Antibiotics produced by Streptomyces

Streptomyces is a genus of Gram-positive bacteria that grows in various environments, and its shape resembles filamentous fungi. The morphological differentiation of Streptomyces involves the formation of a layer of hyphae that can differentiate into a chain of spores. The most interesting property of Streptomyces is the ability to produce bioactive secondary metabolites, such as antifungals, antivirals, antitumorals, anti-hypertensives, immunosuppressants, and especially antibiotics. The production of most antibiotics is species specific, and these secondary metabolites are important for Streptomyces species in order to compete with other microorganisms that come in contact, even within the same genre. Despite the success of the discovery of antibiotics, and advances in the techniques of their production, infectious diseases still remain the second leading cause of death worldwide, and bacterial infections cause approximately 17 million deaths annually, affecting mainly children and the elderly. Self-medication and overuse of antibiotics is another important factor that contributes to resistance, reducing the lifetime of the antibiotic, thus causing the constant need for research and development of new antibiotics.     

Harnessing the Immunomodulatory and Tissue Repair Properties of Mesenchymal Stem Cells to Restore β Cell Function

Islet cell transplantation has therapeutic potential to cure type 1 diabetes (T1D), which is characterized by autoimmune-mediated destruction of insulin-producing β cells. However, current success rates are limited by long-term decline in islet graft function resulting partially from poor revascularization and immune destruction. Mesenchymal stem cells (MSCs) have the potential to enhance islet transplantation and prevent disease progression by a multifaceted approach. MSCs have been shown to be effective at inhibiting inflammatory-mediated immune responses and at promoting tissue regeneration. The immunomodulatory and tissue repairing properties of MSCs may benefit β cell regeneration in the context of T1D. This review will elucidate how MSCs can minimize β cell damage by providing survival signals and simultaneously modulate the immune response by inhibiting activation, and proliferation of several immune cell types. In addition, MSCs can enhance islet graft revascularization, maintaining long-term β cell viability and function.     

Achieving Speaker Gender Equity at the SIR Annual Scientific Meeting: The Effect of Female Session Coordinators

PurposeTo examine the impact of targeted efforts to increase the number of female speakers at the Society of Interventional Radiology (SIR) Annual Scientific Meeting (ASM) by reporting gender trends for invited faculty in 2017/2018 vs 2016.Materials and MethodsFaculty rosters for the 2016, 2017, and 2018 SIR ASMs were stratified by gender to quantify female representation at plenary sessions, categorical courses, symposia, self-assessment modules, and “meet-the-expert” sessions. Keynote events, scientific abstract presentations, and award ceremonies were excluded. In 2017, the SIR Annual Meeting Committee issued requirements for coordinators to invite selected women as speakers. Session coordinators are responsible for issuing speaker invitations, and invited speakers have the option to decline.ResultsYears 2017 and 2018 showed increases in female speaker representation, with women delivering 13% (89 of 687) and 14% (85 of 605) of all assigned presentations, compared with 9% in 2016 (46 of 514; P = .03 and P = .01, respectively). Gender diversity correlated with the gender of the session coordinator(s). When averaged over a 3-year period, female speakers constituted 7% of the speaker roster (112 of 1,504 presentations) for sessions led by an all-male coordinator team, compared with 36% (108 of 302) for sessions led by at least 1 female coordinator (P < .0001). Results of the linear regression model confirmed the effect of coordinator team gender composition (P < .0001).ConclusionsHaving a woman as a session coordinator increased female speaker participation, which suggests that the inclusion of more women as coordinators is one mechanism for achieving gender balance at scientific meetings.     

Comparison of survival outcomes between Expanded Criteria Donor and Standard Criteria Donor kidney transplant recipients: a systematic review and meta‐analysis

In 2002, the United Network for Organ Sharing proposed increasing the pool of donor kidneys to include Expanded Criteria Donor (ECD). Outside the USA, the ECD definition remains the one used without questioning whether such a graft allocation criterion is valid worldwide. We performed a meta‐analysis to quantify the differences between ECD and Standard Criteria Donor (SCD) transplants. We paid particular attention to select studies in which the methodology was appropriate and we took into consideration the geographical area. Thirty‐two publications were included. Only five studies, all from the USA, reported confounder‐adjusted hazard ratios comparing the survival outcomes between ECD and SCD kidney transplant recipients. These five studies confirmed that ECD recipients seemed to have poorer prognosis. From 29 studies reporting appropriate survival curves, we estimated the 5‐year pooled nonadjusted survivals for ECD and SCD recipients. The relative differences between the two groups were lower in Europe than in North America, particularly for death‐censored graft failure. It is of primary importance to propose appropriate studies for external validation of the ECD criteria in non‐US kidney transplant recipients.     

On-line quality assurance of rotational radiotherapy treatment delivery by means of a 2D ion chamber array and the Octavius phantom

For routine pretreatment verification of innovative treatment techniques such as (intensity modulated) dynamic arc therapy and helical TomoTherapy, an on-line and reliable method would be highly desirable. The present solution proposed by TomoTherapy, Inc. (Madison, WI) relies on film dosimetry in combination with up to two simultaneous ion chamber point dose measurements. A new method is proposed using a 2D ion chamber array (Seven29, PTW, Freiburg, Germany) inserted in a dedicated octagonal phantom, called Octavius. The octagonal shape allows easy positioning for measurements in multiple planes. The directional dependence of the response of the detector was primarily investigated on a dual energy (6 and 18 MV) Clinac 21EX (Varian Medical Systems, Palo Alto, CA) as no fixed angle incidences can be calculated in the Hi-Art TPS of TomoTherapy. The array was irradiated from different gantry angles and with different arc deliveries, and the dose distributions at the level of the detector were calculated with the AAA (Analytical Anisotropic Algorithm) photon dose calculation algorithm implemented in Eclipse (Varian). For validation on the 6 MV TomoTherapy unit, rotational treatments were generated, and dose distributions were calculated with the Hi-Art TPS. Multiple cylindrical ion chamber measurements were used to cross-check the dose calculation and dose delivery in Octavius in the absence of the 2D array. To compensate for the directional dependence of the 2D array, additional prototypes of Octavius were manufactured with built-in cylindrically symmetric compensation cavities. When using the Octavius phantom with a 2 cm compensation cavity, measurements with an accuracy comparable to that of single ion chambers can be achieved. The complete Octavius solution for quality assurance of rotational treatments consists of: The 2D array, two octagonal phantoms (with and without compensation layer), an insert for nine cylindrical ion chambers, and a set of inserts of various tissue equivalent materials of different densities. The combination of the 2D array with the Octavius phantom proved to be a fast and reliable method for pretreatment verification of rotational treatments. Quality control of TomoTherapy patients was reduced to a total of approximately 25 min per patient.     

Identification and characterization of cholest-4-en-3-one, oxime (TRO19622), a novel drug candidate for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive death of cortical and spinal motor neurons, for which there is no effective treatment. Using a cell-based assay for compounds capable of preventing motor neuron cell death in vitro, a collection of approximately 40,000 low-molecular-weight compounds was screened to identify potential small-molecule therapeutics. We report the identification of cholest-4-en-3-one, oxime (TRO19622) as a potential drug candidate for the treatment of ALS. In vitro, TRO19622 promoted motor neuron survival in the absence of trophic support in a dose-dependent manner. In vivo, TRO19622 rescued motor neurons from axotomy-induced cell death in neonatal rats and promoted nerve regeneration following sciatic nerve crush in mice. In SOD1(G93A) transgenic mice, a model of familial ALS, TRO19622 treatment improved motor performance, delayed the onset of the clinical disease, and extended survival. TRO19622 bound directly to two components of the mitochondrial permeability transition pore: the voltage-dependent anion channel and the translocator protein 18 kDa (or peripheral benzodiazepine receptor), suggesting a potential mechanism for its neuroprotective activity. TRO19622 may have therapeutic potential for ALS and other motor neuron and neurodegenerative diseases.