Hyrax appliance opening and pattern of skeletal maxillary expansion after surgically assisted rapid palatal expansion: a computed tomography evaluation

Objective. The objective of this study was to evaluate, using computed tomography, correlations between Hyrax appliance opening and post-SARPE skeletal changes. Study design. Fifteen patients underwent SARPE according to a specific protocol and were followed. Linear and angular measurements of the anterior, intermediate, and posterior portions of the maxilla were evaluated. The correlation between maxillary expansion and appliance opening was investigated. Results. Significant overall expansion was observed. In the anterior and intermediate portions of the maxilla, the increase in maxillary width was greater than that observed in the posterior portion. The degree of appliance opening was significantly greater than that of the skeletal expansion. Also, no linear correlation between appliance opening and regional maxillary expansion was established. Conclusion. The transverse expansion of the maxilla was less than uniform. The lack of linear correlation between appliance opening and skeletal expansion is attributable to multiple factors, including those related to the device, the surgical technique, and the craniofacial deformity itself. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008; 106: 812-819)

Effectiveness of medial-wedge insole treatment for valgus knee osteoarthritis

Objective. To assess the efficacy of medial-wedge insoles in valgus knee osteoarthritis (OA). Methods. Thirty consecutive women with valgus-deformity knee OA a:8 degrees were randomized into 2 groups: medial insole (insoles with B-mm medial elevation at the rearfoot [n = 161) and neutral insole (similar insole without elevation [n = 14]). Both groups also wore ankle supports. A blinded examiner assessed pain on movement, at rest, and at night with a visual analog scale (VAS), the Lequesne index., and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index. Femorotibial, talocalcaneal, and talar tilt angles were evaluated at baseline and after 8 weeks of insole use. Results. Significant reductions in the medial insole group were observed for pain on movement (mean +/- SD VAS pre- and postintervention 8.1 +/- 1.5 versus 1 4.2 +/- 2.4; P = 0.001), at rest (5.1 +/- 2.3 versus 2.7 +/- 2.4; P = 0.002), and at night (6.1 +/- 2.7 versus 3.1 +/- 2.1; P = 0.001). In addition, a decrease in Lequesne (14.7 +/- 3.4 versus 9.6 +/- 3.8; P = 0.001) and WOMAC scores (74.1 +/- 14.2 versus 56.1 +/- 14.9; P = 0.001) was observed for the medial insole group. In the neutral insole group, a significant reduction was observed only for night pain (mean SD VAS pre- and postintervention 5.8 +/- 2.4 versus 4.6 +/- 2.4; P = 0.019). An increase in femorotibial angle (169.0 +/- 3.4 versus 170.8 +/- 2.4; P = 0.019). An increase in femorotibial angle (169.0 +/- 3.4 versus 170.8 +/- 3.7; P = 0.001) occurred only in the medial 3.7; P = 0.001) occurred only in the medial insole group. Moreover, the difference in measured fernorotibial angles pre- and postintervention was 1.84 +/- 1.42 versus -0.18 +/- 0.67 (P < 0.001) for the medial and neutral insole groups. Conclusion. The use of medial-wedge insoles was highly effective in reducing pain at rest and on movement and promoted a functional improvement of valgus knee OA.

Challenges in Using Stem Cells for Cardiac Repair

Of the many diseases discussed in the context of stem cell therapy, those concerning the heart account for almost one-third of the publications in the field. However, the long-term clinical outcomes have been disappointing, in part because of preclinical studies failing to optimize the timing, number, type, and method of cell delivery and to account for shape changes that the heart undergoes during failure. In situations in which cardiomyocytes have been used in cell therapy, their alignment and integration with host tissue have not been realized. Here we review the present status of direct delivery of stem cells or their derivative cardiomyocytes to the heart and the particular challenges each cell type brings, and consider where we should go from here.

Clinical End Points and Response Criteria in Mycosis Fungoides and Sezary Syndrome: A Consensus Statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer

Mycosis fungoides (MF) and Sezary syndrome (SS), the major forms of cutaneous T-cell lymphoma, have unique characteristics that distinguish them from other types of non-Hodgkin`s lymphomas. Clinical trials in MF/SS have suffered from a lack of standardization in evaluation, staging, assessment, end points, and response criteria. Recently defined criteria for the diagnosis of early MF, guidelines for initial evaluation, and revised staging and classification criteria for MF and SS now offer the potential for uniform staging of patients enrolled in clinical trials for MF/SS. This article presents consensus recommendations for the general conduct of clinical trials of patients with MF/SS as well as methods for standardized assessment of potential disease manifestations in skin, lymph nodes, blood, and visceral organs, and definition of end points and response criteria. These guidelines should facilitate collaboration among investigators and collation of data from sponsor-generated or investigator-initiated clinical trials involving patients with MF or SS. J Clin Oncol 29:2598-2607. (C) 2011 by American Society of Clinical Oncology

Musculoskeletal Dysfunction and Pain in Adults with Asthma

Background. The mechanical alterations related to the overload of respiratory muscles observed in adults with persistent asthma might lead to the development of chronic alterations in posture, musculoskeletal dysfunction and pain; however, these changes remain poorly understood. Objective. This study aimed to assess postural alignment, muscle shortening and chronic pain in adults with persistent asthma. Methods. This cross-sectional and controlled study enrolled 30 patients with mild (n = 17) and severe ( n = 13) persistent asthma. Fifteen non-asthmatic volunteers were also assessed. Asthma was classified by the Global Initiative for Asthma (GINA) guidelines. Postural alignment and muscle shortening were evaluated by head and shoulder positions, chest wall mobility, and posterior ( trunk and lower limb) muscle flexibility. In addition, the measures used were previously tested for their reproducibility. Pain complaints were also assessed. Results. In comparison with non-asthmatic subjects, patients with mild or severe persistent asthma held their head and shoulders more forward and had lower chest wall expansion, decreased shoulder internal rotation, and decreased thoracic spine flexibility. Chronic lower thoracic, cervical, and shoulder pain was significantly increased in patients with mild or severe asthma compared with non-asthmatic subjects (p < 0.05). Conclusion. Adults with persistent asthma have musculoskeletal dysfunction and chronic pain that is independent of the severity of their disease but that might be related to their age at the onset of disease symptoms.

THE TEMPO AND MODE OF EVOLUTION OF TRANSPOSABLE ELEMENTS AS REVEALED BY MOLECULAR PHYLOGENIES RECONSTRUCTED FROM MOSQUITO GENOMES

Although many mathematical models exist predicting the dynamics of transposable elements (TEs), there is a lack of available empirical data to validate these models and inherent assumptions. Genomes can provide a snapshot of several TE families in a single organism, and these could have their demographics inferred by coalescent analysis, allowing for the testing of theories on TE amplification dynamics. Using the available genomes of the mosquitoes Aedes aegypti and Anopheles gambiae, we indicate that such an approach is feasible. Our analysis follows four steps: (1) mining the two mosquito genomes currently available in search of TE families; (2) fitting, to selected families found in (1), a phylogeny tree under the general time-reversible (GTR) nucleotide substitution model with an uncorrelated lognormal (UCLN) relaxed clock and a nonparametric demographic model; (3) fitting a nonparametric coalescent model to the tree generated in (2); and (4) fitting parametric models motivated by ecological theories to the curve generated in (3).

Identification of FAM46D as a novel cancer/testis antigen using EST data and serological analysis

Cancer/testis Antigens (CTAs) are immunogenic proteins with a restricted expression pattern in normal tissues and aberrant expression in different types of tumors being considered promising candidates for immunotherapy. We used the alignment between EST sequences and the human genome sequence to identify novel CT genes. By examining the EST tissue composition of known CT clusters we defined parameters for the selection of 1184 EST clusters corresponding to putative CT genes. The expression pattern of 70 CT gene candidates was evaluated by RT-PCR in 21 normal tissues, 17 tumor cell lines and 160 primary tumors. We were able to identify 4 CT genes expressed in different types of tumors. The presence of antibodies against the protein encoded by 1 of these 4 CT genes (FAM46D) was exclusively detected in plasma samples from cancer patients. Due to its restricted expression pattern and immunogenicity FAM46D represents a novel target for cancer immunotherapy. (c) 2009 Elsevier Inc. All rights reserved.

Timing of Dose Relative to Sexual Intercourse Attempt in Previous Sildenafil Citrate Users Treated with Tadalafil: A Geographical Comparison from a Single Arm, Open-Label Study

Introduction. Previous research has demonstrated that sildenafil citrate users alter dosing-sexual attempt behavior when switched to tadalafil. The impact of geography and culture on sexual behavior with phosphodiesterase type 5 (PDE5) inhibitor treatment has not been fully investigated. Aim. To describe and compare the changes in dosing-sexual attempt behavior with sildenafil citrate vs. tadalafil treatment across four distinct geographies: Asia, Australia/New Zealand (ANZ), Central Eastern Europe/Middle East (CEE/ME), and Latin America (LA). Methods. Data from a single-arm, open-label clinical trial conducted in 21 countries from November 2002 to May 2004 were used in this analysis. Men with erectile dysfunction and a history of >= 6-week prior sildenafil citrate use continued sildenafil citrate treatment for 4 weeks then switched to tadalafil for 8 weeks. Dosing instructions were provided. Main Outcomes Measures. Timing of dose and sexual intercourse was assessed through patient diaries for the final 4 weeks of each treatment period. Results. A total of 2,760 men were enrolled: Asia 15.8%; ANZ 29.4%; CEE/ME 19.7%; LA 35.1%. The median time from dosing to intercourse was significantly increased during tadalafil treatment across all geographical regions; however, the magnitude of increase differed significantly by geography (P < 0.0001). The Asian cohort demonstrated the shortest duration between dosing and sexual intercourse attempts (irrespective of drug), and altered sexual behavior the least upon switching to tadalafil. The ANZ cohort demonstrated the longest duration between dosing and sexual intercourse attempts (irrespective of drug), and altered sexual behavior the most upon switching to tadalafil. Conclusion. Men with a history of established sildenafil citrate use alter their dose-attempt behavior when treated with tadalafil irrespective of geography. However, the extent to which sexual behavior alters is not uniform across geographical regions, suggesting that dosing instructions and duration of drug effectiveness, in combination with personal and cultural preferences, may determine sexual behavior with PDE5 inhibitor use. Rubio-Aurioles E, Glina S, Abdo CHN, Hernandez-Serrano R, Rampazzo C, Sotomayor M, West TM, Gallagher GL, and Lenero E. Timing of dose relative to sexual intercourse attempt in previous sildenafil citrate users treated with tadalafil: A geographical comparison from a single arm, open-label study. J Sex Med 2009;6:2836-2850.

Particulate urban air pollution affects the functional morphology of mouse placenta

in humans, adverse pregnancy outcomes (low birth weight, prematurity, and intrauterine growth retardation) are associated with exposure to urban air pollution. Experimental data have also shown that such exposure elicits adverse reproductive outcomes. We hypothesized that the effects of urban air pollution on pregnancy outcomes could be related to changes in functional morphology of the placenta. To test this, future dams were exposed during pregestational and gestational periods to filtered or nonfiltered air in exposure chambers. Placentas were collected from near-term pregnancies and prepared for microscopical examination. Fields of view on vertical uniform random tissue slices were analyzed using stereological methods. Volumes of placental compartments were estimated, and the labyrinth was analyzed further in terms of its maternal vascular spaces, fetal capillaries, trophoblast, and exchange surface areas. From these primary data, secondary quantities were derived: vessel calibers (expressed as diameters), trophoblast thickness (arithmetic mean), and total and mass-specific morphometric diffusive conductances for oxygen of the intervascular barrier. Two-way analysis of variance showed that both periods of exposure led to significantly smaller fetal weights. Pregestational exposure to nonfiltered air led to significant increases in fetal capillary surface area and in total and mass-specific conductances. However, the calibers of maternal blood spaces were reduced. Gestational exposure to nonfiltered air was associated with reduced volumes, calibers, and surface areas of maternal blood spaces and with greater fetal capillary surfaces and diffusive conductances. The findings indicate that urban air pollution affects placental functional morphology. Fetal weights are compromised despite attempts to improve diffusive transport across the placenta.

Prevalence and Correlates of Bipolar Spectrum Disorder in the World Mental Health Survey Initiative

Context: There is limited information on the prevalence and correlates of bipolar spectrum disorder in international population-based studies using common methods. Objectives: To describe the prevalence, impact, patterns of comorbidity, and patterns of service utilization for bipolar spectrum disorder (BPS) in the World Health Organization World Mental Health Survey Initiative. Design, Setting, and Participants: Crosssectional, face-to-face, household surveys of 61 392 community adults in 11 countries in the Americas, Europe, and Asia assessed with the World Mental Health version of the World Health Organization Composite International Diagnostic Interview, version 3.0, a fully structured, lay-administered psychiatric diagnostic interview. Main Outcome Measures: Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) disorders, severity, and treatment. Results: The aggregate lifetime prevalences were 0.6% for bipolar type I disorder (BP-I), 0.4% for BP-II, 1.4% for subthreshold BP, and 2.4% for BPS. Twelve-month prevalences were 0.4% for BP-I, 0.3% for BP-II, 0.8% for subthreshold BP, and 1.5% for BPS. Severity of both manic and depressive symptoms as well as suicidal behavior increased monotonically from subthreshold BP to BP-I. By contrast, role impairment was similar across BP subtypes. Symptom severity was greater for depressive episodes than manic episodes, with approximately 74.0% of respondents with depression and 50.9% of respondents with mania reporting severe role impairment. Three-quarters of those with BPS met criteria for at least 1 other disorder, with anxiety disorders (particularly panic attacks) being the most common comorbid condition. Less than half of those with lifetime BPS received mental health treatment, particularly in low-income countries, where only 25.2% reported contact with the mental health system. Conclusions: Despite cross-site variation in the prevalence rates of BPS, the severity, impact, and patterns of comorbidity were remarkably similar internationally. The uniform increases in clinical correlates, suicidal behavior, and comorbidity across each diagnostic category provide evidence for the validity of the concept of BPS. Treatment needs for BPS are often unmet, particularly in low-income countries.

Inter- and intra-tester reliability of clinical measurement to determine medio-lateral patellar position using a pachymeter or visual assessment

The aim was to investigate inter-tester and intra-tester reliability and parallel reliability between a visual assessment method and a method using a pachymeter for locating the mid-point of the patella in determining the medial/lateral patella orientation. Fifteen asymptomatic subjects were assessed and the mid-point of the patella was determined by both methods on two separate occasions two weeks apart. Inter-tester reliability was obtained by ANOVA and by intraclass correlation coefficient (ICC); intra-tester reliability was obtained by a paired t-test and ICC; and parallel reliability was obtained by Pearson`s Correlation and ICC, for the measurement on the first and second evaluations. There was acceptable inter-tester agreement (p = 0.490) and reliability for the visual inspection (ICC = 0.747) and for the pachymeter (ICC = 0.716) at the second evaluation. The inter-tester reliability in the first evaluation was unacceptable (visual ICC = 0.604; pachymeter ICC = 0.612). Although there was statistical similarity between measurements for the first and second evaluations for all testers, intra-tester reliability was not acceptable for both methods: visual (examiner 1 ICC = 0.175; examiner 2 ICC = 0.189; examiner 3 ICC = 0.155) and pachymeter (examiner 1 ICC = 0.214; examiner 2 ICC = 0.246; examiner 3 ICC = 0.069). Parallel reliability gave a perfect correlation at the first evaluation (r=0.828; p<0.001) and at the second (r=0.756; p<0.001) and reliability was between acceptable and very good (ICC = [0.748-0.813]). Both visual and pachymeter methods provide reliable and similar medial/lateral patella orientation and are reliable between different examiners, but the results between the two assessments at 2 weeks` interval demonstrated an unacceptable reliability. (C) 2009 Elsevier B.V. All rights reserved.

Cisplatin and Etoposide in Childhood Germ Cell Tumor: Brazilian Pediatric Oncology Society Protocol GCT-91

Purpose In 1988, we formed a consortium of Brazilian institutions to develop uniform standards for the diagnostic assessment and multidisciplinary treatment of children and adolescents with germ cell tumors. We also implemented the first childhood Brazilian germ cell tumor protocol, GCT-91, evaluating two-agent chemotherapy with cisplatin and etoposide (PE). We now report on the clinical characteristics and survival of children and adolescents with germ cell tumors treated on this protocol. Patients and Methods From May 1991 to April 2000, 115 patients (106 assessable patients) were enrolled onto the Brazilian protocol with a diagnosis of germ cell tumor. Results Patients were treated with surgery only (n = 35) and chemotherapy (n = 71). Important prognostic factors included stage (P = .025), surgical procedure at diagnosis according to resectability (P = .032), and abnormal lactate dehydrogenase value at diagnosis (P = .001). Conclusion The improvement in survival by the introduction of a standard protocol is an important achievement. This is of particular importance for smaller institutions with previous limited experience in the treatment of childhood germ cell tumors. In addition, the results of a two-agent regimen with PE were favorable (5-year overall survival rate is 83.3% for patients in the high-risk group [n = 36] who received PE v 58.8% for patients in the high-risk patients group who received PE plus ifosfamide, vinblastine, and bleomycin [n = 17; P = .017]). Thus for selected patients, complex three-agent regimens may not be necessary to achieve long-term survival, even for some patients with advanced disease.

Current management practices for acromegaly: an international survey

To determine whether peer-reviewed consensus statements have changed clinical practice, we surveyed acromegaly care in specialist centers across the globe, and determined the degree of adherence to published consensus guidelines on acromegaly management. Sixty-five acromegaly experts who participated in the 7th Acromegaly Consensus Workshop in March 2009 responded. Results indicated that the most common referring sources for acromegaly patients were other endocrinologists (in 26% of centers), neurosurgeons (25%) and primary care physicians (21%). In sixty-nine percent of patients, biochemical diagnoses were made by evaluating results of a combination of growth hormone (GH) nadir/basal GH and elevated insulin like growth factor-I (IGF-I) levels. In both Europe and the USA, neurosurgery was the treatment of choice for GH-secreting microadenomas and for macroadenomas with compromised visual function. The most widely used criteria for neurosurgical outcome assessment were combined measurements of IGF-I and GH levels after oral glucose tolerance test (OGTT) 3 months after surgery. Ninety-eight percent of respondents stated that primary treatment with somatostatin receptor ligands (SRLs) was indicated at least sometime during the management of acromegaly patients. In nearly all centers (96%), the use of pegvisomant monotherapy was restricted to patients who had failed to achieve biochemical control with SRL therapy. The observation that most centers followed consensus statement recommendations encourages the future utility of these workshops aimed to create uniform management standards for acromegaly.

Molecular cloning, sequencing, and expression analysis of presenilin cDNA from Schistosoma mansoni

Presenilins (PS) are integral membrane proteins involved, among other functions, in regulated intramembrane proteolysis. In this study, we report the identification and characterization of a complementary DNA from Schistosoma mansoni exhibiting a significant homology to human and nonvertebrate presinilins. S. mansoni contained a 1,485 bp open reading frame encoding a predicted protein of 494 amino acids. Alignment of predicted amino acid sequence of S. mansoni with PS (SmPS) from other species revealed up to 40% similarity shared among the investigated organisms. In addition, phylogenetic analyses demonstrated SmPS being closely related to its orthologues found in Schistosoma japonicum and Caenorhabditis elegans. Expression analysis of SmPS using quantitative real-time PCR revealed that the transcript is up-regulated in the egg stage. We hypothesize that the high level of SmPS in the S. mansoni embryo correlates to an important role during cellular signaling associated to larval development. To our knowledge, this study represents the first attempt to investigate the existence and abundance of PS from a helminth parasite.

Myosin Va phosphorylated on ser(1650) is found in nuclear speckles and redistributes to nucleoli upon inhibition of transcription

Nuclear actin and nuclear myosins have been implicated in the regulation of geneexpression in vertebrate cells. Myosin V is a class of actin-based motor proteins involved in cytoplasmic vesicle transport and anchorage, spindle-pole alignment and mRNA translocation. In this study, myosin-Va, phosphorylated on a conserved serine in the tail domain (phospho-ser(1650) MVa), was localized to subnuclear compartments. A monoclonal antibody, 9E6, raised against a peptide corresponding to phosphoserine(1650) and flanking regions of the murine myosin Va sequence, was immunoreactive to myosin Va heavy chain in cellular and nuclear extracts of HeLa cells, PC12 cells and B16-F10 melanocytes. Immunofluorescence microscopy with this antibody revealed discrete irregular spots within the nucleoplasm that colocalized with SC35, a splicing factor that earmarks nuclear speckles. Phospho-ser(1650) MVa was not detected in other nuclear compartments, such as condensed chromatin, Cajal bodies, gems and perinucleolar caps. Although nucleoli also were not labeled by 9E6 under normal conditions, inhibition of transcription in HeLa cells by actinomycin D caused the redistribution of phospho-ser(1650) MVa to nucleoli, as well as separating a fraction of phosphoser(1650) MVa from SC35 into near-neighboring particles. These observations indicate a novel role for myosin Va in nuclear compartmentalization and offer a new lead towards the understanding of actomyosin-based gene regulation.