopados de la superficie de 200 teléfonos. Mediante un cuestionario se indagó la adherencia del personal a las prácticas higiénicas estándar durante la jornada laboral. En 83% de los teléfonos se evidenció contaminación bacteriana y en 29% se identificó agentes con potencial patogénico definido, predominando Enterococcus spp., anaerobios estrictos, Staphylococcus aureus y enterobacterias. Algunas cepas patógenas presentaron patrones de resistencia sugestivos de gérmenes nosocomiales. Un elevado porcentaje del personal abordado admitió no aplicar medidas higiénicas mínimas al utilizar sus teléfonos en el ambiente laboral. Los resultados microbiológicos obtenidos, aunados al bajo nivel de compromiso del personal de laboratorio con las prácticas higiénicas estándar, permiten atribuirle un importante riego microbiológico al uso de teléfonos móviles en los laboratorios clínicos, que podría afectar no sólo a los dueños y manipuladores habituales de tales dispositivos, sino también extenderse a sus manipuladores ocasionales a nivel extra hospitalario.

Remyelination is a crucial regenerative process in demyelinating diseases, limiting persisting damage to the central nervous system (CNS). It restores saltatory nerve conduction and ensures trophic support of axons. In multiple sclerosis (MS) patients, remyelination has been observed in both white and grey matter and found to be more efficient in the cortex. Brain-enriched myelin-associated protein 1 (BCAS1) identifies oligodendrocyte lineage cells in the stage of active myelin formation in development and regeneration. Other than in the white matter, BCAS1+ oligodendrocytes are maintained at high densities in the cortex throughout life. Here, we investigated cortical lesions in human biopsy and autopsy tissue from patients with MS in direct comparison to demyelinating mouse models and demonstrate that following a demyelinating insult BCAS1+ oligodendrocytes in remyelinating cortical lesions shift from a quiescent to an activated, internode-forming morphology co-expressing myelin-associated glycoprotein (MAG), necessary for axonal contact formation. Noteworthy, activated BCAS1+ oligodendrocytes are found at early time points of experimental demyelination amidst ongoing inflammation. In human tissue, activated BCAS 1+ oligodendrocytes correlate with the density of myeloid cells, further supporting their involvement in an immediate regenerative response. Furthermore, studying the microscopically normal appearing non demyelinated cortex in patients with chronic MS, we find a shift from quiescent BCAS1+ oligodendrocytes to mature, myelin-maintaining oligodendrocytes, suggesting oligodendrocyte differentiation and limited replenishment of BCAS1+ oligodendrocytes in long-standing disease. We also demonstrate that part of perineuronal satellite oligodendrocytes are BCAS1+ and contribute to remyelination in human and experimental cortical demyelination. In summary, our results provide evidence from human tissue and experimental models that BCAS1+ cells in the adult cortex represent a population of pre-differentiated oligodendrocytes that rapidly react after a demyelinating insult thus enabling immediate myelin regeneration. In addition, our data suggest that limited replenishment of BCAS1+ oligodendrocytes may contribute to the remyelination failure observed in the cortex in chronic MS., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Visceral Leishmaniasis (VL) has a high death rate, with 500,000 new cases and 50,000 deaths occurring annually. Despite the development of novel strategies and technologies, there is no adequate treatment for the disease. Therefore, the purpose of this study is to find structural analogs of natural products as potential novel drugs to treat VL. We selected structural analogs from natural products that have shown antileishmanial activities, and that may impede the purine salvage pathway using computer-aided drug-design (CADD) approaches. For these, we started with the vastly studied target in the pathway, the adenine phosphoribosyl transferase (APRT) protein, which alone is non-essential for the survival of the parasite. Keeping this in mind, we search for a substance that can bind to multiple targets throughout the pathway. Computational techniques were used to study the purine salvage pathway from Leishmania infantum , and molecular dynamic simulations were used to gather information on the interactions between ligands and proteins. Because of its low homology to human proteins and its essential role in the purine salvage pathway proteins network interaction, the findings further highlight the significance of adenylosuccinate lyase protein (ADL) as a therapeutic target. An analog of the alkaloid Skimmianine, N,N-diethyl-4-methoxy-1-benzofuran-6-carboxamide, demonstrated a good binding affinity to APRT and ADL targets, no expected toxicity, and potential for oral route administration. This study indicates that the compound may have antileishmanial activity, which was granted in vitro and in vivo experiments to settle this finding in the future.

Since the number of drugs based on natural products (NPs) represents a large source of novel pharmacological entities, NPs have acquired significance in drug discovery. Peru is considered a megadiverse country with many endemic species of plants, terrestrial, and marine animals, and microorganisms. NPs databases have a major impact on drug discovery development. For this reason, several countries such as Mexico, Brazil, India, and China have initiatives to assemble and maintain NPs databases that are representative of their diversity and ethnopharmacological usage. We describe the assembly, curation, and chemoinformatic evaluation of the content and coverage in chemical space, as well as the physicochemical attributes and chemical diversity of the initial version of the Peruvian Natural Products Database (PeruNPDB), which contains 280 natural products. Access to PeruNPDB is available for free ( https://perunpdb.com.pe/ ). The PeruNPDB's collection is intended to be used in a variety of tasks, such as virtual screening campaigns against various disease targets or biological endpoints. This emphasizes the significance of biodiversity protection both directly and indirectly on human health., (© 2023. The Author(s).)

Background: Hospitalizations by patients who do not meet acute inpatient criteria are common and overburden healthcare systems. Studies have characterized these alternate levels of care (ALC) but have not delineated prolonged (pALC) versus short ALC (sALC) stays., Objective: To descriptively compare pALC and sALC hospitalizations-groups we hypothesize have unique needs., Designs, Settings, and Participants: A retrospective study of hospitalizations from March-April 2018 at an academic safety-net hospital., Main Outcome and Measures: Levels of care for pALC (>3 days) and sALC (1-3 days) were determined using InterQual©, an industry standard utilization review tool for determining the clinical appropriateness of hospitalization. We examined sociodemographic and clinical characteristics., Results: Of 2365 hospitalizations, 215 (9.1%) were pALC, 277 (11.7%) were sALC, and 1873 (79.2%) had no ALC days. There were 17,683 hospital days included, and 28.3% (n = 5006) were considered ALC. Compared to patients with sALC, those with pALC were older and more likely to be publicly insured, experience homelessness, and have substance use or psychiatric comorbidities. Patients with pALC were more likely to be admitted for care meeting inpatient criteria (89.3% vs. 66.8%, p < .001), had significantly more ALC days (median 8 vs. 1 day, p < .001), and were less likely to be discharged to the community (p < .001)., Conclusions: Patients with prolonged ALC stays were more likely to be admitted for acute care, had greater psychosocial complexity, significantly longer lengths of stay, and unique discharge needs. Given the complexity and needs for hospitalizations with pALC days, intensive interdisciplinary coordination and resource mobilization are necessary., (© 2023 Society of Hospital Medicine.)

Background: loss of skeletal muscle function, strength and mass is common in older adults, with important socioeconomic impacts. Subclinical hypothyroidism is common with increasing age and has been associated with reduced muscle strength. Yet, no randomized placebo-controlled trial (RCT) has investigated whether treatment of subclinical hypothyroidism affects muscle function and mass., Methods: this is an ancillary study within two RCTs conducted among adults aged ≥65 years with persistent subclinical hypothyroidism (thyrotropin (TSH) 4.60-19.99 mIU/l, normal free thyroxine). Participants received daily levothyroxine with TSH-guided dose adjustment or placebo and mock titration. Primary outcome was gait speed at final visit (median 18 months). Secondary outcomes were handgrip strength at 1-year follow-up and yearly change in muscle mass., Results: we included 267 participants from Switzerland and the Netherlands. Mean age was 77.5 years (range 65.1-97.1), 129 (48.3%) were women, and their mean baseline TSH was 6.36 mIU/l (standard deviation [SD] 1.9). At final visit, mean TSH was 3.8 mIU/l (SD 2.3) in the levothyroxine group and 5.1 mIU/l (SD 1.8, P < 0.05) in the placebo group. Compared to placebo, participants in the levothyroxine group had similar gait speed at final visit (adjusted between-group mean difference [MD] 0.01 m/s, 95% confidence interval [CI] -0.06 to 0.09), similar handgrip strength at one year (MD -1.22 kg, 95% CI -2.60 to 0.15) and similar yearly change in muscle mass (MD -0.15 m2, 95% CI -0.49 to 0.18)., Conclusions: in this ancillary analysis of two RCTs, treatment of subclinical hypothyroidism did not affect muscle function, strength and mass in individuals 65 years and older., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: After menopause, body composition changes with body fat accumulation, and an increase in cardiometabolic risk factors. Total fat mass, regional fat mass, and visceral adipose tissue (VAT) may be estimated with anthropometric measures, bioelectrical impedance analysis (BIA), and dual-energy X-ray absorptiometry (DXA). The aim of our study was to assess which measurement correlated best with cardiometabolic risk factors in healthy nonobese postmenopausal women., Methods: The CoLaus/OsteoLaus cohort included 1,500 postmenopausal women (age range 50-80). We analyzed correlations between: 1) measurements of body composition assessed by anthropometric measures, BIA, and DXA and 2) these measurements and different selected cardiometabolic risk factors, such as blood pressure, lipid markers (cholesterol subtypes and triglycerides), and metabolic markers (glucose, insulin, adiponectin, and leptin). Spearman correlation coefficient, stepwise forward regression, and linear regression analyses were used to determine association between anthropometric measurements and cardiometabolic risk factors., Results: In the 803 included participants (mean age 62.0 ± 7.1 y, mean body mass index 25.6 kg/m2 ± 4.4), correlations between total fat mass measured by BIA and total fat mass, android fat, gynoid fat, or VAT measured by DXA are very strong (from r = 0.531, [99% confidence interval (CI), 0.443-0.610] to r = 0.704, [99% CI, 0.640-0.758]). Body mass index and waist circumference have a higher correlation with VAT (r = 0.815, [99% CI, 0.772-0.851] and r = 0.823 [99% CI, 0.782-0.858], respectively) than BIA (r = 0.672 [99% CI, 0.603-0.731]). Among the anthropometric measurement and the measurements derived from DXA and BIA, VAT is the parameter most strongly associated with cardiometabolic risk factors. VAT better explains the variation of most of the cardiometabolic risk factors than age and treatment. For example, nearly 5% of the variability of the diastolic blood pressure (9.9 vs 4.9), nearly 15% of the variability of high-density lipoprotein cholesterol (20.3 vs 3.8) and triglyceride (21.1 vs 6.5), 25.3% of the variability of insulin (33.3 vs 8.1), and 37.5% of the variability of leptin (37.7 vs 1.1) were explained by VAT., Conclusions: BIA seems not to be a good tool to assess VAT. At the population level, waist circumference and body mass index seem to be good tools to estimate VAT. VAT measured by DXA is the parameter most correlated with cardiometabolic risk factors and could become a component of the cardiometabolic marker on its own., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2022 by The North American Menopause Society.)

The fallow deer (Dama dama) is a species of Cervidae commonly kept in captivity, either in commercial farms or in zoos. The reproductive seasonality of this species is well known in the northern hemisphere, where photoperiod is a decisive factor in androgenic activity and, consequently, in the development of secondary sexual characteristics among male adults. The maintenance of this species in tropical regions has been successful, but there are no studies that demonstrate the maintenance of reproductive seasonality under these climatic conditions, which was the objective of the present study. To do so, the present investigation involved 27 fallow deer (D. dama) specimens, of which 14 were adults and 13 prepubescent (<8 months) individuals, all assessed during and outside (December-February) the reproductive season (June-August). The serum concentrations of testosterone, testicular volume, and neck circumference were analyzed among all animals during both seasons. The reproductive season was marked by expressive hormonal concentrations, increasing neck circumference and testicular volume, differing significantly between adults and prepubescent individuals outside the season. Positive correlations were observed among all analyzed variables: mean testicular volume and neck circumference (r = 0.92, p < 0.0001), testicular volume and testosterone concentrations (r = 0.79, p < 0.0001) and between neck circumference and testosterone concentrations (r = 0.67, p < 0.0001). Given the results found, the conclusion is that even under tropical climate conditions the reproductive seasonality of the fallow deer is well defined and may be related to photoperiod., (© 2019 Wiley Periodicals, Inc.)

Introduction: Severe trauma is accompanied by endothelial glycocalyx disruption, which drives coagulopathy, increasing transfusion requirements and death. This syndrome has been termed endotheliopathy of trauma (EOT). Some have suggested EOT results from endothelial cellular damage and apoptosis. Endothelial microvesicles (EMVs) represent cellular damage. We hypothesized that EOT is associated with endothelial damage and apoptosis resulting in an increase in circulating EMVs., Methods: Prospective, observational study enrolling severely injured patients. Twelve patients with EOT, based on elevated Syndecan-1 levels, were matched with 12 patients with lower levels, based on Injury Severity Score (ISS), abbreviated injury scale profile, and age. Thrombelastography and plasma levels of biomarkers indicative of cellular damage were measured from blood samples collected on admission. EMVs were determined by flow cytometry using varied monoclonal antibodies associated with endothelial cells. Significance was set at P < 0.05., Results: Admission physiology and ISS (29 vs. 28) were similar between groups. Patients with EOT had higher Syndecan-1, 230 (158, 293) vs. 19 (14, 25) ng/mL, epinephrine, and soluble thrombomodulin levels. Based on thrombelastography, EOT had reductions in clot initiation, amplification, propagation and strength, and a greater frequency of transfusion, 92% vs. 33%. There were no differences in EMVs irrespective of the antibody used. Plasma norepinephrine, sE-selectin, sVE-cadherin, and histone-complexed DNA fragments levels were similar., Conclusion: In trauma patients presenting with EOT, endothelial cellular damage or apoptosis does not seem to occur based on the absence of an increase in EMVs and other biomarkers. Thus, this suggests endothelial glycocalyx disruption is the underlying primary cause of EOT.

Purpose of Review: Denosumab discontinuation is associated with a rebound effect manifesting by an increased risk of multiple spontaneous vertebral fractures. The purpose of this review is to (1) better characterize this risk and (2) find solutions to avoid it., Recent Findings: In the absence of a potent bisphosphonate prescription at denosumab discontinuation, the frequency of multiple vertebral fractures is common or frequent (≥ 1/100 and < 1/10). In five recent case series, the median number of vertebral fractures was 5 within 7 to 20 months (median 11) after the last denosumab injection. Prescribing bisphosphonate before starting denosumab and/or after stopping denosumab may reduce this risk. However, only small case series have evaluated these strategies. After the second denosumab dose, there is a rebound effect with an increased risk of multiple vertebral fractures. A potent bisphosphonate prescribed at denosumab discontinuation could reduce this risk. As denosumab discontinuation is characterized by many uncertainties, denosumab is a second-line treatment for osteoporosis. Studies are urgently needed to define the management of denosumab discontinuation.

Cerebral cortex shows a high endogenous propensity for remyelination. Yet, widespread subpial cortical demyelination (SCD) is a common feature in progressive multiple sclerosis (MS) and can already be found in early MS. In the present study, we compared oligodendroglial loss in SCD in early and chronic MS. Furthermore, we addressed in an experimental model whether repeated episodes of inflammatory SCD could alter oligodendroglial repopulation and subsequently lead to persistently demyelinated cortical lesions. NogoA(+) mature oligodendrocytes and Olig2(+) oligodendrocyte precursor cells were examined in SCD in patients with early and chronic MS, normal-appearing MS cortex, and control cortex as well as in the rat model of repeated targeted cortical experimental autoimmune encephalomyelitis (EAE). NogoA(+) and Olig2(+) cells were significantly reduced in SCD in patients with chronic, but not early MS. Repeated induction of SCD in rats resulted only in a transient loss of NogoA(+), but not Olig2(+) cells during the demyelination phase. This phase was followed by complete oligodendroglial repopulation and remyelination, even after four episodes of demyelination. Our data indicate efficient oligodendroglial repopulation in subpial cortical lesions in rats after repeated SCD that was similar to early, but not chronic MS cases. Accordingly, four cycles of experimental de- and remyelination were not sufficient to induce sustained remyelination failure as found in chronic cortical MS lesions. This suggests that alternative mechanisms contribute to oligodendrocyte depletion in chronic cortical demyelination in MS.

The Artery of Percheron is a rare vascular variant in which a single dominant thalamoperforating artery arises from one P1 segment and bifurcates to supply both paramedian thalami. Occlusion of this uncommon vessel results in a characteristic pattern of bilateral paramedian thalamic infarcts with or without mesencephalic infarctions. We report a case of a 31-year-old man with acute bilateral thalamic infarcts and a truncated Artery of Percheron demonstrated on magnetic resonance angiography (MRA). Occlusion of the vessel was presumably due to embolism from a patent foramen ovale that was subsequently closed. The case presentation is followed by a discussion of bilateral paramedian thalamic infarcts including the causes and clinical presentation. The differential diagnosis of vascular and nonvascular etiologies of bilateral thalamic lesions is also discussed.

Background: Cholinesterase inhibitors and memantine are prescribed to slow the progression dementia. Although the efficacy of these drugs has been demonstrated, their effectiveness, from the perspective of patients and caregivers, has been questioned. Little is known about whether the demand for cholinesterase inhibitors and memantine are sensitive to out-of-pocket cost. Using the 2006 implementation of Medicare Part D as a natural experiment, this study examines the impact of changes in drug coverage on use of cholinesterase inhibitors and memantine by comparing use before and after Medicare Part D implementation among older adults who did and did not experience a change in coverage., Methods: Retrospective analyses of claims data from 35,102 community-dwelling Medicare beneficiaries in Pennsylvania aged 65 or older. Beneficiaries were continuously enrolled in a Medicare Advantage plan from 2004 to 2007. Outcome variables were any use of donepezil (Aricept(®)), galantamine (Razadyne(®)), rivastigmine (Exelon(®)), tacrine (Cognex(®)), or memantine (Namenda(®)) each year and the number of 30-day prescriptions filled for these drugs. Independent variables included type of drug benefit pre-Part D (No coverage, $150 cap, $350 cap, and No cap as the reference group), time period, and their interaction. Sensitivity analyses were conducted to test if there are differences in use by drug class or if beneficiaries with a diagnosis of dementia pre-Part D experienced an increase in use post-Part D., Results: The No coverage group had a 38% increase in the odds ratio of any use of antidementia medications (P = 0.0008) post-Part D relative to the No cap group. All four coverage groups had significant increases in number of 30-day prescriptions (P < 0.001) over the study period. In adjusted models that included the sub-sample with any use pre-Part D, the No coverage group had a 36% increase in prescriptions (P = 0.002) and the $350 cap group had a 15% increase (P = 0.003) after adjusting for trends in the No cap group. Results from the sensitivity analysis for the sub-sample with a diagnosis of dementia pre-Part D show that each group had significant increases in 30-day prescriptions compared to the No cap control group (P < 0.05)., Conclusions: Use of cholinesterase inhibitors and memantine in our sample increased and a greater increase in use was observed among Medicare beneficiaries who experienced improvements in drug coverage under Medicare Part D.

Central diabetes insipidus (CDI) is caused by deficient secretion of antidiuretic hormone (ADH) due to different conditions that can affect the hypothalamic neurons. It results in an inability to retain normal quantities of free water, which leads to polyuria, including at night, and polydipsia. In adults, it is mostly due to the "idiopathic" form or present after pituitary surgery or a traumatic brain injury. In rare cases, an underlying systemic disease is found. The diagnosis of CDI is based on the water deprivation test. Pituitary MRI and specific clinical and biological work-up are recommended to precise etiology. Treatment of choice is desmopressin, a synthetic analogue of the endogenous ADH hormone. A multidisciplinary team generally provides management and monitoring of CDI.

The glucocorticoid-induced leucine zipper (Tsc22d3-2) is a widely expressed dexamethasone-induced transcript that has been proposed to be important in immunity, adipogenesis, and renal sodium handling based on in vitro studies. To address its function in vivo, we have used Cre/loxP technology to generate mice deficient for Tsc22d3-2. Male knockout mice were viable but surprisingly did not show any major deficiencies in immunological processes or inflammatory responses. Tsc22d3-2 knockout mice adapted to a sodium-deprived diet and to water deprivation conditions but developed a subtle deficiency in renal sodium and water handling. Moreover, the affected animals developed a mild metabolic phenotype evident by a reduction in weight from 6 months of age, mild hyperinsulinemia, and resistance to a high-fat diet. Tsc22d3-2-deficient males were infertile and exhibited severe testis dysplasia from postnatal d 10 onward with increases in apoptotic cells within seminiferous tubules, an increased number of Leydig cells, and significantly elevated FSH and testosterone levels. Thus, our analysis of the Tsc22d3-2-deficient mice demonstrated a previously uncharacterized function of glucocorticoid-induced leucine zipper protein in testis development.

The aim of this study was to evaluate the tissue compatibility of a silorane-based resin system (Filtek™ Silorane) and a methacrylate-based nanoparticle resin (Filtek™ Supreme XT) after implantation in the subcutaneous connective tissue of isogenic mice. One hundred and thirty five male isogenic BALB/c mice were randomly assigned to 12 experimental and 3 control groups, according to the implanted material and the experimental period of 7, 21 and 63 days. At the end of each period, the animals were killed and the tubes with the surrounding tissues were removed and processed for microscopic analysis. Samples were subjected to a descriptive and a semi-quantitative analyses using a 4-point scoring system (0-3) to evaluate the collagen fiber formation and inflammatory infiltrate. Data were statistically analyzed using the Kruskal Wallis test (α=0.05). The results showed that there was no significant difference between the experimental and control groups considering the three evaluation periods (p>0.05). The silorane-based and the methacrylate-based nanoparticle resins presented similar tissue response to that of the empty tube (control group) after subcutaneous implantation in isogenic mice.

Subjective memory complaints (SMCs) are known to be inconsistently related to current memory impairment in older adults but this association has not been well investigated in primary care provider (PCP) settings. To characterize the complexity of the relationship between SMCs and objective memory in older outpatients of PCPs, we collected neuropsychological, subjective memory, depression and medical chart data from outpatients aged 65 and older, without documented dementia diagnoses, in eleven PCP offices in and around the Pittsburgh metropolitan area. Results indicated that self-estimates of current memory ability were most strongly associated with objective memory performance; in contrast, perception of worsening memory over the past year showed no association; and specific memory-related activities were only weakly associated. Women were more likely than men to show inconsistency between SMCs and objective memory performance. Only two of the 11 most significantly memory-impaired participants endorsed SMCs and only four had PCP chart documentation of memory problems. Eliciting SMCs in non-demented older adults can be of clinical value in a PCP setting, but significant limitations of patient self-report in more memory-impaired patients underscore the need to develop brief, objective indicators of memory impairment for PCP office use when there is suspicion of decline.

Adrenal steroid hormones and neuronal growth factors are two interacting systemic factors that mediate the environment's influence on the brain's structure and function. In order to further elucidate their role and relationship in the effects of early stressful experience and isolated rearing (IR), this study measured blood corticosterone titres and relative adrenal weights and assessed nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) concentrations in brain regions of both hemispheres of young adult Mongolian gerbils injected on postnatal day 14 with a single high dose of methamphetamine (MA) or saline and raised after weaning either in an enriched or an impoverished environment. Irrespective of MA challenge, IR decreased corticosterone titres to about half, but increased relative adrenal weights. BDNF concentrations were decreased by IR in saline-injected animals in the left prefrontal and parietal cortices and right entorhinal and hippocampal cortices, and in the subcortical regions of both hemispheres. NGF concentrations were unaltered by IR in saline-injected animals, but increased in MA challenged animals in the entorhinal/hippocampal cortices and subcortical areas of both hemispheres. MA application induced shifts of the lateral asymmetry in NGF contents in prefrontal and entorhinal cortices. The results suggest that an early pharmacological traumatization can set a switch for further brain development, and that growth factor concentrations might possibly be influenced by peripheral stress hormones.

Objective: The objective of this study was to examine associations between discrepancies in health information provided to primary care providers and severity of impairment in older patients with and without dementia., Methods: This study included brief assessment and medical record review of 1,107 patients with a mean (standard deviation) age of 76.3 (6.6) years (range: 65-100 years) in seven small-town primary care practices. In 358 patients, detailed in-home assessment included demographics; dementia by Clinical Dementia Rating (CDR) scale; and frequencies of memory complaints, falls, and inadvertent medication nonadherence determined from medical records and standardized in-home research assessments. Main outcome variables were trends in discrepancies between chart reviews and research assessments. Main explanatory variable was CDR box total scores., Results: Proportions of patients reporting memory complaints and falls, and evidence of inadvertent nonadherence, in the charts and by research assessment increased with CDR. Discrepancies between medical record and research assessment, were also associated with CDR, showing linear trends for memory complaints and inadvertent nonadherence and a quadratic trend for falls., Conclusion: Memory complaints, falls, and inadvertent medication nonadherence increase with dementia severity. The levels of discrepancy between information patients provided to their physicians and information they provided in response to detailed, standardized assessments, also varied with dementia severity. Physicians should be alert to the possibility of receiving unreliable health information from even mildly demented patients, whether or not dementia has been detected.

This article presents the results of a retrospective review of six osteochondral lesions on six patients (five men and one woman) treated with transplantation of cryopreserved talar allograft and ankle joint distraction. All patients complained of ankle pain existing for a long time secondary to a traumatic episode confirmed through MRI. Lesions ranged in measurement from 0.8 cm x 0.8 cm to 3.2 cm x 1.8 cm with an average size of 2.1 cm x 1.5 cm. Each patient underwent talar dome transplantation using fresh frozen talar allograft followed by ankle distraction. Distraction was obtained using a three-ring multiplanar external fixation device. All surgeries were performed between 2002 and 2004. All external fixators were removed at 8 weeks and patients remained partial-weight bearing in a removable cast boot for an additional 8 weeks. Serial postoperative radiographs showed complete consolidation of the allograft within 16 weeks. The average follow up time was 24 months, and all patients related a subjective decrease in symptoms and increase in activity levels. Patients were also evaluated utilizing the Maryland Foot Score both pre- and postoperatively. Preoperatively, four patients were graded as fair and two were graded as poor. Postoperatively, two patients related excellent results, three patients related good results, and one patient related fair results. Several patients experienced minor complications such as pin site irritation (five patients), painful talar wire (one patient), and periostitis (one patient). No patients experienced any major complications and none have required additional surgery. We feel that these initial results warrant further investigation of this treatment.

Study Objective: To evaluate the effectiveness of a program in which pharmacists screened at-risk patients for peripheral arterial disease using a handheld doppler device., Design: Prospective study., Setting: Primary care and consultative outpatient clinic., Patients: Forty-one physician-referred patients older than 55 years who had no documented history of peripheral arterial disease., Intervention: The pharmacists administered the San Diego Claudication Questionnaire and performed doppler examinations to calculate ankle-to-brachial indexes (ABIs). Patients with symptoms of claudication or with an ABI of 0.9 or less were considered to have possible peripheral arterial disease. Each diagnosis was confirmed by a physician. These patients were either referred for further evaluation, provided with immediate treatment, or told to continue their current drug regimen, if appropriate., Measurements and Main Results: Eight (19.5%) of the 41 patients were diagnosed with peripheral arterial disease. Antiplatelet therapy was started in five patients, and one patient was referred to a vascular specialist., Conclusion: This pharmacist-initiated program effectively detected peripheral arterial disease in previously unscreened patients.

Transition through telomere crisis is thought to be a crucial event in the development of most breast carcinomas. Our goal in this study was to determine where this occurs in the context of histologically defined breast cancer progression. To this end, we assessed genome instability (using fluorescence in situ hybridization) and other features associated with telomere crisis in normal ductal epithelium, usual ductal hyperplasia, ductal carcinoma in situ and invasive cancer. We modeled this process in vitro by measuring these same features in human mammary epithelial cell cultures during ZNF217-mediated transition through telomere crisis and immortalization. Taken together, the data suggest that transition through telomere crisis and immortalization in breast cancer occurs during progression from usual ductal hyperplasia to ductal carcinoma in situ.

Objectives: To compare the use of lipid-lowering drugs in community-dwelling older adults with and without dementia., Design: Comparison of lipid-lowering drug use by demented cases and nondemented controls based on secondary analysis of data from a longitudinal epidemiologic study., Setting: Longitudinal study of a largely rural, low- socioeconomic-status, community-based cohort of older persons residing in the mid-Monongahela Valley of South-west Pennsylvania (the Monongahela Valley Independent Elders Survey)., Participants: Eight hundred forty-five individuals of mean +/- standard deviation (SD) age of 80.5 +/- 4.6, participating in the fifth biennial wave of data collection., Measurements: Demographics; medical history; medication regimen (including examination of prescription bottle labels); self-report of most recent visit to primary care physician (PCP); and standardized clinical assessment to determine presence of dementia, including Clinical Dementia Rating (CDR)., Results: One hundred seventy participants (20.1% of total subject cohort) had dementia, with a CDR of 0.5 or greater. Mean ages of demented and nondemented individuals were 83.5 +/- 5.1 and 79.8 +/- 4.2, respectively. Similar proportions, 87.7% and 89.5%, of these groups reported PCP visits in the previous year. Of the total sample, 9.4% (3.5% of the demented and 10.8% of the nondemented) were taking lipid-lowering drugs. After adjustment for age, sex, education, visit with PCP within the past year, and potential confounding clinical and lifestyle variables (self-reported heart disease, stroke or transient ischemic attacks, hypertension, smoking, and alcohol consumption), dementia was associated with a lower likelihood of taking a lipid-lowering drug (odds ratio = 0.39, 95% confidence interval = 0.16-0.95). In post hoc subgroup analyses, similar results were found when restricting lipid-lowering drugs to statins alone but were not statistically significant. Drug use was not associated with severity of dementia (CDR = 0.5 vs CDR >or= 1)., Conclusions: Demented individuals were less likely than their nondemented counterparts to be taking lipid-lowering drugs. This finding could reflect different prescribing patterns by physicians for demented and nondemented patients or a possible protective effect of these drugs against dementia.

The immune response against hepatitis B surface and core antigens was evaluated by either coinoculation or independent intramuscular administration of pAEC compact DNA immunization vectors carrying their genes. The pAEC vectors bear just the essential elements for mammalian expression and bacterial amplification. Balb/c mice were immunized with 100 microg of each construct, either alone or in combination. In spite of lacking known immunostimulatory sequences (e.g., AACGTT), significant cellular (proliferative) and humoral immune responses were raised against both antigens. Coadministration of both plasmids maintained the immune response against the two antigens, without interference between them. Modulation of the antigen expression and further immune response, by using the Kozak's translation initiation sequence, was also analyzed. No differences due to its presence or absence were observed., (Copyright 2001 Academic Press.)

The dosage compensation machinery of Caenorhabditis elegans is targeted specifically to the X chromosomes of hermaphrodites (XX) to reduce gene expression by half. Many of the trans-acting factors that direct the dosage compensation machinery to X have been identified, but none of the proposed cis-acting X chromosome-recognition elements needed to recruit dosage compensation components have been found. To study X chromosome recognition, we explored whether portions of an X chromosome attached to an autosome are competent to bind the C. elegans dosage compensation complex (DCC). To do so, we devised a three-dimensional in situ approach that allowed us to compare the volume, position, and number of chromosomal and subchromosomal bodies bound by the dosage compensation machinery in wild-type XX nuclei and XX nuclei carrying an X duplication. The dosage compensation complex was found to associate with a duplication of the right 30% of X, but the complex did not spread onto adjacent autosomal sequences. This result indicates that all the information required to specify X chromosome identity resides on the duplication and that the dosage compensation machinery can localize to a site distinct from the full-length hermaphrodite X chromosome. In contrast, smaller duplications of other regions of X appeared to not support localization of the DCC. In a separate effort to identify cis-acting X recognition elements, we used a computational approach to analyze genomic DNA sequences for the presence of short motifs that were abundant and overrepresented on X relative to autosomes. Fourteen families of X-enriched motifs were discovered and mapped onto the X chromosome.

Objective: To determine the extent to which conditions suggesting dementia are reported on death certificates of older adults and to identify the factors associated with reporting of dementia., Design: A prospective epidemiological study in which community-dwelling subjects with and without dementia were identified and followed until death, after which their death certificates were examined., Population: A total of 527 individuals who died during 8 years of follow-up of a population-based cohort of 1422 persons aged 65 and older at study entry., Measurements: Demographic; study diagnoses, including Clinical Dementia Rating (CDR) Scale stages and diagnoses of Probable and Possible Alzheimer's disease (AD) by NINCDS-ADRDA criteria; disorders listed on death certificates as immediate, underlying, or contributory causes of death., Results: Of 172 deceased subjects with study diagnoses of dementia, 30.2% had CDR = .5 and 69.8% had CDR > or = 1. Of 168 subjects in which dementia subtype could be diagnosed, Probable AD was diagnosed in 31.0% and Possible AD in 38.7%. On their death certificates, conditions indicating or suggesting dementia were reported in 23.8% of dementias overall; in 1.9% of those with CDR = .5 and 33.3% of those with CDR > or = 1; in 36.5% of those with Probable AD and 21.5% of those with Possible AD. In a multiple logistic regression model, variables associated independently with the reporting of dementia in demented individuals were: higher CDR stage of dementia (odds ratio (OR) 22.6; 95% confidence interval (CI), 2.9-174.7); likely etiology of dementia, Probable AD (OR = 3.5; CI, 1.1-10.6); and place of death, long-term care institution (OR = 3.8; 95% CI, 1.6-9.0)., Conclusions: Although Alzheimer's disease is widely regarded as a leading cause of death, dementias are reported on the death certificates of only a quarter of demented individuals in the population at large. Reporting is more likely in those with more advanced dementia, with Probable Alzheimer's disease, and those who die in long-term care institutions.