Phenolic Compounds of the Medicinal Plants in an Anthropogenically Transformed Environment.

In this article, the impact of an anthropogenically transformed environment on the content of pharmaceutically valuable biologically active compounds in medicinal plants is analyzed. The studied biologically active substances included phenolic compounds (flavonoids, anthocyanins, tannins, and phenolic acids). The number of transmissible forms of heavy metals (HMs), including cadmium, lead, and mercury, were discharged from factories that are present in the soil. Plants uptake these toxic metals from the soil. HM causes changes in the activity of the several enzymes such as phenylalanine ammonia lyase (PAL), chalcone synthase (CHS), chalcone isomerase (CHI) and other enzymes. These enzymes play an important role in biosynthesis of phenolic compounds in medicinal plants. It has been demonstrated that plant materials possess high antioxidant potential due to their high phenolic content. As a result, the present review discusses a thorough investigation of anthropogenically transformed environment effects on the quantity of pharmaceutically valuable phenolic compounds in medicinal plants.

Resonance scattering of plane waves by a soft elliptic cavity with a variably placed longitudinal slit.

Using previous results [Vinogradova, J. Acoust. Soc. Am. 144(3), 1146-1153 (2018)] on the spectrum of complex eigenvalues for an open elliptic cavity with variably placed longitudinal slits, the author investigates the resonance excitation of such a cavity by obliquely incident plane waves. The complete investigation of the resonance response is based on accurate calculation of the monostatic and bi-static sonar cross-sections, as well as calculation of the jump in normal velocity at the cavity surface. High-accuracy calculations are obtained by employing the rigorous Method of Analytical Regularization. Furthermore, studies of semi-elliptic cavities with high eccentricities, modelling the extremely deep acoustical cavities, are also performed.

Complex eigenvalues of slotted arbitrary cylindrical cavities: Sound-soft elliptic cavity with variably placed longitudinal slit.

A generalization of the rigorous method of regularization is implemented to calculate the complex eigenvalues for a two dimensional arbitrarily shaped acoustically soft cavity with a longitudinal slit. The problem is reduced to the finding of non-trivial solutions of the coupled homogeneous well-conditioned Fredholm second kind infinite systems of linear algebraic equations that are solved numerically by the truncation method. The guaranteed fast convergence of the solution of the truncated system to the exact solution allows one to achieve any pre-determined accuracy by proper choice of truncation number. Formally, the complex eigenvalues coincide with the complex roots of the characteristic equation of the truncated infinite system. All calculations are performed with an accuracy of six significant decimal digits. The algorithm is free from limitations on the slit width, frequency band, and slit location along the bounding contour of a cavity. As an example, the spectrum of the complex eigenvalues for open elliptic cavity with moveable longitudinal slit is accurately investigated for various ellipse eccentricities, including the case of degenerated elliptic cavity-circular cavity. The slit width varies from zero value (closed cavity) to open semi-elliptic cavity.

Differentiation of Effect Across Systemic Literacy Programs in Rwanda, the Philippines, and Senegal.

In this article, we compare three localized applications (in Rwanda, Senegal, and the Philippines) of a literacy approach for resource-lean environments and examine the factors influencing its impact in each context, considering dosage, duration, and environment. In Rwanda, a bilingual early grade literacy initiative implemented in partnership with the ministry of education included literacy standards development, training for early grade teachers, materials development, leadership support, and community-based activities. In the Philippines, a primary grades trilingual curriculum was implemented in close collaboration with the Department of Education to strengthen its literacy component through standards development, teacher and school leader training, materials development, and awareness campaigns. Finally, in Senegal, a program was conducted supporting the YMCA's efforts to improve local educational outcomes by training youth volunteers to mentor students at risk and by engaging families and communities.

Development of a T Cell-Based COVID-19 Vaccine Using a Live Attenuated Influenza Vaccine Viral Vector.

The COVID-19 pandemic emerged in 2020 and has caused an unprecedented burden to all countries in the world. SARS-CoV-2 continues to circulate and antigenically evolve, enabling multiple reinfections. To address the issue of the virus antigenic variability, T cell-based vaccines are being developed, which are directed to more conserved viral epitopes. We used live attenuated influenza vaccine (LAIV) virus vector to generate recombinant influenza viruses expressing various T-cell epitopes of SARS-CoV-2 from either neuraminidase (NA) or non-structural (NS1) genes, via the P2A self-cleavage site. Intranasal immunization of human leukocyte antigen-A*0201 (HLA-A2.1) transgenic mice with these recombinant viruses did not result in significant SARS-CoV-2-specific T-cell responses, due to the immunodominance of NP366 influenza T-cell epitope. However, side-by-side stimulation of peripheral blood mononuclear cells (PBMCs) of COVID-19 convalescents with recombinant viruses and LAIV vector demonstrated activation of memory T cells in samples stimulated with LAIV/SARS-CoV-2, but not LAIV alone. Hamsters immunized with a selected LAIV/SARS-CoV-2 prototype were protected against challenge with influenza virus and a high dose of SARS-CoV-2 of Wuhan and Delta lineages, which was confirmed by reduced weight loss, milder clinical symptoms and less pronounced histopathological signs of SARS-CoV-2 infection in the lungs, compared to LAIV- and mock-immunized animals. Overall, LAIV is a promising platform for the development of a bivalent vaccine against influenza and SARS-CoV-2.

Rapid HIV testing and prevention of perinatal HIV transmission in high-risk maternity hospitals in St. Petersburg, Russia.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of a human immunodeficiency virus (HIV) rapid testing (RT) program. STUDY DESIGN: From April 13, 2004, to April 13, 2005, pregnant women at 2 high-risk maternity hospitals with no or incomplete HIV testing results (negative tests at <34 weeks, none thereafter) were offered point-of-care RT, with antiretroviral prophylaxis for RT-positive women and their infants. RESULTS: Overall, 89.2% of eligible women (3671/4117) underwent RT, of whom 90.4% received results before delivery. HIV seroprevalence among all women who underwent RT was 2.7% (100/3671 women); among previously untested women, seroprevalence was 6.5% (90/1375 women); the incidence of HIV seroconversion among women with previous negative tests during pregnancy was 0.4% (10/2296 women). After adjustment, the main predictor of receiving RT results after delivery was late admission. Among HIV-exposed infants, 97.9% (92/94) received prophylaxis; 61.7% (58/94) had available follow-up data, and 8.6% (5/58) met criteria for definitive or presumptive HIV infection. CONCLUSION: The RT program achieved timely detection of HIV-infected women in labor with unknown HIV status and effectively prevented perinatal HIV transmission.

HIV seroprevalence in street youth, St. Petersburg, Russia.

BACKGROUND: Reliable data on HIV infection among Russian street youth are unavailable. The purpose of this study was to assess HIV seroprevalence among street youth in St Petersburg and to describe social, sexual, and behavioral characteristics associated with HIV infection. METHODS: A cross-sectional assessment conducted during January-May 2006 included city-wide mapping of 41 street youth locations, random selection of 22 sites, rapid HIV testing for all consenting 15-19-year-old male and female street youth at these sites, and an interviewer-administered survey. Adjusted odds ratios (AOR) were calculated using logistic regression, accounting for intracluster homogeneity. RESULTS: Of 313 participants, 117 (37.4%, 95% confidence interval 26.1-50.2%) were HIV infected. Subgroups with the highest seroprevalences included double orphans (64.3%), those with no place to live (68.1%), those previously diagnosed with a sexually transmitted infection (STI; 70.5%), those currently sharing needles (86.4%), and those currently using inhalants (60.5%) or injection drugs (78.6%), including Stadol (82.3%) or heroin (78.1%). Characteristics independently associated with HIV infection included injecting drugs (AOR 23.0), sharing needles (AOR 13.3), being a double or single orphan (AOR 3.3 and 1.8), having no place to live (AOR 2.4), and being diagnosed with a STI (AOR 2.1). Most HIV-infected street youth were sexually active (96.6%), had multiple partners (65.0%), and used condoms inconsistently (80.3%). DISCUSSION: Street youth aged 15-19 years in St Petersburg, Russia, have an extraordinarily high HIV seroprevalence. In street youth who are injection drug users, HIV seroprevalence is the highest ever reported for eastern Europe and is among the highest in the world.

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%).

Extrathymic production of thymulin induced by oxidative stress, heat shock, apoptosis, or necrosis.

Thymic peptides are immune regulators produced mainly in the thymus. However, thymic peptides such as thymosin-α and thymopoietin have precursors widely expressed outside the thymus, localized in cell nuclei, and involved in vital nuclear functions. In stress-related conditions, they can relocalize. We hypothesized that another thymic peptide, thymulin, could be similarly produced by non-thymic cells during stress and have a precursor therein. Non-thymic cells, including macrophages and fibroblasts, were exposed to oxidative stress, heat, apoptosis, or necrosis. Extracellular thymulin was identified in media of both cell types 2 h after exposure to stress or lethal signals. Therefore, thymulin is released by non-thymic cells. To examine possible thymulin precursors in non-thymic cells, macrophage lysates were analyzed by western blotting. Bands stained with anti-thymulin antibody were detected in two locations, approximately 60 kDa and 10 kDa, which may be a possible precursor and intermediate. All of the exposures except for heat were effective for induction of the 10 kDa protein. BLAST search using thymulin sequence identified SPATS2L, an intranucleolar stress-response protein with molecular weight of 62 kDa, containing thymulin-like sequence. Comparisons of blots stained with anti-thymulin and anti-SPATS2L antibodies indicate that SPATS2L may be a possible candidate for the precursor of thymulin.

Short-term antiviral activity of TMC278--a novel NNRTI--in treatment-naive HIV-1-infected subjects.

OBJECTIVE: To evaluate antiviral activity, pharmacokinetics, tolerability and safety of TMC278, a non-nucleoside reverse transcriptase inhibitor (NNRTI), when given as a 25, 50, 100 or 150 mg once-daily dose for 7 days to antiretroviral-naive HIV-infected subjects. DESIGN: Randomized, double-blind, placebo-controlled, phase IIa clinical trial. METHODS: Participants were 47 antiretroviral naive HIV-infected subjects. Primary outcome was the change in plasma HIV-1 RNA viral load from baseline to day 8. Secondary outcomes were evaluation of pharmacokinetics of TMC278, immunologic changes, safety and tolerability, and evolution of viral genotypic and phenotypic patterns. RESULTS: Patients treated with TMC278 achieved a median decrease in plasma viral load from baseline of 1.199 log10 copies/ml compared with a 0.002 log10 copies/ml gain in the placebo group (P < 0.01). A significantly higher proportion of subjects in the TMC278 groups obtained a viral load decrease of > 1.0 log10 compared with the placebo group (25/36 versus 0/11) (P < 0.01). No significant dose differences were noted in either antiviral effect or safety. No genotypic changes associated with antiretroviral resistance were detected between baseline and the end of the trial. Plasma concentrations of TMC278 were above the target concentration (13.5 ng/ml) at all time points for all TMC278-treated subjects. The most common reported adverse event was headache (TMC278 14%; placebo 18%). CONCLUSIONS: TMC278 showed antiviral activity when given as monotherapy for 7 days at all doses studied and the drug was safe and well tolerated. Trials of longer treatment duration with TMC278, in combination with other antiretroviral drugs, are underway to assess the long-term durability of antiviral response, safety and tolerability.

Genetic diversity of Culex pipiens mosquitoes in distinct populations from Europe: contribution of Cx. quinquefasciatus in Mediterranean populations.

BACKGROUND: Mosquitoes of the Culex pipiens complex are cosmopolitan, and important vectors of neglected tropical diseases, such as arbovirosis and lymphatic filariasis. Among the complex taxa, Cx. pipiens (with two forms pipiens and molestus) and Cx. quinquefasciatus are the most ubiquitous mosquitoes in temperate and tropical regions respectively. Mosquitoes of this taxa lack of morphological differences between females, but have frank behavioral and physiological differences and have different trophic preferences that influence their vectorial status. Hybridization may change the vectorial capacity of these mosquitoes, increasing vector efficiency and medical importance of resulting hybrids. METHODS: Culex pipiens s.l. from 35 distinct populations were investigated by the study of mtDNA, symbiotic bacterium Wolbachia pipientis, nuclear DNA and flanking region of microsatellite CQ11 polymorphism using PCR with diagnostic primers, RFLP analysis and sequencing. RESULTS: Six different mitochondrial haplotypes were revealed by sequencing of the cytochrome oxidase subunit I (COI) gene and three different Wolbachia (wPip) groups were identified. A strong association was observed between COI haplotypes/groups, wPip groups and taxa; haplogroup A and infection with wPipII appear to be typical for Cx. pipiens form pipiens, haplotype D and infection with wPipIV for form molestus, while haplogroup E, characteristic of Cx. quinquefasciatus, were correlated with wPipI and found in Cx. pipiens sl. from coastal regions of Southern Europe and Mediterranean region. Analysis of microsatellite locus and nuclear DNA revealed hybrids between Cx. pipiens form pipiens and form molestus, as well as between Cx. pipiens and Cx. quinquefasciatus, in Mediterranean populations, as opposed to Northern Europe. Phylogenetic analysis of COI sequences yielded a tree topology that supported the RFLP analysis with significant bootstrap values for haplotype D and haplogroup E. CONCLUSIONS: Molecular identification provides the first evidence of the presence of hybrids between Cx. quinquefasciatus and Cx. pipiens as well as cytoplasmic introgression of Cx. quinquefasciatus into Cx. pipiens as a result of hybridization events in coastal regions of Southern Europe and Mediterranean region. Together with observed hybrids between pipiens and molestus forms, these findings point to the presence of hybrids in these areas, with consequent higher potential for disease transmission.

Are specific antiretrovirals associated with an increased risk of discontinuation due to toxicities or patient/physician choice in patients with hepatitis C virus coinfection?

BACKGROUND: Liver damage associated with hepatitis C (HCV) may influence the likelihood of experiencing discontinuation due to toxicities or patient/physician choice (TOXPC) in patients taking combination antiretroviral therapy (cART). Little information to address this concern is available from clinical trials as patients with HCV are often excluded. AIMS: To compare incidence rates of discontinuation due to TOXPC associated with specific antiretrovial drugs in patients with or without HCV. PATIENTS/METHODS: A total of 4929 patients from EuroSIDA under follow-up from January 1999 on a specific nucleoside pair (zidovudine/lamivudine, didanosine/stavudine, stavudine/lamivudine, or other) with a third drug (abacavir, nelfinavir, indinavir, nevirapine, efavirenz, lopinavir/ritonavir or other boosted-protease inhibitor (PI)-containing regimen) and with known HCV serostatus were studied for the incidence of discontinuation of any nucleoside pair or third drug due to TOXPC. Incidence rate ratios were derived from Poisson regression models. RESULTS: In total 1358 patients had HCV (27.5%). During 12 799 person-years of follow-up there were 2141 discontinuations due to TOXPC for nucleoside pairs and 2501 for third drugs. The incidence of discontinuation due to TOXPC was consistently higher in patients with HCV after stratification by nucleoside pair or third drug. After adjustment for CD4+ count, gender, exposure group, time on HAART, region and treatment regimen, there were few differences in the rate of discontinuation due to TOXPC in those with HCV compared with those without for any nucleoside pairs or third drugs. Similar results were seen when concentrating on discontinuation due to toxicities alone. CONCLUSIONS: Although patients with HCV generally had higher rates of discontinuation due to TOXPC compared with patients without HCV, there was little evidence to suggest that this was associated with any specific nucleoside pair or third drug used as part of cART. Our results do not suggest that any specific component of cART is more poorly tolerated in patients with HCV or that the presence of HCV should influence the choice between antiretrovirals used as part of a cART regimen.

Antiretroviral prophylaxis to prevent perinatal HIV transmission in St. Petersburg, Russia: too little, too late.

BACKGROUND: We evaluated the influence of type and timing of prophylaxis on perinatal HIV transmission in St. Petersburg, Russia. METHODS: We linked surveillance data for 1498 HIV-infected mothers delivering from 2004 to 2007 with polymerase chain reaction data for 1159 infants to determine predictors of transmission. RESULTS: The overall perinatal transmission rate was 6.3% [73 of 1159, 95% confidence interval (CI) 4.9% to 7.7%]. Among the 12.8% (n = 149) of mother-infant pairs receiving full course (antenatal, intrapartum, postnatal) dual/triple antiretroviral prophylaxis, the transmission rate was 2.7%. Among the 1010 receiving less complete regimens (full course zidovudine, single-dose nevirapine, or incomplete), transmission ranged from 4.1% to 12.2%. Among the 28.9% (330) of mothers initiating antiretroviral drugs or=29 weeks (or not at all) had increased transmission odds (adjusted odds ratio: 4.9, 95% CI: 1.8 to 12.9; odds ratio: 5.1, 95% CI: 2.0 to 13.1, respectively). CONCLUSIONS: In St. Petersburg, the potential for further reductions in perinatal transmission is evident, given low transmission among women receiving early combination prophylaxis.

Decline in esophageal candidiasis and use of antimycotics in European patients with HIV.

BACKGROUND: Esophageal candidiasis (EC) remains one of the most common AIDS defining illnesses in patients with human immunodeficiency virus (HIV) in the era of highly active antiretroviral therapy (HAART), but little is known about factors associated with EC after starting HAART. OBJECTIVES: To describe changes in the use of antimycotic medication, the incidence of EC and factors associated with EC before and after starting HAART. METHODS: Patients from EuroSIDA, a pan-European longitudinal, prospective observational study. Generalized linear models and poisson regression models were used to investigate the relationships. RESULTS: A total of 9,873 patients did not have EC at recruitment, subsequently 537 (15.8%) developed EC. The proportion of patients taking any antimycotic dropped from 18% at January 1995 to 2% at January 2004 (p < 0.0001); the duration of treatment declined from 10 to 3 months over the same period (p < 0.0001). There was a 32% annual decline in the incidence of EC (95% CI 30-35%, p < 0.0001). There was a significant annual decline in the incidence of EC pre-HAART in time-updated, adjusted models, (incidence rate ratio (IRR) 0.80, 95% CI 0.76-0.85, p < 0.0001) but not post-HAART (IRR 0.97; 95% CI 0.90-1.06, p= 0.54). Older patients and those with low CD4 counts had the greatest incidence of EC in the post-HAART era. CONCLUSIONS: There has been a marked decline in the incidence of EC between 1994 and 2004. This was accompanied by a decline in markers associated with fungal disease, including use of antimycotics and a decline in duration of treatment.