Evaluation of methods to account for release from nanofiber scaffolds

Electrospinning is a common technique utilized to form fibers from the micro- to nanometer range. Nanofibers form through electrospinning can be utilized as scaffolds since the fiber structures are similar to the structures within the extracellular matrix. Researchers use additives, such as growth factors, to help facilitate cell proliferation and function. Also, researchers are attempting to use electrospun fibers for drug delivery and as wound dressings since the electrospun fibers have high surface area to volume ratio. In both situations, the release of either the additive or the drug needs to be controlled so that the fibers would release the additive or drug in a desired manner. To understand the release from the electrospun fibers, researchers develop mathematical models that rely on the release data. Additionally, researchers utilize models based on Fick\u27s second law of diffusion to predict release in cylindrical coordinates. This work aims to understand the release from electrospun fibers by finding the relationship between Fick\u27s second law of diffusion and the mathematical models from experimental data. Three different release studies for electrospun fibers are investigated. Predicted mutual diffusion coefficients are developed so that the coefficients could be used for future predictive releases

Design of a new non-sterile glove-dispensing unit

BackgroundDespite best efforts by healthcare providers to sterilize their hands through hand washing prior to touching medical equipment and patients, bacteria are still present and can be spread through physical contact. We aimed to reduce the spread of touch-induced and airborne bacteria and virus spreading by using a touch-free glove-dispensing system that minimally exposes gloves in the box to air. MethodThe team met multiple times to undertake early prototyping and present ideas for the design. We experimented with folding gloves in varying patterns, similar to facial tissue-dispensing boxes, and tried several methods of opening/closing the glove box to determine the most effective way to access gloves with the least amount of physical contact. We considered the user experience and obtained user feedback after each design iteration.ResultsUltimately, we decided on a vertically oriented box with optional holes for dispensing a glove on the side of the box or on the bottom by means of the pull-down drawer mechanism. This system will dispense a single glove at a time to the user with the option of using a pull-down drawer trigger to decrease the likelihood of physical contact with unused gloves. Both methods dispense a single glove. ConclusionBy reducing physical contact between the healthcare practitioner and the gloves, we are potentially reducing the spread of bacteria. This glove box design ensures that gloves are not exposed to the air in the clinic or hospital setting, thereby further reducing spread of airborne germs. This could assist in decreasing the risk of nosocomial infections in healthcare settings

Thoracic outlet syndrome: Pattern of clinical success after operative decompression

ObjectiveTo evaluate the pattern of clinical results in patients with neurogenic thoracic outlet syndrome (N-TOS) after operative decompression and longitudinal follow-up.MethodsFrom May 1994 to December 2002, 254 operative sides in 185 patients with N-TOS were treated by the same operative protocol: (1) transaxillary first rib resection and the lower part of scalenectomy for the primary procedure with or without (2) the subsequent upper part of scalenectomy with supraclavicular approach for patients with persistent or recurrent symptoms. This retrospective cohort study included 38 men and 147 women with an age range of 19 to 80 years (mean, 40 years). Evaluated were primary success, defined as uninterrupted success with no procedure performed, and secondary success, defined as success maintained by the secondary operation after the primary failure. Success was defined as ≥50% symptomatic improvement judged by the patient using a 10-point scale, returning to preoperational work status, or both.ResultsFollow-up was 2 to 76 months (mean, 25 months). Eighty sides underwent a secondary operation for the primary clinical failure. No technical failures and no deaths occurred ≤30 days after the operations. The complication rate was 4% (13/334) and consisted of 7 pneumothoraxes, 3 subclavian vein injuries, 1 nerve injury, 1 internal mammary artery injury, and 1 suture granuloma. Of 254 operative sides, the primary and secondary success was 46% (118/254) and 64% (163/254). Most the primary failures (90%, 122/136) and the secondary failures (66%, 23/35) occurred ≤18 months after the respective operation.ConclusionsThe long-term results of operations for TOS in this study were much worse than those initially achieved, and most of the primary and secondary failures occurred ≤12 months of the respective operations. A minimum of 18-month follow-up on patients and standardized definition of the outcomes are necessary to determine the true effectiveness and outcome of operative treatment of N-TOS

Local-regional recurrence in women with small node-negative, HER2-positive breast cancer: results from a prospective multi-institutional study (the APT trial).

PurposeWomen with HER2-positive breast cancer treated prior to effective anti-HER2 therapy have higher rates of local-regional recurrence (LRR) than those with HER2-negative disease. Effective systemic therapy, however, has been shown to decrease LRR. This study examines LRR in women with HER2-positive breast cancer treated on a single-arm prospective multicenter trial of adjuvant trastuzumab (H) and paclitaxel (T).MethodsPatients with HER2-positive tumors ≤ 3.0 cm with negative axillary nodes or micrometastatic disease were eligible. Systemic therapy included weekly T and H for 12 weeks followed by continuation of H to complete 1 year. Radiation therapy (RT) was required following breast-conserving surgery (BCS), but dose and fields were not specified. Disease-free survival (DFS) and LRR-free survival were calculated using the Kaplan-Meier method.ResultsOf the 410 patients enrolled from September 2007 to September 2010, 406 initiated protocol therapy and formed the basis of this analysis. A total of 272 (67%) had hormone receptor-positive tumors. Of 162 patients undergoing mastectomy, local therapy records were unavailable for two. None of the 160 for whom records were available received RT. Among 244 BCS patients, detailed RT records were available for 217 (89%). With a median follow-up of 6.5 years, 7-year DFS was 93.3% (95% CI 90.4-96.2), and LRR-free survival was 98.6% (95% CI 97.4-99.8).ConclusionLRR in this select group of early-stage patients with HER2-positive disease receiving effective anti-HER2 therapy is extremely low. If confirmed in additional studies, future investigational efforts should focus on de-escalating local therapy

RNA-binding deficient TDP-43 drives cognitive decline in a mouse model of TDP-43 proteinopathy

TDP-43 proteinopathies including frontotemporal lobar dementia (FTLD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders characterized by aggregation and mislocalization of the nucleic-acid binding protein TDP-43 and subsequent neuronal dysfunction. Here, we developed an endogenous model of sporadic TDP-43 proteinopathy based on the principle that disease-associated TDP-43 acetylation at lysine 145 (K145) alters TDP-43 conformation, impairs RNA-binding capacity, and induces downstream mis-regulation of target genes. Expression of acetylation-mimic TDP-43K145Q resulted in stress-induced nuclear TDP-43 foci and loss-of-TDP-43-function in primary mouse and human induced pluripotent stem cell (hiPSC)-derived cortical neurons. Mice harboring the TDP-43K145Q mutation recapitulated key hallmarks of FTLD, including progressive TDP-43 phosphorylation and insolubility, TDP-43 mis-localization, transcriptomic and splicing alterations, and cognitive dysfunction. Our study supports a model in which TDP-43 acetylation drives neuronal dysfunction and cognitive decline through aberrant splicing and transcription of critical genes that regulate synaptic plasticity and stress response signaling. The neurodegenerative cascade initiated by TDP-43 acetylation recapitulates many aspects of FTLD and provides a new paradigm to further interrogate TDP-43 proteinopathies

Emerging technologies for the management of Type 1 diabetes in pregnancy

Purpose of Review: The purpose of the study is to discuss emerging technologies available in the management of type 1 diabetes in pregnancy. Recent Findings: The latest evidence suggests that continuous glucose monitoring (CGM) should be offered to all women on intensive insulin therapy in early pregnancy. Studies have additionally demonstrated the ability of CGM to help gain insight into specific glucose profiles as they relate to glycaemic targets and pregnancy outcomes. Despite new studies comparing insulin pump therapy to multiple daily injections, its effectiveness in improving glucose and pregnancy outcomes remains unclear. Sensor-integrated insulin delivery (also called artificial pancreas or closed-loop insulin delivery) in pregnancy has been demonstrated to improve time in target and performs well despite the changing insulin demands of pregnancy. Summary: Emerging technologies show promise in the management of type 1 diabetes in pregnancy; however, research must continue to keep up as technology advances. Further research is needed to clarify the role technology can play in optimising glucose control before and during pregnancy as well as to understand which women are candidates for sensor-integrated insulin delivery

Early Last Interglacial ocean warming drove substantial ice mass loss from Antarctica

The future response of the Antarctic ice sheet to rising temperatures remains highly uncertain. A useful period for assessing the sensitivity of Antarctica to warming is the Last Interglacial (LIG) (129 to 116 ky), which experienced warmer polar temperatures and higher global mean sea level (GMSL) (+6 to 9 m) relative to present day. LIG sea level cannot be fully explained by Greenland Ice Sheet melt (∼2 m), ocean thermal expansion, and melting mountain glaciers (∼1 m), suggesting substantial Antarctic mass loss was initiated by warming of Southern Ocean waters, resulting from a weakening Atlantic meridional overturning circulation in response to North Atlantic surface freshening. Here, we report a blue-ice record of ice sheet and environmental change from the Weddell Sea Embayment at the periphery of the marine-based West Antarctic Ice Sheet (WAIS), which is underlain by major methane hydrate reserves. Constrained by a widespread volcanic horizon and supported by ancient microbial DNA analyses, we provide evidence for substantial mass loss across the Weddell Sea embayment during the LIG, most likely driven by ocean warming and associated with destabilization of subglacial hydrates. Ice sheet modeling supports this interpretation and suggests that millennial-scale warming of the Southern Ocean could have triggered a multimeter rise in global sea levels. Our data indicate that Antarctica is highly vulnerable to projected increases in ocean temperatures and may drive ice–climate feedbacks that further amplify warming

Sequence Variants of the Phytophthora sojae RXLR Effector Avr3a/5 Are Differentially Recognized by Rps3a and Rps5 in Soybean

The perception of Phytophthora sojae avirulence (Avr) gene products by corresponding soybean resistance (Rps) gene products causes effector triggered immunity. Past studies have shown that the Avr3a and Avr5 genes of P. sojae are genetically linked, and the Avr3a gene encoding a secreted RXLR effector protein was recently identified. We now provide evidence that Avr3a and Avr5 are allelic. Genetic mapping data from F2 progeny indicates that Avr3a and Avr5 co-segregate, and haplotype analysis of P. sojae strain collections reveal sequence and transcriptional polymorphisms that are consistent with a single genetic locus encoding Avr3a/5. Transformation of P. sojae and transient expression in soybean were performed to test how Avr3a/5 alleles interact with soybean Rps3a and Rps5. Over-expression of Avr3a/5 in a P. sojae strain that is normally virulent on Rps3a and Rps5 results in avirulence to Rps3a and Rps5; whereas silencing of Avr3a/5 causes gain of virulence in a P. sojae strain that is normally avirulent on Rps3a and Rps5 soybean lines. Transient expression and co-bombardment with a reporter gene confirms that Avr3a/5 triggers cell death in Rps5 soybean leaves in an appropriate allele-specific manner. Sequence analysis of the Avr3a/5 gene identifies crucial residues in the effector domain that distinguish recognition by Rps3a and Rps5

Biodiversity of soils and farming innovations for improved resilience of European wheat agrosystems (BIOFAIR)

IOFAIR holistically determines soil biodiversity under different farming practices and environmental stressors to anticipate negative impacts of climate change on belowground processes and provide adaptation strategies. The BIOFAIR project comprehensively addresses the diversity of soil organisms, from microbes to mites, and how they link to soil functioning in terms of disease suppression and carbon and nutrient cycling. On the crop site, a specific focus is given to grain quality parameters such as vitamin and mineral nutrient contents essential for many human body functions, and to technological bread making properties such as flour viscosity, to ensure the crops of the future have a high nutritious value and are suitable for food production

Modeling rare gene variation to gain insight into the oldest biomarker in autism: construction of the serotonin transporter Gly56Ala knock-in mouse

Alterations in peripheral and central indices of serotonin (5-hydroxytryptamine, 5-HT) production, storage and signaling have long been associated with autism. The 5-HT transporter gene (HTT, SERT, SLC6A4) has received considerable attention as a potential risk locus for autism-spectrum disorders, as well as disorders with overlapping symptoms, including obsessive-compulsive disorder (OCD). Here, we review our efforts to characterize rare, nonsynonymous polymorphisms in SERT derived from multiplex pedigrees carrying diagnoses of autism and OCD and present the initial stages of our effort to model one of these variants, Gly56Ala, in vivo. We generated a targeting vector to produce the Gly56Ala substitution in the Slc6a4 locus by homologous recombination. Following removal of a neomycin resistance selection cassette, animals exhibiting germline transmission of the Ala56 variant were bred to establish a breeding colony on a 129S6 background, suitable for initial evaluation of biochemical, physiological and behavioral alterations relative to SERT Gly56 (wildtype) animals. SERT Ala56 mice were achieved and exhibit a normal pattern of transmission. The initial growth and gross morphology of these animals is comparable to wildtype littermate controls. The SERT Ala56 variant can be propagated in 129S6 mice without apparent disruption of fertility and growth. We discuss both the opportunities and challenges that await the physiological/behavioral analysis of Gly56Ala transgenic mice, with particular reference to modeling autism-associated traits