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A Universidade de Harvard (em inglês: Harvard University) é uma universidade privada membro da Ivy League, localizada em Cambridge, Massachusetts, Estados Unidos, e cuja história, influência e riqueza tornam-a uma das mais prestigiadas universidades do mundo.

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Mutant human torsinA, responsible for early-onset dystonia, dominantly suppresses GTPCH expression, dopamine levels and locomotion in Drosophila melanogaster

Wakabayashi-Ito, Noriko; Ajjuri, Rami R.; Henderson, Benjamin W.; Doherty, Olugbenga M.; Breakefield, Xandra O.; O'Donnell, Janis M.; Ito, Naoto
Fonte: The Company of Biologists Publicador: The Company of Biologists
Tipo: Artigo de Revista Científica
EN_US
Dystonia represents the third most common movement disorder in humans with over 20 genetic loci identified. TOR1A (DYT1), the gene responsible for the most common primary hereditary dystonia, encodes torsinA, an AAA ATPase family protein. Most cases of DYT1 dystonia are caused by a 3 bp (ΔGAG) deletion that results in the loss of a glutamic acid residue (ΔE302/303) in the carboxyl terminal region of torsinA. This torsinAΔE mutant protein has been speculated to act in a dominant-negative manner to decrease activity of wild type torsinA. Drosophila melanogaster has a single torsin-related gene, dtorsin. Null mutants of dtorsin exhibited locomotion defects in third instar larvae. Levels of dopamine and GTP cyclohydrolase (GTPCH) proteins were severely reduced in dtorsin-null brains. Further, the locomotion defect was rescued by the expression of human torsinA or feeding with dopamine. Here, we demonstrate that human torsinAΔE dominantly inhibited locomotion in larvae and adults when expressed in neurons using a pan-neuronal promoter Elav. Dopamine and tetrahydrobiopterin (BH4) levels were significantly reduced in larval brains and the expression level of GTPCH protein was severely impaired in adult and larval brains. When human torsinA and torsinAΔE were co-expressed in neurons in dtorsin-null larvae and adults...

Cerebrospinal fluid amyloid-β 42/40 ratio in clinical setting of memory centers: a multicentric study

Dumurgier, Julien; Schraen, Susanna; Gabelle, Audrey; Vercruysse, Olivier; Bombois, Stéphanie; Laplanche, Jean-Louis; Peoc’h, Katell; Sablonnière, Bernard; Kastanenka, Ksenia V; Delaby, Constance; Pasquier, Florence; Touchon, Jacques; Hugon, Jacques;
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
EN_US
Introduction: The cerebrospinal fluid (CSF) biomarkers amyloid-β (Aβ), tau and phosphorylated tau (p-tau181) are now used for the diagnosis of Alzheimer’s disease (AD). Aβ40 is the most abundant Aβ peptide isoform in the CSF, and the Aβ 42/40 ratio has been proposed to better reflect brain amyloid production. However, its additional value in the clinical setting remains uncertain. Methods: A total of 367 subjects with cognitive disorders who underwent a lumbar puncture were prospectively included at three French memory centers (Paris-North, Lille and Montpellier; the PLM Study). The frequency of positive, negative and indeterminate CSF profiles were assessed by various methods, and their adequacies with the diagnosis of clinicians were tested using net reclassification improvement (NRI) analyses. Results: On the basis of local optimum cutoffs for Aβ42 and p-tau181, 22% of the explored patients had indeterminate CSF profiles. The systematic use of Aβ 42/40 ratio instead of Aβ42 levels alone decreased the number of indeterminate profiles (17%; P = 0.03), but it failed to improve the classification of subjects (NRI = −2.1%; P = 0.64). In contrast, the use of Aβ 42/40 ratio instead of Aβ42 levels alone in patients with a discrepancy between p-tau181 and Aβ42 led to a reduction by half of the number of indeterminate profiles (10%; P < 0.001) and was further in agreement with clinician diagnosis (NRI = 10.5%; P = 0.003). Conclusions: In patients with a discrepancy between CSF p-tau181 and CSF Aβ42...

Multidimensional Dyspnea Profile: an instrument for clinical and laboratory research

Banzett, Robert B.; O'Donnell, Carl R.; Guilfoyle, Tegan E.; Parshall, Mark B.; Schwartzstein, Richard M.; Meek, Paula M.; Gracely, Richard H.; Lansing, Robert W.
Fonte: European Respiratory Society Publicador: European Respiratory Society
Tipo: Artigo de Revista Científica
EN_US
There is growing awareness that dyspnoea, like pain, is a multidimensional experience, but measurement instruments have not kept pace. The Multidimensional Dyspnea Profile (MDP) assesses overall breathing discomfort, sensory qualities, and emotional responses in laboratory and clinical settings. Here we provide the MDP, review published evidence regarding its measurement properties and discuss its use and interpretation. The MDP assesses dyspnoea during a specific time or a particular activity (focus period) and is designed to examine individual items that are theoretically aligned with separate mechanisms. In contrast, other multidimensional dyspnoea scales assess recalled recent dyspnoea over a period of days using aggregate scores. Previous psychophysical and psychometric studies using the MDP show that: 1) subjects exposed to different laboratory stimuli could discriminate between air hunger and work/effort sensation, and found air hunger more unpleasant; 2) the MDP immediate unpleasantness scale (A1) was convergent with common dyspnoea scales; 3) in emergency department patients, two domains were distinguished (immediate perception, emotional response); 4) test–retest reliability over hours was high; 5) the instrument responded to opioid treatment of experimental dyspnoea and to clinical improvement; 6) convergent validity with common instruments was good; and 7) items responded differently from one another as predicted for multiple dimensions.

Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE

Ayton, Scott; Faux, Noel G.; Bush, Ashley I.; Weiner, Michael W.; Aisen, Paul; Petersen, Ronald; Jack Jr., Clifford R.; Jagust, William; Trojanowki, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Shaw, Leslie
Fonte: Nature Pub. Group Publicador: Nature Pub. Group
Tipo: Artigo de Revista Científica
EN_US
Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. Ferritin was strongly associated with CSF apolipoprotein E levels and was elevated by the Alzheimer's risk allele, APOE-ɛ4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-ɛ4 being the major genetic risk factor for AD.

Reconstruction of the arcuate fasciculus for surgical planning in the setting of peritumoral edema using two-tensor unscented Kalman filter tractography

Chen, Zhenrui; Tie, Yanmei; Olubiyi, Olutayo; Rigolo, Laura; Mehrtash, Alireza; Norton, Isaiah; Pasternak, Ofer; Rathi, Yogesh; Golby, Alexandra J.; O'Donnell, Lauren J.
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
EN_US
Background: Diffusion imaging tractography is increasingly used to trace critical fiber tracts in brain tumor patients to reduce the risk of post-operative neurological deficit. However, the effects of peritumoral edema pose a challenge to conventional tractography using the standard diffusion tensor model. The aim of this study was to present a novel technique using a two-tensor unscented Kalman filter (UKF) algorithm to track the arcuate fasciculus (AF) in brain tumor patients with peritumoral edema. Methods: Ten right-handed patients with left-sided brain tumors in the vicinity of language-related cortex and evidence of significant peritumoral edema were retrospectively selected for the study. All patients underwent 3-Tesla magnetic resonance imaging (MRI) including a diffusion-weighted dataset with 31 directions. Fiber tractography was performed using both single-tensor streamline and two-tensor UKF tractography. A two-regions-of-interest approach was applied to perform the delineation of the AF. Results from the two different tractography algorithms were compared visually and quantitatively. Results: Using single-tensor streamline tractography, the AF appeared disrupted in four patients and contained few fibers in the remaining six patients. Two-tensor UKF tractography delineated an AF that traversed edematous brain areas in all patients. The volume of the AF was significantly larger on two-tensor UKF than on single-tensor streamline tractography (p < 0.01). Conclusions: Two-tensor UKF tractography provides the ability to trace a larger volume AF than single-tensor streamline tractography in the setting of peritumoral edema in brain tumor patients.

Objective Assessment of Fall Risk in Parkinson's Disease Using a Body-Fixed Sensor Worn for 3 Days

Weiss, Aner; Herman, Talia; Giladi, Nir; Hausdorff, Jeffrey M.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
EN_US
Background: Patients with Parkinson's disease (PD) suffer from a high fall risk. Previous approaches for evaluating fall risk are based on self-report or testing at a given time point and may, therefore, be insufficient to optimally capture fall risk. We tested, for the first time, whether metrics derived from 3 day continuous recordings are associated with fall risk in PD. Methods and Materials 107 patients (Hoehn & Yahr Stage: 2.6±0.7) wore a small, body-fixed sensor (3D accelerometer) on lower back for 3 days. Walking quantity (e.g., steps per 3-days) and quality (e.g., frequency-derived measures of gait variability) were determined. Subjects were classified as fallers or non-fallers based on fall history. Subjects were also followed for one year to evaluate predictors of the transition from non-faller to faller. Results: The 3 day acceleration derived measures were significantly different in fallers and non-fallers and were significantly correlated with previously validated measures of fall risk. Walking quantity was similar in the two groups. In contrast, the fallers walked with higher step-to-step variability, e.g., anterior-posterior width of the dominant frequency was larger (p = 0.012) in the fallers (0.78±0.17 Hz) compared to the non-fallers (0.71±0.07 Hz). Among subjects who reported no falls in the year prior to testing...

A Pilot Study on Women's Health Education in Rural Guatemala: Impact on Beliefs and Behaviors

Messmer, Sarah Elizabeth
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation; text Formato: application/pdf
EN
Great disparities exist in women’s health outcomes in rural indigenous communities in Guatemala; indigenous women are less likely to utilize family planning and cervical cancer screening services. This pilot study assessed baseline women’s health knowledge and the effects of a comprehensive women’s health course on women’s health knowledge and behaviors. From February to November 2013, 61 participants in a seven-week language-appropriate women’s health curriculum were evaluated before and after the course using a 10-item knowledge assessment. Cervical cancer screening and contraceptive utilization rates were assessed by self-report before and after the course. Several women’s health knowledge deficits were noted: belief that contraception causes cancer, inability to name symptoms of STIs, lack of understanding of pap smears, and lack of familiarity with condoms. The average pre-test score was 54.6%; increasing to 83.7% on the post-test (p<0.0001). 79% had received a pap smear prior to the course; this increased to 92% at the post-test (p=0.013). 53% had utilized contraception prior to the course; at the time of the post-test the percentage was 54% (p=1). This study reveals important patterns in women’s health beliefs in rural Guatemala...

Why They Hate Us: The Role of Social Dynamics

Sunstein, Cass Robert
Fonte: Harvard University, Harvard Law School Publicador: Harvard University, Harvard Law School
Tipo: Artigo de Revista Científica
EN_US

A Bio-Inspired Swellable Microneedle Adhesive for Mechanical Interlocking with Tissue

Yang, Seung Yun; O'Cearbhaill, Eoin D.; Sisk, Geoffroy C.; Park, Kyeng Min; Cho, Woo Kyung; Villiger, Martin; Bouma, Brett E.; Pomahac, Bohdan; Karp, Jeffrey M.
Fonte: Harvard University Publicador: Harvard University
Tipo: Artigo de Revista Científica
EN_US
Achieving significant adhesion to soft tissues while minimizing tissue damage poses a considerable clinical challenge. Chemical-based adhesives require tissue-specific reactive chemistry, typically inducing a significant inflammatory response. Staples are fraught with limitations including high-localized tissue stress and increased risk of infection, and nerve and blood vessel damage. Here, inspired by the endoparasite Pomphorhynchus laevis which swells its proboscis to attach to its host’s intestinal wall, we have developed a biphasic microneedle array that mechanically interlocks with tissue through swellable microneedle tips, achieving ~ 3.5 fold increase in adhesion strength compared to staples in skin graft fixation, and removal force of ~ 4.5 N/cm2 from intestinal mucosal tissue. Comprising a poly(styrene)-block-poly(acrylic acid) swellable tip and non-swellable polystyrene core, conical microneedles penetrate tissue with minimal insertion force and depth, yet high adhesion strength in their swollen state. Uniquely, this design provides universal soft tissue adhesion with minimal damage, less traumatic removal, reduced risk of infection and delivery of bioactive therapeutics.

Multiple synchronous sites of origin of vestibular schwannomas in neurofibromatosis Type 2

Stivaros, Stavros M; Stemmer-Rachamimov, Anat O; Alston, Robert; Plotkin, Scott R; Nadol, Joseph B; Quesnel, Alicia; O'Malley, Jennifer; Whitfield, Gillian A; McCabe, Martin G; Freeman, Simon R; Lloyd, Simon K; Wright, Neville B; Kilday, John-Paul; Kamaly
Fonte: BMJ Publishing Group Publicador: BMJ Publishing Group
Tipo: Artigo de Revista Científica
EN_US
Background: Neurofibromatosis Type 2 (NF2) is a dominantly inherited tumour syndrome with a phenotype which includes bilateral vestibular (eighth cranial nerve) schwannomas. Conventional thinking suggests that these tumours originate at a single point along the superior division of the eighth nerve. Methods: High resolution MRI was performed in children genetically proven to have NF2. The superior vestibular nerve (SVN) and inferior vestibular nerve (IVN) were visualised along their course with points of tumour origin calculated as a percentage relative to the length of the nerve. Results: Out of 41 patients assessed, 7 patients had no identifiable eighth cranial nerve disease. In 16 patients there was complete filling of the internal auditory meatus by a tumour mass such that its specific neural origin could not be determined. In the remaining 18 cases, 86 discrete separate foci of tumour origin on the SVN or IVN could be identified including 23 tumours on the right SVN, 26 tumours on the right IVN, 18 tumours on the left SVN and 19 tumours on the left IVN. Discussion This study, examining the origins of vestibular schwannomas in NF2, refutes their origin as being from a single site on the transition zone of the superior division of the vestibular nerve. We hypothesise a relationship between the number of tumour foci...

Impact of Vitamin D and Asthma on Preeclampsia Development: A Sequential Evidence-Based Approach to Genomic Analysis

Mirzakhani, Hooman
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation; text Formato: application/pdf
EN
The biologic evidence regarding the role for vitamin D in immunologic mechanisms and reproductive outcomes is strong. Epidemiologic studies have shown a high prevalence of vitamin D deficiency among pregnant women, especially among high-risk groups. Vitamin D has been also been linked to asthma attacks, another proposed risk factor for preeclampsia. Association of vitamin D and severe asthma has been studied in general population . Along with a clear genetic basis in atopic asthma, environmental factors, including early neonatal nutrition, may have an important influence on asthma development. Vitamin D may be an important environmental factor influencing asthma outcomes. A recent meta-analysis investigated the adverse perinatal outcomes in women with asthma and concluded that as much as a 50% increase risk of PE development in asthmatic pregnant women. Interestingly, in preeclampsia, epidemiologic studies have implicated alterations in vitamin D metabolism and low vitamin D status during pregnancy. The objective of this dissertation is to investigate the potential confounding/modulating effect of vitamin D in the association of asthma and preeclampsia as well as its role in gene expressions in early pregnancy of preeclamptic women. To achieve this goal...

Exome Array Analysis of Chronic Obstructive Pulmonary Disease

Hobbs, Brian
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation; text Formato: application/pdf
EN
Background: Chronic obstructive pulmonary disease (COPD) susceptibility is in part related to genetic variants. Most genetic studies have focused on common variation, but rare coding variants are known to affect COPD susceptibility. We hypothesized that an exome array analysis would identify single non-synonymous variants and gene-based aggregates of non-synonymous variants associated with COPD. Methods: We used the Illumina HumanExome array to genotype individuals in six COPD cohorts: Caucasian subjects from the family-based Boston Early-Onset COPD Study (BEOCOPD) and International COPD Genetics Network (ICGN), and the case-control COPDGene (non-Hispanic whites and African-Americans) and Transcontinental COPD Genetics Study (Poland and Korea). Cases were defined as GOLD Grade 2 and above COPD. Controls had normal lung function; the vast majority were current or former smokers. We tested single non-synonymous, stop and splice variants with a minor allele frequency (MAF) of > 0.5% in an additive model using logistic regression and combined results in a fixed-effects meta-analysis. Our gene-based testing was performed on non-synonymous, stop, and splice variants with MAF < 5% and used SKAT-O with meta-analysis in the MetaSKAT software in R. We performed meta-analyses for all subjects and separately by ethnicity. We adjusted all analyses for age...

Association of Clinical Features With Incidental Findings From Exome Sequencing in 3,223 African Americans

Natarajan, Pradeep
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation; text Formato: application/pdf
EN
Importance. The American College of Medical Genetics and Genomics recommends informing individuals who carry mutations in a set of Mendelian disease genes that might require clinical action regardless of genetic testing indication. However, whether such mutations lead to an increased risk for diseases in individuals not referred for clinical genetic testing has not been evaluated. Objective. To evaluate whether those in the unselected general population who carry potentially actionable mutations are more likely to manifest the associated diseases than those without such mutations. Design, Setting, and Participants. Cross-sectional observational study of participants enrolled in the Jackson Heart Study (Jackson, MS) between 2000 and 2004 who underwent whole exome sequencing (n = 3223). All participants were on African descent. Exposures. Mutations across a set of 56 recommended clinically actionable genes ascertained by whole exome sequencing. Main Outcomes and Measures. Evidence for pathogenicity for all mutations identified in 56 genes was determined by bioinformatic analyses and extensive literature review. Anticipated clinical findings for each of the 56 genes were extracted from study surveys, echocardiography, electrocardiography...

Improving Health Care Proxy Documentation Using a Web-Based Interview Through a Patient Portal

Bajracharya, Adarsha S.
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation; text Formato: application/pdf
EN
Objective: Health care proxy (HCP) documentation is suboptimal. To improve rates of proxy selection and documentation, we sought to develop and evaluate a web-based interview to guide patients in their selection, and to capture their choices in their electronic health record (EHR). Methods: We developed and implemented a HCP interview within the patient portal of a large academic health system. We analyzed the experience, together with demographic and clinical factors, of the first 200 patients who used the portal to complete the interview. We invited users to comment about their experience and analyzed their comments using established qualitative methods. Results: From January 20, 2015 to March 13, 2015, 139 of the 200 patients who completed the interview submitted their health care proxy information for their clinician to review in the EHR. These patients had a median age of 57 years (IQR 45-67) and most were healthy. The 99 patients who did not previously have health care proxy information in their electronic health record were more likely to complete and then submit their information than the 101 patients who previously had a proxy in their health record (Odds Ratio 2.4, P= 0.005). Qualitative analysis identified several ways in which the portal-based interview reminded...

Is Childhood Pneumonia Associated With Future Disease Susceptibility? An Investigation Into the Early Origins of Chronic Obstructive Pulmonary Disease

Hayden, Lystra P.
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation; text Formato: application/pdf
EN
BACKGROUND Development of adult respiratory disease is influenced by events in childhood. The impact of childhood pneumonia on chronic obstructive pulmonary disease (COPD) is not well defined. We hypothesize that childhood pneumonia is a risk factor for COPD in adult smokers and that genome wide analysis studies (GWAS) will identify genetic loci associated with development of pneumonia. METHODS Smokers between 45–80 years old from the US COPDGene Study were included. Childhood pneumonia was defined by self-report of pneumonia at <16 years. Smokers with and without childhood pneumonia were compared on measures of respiratory disease, lung function, and quantitative analysis of chest CT scans. Childhood and lifetime pneumonia GWAS were performed separately in non-Hispanic whites (NHW) and African Americans (AA) and the results combined in meta-analysis. RESULTS Of 10,192 adult smokers, 854 (8.4%) reported pneumonia in childhood. Childhood pneumonia was associated with COPD (OR 1.40; 95%CI 1.17-1.66), decreased lung function, and increased airway wall thickness on CT, without significant difference in emphysema. Case-control GWAS meta-analysis of childhood pneumonia identified variants of interest in NGR1 (p=6.32E-08) and PAK6 (p=3.277E-07). Meta-analysis of GWAS results in the lifetime pneumonia group identified variants of interest in PRR27 (p=4.341E-07) and near MCPH (p=2.705E-07). CONCLUSIONS Children with pneumonia are at increased risk for future smoking-related respiratory disease including COPD and decreased lung function. The variability in prevalence of childhood pneumonia and the association with increased risk for future disease suggest an underlying genetic susceptibility. We have identified potential genes associated with risk of pneumonia. Further research will be required to determine whether these genes confer risk for childhood pneumonia...

Measuring Patient-Perceived Quality of Care in U.S. Hospitals Using Twitter

Hawkins, Jared Brian
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation; text Formato: application/pdf
EN
BACKGROUND Patients use Twitter to share feedback about their experience receiving health care. Identifying and analyzing the content of posts sent to each hospital may provide a novel real-time measure of quality, supplementing traditional, survey-based approaches. OBJECTIVE To assess the use of Twitter as a supplemental data stream for measuring patient-perceived quality of care in U.S. hospitals and compare patient sentiments about hospitals on Twitter to established quality measures. DESIGN Tweets directed to U.S. hospitals over a 1-year period were classified as having to do with patient experience using a machine learning approach. Additionally, sentiment was calculated for patient experience tweets using natural language processing. KEY RESULTS Roughly half of the hospitals in the U.S. have a presence on Twitter. Of the tweets directed toward these hospitals, ~9% were related to patient experience. Analyses revealed that specific hospital characteristics were associated with lower sentiment. Finally, hospital sentiment was moderately correlated with a commonly used measure of quality. CONCLUSIONS Tweets describing patient experiences in hospitals cover a wide range of patient care aspects and can be identified using automated approaches. These tweets represent a reliable predictor of treatment quality and may be valuable to patients...

Abnormal rib count in scoliosis surgery: impact on the reporting of spinal fusion levels

Spencer, Hillard T.; Gold, Meryl E.; Hresko, M. Timothy
Fonte: Springer Berlin Heidelberg Publicador: Springer Berlin Heidelberg
Tipo: Artigo de Revista Científica
EN_US
Purpose Variation in rib numbering has been noted in adolescent idiopathic scoliosis (AIS), but its effect on the reporting of fusion levels has not been studied. We hypothesized that vertebral numbering variations can lead to differing documentation of fusion levels. Methods: We examined the radiographs of 161 surgical AIS patients and 179 control patients without scoliosis. For AIS patients, the operative report of fusion levels was compared to conventional vertebral labeling from the first thoracic level and proceeding caudal. We defined normal counts as 12 thoracic (rib-bearing) and five lumbar (non-rib-bearing) vertebrae. We compared our counts with data from 181 anatomic specimens. Results: Among AIS patients, 22 (14 %) had an abnormal number of ribs and 29 (18 %) had either abnormal rib or lumbar count. In 12/29 (41 %) patients, the operative report differed from conventional labeling by one level, versus 3/132 (2 %) patients with normal numbering (p < 0.001). However, there were no cases seen of wrong fusion levels based on curve pattern. Among controls, 11 % had abnormal rib count (p = 0.41) compared to the rate in AIS. Anatomic specimen data did not differ in abnormal rib count (p = 1.0) or thoracolumbar pattern (p = 0.59). Conclusions: The rate of numerical variations in the thoracolumbar vertebrae of AIS patients is equivalent to that in the general population. When variations in rib count are present...

Coexistence of Histologically Confirmed Hashimoto's Thyroiditis with Different Stages of Papillary Thyroid Carcinoma in a Consecutive Chinese Cohort

Liu, Xiaoyun; Zhu, Lijun; Cui, Dai; Wang, Zhixiao; Chen, Huanhuan; Duan, Yu; Shen, Meiping; Wu, Yunsong; Rong, Rong; Zhang, Zhihong; Wang, Xiaodong; Chen, Jiawei; Alexander, Erik K.; Yang, Tao
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
EN_US
Purpose. To determine the relationship between Hashimoto's thyroiditis (HT) and all stages of papillary thyroid carcinoma (PTC) with or without local lymph node metastasis (LNM). Methods:. We conducted a retrospective study of thyroidectomies from 2008–2013 in First Affiliated Hospital of Nanjing Medical University. We categorized patients according to the presence of histopathologically proven HT. The prevalence of mPTC (maximum diameter ≤ 10 mm) and crPTC (clinical relevant PTC) and local LNM rates were compared. Results:. We evaluated 6,432 consecutive thyroidectomies. In total, 1,328 specimens were confirmed as HT. The prevalence of PTC in this HT cohort was 43.8%, significantly higher than non-HT group. After adjustment of gender and age, the prevalence of PTC was still higher in HT group. HT was a risk factor for PTC in multivariate analysis with odds ratio 2.725 (95% CI, 2.390–3.109) (P < 0.001). However, no correlation was found between HT and LNM of PTC. Conclusion:. HT was associated with an increased prevalence of all stages of PTC, independent of tumor size, gender, and age. In contrast, locally advanced disease defined by LNM was unrelated to HT. These data suggest an association of HT with low risk PTC and a potential protective immunologic effect from further disease progression.

Prognosis of patients with AIDS-associated Kaposi's sarcoma receiving antiretroviral therapy +/- chemotherapy in Kwazulu-Natal, South Africa: an analysis of 1-yr survival data from NCT00380770

Uldrick, TS; Mosam, A; Shaik, F; Friedland, G; Skadden, D; Jordaan, JP; Aboobaker, J; Coovadia, HM
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Outros
EN_US

MicroRNAs Located in the Hox Gene Clusters Are Implicated in Huntington's Disease Pathogenesis

Hoss, Andrew G.; Kartha, Vinay K.; Dong, Xianjun; Latourelle, Jeanne C.; Dumitriu, Alexandra; Hadzi, Tiffany C.; MacDonald, Marcy E.; Gusella, James F.; Akbarian, Schahram; Chen, Jiang-Fan; Weng, Zhiping; Myers, Richard H.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
EN_US
Transcriptional dysregulation has long been recognized as central to the pathogenesis of Huntington's disease (HD). MicroRNAs (miRNAs) represent a major system of post-transcriptional regulation, by either preventing translational initiation or by targeting transcripts for storage or for degradation. Using next-generation miRNA sequencing in prefrontal cortex (Brodmann Area 9) of twelve HD and nine controls, we identified five miRNAs (miR-10b-5p, miR-196a-5p, miR-196b-5p, miR-615-3p and miR-1247-5p) up-regulated in HD at genome-wide significance (FDR q-value<0.05). Three of these, miR-196a-5p, miR-196b-5p and miR-615-3p, were expressed at near zero levels in control brains. Expression was verified for all five miRNAs using reverse transcription quantitative PCR and all but miR-1247-5p were replicated in an independent sample (8HD/8C). Ectopic miR-10b-5p expression in PC12 HTT-Q73 cells increased survival by MTT assay and cell viability staining suggesting increased expression may be a protective response. All of the miRNAs but miR-1247-5p are located in intergenic regions of Hox clusters. Total mRNA sequencing in the same samples identified fifteen of 55 genes within the Hox cluster gene regions as differentially expressed in HD, and the Hox genes immediately adjacent to the four Hox cluster miRNAs as up-regulated. Pathway analysis of mRNA targets of these miRNAs implicated functions for neuronal differentiation...