Supporting the provision of pharmacy medication reviews to marginalised (medically underserved) groups: a before/after questionnaire study investigating the impact of a patient-professional co-produced digital educational intervention.
People who are marginalised (medically underserved) experience significant health disparities and their voices are often 'seldom heard'. Interventions to improve professional awareness and engagement with these groups are urgently needed. This study uses a co-production approach to develop an online digital educational intervention in order to improve pharmacy staffs' intention to offer a community pharmacy medication review service to medically underserved groups. Before/after (3 months) self-completion online questionnaire. Community pharmacies in the Nottinghamshire (England) geographical area. Community pharmacy staff. Online digital educational intervention. The primary outcome measure was 'behaviour change intention' using a validated 12-item survey measure. The secondary outcome measure was pharmacist self-reported recruitment of underserved groups to the medication review service. All pharmacies in the Nottinghamshire area (n=237) were approached in June 2017 and responses were received from 149 staff (from 122 pharmacies). At 3 months (after completing the baseline questionnaire), 96 participants (from 80 pharmacies) completed a follow-up questionnaire, of which two-thirds (n=62) reported completing the e-learning. A before/after comparison analysis found an improving trend in all the five constructs of behaviour change intention (intention, social influence, beliefs about capabilities, moral norms and beliefs about consequences), with a significant increase in mean score of participants' 'beliefs about capabilities' (0.44; 95% CI 0.11 to 0.76, p=0.009). In the short-term, no significant change was detected in the number of patients being offered and the patient completing a medication review. Although increases in the numbers of patients being offered a medication review was not detected, the intervention has the potential to significantly improve pharmacy professionals' 'beliefs about capabilities' in the short-term. Wider organisational and policy barriers to engagement with marginasied groups may need to be addressed. Future research should focus on the interplay between digital learning and practice to better identify and understand effective practice change pathways.


The introduction of tobacco excise taxation in the Gulf Cooperation Council Countries: a step in the right direction of advancing public health.
The Gulf Cooperation Council (GCC) countries relied, until recently, solely on import duties for tobacco products. The agreement for the introduction of an excise and value added tax (VAT) in 2016 and 2017, respectively, in most GCC countries, was a major breakthrough for public health. There is, however, ample room for improvement. The study examines the outcomes of tax reforms, for both public health and public finances, based on the World Health Organization (WHO) recommendations and best practices worldwide. Tax simulations were performed using the WHO TaXSiM model. The study is based on data from Saudi Arabia, the only GCC country for which sufficient data existed. We recommend a stepwise tax reform, which involves increasing the current ad valorem excise tax rate, phasing out import duties keeping total tax share constant and introducing a minimum excise, and finally switching to a revenue-neutral specific excise. Specific excises must be adjusted for inflation and income increases. If implemented, cigarette tax reform simulations show that the recommended reforms would lead to a higher than 50% increase in cigarette prices, 16% reduction in cigarette sales and almost 50% increase in total cigarette tax revenue. A significant number of cigarette-related deaths would be averted. The recommended tax reforms are expected to lead to significant improvements in both public health and tobacco tax revenues. Our results provide useful insights that are of relevance to the whole GGC region. The effectiveness of the reforms, however, requires a strong tax and customs administration, including the establishment of a good database to monitor and advance public health.


A genomic approach to coral-dinoflagellate symbiosis: studies of Acropora digitifera and Symbiodinium minutum.
Far more intimate knowledge of scleractinian coral biology is essential in order to understand how diverse coral-symbiont endosymbioses have been established. In particular, molecular and cellular mechanisms enabling the establishment and maintenance of obligate endosymbiosis with photosynthetic dinoflagellates require further clarification. By extension, such understanding may also shed light upon environmental conditions that promote the collapse of this mutualism. Genomic data undergird studies of all symbiotic processes. Here we review recent genomic data derived from the scleractinian coral, Acropora digitifera, and the endosymbiotic dinoflagellate, Symbiodinium minutum. We discuss Acropora genes involved in calcification, embryonic development, innate immunity, apoptosis, autophagy, UV resistance, fluorescence, photoreceptors, circadian clocks, etc. We also detail gene loss in amino acid metabolism that may explain at least part of the Acropora stress-response. Characteristic features of the Symbiodinium genome are also reviewed, focusing on the expansion of certain gene families, the molecular basis for permanently condensed chromatin, unique spliceosomal splicing, and unusual gene arrangement. Salient features of the Symbiodinium plastid and mitochondrial genomes are also illuminated. Although many questions regarding these interdependent genomes remain, we summarize information necessary for future studies of coral-dinoflagellate endosymbiosis.


Smoking habit and psychometric scores: a community study.
During the Milton health survey subjects completed a psychometric inventory consisting of the 48 questions of the Middlesex Hospital questionnaire (MHQ) and 26 from the hostility and direction of hostility questionnaire (HDHQ) designed to examine nine psychological dimensions. The 1209 subjects were classified into smoking categories and the scores for each psychometric trait were calculated. Women scored higher than men and heavy smokers scored higher than "never smokers". The psychometric traits and the scores of the four smoking categories after correcting for age and Quetelet's index showed statistically significant differences by analysis of variance in respect of somatic anxiety and depression for both men and women; and free-floating anxiety, phobic anxiety, hysteria, acting out hostility, self criticism and guilt in women. For somatic anxiety the increase in score almost exactly paralleled the increasing quantity of tobacco consumed.


Incidence of thyroid cancer and medical cost among patients with newly diagnosed thyroid nodules in Korea: A retrospective cohort study using nationwide data.
The frequency of newly diagnosed thyroid nodules is increasing in South Korea. However, few studies have investigated the incidence of thyroid cancer in patients with thyroid nodules using national data. Therefore, this study was conducted to investigate the incidence of thyroid cancer and medical costs among patients newly diagnosed with thyroid nodules in South Korea. This was a retrospective cohort study. Subjects and Methods: We analyzed the national health claim database, which includes all hospital records and covers almost every population managed by the National Health Insurance System. We selected patients aged 20-120 years with new thyroid nodules in 2008 using the International Classification of Diseases, Tenth Edition codes. We followed the selected cases for at least 2 years after thyroid nodule diagnosis to investigate cancer development and medical costs. Frequency analysis was used. We identified 283,844 eligible patients with thyroid nodules. Their mean age was 48 ± 13.2, and 234,388 (82.58%) cases were female. During the median follow-up of 2.4 years, 21,538 (7.6%) patients were diagnosed with thyroid cancer, and 93.5% of them underwent treatment such as thyroidectomy, chemotherapy, or radiotherapy. The average medical cost was 3,996,391 KRW after diagnosis of thyroid cancer. Here, national representative statistics regarding the incidence and medical costs of thyroid nodule and thyroid cancer are presented. The information provided herein will improve understanding of the natural course of thyroid nodules in Asians. Further study is needed to identify the risk factors of thyroid cancer in patients with thyroid nodules.


Causes and risk factors for 30-day unplanned readmissions after pediatric spinal deformity surgery.
Retrospective review of a prospective cohort. To determine the incidence, risk factors, and causes for 30-day unplanned readmission after pediatric spinal deformity surgery. The government has targeted 30-day readmissions as a quality of care measure. However, few studies have analyzed readmission in pediatric cohorts. A multicenter registry designed to collect pediatric surgical outcomes was queried for patients undergoing spinal deformity surgery in 2012. Patients were divided into groups of those with and without an unplanned readmission within 30 days postoperatively. Univariate and multivariate logistic regression analyses were used to compare the cohorts, and to identify variables associated with readmission. In total, 75 of 1890 pediatric patients undergoing spinal fusion for deformity had an unplanned 30-day readmission (3.96%). Readmissions were highest in the neuromuscular group (6.83%) and lowest in the idiopathic (2.66%) and infantile (1.31%) cohorts, (P < 0.01). The top reasons for readmission included wound complications (73.3%) and gastrointestinal disturbances (13.3%). In the univariate analysis, increasing surgical complexity, particularly fusions to the pelvis and isolated anterior spinal fusions, as well as increasing medical comorbidity burden were each associated with readmission (P < 0.05 for each). In the subsequent multivariate analysis, isolated anterior spinal fusions (odds ratio, 7.65; 95% confidence interval, 1.32-44.3) structural pulmonary abnormalities (odds ratio, 2.53; 95% confidence interval, 1.22-5.23) and an American Society of Anesthesiologists class of 3 or 4 (odds ratio, 2.18; 95% confidence interval, 1.07-4.47) were independently associated with readmission. The overall rate of 30-day unplanned readmissions after pediatric deformity surgery was low, but not insignificant. Surgeons should consider discharge optimization in the at-risk patient cohorts defined here, and should focus on wound complications and gastrointestinal disturbances to minimize readmissions. Quality reporting metrics should incorporate these risk factors to avoid unduly penalizing surgeons who take on complex cases. 3.


Molecular cloning and characterization of avian sarcoma virus circular DNA molecules.
Supercoiled DNA molecules were used for the molecular cloning of full-length avian sarcoma virus (ASV) DNA. Viral DNA produced by the Schmidt-Ruppin A (SR-A) strain of ASV was isolated from acutely infected transformed quail cells. Supercoiled DNA was separated from linear and open circular DNA by acid phenol extraction, opened into a full-length linear form by cleavage with the restriction endonuclease SacI, and cloned into lambda gtWES x lambda B. Four different cloned viral DNA molecules were isolated: SRA-1 contains two copies of the 330-base pair terminal redundancy normally found at each end of the linear DNA molecules, but harbors a 63-base pair deletion that spans the site at which the two copies of the terminal redundancy are joined in circular DNA molecules; SRA-2 contains two complete copies of the terminal redundancy; SRA-3 probably contains only one copy of the terminal redundancy but in all other respects appears to be similar to SRA-2; SRA-4 contains a 2,500-base pair deletion that removes all of the src gene (the gene responsible for transformation by ASVs) plus additional nucleotides adjacent to the src gene whose precise locations have not been determined. Transfection of chicken embryo fibroblasts by either SRA-1 or SRA-2 resulted both in the appearance of transformed cells and in the production of infectious virus. These results demonstrate that the cloned DNA molecules are functionally identical to viral DNA produced in vivo; therefore, molecular cloning did not cause any major alterations of the DNA. The infectivity of SRA-1 DNA indicates that the 63 base pairs missing from that molecule are not required for the initiation of viral RNA synthesis, even though the deletion is located in a copy of the terminal redundancy thought to carry a promoter for RNA synthesis. This suggests that the deletion does not remove any sequences required for the initiation of transcription.


Climate-driven introduction of the Black Death and successive plague reintroductions into Europe.
The Black Death, originating in Asia, arrived in the Mediterranean harbors of Europe in 1347 CE, via the land and sea trade routes of the ancient Silk Road system. This epidemic marked the start of the second plague pandemic, which lasted in Europe until the early 19th century. This pandemic is generally understood as the consequence of a singular introduction of Yersinia pestis, after which the disease established itself in European rodents over four centuries. To locate these putative plague reservoirs, we studied the climate fluctuations that preceded regional plague epidemics, based on a dataset of 7,711 georeferenced historical plague outbreaks and 15 annually resolved tree-ring records from Europe and Asia. We provide evidence for repeated climate-driven reintroductions of the bacterium into European harbors from reservoirs in Asia, with a delay of 15 ± 1 y. Our analysis finds no support for the existence of permanent plague reservoirs in medieval Europe.


Cleavage mechanism of human Mus81-Eme1 acting on Holliday-junction structures.
Recombination-mediated repair plays a central role in maintaining genomic integrity during DNA replication. The human Mus81-Eme1 endonuclease is involved in recombination repair, but the exact structures it acts on in vivo are not known. Using kinetic and enzymatic analysis of highly purified recombinant enzyme, we find that Mus81-Eme1 catalyzes coordinate bilateral cleavage of model Holliday-junction structures. Using a self-limiting, cruciform-containing substrate, we demonstrate that bilateral cleavage occurs sequentially within the lifetime of the enzyme-substrate complex. Coordinate bilateral cleavage is promoted by the highly cooperative nature of the enzyme and results in symmetrical cleavage of a cruciform structure, thus, Mus81-Eme1 can ensure coordinate, bilateral cleavage of Holliday junction-like structures.


Thromboprophylaxis in orthopedic surgery.
More than 2 million people undergo major orthopedic surgery each year, and this rate is expected to continue rising as our population ages. Our patients are at particularly high risk for deep vein thrombosis (DVT) and pulmonary embolism. The latest guidelines from the American College of Chest Physicians recommend thromboprophylaxis for high-risk orthopedic surgery patients. Although specific recommendations vary by type of surgery, low-molecular-weight heparin, fondaparinux, warfarin, and sometimes low-dose unfractionated heparin are effective alone or with mechanical prophylaxis. Goals of treatment are to prevent proximal and distal DVT, pulmonary death, chronic pulmonary hypertension, and postthrombotic syndrome.


9 alpha- and 9 beta-Hydroxyphenylmorphans.
Platinum-oxide hydrogenation of 5-m-methoxyphenyl-2-methyl-9-oxomorphan (I) gave the 9 alpha-hydroxy racemate (II) whose phenolic analogue (III) is a strong antinociceptive agent, fully supportive of morphine dependence in rhesus monkeys. The di-O-acetyl derivative (VI) of III was similar to III in its profile of activity. The diastereoisomer of III (VII), obtained by hydrogenation of the methobromide of I (IV), extrusion of methyl bromide, and O-demethylation of the resultant free base (VIII), was almost inactive antinociceptively and did not suppress withdrawal symptoms in morphine-dependent monkeys. The orientation of the C-9 hydroxyl groups was deduced from spectral data and by analogy.


Relationship between circulating VCAM-1, ICAM-1, E-selectin and MMP9 and the extent of coronary lesions.
Inflammatory molecules play a role in the development of atherosclerosis, which is the primary origin of cardiovascular disorders. However, to the best of our knowledge, no study has attempted to investigate the relationship between these circulating molecules and the prediction of cardiovascular risk. The present study aimed to investigate the relationships of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin and matrix metalloproteinase 9 serum concentrations with the extent of coronary lesions. Seventy-four individuals who were undergoing coronary angiography for the first time for diagnostic purposes were enrolled in this study. The extent of the coronary lesion was assessed using the Friesinger Index, and subjects were classified into four groups: no lesions, minor lesions, intermediate lesions and major lesions. Serum biochemical parameters and serum concentrations of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin and matrix metalloproteinase 9 were analyzed. The vascular cell adhesion molecule-1 concentration was higher than 876 ng/mL in individuals with intermediate and major lesions (p<0.001 and p=0.020, respectively). Moreover, logistic regression analysis showed that these patients had an increased risk of having an intermediate lesion (p=0.007). Interestingly, all individuals with major lesions had vascular cell adhesion molecule-1 concentrations higher than 876 ng/mL. No association was found between the concentrations of the other proteins and the Friesinger Index. Serum vascular cell adhesion molecule-1 may be associated with the extent of coronary lesions. Moreover, it may represent an alternative to improve the cardiovascular risk classification in patients without acute coronary syndrome.


Neck strength: a protective factor reducing risk for concussion in high school sports.
As the number of high school students participating in athletics continues to increase, so will the number of sports-related concussions unless effective concussion prevention programs are developed. We sought to develop and validate a cost-effective tool to measure neck strength in a high school setting, conduct a feasibility study to determine if the developed tool could be reliably applied by certified athletic trainers (ATs) in a high school setting, and conduct a pilot study to determine if anthropometric measurements captured by ATs can predict concussion risk. In the study's first phase, 16 adult subjects underwent repeated neck strength testing by a group of five ATs to validate the developed hand-held tension scale, a cost effective alternative to a hand-held dynamometer. In the second phase, during the 2010 and 2011 academic years, ATs from 51 high schools in 25 states captured pre-season anthropometric measurements for 6,704 high school athletes in boys' and girls' soccer, basketball, and lacrosse, as well as reported concussion incidence and athletic exposure data. We found high correlations between neck strength measurements taken with the developed tool and a hand-held dynamometer and the measurements taken by five ATs. Smaller mean neck circumference, smaller mean neck to head circumference ratio, and weaker mean overall neck strength were significantly associated with concussion. Overall neck strength (p < 0.001), gender (p < 0.001), and sport (p = 0.007) were significant predictors of concussions in unadjusted models. After adjusting for gender and sport, overall neck strength remained a significant predictor of concussion (p = 0.004). For every one pound increase in neck strength, odds of concussion decreased by 5 % (OR = 0.95, 95 % CI 0.92-0.98). We conclude that identifying differences in overall neck strength may be useful in developing a screening tool to determine which high school athletes are at higher risk of concussion. Once identified, these athletes could be targeted for concussion prevention programs.


Role of Bentonite on the Mobility of Antibiotic Resistance Genes, and Microbial Community in Oxytetracycline and Cadmium Contaminated Soil.
The effects of bentonite (BT), a commonly used heavy metal deactivator, on the ARGs and microbial communities in soils and lettuce systems contaminated by heavy metals and antibiotics are unclear. A study was conducted to investigate the effect of BT on the mobility of antibiotic resistance genes in oxytetracycline and cadmium contaminated soil. Results showed that the addition of BT reduced the accumulation of OTC and ARGs in the soil and lettuce roots, but increased the abundance of ARGs in lettuce leaves, and increase the risk of human pathogenic bacteria (HPB) transferring to lettuce leaves. Redundancy analysis showed that environmental factors (OTC, H2O, SOM, and pH) were the dominant factors that influence the distribution of ARGs and intI1. Network analysis showed that Proteobacteria and Bacteroidetes were the major host bacteria which caused changes in ARGs and intI1. There were significant positive correlations between ermX and ermQ, and a large number of HPB. The co-occurrence of intl1 with some ARGs (tetC, tetG, ermQ, sul1, and sul2), may threaten human health due to the dispersion of ARGs via horizontal gene transfer.


Spectral symmetry analysis.
We present a spectral approach for detecting and analyzing rotational and reflectional symmetries in n-dimensions. Our main contribution is the derivation of a symmetry detection and analysis scheme for sets of points in IRn and its extension to image analysis by way of local features. Each object is represented by a set of points S 2 IRn, where the symmetry is manifested by the multiple self-alignments of S. The alignment problem is formulated as a quadratic binary optimization problem, with an efficient solution via spectral relaxation. For symmetric objects, this results in a multiplicity of eigenvalues whose corresponding eigenvectors allow the detection and analysis of both types of symmetry. We improve the scheme's robustness by incorporating geometrical constraints into the spectral analysis. Our approach is experimentally verified by applying it to 2D and 3D synthetic objects as well as real images.


Mouse sperm antigens that participate in fertilization. II. Inhibition of sperm penetration through the zona pellucida using monoclonal antibodies.
To dissect the process of mammalian sperm interaction with the egg at a molecular level, we have generated monoclonal antibodies (mAbs) to mature mouse sperm using syngeneic mouse testis as the immunogen. In this paper, we report upon three members of a mAb family, all of which displayed identical immunofluorescence patterns on cauda epididymal mouse sperm. Each of these mAbs, termed M42, M5, and M41, localized to a restricted region of plasma membrane overlying the acrosome. When tested for an effect on the fertilization process in vitro, two of the mAbs, M42 and M5, demonstrated significant inhibition. The inhibitory capacity was dependent upon the presence of the zona pellucida; neither M42 nor M5 was capable of blocking fertilization when zona pellucida-free mouse eggs were used. Identification of the antigens recognized by this group of mAbs was achieved by immunologic detection of sodium dodecyl sulfate-extracted sperm components separated via electrophoresis on 12% sodium dodecyl sulfate-polyacrylamide gels followed by transfer to nitrocellulose. M42, which blocked fertilization, recognized a high molecular weight cluster of bands with Mr of approximately 220,000 to 240,000. M5, which also prevented fertilization, specifically recognized a sperm component with subunit molecular weight of approximately 54,000. M41, which did not interfere with fertilization, did not interact with any high molecular weight components, but recognized components with Mr of approximately 60,000, 35,000, and 21,000. Taken together with the work presented in a companion paper (Saling, Irons, and Waibel, this issue), we have demonstrated that it is possible to describe particular cellular regions of mammalian sperm with respect not only to location and function, but also to the molecules that are candidates for a role in that function.


[Modeling calcium-45 metabolism in tissue, taking into account the structure and hemodynamics of the capillary system].
The accumulation of Ca-45 in the tissues and the degree of its desorption during the perfusion in the sufficiently extensive limits does not depend upon the rate of the perfused solution and is the function of the perfused solution volume. Taking into account strong dependence of the volume rate of filling the capillaries with the solution upon the capilliary radii (r-4) one may come to the conclusion that Ca-45 saturation of the paracapillary spaces in the wide capillaries occurs much sooner than in the narrow ones. As a result of developing these postulates, we have got the formulae which associates these two functions. It is shown that according to the theory the accumulation and desorption processes are interrelated and may be calculated.


[Genome-wide association study for ischemic stroke based on the Hisayama study].
Ischemic stroke is a major cause of death and disability, and occurs owing to a combination of multiple environmental and genetic risk factors. Although twin studies and family-based studies have suggested the existence of genetic risk factors for ischemic stroke, few candidate genes have been discovered. To identify genes for susceptibility to ischemic stroke, we performed a genome-wide association study using 52,608 single nucleotide polymorphism (SNP) markers. After comparison of allele frequencies between 1,112 patients with ischemic stroke and the same number of age- and sex-matched control subjects, who were selected from among the residents of the town of Hisayama, Japan, we identified three novel candidate genes for ischemic stroke: PRKCH (protein kinase C eta (PKCη)), AGTRL1 (apelin receptor), and ARHGEF10 (Rho guanine nucleotide exchange factor 10). In the functional analyses, we found that PKCη was expressed mainly in vascular endothelial cells and foamy macrophages in human atherosclerotic lesions, and that the kinase activity of PKCη was modified by a nonsynonymous SNP in PRKCH (rs2230500). We also clarified that functional SNPs in AGTRL1 (rs9943582) and ARHGEF10 (rs4376531) affected transcriptional activities owing to the different Sp1-binding affinities. In a 14-year follow-up cohort study of Hisayama residents, all of these SNPs were significantly associated with the development of ischemic stroke. Although the mechanisms of these genes in the pathogenesis of ischemic stroke are still to be elucidated, our findings might contribute to a better understanding of ischemic stroke in the future.


Accelerated Reaction Kinetics in Microdroplets: Overview and Recent Developments.
Various organic reactions, including important synthetic reactions involving C-C, C-N, and C-O bond formation as well as reactions of biomolecules, are accelerated when the reagents are present in sprayed or levitated microdroplets or in thin films. The reaction rates increase by orders of magnitude with decreasing droplet size or film thickness. The effect is associated with reactions at the solution-air interface. A key factor is partial solvation of the reagents at the interface, which reduces the critical energy for reaction. This phenomenon is of intrinsic interest and potentially of practical value as a simple, rapid method of performing small-scale synthesis.


[Neurological involvement in pre-eclampsia/eclampsia: the role of neuroimaging].
Pre-eclampsia is a disease that can affect several organs and systems. Neurologic repercussions are particularly feared, provoking, among other manifestations, seizures and blindness. Imaging techniques are available to elucidate the pathogenesis of this complication, also allowing us to diagnose other brain lesions: CT, MRI and transcranial Doppler. The authors present some aspects of imaging techniques related to the neurologic complications in preeclampsia/eclampsia.


A mathematical model for growth and osmoregulation in halophilic bacteria.
Many molecular details of the ecophysiology of halophilic bacteria that use compatible solutes to maintain osmotic equilibrium have been examined. We ask whether the details are consistent and complete enough to predict growth and osmoregulation in these bacteria by integrating this information in a mathematical model. Parameterized for the halophilic organism Halomonas elongata, the model predicts the substrate and salt dependence of growth, the uptake of potassium and ectoine and the synthesis of ectoine. It is shown that salt (NaCl) dependence of growth can be modelled by substrate inhibition kinetics. Osmoregulation is known to involve accumulation of both ectoine and potassium glutamate in H. elongata. Using published and newly determined parameters, osmoregulatory models using either direct turgor or two-step (turgor and potassium) signalling are compared. The results are consistent with a role for potassium as a second messenger for hyperosmotic stress. Simulations of osmotic upshifts show a transient overregulation of the intracellular solute levels, as has been previously observed in experiments. A possible adaptive value of this overregulation as 'pre-emptive' behaviour in an environment with frequent dry periods leading to steadily increasing osmolarity is proposed. As a result of growth parameter estimation, a maximum P : O value of 2 for H. elongata can be inferred. In conclusion, the model developed here reproduces essential aspects of growth and osmoregulation in halophilic bacteria with a minimal set of assumptions.


Captive-housed male cheetahs (Acinonyx jubatus soemmeringii) form naturalistic coalitions: measuring associations and calculating chance encounters.
Cheetahs are known to reproduce poorly in captivity and research suggests that the reasons for this are behavioral, rather than physiological. In the wild, male cheetahs remain in stable groups, or coalitions, throughout their lifetime. Appropriate social group housing is important in enhancing welfare and reproductive success in captivity and this study examined the effect of changes in social group composition on the behavior of four male cheetahs: two siblings and two half siblings. During the study, the cheetahs were housed both in pairs and as a group of four, before one male was relocated. The remaining cheetahs were then housed in a trio. Affiliative behaviors were frequently shown within pairs and overt aggression was seldom observed. Association indices were calculated for each cheetah pair and corrected for chance encounters based on data generated from a Monte Carlo simulation. The indices showed that two coalitions existed before the relocated male departed. Following the relocation of one of the half siblings, the remaining cheetahs appeared to form a coalition of three, as the indices of association between the unrelated male and the siblings increased and allogrooming between unrelated individuals was observed. The findings of this study indicate that natural social groupings of male cheetahs can be successfully replicated in captivity, which could potentially improve the chances of reproductive success when they are introduced to female cheetahs.


Health-related quality of life in asymptomatic patients with HIV. Evaluation of the SF-36 health survey in Italian patients.
To investigate the psychometric performance and clinical validity of the 36-Item Short Form (SF-36) health survey when completed by asymptomatic HIV-positive Italian patients and to compare their health profile with a representative sample of 2031 Italian citizens (the Italian norm). This was an observational, multicentre, cross-sectional survey. Microbiologists throughout Italy recruited asymptomatic HIV-positive individuals who were aged at least 18 years and aware of their infection. Investigators collected demographic, social, clinical and treatment data. Patients, classified into 2 clinical categories (A1 and A2) according to explicit pre-defined criteria, completed the SF-36 health survey in the context of a medical visit. Between April and July 1996, 46 microbiologists recruited 214 patients (201 evaluable). No inconsistent responses were observed in 96% of the sample. The usually recommended psychometric standards were satisfied, and the internal consistency reliability indices were always greater than 0.70. Weak to moderate associations were found between SF-36 health survey scores and physicians' estimates of patients' physical performance, while no significant associations were found with CD4+ counts. On average, HIV-positive patients reported lower scores than the Italian norm, and patients in category A2 showed lower scores than patients in A1. These differences were more relevant in scales describing role limitations, general health perception, and psychological well-being. Our study showed that the SF-36 health survey maintained its psychometric properties in a sample of Italian asymptomatic HIV-positive patients and produced data that showed its validity and robustness in such a setting.


Parental deployment and distress, and adolescent disordered eating in prevention-seeking military dependents.
Parental military deployment can lead to stress in the family system due to concerns about the deployed service-member's safety and increased responsibilities for those not deployed. Parent-related stress can impact adolescent disordered eating. Given the important role that stress plays in disordered eating and obesity, it is crucial to understand the impacts of unique stressors to which vulnerable populations are exposed. We studied 126 adolescent (14.3 ± 1.6 years; 59.5% girls; 44.4% non-Hispanic White; BMI-z, 1.91 ± .39) military dependents prior to entering an obesity and binge-eating disorder prevention trial. The Eating Disorder Examination was used to assess adolescent disordered eating. Parents self-reported their own distress and family deployment history that occurred during the adolescent's lifetime. Parental distress interacted with frequency of parental deployments such that for those with high parental distress, more frequent deployment was associated with greater adolescent shape and weight concerns (β = .21, p = .012) and global eating pathology (β = .18, p = .024). In this hypothesis-generating study, the combination of number of deployments and parental distress may be associated with disordered eating among adolescent military dependents seeking prevention of binge-eating disorder and adult obesity. If these preliminary findings are supported longitudinally, interventions to reduce parental stress related to deployment may be warranted to reduce disordered eating in adolescent dependents.


Artemisia plants, arachidonic and other polyunsaturated fatty acids.
Arachidonic acid (AA or ARA) is an extremely important fatty acid involved in cell regulation. It is a polyunsaturated fatty acid (20:4n6) covalently bound in esterified form in membrane phospholipids of most body cells. Following irritation or injury, arachidonic acid is released and oxygenated by enzyme systems leading to the formation of an important group of inflammatory mediators, to the prostaglandins (PGE₂) by the cyclooxygenase enzyme. This paper describes the positive health effects of arachidonic acid on malaria and other tropical diseases.


Palladium-Catalyzed meta-C-H Allylation of Arenes: A Unique Combination of a Pyrimidine-Based Template and Hexafluoroisopropanol.
Controlling remote selectivity and delivering novel functionalities at distal positions in arenes are an important endeavor in contemporary organic synthesis. In this vein, template engineering and mechanistic understanding of new functionalization strategies are essential for enhancing the scope of such methods. Herein, meta-C-H allylation of arenes has been achieved with the aid of a palladium catalyst, pyrimidine-based auxiliary, and allyl phosphate. 1,1,1,3,3,3-Hexafluoroisopropanol (HFIP) was found as a critical solvent in this transformation. The role of HFIP throughout the catalytic cycle has been systematically studied. A broad substrate scope with phenethyl ether, phenol, benzylsulfonyl ester, phenethylsulfonyl ester, phenylacetic acid, hydrocinnamic acid, and 2-phenylbenzoic acid derivatives has been demonstrated. Interestingly, conformationally flexible arenes have also been selectively allylated at the meta-position using allyl phosphate. A combination of 1H NMR, 31P NMR, ESI-MS, kinetic experiments, and density functional theory (DFT) computations suggested that reaction proceeds through a ligand-assisted meta-C-H activation, allyl addition forming a Pd-π-allyl complex which is then followed by a turnover determining the C-C bond formation step leading to the meta-allylated product.


Congenital dislocation of the knee in a three-year-old-child with Larsen syndrome: Treatment with a hexapod-type external fixator.
Congenital knee dislocation (CDK) is a rare condition, and its treatment is subject to debate. Here, we report on a new treatment for CDK (using a hexapod-type external fixator, HEF) in a three-year-old child with Larsen syndrome and grade III anterior dislocations of both knees. The left knee was treated with serial splints, whereas an HEF was used to treat an irreducible dislocation of the right knee. Two HEF aluminium rings were applied surgically. The procedure involved a distraction of the knee, then tibial posterior translation, and lastly progressive flexion. The clinical and radiological outcomes were good; after four years of follow-up, the right knee had stabilized and had a range of motion of 110°. We conclude that as an innovative, effective option for the management of CDK, the use of an HEF may constitute a relatively advantageous alternative to quadriceps tenotomy.


The ventral nucleus of the lateral lemniscus of the gerbil (Meriones unguiculatus): organization of connections with the cochlear nucleus and the inferior colliculus.
The spatial organization of projections from the ventral cochlear nucleus (VCN) to the ventral nucleus of the lateral lemniscus (VNLL) and from the VNLL to the central nucleus of the inferior colliculus (CNIC) was investigated by using neuroanatomical tracing methods in the gerbil. In order to label cells in the VNLL that project to the CNIC, focal injections of biotinylated dextran amine (BDA) were made into different CNIC regions. Retrogradely labeled cells were distributed throughout the dorsal-to-ventral axis of the VNLL in all cases. In contrast, the distribution of labeled cells across the lateral-to-medial dimension of the VNLL was related to the location of the injection site along the dorsolateral to ventromedial (frequency) axis of the CNIC. Cells projecting to dorsolateral (low-frequency) regions of the CNIC were located peripherally in the VNLL, mainly laterally and caudally, whereas those projecting to ventromedial (high-frequency) regions of the CNIC tended to be clustered centrally. Projections to the VNLL were labeled anterogradely following injections of BDA in the VCN. The distribution of terminal fields in the VNLL closely paralleled the topographic arrangement of cells projecting to the CNIC; projections from ventrolateral (low-frequency) areas of the VCN terminated mainly along the lateral and caudal borders of the VNLL, whereas projections from dorsomedial (high-frequency) areas terminated in more central regions. The results demonstrate a topographic organization of the major afferent and efferent connections of the gerbil VNLL.


The differential contribution by individual enzymes of glycolysis and protein catabolism to the relationship between heterozygosity and growth rate in the coot clam, Mulinia lateralis.
The locus-specific effects of heterozygosity upon individual growth rate were determined for 15 polymorphic enzymes among 1906 individuals from a single cohort sample of the marine bivalve Mulinia lateralis. Two measures of individual growth rate (total wet weight and shell length) were made at collection and after a period of growth in the laboratory. The correlation between heterozygosity and growth rate was independently determined for each locus using multiple linear regression, thereby providing a rank of individual locus effects; these differed significantly. The four estimated rankings of relative locus effects (initial length, initial weight, length added in the laboratory, and added weight) were not statistically different. That is, a locus with a large effect of heterozygosity on growth rate in nature had a similarly large effect on laboratory growth rate. The effect of a locus was not related to heterozygosity per se; some highly heterozygous loci had no detectable correlation with growth rate. The data contained two pairs of relatively tightly linked loci; in both cases one locus of a pair had significant effects on growth rate, while the other had no effect. Loci with large and significant correlations with growth rate synthesize enzymes which function in protein catabolism or glycolysis; heterozygosity in enzymes of the pentose shunt, redox balance, or other miscellaneous metabolic roles was not correlated with growth rate. Since the metabolic basis for the correlation is known to derive from individual differences in net energy status, particularly energetic costs of whole-body protein turnover, these data indicate that phenotypic effects (e.g., variation in growth rate) are determined by heterozygosity at the studied genes, not other linked loci.


Dynamics of Phase Synchronization between Solar Polar Magnetic Fields Assessed with Van Der Pol and Kuramoto Models.
We establish the similarity in two model-based reconstructions of the coupling between the polar magnetic fields of the Sun represented by the solar faculae time series. The reconstructions are inferred from the pair of the coupled oscillators modelled with the Van der Pol and Kuramoto equations. They are associated with the substantial simplification of solar dynamo models and, respectively, a simple ad hoc model reproducing the phenomenon of synchronization. While the polar fields are synchronized, both of the reconstruction procedures restore couplings, which attain moderate values and follow each other rather accurately as the functions of time. We also estimate the evolution of the phase difference between the polar fields and claim that they tend to move apart more quickly than approach each other.


Role of p21 as a determinant of 1,6-Bis[4-(4-amino-3-hydroxyphenoxy)phenyl] diamantane response in human HCT-116 colon carcinoma cells.
1,6-Bis[4-(4-amino-3-hydroxyphenoxy)phenyl]diamantane (DPD) induces growth inhibition in human cancer cells. In our previous study, we discovered that DPD irreversibly inhibits the growth of Colo 205 colon cancer cells at the G0/G1 phase and induces cell differentiation. However, the detailed mechanism is still unknown. In this study, we examined the functional importance of p21 and p53 in DPD-induced anticancer effects. We used three isogenic cell lines, HCT-116, HCT-116 p53-/- and HCT-116 p21-/-, to evaluate the roles of p21 and p53 in the in vitro anticancer effects of DPD. The in vivo anti-proliferative effect of DPD was demonstrated by HCT-116 and HCT-116 p21-/- xenograft models. DPD significantly inhibited the growth as well as increased the number of HCT-116 cells in the G0/G1 phase, but not in HCT-116 p53-/- and HCT-116 p21-/- cells examined by flow cytometry. Additionally, western blot analysis showed that DPD treatment induced p21, but not p53 protein expression in HCT-116 cells. The p21-associated cell cycle regulated proteins, such as cyclin D, CDK4 and pRb were decreased after DPD treatment in HCT-116 cells. The DPD-increased G0/G1 phase and induced cell cycle regulated protein expression were not observed in HCT-116 p21-/- and HCT-116 p53-/- cells. DPD decreased cell migration in HCT-116 and HCT-116 p53-/- but not in HCT-116 p21-/- cells. p21 was required for the DPD-induced in vitro anti-colon cancer effect. The in vivo study also showed that DPD significantly inhibited tumor growth through p21 signaling. Our results clearly demonstrate that DPD-induced in vitro and in vivo anticancer effects through the activation of p21 in HCT-116 cells.


Hydroxylation at carbon-2 of ent-16-oxo-17-norkauran-19-oic acid by Fusarium proliferatum.
A new product of biotransformation of ent-16-oxo-17-norkauran-19-oic acid (1) by Fusarium proliferatum was isolated and identified as a 2beta-hydroxy derivative (2). The structure of 2 was elucidated on the basis of spectroscopic data interpretation and single-crystal X-ray diffraction analysis. The allelopathic activity of compound 2 was evaluated on the growth of radicals and shoots of Lactuca sativa (lettuce). This is the first time that fungal hydroxylation at position C-2 has been reported on an ent-kaurane diterpene skeleton.


Allylmagnesium Halides Do Not React Chemoselectively Because Reaction Rates Approach the Diffusion Limit.
Competition experiments demonstrate that additions of allylmagnesium halides to carbonyl compounds, unlike additions of other organomagnesium reagents, occur at rates approaching the diffusion rate limit. Whereas alkylmagnesium and alkyllithium reagents could differentiate between electronically or sterically different carbonyl compounds, allylmagnesium reagents reacted with most carbonyl compounds at similar rates. Even additions to esters occurred at rates competitive with additions to aldehydes. Only in the case of particularly sterically hindered substrates, such as those bearing tertiary alkyl groups, were additions slower.


Monoclonal antibodies against rat Leydig cell surface antigens.
Monoclonal antibodies (MAbs) directed against the Leydig cell surface may be used to identify this cell in testicular preparations. Collagenase-dispersed adult rat interstitial cells were fractionated on Percoll density gradients, and Leydig cell-enriched fractions were used to prepare MAbs. Hybridomas were screened by enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IIF) on isolated testicular cells and immunocytochemical localization on paraffin sections of adult testes. In density gradient fractions, immunoglobulin (Ig) M MAbs (LC-1C6 and LC-6H6) labeled the surface of cells possessing the morphological characteristics of Leydig cells. The density gradient profiles of MAb-binding activity observed by IIF and ELISA were parallel with the Leydig cell distribution as determined by [125I]-human chorionic gonadotropin (hCG) binding, testosterone response to hCG in vitro, 3 beta-hydroxysteroid dehydrogenase histochemistry and electron microscopy. The MAbs prominently labeled most interstitial cells in sections, but there was little or no labeling of connective tissue, endothelial or seminiferous tubule cells. Both MAbs recognized components of Mr 58,000 in Western blots of Leydig cell-enriched extracts. The results indicate that LC-1C6 and LC-6H6 recognize antigens on the Leydig cell surface that are not present on other isolated testicular cells from the adult rat. These MAbs are specific markers of the Leydig cell in situ and in vitro.


Improving Adherence to Intraoperative Lung-Protective Ventilation Strategies at a University Medical Center.
Intraoperative lung-protective ventilation (ILPV) is defined as tidal volumes <8 mL/kg ideal bodyweight and is increasingly a standard of care for major abdominal surgical procedures performed under general anesthesia. In this study, we report the result of a quality improvement initiative targeted at improving adherence to ILPV guidelines in a large academic teaching hospital. We performed a time-series study to determine whether anesthesia provider adherence to ILPV was affected by certain improvement interventions and patient ideal body weight (IBW). Tidal volume data were collected at 3 different time points for 191 abdominal surgical cases from June 2014 through April 2015. Improvement interventions during that period included education at departmental grand rounds, creation of a departmental ILPV policy, feedback of tidal volume and failure rate data at grand rounds sessions, and reducing default ventilator settings for tidal volume. Mean tidal volume per kilogram of ideal body weight (VT/kg IBW) and rates of noncompliance with ILPV were analyzed before and after the interventions. A survey was administered to assess provider attitudes after implementation of improvement interventions. Responses before and after interventions and between physician and nonphysician providers were analyzed. Reductions in mean VT/kg IBW and rates of failure for providers to use ILPV occurred after improvement interventions. Patients with IBW <65 kg received higher VT/kg IBW and had higher rates of failure to use ILPV than patients with IBW >65 kg. Surveyed providers demonstrated stronger agreement to having knowledge and practice consistent with ILPV after interventions. Our interventions improved anesthesia provider adherence to low tidal volume ILPV. IBW was found to be an important factor related to provider adherence to ILPV. Provider attitudes about their knowledge and practice consistent with ILPV also changed with our interventions.


Preparation and characterization of isoniazid-loaded crude soybean lecithin liposomes.
Tuberculosis (TB) is a poverty related infectious disease that is rapidly giving rise to public health concerns. Lengthy drug administration and frequent adverse side-effects associated with TB treatment make anti-tubercular drugs (ATDs) good candidates for drug delivery studies. This work aimed to formulate and prepare liposomes as a cost-effective option for ATD delivery. Liposomes were prepared by film hydration using crude soybean lecithin (CL) and not pure phospholipids as in the normal practice. Cholesterol was also used (up to 25% mass ratio), and isoniazid (INH) was encapsulated as model drug using a freeze-thaw loading technique. Purified soybean lecithin (PL) was also used for comparative purposes, under the same conditions. INH-loaded liposomes were characterized for particle size, Zeta Potential (ZP), encapsulation efficiency (EE) and drug release. Physicochemical properties were investigated using thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction and Fourier transform infrared. INH-loaded CL-based liposomes showed high EE (79±2.45%). The average particle size (813.00±9.21nm) and ZP (-42.80±4.31mV) of this formulation are promising for the treatment of TB by pulmonary delivery. These findings suggest the possibility of encapsulating ATDs in liposomes made of crude soybean lecithin that is cheap and readily available.


Ultra-High-Field Magnetic Resonance Spectroscopy in Psychiatry.
The advantages of ultra-high-field (UHF ≥ 7T) MR have been demonstrated in a variety of MR acquisition modalities. Magnetic resonance spectroscopy (MRS) can particularly benefit from substantial gains in signal-to-noise ratio (SNR) and spectral resolution at UHF, enabling the quantification of numerous metabolites, including glutamate, glutamine, glutathione, and γ-aminobutyric acid that are relevant to psychiatric disorders. The aim of this review is to give an overview about the advantages and advances of UHF MRS and its application to psychiatric disorders. In order to provide a practical guide for potential applications of MRS at UHF, a literature review is given, surveying advantages and disadvantages of MRS at UHF. Key concepts, emerging technologies, practical considerations, and applications of UHF MRS are provided. Second, the strength of UHF MRS is demonstrated using some examples of its application in psychiatric disorders.


Protective Effect of Tocotrienol on In Vitro and In Vivo Models of Parkinson's Disease.
Parkinson's disease (PD) is a common progressive neurodegenerative disease. It has been reported that oxidative stress contributes, at least in part, to its pathogenesis. Although dietary epidemiological studies suggest that sufficient intake of vitamin E may prevent the onset of PD, antioxidative therapy for PD with exogenous antioxidants involving α-tocopherol has not been successful in the clinical setting thus far. In recent years, the non-antioxidant activities of vitamin E have been given attention to. In the present study, to determine the antioxidant-independent cytoprotective activity of vitamin E, we investigated whether tocotrienols (T3s), another members of vitamin E family, exhibit the neuroprotective effect in cell and mouse models of PD independently of their antioxidant activities. Treatment with T3s, especially γ- and δ-T3s, exhibited cytoprotective effects via activation of PI3K/Akt signaling pathway in a cellular PD model. We also identified estrogen receptor (ER) β as an upstream mediator of PI3K/Akt signaling and demonstrated the direct binding of T3 to ERβ in vitro. Silencing expression of caveolin suppressed the cytoprotective effects of T3, indicating that caveola formation plays an important role in the cytoprotection by T3 via ERβ/PI3K/Akt signaling pathway. Thus it has been shown that T3 exerts cytoprotective function by a novel mechanism, which includes membrane ERβ/PI3K/Akt signaling via caveola formation as well as its antioxidant activity. Furthermore, we revealed that δ-T3 treatment relieved PD-related symptoms in PD model mice. These results suggest that T3 elicits the cytoprotective effects via ERβ/PI3K/Akt signaling pathway in cellular and murine PD models.


Genome-Wide Quantification of the Effect of Gene Overexpression on Escherichia coli Growth.
Recombinant protein production plays an essential role in both biological studies and pharmaceutical production. Escherichia coli is one of the most favorable hosts for this purpose. Although a number of strategies for optimizing protein production have been developed, the effect of gene overexpression on host cell growth has been much less studied. Here, we performed high-throughput tests on the E. coli a complete set of E. coli K-12 ORF archive (ASKA) collection to quantify the effects of overexpressing individual E. coli genes on its growth. The results indicated that overexpressing membrane-associated proteins or proteins with high abundances of branched-chain amino acids tended to impair cell growth, the latter of which could be remedied by amino acid supplementation. Through this study, we expect to provide an index for a fast pre-study estimate of host cell growth in order to choose proper rescuing approaches when working with different proteins.


Effects of calcium and pressure treatment on thermal gelation of soybean protein.
The effect of calcium and high-pressure (HP) treatment on the heat gelation of soybean proteins was investigated. In the presence of calcium (2 to 25 mM), the gelation of dispersions of soybean protein isolate (SPI), a beta-conglycinin-enriched fraction (7SEF), and a glycinin-enriched fraction (11SEF) started with protein having a lower degree of denaturation. The gels from these dispersions had greater stiffness than the samples without added calcium. HP treatment had different effects on heat-induced gelation depending on the presence of calcium and on the nature of the proteins. In the absence of calcium, gels with low stiffness were formed after HP treatment, compared with untreated samples, and regardless of the sample type (SPI, 7SEF, 11SEF). In the presence of calcium, gel stiffness was increased after HP treatment of dispersions containing beta-conglycinin (SPI and 7SEF), while the opposite effect was observed for 11SEF. In the presence of calcium, HP treatment promoted a greater contribution of hydrophobic interactions in SPI and 7SEF. In the dispersions containing beta-conglycinin, these conditions also promoted the appearance of a heterogeneous distribution of molecular sizes, from enormous aggregates to dissociated species. Our results suggest that, in the presence of calcium, HP treatment has an opposite effect on the ability of glycinin and beta-conglycinin to participate in the formation of a 3-dimensional network upon heating.


Direct and Indirect Effects of Personality Traits on Psychological Distress in Women With Pelvic Floor Disorders.
The diagnosis and treatment of pelvic floor disorders may involve subjective self-report symptom measures that may be related to personality traits. We aimed to construct a model that integrates pelvic floor disorders, personality variables (optimism and neuroticism), psychological distress, and related demographic variables. In a cross-sectional study, conducted between August 2014 and June 2015, 155 women following an intake to an urogynecology outpatient clinic of a tertiary health center completed personality questionnaires of optimism and neuroticism (Life Orientation Test-Revised, 10-item Big Five Inventory), pelvic floor symptoms (Pelvic Floor Distress Inventory Short Form), psychological distress (18-item Brief Symptom Inventory), and a demographic questionnaire. A path analysis mediation model showed that patients who had more pelvic floor symptoms felt more psychological distress and that psychological distress increased as the level of neuroticism increased. As for optimism, the correlation to pelvic floor symptoms was nearly significant. Optimism and neuroticism had indirect effects on psychological distress through pelvic floor symptoms in women with urinary incontinence and pelvic organ prolapse. Neuroticism had a direct effect on psychological distress in these women as well. Our suggested statistical path analysis model supports the important role of personality traits in pelvic floor disorder self-reports and the effect of these traits on psychological distress. Therefore, the optimal treatment for pelvic floor symptoms should include psychological interventions in addition to traditional medical or surgical therapy in hope of reducing psychology distress associated with urinary incontinence and pelvic organ prolapse.


A new expanded modelling approach for investigating the bioprotective capacity of Latilactobacillus sakei CTC494 against Listeria monocytogenes in ready-to-eat fish products.
Understanding the role of food-related factors on the efficacy of protective cultures is essential to attain optimal results for developing biopreservation-based strategies. The aim of this work was to assess and model growth of Latilactobacillus sakei CTC494 and Listeria monocytogenes CTC1034, and their interaction, in two different ready-to-eat fish products (i.e., surimi-based product and tuna pâté) at 2 and 12 °C. The existing expanded Jameson-effect and a new expanded Jameson-effect model proposed in this study were evaluated to quantitatively describe the effect of microbial interaction. The inhibiting effect of the selected lactic acid bacteria strain on the pathogen growth was product dependent. In surimi product, a reduction of lag time of both strains was observed when growing in coculture at 2 °C, followed by the inhibition of the pathogen when the bioprotective L. sakei CTC494 reached the maximum population density, suggesting a mutualism-antagonism continuum phenomenon between populations. In tuna pâté, L. sakei CTC494 exerted a strong inhibition of L. monocytogenes at 2 °C (<0.5 log increase) and limited the growth at 12 °C (<2 log increase). The goodness-of-fit indexes indicated that the new expanded Jameson-effect model performed better and appropriately described the different competition patterns observed in the tested fish products. The proposed expanded competition model allowed for description of not only antagonistic but also mutualism-based interactions based on their influence on lag time.


Robust meta gradient learning for high-dimensional data with noisy-label ignorance.
Large datasets with noisy labels and high dimensions have become increasingly prevalent in industry. These datasets often contain errors or inconsistencies in the assigned labels and introduce a vast number of predictive variables. Such issues frequently arise in real-world scenarios due to uncertainties or human errors during data collection and annotation processes. The presence of noisy labels and high dimensions can significantly impair the generalization ability and accuracy of trained models. To address the above issues, we introduce a simple-structured penalized γ-divergence model and a novel meta-gradient correction algorithm and establish the foundations of these two modules based on rigorous theoretical proofs. Finally, comprehensive experiments are conducted to validate their effectiveness in detecting noisy labels and mitigating the curse of dimensionality and suggest that our proposed model and algorithm can achieve promising outcomes. Moreover, we open-source our codes and distinctive datasets on GitHub (refer to https://github.com/DebtVC2022/Robust_Learning_with_MGC).


Response of pre-adult and adult stages of Trichuris muris to common anthelmintics in mice.
The common anthelmintics, oxantel, mebendazole, albendazole and pyrantel were assessed for their comparative activity against Trichuris muris in mice. Mice were infected with T. muris and the infection was maintained by a brief cortisone administration during the second week of infection. Mice carrying the infection with different life cycle stages, viz. fourth stage larvae (L4), pre-adult and adult stages were dosed with anthelminitics. The worm burdens in control infection groups varied although infection dose and other conditions were uniformly followed. With various dose regimens tested, oxantel was highly potent; it eliminated completely pre-adult and adult stages, respectively at 25 and 12.5 mg kg-1 dose levels with significant activity also against adult worms at a 1.56 mg kg-1 dose level and against pre-adults at a 6.25 mg kg-1 level. Pre-adults required twice the dose given to that of adults for complete (100%) activity. Mebendazole was the next most active; a dosage of 37.5 mg kg-1 was completely active against pre-adults whereas a dosage of 2 x 50 mg kg-1 was required for complete elimination of adult worms. In addition, about 90% of the worms were eliminated with a single dose of 150 mg kg-1. However, a significant activity was seen against adults at a 25 mg kg-1 level and pre-adults at 37.5 mg kg-1, the lowest level tested. In comparison, albendazole did not induce complete clearance of pre-adult and adult stages even when tested at dose levels as high as 150 and 2 x 75 mg kg-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Transcranial direct current stimulation: State of the art 2008.
Effects of weak electrical currents on brain and neuronal function were first described decades ago. Recently, DC polarization of the brain was reintroduced as a noninvasive technique to alter cortical activity in humans. Beyond this, transcranial direct current stimulation (tDCS) of different cortical areas has been shown, in various studies, to result in modifications of perceptual, cognitive, and behavioral functions. Moreover, preliminary data suggest that it can induce beneficial effects in brain disorders. Brain stimulation with weak direct currents is a promising tool in human neuroscience and neurobehavioral research. To facilitate and standardize future tDCS studies, we offer this overview of the state of the art for tDCS.


The Polyamorous Childbearing and Birth Experiences Study (POLYBABES): a qualitative study of the health care experiences of polyamorous families during pregnancy and birth.
As many as 1 in 5 adults practise some type of consensual nonmonogamy such as polyamory; many are married, have children, or both. Polyamorous families face unique challenges when accessing care during pregnancy and birth, and qualitative descriptive studies are needed to understand their experiences and inform health care providers' practice. Participants, who self-identified as polyamorous, had given birth in the last 5 years and received at least some prenatal care, were recruited through convenience sampling on social media. Any of the birthing individual's partners were also invited to participate. All participants completed a short demographic questionnaire and participated in a semistructured interview. Interview transcripts were coded using Braun and Clarke's iterative thematic analysis. A total of 24 participants, 11 who had given birth and 13 partners, were interviewed. Of those who had given birth, 5 received midwifery care only, 4 received obstetric care exclusively and 2 received shared care. Polyamorous families described sharing many common experiences during pregnancy and birth that were affected by their polyamorous identity. Although participants reported both positive and negative experiences with health care providers, when accessing health care all had experienced some form of marginalization that was related to their polyamorous status. One particular challenge for families was with respect to disclosure of polyamorous identity in hospital environments. Participants offered suggestions for improving the health care of polyamorous families during pregnancy and birth, including creating nonjudgmental spaces, accommodating difference through minimizing administrative barriers and allying with patients by providing patient-led care. Polyamorous families face marginalization when accessing pregnancy and birth care. Care experiences for polyamorous families can be improved by nonjudgmental, open attitudes of health care providers, and modifications to hospital policies to support multiparent families.


Beta adrenoceptors mediate the catecholamine-induced stimulation of oxytocin secretion from cultured bovine granulosa cells.
Bovine granulosa cells were treated in culture with alpha- and beta-adrenoceptor ligands to determine the receptor subtype mediating their response to catecholamines. The secretion of oxytocin by granulosa cells in serum-free medium was measured on the fourth day of culture (during the period of acquisition of a luteal phenotype). Cultures were performed in the presence of 0.5 mM ascorbic acid, which increased hormone output and potentiated the response to catecholamines. The effects of adrenaline and noradrenaline on oxytocin secretion were concentration-dependent; maximum stimulation was over 700% with adrenalin (EC50 92 nM) and 500% with noradrenaline (EC50 87 nM). The response to noradrenaline (10(-6) M) and adrenaline (10(-6) M) could be blocked by propranolol but not by phentolamine, suggesting that beta- rather than alpha-adrenoceptors were involved. Blockade by metoprolol and practolol (beta 1-adrenoceptor antagonists) was poor and dobutamine (beta 1-agonist) was weakly stimulatory. A concentration-dependent stimulatory response (EC50 200 nM) was obtained with salbutamol (beta 2-adrenoceptor agonist) and stimulation by adrenaline or salbutamol could be blocked by a selective beta 2-adrenoceptor antagonist (ICI 118,551). It is concluded that, during luteinization, the long-term response of bovine granulosa cells to stimulation induced by catecholamines is mediated through beta- rather than alpha-adrenoceptors. Although the beta 2-subtype is probably involved, the similar potencies of adrenaline and noradrenaline are uncharacteristic of beta 2-adrenoceptors and may be peculiar to the long-term response shown by these cells.


Conditional cash transfers to improve use of health facilities by mothers and newborns in conflict affected countries, a prospective population based intervention study from Afghanistan.
The effects of conditional cash transfer (CCT) programs on maternal and child health (MCH) service use in conflicted affected countries such as Afghanistan are not known. We conducted a non-randomised population based intervention study in six Afghanistan districts from December 2016 to December 2017. Six control districts were purposively matched. Women were eligible to be included in the baseline and endline evaluation surveys if they had given birth to one or more children in the last 12 months. The intervention was a CCT program including information, education, communication (IEC) program about CCT to community members and financial incentives to community health workers (CHWs) and families if mothers delivered their child at a health facility. Control districts received standard care. The primary objective was to assess the effect of CCT on use of health facilities for delivery. Secondary objectives were to assess the effect of CCT on antenatal care (ANC), postnatal care (PNC) and CHW motivation to perform home visits. Outcomes were analysed at 12 months using multivariable difference-in-difference linear regression models adjusted for clustering and socio demographic variables. Overall, facility delivery increased in intervention villages by 14.3% and control villages by 8.4% (adjusted mean difference [AMD] 3.3%; 95% confidence interval [- 0.14 to 0.21], p value 0.685). There was no effect in the poorest quintile (AMD 0.8% [- 0.30 to 0.32], p value 0.953). ANC (AMD 45.0% [0.18 to 0.72] p value 0.004) and PNC (AMD 31.8% [- 0.05 to 0.68] p value 0.080) increased in the intervention compared to the control group. CHW home visiting changed little in intervention villages (- 3.0%) but decreased by - 23.9% in control villages (AMD 12.2% [- 0.27 to 0.51], p value 0.508). CCT exposure was 27.3% (342/1254) overall and 10.2% (17/166) in the poorest quintile. Our study demonstrated that a CCT program provided to women aged 16-49 years can be implemented in a highly conservative conflict affected population. CCT should be scaled up for the poorest women in Afghanistan.


Non-linear feeding functional responses in the Greater Flamingo (Phoenicopterus roseus) predict immediate negative impact of wetland degradation on this flagship species.
Accurate knowledge of the functional response of predators to prey density is essential for understanding food web dynamics, to parameterize mechanistic models of animal responses to environmental change, and for designing appropriate conservation measures. Greater flamingos (Phoenicopterus roseus), a flagship species of Mediterranean wetlands, primarily feed on Artemias (Artemia spp.) in commercial salt pans, an industry which may collapse for economic reasons. Flamingos also feed on alternative prey such as Chironomid larvae (e.g., Chironomid spp.) and rice seeds (Oryza sativa). However, the profitability of these food items for flamingos remains unknown. We determined the functional responses of flamingos feeding on Artemias, Chironomids, or rice. Experiments were conducted on 11 captive flamingos. For each food item, we offered different ranges of food densities, up to 13 times natural abundance. Video footage allowed estimating intake rates. Contrary to theoretical predictions for filter feeders, intake rates did not increase linearly with increasing food density (type I). Intake rates rather increased asymptotically with increasing food density (type II) or followed a sigmoid shape (type III). Hence, flamingos were not able to ingest food in direct proportion to their abundance, possibly because of unique bill structure resulting in limited filtering capabilities. Overall, flamingos foraged more efficiently on Artemias. When feeding on Chironomids, birds had lower instantaneous rates of food discovery and required more time to extract food from the sediment and ingest it, than when filtering Artemias from the water column. However, feeding on rice was energetically more profitable for flamingos than feeding on Artemias or Chironomids, explaining their attraction for rice fields. Crucially, we found that food densities required for flamingos to reach asymptotic intake rates are rarely met under natural conditions. This allows us to predict an immediate negative effect of any decrease in prey density upon flamingo foraging performance.


Expression of programmed death ligand-1 and programmed death 1 in hepatocellular carcinoma and its clinical significance.
To investigate the correlation between the expression of programmed death 1 (PD-1) and PD ligand-1 (PD-L1) in hepatocellular carcinoma (HCC) and clinical parameters. The study comprised tumor sections from 45 HCC patients treated with curative resection, which were evaluated for PD-1 and PD-L1 protein expression by immunohistochemistry. PD-1 and PD-L1 expression was increased in cancers compared to adjacent normal tissues, with a positive rate of 37.78% (17/45) and 62.22% (28/45), respectively, which was positively correlated with the tumor stage and lymph node metastasis, negatively with postoperative prognosis. PD-1 positivity was most frequently observed in stromal tumor-infiltrating lymphocytes. The number of PD-1 positive lymphocyte was correlated with PD-L1 positive expression. PD-L1 and PD-1 are overexpressed in HCC tissues. PD-L1 expression plays a critical role in the pathogenesis of human HCC, suggesting that it might be used as a new biomarker to predict the disease progression and prognosis.


The temporal precedence of metacognition in the development of anxiety and depression symptoms in the context of life-stress: a prospective study.
According to the metacognitive theory of psychological disorder, metacognitions are vulnerability factors in predicting development of psychological symptoms. The present study investigated metacognitive factors and life stress in a prospective test of their proposed temporal precedence in the development of anxiety and depression symptoms. Participants were 172 students and adults recruited in Ankara and Bolu, Turkey. Two separate sets of hierarchical regression analyses were conducted. In these analyses, Time 2 anxiety or depression was regressed on the main and interaction effects of metacognition and stress after controlling for baseline symptom levels measured at Time 1, age, and gender. Results revealed that negative metacognitive beliefs about the uncontrollability and danger of worry significantly predicted residual change in both anxiety and depression after controlling for the negative effect of stressful life events. Furthermore, lack of cognitive confidence interacted with daily hassles to predict the change in anxiety, when the baseline level of anxiety and other individual differences were controlled. Our results support the metacognitive theory of psychopathology.


Transgender and non-binary people's experiences with alcohol reduction in the UK: A cross-sectional study.
Transgender (trans) and non-binary people experience disproportionate harm from alcohol use, have a greater likelihood of developing dependence, and experience exclusion from both clinical and peer-based support systems. This study aimed to understand experiences with and preferences for alcohol reduction support among UK-based transgender and non-binary people. The study team and community stakeholders co-produced a cross-sectional survey and administered it to a purposive sample of trans and non-binary people from 1st February to 31st March 2022. The study recruited participants through social media, mailing lists, blog posts, and news articles. Participants (n = 565) had a lifetime history of alcohol use, were in one of five gender categories, and were classified as people who drink or formerly drank alcohol. Open- and closed-ended questions measured motivations for alcohol reduction and views surrounding various support modalities. More than 15 % of the sample no longer drink alcohol and reported long-term abstinence, achieved without support, and were motivated by a loss of control over drinking behaviour and a desire to improve both physical and mental health. Mental illness, gender dysphoria, and a culture of alcohol excess were common antecedents of alcohol use. Thirty percent of participants who drink alcohol wanted to reduce their consumption. They suggested that this could be achieved with self-help tools, specialist trans and non-binary or LGBT+ services, access to both gender-affirming medical services, and sober queer social spaces. UK-based trans and non-binary people face unique gender minority-related stressors which contribute to patterns of alcohol use that are perceived to be out of control and harmful to health. While many wanted access to self-help tools, there was interest in the availability of specialist alcohol reduction services and more inclusive general services. Conducting needs assessments to inform Needs assessments should inform the development of such services and trans-affirmative training should be mandated for all who provide support with alcohol reduction.


Occurrence, transplantation, and histologic characteristics of nephroblastoma in the Nb hooded rat.
Ten kidney tumors conforming to nephroblastoma were encountered during a 10-year period in a closed colony of Nb hooded rats. Histologic examination of the primary neoplasms, and of a limited number of transplanted derivatives, indicates that spontaneous nephroblastoma in the rat is exclusively an epithelial neoplasm, consisting of dense aggregates of undifferentiated, basophilic blast cells set in a connective tissue stroma of benign character. This uniform entity should be clearly distinguished from renal mesenchymal tumor, a connective tissue neoplasm of heterogeneous form which is induced frequently in rats by certain chemical carcinogens.


Predicting environmental stressor levels with machine learning: a comparison between amplicon sequencing, metagenomics, and total RNA sequencing based on taxonomically assigned data.
Microbes are increasingly (re)considered for environmental assessments because they are powerful indicators for the health of ecosystems. The complexity of microbial communities necessitates powerful novel tools to derive conclusions for environmental decision-makers, and machine learning is a promising option in that context. While amplicon sequencing is typically applied to assess microbial communities, metagenomics and total RNA sequencing (herein summarized as omics-based methods) can provide a more holistic picture of microbial biodiversity at sufficient sequencing depths. Despite this advantage, amplicon sequencing and omics-based methods have not yet been compared for taxonomy-based environmental assessments with machine learning. In this study, we applied 16S and ITS-2 sequencing, metagenomics, and total RNA sequencing to samples from a stream mesocosm experiment that investigated the impacts of two aquatic stressors, insecticide and increased fine sediment deposition, on stream biodiversity. We processed the data using similarity clustering and denoising (only applicable to amplicon sequencing) as well as multiple taxonomic levels, data types, feature selection, and machine learning algorithms and evaluated the stressor prediction performance of each generated model for a total of 1,536 evaluated combinations of taxonomic datasets and data-processing methods. Sequencing and data-processing methods had a substantial impact on stressor prediction. While omics-based methods detected a higher diversity of taxa than amplicon sequencing, 16S sequencing outperformed all other sequencing methods in terms of stressor prediction based on the Matthews Correlation Coefficient. However, even the highest observed performance for 16S sequencing was still only moderate. Omics-based methods performed poorly overall, but this was likely due to insufficient sequencing depth. Data types had no impact on performance while feature selection significantly improved performance for omics-based methods but not for amplicon sequencing. We conclude that amplicon sequencing might be a better candidate for machine-learning-based environmental stressor prediction than omics-based methods, but the latter require further research at higher sequencing depths to confirm this conclusion. More sampling could improve stressor prediction performance, and while this was not possible in the context of our study, thousands of sampling sites are monitored for routine environmental assessments, providing an ideal framework to further refine the approach for possible implementation in environmental diagnostics.


Factors influencing the accuracy of fetal weight estimation with a focus on preterm birth at the limit of viability: a systematic literature review.
Fetal weight estimation (FWE) is an important factor for clinical management decisions, especially in imminent preterm birth at the limit of viability between 23(0/7) and 26(0/7) weeks of gestation. It is crucial to detect and eliminate factors that have a negative impact on the accuracy of FWE. In this systematic literature review, we investigated 14 factors that may influence the accuracy of FWE, in particular in preterm neonates born at the limit of viability. We found that gestational age, maternal body mass index, amniotic fluid index and ruptured membranes, presentation of the fetus, location of the placenta and the presence of multiple fetuses do not seem to have an impact on FWE accuracy. The influence of the examiner's grade of experience and that of fetal gender were discussed controversially. Fetal weight, time interval between estimation and delivery and the use of different formulas seem to have an evident effect on FWE accuracy. No results were obtained on the impact of active labor. This review reveals that only few studies investigated factors possibly influencing the accuracy of FWE in preterm neonates at the limit of viability. Further research in this specific age group on potential confounding factors is needed.


Eptacog alfa activated: a recombinant product to treat rare congenital bleeding disorders.
Glanzmann's thrombasthenia (GT) and congenital factor VII deficiency (FVII CD) are rare autosomal recessive bleeding disorders: GT is the most frequent congenital platelet function disorder, and FVII CD is the most common factor-deficiency disease after haemophilia. The frequency of these disorders in the general population ranges from 1:500,000 to 1:2,000,000. Because GT and FVII CD are both rare, registries are the only approach possible to allow the collection and analysis of sufficient observational data. Recombinant activated factor VII (rFVIIa, eptacog alfa activated) is indicated for the treatment of acute bleeding episodes and for surgery coverage in patients with GT who are refractory to platelets and have antiplatelet or anti-human leukocyte antigen (HLA) antibodies, and for the prevention and treatment of bleeding in patients with FVII CD. This article summarises published data on the mechanism of action and use of rFVIIa in these disorders from two international, prospective, observational registries: the Glanzmann's Thrombasthenia Registry (GTR) for GT; and the Seven Treatment Evaluation Registry (STER) for FVII CD. Haemostatic effectiveness rates with rFVIIa were high across all patients with GT and those with FVII CD, and treatment with rFVIIa in the GTR and STER registries was well tolerated. The GTR and the STER are the largest collections of data in GT and FVII CD, respectively, and have expanded our knowledge of the management of these two rare bleeding disorders.


X IRRADIATION OF A SENSITIVE AND A RESISTANT STRAIN OF ESCHERICHIA COLI UNDER CONTROLLED OXYGEN CONCENTRATIONS.
van Soestbergen, A. A. (Brookhaven National Laboratory, Upton, N.Y.). X irradiation of a sensitive and a resistant strain of Escherichia coli under controlled oxygen concentrations. J. Bacteriol. 89:1032-1034. 1965.-Radiosensitive and radioresistant strains of Escherichia coli were given an X-ray dose of 4,544 rad at various controlled O(2) concentrations, and the results were subjected to probit analysis. A varkappa(2) test gave no evidence of heterogeneity of departure from fitted parallel probit lines obtained after plotting the probit of the surviving fractions of each of the two strains on the logarithm of the O(2) concentration. Under the conditions of the experiment, the ratio of the oxygen concentrations at which equal fractions of populations of E. coli B/r and E. coli B-s were killed by X irradiation was estimated to be about 4.4.


EGF-induced redistribution of erbB2 on breast tumor cells: flow and image cytometric energy transfer measurements.
erbB2, a member of the epidermal growth factor (EGF) receptor-type tyrosine kinase receptor family, is overexpressed in breast carcinomas with poor prognosis. We examined the cell surface association of this receptor with itself and with other cell surface proteins by the Förster-type fluorescence resonance energy transfer using whole antibodies and Fab fragments. We found that erbB2 molecules homoassociate in unstimulated SK-BR-3, BT474 and BT474-M (a metastatic version of the parent BT474 line) breast tumor cells, and that the interaction was enhanced by EGF treatment in suspensions of SK-BR-3 and BT474-M cells. BT474 cells (with low EGF receptor expression) and attached SK-BR-3 cells do not respond to EGF. Image microscopic energy transfer measurements found considerable pixel-by-pixel heterogeneity in the homoassociation state of erbB2. In accordance with the EGF-induced redistribution of erbB2, EGF receptor was found to be in close proximity to erbB2 in FRET measurements. By labeling different epitopes on erbB2 and the lipid bilayer, we were able to prepare an epitope map of erbB2 molecule. Our data suggest the existence of dynamic cell surface patterns of erbB2 and point to functions fulfilled by these molecular complexes.


Sexuality after breast cancer treatment: changes and coping strategies among Japanese survivors.
Sexuality after a cancer diagnosis has long been neglected in the clinical and research settings in many countries. In particular, research in Asia on sexuality and cancer among women is extremely scarce. Semi-structured interviews were conducted with 21 Japanese women with breast cancer (mean age 42.2 years; median length between surgery and first interview 17 months) to explore their views on sexuality following breast cancer treatment. Analysis using the Grounded Theory approach revealed four major themes: (a) hesitation in resuming sex after treatment, (b) sexual changes after resuming sex, (c) coping attitudes to the changes, and (d) long-term outcomes of the relationship with partners. Contrary to Japanese breast surgeons' optimistic outlooks, the majority of informants referred to the impact of treatment on the physical as well as psychological aspects of their sexuality. Factors that influenced women's experiences included the pace of their psychological and physical recovery after treatment, fear of their partner's negative response, the importance of the sexual relationship for the couple, and their partner's understanding and support. Suggestions for medical professionals on how to support women's sexuality after cancer are discussed with reference to the Japanese socio-cultural and medical context.


Nano-Formulation of Ethambutol with Multifunctional Graphene Oxide and Magnetic Nanoparticles Retains Its Anti-Tubercular Activity with Prospects of Improving Chemotherapeutic Efficacy.
Tuberculosis (TB) is a dreadful bacterial disease, infecting millions of human and cattle every year worldwide. More than 50 years after its discovery, ethambutol continues to be an effective part of the World Health Organization's recommended frontline chemotherapy against TB. However, the lengthy treatment regimens consisting of a cocktail of antibiotics affect patient compliance. There is an urgent need to improve the current therapy so as to reduce treatment duration and dosing frequency. In this study, we have designed a novel anti-TB multifunctional formulation by fabricating graphene oxide with iron oxide magnetite nanoparticles serving as a nano-carrier on to which ethambutol was successfully loaded. The designed nanoformulation was characterised using various analytical techniques. The release of ethambutol from anti-TB multifunctional nanoparticles formulation was found to be sustained over a significantly longer period of time in phosphate buffer saline solution at two physiological pH (7.4 and 4.8). Furthermore, the nano-formulation showed potent anti-tubercular activity while remaining non-toxic to the eukaryotic cells tested. The results of this in vitro evaluation of the newly designed nano-formulation endorse its further development in vivo.


[The evaluation of gonadal function in postpubertal patients treated for cryptorchism in childhood].
Descent of the testes is essential for normal function, with cryptorchidism being associated with defective spermatogenesis. The postpubertal function of cryptorchid testicles seems to be related to the original location of the undescended testis and the age at the moment of treatment. The objective of this study was to evaluate the pubertal development and gonadal function in postpubertal patients treated for cryptorchidism during childhood. Twenty postpubertal males with a mean age of 17.35 years (range: 15-21 years) and treated for cryptorchidism during childhood were evaluated for pubertal development and gonadal function. A hormonal study which included basal determinations of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), testicular volume assessed by Prader's orchidometer and semen analysis was performed on each patient. Complete virilization was observed in all patients. The start and development of puberty were normal in all cases (except one patient that started puberty at 10 years of age). Basal studies in all patients showed normal levels of LH and testosterone. FSH levels were increased in 3 patients and normal in the other 17 patients. Fourteen patients achieved normal spermatogenesis with more than 20 million spermatozoa/ml. In the other 7 patients (35%), 5 with unilateral cryptorchidism and 2 with bilateral cryptorchidism, the sperm count remained below 20 million with a range of 0.8 to 18.4 x 10(6) spermatozoa/ml. The three males with elevated levels of FSH also presented oligospermia. The results obtained show that pubertal development is normal after cryptorchidism. Impaired spermatogenesis is a major factor in undescended testes. Basal SH levels can be useful in predicting germinal damage secondary to cryptorchidism.


Hollow crescents, helices, and macrocycles from enforced folding and folding-assisted macrocyclization.
This Account reviews the progress made by us on creating porous molecular crescents, helices, and macrocycles based on aromatic oligoamides. Inspired by natural pore- or cavity-containing secondary structures, work described in this Account stemmed from the development of foldamers consisting of benzene rings linked by secondary amide groups. Highly stable, three-center intramolecular hydrogen bonds involving the amide linkages are incorporated into these aromatic oligoamides, which, along with meta-linked benzene units that introduce curvatures into the corresponding backbones, leads to tape-like, curved backbones. Depending on their chain lengths, aromatic oligoamides that fold into crescent and helical conformations have been obtained. Combining results from modeling and experimentally measured data indicates that the folding of these oligomers is readily predictable, determined by the localized intramolecular three-center H-bonds and is independent of side-chain substitution. As a result, a variety of reliably folded, modifiable scaffolds can now be constructed. The well-defined crescent or helical conformations contain noncollapsible internal cavities having multiple introverted amide oxygen atoms. Changing the backbone curvature by tuning the ratio of meta- to para-linked benzene units leads to crescents or helices with cavities of tunable sizes. For example, oligoamides consisting of meta-linked units contain cavities of approximately 9 A across, while those with alternating meta- and para-linked units have cavities of over 30 A across. The generality of such a folding and cavity-creating strategy has also been demonstrated by the enforced folding of other types of aromatic oligomers such as oligo(phenylene ethynylene)s, aromatic oligoureas, and aromatic oligosulfonamides. More recently, the folding of aromatic oligoamides was found to assist efficient macrocyclization reactions, which has provided a convenient method for preparing a new class of large shape-persistent macrocycles in high yields. The folded and cyclic structures were extensively characterized based on multiple techniques such as one- and two-dimensional NMR, mass spectrometry, and X-ray crystallography, as well as theoretical calculations. The enforced folding and folding-assisted cyclization of oligomers have provided a predictable strategy for developing crescent, helical, and cyclic structures containing nanosized voids that are mostly associated with the tertiary and quaternary structures of proteins. The availability of these porous molecules has supplied a new class of nanosized building blocks that provide both opportunities and challenges for creating the next-generation nanostructures capable of presenting multiple introverted functional groups, forming various pores and channels, and finally, developing protein-like pockets.


Proteomic approaches in biological and medical sciences: principles and applications.
After the first introduction of the concept of "proteome" more than 10 years ago, large-scale studies of protein expression, localization, activities and interactions have gained an exponential increase of interest, leading to extensive research and technology development. Proteomics is expansively applied in many areas, ranging from basic research, various disease and malignant tumors diagnostic and biomarker discovery to therapeutic applications. Several proteomics approaches have been developed for protein separation and identification, and for the characterization of protein function and structure. Two-dimensional gel electrophoresis, chromatography, capillary electrophoresis and mass spectrometry have become the most used proteomics methods. These techniques are also under constant development. This review provides an overview of the main techniques and their combinations, used in proteomics. The emphasis is made on description of advantages and disadvantages of each technique, to navigate in selection of the best application for solving a specific problem.


Cervical stenosis in adults undergoing thoracolumbar deformity surgery: incidence, treatment, and complications: clinical article.
The goals of this study were to determine the incidence of occult cervical stenosis in patients over 50 years old with thoracolumbar deformity and to assess the risk of progressive cervical myelopathy after complex thoracolumbar reconstruction in asymptomatic or mildly symptomatic patients with cervical stenosis. Charts and cervical imaging for patients who were over 50 years old when they had undergone thoracolumbar deformity surgery between 2005 and 2008 were reviewed. Patients with primary neurological disorders were excluded from the study. Seventy-three patients (56 women and 17 men) met the study inclusion criteria. The minimum follow-up time was 2 years. Fifty-eight percent of patients (42 of 73) had cervical stenosis on advanced imaging. Thirty-three patients had mild or moderate stenosis; only 3 of these patients had clinical myelopathy. Nine patients (12%) had critical cervical stenosis, as determined from imaging; among these patients, 3 had moderate or severe myelopathy. Patients with noncritical stenosis and no or mild myelopathy underwent thoracolumbar reconstruction without any postoperative progression of myelopathy. Patients with critical stenosis and/or moderate or severe myelopathy were offered cervical decompression prior to thoracolumbar reconstruction; those who accepted this offer did not have progression of myelopathy. One patient underwent thoracolumbar reconstruction first despite critical cervical stenosis. At 20 months, her cervical myelopathy had progressed, and she ultimately required cervical decompression. Cervical stenosis, even critical stenosis in some cases, was seen in more than one-half of the patients. Most presented without obvious cervical complaints. In those with mild to moderate stenosis and no or mild myelopathy, lengthy thoracolumbar reconstruction procedures were not associated with progression of the myelopathy. The authors recommend that all adults with thoracolumbar deformity undergo a detailed upper- and lower-extremity neurological examination prior to major thoracolumbar reconstruction.


Adaptive methods: when and how should they be used in clinical trials?
Adaptive clinical trial designs are defined as designs that use data cumulated during trial to possibly modify certain aspects without compromising the validity and integrity of the said trial. Compared to more traditional trials, in theory, adaptive designs allow the same information to be generated but in a more efficient manner. The advantages and limits of this type of design together with the weight of the constraints, in particular of a logistic nature, that their use implies, differ depending on whether the trial is exploratory or confirmatory with a view to registration. One of the key elements ensuring trial integrity is the involvement of an independent committee to determine adaptations in terms of experimental design during the study. Adaptive methods for clinical trials are appealing and may be accepted by the relevant authorities. However, the constraints that they impose must be determined well in advance.