Treatment results and prognostic factors in primary thyroid lymphoma patients: a Rare Cancer Network study

Background: This study analyzed prognostic factors and treatment outcomes of primary thyroid lymphoma. Patients and Methods: Data were retrospectively collected for 87 patients (53 stage I and 34 stage II) with median age 65 years. Fifty-two patients were treated with single modality (31 with chemotherapy alone and 21 with radiotherapy alone) and 35 with combined modality treatment. Median follow-up was 51 months. Results: Sixty patients had aggressive lymphoma and 27 had indolent lymphoma. The 5- and 10-year overall survival (OS) rates were 74% and 71%, respectively, and the disease-free survival (DFS) rates were 68% and 64%. Univariate analysis revealed that age, tumor size, stage, lymph node involvement, B symptoms, and treatment modality were prognostic factors for OS, DFS, and local control (LC). Patients with thyroiditis had significantly better LC rates. In multivariate analysis, OS was influenced by age, B symptoms, lymph node involvement, and tumor size, whereas DFS and LC were influenced by B symptoms and tumor size. Compared with single modality treatment, patients treated with combined modality had better 5-year OS, DFS, and LC. Conclusions: Combined modality leads to an excellent prognosis for patients with aggressive lymphoma but does not improve OS and LC in patients with indolent lymphom

Penicillin-Induced Epileptiform Ecog Activity in Gerbils: Effects of Physical Exercise and a Diospyros Kaki Extract

Mongolian gerbils (28 males) were divided into four groups, control (C), treadmill-exercised (Ex), treated with the extract of Diospyros kaki (Dk), and treated with the Dk extract plus exercised (Ex+Dk) groups. Animals of the respective groups were running-exercised for 30 min per day during 8 weeks, and the Dk extract (dose 20mg/kg) was given by gavage during five days per week within the same period. After the treatment and exercise period, an epilepsy model was produced by penicillin G injection (500 IU) into the left somatomotor cortex, and electrocorticogram (ECoG) was recorded during 120 min. The mean frequency of spike/wave complexes was significantly smaller in the Ex and Ex+Dk groups from the 65th min of the observation period and, in the Dk group, from the 75th min than the respective value in the C group (P < 0.01, P < 0.05, and P < 0.01, respectively). The differences in the amplitude values and latency to onset of the spike/wave events among all groups usally did not reach the significance level (P > 0.05), but, visin late stages of the observation period, an antiseisure effect of the Dk extract was obvious. Thus, both the running exercise and Dk extract applications inhibit penicillin-induced epileptiform activity by altering the spike/ wave frequency or severity of seizures observed in ECoG recordings. Further studies are needed to determine the effects of physical activity of different intensities and forms and to analyze the active compounds in the Dk extract.Монгольські піщанки (28 самців) були поділені на чотири групи – контрольну (C), піддану тренуванню на тредбані (Ex), групу з уведенням екстракту Diospyros kaki (східної хурми, група Dk) та групу з уведенням вказаного екстракту, комбінованим із тренуванням (Ex+Dk). Тварин відповідних груп тренували, примушуючи бігати 30 хв на день протягом восьми тижнів; екстракт Dk (20 мг/кг) уводився перорально п’ять днів на тиждень протягом того самого періоду. Після періоду тренування та введення екстракту у щурів індукували модельну епілепсію за допомогою ін’єкції 500 МО пеніциліну G у ліву соматомоторну кору і відводили електрокортикограму (ЕКоГ) протягом 20 хв. У групах Ex та Ex+Dk середня частота виникнення комплексів пік/хвиля була вірогідно меншою, ніж у контролі, починаючи з 65-ї хв періоду спостереження; те саме відмічалося в групі Dk починаючи з 75-ї хв вказаного періоду (P < 0.01, P < 0.05 та P < 0.01 відповідно). Відмінності значень амплітуди ЕКоГ та латентного періоду до появи комплексів пік/хвиля в усіх групах звичайно не досягали рівня вірогідності (P > 0.05), але на пізній ділянці періоду спостереження антисудомний вплив екстракту Dk був очевидним. Отже, тренування бігом та уведення екстракту хурми східної пригнічує індуковану пеніциліном епілептиформну активність, змінюючи частоту комплексів пік/хвиля та інтенсивність судомної активності, що спостерігається в ЕКоГ. Потрібні подальші дослідження для того, щоб визначити ефекти фізичної активності різної інтенсивності та форми та проаналізувати активні компоненти екстракту хурми

Design, fabrication and control of soft robots

Conventionally, engineers have employed rigid materials to fabricate precise, predictable robotic systems, which are easily modelled as rigid members connected at discrete joints. Natural systems, however, often match or exceed the performance of robotic systems with deformable bodies. Cephalopods, for example, achieve amazing feats of manipulation and locomotion without a skeleton; even vertebrates such as humans achieve dynamic gaits by storing elastic energy in their compliant bones and soft tissues. Inspired by nature, engineers have begun to explore the design and control of soft-bodied robots composed of compliant materials. This Review discusses recent developments in the emerging field of soft robotics.National Science Foundation (U.S.) (Grant IIS-1226883

Antigen-Displaying Lipid-Enveloped PLGA Nanoparticles as Delivery Agents for a Plasmodium vivax Malaria Vaccine

The parasite Plasmodium vivax is the most frequent cause of malaria outside of sub-Saharan Africa, but efforts to develop viable vaccines against P. vivax so far have been inadequate. We recently developed pathogen-mimicking polymeric vaccine nanoparticles composed of the FDA-approved biodegradable polymer poly(lactide-co-glycolide) acid (PLGA) “enveloped” by a lipid membrane. In this study, we sought to determine whether this vaccine delivery platform could be applied to enhance the immune response against P. vivax sporozoites. A candidate malaria antigen, VMP001, was conjugated to the lipid membrane of the particles, and an immunostimulatory molecule, monophosphoryl lipid A (MPLA), was incorporated into the lipid membranes, creating pathogen-mimicking nanoparticle vaccines (VMP001-NPs). Vaccination with VMP001-NPs promoted germinal center formation and elicited durable antigen-specific antibodies with significantly higher titers and more balanced Th1/Th2 responses in vivo, compared with vaccines composed of soluble protein mixed with MPLA. Antibodies raised by NP vaccinations also exhibited enhanced avidity and affinity toward the domains within the circumsporozoite protein implicated in protection and were able to agglutinate live P. vivax sporozoites. These results demonstrate that these VMP001-NPs are promising vaccines candidates that may elicit protective immunity against P. vivax sporozoites.United States. Dept. of Defense (contract W911NF-07-D-0004)Ragon Institute of MGH, MIT and Harvar

Spectrofluorimetric determination of sertraline in dosage forms and human plasma through derivatization with 9-fluorenylmethyl chloroformate

<p>Abstract</p> <p>Background</p> <p>Sertraline is primarily used to treat major depression in adult outpatients as well as obsessive-compulsive, panic and social anxiety disorders in both adults and children. A survey of the literature reveals that most of the reported methods are either insufficiently sensitive or tedious and require highly sophisticated and dedicated instrumentation. The proposed method is considered to be specific for determination of SER in presence of its metabolite (deaminated form).</p> <p>Results</p> <p>A sensitive, simple and specific spectrofluorimetric method was developed for the determination of sertraline (SER) in pharmaceutical formulations and biological fluids. The method is based on its reaction with 9-fluorenylmethyl chloroformate (FMOC-Cl) in borate buffer of pH 8.0 to yield a highly fluorescent derivative peaking at 315 nm after excitation at 265 nm. The different experimental parameters affecting the development and stability of the reaction product were carefully studied and optimized. The fluorescence concentration plot was rectilinear over the range of 0.05-1.0 μg mL^-1with a lower detection limit of 5.34 × 10^-3μg mL^-1and limit of quantitation of 0.016 μg mL^-1.</p> <p>Conclusions</p> <p>The proposed method was successfully applied to the analysis of commercial tablets and the results obtained were in good agreement with those obtained using the reference method. Furthermore, the method was applied for the determination of SER in spiked and real human plasma. The mean % recovery (n = 3) was 94.33 ± 1.53 and 92.00 ± 2.65, respectively. A proposal of the reaction pathway was postulated.</p

Increased autophagy in EphrinB2-deficient osteocytes is associated with elevated secondary mineralization and brittle bone

Mineralized bone forms when collagen-containing osteoid accrues mineral crystals. This is initiated rapidly (primary mineralization), and continues slowly (secondary mineralization) until bone is remodeled. The interconnected osteocyte network within the bone matrix differentiates from bone-forming osteoblasts; although osteoblast differentiation requires EphrinB2, osteocytes retain its expression. Here we report brittle bones in mice with osteocyte-targeted EphrinB2 deletion. This is not caused by low bone mass, but by defective bone material. While osteoid mineralization is initiated at normal rate, mineral accrual is accelerated, indicating that EphrinB2 in osteocytes limits mineral accumulation. No known regulators of mineralization are modified in the brittle cortical bone but a cluster of autophagy-associated genes are dysregulated. EphrinB2-deficient osteocytes displayed more autophagosomes in vivo and in vitro, and EphrinB2-Fc treatment suppresses autophagy in a RhoA-ROCK dependent manner. We conclude that secondary mineralization involves EphrinB2-RhoA-limited autophagy in osteocytes, and disruption leads to a bone fragility independent of bone mass

One-year prevalence and the impact of migraine and tension-type headache in Turkey: a nationwide home-based study in adults

Several studies have shown that the prevalence of migraine and tension-type headache (TTH) varied between different geographical regions. Therefore, there is a need of a nationwide prevalence study for headache in our country, located between Asia and Europe. This nationwide study was designed to estimate the 1-year prevalence of migraine and TTH and analyse the clinical features, the impact as well as the demographic and socio-economic characteristics of the participant households in Turkey. We planned to investigate 6,000 representative households in 21 cities of Turkey; and a total of 5,323 households (response rate of 89%) aged between 18 and 65 years were examined for headache by 33 trained physicians at home on the basis of the diagnostic criteria of the second edition of the International Classification of Headache Disorders (ICHD-II). The electronically registered questionnaire was based on the headache features, the associated symptoms, demographic and socio-economic situation and history. Of 5,323 participants (48.8% women; mean age 35.9 ± 12 years) 44.6% reported recurrent headaches during the last 1 year and 871 were diagnosed with migraine at a prevalence rate of 16.4% (8.5% in men and 24.6% in women), whereas only 270 were diagnosed with TTH at a prevalence rate of 5.1% (5.7% in men and 4.5% in women). The 1-year prevalence of probable migraine was 12.4% and probable TTH was 9.5% additionally. The rate of migraine with aura among migraineurs was 21.5%. The prevalence of migraine was highest among 35–40-year-old women while there were no differences in age groups among men and in TTH overall. More than 2/3 of migraineurs had ever consulted a physician whereas only 1/3 of patients with TTH had ever consulted a physician. For women, the migraine prevalence was higher among the ones with a lower income, while among men, it did not show any change by income. Migraine prevalence was lower in those with a lower educational status compared to those with a high educational status. Chronic daily headache was present in 3.3% and the prevalence of medication overuse headache was 2.1% in our population. There was an important impact of migraine with a monthly frequency of 5.9 ± 6, and an attack duration of 35.1 ± 72 h, but only 4.9% were on prophylactic treatment. The one-year prevalence of migraine estimated as 16.4% was similar or even higher than world-wide reported migraine prevalence figures and identical to a previous nation-wide study conducted in 1998, whereas the TTH prevalence was much lower using the same methodology with the ICHD-II criteria