First-time patellar dislocation with resultant habitual dislocation two years later, which was not demonstrated on plain X-rays halfway: a case report

We present an instructive case of habitual left patellar dislocation in which the patella had appeared odd due to lateral tilt relative to contralateral side, but had been radiologically confirmed to be on the trochlea at 1 year prior to the referral. An 11-year-old girl presented to our hospital 2 years after the left patella had dislocated with a 'giving way' when cutting to the left. Our physical and radiological examinations confirmed that the left patella was laterally tilted in the patellar groove with the knee in extension but was dislocated in flexion beyond 45°. In spite of these findings, she had been untreated at the previous hospital since all plain X-rays, including a skyline patellar view, had failed to demonstrate the dislocation. Consequently, in addition to reconstruction of medial patellofemoral ligament, she had to undergo a lateral retinacular release, which might have been unnecessary if treated earlier. This case illustrates that first-time patellar dislocation can gradually lead to habitual dislocation subsequently, and that cautious physical examinations in regard to patella tracking are essential since radiological examinations do not always reveal the pathophysiology of patellar instability

The landscape of Neandertal ancestry in present-day humans

Analyses of Neandertal genomes have revealed that Neandertals have contributed genetic variants to modern humans1–2. The antiquity of Neandertal gene flow into modern humans means that regions that derive from Neandertals in any one human today are usually less than a hundred kilobases in size. However, Neandertal haplotypes are also distinctive enough that several studies have been able to detect Neandertal ancestry at specific loci1,3–8. Here, we have systematically inferred Neandertal haplotypes in the genomes of 1,004 present-day humans12. Regions that harbor a high frequency of Neandertal alleles in modern humans are enriched for genes affecting keratin filaments suggesting that Neandertal alleles may have helped modern humans adapt to non-African environments. Neandertal alleles also continue to shape human biology, as we identify multiple Neandertal-derived alleles that confer risk for disease. We also identify regions of millions of base pairs that are nearly devoid of Neandertal ancestry and enriched in genes, implying selection to remove genetic material derived from Neandertals. Neandertal ancestry is significantly reduced in genes specifically expressed in testis, and there is an approximately 5-fold reduction of Neandertal ancestry on chromosome X, which is known to harbor a disproportionate fraction of male hybrid sterility genes20–22. These results suggest that part of the reduction in Neandertal ancestry near genes is due to Neandertal alleles that reduced fertility in males when moved to a modern human genetic background

Ovarian carcinoma associated with pregnancy: A clinicopathologic analysis of 23 cases and review of the literature

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to analyze and describe cases of ovarian cancer in pregnant women treated at our center and to review the literature concerned, and to discuss the rationale for therapy.</p> <p>Methods</p> <p>Twenty-Three patients of ovarian malignancies during pregnancy were treated at Vali- Asr Hospital between 1991 and 2002. Data on treatment and follow-up were evaluated.</p> <p>Results</p> <p>The incidence of ovarian carcinoma associated with pregnancy in our series was 0.083/1000 deliveries. Eleven (47.8%) were found with ovarian malignant germ cell tumors, five (21.7%) with low malignant potential tumors, four (17.4%) with invasive epithelial tumors, and three (13%) with sex cord stromal tumors. Seventeen (73.9%) of the patients were diagnosed in stage I and had complete remission. Five of the six in advanced stage died. The mean follow-up was 36.3 months. The prognosis was significantly related with stage and histological type (<it>P </it>< 0.05). Sixteen healthy live babies were recorded in this group, and two premature newborn died of respiratory distress syndrome. Chemotherapy was administered to 44% of the patients, in two cases during pregnancy. Overall survival at 5 years was 61%. In most of case conservative surgical treatment could be performed with adequate staging and debulking.</p> <p>Conclusion</p> <p>Early finding of ascitis by ultrasound and persistent large ovarian mass during pregnancy may be related to malignancy and advanced stage. Pregnant women in advanced stage of ovarian cancer seem to have poor prognosis.</p

Design and Synthesis of Potent in Vitro and in Vivo Anticancer Agents Based on 1-(3′,4′,5′-Trimethoxyphenyl)-2-Aryl-1H-Imidazole

A novel series of tubulin polymerization inhibitors, based on the 1-(3',4',5'-trimethoxyphenyl)-2-aryl-1H-imidazole scaffold and designed as cis-restricted combretastatin A-4 analogues, was synthesized with the goal of evaluating the effects of various patterns of substitution on the phenyl at the 2-position of the imidazole ring on biological activity. A chloro and ethoxy group at the meta- and para-positions, respectively, produced the most active compound in the series (4o), with IC50 values of 0.4-3.8 nM against a panel of seven cancer cell lines. Except in HL-60 cells, 4o had greater antiproliferative than CA-4, indicating that the 3'-chloro-4'-ethoxyphenyl moiety was a good surrogate for the CA-4 B-ring. Experiments carried out in a mouse syngenic model demonstrated high antitumor activity of 4o, which significantly reduced the tumor mass at a dose thirty times lower than that required for CA-4P, which was used as a reference compound. Altogether, our findings suggest that 4o is a promising anticancer drug candidate that warrants further preclinical evaluation

Rheo-PIV of a shear-banding wormlike micellar solution under large amplitude oscillatory shear

We explore the behavior of a wormlike micellar solution under both steady and large amplitude oscillatory shear (LAOS) in a cone–plate geometry through simultaneous bulk rheometry and localized velocimetric measurements. First, particle image velocimetry is used to show that the shear-banded profiles observed in steady shear are in qualitative agreement with previous results for flow in the cone–plate geometry. Then under LAOS, we observe the onset of shear-banded flow in the fluid as it is progressively deformed into the non-linear regime—this onset closely coincides with the appearance of higher harmonics in the periodic stress signal measured by the rheometer. These harmonics are quantified using the higher-order elastic and viscous Chebyshev coefficients e [subscript n] and v [subscript n] , which are shown to grow as the banding behavior becomes more pronounced. The high resolution of the velocimetric imaging system enables spatiotemporal variations in the structure of the banded flow to be observed in great detail. Specifically, we observe that at large strain amplitudes (γ [subscript 0] ≥ 1), the fluid exhibits a three-banded velocity profile with a high shear rate band located in-between two lower shear rate bands adjacent to each wall. This band persists over the full cycle of the oscillation, resulting in no phase lag being observed between the appearance of the band and the driving strain amplitude. In addition to the kinematic measurements of shear banding, the methods used to prevent wall slip and edge irregularities are discussed in detail, and these methods are shown to have a measurable effect on the stability boundaries of the shear-banded flow.Spain. Ministerio de Educación y Ciencia (MEC) (Project FIS2010-21924-C02-02

Cancer Induces Cardiomyocyte Remodeling and Hypoinnervation in the Left Ventricle of the Mouse Heart

Cancer is often associated with cachexia, cardiovascular symptoms and autonomic dysregulation. We tested whether extracardiac cancer directly affects the innervation of left ventricular myocardium. Mice injected with Lewis lung carcinoma cells (tumor group, TG) or PBS (control group, CG) were analyzed after 21 days. Cardiac function (echocardiography), serum levels of TNF-α and Il-6 (ELISA), structural alterations of cardiomyocytes and their innervation (design-based stereology) and levels of innervation-related mRNA (quantitative RT-PCR) were analysed. The groups did not differ in various functional parameters. Serum levels of TNF-α and Il-6 were elevated in TG. The total length of axons in the left ventricle was reduced. The number of dense core vesicles per axon profile was reduced. Decreased myofibrillar volume, increased sarcoplasmic volume and increased volume of lipid droplets were indicative of metabolic alterations of TG cardiomyocytes. In the heart, the mRNA level of nerve growth factor was reduced whereas that of β1-adrenergic receptor was unchanged in TG. In the stellate ganglion of TG, mRNA levels of nerve growth factor and neuropeptide Y were decreased and that of tyrosine hydroxylase was increased. In summary, cancer induces a systemic pro-inflammatory state, a significant reduction in myocardial innervation and a catabolic phenotype of cardiomyocytes in the mouse. Reduced expression of nerve growth factor may account for the reduced myocardial innervation

Comparative genomics of the bacterial genus Listeria: Genome evolution is characterized by limited gene acquisition and limited gene loss

<p>Abstract</p> <p>Background</p> <p>The bacterial genus <it>Listeria </it>contains pathogenic and non-pathogenic species, including the pathogens <it>L. monocytogenes </it>and <it>L. ivanovii</it>, both of which carry homologous virulence gene clusters such as the <it>prfA </it>cluster and clusters of internalin genes. Initial evidence for multiple deletions of the <it>prfA </it>cluster during the evolution of <it>Listeria </it>indicates that this genus provides an interesting model for studying the evolution of virulence and also presents practical challenges with regard to definition of pathogenic strains.</p> <p>Results</p> <p>To better understand genome evolution and evolution of virulence characteristics in <it>Listeria</it>, we used a next generation sequencing approach to generate draft genomes for seven strains representing <it>Listeria </it>species or clades for which genome sequences were not available. Comparative analyses of these draft genomes and six publicly available genomes, which together represent the main <it>Listeria </it>species, showed evidence for (i) a pangenome with 2,032 core and 2,918 accessory genes identified to date, (ii) a critical role of gene loss events in transition of <it>Listeria </it>species from facultative pathogen to saprotroph, even though a consistent pattern of gene loss seemed to be absent, and a number of isolates representing non-pathogenic species still carried some virulence associated genes, and (iii) divergence of modern pathogenic and non-pathogenic <it>Listeria </it>species and strains, most likely circa 47 million years ago, from a pathogenic common ancestor that contained key virulence genes.</p> <p>Conclusions</p> <p>Genome evolution in <it>Listeria </it>involved limited gene loss and acquisition as supported by (i) a relatively high coverage of the predicted pan-genome by the observed pan-genome, (ii) conserved genome size (between 2.8 and 3.2 Mb), and (iii) a highly syntenic genome. Limited gene loss in <it>Listeria </it>did include loss of virulence associated genes, likely associated with multiple transitions to a saprotrophic lifestyle. The genus <it>Listeria </it>thus provides an example of a group of bacteria that appears to evolve through a loss of virulence rather than acquisition of virulence characteristics. While <it>Listeria </it>includes a number of species-like clades, many of these putative species include clades or strains with atypical virulence associated characteristics. This information will allow for the development of genetic and genomic criteria for pathogenic strains, including development of assays that specifically detect pathogenic <it>Listeria </it>strains.</p

Rotavirus Rearranged Genomic RNA Segments Are Preferentially Packaged into Viruses Despite Not Conferring Selective Growth Advantage to Viruses

The rotavirus (RV) genome consists of 11 double-stranded RNA segments. Sometimes, partial sequence duplication of an RNA segment leads to a rearranged RNA segment. To specify the impact of rearrangement, the replication efficiencies of human RV with rearranged segments 7, 11 or both were compared to these of the homologous human wild-type RV (wt-RV) and of the bovine wt-RV strain RF. As judged by viral growth curves, rotaviruses with a rearranged genome (r-RV) had no selective growth advantage over the homologous wt-RV. In contrast, r-RV were selected over wt-RV during competitive experiments (i.e mixed infections between r-RV and wt-RV followed by serial passages in cell culture). Moreover, when competitive experiments were performed between a human r-RV and the bovine wt-RV strain RF, which had a clear growth advantage, rearranged segments 7, 11 or both always segregated in viral progenies even when performing mixed infections at an MOI ratio of 1 r-RV to 100 wt-RV. Lastly, bovine reassortant viruses that had inherited a rearranged segment 7 from human r-RV were generated. Although substitution of wt by rearranged segment 7 did not result in any growth advantage, the rearranged segment was selected in the viral progenies resulting from mixed infections by bovine reassortant r-RV and wt-RV, even for an MOI ratio of 1 r-RV to 107 wt-RV. Lack of selective growth advantage of r-RV over wt-RV in cell culture suggests a mechanism of preferential packaging of the rearranged segments over their standard counterparts in the viral progeny

Dielectric relaxation dynamics of high-temperature piezoelectric polyimide copolymers

Polyimide co-polymers have been prepared based on different diamines as co-monomers: a diamine without CN groups and a novel synthesized diamine with two CN groups prepared by polycondensation reaction followed by thermal cyclodehydration. Dielectric spectroscopy measurements were performed and the dielectric complex function, ac conductivity and electric modulus of the co-polymers were investigated as a function of CN group content in the frequency range from 0.1 Hz to 107 Hz at temperatures from 25 to 260 °C. For all samples and temperatures above 150ºC, the dielectric constant increases with increasing temperature due to increaseing conductivity. The α-relaxation is just detected for the sample without CN groups, being this relaxation overlapped by the electrical conductivity contributions in the remaining samples. For the copolymer samples and the polymer with CN groups an important Maxwell-Wagner-Sillars contribution is detected. The mechanisms responsible for the dielectric relaxation, conduction process and electric modulus response have been discussed as a function of the CN groups content present in the samples.This work was supported by FEDER through the COMPETE Program and by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Project PESTC/FIS/UI607/2011 and grants SFRH/BD/ 62507/2009 (A.C.L.) SFRH/BD/68499/2010 (C.M.C.). The authors also thank funding from “Matepro – Optimizing Materials and Processes”, ref. NORTE-07-0124-FEDER-000037”, co-funded by the “Programa Operacional Regional do Norte” (ON.2 – O Novo Norte), under the “Quadro de Referência Estratégico Nacional” (QREN), through the “Fundo Europeu de Desenvolvimento Regional” (FEDER). RSS acknowledge the support of the Spanish Ministry of Economy and Competitiveness through the project MAT2012-38359-C03-01 (including the FEDER financial support). Authors also thank the Basque Country Government for financial support (ACTIMAT project, ETORTEK Program, IE13-380, and Ayudas para Grupos de Investigación del Sistema Universitario Vasco Program, IT718-13)

Research protocol of the NeedYD-study (Needs in Young onset Dementia): a prospective cohort study on the needs and course of early onset dementia

Contains fulltext : 89407.pdf (publisher's version ) (Open Access)BACKGROUND: Early onset dementia has serious consequences for patients and their family members. Although there has been growing attention for this patient group, health care services are still mainly targeted at the elderly. Specific knowledge of the needs of early onset dementia patients and their families is limited but necessary for the development of adequate health care services and specific guidelines. This research project is mainly targeted at delineating the course of early onset dementia, the functional characteristics and needs of early onset dementia patients and their caregivers, the risk factors for institutionalization and the interaction with the caring environment. METHODS/DESIGN: The NeedYD-study (Needs in Young Onset Dementia) is a longitudinal observational study investigating early onset dementia patients and their caregivers (n = 217). Assessments are performed every six months over two years and consist of interviews and questionnaires with patients and caregivers. The main outcomes are (1) the needs of patients and caregivers, as measured by the Camberwell Assessment of Needs for the Elderly (CANE) and (2) neuropsychiatric symptoms, as measured by the NeuroPsychiatric Inventory (NPI). Qualitative analyses will be performed in order to obtain more in-depth information on the experiences of EOD patients and their family members. The results of this study will be compared with comparable data on late onset dementia from a historical cohort. DISCUSSION: The study protocol of the NeedYD-study is presented here. To our knowledge, this study is the first prospective cohort study in this research area. Although some limitations exist, these do not outweigh the strong points of this study design