Woodruffstevens2852

Membrane nanotubes (NTs) and their networks play an important role in intracellular membrane transport and intercellular communications. The transport characteristics of the NT lumen resemble those of conventional solid-state nanopores. However, unlike the rigid pores, the soft membrane wall of the NT can be deformed by forces driving the transport through the NT lumen. This intrinsic coupling between the NT geometry and transport properties remains poorly explored. Using synchronized fluorescence microscopy and conductance measurements, we revealed that the NT shape was changed by both electric and hydrostatic forces driving the ionic and solute fluxes through the NT lumen. Far from the shape instability, the strength of the force effect is determined by the lateral membrane tension and is scaled with membrane elasticity so that the NT can be operated as a linear elastic sensor. Near shape instabilities, the transport forces triggered large-scale shape transformations, both stochastic and periodic. The periodic oscillations were coupled to a vesicle passage along the NT axis, resembling peristaltic transport. The oscillations were parametrically controlled by the electric field, making NT a highly nonlinear nanofluidic circuitry element with biological and technological implications.Minicircles (MCs) are DNA molecules that are produced in Escherichia coli by replicating a parental plasmid (PP) and inducing its site-specific intramolecular recombination into miniplasmid (MP; containing the prokaryotic backbone) and MC molecules (comprised by the eukaryotic cassette). The determination of the recombination efficiency and the monitoring of PP, MC and MP species during processing and in the final product are critical aspects of MC manufacturing. This work describes a real-time PCR method for the specific identification of PP, MP or MC that uses sets of primers specific for each species. The method was evaluated using artificial mixtures of (i) PP and MP, (ii) PP and MC and (iii) MP and MC that were probed for all three DNA molecules. The ratio of molecules of each DNA species in these mixtures were determined with differences lower than 10% relatively to the expected ratio of the species in 90% of the mixtures. Next, the recombination efficiency was successfully estimated by analysing pre-purified DNA samples obtained from cell cultures. A standard deviation less then 2% was obtained between replicas and results closely correlated with those obtained by densitometry analysis of agarose gels. Further optimization is required to determine recombination efficiency directly from whole cells.We present the clinical and molecular studies of a family with Pendred syndrome, in which one affected individual developed follicular thyroid cancer. Two siblings with classic Pendred syndrome triad were operated on because of enormous multinodular goiter. Histopathology showed a follicular thyroid cancer in the male and a multinodular goiter in the female. PDS gene analysis revealed G-to-A transition in the splice donor site of intron 8 (IVS8+1G>A/c.1001+1G>A). Careful surveillance is needed in all cases of thyroid nodules in patients with Pendred syndrome, due to the high risk of malignancy.

To examine the ultrastructure of the natural plane of separation in grafted corneas and evaluate the outcomes of stromal peeling.

Interventional case series METHODS In this multicenter study, stromal peeling was attempted in 96 consecutive eyes with unsatisfactory vision following penetrating keratoplasty (PK) for keratoconus(n=79), herpetic keratitis(n=11) and granular dystrophy(n=6). Stromal exchange was performed by 1) 9mm partial-thickness trephination; 2) creation of a corneal flap across the PK wound; 3) opening of the stromal component of the PK wound until a smooth, translucent natural plane was identified; 4) severing the attachment of the PK scar; 5) stromal peeling along the identified plane; 6) suturing of donor lamella. Grafted corneas from cases which mandated conversion to PK were processed for transmission electron microscopy.

The natural plane of separation was identified in all cases. Stromal exchange was successfully completed in 84 cases (87.5%). Snellen visual acuity ≥20/40 and ≥20/25 was reached in 93% and 72% of cases at 3 years(n=49) and 86% and 62% at 4 years(n=21) postoperatively. Mean endothelial cell loss at 1 year was 6.6±9.5%. Stromal peeling occurred along a plane lined with a continuous layer of keratocytes separating pre-Descemet membrane (DM) stroma, DM and endothelium from the anterior stroma. Pre-DM stroma was made of poorly organized lamellae containing widely-spaced randomly arranged collagen fibrils.

Ultrastructural alterations in the stromal microarchitecture of grafted corneas provide evidence of a natural plane of separation identified intraoperatively. Stromal peeling can be successfully performed in post-PK eyes with various stromal pathology.

Ultrastructural alterations in the stromal microarchitecture of grafted corneas provide evidence of a natural plane of separation identified intraoperatively. Stromal peeling can be successfully performed in post-PK eyes with various stromal pathology.

Data generated from retrospective studies on primary mediastinal B-cell lymphoma (PMBCL) outcome are valuable as no prospective phase 3 trials have been conducted in this rare type of lymphoma.

Our goal was to assess the long-term outcome of 41 patients with PMBCL who were treated at the Kuwait Cancer Center. We evaluated two types of multidrug treatment, R-CHOP (rituximab, vincristine, doxorubicin, cyclophosphamide, and prednisone) and DA-EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab), and determined overall survival and complete response (CR) as primary endpoints.

In our cohort, 27 (66%) cases were treated with R-CHOP and 14 (34%) cases were treated with DA-EPOCH-R. The overall median follow-up time was 34months. Among the patients treated with R-CHOP, 23 out of 27 (92.6%) patients achieved CR; similarly, 10 out of 14 patients (85.7%) in the DA-EPOCH-R group achieved CR after initial treatment. There were no differences in OS between patients treated with R-CHOP versus DA-EPOCH-R.

The findings of this study indicate that combined chemotherapy and immunotherapy results in excellent long-term outcome of patients with PMBCL. At our center, we prefer R-CHOP to DA-EPOCH-R for low-risk patients with nonbulky disease.

The findings of this study indicate that combined chemotherapy and immunotherapy results in excellent long-term outcome of patients with PMBCL. At our center, we prefer R-CHOP to DA-EPOCH-R for low-risk patients with nonbulky disease.Autoinflammatory keratinization disease (AiKD) is a novel clinical concept encompassing diseases with a genetic background and mixed pathogenic mechanisms of autoinflammation and autoimmunity, leading to an aberrant keratinization of the skin. Recent advances in medical genetics have revealed genetic causes and/or predisposing factors for a number of AiKD's, such as mutations in IL36RN related with pustular psoriasis, acrodermatitis continua and hidradenitis suppurativa, in CARD14 in pityriasis rubra pilaris type V and some forms of pustular psoriasis, and in NLRP1 related with familial keratosis lichenoides chronica (KLC). It is suspected that AiKD pathophysiology would also be involved in non-monogenic disorders. The bidirectional relationship between inflammation and keratinization should be understood in order to outline optimal management, and new drug development should take both targets into account. FK506 We assume that new inflammatory keratinization diseases may be recognized as AiKDs in the coming years.Ocular toxoplasmosis (OT) is the most common form of posterior uveitis, and in some countries, it is the most frequent cause of visual impairment. Studies demonstrate that the polymorphism in genes involved with the immune response can be related both to the occurrence and to the recurrence of OT. Thus, the present study aimed to analyze the association between OT and the polymorphism of the APEX1 (rs1130409) and MyD88 (rs7744) genes. The studied sample consisted of 48 volunteers with OT and 96 asymptomatic volunteers, but positive for anti - T. gondii IgG (control group). Blood collection was performed for serological analysis (ELISA) and DNA extraction. Genotyping of the polymorphism was performed using real-time PCR. To analyze the association between gene polymorphism and OT, logistic regression was performed. The results showed no association between the MYD88 gene polymorphism and the development of OT. However, a significant association was found between OT and APEX1 gene polymorphism, indicating that individuals expressing polymorphic (GG) or heterozygous (GT) alleles are more likely to develop the disease (P-value = 0.02 and 0.03 respectively). These results suggest that APEX1 (rs1130409) polymorphism is a risk factor for the occurrence of ocular toxoplasmosis in the studied population.Establishing a diagnosis of melioidosis based on clinical grounds is difficult in hospitalized patients with sepsis or community acquired pneumonia (CAP). We aimed to ascertain the prevalence, clinico-epidemiological and laboratory profile of melioidosis in hospitalized patients with sepsis or CAP, and to evaluate the diagnostic utility of rapid lateral flow immunoassay (LFI) and PCR in comparison with culture. In all patients with sepsis or CAP, blood, sputum/throat swab, and urine sample were subjected to culture along with other samples based on clinical presentation. In addition, PCR assay targeting the type III secretion system 1 (TTS1) and LFI was performed. Thirty-three (33/196, 17%) out of the total 196 cases were diagnosed as melioidosis by culture. The prevalence of melioidosis in patients who had only sepsis without CAP, had both sepsis and CAP, had CAP without sepsis was 31% (26/84), 22 % (4/18) and 3%(3/94) respectively. All the LFI or PCR positive cases were culture positive from at least one orticaemic melioidosis.In this study, 196 strains of actinomycetes isolated from marshland soil samples were tested for molluscicidal activity against Oncomelania hupensis. Five strains demonstrated molluscicidal activity, of which the molluscicidal efficiency of Actinomycetes strain A183 was the maximum. After the fermentation supernatant of actinomycetes A183 was extracted with ethyl acetate (EWEA), the LC50 of the EWEA after leaching for 48 h and 72 h were 0.2688 and 0.2195 mg/L, respectively. The effect of EWEA on the key points of energy metabolism was determined. We noted that 1 mg/L of EWEA (A813) significantly reduced the activity of mitochondrial respiratory chain complex I (P less then 0.05), while no significant changes were observed in the activities of complexes II, III, and IV. In addition, EWEA (A813) could decrease the membrane potential of O. hupensis purified mitochondria in vitro. The LC50 of the 3 uncoupler (FCCP, DNP, and Tyrphostin A9) after immersion for 24 h were 0.065, 0.135, and 0.110 mg/L, respectively; LC50 after 48 h treatment was 0.064, 0.124, and 0.082 mg/L, respectively; LC50 after 72 h treatment was 0.063, 0.129, and 0.061 mg/L, respectively, and all uncoupler showed strong molluscicidal activities, demonstrating that the mitochondrial membrane potential uncoupling is a potential target for molluscicides against O. hupensis. Moreover, the molluscicidal active substance of strain A183 needs to be further isolated, purified, and structurally characterized considering its promising potential applications.