Homoallylglycine residues are superior precursors to orthogonally modified thioether containing polypeptides.

Homoallylglycine N-carboxyanhydride, Hag NCA, monomers were synthesized and used to prepare polypeptides containing Hag segments with controllable lengths of up to 245 repeats. Poly(l-homoallylglycine), GHA, was found to adopt an α-helical conformation, which provided good solubility in organic solvents and allowed high yield functionalization of its alkene side-chains via radical promoted addition of thiols. The conformations of these derivatives were shown to be switchable between α-helical and disordered states in aqueous media using thioether alkylation or oxidation reactions. Incorporation of GHA segments into block copolymers with poly(l-methionine), M, segments provided a means to orthogonally modify thioether side-chains different ways in separate copolypeptide domains. This approach allows preparation of functional polypeptides containing discrete domains of oxidized and alkylated thioether containing residues, where chain conformation and functionality of each domain can be independently modified

Modification of Poly(5,6-epoxy-l-norleucine) Gives Functional Polypeptides with Alternative Side-Chain Linkages.

The preparation and characterization of a new epoxide containing polypeptide, poly(5,6-epoxy-l-norleucine), via postpolymerization modification of poly(l-homoallylglycine) is described. Addition of thiols to the epoxide groups in poly(5,6-epoxy-l-norleucine) was studied as a means to prepare side-chain functional polypeptides. The solution properties of the derivatized polypeptides were studied in water and compared to similar thioether containing functional polypeptides prepared via different routes. Subtle differences in side-chain linkage chemistry were found to influence polypeptide solubility, chain conformation in solution, and thermoresponsive behavior. Poly(5,6-epoxy-l-norleucine) was found to be useful as a readily prepared intermediate that can be reacted with thiols to give a variety of functional polypeptides

Polypeptide gels incorporating the exotic functional aromatic amino acid 4-amino-L-phenylalanine

High-molecular-weight polypeptides with functional aromatic side chains, poly(4-amino-l-phenylalanine), were prepared by the metal-initiated polymerization of the Nα-carboxyanhydride of the corresponding amino acid, which is a microbial derivative of phenylalanine

A Systematic Review of Comparative Efficacy of Treatments and Controls for Depression

Background: Although previous meta-analyses have examined effects of antidepressants, psychotherapy, and alternative therapies for depression, the efficacy of these treatments alone and in combination has not been systematically compared. We hypothesized that the differences between approved depression treatments and controls would be small. Methods and Findings: The authors first reviewed data from Food and Drug Administration Summary Basis of Approval reports of 62 pivotal antidepressant trials consisting of data from 13,802 depressed patients. This was followed by a systematic review of data from 115 published trials evaluating efficacy of psychotherapies and alternative therapies for depression. The published depression trials consisted of 10,310 depressed patients. We assessed the percentage symptom reduction experienced by the patients based on treatment assignment. Overall, antidepressants led to greater symptom reduction compared to placebo among both unpublished FDA data and published trials (F = 38.5, df = 239, p<0.001). In the published trials we noted that the magnitude of symptom reduction with active depression treatments compared to controls was significantly larger when raters evaluating treatment effects were un-blinded compared to the trials with blinded raters (F = 2.17, df = 313, p<0.05). In the blinded trials, the combination of antidepressants and psychotherapy provided a slight advantage over antidepressants (p = 0.027) and psychotherapy (p = 0.022) alone. The magnitude of symptom reduction was greater with psychotherapies compared to placebo (p = 0.019), treatment-as-usual (p = 0.012) and waiting-list (p<0.001). Differences were not seen with psychotherapy compared to antidepressants, alternative therapies or active intervention controls. Conclusions: In conclusion, the combination of psychotherapy and antidepressants for depression may provide a slight advantage whereas antidepressants alone and psychotherapy alone are not significantly different from alternative therapies or active intervention controls. These data suggest that type of treatment offered is less important than getting depressed patients involved in an active therapeutic program. Future research should consider whether certain patient profiles might justify a specific treatment modality

Turkiya : geografya shel mamlekhet Turkiya ha-Asit ve-ha-Eropit

https://www.ester.ee/record=b5454920*es

Verbal and physical violence towards hospital- and community-based physicians in the Negev: an observational study

BACKGROUND: Over recent years there has been an increasing prevalence of verbal and physical violence in Israel, including in the work place. Physicians are exposed to violence in hospitals and in the community. The objective was to characterize acts of verbal and physical violence towards hospital- and community-based physicians. METHODS: A convenience sample of physicians working in the hospital and community completed an anonymous questionnaire about their experience with violence. Data collection took place between November 2001 and July 2002. One hundred seventy seven physicians participated in the study, 95 from the hospital and 82 from community clinics. The community sample included general physicians, pediatricians, specialists and residents. RESULTS: Ninety-nine physicians (56%) reported at least one act of verbal violence and 16 physicians (9%) reported exposure to at least one act of physical violence during the previous year. Fifty-one hospital physicians (53.7%) were exposed to verbal violence and 9 (9.5%) to physical violence. Forty-eight community physicians (58.5%) were exposed to verbal violence and 7 (8.5%) to physical violence. Seventeen community physicians (36.2%) compared to eleven hospital physicians (17.2%) said that the violence had a negative impact on their family and on their quality of life (p < 0.05). The most common causes of violence were long waiting time (46.2%), dissatisfaction with treatment (15.4%), and disagreement with the physician (10.3%). CONCLUSION: Verbal and/or physical violence against physicians is common in both the hospital and in community clinics. The impatience that accompanies waiting times may have a cultural element. Shortening waiting times and providing more information to patients and families could reduce the rate of violence, but a cultural change may also be required

The Genomic Signature of Crop-Wild Introgression in Maize

The evolutionary significance of hybridization and subsequent introgression has long been appreciated, but evaluation of the genome-wide effects of these phenomena has only recently become possible. Crop-wild study systems represent ideal opportunities to examine evolution through hybridization. For example, maize and the conspecific wild teosinte Zea mays ssp. mexicana, (hereafter, mexicana) are known to hybridize in the fields of highland Mexico. Despite widespread evidence of gene flow, maize and mexicana maintain distinct morphologies and have done so in sympatry for thousands of years. Neither the genomic extent nor the evolutionary importance of introgression between these taxa is understood. In this study we assessed patterns of genome-wide introgression based on 39,029 single nucleotide polymorphisms genotyped in 189 individuals from nine sympatric maize-mexicana populations and reference allopatric populations. While portions of the maize and mexicana genomes were particularly resistant to introgression (notably near known cross-incompatibility and domestication loci), we detected widespread evidence for introgression in both directions of gene flow. Through further characterization of these regions and preliminary growth chamber experiments, we found evidence suggestive of the incorporation of adaptive mexicana alleles into maize during its expansion to the highlands of central Mexico. In contrast, very little evidence was found for adaptive introgression from maize to mexicana. The methods we have applied here can be replicated widely, and such analyses have the potential to greatly informing our understanding of evolution through introgressive hybridization. Crop species, due to their exceptional genomic resources and frequent histories of spread into sympatry with relatives, should be particularly influential in these studies

Magnetic Order and Magneto-Elasticity in the Electronic Excitations of Gd-ii-MAX

We report the investigation of electronic collective modes in rare-earth-based magnets (Mo$_{2/3}$RE$_{1/3}$)$_2$AlC (also known as RE-$i$-MAX phases), where RE=Gd, Yb, and Dy, using single crystal samples. A detailed investigation of the Raman spectra of Gd-$i$-MAX samples at low temperatures, with a focus on the phonon behavior in relation to the antiferromagnetic (AFM) phase transition at 26 K is presented. Significant shifts in the central frequencies of several low-frequency phonon modes were observed below 25 K, correlating with the N\'{e}el transition. Integrated Raman intensity measurements indicated a reduction in the electronic background below the AFM transition temperature, suggesting the opening of a magnetic gap. Our analysis showed no new phonon modes. Therefore, we do not see any indication of a Brillouin zone folding of phonon mode to the $\Gamma$-point in our measurement. However, the hardening of all phonon modes at low temperatures points to a strong spin-phonon coupling effect. Using a temperature-dependent model of phonon frequency, we determined the spin-phonon coupling constant $\lambda$ to be less than 0.1 cm$^{-1}$ for all frequencies, which is of the same order of magnitude as found in other antiferromagnetic materials such as MnF$_{2}$ and FeF$_{2}$ with $T_N=68~K$ and $T_N=78~K$, respectively, but significantly lower than that of $CuO$ with $T_N=213~K$.Comment: 9 pages, 13 figure

Reproductive health and burn-out among female physicians: nationwide, representative study from Hungary

BACKGROUND: There is a worldwide rising tendency of women deciding to become physicians; hence, one of the most remarkable fields of investigation is the wellbeing of female doctors. The aim of this study was to describe female physicians' reproductive health in Hungary and to explore the potential correlation between their reproductive disorders and burnout symptoms. Up to our present knowledge, there have not been any studies investigating the correlation between reproductive disorders and burnout of female physicians; therefore, our study represents a unique approach. METHODS: Data in this representative cross-sectional epidemiological study were obtained from online questionnaires completed by 3039 female physicians. Participants in a representative nationwide survey (Hungarostudy, 2013) served as controls (n = 1069). Differences between physicians and the control group were disclosed by chi-square test. Correlations between certain factors of reproductive health and the three dimensions of burnout were detected by Pearson correlations and X2 test. Binary logistic regression analysis was used to determine the association between burnout and reproductive health. RESULTS: Female physicians were more often characterised by time-to-pregnancy interval longer than one year (18.4% vs. 9.8%), were bearing more high-risk pregnancies (26.3% vs.16.3%), and were more likely to be undergoing infertility therapy (8.5% vs. 3.4%) and experiencing miscarriage (20.8% vs. 14.6%) during their reproductive years, compared with the general female population. With the exception of miscarriages, the difference remained significant in all comparisons with the professional control group. Both high-risk pregnancies and miscarriages of doctors were associated with depersonalisation (p = 0.028 and p = 0.012 respectively) and personal accomplishment (p = 0.016 and p = 0.008 respectively) dimensions of burnout. Results of the multivariate analysis showed that, beside traditional risk factors, depersonalisation acted as an important explanatory factor in case of high-risk pregnancies (OR = 1.086). CONCLUSIONS: There is a circulatory causality between burnout and the development of reproductive disorders. Burnout is an important risk factor for high-risk pregnancies and miscarriages, and it has a negative effect on the outcome of pregnancies. At the same time, women suffering from reproductive disorders are more likely to develop burnout syndrome. Improvement of working conditions and prevention of burnout in female doctors are equally important tasks