Fingerprints of the Local Moment Formation and its Kondo Screening in the Generalized Susceptibilities of Many-Electron Problems.

We identify the precise hallmarks of the local magnetic moment formation and its Kondo screening in the frequency structure of the generalized charge susceptibility. The sharpness of our identification even pinpoints an alternative criterion to determine the Kondo temperature of strongly correlated systems on the two-particle level, which only requires calculations at the lowest Matsubara frequency. We showcase its strength by applying it to the single impurity and the periodic Anderson model as well as to the Hubbard model. Our results represent a significant progress for the general understanding of quantum field theory at the two-particle level and allow for tracing the limits of the physics captured by perturbative approaches for correlated systems.

Digital messaging to support control for type 2 diabetes (StAR2D): a multicentre randomised controlled trial.

BACKGROUND: Failure to take medicines for diabetes as prescribed contributes to poor outcomes from the condition. Mobile phones are ubiquitous and short message service (SMS) texts have shown promise as a low-cost intervention. We tested the effectiveness of SMS-text messaging in improving outcomes in adults with type 2 diabetes. METHODS: StAR2D was a 12-month two-arm randomised trial of SMS-text messaging and usual care in Cape Town, South Africa and Lilongwe, Malawi. Messages used behaviour change theory and were developed with patients and staff. The intervention group received four messages each week. The primary outcome was change in HbA1c. Secondary outcomes were the proportion of patients who collected > 80% medication and changes in systolic blood pressure, lipids, cardiovascular risk, and the proportion of the participants reaching treatment goals. RESULTS: The trial took place between 1 October, 2016 and 1 October 2018, 1186 participants were randomised to intervention (593) and control (593) groups. 91% of participants completed follow-up. There was a reduction in HbA1c (DCCT) in both groups but not in mean change (95% CI) between groups (- 0.08% (- 0.31 to 0.16) (IFCC - 0.82 mmol/mol (- 3.44 to 1.79). There was a small but not significant increase in the proportions of participants likely to have collected 80% or more of medication (Relative risk 1.11 (0.84 to 1.47; P = 0.47). There was a significant difference between groups in change in systolic blood pressure from baseline of 3.46 mmHg (1.48 to 5.44, P = 0.001) in favour of the intervention group. The between group difference in change in 10-year risk of coronary heart disease was - 0.71% (- 1.46 to 0.04, P = 0.064). The proportion of participants meeting treatment goals in the intervention group was 36.0% and in the control group 26.8% (Relative risk 1.36 (1.13 to 1.63, P = 0.001). Participants reported many challenges to adherence despite finding messages acceptable and useful. CONCLUSIONS: Whilst SMS text messages do not lead to improved glycaemia in these low-resource settings there appeared to be an impact on blood pressure and achievement of treatment goals but the mechanisms for this are unclear. Text messages alone, may be unsuccessful unless accompanied by health system strengthening and other forms of self-management support for type 2 diabetes. TRIAL REGISTRATION: Trial registration: ISRCTN, ISRCTN70768808. Registered 1 July 2015, http://www.isrctn.com/I ISRCTN70768808.

Characteristic Timescales of the Local Moment Dynamics in Hund's Metals.

We study the characteristic timescales of the fluctuating local moments in Hund's metal systems for different degrees of correlation. By analyzing the dynamical spin susceptibility in the real-time domain, we determine the timescales controlling oscillation and damping of on-site fluctuations-a crucial factor for the detection of local moments with different experimental probes. We apply this procedure to different families of iron pnictides or chalcogenides, explaining the material trend in the discrepancies reported between experimental and theoretical estimates of their magnetic moments.

Attractive Effect of a Strong Electronic Repulsion: The Physics of Vertex Divergences.

While the breakdown of the perturbation expansion for the many-electron problem has several formal consequences, here we unveil its physical effect: flipping the sign of the effective electronic interaction in specific scattering channels. By decomposing local and uniform susceptibilities of the Hubbard model via their spectral representations, we prove how entering the nonperturbative regime causes an enhancement of the charge response, ultimately responsible for the phase-separation instabilities close to the Mott metal-insulator transition. Our analysis opens a new route for understanding phase transitions in the nonperturbative regime and clarifies why attractive effects emerging from a strong repulsion can induce phase separations but not s-wave pairing or charge-density wave instabilities.

Anti-C1q autoantibodies are linked to autoimmune thyroid disorders in pregnant women.

Anti-C1q antibodies (anti-C1q) have been implicated in the pathogenesis of autoimmune diseases, including autoimmune thyroid disorders (AITD). The aim of this study was to evaluate the association between anti-C1q and thyroid function in pregnancy-associated AITD. In 96 pregnant women screened positive for AITD (thyroid dysfunction and/or antibodies against thyroperoxidase - TPOAb), anti-C1q were measured during the 9-11th gestational week and after delivery (median 16 months after delivery), and compared to the corresponding serum levels of thyroid hormones. As controls, 80 healthy pregnant women, 72 non-pregnant AITD patients and 72 blood donors were included. In the non-pregnant AITD group, two serum samples ≥ 6 months apart were analysed. Compared to blood donors, anti-C1q levels were substantially higher in all pregnant women analysed. In pregnancy, anti-C1q levels were higher in the TPOAb-positive women than in controls (37 versus 17·5%, P < 0·0001). Anti-C1q-positive pregnant women screened positive for AITD had higher thyroid-stimulating hormone (TSH) levels than anti-C1q-negative women (2·41 versus 1·94 mU/l, P = 0·01), and TSH correlated positively with anti-C1q (r = 0·226, P = 0·045) in the TPOAb-positive women. After delivery, serum levels of anti-C1q decreased in the positively screened TPOAb-negative women (8·8 versus 5·9 U/l, P = 0·002), but not in the TPOAb-positive ones, and they no longer correlated with TSH. Anti-C1q antibody levels increase during pregnancy in general and even more in the context of AITD, where they correlate with thyroid stimulating hormone levels.

Immunohistochemistry and serum values of S-100B, glial fibrillary acidic protein, and hyperphosphorylated neurofilaments in brain injuries.

INTRODUCTION: Traumatic brain injury (TBI) triggers a series of reactions resulting in cytoskeletal-related changes varying between focal and diffuse injuries. METHODS: The patients (n=38) were divided into group of diffuse axonal injuries (DAI, n=10) and focal (n=28) injuries. Serum hyperphosphorylated neurofilaments (NF-H) and glial fibrillary acidic protein (GFAP) were measured by Biovendor immunoassay, and serum S-100B protein was measured by Cobas e411 (Roche) by immunoassay. Immunohistochemistry was performed with monoclonal antibodies (Chemicon, USA). RESULTS: The median serum S-100B concentration was higher in patients with focal mass lesions (1.72±0.4 µg/l vs. 0.37±0.1 µg/l, p<0,05) compared to patients with DAI during 10 days of hospitalisation. With respect to all patients, the highest peak of serum S-100B values (4.21±1.1 µg/l) and GFAP (8.58±2.4 µg/l) were found in expansive lesions. The median serum NF-H was higher in DAI compared to focal TBI (0.625±0.14 vs 0.139±0.02 ng/l, p<0.05) during all 10 days after admission. Further, immunohistochemical investigation, in deceased patients with DAI , using NF-H antibody proved positive varicose and waving axons, and retraction balls. Time-dependent profile of serum NF-H demonstrated the increase of values within 4th up to 10th day in both groups. Values ranged from 0.263 up to 1.325 ng/l in DAI, and from 0.103 up to 1.108 ng/l in focal injuries. Patients with expansive contusions had similar levels of serum NF-H as patients without expansive lesions. Immunohistochemistry of cytoskeletal proteins presented strong positive staining of vinculin, vimentin in vessels, GFAP, and S-100B in DAI compared to weak staining in expansive lesions. CONCLUSION: The time-profile kinetics of all markers may reflect different types of pathophysiological changes of the BBB or axonal damage in focal and diffuse injuries. KEYWORDS: brain contusions - diffuse axonal injury - S-100B protein - GFAP - hyperphosphorylated neurofilaments.

[Protein S100b in differential diagnosis of brain concussion and superficial scalp injury in inebriated patients]. / Protein S-100b v diferenciální diagnostice komoce mozkové a povrchního poranení hlavy u pacientu v ebriete

INTRODUCTION: Concussion cannot be differentiated from superficial scalp injury, especially in inebriated or uncooperative patients. This can have serious medical or forensic consequences. The aim of the study was to determine whether serum concentrations of S-100b in mild traumatic brain injury (MTBI) patients are significantly higher than those in patients with superficial scalp injury with scalp wound and alcohol intoxication. MATERIAL AND METHODS: A total of 50 patients with head injury, 25 with mild concussion without scalp wound and alcohol intoxication, 25 superficial scalp injury patients with scalp wound and clinical signs of inebriety. Neurological status and cranial CT scan were evaluated 60-120 minutes after injury in all the 50 patients to exclude focal cerebral injury or skull fracture. RESULTS: The serum levels of S-100b were significantly increased in patients with concussion (median 0.36 ± 0.15 µg/l ) in comparison with the group of patients with scalp injury and alcohol intoxication (median 0.09 ± 0.002 µg/l). All 50 patients had a normal cranial CT finding and neurological status. In all superficial scalp injury patients alcohol intoxication was confirmed (0.96 - 3.11s). CONCLUSION: We proved significantly higher values of S-100b in patients with brain concussion. Diagnostically decisive value of S-100b concentration in the serum was set at 146 µg/l and higher (94% sensitivity and 100% specificity). Alcohol intoxication (up to 3.11 s) and scalp wound seem to have had no crucial impact on serum S-100b level.

Music Therapy Knowledge and Interest: A Survey of Music Education Majors.

Music teachers play an important role in exposing students to career options in the field of music. As a result, there is a need to explore music education students' interest in and knowledge of music therapy. The purpose of this study was to investigate music education students' exposure to, knowledge of, and willingness to promote music therapy as a career option for prospective collegiate students. A survey was given to 254 music education majors from four research institutions, two with and two without music therapy degree programs. Participants answered demographic, yes/no, Likert-type scale, and open-ended questions about their exposure to, knowledge of, and willingness to promote careers in music therapy. Results indicate that exposure to music therapy occurred in both pre-collegiate and college settings, and that music teachers appear to be influential in exposing students to music therapy. Students often sought out information on music therapy independently, which played an important role in how individuals learned about music therapy, though it has the potential of providing misinformation. Significant differences were found in participants' knowledge and willingness to promote music therapy as a career option based on the presence of music therapy degree programs. Exposure seemed to be a key factor in music therapy knowledge and promotion; thus, music therapists need to ensure accurate dissemination of music therapy-related information in both pre-collegiate and college settings. Increasing the visibility of the field has the potential to expand interest and potentially attract young musicians well suited for a career in music therapy.

Profiling mitochondrial proteins in radiation-induced genome-unstable cell lines with persistent oxidative stress by mass spectrometry.

Previous work by Morgan and coworkers on radiation-induced genome instability in Chinese hamster ovary (CHO) cell lines showed that unstable LS-12 cells had persistently elevated levels of reactive oxygen species (ROS) that were likely due to dysfunctional mitochondria. To further investigate the correlation between radiation-induced genome instability and dysfunctional mitochondria, we performed quantitative high-throughput mass spectrometry on samples enriched in mitochondrial proteins from three chromosomally unstable CHO cell lines and their stable unirradiated GM10115 parental cell line. Out of several hundred identified proteins, sufficient data were collected on 74 mitochondrial proteins to test for statistically significant differences in their abundance between unstable and stable cell lines. The LS-12 cell line, which exhibited the highest level of ROS among the three unstable cell lines, was characterized by eight significantly down-regulated mitochondrial proteins, all associated with the TCA (tricarboxylic acid). Elevated levels of ROS relative to the unirradiated parental control were also statistically significant for the CS-9 cell line. The protein profile of CS-9 revealed five significantly up-regulated mitochondrial proteins, three of which are involved in oxidative phosphorylation. Elevation of ROS in the unstable 115 cell line was nearly as large as that seen in CS-9 cells but was not statistically significant. The mitochondrial protein profile of 115 cells showed significant down-regulation of acetyl-CoA-acetyltransferase, which was also down-regulated in LS-12, and two other proteins with abundances that were significantly different from control levels but were not directly related to either the TCA or oxidative phosphorylation. These results provide further evidence that elevated ROS and mitochondrial dysfunction are associated with radiation-induced genome instability; however, additional work is required to establish a firm mechanistic relationship between these end points.

Influence of chemotherapy to hormonal levels in postmenopausal breast cancer patients.

Targeting and tailoring of therapy is the latest trend in breast cancer treatment. The efficacy of the available treatment must be estimated and the probable benefit for the patient determined. The aim of this project was to find out wether also in postmenopausal women chemotherapy can affect hormonal levels in serum and if even the levels of IGF-1 and IGFBP-3 can be changed. In the group of 72 postmenopausal breast cancer patients blood samples were taken before, during and after adjuvant chemotherapy and levels of estradiol, progesterone, LH, FSH, IGF-1 and IGFBP-3 were evaluated. We did not find any statistically significant dependence on tumor stage, expression of hormonal receptors or HER-2 and treatment regimen with studied hormones. Serum levels before treatment in comparison with status during treatment were significantly different in LH, FSH and progesterone value. Hormone levels after the treatment in comparison with status during treatment were significantly different only in levels of estradiol. Significant differences in all parameters were found except IGF-1. There was not any statistical dependence on the menopausal gap, age, weight or type of chemotherapy. We can conclude, that also in postmenopausal women hormonal changes can take part in the final effect of adjuvant treatment.

[Down's syndrome screening in the Czech Republic]. / Moznosti screeningu Downova syndromu v Ceské republice.

We have better options how to screen for genetic defects during the last decade, but unfortunately in some areas of the country are not all types of the screening available. Strangely, this effect is caused by our demand for higher quality of our services, especially in ultrasound measurment. Gynaecologists should have good knowledge of all possibilities how to screen, should know the advantages, the disadvantages and the limitations of all screening tests. The article gives an overview of screening tests and it should be a guide for physicians and pregnant women what kind of screening is possible to do and what to expect from it.

Stability of free beta-hCG in the routine screening of Down syndrome in the first trimester of pregnancy.

Stability of free beta-human chorionic gonadotropin in maternal blood upon storage at ambient and refrigerator temperatures as well as stability under conditions simulating postal transport were studied. A group of 26 women in the first trimester of pregnancy were included in the study, blood samples were taken during the routine check-up. Blood samples were aliquoted stored in different conditions that should mimic the transportation and then analysed for free beta-hCG. No significant differences were found in the free beta-hCG levels in samples after 24 and 48 hours resp., stored in refrigerator (2-8 degrees C) without separation. In samples stored in laboratory temperature without separation the average concentration increased from 11 to 20%. Six blood samples were stored at 35 degrees C for 5 hours and then in laboratory temperature. In this group the average increase of results was from 14.3% to 132.2%. Separation of the sera for Down syndrome screening in 4 hours after withdrawal is necessary. Cooling during any storage, including transportation is highly recommended as the preanalytical phase has a high impact for the analysis.

HER-2 tissue expression correlated with serum levels in breast cancer patients.

We explored the relationship between circulating HER-2 extracellular domain and tissue HER-2 status in a group of 42 postmenopausal breast cancer patients. All patients were examined before adjuvant chemotherapy or other adjuvant treatment. Serum levels were measured by BAYER Advia Centaur System, Golden, CO (the cut-off level was in our conditions considered at 12 ng/ml). Tissue expression was assayed with the DAKO HercepTest, North America, Inc, Carpinteria, CA. Our findings that serum levels are in consonance with tissue expression could be important in metastatic breast cancer, when it is impossible to get a new tumour sample and establish the actual HER-2 status, which may be different from the primary tumour. Although we know that serum HER-2 concentration cannot be substituted for IHC or FISH, we have observed a statistically significant correlation between serum level concentration and tissue HER-2 status.

[Thyroid malfunction in pregnancy]. / Poruchy stítné zlázy v tehotenství--souhrn výsledku nezávislých studií.

CONTEXT: Over the past 15 years there have been discussions about advisability of thyroid gland function screening in pregnant women, recommendations are being defined at least ten years. The reasoning is based on fact, that not only complications in pregnancy or after delivery were proved, but also problems in mental development of children, the mothers of which suffered impairement of thyroid gland function. OBJECTIVE: We are presenting thyroid parametres TSH, TPOAb, in part also FT4, in 1st trimestr of pregnancy. Examination were performed in three Czech centers and included 4500 pregnant women. RESULTS: The TSH suppression was proved in 3.6%, mostly without link to thyroid gland function, the increased TSH concentration in connection with (sub)clinical hypothyroidism was found in 5% of women, the low FT4 concentration under 9.8 pmol/I, which endangers fetal intellectual development, was found in 17 of 120 investigated woman with TSH higher than 4.00 mU/l. Thus exists a risk of minimum 1 to 170 in all group, that insufficient fetal brain development occurs. TPOAb were positive in 15% women. Increased risk of thyroid malfunction progress in women with positive TPOAb in pregnancy (and up to 50% after delivery) was repeatedly proved. CONCLUSION: Based on the results (5% hypothyroidism, 15% with TPOAb pregnant women) we would like to commence discussion concerning screening in pregnancy in CR, preferably before the planned conception, or at latest just before the actual pregnancy. Systematic cooperation among gynecologists, endocrinologists, general practitioners and laboratories should be established to solve the problems, as laboratory normal range, pregnancy timing for examination, unification of diagnostic procedures and correct interpretation of the results.

Can the gold standard be beaten? How reliable are various modifications of the Synacthen test compared to the insulin tolerance test.

Criteria for the evaluation of the insulin tolerance test (ITT) and Synacthen test are still a matter of debate. The objective of the study was to make a comparison of serum and salivary cortisol during four stimulation tests. Sixty four healthy volunteers underwent the ITT, the Synacthen test with 1 (LDST), 10 (MDST) and 250 (HDST) microg dose of ACTH. Maximum serum cortisol response was observed at the 90 min of the ITT (49 %), HDST (89 %) and MDST (56 %) and at the 40 min of the LDST (44 %). Results expressed as 95 % confidence intervals: 408.0-843.6 and 289.5-868.1 nmol/l in the IIT at 60 and 90 min. In the HDST and the MDST serum cortisol reached the maximum at 90 min 542.6-1245.5 and 444.2-871.3 nmol/l. Levels of salivary cortisol followed the same pattern as serum cortisol. Salivary cortisol reached the maximum response in the HDST and the MDST at 90 min and at 40 min in the LDST. We confirmed good reliability of all tests with respect to timing of response and maximum response compared to the ITT. We proved that the MDST test can provide the similar response in serum cortisol to the HDST. Measuring either salivary cortisol or ACTH levels did not provide any additional benefit then measuring serum cortisol by itself.

The influence of hormonal changes during menstrual cycle on serum adiponectin concentrations in healthy women.

Adiponectin is an adipocyte-derived hormone involved in the regulation of carbohydrate and lipid metabolism. Its concentrations are decreased in patients with obesity, type 2 diabetes and atherosclerosis and are higher in females than in males. Gender differences of adiponectin levels raise the possibility that sex hormones directly regulate its serum concentrations, which may in turn influence insulin sensitivity in different phases of the menstrual cycle. To test this hypothesis we measured serum adiponectin, estradiol, progesterone, luteinizing hormone and follicle-stimulating hormone concentrations daily throughout the menstrual cycle in six healthy women. Mean adiponectin levels strongly positively correlated with serum cortisol concentrations [R=0.94286; p=0.0048 (Spearman correlation test)], but were not significantly related to other anthropometric, biochemical and hormonal characteristics of the subjects (BMI, blood glucose, insulin, testosterone, prolactin, cholesterol, HDL cholesterol, LDL cholesterol, triglycerides concentrations, or atherogenic index). Furthermore, no significant changes of serum adiponectin levels were found throughout the menstrual cycle. We conclude that changes in sex hormones during the menstrual cycle do not affect total circulating adiponectin levels in healthy women. Therefore, the differences in insulin sensitivity in various phases of the menstrual cycle are not due to changes of circulating adiponectin levels.

Characterization of medium conditioned by irradiated cells using proteome-wide, high-throughput mass spectrometry.

Shedding, the release of cell surface proteins by regulated proteolysis, is a general cellular response to injury and is responsible for generating numerous bioactive molecules including growth factors and cytokines. The purpose of our work is to determine whether low doses of low-linear energy transfer (LET) radiation induce shedding of bioactive molecules. Using a mass spectrometry-based global proteomics method, we tested this hypothesis by analyzing for shed proteins in medium from irradiated human mammary epithelial cells (HMEC). Several hundred proteins were identified, including transforming growth factor beta (TGFB); however, no changes in protein abundances attributable to radiation exposure, based on immunoblotting methods, were observed. These results demonstrate that our proteomic-based approach has the sensitivity to identify the kinds of proteins believed to be released after low-dose radiation exposure but that improvements in mass spectrometry-based protein quantification will be required to detect the small changes in abundance associated with this type of insult.

An update on inhibitors of human 14 kDa Type II s-PLA2 in development.

Recent progress in the development of inhibitors of human Type II s-PLA2 as potential anti-inflammatory agents is presented. While many companies have curtailed their efforts in the PLA2 area, Eli Lilly and Shionogi are continuing to advance LY-315920 (S-5920) as a potential treatment for sepsis and other diseases that have an inflammatory component. The Lilly developmental effort leading to LY-315920 is extensively reviewed, as well as the current status of other small molecular weight inhibitors of Type II s-PLA2 that have been reported to be in late-stage development