The association of military sexual assault and nonsuicidal self-injury in U.S. Gulf War-I era veterans.
Military sexual assault (MSA) is a prevalent issue among military personnel that has been linked to adverse mental and physical health outcomes, including posttraumatic stress disorder (PTSD) and suicidal thoughts and behaviors. The present study sought to investigate the relationship between MSA and nonsuicidal self-injury (NSSI) in a national sample of Gulf War-I Era U.S. veterans. The study analyzed data from 1,153 Gulf War-I veterans collected through a cross-sectional survey that assessed demographic information, clinical outcomes, military background, and history of MSA and NSSI. MSA was found to be significantly associated with NSSI at the bivariate level (OR = 2.19, p < .001). Further, MSA remained significantly associated with NSSI (AOR = 2.50, p = .002) after controlling for relevant demographics and clinical outcomes. Veterans with a history of MSA were approximately two and half times more likely to engage in NSSI than veterans who had not experienced MSA. The present findings provide preliminary evidence linking MSA and NSSI. Further, the findings highlight the importance of assessing MSA and NSSI in veteran populations, particularly among those seeking treatment for PTSD.


Proteomic analysis of sea urchin (Strongylocentrotus purpuratus) spicule matrix.
The sea urchin embryo has been an important model organism in developmental biology for more than a century. This is due to its relatively simple construction, translucent appearance, and the possibility to follow the fate of individual cells as development to the pluteus larva proceeds. Because the larvae contain tiny calcitic skeletal elements, the spicules, they are also important model organisms for biomineralization research. Similar to other biominerals the spicule contains an organic matrix, which is thought to play an important role in its formation. However, only few spicule matrix proteins were identified previously. Using mass spectrometry-based methods we have identified 231 proteins in the matrix of the S. purpuratus spicule matrix. Approximately two thirds of the identified proteins are either known or predicted to be extracellular proteins or transmembrane proteins with large ectodomains. The ectodomains may have been solubilized by partial proteolysis and subsequently integrated into the growing spicule. The most abundant protein of the spicule matrix is SM50. SM50-related proteins, SM30-related proteins, MSP130 and related proteins, matrix metalloproteases and carbonic anhydrase are among the most abundant components. The spicule matrix is a relatively complex mixture of proteins not only containing matrix-specific proteins with a function in matrix assembly or mineralization, but also: 1) proteins possibly important for the formation of the continuous membrane delineating the mineralization space; 2) proteins for secretory processes delivering proteinaceous or non-proteinaceous precursors; 3) or proteins reflecting signaling events at the cell/matrix interface. Comparison of the proteomes of different skeletal matrices allows prediction of proteins of general importance for mineralization in sea urchins, such as SM50, SM30-E, SM29 or MSP130. The comparisons also help point out putative tissue-specific proteins, such as tooth phosphodontin or specific spicule matrix metalloproteases of the MMP18/19 group. Furthermore, the direct sequence analysis of peptides by MS/MS validates many predicted genes and confirms the existence of the corresponding proteins.


Structure-guided design of a high affinity inhibitor to human CtBP.
Oncogenic transcriptional coregulators C-terminal Binding Protein (CtBP) 1 and 2 possess regulatory d-isomer specific 2-hydroxyacid dehydrogenase (D2-HDH) domains that provide an attractive target for small molecule intervention. Findings that the CtBP substrate 4-methylthio 2-oxobutyric acid (MTOB) can interfere with CtBP oncogenic activity in cell culture and in mice confirm that such inhibitors could have therapeutic benefit. Recent crystal structures of CtBP 1 and 2 revealed that MTOB binds in an active site containing a dominant tryptophan and a hydrophilic cavity, neither of which are present in other D2-HDH family members. Here, we demonstrate the effectiveness of exploiting these active site features for the design of high affinity inhibitors. Crystal structures of two such compounds, phenylpyruvate (PPy) and 2-hydroxyimino-3-phenylpropanoic acid (HIPP), show binding with favorable ring stacking against the CtBP active site tryptophan and alternate modes of stabilizing the carboxylic acid moiety. Moreover, ITC experiments show that HIPP binds to CtBP with an affinity greater than 1000-fold over that of MTOB, and enzymatic assays confirm that HIPP substantially inhibits CtBP catalysis. These results, thus, provide an important step, and additional insights, for the development of highly selective antineoplastic CtBP inhibitors.


S1RA, a selective sigma-1 receptor antagonist, inhibits inflammatory pain in the carrageenan and complete Freund's adjuvant models in mice.
The therapeutic potential of S1RA (E-52862), a selective sigma-1 receptor (σ1R) antagonist, has been explored in experimental neuropathic pain, but not in inflammatory pain models. The present study investigated the effect of the intraperitoneal administration of S1RA on the hind paw withdrawal response to thermal and mechanical stimulation following an intraplantar injection of carrageenan (CARR) and complete Freund's adjuvant (CFA), which are two well-characterized models of acute and chronic inflammatory pain, respectively. S1RA fully reversed both mechanical [dose of drug that produced half of its maximal response (ED50)=35.9 and 42.1 mg/kg for CARR-induced and CFA-induced pain, respectively] and thermal (ED50=27.9 mg/kg, CARR) hypersensitivity, whereas ibuprofen (CARR, mechanical allodynia) and celecoxib (CARR, thermal hyperalgesia; CFA, mechanical allodynia) failed to reach maximum efficacy. Morphine also showed maximum efficacy in all tests. Unlike celecoxib and ibuprofen, which decreased paw volume significantly, CARR-induced paw oedema was not reduced by S1RA and morphine, thus suggesting that the antinociceptive effect of S1RA does not involve a major anti-inflammatory (antioedema) action. S1RA was devoid of efficacy when administered to σ1R knockout mice, thus suggesting the involvement of σ1R in the antinociceptive effects exerted by S1RA. We conclude that S1RA represents a promising novel analgesic therapy for inflammatory pain.


Women in tunicate research: Pioneers of the past and their present legacy.
The search for female scientists who pioneered the research on tunicates is hindered by the tradition of reporting only the first initials of authors' names on scientific publications using only the initials of their first names. While this practice has the theoretical merit of broadening the readership by preventing the possible bias that could be caused by the gender of the author(s) in some of the readers, it rendered the identification of female researchers active in, or before, the first half of the 20th century quite challenging. Sifting through several dozen electronic records, and with the help of references and/or quotes found online, we have stitched together the information that we were able to retrieve on the life of female scientists who authored some of the earliest publications on tunicates, and we have organized them in (approximate) chronological order. We have also compiled brief synopses of the findings of scientists active in the field of tunicate biology in more recent times, and organized them by subdiscipline.


Analysis of surgical and MRI factors associated with cerebellar mutism.
The surgical risk factors and neuro-imaging characteristics associated with cerebellar mutism (CM) remain unclear and require further investigation. Therefore, we aimed to examine surgical and MRI findings associated with CM in children following posterior fossa tumor resection. Using our data registry, we retrospectively collected data from pediatric patients who acquired CM and were matched based on age and pathology type with individuals who did not acquire CM after posterior fossa surgery. The strength of association between surgical and MRI variables and CM were examined using odds ratios (ORs) and corresponding 95% confidence intervals (CIs). A total of 22 patients (11 with and 11 without CM) were included. Medulloblastoma was the most common pathology among CM patients (91%); the remaining 9% were diagnosed with a pilocytic astrocytoma. Tumor attachment to the floor of the fourth ventricle (OR 6; 95% CI 0.7-276), calcification/hemosiderin deposition (OR 7; 95% CI 0.9-315.5), and post-operative peri-ventricular ischemia on MRI (OR 5; 95% CI 0.5-236.5) were found to have the highest measures of association with CM. Our results may suggest that tumor attachment to the floor of the fourth ventricle, pathological calcification, and post-operative ischemia have a relatively higher prevalence in patients with CM. Collectively, our work calls for a larger multi-institutional cohort study of CM patients to encourage further investigation of the determinants and management of CM in order to potentially minimize its development and predict onset.


Evaluation of recombinant human vascular endothelial growth factor VEGF121-loaded poly-l-lactide microparticles as a controlled release delivery system.
Vascular endothelial growth factor A (VEGF-A) is an important growth factor that plays a major role in angiogenesis. With different isoforms distributed in various tissues, the shortest isoform of VEGF-A is VEGF121, one of the physiologically functional variants next to VEGF165. It is well known that VEGF has a shorter half-life, and the stability of the protein must be considered in therapeutic aspects. Poly-l-lactide (PLA) microparticles can release the encapsulated protein in a sustained release mode. In this study, the VEGF121 gene was cloned and expressed in a prokaryotic expression system (Escherichia coli). The recombinant VEGF121 was encapsulated with PLA microparticles and studied in vitro and ex ovo for the sustained release mechanism. The PLA-VEGF microparticles and the recombinant VEGF121 were explored for their bioactivity in human umbilical vein endothelial cells (HUVEC). VEGF released in vitro from PLA microparticles on days 1, 20, and 30 showed remarkable biological activity compared to PBS-loaded PLA microparticles such as the ability of the cells to proliferate, migrate, and form tubes similar to recombinant VEGF121. Besides, PLA-VEGF microparticles and the recombinant VEGF121 were also tested for their proangiogenic action in embryonated eggs by chicken chorioallantoic membrane assay (CAM), and the effect was observed in both forms. This study suggests that PLA-loaded VEGF microparticles in a sustainable release format can be effectively used in proangiogenic therapy and reduce the adverse effects caused due to multiple dosages.


Plant peptides govern terminal differentiation of bacteria in symbiosis.
Legume plants host nitrogen-fixing endosymbiotic Rhizobium bacteria in root nodules. In Medicago truncatula, the bacteria undergo an irreversible (terminal) differentiation mediated by hitherto unidentified plant factors. We demonstrated that these factors are nodule-specific cysteine-rich (NCR) peptides that are targeted to the bacteria and enter the bacterial membrane and cytosol. Obstruction of NCR transport in the dnf1-1 signal peptidase mutant correlated with the absence of terminal bacterial differentiation. On the contrary, ectopic expression of NCRs in legumes devoid of NCRs or challenge of cultured rhizobia with peptides provoked symptoms of terminal differentiation. Because NCRs resemble antimicrobial peptides, our findings reveal a previously unknown innovation of the host plant, which adopts effectors of the innate immune system for symbiosis to manipulate the cell fate of endosymbiotic bacteria.


Combining AFM and FRET for high resolution fluorescence microscopy.
Here we demonstrate a new microscopic method that combines atomic force microscopy (AFM) with fluorescence resonance energy transfer (FRET). This method takes advantage of the strong distance dependence in Förster energy transfer between dyes with the appropriate donor/acceptor properties to couple an optical dimension with conventional AFM. This is achieved by attaching an acceptor dye to the end of an AFM tip and exciting a sample bound donor dye through far-field illumination. Energy transfer from the excited donor to the tip immobilized acceptor dye leads to emission in the red whenever there is sufficient overlap between the two dyes. Because of the highly exponential distance dependence in this process, only those dyes located at the apex of the AFM tip, nearest the sample, interact strongly. This limited and highly specific interaction provides a mechanism for obtaining fluorescence contrast with high spatial resolution. Initial results in which 400 nm resolution is obtained through this AFM/FRET imaging technique are reported. Future modifications in the probe design are discussed to further improve both the fluorescence resolution and imaging capabilities of this new technique.


Bibliometric assessment and key messages of sporotrichosis research (1945-2018).
Background: Sporotrichosis has recently emerged as an important mycosis worldwide, with diverse transmission and epidemiologic profiles. For instance, in Brazil most cases are related to zoonotic transmission from naturally infected cats, and the majority of cases in China are due to external injury with environmental materials. Publications on sporotrichosis and on its etiologic agent may guide the direction of the research in this field. It can also define priorities for future studies. Methods: In this study, we evaluated the trends of global research in Sporothrix and sporotrichosis, based on publications records retrieved from Scopus and Web of Science databases for the period of 1945 to 2018. The overall productivity in the field, its geographical and temporal distribution, research themes, co-authorship networks, funding sources, and if audience and research findings are addressed in the abstracts. Results: A total of 4,007 unique publications involving 99 countries were retrieved, most of them published after 2000. Authors based on institutions from the United States of America and Brazil accounted for 57.4% of the publications. Brazil was the leading country in terms of research collaboration and networking, with co-authorship with 45 countries. The thematic mapping revealed a temporal shift from clinical to applied research. Despite the large number of countries publishing in this field, most of funded studies came from Brazil, Mexico, China, South Africa, or the United States of America. The analysis of content identified few specific public health recommendations for prevention, case-management, or research. Moreover, most papers do not have a clearly defined intended audience. Conclusion: As the research in this field is emerging in several countries, with the generation of a large amount of data, it is necessary that scientists strengthen efforts to translate the research results into practice to curb this neglected infection.


New in vitro model to study the effect of antibiotic concentration and rate of elimination on antibacterial activity.
A new apparatus is described which serves to investigate the in vitro antibacterial activity of antibiotics as a function of different concentration time curves. The apparatus can be adjusted to simulate the biexponential serum level curves observed in vivo after oral or intramuscular administration. Preliminary studies were carried out with a cephalosporin derivative, cefazolin, against Escherichia coli and Klebsiella sp. strains simulating initial concentrations of 5, 10, and 20 mug/ml that decreased exponentially with half-lives of 30, 60, and 120 min. Surviving cells were counted at 1-h intervals for 10 h. In all the situations tested there was an initial phase of rapid bactericidal activity followed by a phase of bacteriostatic activity, whose length depended on the drug elimination rate but was relatively independent of the initial concentrations. Bacterial regrowth occurred when the antibiotic concentration fell below the minimum inhibitory concentration of the drug against the strains tested. The antibacterial activity of cefazolin, cephacetrile, and cephradine against E. coli and Klebsiella strains was also investigated, in a medium containing 4% human albumin, simulating the serum level curves observed in humans after an intramuscular dose of 1 g. The results obtained suggest that, for cephalosporins, a longer half-life might be more useful than higher peak levels.


Robotic-assisted gastroplication in a morbidly obese adolescent: early improvement in metabolic and neurohormonal parameters.
Bariatric surgery has to be considered in the management of severely obese adolescents when all conservative measures have been proven to be unresponsive. Short term metabolic and neurohormonal profile changes after robotic-assisted gastroplication are evaluated. The benefits and the usefulness of this surgical - reversal procedure in adolescent need to be defined. Fiveteen years old girl with body mass index 42.2 kg/m(2), hyperinsulinism, hyperandrogenism, amenorrhea, polycystic ovarian syndrome, hypertension with left ventricular hypertrophy. Gastric volume after surgical procedure reduction was 80-100 mL. One month postoperatively significant weigh loss was obtained. Insulin levels, insulin-resistance, leptin and ghrelin concentration were substantially ameliorated. We can conclude that bariatric surgery should be considered for a minority of severely obese adolescents under the supervision of a multidisciplinary pediatric team. Our experience confirmed that the gastroplication is safe, feasible and effective and furthermore is a reversible technique. The early improvement of the obesity co-morbities is allowed. The increased surgical accuracy in robotic assistance could limit postoperative complications rate in obese adolescents.


Role of RNA synthesis in the estrogen induction of a specific uterine protein.
The rate of amino acid incorporation into a specific uterine protein (induced protein band) isolated by gel electrophoresis has been shown to be markedly stimulated within an hour after estrogen administration. Injection of actinomycin D (8 mg/kg) prior to estrogen blocks the synthesis of induced protein. The accumulation of the product of the actinomycin D-sensitive step (induced protein band RNA) is significant 15 minutes after estrogen, and its synthesis would appear to be initiated as soon as the estrogen-receptor complex reaches the nucleus. Blocking protein synthesis with puromycin or cycloheximide did not affect the accumulation of induced protein band RNA, indicating that this is one of the earliest macromolecular synthetic events to occur after estrogen administration.


Doctors' willingness to give honest answers about end-of-life practices: a cross-sectional study.
We aimed to (1) evaluate the extent to which doctors in New Zealand would be willing to answer honestly questions about their care of patients at the end of their lives and (2) identify the assurances that would encourage this. Results were compared with findings from a previous pilot study from the UK. Survey study involving a mailed questionnaire. New Zealand hospital and community-based medical care settings. The questionnaire was mailed to a random sample of 800 doctors in New Zealand who were vocationally registered with the Medical Council of New Zealand in disciplines involving caring for patients at the end of their lives. Willingness to provide honest answers about various aspects of end-of-life care; assurances that might increase willingness to provide honest answers to questions about end-of-life practices. Completed questionnaires were returned by 436 doctors. The majority of respondents (59.9-91.5%) indicated willingness to provide honest answers to such questions. However, more than a third of doctors were unwilling to give honest answers to certain questions regarding euthanasia. These results are comparable with the UK data. Complete anonymity was the assurance most likely to encourage honest answering, with most of the respondents preferring the use of anonymous written replies. Respondents were less reassured by survey endorsements from regulatory bodies. Themes in free comments included the deterrent effect of medicolegal consequences, fear of censure from society, peers and the media and concerns about the motivations and potential uses of such research. Many New Zealand doctors were willing to give honest answers to questions about end-of-life practices, particularly if anonymity was guaranteed; others, however, expressed doubts or indicated that they would not be willing to provide honest answers to questions of this sort.


[Pain management in gastrointestinal oncology].
Abdominal cancer is commonly associated with pain needing medical attention. Effective pain management is available to control pain. Oral opioids are the foundation of analgesic therapy. With adequate implementation of therapeutic guidelines into clinical practice including the use of co-analgesics, adjuvants and non-pharmacological treatment options the quality of life of abdominal cancer patients can be considerably improved. Only in a minority of patients with refractory pain more sophisticated options of pain management will be necessary, e. g., epidural, intrathecal or neurolytic techniques. In this situation the consultation of a pain therapist is recommended.


Harvest strategies for the elimination of low prevalence wildlife diseases.
The intensive harvesting of hosts is often the only practicable strategy for controlling emerging wildlife diseases. Several harvesting approaches have been explored theoretically with the objective of lowering transmission rates, decreasing the transmission period or specifically targeting spatial disease clusters or high-risk demographic groups. Here, we present a novel model-based approach to evaluate alternative harvest regimes, in terms of demographic composition and rates, intended to increase the probability to remove all infected individuals in the population during the early phase of an outbreak. We tested the utility of the method for the elimination of chronic wasting disease based on empirical data for reindeer (Rangifer tarandus) in Norway, in populations with (Nordfjella) and without (Hardangervidda) knowledge about exact disease prevalence and population abundance. Low and medium harvest intensities were unsuccessful in eliminating the disease, even at low prevalence. High-intensity harvesting had a high likelihood of eliminating the disease, but probability was strongly influenced by the disease prevalence. We suggest that the uncertainty about disease prevalence can be mitigated by using an adaptive management approach: forecast from models after each harvest season with updated data, derive prevalence estimates and forecast further harvesting. We identified the problems arising from disease surveillance with large fluctuations in harvesting pressure and hence sample sizes. The elimination method may be suitable for pathogens that cause long-lasting infections and with slow epidemic growth, but the method should only be attempted if there is a low risk of reinfection, either by a new disease introduction event (e.g. dispersing hosts) or due to environmental reservoirs. Our simulations highlighted the short time window when such a strategy is likely to be successful before approaching near complete eradication of the population.


Protective effect of HLA-DRB1*13 alleles during specific phases in the development of ACPA-positive RA.
Human leucocyte antigen (HLA)-DRB1*13 alleles are associated with protection from anticitrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA). It is, however, unknown at which phase of disease development (seroconversion, ACPA maturation, disease onset or outcome) these alleles are most important. We therefore examined the effect of HLA-DRB1*13 on: ACPA presence (systemic autoimmunity associated with RA) in individuals with and without RA, on ACPA characteristics and on clinical outcome measures. The effect of HLA-DRB1*13 on ACPA presence in subjects with or without RA (non-RA) was assessed in the Swedish twin registry (n=10 748). ACPA characteristics were studied in patients with ACPA-positive RA from the Swedish Epidemiological Investigation of RA (EIRA, n=1224) and the Dutch Leiden Early Arthritis Clinic (EAC, n=441). Disease activity at inclusion and disease outcome (disease-modifying antirheumatic drugs (DMARD)-free sustained remission and radiographic progression) was assessed in patients with RA from the EAC. HLA-DRB1*13 is associated with protection from ACPA-positive RA (prevalence 16% vs 28% in ACPA-negative non-RA), but not with significant protection from ACPA in individuals without RA (prevalence: 22%, p value 0.09). HLA-DRB1*13 is associated with lower ACPA-levels (EIRA: 447 U/ml versus 691 U/ml, p value= 0.0002) and decreased citrullinated epitope recognition (EIRA: p<0.0001). No association between HLA-DRB1*13 and disease activity or outcome was found. These data indicate that HLA-DRB1*13 mainly affects the onset of ACPA-positive RA in ACPA-positive non-RA individuals. In RA, HLA-DRB1*13 influences ACPA characteristics but not the disease course. This implies that therapeutic strategies aimed at emulating the HLA-DBR1*13 protective effect may be most effective in ACPA-positive healthy individuals at risk for RA.


[Post-infectious irritable bowel syndrome. A review based on current evidence].
Pathophysiology of irritable bowel syndrome (IBS) is multifactorial. Recent investigations have associated episodes of infectious gastroenteritis with development of IBS. This condition is named post-infectious IBS (PI-IBS). The role of inflammation-infection in IBS pathogenesis is not well understood. To review published scientific evidence on PI-IBS regarding risk factors, causal agents, histopathological changes, and treatment. An electronic search in MEDLINE and abstracts presented at national and international GI meetings was performed, looking for information published in the past 50 years including animal studies, cohort studies, case-control studies, and series of cases and case reports, using the key words post-infectious enteritis, post-dysenteric or post-infectious irritable bowel syndrome (PI-IBS), and post-infectious colitis. Fifty one papers were included. These studies were classified according to pathophysiologic mechanisms, infectious agents involved, animal or human studies, and treatment. Current evidence shows a strong association between colonic infection and inflammation with development of IBS. Approximately 25% of patients with IBS have a history of infectious enteritis. Microbial agents related with PI-IBS include bacteria (Campylobacter, Salmonella) and parasites (Trichinella spiralis). Increased number of enteroendocrine cells, CD3 lymphocytes and mast cells within the colonic muscle wall, release of pro-inflammatory substances, and increased number of inflammatory cells with intestinal nervous endings are the most common histopathologic findings. Patients developing PI-IBS have a higher frequency of psychological disorders and stressful events prior to the gastroenteritis episode. Therapeutic interventions with steroids, COX-2 inhibitors, antibiotics and probiotics require further investigation.


Efficient removal of cesium ions using Prussian blue loaded on magnetic porous biochar synthesized by one-step calcination.
Prussian blue (PB) is widely used for the selective removal of radioactive cesium ions (Cs+) from aqueous solutions. Due to its small size and easy dispersion in water, PB requires a carrier that is both inexpensive and easily separable. Magnetic porous biochar (MPBC) was formed by activating starch with FeCl3 through a one-step calcination method. MPBC can be used as a carrier for Prussian blue, which is easily separated from the solution. This composite material (PB/MPBC) has a rich pore structure and maintains effective surface area, which can facilitate the penetration of Cs+ into the adsorbent. Besides, PB/MPBC exhibits high selectivity and good adsorption capacity achieving a large removal capacity of 101.43 mg/g. Thus, this study provides a novel approach for preparing composites with efficient removal of Cs+.


Thermally reversible VPBA-NIPAM copolymer gels for nucleotide adsorption.
A thermosensitive gel matrix was prepared by free radical copolymerization of N-isopropylacrylamide (NIPAM) with a boronic acid-carrying monomer (i.e. 4-vinylphenylboronic acid, VPBA). The synthesis of the gel was performed at 70 degrees C in an alcohol-water mixture, using azobisisobutyronitrile and methylenebisacrylamide as the initiator and the crosslinker, respectively. To produce thermosensitive gels with a higher diol-binding affinity, an amino-containing comonomer, N-[3-(dimethylamino)propyl]methacrylamide (DMAPM) was included in the gel formation recipe. Thermally reversible VPBA-NIPAM and VPBA-DMAPM-NIPAM gels with different swelling properties were obtained by changing the feed concentrations of VPBA and DMAPM. To test the usability of the produced gels as sorbents in nucleotide adsorption, beta-nicotinamide adenine dinucleotide (beta-NAD) was selected as a model biomolecule. Then the adsorption isotherm for beta-NAD was obtained at +4 degrees C in HEPES buffer medium with a pH of 8.5. The support material was in a highly swollen form under these conditions, due to its thermosensitive character. This property was then used to enhance beta-NAD adsorption onto the gel matrix. Equilibrium adsorption capacities up to 70 mg beta-NAD/g dry gel could be achieved with the thermosensitive support prepared with the 12.9 mol% VPBA feed. The gels produced with higher VPBA and DMAPM feed concentrations exhibited higher equilibrium adsorption capacities for beta-NAD.


Molecular identification of potentially probiotic lactobacilli.
The rRNA-targeted oligonucleotide probes are useful for the identification of Lactobacillus acidophilus, L. gasseri, L. johnsonii, L. crispatus, and L. amylovorus. However, the oligonucleotide probe designed for L. helveticus hybridized with nucleic acids of type strains of L. gallinarum and L. helveticus. Hence, the similarity among the 73 strains of lactobacilli was evaluated on the basis of their randomly amplified polymorphic DNA (RAPD) profiles derived from five single-primer reactions. These strains were grouped into seven clusters at a similarity level of 30%, which corresponded to six separate species of the L. acidophilus complex (L. johnsonii, L. gallinarum, L. amylovorus, L. crispatus, L. acidophilus, and L. gasseri, respectively) and L. helveticus. For the first time, strains of L. gallinarum were characterized by RAPD and PFGE analyses. The genome length in that species was estimated to be near 1.45 Mb with the summation of ApaI fragments, and near 1.95 Mb with the summation of SmaI fragments.


Endocrine and nutritional regulation of fetal adipose tissue development.
In the fetus, adipose tIssue comprises both brown and white adipocytes for which brown fat is characterised as possessing the unique uncoupling protein (UCP)1. The dual characteristics of fetal fat reflect its critical role at birth in providing lipid that is mobilised rapidly following activation of UCP1 upon cold exposure to the extra-uterine environment. A key stage in the maturation of fetal fat is the gradual rise in the abundance of UCP1. For species with a mature hypothalamic-pituitary axis at birth there is a gradual increase in the amount and activity of UCP1 during late gestation, in conjunction with an increase in the plasma concentrations of catecholamines, thyroid hormones, cortisol, leptin and prolactin. These may act individually, or in combination, to promote UCP1 expression and, following the post-partum surge in each hormone, UCP1 abundance attains maximal amounts. Adipose tIssue grows in the fetus at a much lower rate than in the postnatal period. However, its growth is under marked nutritional constraints and, in contrast to many other fetal organs that are unaffected by nutritional manipulation, fat mass can be significantly altered by changes in maternal and, therefore, fetal nutrition. Fat deposition in the fetus is enhanced during late gestation following a previous period of nutrient restriction up to mid gestation. This is accompanied by increased mRNA abundance for the receptors of IGF-I and IGF-II. In contrast, increasing maternal nutrition in late gestation results in less adipose tIssue deposition but enhanced UCP1 abundance. The pronounced nutritional sensitivity of fetal adipose tIssue to both increased and decreased maternal nutrition may explain why the consequences of an adverse nutritional environment persist into later life.


Toward functional screening of cardioactive and cardiotoxic drugs with zebrafish in vivo using pseudodynamic three-dimensional imaging.
Given the high mortality in patients with cardiovascular diseases and the life-threatening consequences of drugs with unforeseen adverse effects on hearts, a critical evaluation of the pharmacological response of cardiovascular function on model animals is important especially in the early stages of drug development. We report a proof-of-principle study to demonstrate the utility of zebrafish as an analytical platform to predict the cardiac response of new drugs or chemicals on human beings. With pseudodynamic 3D imaging, we derive individual parameters that are central to the cardiac function of zebrafish, including the ventricular stroke volume, ejection fraction, cardiac output, heart rate, diastolic filling function, and ventricular mass. We evaluate both inotropic and chronotropic responses of the heart of zebrafish treated with drugs that are commonly prescribed and possess varied known cardiac activities. We reveal deranged cardiac function of a zebrafish model of cardiomyopathy induced with a cardiotoxic drug. The cardiac function of zebrafish exhibits a pharmacological response similar to that of human beings. We compare also cardiac parameters obtained in this work with those derived with conventional 2D approximation and show that the latter tends to overestimate the cardiac parameters and produces results of greater variation. In view of the growing interest of using zebrafish in both fundamental and translational biomedical research, we envisage that our approach should benefit not only contemporary pharmaceutical development but also exploratory research such as gene, stem cell, or regenerative therapies targeting congenital or acquired heart diseases.


Analgesic efficacy and safety of oxycodone in combination with naloxone as prolonged release tablets in patients with moderate to severe chronic pain.
This randomized, double-blind, placebo- and active-controlled, parallel-group study was designed to demonstrate the superiority of oxycodone in combination with naloxone in a prolonged release (PR) formulation over placebo with respect to analgesic efficacy. The active control group was included for sensitivity and safety analyses, and furthermore to compare the analgesic efficacy and bowel function of oxycodone PR/naloxone PR with oxycodone PR alone. The analgesic efficacy was measured as the time from the initial dose of study medication to multiple pain events (ie, inadequate analgesia) in patients with moderate to severe chronic low back pain. The full analysis population consisted of 463 patients. The times to recurrent pain events were significantly longer in the oxycodone PR/naloxone PR group compared with placebo (P < .0001-.0003); oxycodone PR/naloxone PR reduced the risk of pain events by 42% (P < .0001; full analysis population). The appearance of pain events was comparable for oxycodone PR/naloxone PR versus oxycodone PR, confirming that the addition of naloxone PR to oxycodone PR in a combination tablet did not negatively affect analgesic efficacy of the opioid. Furthermore, oxycodone PR/naloxone PR offers benefits in terms of an improvement in bowel function. In a therapeutic area of great unmet need, therefore, the combination tablet of oxycodone PR/naloxone PR offers patients effective analgesia while improving opioid-induced bowel dysfunction. Taken together with the observation that the safety profile of oxycodone PR/naloxone PR is consistent with that expected from other opioid analgesics except opioid-induced constipation, these findings indicate that the addition of naloxone to oxycodone in a PR combination tablet offers improved tolerability. Oxycodone PR/naloxone PR is therefore a promising new treatment approach for the management of chronic pain. This study evaluated the analgesic efficacy and safety of the combination of oxycodone PR/naloxone PR in chronic nonmalignant pain. Opioids are often reduced in dosage or even discontinued as a result of impaired bowel function, leading to insufficient pain treatment. Not only does oxycodone PR/naloxone PR demonstrate analgesic efficacy comparable with oxycodone PR, but it also improves opioid-induced bowel dysfunction, and may therefore improve the acceptability of long-term opioid treatment for chronic pain.


Boundary-Weighted Domain Adaptive Neural Network for Prostate MR Image Segmentation.
Accurate segmentation of the prostate from magnetic resonance (MR) images provides useful information for prostate cancer diagnosis and treatment. However, automated prostate segmentation from 3D MR images faces several challenges. The lack of clear edge between the prostate and other anatomical structures makes it challenging to accurately extract the boundaries. The complex background texture and large variation in size, shape and intensity distribution of the prostate itself make segmentation even further complicated. Recently, as deep learning, especially convolutional neural networks (CNNs), emerging as the best performed methods for medical image segmentation, the difficulty in obtaining large number of annotated medical images for training CNNs has become much more pronounced than ever. Since large-scale dataset is one of the critical components for the success of deep learning, lack of sufficient training data makes it difficult to fully train complex CNNs. To tackle the above challenges, in this paper, we propose a boundary-weighted domain adaptive neural network (BOWDA-Net). To make the network more sensitive to the boundaries during segmentation, a boundary-weighted segmentation loss is proposed. Furthermore, an advanced boundary-weighted transfer leaning approach is introduced to address the problem of small medical imaging datasets. We evaluate our proposed model on three different MR prostate datasets. The experimental results demonstrate that the proposed model is more sensitive to object boundaries and outperformed other state-of-the-art methods.


Interleukin-10 and Interferon Gamma Gene Polymorphisms and Hepatitis C Virus-Related Liver Cirrhosis Risk.
The aim of the study was to evaluate the association between the gene polymorphisms in interleukin-10 (IL-10) and interferon gamma (IFN-γ) genes with susceptibility and severity of hepatitis C virus (HCV) infection among Egyptian patients. Interleukin-10 -592 A/C, -1082 G/A and IFN-γ +874 T/A genotypes were determined in 100 chronic HCV patients and 50 healthy controls using restriction fragment length polymorphism (RFLP) and the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) respectively. IL-10 -592 A/C polymorphism genotyping revealed that the frequency of CC genotype was significantly higher in chronic HCV patients than in controls (58% versus 30%, P < 0.05). Regarding IL-10 -1082 G/A polymorphism genotyping, a higher frequency of GG genotype was found in chronic HCV patients compared to controls (31% versus 10%, P < 0.05). IFN-γ +874 T/A genotyping showed that TT genotype was significantly higher in chronic HCV participants than controls (31% versus 18%, P < 0.05), while a higher frequency of T allele was found in cirrhotic patients compared to noncirrhotic patients (P < 0.05). Our observations suggested that IL-10 -592 A/C, -1082 G/A, and IFN-γ +874 T/A polymorphisms had a strong association with susceptibility to HCV infection. However, no significant association was observed between the cytokines (IL-10 and IFN-γ) genotypes profile and HCV-liver cirrhosis risk in the studied population, except for the high frequency of IFN-γ +874 T allele in cirrhotic patients.


In vitro interaction of aminobenzenesulfonic acids and their N-acetylated derivatives with rat liver glutathione S-transferase.
The in vitro interaction of the three aminobenzenesulfonic acids sulfanilic-, metanilic- and orthanilic acid, and their N-acetylated derivatives with rat liver glutathione S-transferase (GST) was studied. All inhibited the enzymatic conjugation of 1-chloro-2, 4-dinitro-benzene with glutathione. The sulfonate group and the benzene ring are molecular parts required for this inhibition. Each of the GST isoenzymes (AA, A, B, C, E and M) was inhibited, albeit at different degrees. Kinetic studies always revealed a mixed type function inhibition, towards glutathione and 1-chloro-2,4-dinitrobenzene as well. Conjugates of the six investigated compounds with glutathione were not formed. The results indicate that the aminobenzenesulfonic acids and their N-acetylates interact with GST by direct binding to this protein. It is suggested that the binding to GST of these compounds, from which several are metabolites of colors used in human food, could have a protective function against these dyes.


Effect of Personalized Risk-Reduction Strategies on Cognition and Dementia Risk Profile Among Older Adults: The SMARRT Randomized Clinical Trial.
Modifiable risk factors are hypothesized to account for 30% to 40% of dementia; yet, few trials have demonstrated that risk-reduction interventions, especially multidomain, are efficacious. To determine if a personalized, multidomain risk reduction intervention improves cognition and dementia risk profile among older adults. The Systematic Multi-Domain Alzheimer Risk Reduction Trial was a randomized clinical trial with a 2-year personalized, risk-reduction intervention. A total of 172 adults at elevated risk for dementia (age 70-89 years and with ≥2 of 8 targeted risk factors) were recruited from primary care clinics associated with Kaiser Permanente Washington. Data were collected from August 2018 to August 2022 and analyzed from October 2022 to September 2023. Participants were randomly assigned to the intervention (personalized risk-reduction goals with health coaching and nurse visits) or to a health education control. The primary outcome was change in a composite modified Neuropsychological Test Battery; preplanned secondary outcomes were change in risk factors and quality of life (QOL). Outcomes were assessed at baseline and 6, 12, 18, and 24 months. Linear mixed models were used to compare, by intention to treat, average treatment effects (ATEs) from baseline over follow-up. The intervention and outcomes were initially in person but then, due to onset of the COVID-19 pandemic, were remote. The 172 total participants had a mean (SD) age of 75.7 (4.8) years, and 108 (62.8%) were women. After 2 years, compared with the 90 participants in the control group, the 82 participants assigned to intervention demonstrated larger improvements in the composite cognitive score (ATE of SD, 0.14; 95% CI, 0.03-0.25; P = .02; a 74% improvement compared with the change in the control group), better composite risk factor score (ATE of SD, 0.11; 95% CI, 0.01-0.20; P = .03), and improved QOL (ATE, 0.81 points; 95% CI, -0.21 to 1.84; P = .12). There were no between-group differences in serious adverse events (24 in the intervention group and 23 in the control group; P = .59), but the intervention group had greater treatment-related adverse events such as musculoskeletal pain (14 in the intervention group vs 0 in the control group; P < .001). In this randomized clinical trial, a 2-year, personalized, multidomain intervention led to modest improvements in cognition, dementia risk factors, and QOL. Modifiable risk-reduction strategies should be considered for older adults at risk for dementia. ClinicalTrials.gov Identifier: NCT03683394.


Recombinant keratinocyte growth factor 1 in tobacco potentially promotes wound healing in diabetic rats.
Keratinocyte growth factor 1 (KGF1) is a growth factor that promotes epidermal cell proliferation, migration, differentiation, and wound repair. It is expressed at low levels in a form of inclusion body in E. coli. In order to increase its expression and activity, we produced tobacco plants expressing KGF1 via Agrobacterium-mediated transformation using a potato virus X (PVX)-based vector (pgR107). The vector contained the sequence encoding the KGF1 gene fused with a green florescence protein. The recombinant plasmid was introduced into leaf cells of Nicotiana benthamiana (a wild Australian tobacco) via Agrobacterium-mediated agroinfiltration. As determined by fluorescence and Western blot of leaf extracts, the KGF1 gene was correctly translated into the tobacco plants. The recombinant KGF1 was purified from plant tissues by heparin affinity chromatography, and cell proliferation in NIH/3T3 cells was stimulated by the purified KGF1. The purified KGF1 was also applied to the wounds of type-II diabetic rats. KGF1 had accumulated to levels as high as 530 μ g/g fresh weight in the leaves of agroinfected plants. We show that plant-derived KGF1 can promote the proliferation of NIH/3T3 cells and have significant effects on the type-II diabetic rat. The present findings indicated that KGF1 from tobacco maintains its biological activity, implying prospective industrial production in a plant bioreactor.


[Guideline 'Resuscitation', revision 2002].
In 2002, the Netherlands Resuscitation Council published a translation of guidelines on Basic Life Support, use of the Automated External Defibrillator, and Advanced Life Support for adults and children, as laid down in 2000 by the International Liaison Committee on Resuscitation. The Dutch situation has altered in that there has been a change from the Netherlands-specific 'CAB' scheme to the internationally accepted 'ABC' scheme. This means that upon encountering a patient, the airways should be checked first (A), then artificial ventilation should be administered twice (B), after which the circulation should be checked in the third place (C) and chest compression should be initiated if necessary. In the Dutch guideline 'assessment of signs of circulation' for the identification of circulatory arrest by lay people was not accepted, but the pulse check at the carotid artery has been maintained. Medical professionals should also assess possible circulatory arrest in this way. Regardless of the number of people attending the patient, the ratio of chest compressions to artificial ventilation in adults is now 15:2 rather than the previously-advocated ratio of 5:1. This ratio is more effective in building up the blood pressure during the chest compressions. In terms of medication, the most important modification is the addition of amiodarone for persistent ventricular fibrillation.


Brain-Derived Neurotrophic Factor: A Key Molecule for Memory in the Healthy and the Pathological Brain.
Brain Derived Neurotrophic Factor (BDNF) is a key molecule involved in plastic changes related to learning and memory. The expression of BDNF is highly regulated, and can lead to great variability in BDNF levels in healthy subjects. Changes in BDNF expression are associated with both normal and pathological aging and also psychiatric disease, in particular in structures important for memory processes such as the hippocampus and parahippocampal areas. Some interventions like exercise or antidepressant administration enhance the expression of BDNF in normal and pathological conditions. In this review, we will describe studies from rodents and humans to bring together research on how BDNF expression is regulated, how this expression changes in the pathological brain and also exciting work on how interventions known to enhance this neurotrophin could have clinical relevance. We propose that, although BDNF may not be a valid biomarker for neurodegenerative/neuropsychiatric diseases because of its disregulation common to many pathological conditions, it could be thought of as a marker that specifically relates to the occurrence and/or progression of the mnemonic symptoms that are common to many pathological conditions.


Organic-inorganic hybrids for CO2 sensing, separation and conversion.
Motivated by the air pollution that skyrocketed in numerous regions around the world, great effort was placed on discovering new classes of materials that separate, sense or convert CO2 in order to minimise impact on human health. However, separation, sensing and conversion are not only closely intertwined due to the ultimate goal of improving human well-being, but also because of similarities in material prerequisites -e.g. affinity to CO2. Partly inspired by the unrivalled performance of complex natural materials, manifold inorganic-organic hybrids were developed. One of the most important characteristics of hybrids is their design flexibility, which results from the combination of individual constituents with specific functionality. In this review, we discuss commonly used organic, inorganic, and inherently hybrid building blocks for applications in separation, sensing and catalytic conversion and highlight benefits like durability, activity, low-cost and large scale fabrication. Moreover, we address obstacles and potential future developments of hybrid materials. This review should inspire young researchers in chemistry, physics and engineering to identify and overcome interdisciplinary research challenges by performing academic research but also - based on the ever-stricter emission regulations like carbon taxes - through exchanges between industry and science.


Purification and characterization of an outer membrane protein adhesin from Haemophilus parainfluenzae HP-28.
Outer membranes were isolated from Haemophilus parainfluenzae HP-28 by a mild extraction method followed by Sephadex G-150 gel filtration chromatography. The first peak (pool 1) recovered contained an activity which inhibited adherence of HP-28 cells to saliva-coated spheroidal hydroxyapatite. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of pool 1 revealed a dominant protein band of 34 kDa. The SDS-PAGE-purified 34-kDa protein was excised from the gel and used for antibody preparation in rabbits. The antiserum produced was analyzed by immunoblot and was shown to be monospecific for the 34-kDa protein. Anti-34-kDa protein antibody was purified from the rabbit antiserum by protein A-Sepharose 6MB affinity chromatography. This antibody was then cross-linked to protein A-Sepharose 6MB to construct a second affinity column. The 34-kDa proteins were purified from outer membranes by this affinity chromatography. The 34-kDa protein was homogeneous, as confirmed by SDS-PAGE, isoelectric focusing, and reverse-phase chromatography analyses. Fab and Fc fragments of the purified anti-34-kDa protein antibodies were prepared by papain digestion, followed by carboxymethyl cellulose chromatography. Fab fragments from the anti-34-kDa protein antibody and the affinity-purified 34-kDa protein both showed significant inhibition of parent H. parainfluenzae HP-28 cell adherence to experimental salivary pellicle and to Streptococcus sanguis SA-1.


Does hereditary nonpolyposis colorectal cancer explain the observed excess risk of colorectal cancer associated with family history?
Several studies have found an increased risk of colorectal cancer associated with a family history of colorectal cancer. Some studies, although not all, have also suggested that family history of colorectal cancer may be a risk factor for adenomatous polyps. Hereditary nonpolyposis colorectal cancer is a known genetic syndrome predisposing to colorectal cancer. The hypothesis of this paper is that the preponderance of the genetic or familial risk for colorectal cancer in the United States is mediated by hereditary nonpolyposis colorectal cancer. To test this hypothesis, I have incorporated what is known about hereditary nonpolyposis colorectal cancer into a genetic model that generates probabilities of family clustering of colorectal cancer. Using this model, which assumes that all familial risk for colorectal cancer is due to hereditary nonpolyposis colorectal cancer, the expected relative risks for colorectal cancer (and adenomas) associated with given types of family histories were calculated. The relative risks predicted by the model fairly closely matched the results found in the literature, especially those reported from a large cohort study. As observed in several studies, the model predicts that relative risks decrease sharply with age. In contrast to the elevated risk for colorectal cancer, the model predicts no elevated risk for adenomas associated with family history of colorectal cancer.


Synthesis of Novel Benzazole Derivatives and Evaluation of Their Antidepressant-Like Activities with Possible Underlying Mechanisms.
Novel benzazole derivative compounds 4a⁻4h were obtained by the reaction of corresponding 2-(benzazol-2-ylthio)acetohydrazide and appropriate 4-substituted benzaldehydes. The chemical structures of the synthesized compounds were elucidated by FT-IR, ¹H-NMR, 13C-NMR and LCMS spectroscopic methods. Antidepressant-like effects of the compounds were evaluated by tail suspension test (TST) and modified forced swimming tests (MFST). Moreover, locomotor activities of the animals were assessed by an activity cage apparatus. In the series, compounds 4a, 4b, 4e and 4f (at 50 mg/kg) significantly decreased the immobility time of mice in both of the TST and MFST. The same compounds prolonged the swimming time of animals in MFST without any change in the climbing duration. These data indicated that compounds 4a, 4b, 4e and 4f possess significant antidepressant-like activities. Moreover, pre-treatments with p-chloro-phenylalanine methyl ester (an inhibitor of serotonin synthesis), NAN-190 (a 5-HT1A antagonist), ketanserin (a 5-HT2A/2C antagonist), and ondansetron (a 5-HT₃ antagonist) reversed the exhibited pharmacological effects. Results of the mechanistic studies suggested the involvement of serotonergic system and contributions of 5-HT1A, 5-HT2A/2C and 5-HT₃ receptors to the antidepressant-like effects of compounds 4a, 4b, 4e and 4f. Furthermore, unchanged locomotor activity of mice following the administrations of these four derivatives confirmed that the presented antidepressant-like effects are specific.


Recombination signal sequence binding protein Jkappa is constitutively bound to the NF-kappaB site of the interleukin-6 promoter and acts as a negative regulatory factor.
Analysis by electrophoretic mobility shift assays (EMSA) of the different proteins associated with the kappaB sequence of the interleukin-6 (IL-6) promoter (IL6-kappaB) allowed us to detect a specific complex formed with the recombination signal sequence binding protein Jkappa (RBP-Jkappa). Single-base exchanges within the oligonucleotide sequence defined the critical base pairs involved in the interaction between RBP-Jkappa and the IL6-kappaB motif. Binding analysis suggests that the amount of RBP-Jkappa protein present in the nucleus is severalfold higher than the total amount of inducible NF-kappaB complexes but that the latter bind DNA with a 10-fold-higher affinity. A reporter gene study was performed to determine the functional implication of this binding; we found that the constitutive occupancy of the IL6-kappaB site by the RBP-Jkappa protein was responsible for the low basal levels of IL-6 promoter activity in L929sA fibrosarcoma cells and that RBP-Jkappa partially blocked access of NF-kappaB complexes to the IL-6 promoter. We propose that such a mechanism could be involved in the constitutive repression of the IL-6 gene under normal physiological conditions.


Interaction of mouse mammary epithelial cells with collagen substrata: regulation of casein gene expression and secretion.
Mouse mammary epithelial cells (MMEC) secrete certain milk proteins only when cultured on floating collagen gels. We demonstrate here that modulation of milk proteins by substrata is manifested at several regulatory levels; (i) Cells cultured on floating collagen gels have 3- to 10-fold more casein mRNA than cells cultured on plastic or attached collagen gels. (ii) Cells on the latter two "flat" substrata, nevertheless, synthesize a significant amount of caseins, indicating that the remaining mRNA is functional. (iii) Cells on all substrata are inducible for casein mRNA and casein proteins by prolactin, but the extent of induction is greater on collagen than that on plastic--i.e., the substratum confers an altered degree of inducibility. (iv) Cells on all substrata synthesize casein proteins at rates proportional to the amount of casein mRNA, but the newly synthesized caseins in cells on plastic are degraded intracellularly, whereas those synthesized by cells on floating gels are secreted into the medium. (v) Cells on all substrata examined lose virtually all mRNA for whey acidic protein despite the fact that this mRNA is abundant in the mammary gland itself; we conclude that additional, as-yet-unknown, factors are necessary for synthesis and secretion of whey acidic protein in culture.


A non-redundant role for OX40 in the competitive fitness of Treg in response to IL-2.
OX40 stimulation is known to enhance activation of effector T cells and to inhibit induction and suppressive function of Treg. Here we uncovered a novel role of OX40 in sustaining Treg competitive fitness in vivo, during repopulation of lymphopenic hosts and reconstitution of BM chimeras. Defective expansion of OX40-null Treg diminished their ability to suppress inflammation in a model of lymphopenia-driven colitis. OX40-mediated promotion of Treg fitness spanned beyond lymphopenic environments, as endogenous Treg in OX40-null mice showed decreased accumulation during thymic development, enhanced susceptibility to antibody-mediated depletion and defective turnover following thymectomy. In vitro, OX40-deficient Treg were found to be intrinsically hyporesponsive to IL-2, in terms of Stat5 phosphorylation and proliferation, according to elevated SOCS1 content and reduced miR155 expression. Therefore, OX40 is a key factor in shaping Treg sensitivity to IL-2 and promoting their proliferation and survival, toward accurate immune regulation.


Perceptions of Gender and Race Equality in Leadership and Advancement Among Military Family Physicians.
There is increasing interest in assessing gender and race-based disparities in academic medicine and healthcare leadership in civilian medicine and the U.S. Military Health System. Approximately 15% of U.S. active duty service members are women, and racial minorities are 30% of the total active duty force. This study evaluates the following factors among uniformed services family physicians: gender and race representation in attaining early career leadership positions during training and 2 years postresidency; perceptions regarding leadership opportunities and career advancement. Registered attendees (n = 300) of the 2016 Uniformed Services Academy of Family Physicians Annual Meeting were given a voluntary and anonymous online questionnaire. The main outcomes measured were early leadership assignments and perceptions about command/leadership support, gender roles in leadership assignment, confidence to achieve leadership goals, and being passed over for leadership positions. Sixty-eight percent of registered attendees completed the study questionnaire. Statistically significant results, adjusting for service, grade, race, and gender, were that non-Caucasian family physicians were less likely to be chief residents (odds ratio 0.23, 95% CI 0.01-1.00) and less likely to have leadership positions within 2 years postresidency (odds ratio 0.30, 95% CI 0.10-0.91). Female family physicians were more likely to agree that gender has a role in assigning leadership positions (odds ratio 2.33, 95% CI 1.01-5.39). There were no differences in perceptions of command support for leadership; confidence in achieving desired leadership level; or in being passed over for leadership positions. This study provides important information about perceived gender and race equality among uniformed services family physicians. Key findings included that non-Caucasian military family physicians were less likely to attain junior leadership positions or be assigned to academic settings; and female respondents were more likely to agree that gender has a role in assignment of leadership positions. Evaluating composite personnel records of services' family physicians would provide invaluable information to complement this study.


Textbook Outcome: A Composite Measure for Quality of Elective Aneurysm Surgery.
To investigate a new composite quality measurement, which comprises a desirable outcome for elective aneurysm surgery, called "Textbook Outcome" (TO). Single-quality indicators in vascular surgery are often not distinctive and insufficiently reflect the quality of care. All patients undergoing elective abdominal aortic aneurysm repair, registered in the Dutch Surgical Aneurysm Audit between 2014 and 2015 were included. TO was defined as the percentage of patients who had abdominal aortic aneurysm-repair without intraoperative complications, postoperative surgical complications, reinterventions, prolonged hospital stay [endovascular aneurysm repair (EVAR) ≤4 d, open surgical repair (OSR) ≤10 d], readmissions, and postoperative mortality (≤30 d after surgery/at discharge). Case-mix adjusted TO rates were used to compare hospitals and to compare individual hospital results for different procedures. Five thousand one hundred seventy patients were included, of whom 4039 were treated with EVAR and 1131 with OSR. TO was achieved in 71% of EVAR and 53% of OSR. Important obstacles for achieving TO were a prolonged hospital stay, postoperative complications, and readmissions. Adjusted TO rates varied from 38% to 89% (EVAR) and from 0% to 97% (OSR) between individual hospitals. Hospitals with a high TO for OSR also had a high TO for EVAR; however, a high TO for EVAR did not implicate a high TO for OSR. TO generates additional information to evaluate the overall quality of the care of elective aneurysm surgery, which subsequently can be used by hospitals to improve the quality of their care.


Re-Thinking the World with Neutral Monism:Removing the Boundaries Between Mind, Matter, and Spacetime.
Herein we are not interested in merely using dynamical systems theory, graph theory, information theory, etc., to model the relationship between brain dynamics and networks, and various states and degrees of conscious processes. We are interested in the question of how phenomenal conscious experience and fundamental physics are most deeply related. Any attempt to mathematically and formally model conscious experience and its relationship to physics must begin with some metaphysical assumption in mind about the nature of conscious experience, the nature of matter and the nature of the relationship between them. These days the most prominent metaphysical fixed points are strong emergence or some variant of panpsychism. In this paper we will detail another distinct metaphysical starting point known as neutral monism. In particular, we will focus on a variant of the neutral monism of William James and Bertrand Russell. Rather than starting with physics as fundamental, as both strong emergence and panpsychism do in their own way, our goal is to suggest how one might derive fundamental physics from neutral monism. Thus, starting with two axioms grounded in our characterization of neutral monism, we will sketch out a derivation of and explanation for some key features of relativity and quantum mechanics that suggest a unity between those two theories that is generally unappreciated. Our mode of explanation throughout will be of the principle as opposed to constructive variety in something like Einstein's sense of those terms. We will argue throughout that a bias towards property dualism and a bias toward reductive dynamical and constructive explanation lead to the hard problem and the explanatory gap in consciousness studies, and lead to serious unresolved problems in fundamental physics, such as the measurement problem and the mystery of entanglement in quantum mechanics and lack of progress in producing an empirically well-grounded theory of quantum gravity. We hope to show that given our take on neutral monism and all that follows from it, the aforementioned problems can be satisfactorily resolved leaving us with a far more intuitive and commonsense model of the relationship between conscious experience and physics.


Expression of CD94/NKG2-A on human T lymphocytes is induced by IL-12: implications for adoptive immunotherapy.
NK cell receptors (NKRs) are expressed on a subset of human T cells, predominantly CD8(+), within which they can modulate TCR-mediated functions. In an attempt to identify the mechanisms leading to NKR expression, we analyzed the capacity of IL-12 to modulate the expression by T cells of the components of the CD94/NKG2-A inhibitory receptor, a member of the C-type lectin-like family of NKR. We show that IL-12 induces the expression of NKG2-A and/or CD94 by CD8(+) T cells in culture, and that this induction was mediated neither by IFN-gamma nor by IL-15. We also show, using the redirected killing assay, that IL-12-induced expression of both CD94 and NKG2-A led to the acquisition by T cells of a functional inhibitory receptor. Expression of the CD94/NKG2-A inhibitory receptor was also induced by IL-12 during T cell Ag stimulation so that in the presence of this cytokine a high proportion of melanoma-reactive CTL induced from PBL by melanoma peptide stimulation expressed this receptor. This study emphasizes the implication of IL-12 in the modulation of immune responses through NKR induction.


Alteration of the baroreceptor reflex by an effect of propranolol on the isolated carotid sinus.
The present experiments were designed to measure and characterize direct hemodynamic effects of propranolol on vascularly isolated carotid sinuses. dl-Propranolol, when restricted to the isolated carotid sinuses, inhibited in a dose-dependent manner the reflex increases in heart rate and mean arterial pressure during carotid sinus hypotension. When perfused through isolated sinuses at a concentration of 10 micrograms/ml, the drug totally abolished reflex changes to carotid sinus hypotension. Perfusion of the sinuses with d-propranolol or procaine at the same doses also totally inhibited the response. On the other hand, perfusion of the sinuses with sotalol, an adrenergic blocker without membrane stabilizing effects, did not alter resting levels of arterial pressure or heart rate and did not affect reflex changes during sinus hypotension. These results suggest that propranolol at high doses may affect baroreceptor afferents and inhibit the baroreceptor reflex through membrane-stabilizing and local anesthetic properties rather than through hypothesized beta receptors. It seems unlikely that these pathways contribute to the antihypertensive actions of the drug.


Retinoic acid down-regulates Tbx1 expression and induces abnormal differentiation of tongue muscles in fetal mice.
Excess retinoic acid (RA) during pregnancy can cause various developmental anomalies in both humans and rodents. We investigated the mechanisms underlying the aberrant differentiation of tongue muscles in fetal mice exposed to exogenous RA in utero. RA-degrading enzymes (Cyp26a1 and Cyp26b1) were expressed at early stages of normal tongue development, but exogenous RA perturbed their expression in the fetal tongue. RA is normally distributed in the developing tongue muscles but its localization was disrupted by exogenous RA. After RA treatment, myogenic determination factors were reduced and the differentiation was significantly suppressed in tongue muscles. Tbx1, a candidate gene of DiGeorge syndrome, was down-regulated in the fetal tongue in response to excess RA. Moreover, Tbx1 as well as myogenic determination factors were not observed in tongue muscle primordia of Cyp26b1-/- fetuses. Our study suggests that RA signaling may play an essential role in tongue muscle differentiation via the regulation of Tbx1.


Urinary cystatin C and NGAL as early biomarkers for assessment of renal ischemia-reperfusion injury: a serum marker to replace creatinine?
To assess application of cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) as biomarkers for renal ischemic injury. We also evaluated the use of allopurinol as a renoprotective agent. A second goal was to assess cystatin C as a biomarker in patients undergoing partial nephrectomy. Using 58 Sprague-Dawley rats, we evaluated urinary cystatin C (n=26) and NGAL (n=32) as a biomarker for renal ischemia injury. Half of the rats were pretreated with allopurinol; the other cohort served as a control. The right renal hilum was ligated in all rats, thereby creating a solitary kidney model. After a 30-minute stabilization period, the left hilum was clamped for time periods of 15, 30, and 60 minutes. Urinary levels of cystatin C and NGAL were then measured at the following time points: Preclamp (after the 30-minute stabilization period) and postclamp (30, 45, and 60 minute periods after unclamping). For our clinical subjects, serum cystatin C levels (n=17) were obtained preoperatively, at the induction of anesthesia before robot-assisted partial nephrectomy, immediately postoperatively, and on postoperative days 1 and 2. Three of these patients had their tumors excised off clamp and served as controls. We then estimated glomerular filtration rate by using the Creatinine-Cystatin C Equation. Urinary levels of cystatin C and NGAL increased after renal clamping. The 30-minute period of ischemia demonstrated the greatest increase of these biomarkers. Allopurinol did appear to serve a renoprotective function in those animals undergoing 30-minute clamp times. In our clinical patients, the serum cystatin C levels did increase at each postoperative time point, but remained nonelevated in the control group. Cystatin C and NGAL both appear to be useful biomarkers of renal injury. Studies with larger numbers are needed, however. Also, allopurinol does exhibit renoprotective effects against ischemic injury.


Proteolytic enzyme-treated seaweed co-product (Ulva laetevirens) inclusion in corn-soybean and European broiler diets to improve digestibility, health, and performance.
The impact of addition of an Ulva laetevirens (previously Ulva rigida) co-product treated with a broad-spectrum endo-protease when added to a standard corn-soy (S) based diet and a diet based on European protein sources (EU) on performance, in vivo digestibility and multiple gastrointestinal characteristics was investigated in broilers. In total, 624 Ross 308 one-day-old male broilers were fed one of 6 experimental diets (8 replicates) consisting of a basal diet (S or EU), or a basal diet including the U. laetevirens co-product (U) treated without (U-) or with (U+) a proteolytic enzyme. Starter diets contained 0 (wk 1) and 2.5 (wk 2), and the grower diets (wk 3 and 4) 5% seaweed co-product. In the last 2 wk, birds fed the S vs. EU grower diets showed a higher BW, BWG, and FI, as well as a lower FCR (-0.05 g/g) in wk 3 (P < 0.05). Heavier gizzards (+13%; P < 0.001) and heavier gizzard contents (+92%; P < 0.001) were observed in birds fed the EU vs. S diets, as well as longer villi (+8%; P = 0.010). U diets had a higher water holding capacity than the basal diets (+19%). In wk 4, U inclusion resulted in increased FCR (+0.06 g/g; P < 0.001), water intake (+7%; P < 0.001), and duodenal cross section (+5%; P = 0.033). Enzyme treatment did not affect digestibility of any nutrients, except for ash which was increased in birds fed U+ vs. U- diets (+60%; P < 0.001). U in S diets led to higher, and U in EU diets led to lower apparent pre-cecal digestibility of all nutrients (P < 0.001 for all nutrients). Although for both diet types performance was decreased, dietary U. laetevirens inclusion had different effects when added to a standard corn-soy diet and a diet based on European protein sources. No obvious health effects were observed, leading to the conclusion of the absence of performance of health promoting bioactive components in the U. laetevirens co-product, or of diminishing of these effects due to the proteolytic enzyme treatment.


A Road Map to Commercialization of Cartilage Therapy in the United States of America.
Despite numerous efforts in cartilage regeneration, few products see the light of clinical translation as the commercialization process is opaque, financially demanding, and requires collaboration with people of varied skill sets. The aim of this review is to introduce, to an academic audience, the different paradigms involved in the commercialization of cartilage regeneration technology, elucidate the different hurdles associated with the use of cells and materials in developing new technologies, discuss potential commercialization strategies, and inform the reader about the current trends observed in both the clinical and laboratory setting for establishing clinical trials. Although there are review articles on articular cartilage tissue engineering, independent reports provided by the Food and Drug Administration, and separate review articles on animal models, this is the first review that encompasses all of these facets and is presented in a format favorable to the academic investigator interested in clinical translation from bench to bedside.


High-dose BCNU with autologous bone marrow rescue for recurrent glioblastoma multiforme.
Eleven patients with recurrent malignant glioma were treated with single high doses of BCNU ranging from 600 to 1400 mg/sq m. To prevent the characteristic late myelosuppression observed after conventional doses of BCNU, autologous bone marrow harvested just before drug treatment was infused 24 to 36 hours after therapy. Higher doses of BCNU causes earlier and more profound myelosuppression; one patient died on pancytopenia, breakdown of the gut epithelium, and Clostridium septicemia 10 days after receiving 1400 mg/sq m of BCNU. All patients experienced transient emesis; four developed transient elevation of hepatic enzymes, two reversible interstitial pulmonary infiltrates, and two who received 1400 mg/sq m BCNU suffered irreversible cortical damage. Eight patients receiving 600 to 1200 mg/sq m demonstrated reconstitution of polymorphonuclear leukocytes an platelets within at least 30 days after treatment. With a follow-up time of up to 19 months, four patients improved, three stabilized, and three deteriorated and died. The median survival time was 7 months. Computerized tomography performed on patients receiving constant corticosteroids showed diminished contrast enhancement and mass effect in eight patients. High-dose BCNU at doses up to 1200 mg/sq m with marrow rescue is a feasible approach to the treatment of patients with glioblastoma.


Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex.
Disruption of human neural precursor proliferation can give rise to a small brain (microcephaly), and failure of neurons to migrate properly can lead to an abnormal arrest of cerebral cortical neurons in proliferative zones near the lateral ventricles (periventricular heterotopia). Here we show that an autosomal recessive condition characterized by microcephaly and periventricular heterotopia maps to chromosome 20 and is caused by mutations in the gene ADP-ribosylation factor guanine nucleotide-exchange factor-2 (ARFGEF2). By northern-blot analysis, we found that mouse Arfgef2 mRNA levels are highest during embryonic periods of ongoing neuronal proliferation and migration, and by in situ hybridization, we found that the mRNA is widely distributed throughout the embryonic central nervous system (CNS). ARFGEF2 encodes the large (>200 kDa) brefeldin A (BFA)-inhibited GEF2 protein (BIG2), which is required for vesicle and membrane trafficking from the trans-Golgi network (TGN). Inhibition of BIG2 by BFA, or by a dominant negative ARFGEF2 cDNA, decreases cell proliferation in vitro, suggesting a cell-autonomous regulation of neural expansion. Inhibition of BIG2 also disturbed the intracellular localization of such molecules as E-cadherin and beta-catenin by preventing their transport from the Golgi apparatus to the cell surface. Our findings show that vesicle trafficking is an important regulator of proliferation and migration during human cerebral cortical development.


Characterizing glucose, illumination, and nitrogen-deprivation phenotypes of Synechocystis PCC6803 with Raman spectroscopy.
Synechocystis sp. PCC6803 is a model cyanobacterium that has been studied widely and is considered for metabolic engineering applications. Here, Raman spectroscopy and Raman chemometrics (Rametrix™) were used to (i) study broad phenotypic changes in response to growth conditions, (ii) identify phenotypic changes associated with its circadian rhythm, and (iii) correlate individual Raman bands with biomolecules and verify these with more accepted analytical methods. Synechocystis cultures were grown under various conditions, exploring dependencies on light and/or external carbon and nitrogen sources. The Rametrix™ LITE Toolbox for MATLAB® was used to process Raman spectra and perform principal component analysis (PCA) and discriminant analysis of principal components (DAPC). The Rametrix™ PRO Toolbox was used to validate these models through leave-one-out routines that classified a Raman spectrum when growth conditions were withheld from the model. Performance was measured by classification accuracy, sensitivity, and specificity. Raman spectra were also subjected to statistical tests (ANOVA and pairwise comparisons) to identify statistically relevant changes in Synechocystis phenotypes. Finally, experimental methods, including widely used analytical and spectroscopic assays were used to quantify the levels of glycogen, fatty acids, amino acids, and chlorophyll a for correlations with Raman data. PCA and DAPC models produced distinct clustering of Raman spectra, representing multiple Synechocystis phenotypes, based on (i) growth in the presence of 5 mM glucose, (ii) illumination (dark, light/dark [12 h/12 h], and continuous light at 20 µE), (iii) nitrogen deprivation (0-100% NaNO3 of native BG-11 medium in continuous light), and (iv) throughout a 24 h light/dark (12 h/12 h) circadian rhythm growth cycle. Rametrix™ PRO was successful in identifying glucose-induced phenotypes with 95.3% accuracy, 93.4% sensitivity, and 96.9% specificity. Prediction accuracy was above random chance values for all other studies. Circadian rhythm analysis showed a return to the initial phenotype after 24 hours for cultures grown in light/dark (12 h/12 h) cycles; this did not occur for cultures grown in the dark. Finally, correlation coefficients (R > 0.7) were found for glycogen, all amino acids, and chlorophyll a when comparing specific Raman bands to other experimental results.


Robust ellipse detection based on hierarchical image pyramid and Hough transform.
In this research we propose a fast and robust ellipse detection algorithm based on a multipass Hough transform and an image pyramid data structure. The algorithm starts with an exhaustive search on a low-resolution image in the image pyramid using elliptical Hough transform. Then the image resolution is iteratively increased while the candidate ellipses with higher resolution are updated at each step until the original image resolution is reached. After removing the detected ellipses, the Hough transform is repeatedly applied in multiple passes to search for remaining ellipses, and terminates when no more ellipses are found. This approach significantly reduces the false positive error of ellipse detection as compared with the conventional randomized Hough transform method. The analysis shows that the computing complexity of this algorithm is Θ(n(5/2)), and thus the computation time and memory requirement are significantly reduced. The developed algorithm was tested with images containing various numbers of ellipses. The effects of noise-to-signal ratio combined with various ellipse sizes on the detection accuracy were analyzed and discussed. Experimental results revealed that the algorithm is robust to noise. The average detection accuracies were all above 90% for images with less than seven ellipses, and slightly decreased to about 80% for images with more ellipses. The average false positive error was less than 2%.


Light-Intensity Physical Activity and All-Cause Mortality.
Research demonstrates that moderate-to-vigorous physical activity (MVPA) is associated with a reduced risk of all-cause mortality. Few studies have examined the effects of light-intensity physical activity on mortality. Therefore, the purpose of this study was to examine the association between objectively measured light-intensity physical activity and all-cause mortality risk. Longitudinal. National Health and Nutrition Examination Survey 2003-2006 with follow-up through December 31, 2011. Five thousand five hundred seventy-five U.S. adults. Participants wore an accelerometer for at least 4 days and completed questionnaires to assess sociodemographics and chronic disease information, with blood samples taken to assess biological markers. Follow-up mortality status was assessed via death certificate data from the National Death Index. Cox proportional hazard model. After adjusting for accelerometer-determined MVPA, age, gender, race-ethnicity, cotinine, weight status, poverty level, C-reactive protein, and comorbid illness, for every 60-minute increase in accelerometer-determined light-intensity physical activity, participants had a 16% reduced hazard of all-cause mortality (hazard ratio = .84; 95% confidence interval: .78-.91; p < .001). In this national sample of U.S. adults, light-intensity physical activity was inversely associated with all-cause mortality risk, independent of age, MVPA, and other potential confounders. In addition to MVPA, promotion of light-intensity physical activity is warranted.


An Evaluation of the Role of Simulation Training for Teaching Surgical Skills in Sub-Saharan Africa.
An estimated 5 billion people worldwide lack access to any surgical care, whilst surgical conditions account for 11-30% of the global burden of disease. Maximizing the effectiveness of surgical training is imperative to improve access to safe and essential surgical care on a global scale. Innovative methods of surgical training have been used in sub-Saharan Africa to attempt to improve the efficiency of training healthcare workers in surgery. Simulation training may have an important role in up-scaling and improving the efficiency of surgical training and has been widely used in SSA. Though not intended to be a systematic review, the role of simulation for teaching surgical skills in Sub-Saharan Africa was reviewed to assess the evidence for use and outcomes. A systematic search strategy was used to retrieve relevant studies from electronic databases PubMed, Ovid, Medline for pertinent articles published until August 2016. Studies that reported the use of simulation-based training for surgery in Africa were included. In all, 19 articles were included. A variety of innovative surgical training methods using simulation techniques were identified. Few studies reported any outcome data. Compared to the volume of surgical training initiatives that are known to take place in SSA, there is very limited good quality published evidence for the use of simulation training in this context. Simulation training presents an excellent modality to enhance and improve both volume and access to high quality surgical skills training, alongside other learning domains. There is a desperate need to meticulously evaluate the appropriateness and effectiveness of simulation training in SSA, where simulation training could have a large potential beneficial impact. Training programs should attempt to assess and report learner outcomes.


Cone photoreceptor betagamma-transducin: posttranslational modification and interaction with phosducin.
To characterize the structure of cone betagamma-transducin (Tbeta3gamma8) and its interaction with phosducin (pdc). The Tgamma8 subunit of Tbeta3gamma8 was isolated by column chromatography for peptide mapping with mass spectrometry. Tbeta3gamma8 was compared with rod betagamma-transducin (Tbeta1gamma1) in terms of the electrophoretic mobility, pdc binding affinity, and the effects of phosphorylation and methylation, and then the correlation to the crystal structures and functional domains of Tbeta1gamma1 was determined. The mature Tgamma8 is a 65-amino-acid peptide encoded by the Ggamma8 gene with an acetylated and a farnesylated-methylated N- and C-terminus, respectively. Purified Tbeta3gamma8 is similar to Tbeta1gamma1 in that (1) both are heterogeneous, containing methylated and demethylated Tgamma subunits; (2) each demethylated dimer migrates faster than its methylated counterpart during native gel electrophoresis, and the methylation-associated mobility differential is masked by pdc binding; and (3) both dimers bind pdc with the same affinity, and the affinity is reduced threefold by PKA phosphorylation of pdc and twofold by demethylation at the C-terminus of Tgamma. Tbeta3gamma8 differs from Tbeta1gamma1 in exhibiting lower intrinsic electrophoretic mobility, and the difference is unaffected by either pdc binding or the status of Tgamma methylation. Tbeta3gamma8 is identical with Tbeta1gamma1 in Tgamma isoprenylation, the spatial organization, and the mode of pdc binding, indicating that its interaction with pdc does not play an important role in the specialization of cones. Changes in Tbetagamma characteristics by Tgamma methylation reveal conformational changes on a surface domain that is essential for Tbetagamma functions and support a regulatory role for reversible methylation.


Arrested dynamics in a model peptide hydrogel system.
We report here on a peptide hydrogel system, which in contrast to most other such systems, is made up of relatively short fibrillar aggregates, discussing resemblance with colloidal rods. The synthetic model peptides A8K and A10K, where A denotes alanine and K lysine, self-assemble in aqueous solutions into ribbon-like aggregates having an average length 〈L〉 on the order of 100 nm and with a diameter d≈ 6 nm. The aggregates can be seen as weakly charged rigid rods and they undergo an isotropic to nematic phase transition at higher concentrations. Translational motion perpendicular to the rod axis gets strongly hindered when the concentration is increased above the overlap concentration. Similarly, the rotational motion is hindered, leading to very long stress relaxation times. The peptide self-assembly is driven by hydrophobic interactions and due to a net peptide charge the system is colloidally stable. However, at the same time short range, presumably hydrophobic, attractive interactions appear to affect the rheology of the system. Upon screening the long range electrostatic repulsion, with the addition of salt, the hydrophobic attraction becomes more dominant and we observe a transition from a repulsive glassy state to an attractive gel-state of the rod-like peptide aggregates.


The role of calcium ions in the closing of K channels.
The effects of external Ca ion on K channel properties were studied in squid giant axons. Increasing the Ca concentration from 20 to 100 mM slowed K channel opening, and was kinetically equivalent to decreasing the depolarizing step by approximately 25 mV. The same Ca increase had a much smaller effect on closing kinetics, equivalent to making the membrane potential more negative by approximately mV. With regard to the conductance-voltage curve, this Ca increase was about equivalent to decreasing the depolarizing step by approximately 10 mV. The presence of K or Rb in the bath slowed closing kinetics and made the time course more complex: there were pronounced slow components in Rb and, to a lesser extent, in K. Increasing the Ca concentration strongly antagonized the slowing caused by Rb or K. Thus, Ca has a strong effect on closing kinetics only in the presence of these monovalent cations. Rb and K do not significantly alter opening kinetics, nor do they alter Ca's ability to slow opening kinetics. High Ca slightly affects the instantaneous I-V curve by selectively depressing inward current at negative voltages. The results imply that Ca has two actions on K channels, and in only one, the action on closing, does it compete with monovalent cations. We propose (a) that opening kinetics are slowed by binding of Ca to negatively charged parts of the gating apparatus that are at the external surface of the channel protein when the channel is closed; monovalent cations do not compete effectively in this action; (b) Ca (or possibly Mg) normally occupies closed channels and has a latching effect. External K or Rb competes with Ca for channel occupancy. Channels close sluggishly when occupied by a monovalent cation and tend to reopen. Thus, slow closing results from occupancy by K or Rb instead of Ca. The data are well fit by a model based on these ideas.


Excitation wavelength dependent photon anti-bunching/bunching from single quantum dots near gold nanostructures.
In this study, we aim to investigate the change in photon emission statistics of single CdSe/CdS core/shell quantum dots (QDs) on dielectric modified gold nanoparticle (NP) substrates as a function of the excitation wavelength. Photons emitted from single QDs are typically "anti-bunched" and are independent of the excitation wavelength. However, when QDs are coupled to plasmonic substrates, even at the low excitation power regime, we observed a significant change in photoluminescence emission behavior of single QDs; i.e. the emission transformed from incomplete photon anti-bunched to bunched when the excitation was changed from "off" to "on" plasmon resonance. Theoretical studies based on electrodynamics modeling suggested that for the QD-Au NP system, the quantum yield of single excitons decreases while that of biexcitons increases. In addition, when excited at the "on" resonance condition, the absorption is highly enhanced, resulting in an increased population of higher order excitons of the QDs. The higher order exciton emission was directly observed as an additional peak appeared at the blue side of the exciton peak of single QDs. The combined effect of the change in quantum yield and the increase in the absorption cross-section switches the photons emitted by single QDs from anti-bunched to bunched. These results provided direct evidence that not only the plasmonic nanostructures but also the excitation wavelength can effectively control the photon emission statistics of single QDs in the hybrid metal-semiconductor system. Manipulating the multiexciton-plasmon interaction in a hybrid complex like this could possibly open up new doors for applications such as entangled photon pair generation and plasmon-enhanced optoelectronic devices.


Case 257: Leiomyosarcoma of the Inferior Vena Cava.
History A 65-year-old woman presented to her primary care physician with a history of progressive abdominal pain mainly in the upper quadrants, nausea, and edema in the bilateral symmetric lower extremities. Other symptoms and use of medication or related drugs were denied. Physical examination findings were normal. The serum lactate dehydrogenase level was 302 U/L (5.04 μkat/L) (reference range, <247 U/L [4.12 μkat/L]), and all other laboratory data were within normal ranges. Electrocardiography and chest radiography revealed no abnormalities. The patient underwent contrast material-enhanced (100 mL of iomeprol [400 mg iodine per milliliter], Iomeron; Bracco Imaging) CT of the chest, abdomen, and pelvis; dynamic contrast-enhanced (13 mL of gadobenate dimeglumine, Multihance; Bracco Imaging) MRI of the chest and abdomen; and transthoracic echocardiography and cavography for further evaluation.


An angiomatoid fibrous histiocytoma over the left pre auricular region in a 13-year-old boy.
A 13-year-old boy presented to us for the evaluation of a slowly growing mass over the left preauricular region. Physical examination showed a nodular swelling, firm on palpation. The patient had no lymphadenopathy. The findings of magnetic resonance imaging (MRI) and vascular MRI led us to suspect a vascular growth. An incisional biopsy was performed and revealed an angiomatoid fibrous histiocytoma (AFH). Angiomatoid fibrous histiocytoma (AFH) is a rare tumor of the soft tissue with fibrohistiocytic and vascular differentiation that shows an intermediate malignancy grade, mainly occurs in patients younger than 20 years of age, and is usually localized on the extremities. Angiomatoid fibrous histiocytoma is considered to be a tumor of intermediate malignancy because of its less aggressive course in contrast to conventional malignant fibrous histiocytoma (MFH). Our case of AFH is peculiar because of its localization in the pre auricular region and because it appeared in a young patient. Surgical excision with maxillo-facial, chest-abdomen, and neck CT and prolonged follow-up is recommended because rare cases of metastasizing AFH have been reported.


A novel in situ stress measurement method based on acoustic emission Kaiser effect: a theoretical and experimental study.
Measurement of in situ stress is critical to understand the deformation and destruction of the underground space surrounding rock, and dynamic disaster of the coal mine. At present, with the increasing depth of mining, in situ stress parameters are more and more important for coal mine. In this paper, a novel method for in situ stress measurement with Kaiser effect was studied and applied in the Baijiao coal mine. First, we presented a comprehensive analysis method for the identification of Kaiser effect point. Then, a calculation method for in situ stress measurement based on the Kaiser effect on acoustic emissions was suggested. After that, the in situ stress test of Baijiao coal mine is taken as the research object, an experiment using acoustic emissions monitoring during uniaxial compression testing was performed to investigate the mechanical properties and acoustic emissions characteristics. Finally, in situ stress of the study area was calculated using the novel calculation method above and calculation results were verified using stress relief method and hydraulic fracturing method. The results showed that the calculation results obtained using the proposed method were valid and credible. Therefore, the calculation method for in situ stress measurement and the proposed comprehensive analysis method using the Kaiser point could be applied for in situ stress testing using the Kaiser effect method.


Non-Prescription Antibiotics Use and Associated Factors Among Drug Retail Outlets in Ambo, Ethiopia: A Cross-Sectional Study.
To assess the non-prescription use of antibiotics and associated factors in Ambo Town, West Shoa, Oromia, Ethiopia. An institutional-based cross-sectional study design supported with the qualitative study was conducted in Ambo Town from February 1 to March 1, 2020. Data were collected using a pretested semi-structured questionnaire and in-depth interview guide questions. Simple random sampling was used to select retail outlets and systematic random sampling to select study participants. The data analysis was done using SPSS and univariate and multivariate binary logistic regression analysis was performed to identify factors associated with non-prescription use of antibiotics. Thematic framework analysis was applied for the qualitative data. From the 421 study sample, a total of 399 participants were interviewed with a 94.8% response rate. Among the study participants, 214 (53.6) were males, 228 (57.1%) were married, 191 (47.9%) were orthodox by religion, and 343 (86%) were Oromo by ethnicity. One hundred seventy-two (43.1%; 95% CI: 38.6, 48.1) of the participants had used non-prescribed antibiotics. Being male [AOR=2.21 95% CI: 1.276, 3.835], residing in rural area [AOR=3.659, 95% CI: 1.479, 9.054], holding diploma [AOR=0.120, 95% CI: 0.025, 0.591], and hold BSC degree [AOR=0.050, 95% CI: 0.007, 0.378], and being farmer [AOR=0.034, 95% CI: 0.004, 0.285] showed significant association with the non-prescription use of antibiotics. This study concluded that the non-prescription use of antibiotics 172 (43.1%) was relatively high. Being male, residing in a rural area, holding a diploma, BSc degree, and being a farmer were significantly associated with non-prescription use of antibiotics. So, West Shoa Zone regulatory body should actively focus on the prevention of non-prescription use of antibiotics through health communication and public awareness on the demerits of non-prescription use of antibiotics.


Steroid replacement treatment increases beta-endorphin and beta-lipotropin plasma levels in postmenopausal women.
The present study shows the effects of two different steroid replacement therapies, with conjugated estrogens or with a new synthetic steroid derivative, ORG OD14, on plasma beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) levels in postmenopausal subjects. Blood samples were collected before treatment and after 1, 2 and 4 months of treatment; a third group of patients was treated with placebo. After 2 months of treatment both groups of patients who underwent steroid supplementation showed circulating levels of beta-EP and beta-LPH higher than basal levels. ORG OD14 treatment increased beta-EP and beta-LPH levels more than conjugated estrogens at the 2nd month of therapy. No further change was found after 4 months. The two drugs were effective in reducing hot flushes and improving physical and psychological symptoms. These data indicate that sex steroids are able to increase beta-EP and beta-LPH secretion in postmenopausal women, with a concomitant relief of climacteric symptoms.