3T MEGA-PRESS study of N-acetyl aspartyl glutamate and N-acetyl aspartate in activated visual cortex.

OBJECTIVE: To measure N-acetyl aspartyl glutamate (NAAG) and N-acetyl aspartate (NAA) concentrations in visual cortex activated by a continuous stimulation in a 3 T field. METHODS: NAAG and NAA spectra were obtained with MEGA-PRESS pulse sequence (TE/TR = 140/2000 ms; δONNAAG/δOFFNAAG = 4.61/4.15 ppm; δONNAA/δOFFNAA = 4.84/4.38 ppm) in 14 healthy volunteers at rest and upon stimulation by a radial checkerboard flickering at a frequency of 8 Hz. Spectra of all subjects were frequency and phase aligned and then averaged. Additionally, to obtain the time-dependency data, spectra were divided into time sections of 64 s each. The intensities of NAA, NAAG and lactate + macromolecular (Lac + MM) signals were defined by integration of the real part of spectra. The heights of the central resonance of NAAG and NAA signals were measured. RESULTS: The NAAG and NAA concentrations, measured with 2.5% and 0.5% error, respectively, were unaffected by visual activation. A significant increase in the Lac + MM signal by ~ 12% is clearly observed. No stimulation-induced time dependency was found for NAAG or NAA, while the increase in Lac + MM was gradual. The concentration values in visual cortex are in good agreement with the 7 T MRS measurements: [NAAG] = 1.55 mM, [NAA] = 11.95 mM. CONCLUSION: The MEGA-PRESS pulse sequence together with the spectral preprocessing techniques allowed to demonstrate that the concentrations of NAAG and NAA in the visual cortex remain constant during continuous visual stimulation within the margin of error. An increase in the lactate signal intensity signifies the activation of the anaerobic glycolysis in activated visual cortex.

Incidence and risk factors for suicide, death due to substance use, and violent/accidental death in people with HIV.

OBJECTIVE: Deaths due to suicide, substance use and violence/accident may reflect similar risk factors and overlap in their classification. This study aimed to investigate incidence and risk factors of mortality among people with HIV (PWH) due to these three related causes. DESIGN: Prospectively collected data from PWH at least 18 years old and under active follow-up in the EuroSIDA study from 2007 to 2019 were analysed. METHODS: Cause-specific Cox regression analysis was used to assess risk factors. RESULTS: A total of 17 881 participants were included, comprising 149 327 person-years of follow-up (PYFU). Forty participants died by suicide {incidence rate [IR] [95% confidence interval (CI)]: 0.3/1000 PYFU (0.2, 0.4)} 93 from substance use [IR (95% CI): 0.6/1000 PYFU (0.5, 0.8)], and 57 by violence/accident [IR (95% CI): 0.4/1000 PYFU (0.3, 0.5)]. An AIDS diagnosis within the last 12 months was associated with nine-fold increased risk of suicide vs. no history of AIDS [adjusted hazard ratio (aHR): 9.06; 95% CI: 2.07, 39.7]. Male gender was associated with double the risk of violent/accidental death (aHR: 2.28; 95% CI: 1.09, 4.78). PWH in Eastern Europe and those who acquired HIV by injection drug use (IDU) demonstrated a greater risk of death due to substance use or violence/accident. CONCLUSIONS: The association between a recent diagnosis of AIDS and suicide highlights a critical period for intervention. HIV infection acquired through IDU demonstrated an expected relationship with death due to substance use and violent/accidental deaths. Increased risk of death due to substance use and violence/accident in Eastern Europe demands investigation into specific differences that may drive that association.

Emerging microsporidian infections in Russian HIV-infected patients.

Microsporidia were identified in stool specimens by histochemistry and PCR of 30 (18.9%) of 159 HIV-infected patients presenting to the S. P. Botkin Memorial Clinical Hospital of Infectious Diseases, St. Petersburg, Russia. The higher prevalence of Encephalitozoon intestinalis, in 21 (12.8%) patients, than of Enterocytozoon bieneusi, in 2 patients (1.2%), was unexpected. Encephalitozoon cuniculi was detected in three patients: one with strain I and two with strain II. Encephalitozoon hellem was detected in one patient, and two patients were identified as being infected by Microsporidium species. One patient was infected with both E. intestinalis and E. cuniculi. In two patients, the microsporidian species were not identifiable. No statistically significant differences in gender, age, and stage of AIDS were observed between the microsporidian-positive and -negative HIV-infected patients. HIV-infected patients diagnosed with microsporidian infection, however, were significantly more likely to exhibit ≤ 100 CD4(+) T cells/µl blood (20/30 patients [67%]; odds ratio [OR], 3.150; 95% confidence interval [CI(95)], 1.280 to 7.750; P = 0.0116) and weight loss of >10% of the baseline (19/30 patients [63%]; odds ratio, 2.995; CI(95), 1.100 to 8.158; P = 0.0352) than HIV-infected patients not diagnosed with microsporidian infection. In summary, this is the first report describing the diagnosis of microsporidian infection of HIV-infected patients in Russia and the first detection of E. cuniculi strain II in a human.

Molecular dynamics simulations of laser-induced incandescence of soot using an extended ReaxFF reactive force field.

Laser-induced incandescence (LII) of soot has developed into a popular method for making in situ measurements of soot volume fraction and primary particle sizes. However, there is still a lack of understanding regarding the generation and interpretation of the cooling signals. To model heat transfer from the heated soot particles to the surrounding gas, knowledge of the collision-based cooling as well as reactive events, including oxidation (exothermic) and evaporation (endothermic) is essential. We have simulated LII of soot using the ReaxFF reactive force field for hydrocarbon combustion. Soot was modeled as a stack of four graphene sheets linked together using sp(3) hybridized carbon atoms. To calculate the thermal accommodation coefficient of various gases with soot, graphene sheets of diameter 40 Å were used to create a soot particle containing 2691 atoms, and these simulations were carried out using the ReaxFF version incorporated into the Amsterdam Density Functional program. The reactive force field enables us to simulate the effects of conduction, evaporation, and oxidation of the soot particle on the cooling signal. Simulations were carried out for both reactive and nonreactive gas species at various pressures, and the subsequent cooling signals of soot were compared and analyzed. To correctly model N(2)-soot interactions, optimization of N-N and N-C-H force field parameters against DFT and experimental values was performed and is described in this paper. Subsequently, simulations were performed in order to find the thermal accommodation coefficients of soot with various monatomic and polyatomic gas molecules like He, Ne, Ar, N(2), CO(2), and CH(4). For all these species we find good agreement between our ReaxFF results and previously published accommodation coefficients. We thus believe that Molecular Dynamics using the ReaxFF reactive force field is a promising approach to simulate the physical and chemical aspects of soot LII.

ReaxFF Parameter Optimization with Monte-Carlo and Evolutionary Algorithms: Guidelines and Insights.

ReaxFF is a computationally efficient force field to simulate complex reactive dynamics in extended molecular models with diverse chemistries, if reliable force-field parameters are available for the chemistry of interest. If not, they must be optimized by minimizing the error ReaxFF makes on a relevant training set. Because this optimization is far from trivial, many methods, in particular, genetic algorithms (GAs), have been developed to search for the global optimum in parameter space. Recently, two alternative parameter calibration techniques were proposed, that is, Monte-Carlo force field optimizer (MCFF) and covariance matrix adaptation evolutionary strategy (CMA-ES). In this work, CMA-ES, MCFF, and a GA method (OGOLEM) are systematically compared using three training sets from the literature. By repeating optimizations with different random seeds and initial parameter guesses, it is shown that a single optimization run with any of these methods should not be trusted blindly: nonreproducible, poor or premature convergence is a common deficiency. GA shows the smallest risk of getting trapped into a local minimum, whereas CMA-ES is capable of reaching the lowest errors for two-third of the cases, although not systematically. For each method, we provide reasonable default settings, and our analysis offers useful guidelines for their usage in future work. An important side effect impairing parameter optimization is numerical noise. A detailed analysis reveals that it can be reduced, for example, by using exclusively unambiguous geometry optimization in the training set. Even without this noise, many distinct near-optimal parameter vectors can be found, which opens new avenues for improving the training set and detecting overfitting artifacts.

Rapid HIV testing, pregnancy, antiretroviral prophylaxis and infant abandonment in St Petersburg.

In St Petersburg, Russia, a rapid HIV-testing programme was implemented in April 2004 for high-risk women giving birth. Among 670 women without prenatal care who received rapid HIV testing, 6.4% (43) had positive results. Among HIV-positive mothers, receipt of intrapartum antiretroviral prophylaxis increased significantly compared to pre-programme levels (76 versus 41%). Additionally, infant abandonment increased significantly (50% versus 26%), and was 10 times greater in women with unintended versus intended pregnancies (73% versus 7%).

Template-aluminosilicate structures at the early stages of zeolite ZSM-5 formation. A combined preparative, solid-state NMR, and computational study.

Species at three stages in the self-assembly of zeolite ZSM-5 have been studied with one- and two-dimensional magic-angle-spinning 13C, 27Al, 29Si, and 1H NMR spectroscopy and compared with the earlier proposed structures: (1) precursor species containing 33-36 T sites around a tetrapropylammonium (TPA) cation, (2) nanoslabs consisting of a flat 4 x 3 array of such precursors, and (3) the final TPA-ZSM-5 zeolite. Synthesis was carried out in D2O to suppress the water and silanol protons. Under such conditions, the effective Si-H and Al-H distances measured with 29Si-{1H} and 27Al-{1H} rotational echo double resonance (REDOR) reflect the interactions between TPA cations and the surrounding aluminosilica. The 29Si-{1H} REDOR curves for Q4-type silicon atoms at the three mentioned stages are closely similar, as well as the observed 27Al-1H REDOR curve for the precursor species compared to that for the TPA-ZSM-5. This indicates that in addition to externally attached TPA, there is also internal TPA already incorporated at an early stage into the aluminosilicate in a similar way as in the final zeolite, in accordance with the earlier proposed MFI self-assembly pathway (Kirschhock et al. Angew. Chem. Int. Ed. 2001, 40, 2637). However, the effective distances extracted from the initial REDOR curvatures are significantly (10-15%) larger than those computed for the model. Since there is no temperature effect, we tentatively assign this difference to a reduction of the 29Si-1H and 27Al-1H interactions by multispin decoherence effects or self-decoupling caused by proton spin diffusion. By assuming the computed model distances and fitting Anderson-Weiss curves to the observed REDOR data, we obtain similar "decoherence times" in the order of 0.1 ms. The observed 29Si-{1H} REDOR dephasing for the Q3 sites in the precursors is significantly faster than that for the Q4 sites. This is tentatively ascribed to a partial deuteron-proton back exchange at the silanol positions.

Улучшение показателей по неинфекционным заболеваниям: барьеры и возможности систем здравоохранения: страновая оценка – Туркменистан

В Туркменистане высокий уровень преждевременной смертности от неинфекционных заболеваний (НИЗ). Вероятность преждевременной смерти (в возрасте 30–69 лет) от одного из основных НИЗ составляет 26,9%. Значительные социально-экономические последствия этой ситуации для развития страны обусловливают необходимость срочного укрепления потенциала системы здравоохранения для эффективного реагирования на растущее бремя НИЗ. В Туркменистане в этом направлении уже достигнут значительный прогресс, например, в решении проблемы распространенности поведенческих факторов риска и в модернизации инфраструктуры медицинских учреждений, имеется также политическая приверженность, однако показатели по контролю НИЗ все еще нуждаются в улучшении.В настоящем докладе приведен обзор проблем и возможностей системы здравоохранения Туркменистана применительно к наращиванию основных услуг профилактики, ранней диагностики и лечения НИЗ. Также освещены примеры передовой практики борьбы против табака. По результатам оценки сформулированы рекомендации для дальнейших действий.

Better noncommunicable disease outcomes: challenges and opportunities for health systems: Turkmenistan country assessment

Premature mortality due to noncommunicable diseases (NCDs) is high in Turkmenistan. The probability of dying prematurely (between the ages of 30 and 70 years) from one of the major NCDs is 26.9%. This has significant socioeconomic consequences for the development of the country and calls for immediate strengthening of the health system to respond to the growing burden of NCDs. Despite political commitment and significant progress, for example in reducing the prevalence of behavioural risk factors and in upgrading the health facility infrastructure, the outcomes of NCDs could still be improved.This report reviews the challenges and opportunities of the health system in Turkmenistan for scaling up core services for the prevention, early diagnosis and management of NCDs. The report also provides examples of good practice in tobacco control. Policy recommendations are made for further action, based on the assessment.