The Mba1 homologue of Trypanosoma brucei is involved in the biogenesis of oxidative phosphorylation complexes.

Consistent with other eukaryotes, the Trypanosoma brucei mitochondrial genome encodes mainly hydrophobic core subunits of the oxidative phosphorylation system. These proteins must be co-translationally inserted into the inner mitochondrial membrane and are synthesized by the highly unique trypanosomal mitoribosomes, which have a much higher protein to RNA ratio than any other ribosome. Here, we show that the trypanosomal orthologue of the mitoribosome receptor Mba1 (TbMba1) is essential for normal growth of procyclic trypanosomes but redundant in the bloodstream form, which lacks an oxidative phosphorylation system. Proteomic analyses of TbMba1-depleted mitochondria from procyclic cells revealed reduced levels of many components of the oxidative phosphorylation system, most of which belong to the cytochrome c oxidase (Cox) complex, three subunits of which are mitochondrially encoded. However, the integrity of the mitoribosome and its interaction with the inner membrane were not affected. Pull-down experiments showed that TbMba1 forms a dynamic interaction network that includes the trypanosomal Mdm38/Letm1 orthologue and a trypanosome-specific factor that stabilizes the CoxI and CoxII mRNAs. In summary, our study suggests that the function of Mba1 in the biogenesis of membrane subunits of OXPHOS complexes is conserved among yeast, mammals and trypanosomes, which belong to two eukaryotic supergroups.

Mitochondrial Membrane-Associated Protein Mba1 Confers Antifungal Resistance by Affecting the Production of Reactive Oxygen Species in Aspergillus fumigatus.

Azole resistance in the human fungal pathogen Aspergillus fumigatus is becoming a major threat to global health. To date, mutations in the azole target-encoding cyp51A gene have been implicated in conferring azole resistance, but a steady increase in the number of A. fumigatus isolates with azole resistance resulting from non-cyp51A mutations has been recognized. Previous studies have revealed that some isolates with non-cyp51A mutation-induced azole resistance are related to mitochondrial dysfunction. However, knowledge of the molecular mechanism underlying the involvement of non-cyp51A mutations is limited. In this study, using next-generation sequencing, we found that nine independent azole-resistant isolates without cyp51A mutations had normal mitochondrial membrane potential. Among these isolates, a mutation in a mitochondrial ribosome-binding protein, Mba1, conferred multidrug resistance to azoles, terbinafine, and amphotericin B but not caspofungin. Molecular characterization verified that the TIM44 domain of Mba1 was crucial for drug resistance and that the N terminus of Mba1 played a major role in growth. Deletion of mba1 had no effect on Cyp51A expression but decreased the fungal cellular reactive oxygen species (ROS) content, which contributed to mba1-mediated drug resistance. The findings in this study suggest that some non-cyp51A proteins drive drug resistance mechanisms that result from reduced ROS production induced by antifungals.

Paralytic Shellfish Toxins in the Gastropod Concholepas concholepas: Variability, Toxin Profiles and Mechanisms for Toxicity Reduction.

Harmful algal blooms of toxin-producing microalgae are recurrent in southern Chile. Paralytic shellfish poisoning (PSP) outbreaks pose the main threat to public health and the fishing industry in the Patagonian fjords. This study aims to increase understanding of the individual and spatial variability of PSP toxicity in the foot of Concholepas concholepas, Chile's most valuable commercial benthic invertebrate species, extracted from the Guaitecas Archipelago in Chilean Patagonia. The objective is to determine the effect of pigment removal and freezing during the detoxification process. A total of 150 specimens (≥90 mm length) were collected from this area. The live specimens were transferred to a processing plant, where they were measured and gutted, the foot was divided into two equal parts, and pigment was manually removed from one of these parts. The PSP toxicity of each foot (edible tissue) was determined by mouse bioassay (MBA) and high-performance liquid chromatography with fluorescence detection and postcolumn oxidation (HPLC-FLD PCOX). The individual toxicity per loco, as the species is known locally, varied from <30 to 146 µg STX diHCL eq 100 g−1 (CV = 43.83%) and from 5.96 to 216.3 µg STX diHCL eq 100 g−1 (CV = 34.63%), using MBA and HPLC, respectively. A generalized linear model showed a negative relation between individual weight and toxicity. The toxicological profile showed a dominance of STX (>95%), neoSTX and GTX2. The removal of pigment produced a reduction in PSP toxicity of up to 90% and could represent a good detoxification tool moving forward. The freezing process in the muscle with pigment did not produce a clear pattern. There is a significant reduction (p < 0.05) of PSP toxicity via PCOX but not MBA. Furthermore, the study discusses possible management and commercialization implications of the findings regarding small-scale fisheries.

The Proof-of-Concept of MBA121, a Tacrine-Ferulic Acid Hybrid, for Alzheimer's Disease Therapy.

Great effort has been devoted to the synthesis of novel multi-target directed tacrine derivatives in the search of new treatments for Alzheimer's disease (AD). Herein we describe the proof of concept of MBA121, a compound designed as a tacrine-ferulic acid hybrid, and its potential use in the therapy of AD. MBA121 shows good ß-amyloid (Aß) anti-aggregation properties, selective inhibition of human butyrylcholinesterase, good neuroprotection against toxic insults, such as Aß1-40, Aß1-42, and H2O2, and promising ADMET properties that support translational developments. A passive avoidance task in mice with experimentally induced amnesia was carried out, MBA121 being able to significantly decrease scopolamine-induced learning deficits. In addition, MBA121 reduced the Aß plaque burden in the cerebral cortex and hippocampus in APPswe/PS1ΔE9 transgenic male mice. Our in vivo results relate its bioavailability with the therapeutic response, demonstrating that MBA121 is a promising agent to treat the cognitive decline and neurodegeneration underlying AD.

An update on the current status and prospects of nitrosation pathways and possible root causes of nitrosamine formation in various pharmaceuticals.

Over the last two years, global regulatory authorities have raised safety concerns on nitrosamine contamination in several drug classes, including angiotensin II receptor antagonists, histamine-2 receptor antagonists, antimicrobial agents, and antidiabetic drugs. To avoid carcinogenic and mutagenic effects in patients relying on these medications, authorities have established specific guidelines in risk assessment scenarios and proposed control limits for nitrosamine impurities in pharmaceuticals. In this review, nitrosation pathways and possible root causes of nitrosamine formation in pharmaceuticals are discussed. The control limits of nitrosamine impurities in pharmaceuticals proposed by national regulatory authorities are presented. Additionally, a practical and science-based strategy for implementing the well-established control limits is notably reviewed in terms of an alternative approach for drug product N-nitrosamines without published AI information from animal carcinogenicity testing. Finally, a novel risk evaluation strategy for predicting and investigating the possible nitrosation of amine precursors and amine pharmaceuticals as powerful prevention of nitrosamine contamination is addressed.

Yme2, a putative RNA recognition motif and AAA+ domain containing protein, genetically interacts with the mitochondrial protein export machinery.

The mitochondrial respiratory chain is composed of nuclear as well as mitochondrial-encoded subunits. A variety of factors mediate co-translational integration of mtDNA-encoded proteins into the inner membrane. In Saccharomyces cerevisiae, Mdm38 and Mba1 are ribosome acceptors that recruit the mitochondrial ribosome to the inner membrane, where the insertase Oxa1, facilitates membrane integration of client proteins. The protein Yme2 has previously been shown to be localized in the inner mitochondrial membrane and has been implicated in mitochondrial protein biogenesis, but its mode of action remains unclear. Here, we show that multiple copies of Yme2 assemble into a high molecular weight complex. Using a combination of bioinformatics and mutational analyses, we find that Yme2 possesses an RNA recognition motif (RRM), which faces the mitochondrial matrix and a AAA+ domain that is located in the intermembrane space. We further show that YME2 genetically interacts with MDM38, MBA1 and OXA1, which links the function of Yme2 to the mitochondrial protein biogenesis machinery.

Seroprevalence of Chlamydia trachomatis Among Female Adults in the United States: The National Health and Nutrition Examination Surveys.

BACKGROUND: Chlamydia trachomatis is the most common nationally notifiable sexually transmitted infection in the United States; however, the seroprevalence of C. trachomatis infection is unknown. METHODS: This cross-sectional study was conducted among 1725 females aged 18 to 39 years who provided serum and urine samples in the 2013 through 2016 National Health and Nutrition Examination Surveys. Presence of anti-C. trachomatis Pgp3 immunoglobulin G (IgG) was determined using both an enzyme-linked immunosorbent assay (ELISA) and multiplex bead array (MBA). Weighted seroprevalence estimates were calculated. Correlates of seroprevalence were examined by multivariable Poisson regression. RESULTS: In 2013 through 2016, overall seroprevalence of C. trachomatis Pgp3 IgG was 30.0% (95% confidence interval [CI], 25.5-35.0) as measured by ELISA and 29.4% (95% CI, 25.8-33.0) as measured by the MBA assay. Overall agreement between tests was 87.1% (1503/1725). There was a high positive agreement by the MBA assay with current detection of chlamydia in urine (86% [36/42]), a past-year diagnosis of chlamydia (81.8% [27/33]), and a history of treatment for pelvic inflammatory disease (60.7% [37/61]). Seroprevalence of C. trachomatis Pgp3 IgG, as measured by MBA, was significantly higher among non-Hispanic Blacks (68.0%; adjusted prevalence ratio (aPR) = 2.7 [95% CI, 2.3-3.3]), Mexican Americans (30.9%; aPR = 1.5 [95% CI, 1.2-1.9]), and other Hispanics (35.0%; aPR = 1.9 [95% CI, 1.4-2.5]) compared with non-Hispanic Whites (21.4%). A higher lifetime number of sexual partners and a younger age at sexual debut was also associated with higher seroprevalence. CONCLUSION: Both the ELISA and MBA serologic assays revealed a high prevalence of antibodies to C. trachomatis Pgp3 in young adult females in the US household population. There were major racial/ethnic disparities in exposure to C. trachomatis, with increased vulnerability among non-Hispanic Black females.

Development of a Measles and Rubella Multiplex Bead Serological Assay for Assessing Population Immunity.

Serosurveys are important tools for estimating population immunity and providing immunization activity guidance. The measles and rubella multiplex bead assay (MBA) offers multiple advantages over standard serological assays and was validated by comparison with the enzyme-linked immunosorbent assay (ELISA) and the measles plaque reduction neutralization (PRN) assay. Results from a laboratory-produced purified measles virus whole-virus antigen MBA (MeV WVAL) correlated better with ELISA and PRN than results from the baculovirus-expressed measles nucleoprotein (N) MBA. Therefore, a commercially produced whole-virus antigen (MeV WVAC) was evaluated. Serum IgG antibody concentrations correlated significantly with a strong linear relationship between the MeV WVAC and MeV WVAL MBAs (R = 0.962 and R2 = 0.926). IgG concentrations from the MeV WVAC MBA showed strong correlation with PRN titers (R = 0.846), with a linear relationship comparable to values obtained with the MeV WVAL MBA and PRN assay (R2 = 0.716 and R2 = 0.768, respectively). Receiver operating characteristic (ROC) curve analysis of the MeV WVAC using PRN titer as the comparator resulted in a seroprotection cutoff of 153 mIU/ml, similar to the established correlate of protection of 120 mIU/ml, with a sensitivity of 98% and a specificity of 83%. IgG concentrations correlated strongly between the rubella WVA MBA and ELISA (R = 0.959 and R2 = 0.919). ROC analysis of the rubella MBA using ELISA as the comparator yielded a cutoff of 9.36 IU/ml, similar to the accepted cutoff of 10 IU/ml for seroprotection, with a sensitivity of 99% and a specificity of 100%. These results support use of the MBA for multiantigen serosurveys assessing measles and rubella population immunity.

The MBA in Medical Education: Current MD/MBA Student Aspirations, Perceptions, and Motivations.

BACKGROUND: As combined Doctor of Medicine and Master of Business Administration (MD/MBA) programs gain popularity, it is critical to understand the motives, perceptions, and interests of MD/MBA students. The purpose of this study was to investigate career aspirations of MD/MBA students, skills they perceive to gain from the dual degree, and reasons why students enroll in MD/MBA programs. MATERIALS AND METHODS: All 73 MD/MBA programs in the United States were invited to participate in a twelve-question, online survey. Responses were collected between August 2019 and February 2020 from students enrolled during the 2019-2020 academic year. The questions were designed to examine career aspirations, program perceptions, and personal motivations. Data were aggregated into descriptive summary statistics and rank orders. RESULTS: A total of 18 MD/MBA programs agreed to participate in this study, of which 14 met criteria for final analysis. From these programs, 67 of 175 students responded (38%). Among respondents, 100% planned to pursue residency. The most common career interests included the following: clinical practice at an academic hospital (85%), executive leadership in a hospital network (76%), and clinical practice in a community hospital (65%). Students ranked "making a broader impact on health care" and "pursuing leadership in clinical practice" highest among reasons to pursue an MD/MBA. Students reported high rates of acquiring MBA-oriented skills. CONCLUSIONS: MD/MBA students in this study focused on pursuing clinical careers. Students appear satisfied with their education, reporting high rates of skill acquisition. Residency programs interested in MD/MBA students can incorporate leadership and entrepreneurial opportunities to foster students' broad interests.

Hexagonal arrays of plasmonic gold nanopyramids on flexible substrates for surface-enhanced Raman scattering.

Surface-enhanced Raman spectroscopy (SERS) with pyramidal gold nanostructures increases the signal of Raman active analytes, since hotspots form at the edges and tip of a nanopyramid under illumination. 2D hexagonal arrays of pyramidal nanostructures with a quadratic base are fabricated through cost-effective nanosphere lithography and transferred onto elastomeric polydimethylsiloxane. By making use of the {111} crystal plane of a silicon (100) wafer, an inverted pyramidal array is etched, which serves as the complementary negative for the gold nanostructures. Either a continuous gold thin-film with protruding pyramids or separate isolated nanopyramids are produced. Three basic fabrication strategies are presented. The SERS enhancement is verified by Raman mapping of 4-mercaptobenzoic acid (4-MBA) molecules. Fabrication on a flexible substrate paves the way for future applications on curved surfaces orin situtunable resonances.

Deep-Water Fish Are Potential Vectors of Ciguatera Poisoning in the Gambier Islands, French Polynesia.

Ciguatera poisoning (CP) cases linked to the consumption of deep-water fish occurred in 2003 in the Gambier Islands (French Polynesia). In 2004, on the request of two local fishermen, the presence of ciguatoxins (CTXs) was examined in part of their fish catches, i.e., 22 specimens representing five deep-water fish species. Using the radioactive receptor binding assay (rRBA) and mouse bioassay (MBA), significant CTX levels were detected in seven deep-water specimens in Lutjanidae, Serranidae, and Bramidae families. Following additional purification steps on the remaining liposoluble fractions for 13 of these samples (kept at -20 °C), these latter were reanalyzed in 2018 with improved protocols of the neuroblastoma cell-based assay (CBA-N2a) and liquid chromatography tandem mass spectrometry (LC-MS/MS). Using the CBA-N2a, the highest CTX-like content found in a specimen of Eumegistus illustris (Bramidae) was 2.94 ± 0.27 µg CTX1B eq. kg-1. Its toxin profile consisted of 52-epi-54-deoxyCTX1B, CTX1B, and 54-deoxyCTX1B, as assessed by LC-MS/MS. This is the first study demonstrating that deep-water fish are potential ciguatera vectors and highlighting the importance of a systematic monitoring of CTXs in all exploited fish species, especially in ciguatera hotspots, including deep-water fish, which constitute a significant portion of the commercial deep-sea fisheries in many Asian-Pacific countries.

The Optical Signal-to-Crosstalk Ratio for the MBA(N, e, g) Switching Fabric †.

The banyan-type switching networks, well known in switching theory and called the logdN switching fabrics, are composed of symmetrical switching elements of size d×d. In turn, the modified baseline architecture, called the MBA(N,e,g), is only partially built from symmetrical optical switching elements, and it is constructed mostly from asymmetrical optical switching elements. Recently, it was shown that the MBA(N,e,g) structure requires a lower number of passive as well as active optical elements than the banyan-type switching fabric of the same capacity and functionality, which makes it an attractive solution. However, the optical signal-to-crosstalk ratio for the MBA(N,e,g) was not investigated before. Therefore, in this paper, the optical signal-to-crosstalk ratio in the MBA(N,e,g) was determined. Such crosstalk influences the output signal's quality. Thus, if such crosstalk is lower, the signal quality is better. The switching fabric proposed in the author's previous work has lower optical signal losses than a typical Benes and banyan-type switching networks of this same capacity and functionality, which gives better quality of transmitted optical signals at the switching node's output. The investigated MBA(N,e,g) architecture also contains one stage fewer than banyan-type network of the same capacity, which is an essential feature from the optical switching point of view.

Quantitative Structure-Activity Relationship Evaluation of MDA-MB-231 Cell Anti-Proliferative Leads.

In the present endeavor, for the dataset of 219 in vitro MDA-MB-231 TNBC cell antagonists, a (QSAR) quantitative structure-activity relationships model has been carried out. The quantitative and explicative assessments were performed to identify inconspicuous yet pre-eminent structural features that govern the anti-tumor activity of these compounds. GA-MLR (genetic algorithm multi-linear regression) methodology was employed to build statistically robust and highly predictive multiple QSAR models, abiding by the OECD guidelines. Thoroughly validated QSAR models attained values for various statistical parameters well above the threshold values (i.e., R2 = 0.79, Q2LOO = 0.77, Q2LMO = 0.76-0.77, Q2-Fn = 0.72-0.76). Both de novo QSAR models have a sound balance of descriptive and statistical approaches. Decidedly, these QSAR models are serviceable in the development of MDA-MB-231 TNBC cell antagonists.

[Rapid Screening System for Paralytic Shellfish Toxins in Bivalves by Oligonucleotide Lateral Flow Immunoassay].

The mouse bioassay (MBA) for paralytic shellfish toxins (PSTs) in bivalves has been used as an official method in Japan. It is necessary to develop an alternative method to animal experiments in PSTs assay because 3Rs (Replacement, Reduction, and Refinement) of animal experiments are required from the animal welfare point of view. Various methods such as HPLC-FL, receptor binding assay, LC-MS/MS and ELISA have been established to detect PSTs without performing animal experiments. The present study was undertaken to develop a screening method using oligonucleotide lateral flow immunoassay (OLFIA) for detecting PSTs in bivalves. The screening level was defined as positive at 2 MU/g of MBA that is the half regulation limit of PSTs monitoring in Japan. All 20 positive (equal to or more than 2 MU/g) samples judged from MBA showed a positive reaction in the OLFIA. No positive samples resulted in a false negative reaction. The OLFIA exhibited high accuracy at 2 MU/g of screening criteria. The authors demonstrated here that the OLFIA can be useful for rapid detection of PSTs in bivalves.

BioMAX - the first macromolecular crystallography beamline at MAX IV Laboratory.

BioMAX is the first macromolecular crystallography beamline at the MAX IV Laboratory 3 GeV storage ring, which is the first operational multi-bend achromat storage ring. Due to the low-emittance storage ring, BioMAX has a parallel, high-intensity X-ray beam, even when focused down to 20 µm × 5 µm using the bendable focusing mirrors. The beam is tunable in the energy range 5-25 keV using the in-vacuum undulator and the horizontally deflecting double-crystal monochromator. BioMAX is equipped with an MD3 diffractometer, an ISARA high-capacity sample changer and an EIGER 16M hybrid pixel detector. Data collection at BioMAX is controlled using the newly developed MXCuBE3 graphical user interface, and sample tracking is handled by ISPyB. The computing infrastructure includes data storage and processing both at MAX IV and the Lund University supercomputing center LUNARC. With state-of-the-art instrumentation, a high degree of automation, a user-friendly control system interface and remote operation, BioMAX provides an excellent facility for most macromolecular crystallography experiments. Serial crystallography using either a high-viscosity extruder injector or the MD3 as a fixed-target scanner is already implemented. The serial crystallography activities at MAX IV Laboratory will be further developed at the microfocus beamline MicroMAX, when it comes into operation in 2022. MicroMAX will have a 1 µm × 1 µm beam focus and a flux up to 1015 photons s-1 with main applications in serial crystallography, room-temperature structure determinations and time-resolved experiments.

Migraine with brainstem aura: defining the core syndrome.

Migraine with brainstem aura is a rare subtype of migraine with aura. Although this entity has been known for many years, its diagnosis and even its existence are still a matter of debate. Previous studies demonstrated that current diagnostic criteria for migraine with brainstem aura are too open and brainstem symptoms may originate within the cortex and not in the brainstem. The aims of the present study were to analyse whether aura from the brainstem exists, how prevalent such a core syndrome is, to analyse if current diagnostic criteria define such a core syndrome and, if necessary, to develop new diagnostic criteria that define only the core syndrome. We analysed all migraine with brainstem aura cases described in detail in the literature, clinical cases from the Danish Headache Center (DHC) and our large sample of telephone interviewed cases with migraine with aura. We selected the 20 most convincing cases from the literature and convincing cases from the DHC. Of 79 migraine with brainstem aura cases described in detail in the literature, 44 fulfilled the diagnostic criteria for migraine with brainstem aura of the International Classification of Headache Disorders, 3rd edition (ICHD-3). In the DHC after face-to-face interview, neurological examination and imaging, four migraine with brainstem aura of 293 cases with migraine with aura (1.37%) were found, corresponding to 0.04% of the general population. The 20 most convincing cases had symptoms that likely originated in the brainstem. Our telephone-interviewed cohort included 1781 subjects with a diagnosis of migraine with aura or probable migraine with aura. Of these, 228 fulfilled the diagnostic criteria for migraine with brainstem aura of the ICHD-3. Thus, using telephone interview diagnosis according to current diagnostic criteria results in too many cases of migraine with brainstem aura being diagnosed. Therefore, we developed stricter diagnostic criteria in an attempt to include only those rare cases that definitely have aura originating from the brainstem. Migraine with brainstem aura does exist, but it is very rare. Existing diagnostic criteria are too unspecific, but it was possible to develop tighter criteria that define a core syndrome probably caused by brainstem dysfunction.

Application of Six Detection Methods for Analysis of Paralytic Shellfish Toxins in Shellfish from Four Regions within Latin America.

With the move away from use of mouse bioassay (MBA) to test bivalve mollusc shellfish for paralytic shellfish poisoning (PSP) toxins, countries around the world are having to adopt non-animal-based alternatives that fulfil ethical and legal requirements. Various assays have been developed which have been subjected to single-laboratory and multi-laboratory validation studies, gaining acceptance as official methods of analysis and approval for use in some countries as official control testing methods. The majority of validation studies conducted to date do not, however, incorporate shellfish species sourced from Latin America. Consequently, this study sought to investigate the performance of five alternative PSP testing methods together with the MBA, comparing the PSP toxin data generated both qualitatively and quantitatively. The methods included a receptor binding assay (RBA), two liquid chromatography with fluorescence detection (LC-FLD) methods including both pre-column and post-column oxidation, liquid chromatography with tandem mass spectrometry (LC-MS/MS) and a commercial lateral flow assay (LFA) from Scotia. A total of three hundred and forty-nine shellfish samples from Argentina, Mexico, Chile and Uruguay were assessed. For the majority of samples, qualitative results compared well between methods. Good statistical correlations were demonstrated between the majority of quantitative results, with a notably excellent correlation between the current EU reference method using pre-column oxidation LC-FLD and LC-MS/MS. The LFA showed great potential for qualitative determination of PSP toxins, although the findings of high numbers of false-positive results and two false negatives highlighted that some caution is still needed when interpreting results. This study demonstrated that effective replacement methods are available for countries that no longer wish to use the MBA, but highlighted the importance of comparing toxin data from the replacement method using local shellfish species of concern before implementing new methods in official control testing programs.

Indirect surface-enhanced Raman scattering assay of insulin-like growth factor 2 receptor protein by combining the aptamer modified gold substrate and silver nanoprobes.

An indirect aptamer-based SERS assay for insulin-like growth factor 2 receptor (IGF-IIR) protein was developed. The gold substrate and silver nanoparticles (AgNPs) were employed simultaneously to achieve double enhancement for SERS signals. Firstly, the five commercial SERS substrates including Enspectr, Ocean-Au, Ocean-AG, Ocean-SP and Q-SERS substrates were evaluated using 4-mercaptobenzoic acid (4-MBA). The Q-SERS substrate was selected based on low relative standard deviation (RSD, 8.6%) and high enhancement factor (EF, 8.7*105), using a 785 nm laser. The aptamer for IGF-IIR protein was designed to include two sequences: one grafted on gold substrate to specifically capture the IGF-IIR protein and a second one forming a 3' sticky bridge to capture SERS nanotags. The SERS nanotag was composed by AgNPs (20 nm), 4-MBA and DNA probes that can hybridize with the aptamer. Due to the steric-hindrance effect, when the aptamer doesn't combine with IGF-IIR protein, it only can capture the SERS nanotags. Therefore, there was a negative correlation between the concentration of IGF-IIR protein and the intensity of 4-MBA at 1076 cm-1. The detection limit reached to 141.2 fM and linear range was from 10 pM to 1 µM. The SERS aptasensor also exhibits a high reproducibility with an average RSD of 4.5%. The interference test was conducted with other four proteins to verify the accuracy of measuring. The study provides an approach to quantitative determination of proteins based on specific recognition and nucleic acid hybridization of aptamers, to establish sandwich structure for SERS enhancement. Graphical abstractSchematic representation of surface-enhanced Raman scattering (SERS) assay on insulin-like growth factor 2 receptor (IGF-IIR) protein by combining the aptamer modified gold substrate and 4-mercaptobenzoic acid (4-MBA) and DNA probe modified silver nanoparticles.

Transitioning from Practice to Health Care Administration: The Later Years.

Since the late 1800s, the role of the physician has evolved substantially beyond mainstream clinical medicine. As fee for service models expanded in the 1980s, resulting in an unsustainable financial crisis in health care, senior physicians stepped up to provide essential input and expertise to administrators on a national level. This model of physician-administrator has evolved to include dual-degree physicians who are equipped with specialized knowledge even at the outset of their career. As physicians are now vital members of health care administration, many will feel the need to transition from clinical practice to a new position where they can effect change on a larger scale. This article will provide insight into such transitions and dual-career pathways and discuss important considerations when faced with this juncture in one's career.

A novel mba-based Real time PCR approach for genotyping of Ureaplasma parvum validated in a cohort of Mongolian mothers and offspring.

The role of Ureaplasma parvum in abnormal outcomes of human pregnancy has been discussed controversially in the past. Of the 14 known ureaplasma serovars, the Ureaplasma parvum serovars 1, 3, 6 and 14, have been found to derive from smaller genomes. Serovars 3 and 6 have been described more often to cause complications in pregnancy. To elucidate the serovar distribution in U. parvum positive specimens of 200 Mongolian mothers and their offspring, a new set of mba-targeting PCRs was developed enabling a fast and reliable serovar differentiation by melting peak analysis in a Real time PCR approach or by conventional agarose gel electrophoresis. 92% maternal and 55% neonatal samples were retrospectively genotyped and a dominance of serovars 3 and 6 was detected while serovar 14 was almost absent. Transmission from mothers to newborns was detected in 83% of U. parvum positive neonates exhibiting serovar patterns identical to their mothers. No statistically significant correlation between a distinct serovar and pregnancy outcome could be detected. However, neonatal colonization with serovar 1 declined with progressing pregnancy suggesting that a higher ureaplasma load shortened pregnancy and thereby had a potential negative effect on offspring health. Our novel mba-based Real time PCR approach, which can also be used in conventional PCR and gel electrophoretic analysis, provides the proof of principle that the four U. parvum serovars 1, 3, 6 and 14 can be differentially detected and quantified. A larger scale study outside the scope of this work should be conducted to clarify the impact of serovar 1 on pregnancy outcome.