Understanding Refugees Health Experiences in Host Countries: Three Theoretical Perspectives.

Healthcare providers working with forcefully displaced populations often have limited knowledge and skills regarding the care of this population. The reasons are twofold. First, most of the research on refugee health does not consider refugees' adaptive skills, diversity of experiences, and daily life context. Second, healthcare providers' knowledge of how the sociopolitical environment shapes health research and practice in the context of refugee care is often limited. This work aims to specify gaps in refugee healthcare and research by applying a relational approach to three theoretical frameworks. The relational approach supports a pragmatic, in-depth understanding of healthcare practices by shifting the focus of the inquiry from description of social structures toward exploration of processes and relations that propagate and sustain such structures. The focus is on the threefold interaction between refugees, healthcare providers, and healthcare institutions. The three theoretical frameworks are as follows: First, using concepts from the Theory of Practice by Bourdieu, we examine how gaps in care can result from a mismatch between the dispositions and skills that refugees develop through life experience and the cultural-professional practices of healthcare providers in host countries. Second, the Cultural Determinants of Help Seeking by Saint Arnault is applied to posit that gaps in care can result from differences in the meanings that healthcare providers and refugees assign to their interactions. Finally, we use the concept of Othering as described in nursing by Canales to explain how power dynamics inherent in the interaction between refugees and healthcare systems can affect refugee healthcare and research. This relational approach helps to elucidate some of the culture-bound mechanisms of health maintenance and help-seeking and brings attention to the sociopolitical context that shapes the way we care to refugees.

Evaluation of the Cytosolic Uptake of HaloTag Using a pH-Sensitive Dye.

The efficient cytosolic delivery of proteins is critical for advancing novel therapeutic strategies. Current delivery methods are severely limited by endosomal entrapment, and detection methods lack sophistication in tracking the fate of delivered protein cargo. HaloTag, a commonly used protein in chemical biology and a challenging delivery target, is an exceptional model system for understanding and exploiting cellular delivery. Here, we employed a combinatorial strategy to direct HaloTag to the cytosol. We established the use of Virginia Orange, a pH-sensitive fluorophore, and Janelia Fluor 585, a similar but pH-agnostic fluorophore, in a fluorogenic assay to ascertain protein localization within human cells. Using this assay, we investigated HaloTag delivery upon modification with cell-penetrating peptides, carboxyl group esterification, and cotreatment with an endosomolytic agent. We found efficacious cytosolic entry with two distinct delivery methods. This study expands the toolkit for detecting the cytosolic access of proteins and highlights that multiple intracellular delivery strategies can be used synergistically to effect cytosolic access. Moreover, HaloTag is poised to serve as a platform for the delivery of varied cargo into human cells.

Salvia dumetorum essential oil: GC-MS analysis, antibacterial activity and effect on the formation of Streptococcus mutans biofilms.

Salvia dumetorum essential oil (SDEO) was obtained using a Clevenger apparatus by hydrodistillation approach. The chemical composition of the essential oil was determined by GC-MS analysis. In this study SDEO was screened for its antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Candida albicans and the amount of biofilm formed by Streptococcus mutans bacteria. For the first time the chemical composition of SDEO growing in Central Kazakhstan was established. The results obtained from GC-MS showed the predominance of sesquiterpenoids (54.15%). The antibacterial study results showed that SDEO exhibited strong antibacterial activity against B. subtilis and S. aureus in vitro and also demonstrated an inhibitory effect on S. mutans biofilm formation on 1% sucrose medium. During the study, no antibacterial activity was detected against E. coli and C. albicans. These results demonstrated that SDEO can be used in the development of new antibacterial and anti-caries therapeutic dental products.

New Acylcarnitine Ratio as a Reliable Indicator of Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency.

Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (MTP) deficiencies are rare fatal disorders of fatty acid ß-oxidation with no apparent genotype-phenotype correlation. The measurement of acylcarnitines by MS/MS is a current diagnostic workup in these disorders. Nevertheless, false-positive and false-negative results have been reported, highlighting a necessity for more sensitive and specific biomarkers. This study included 54 patients with LCHAD/MTP deficiency that has been confirmed by biochemical and molecular methods. The analysis of acylcarnitines in dried blood spots was performed using ESI-MS/MS. The established "HADHA ratio" = (C16OH + C18OH + C18:1OH)/C0 was significantly elevated in all 54 affected individuals in comparison to the control group. Apart from 54 LCHAD deficiency patients, the "HADHA ratio" was calculated in 19 patients with very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. As VLCAD-deficient patients did not show increased "HADHA ratio", the results emphasized the high specificity of this new ratio. Therefore, the "HADHA ratio" was shown to be instrumental in improving the overall performance of MS/MS-based analysis of acylcarnitine levels in the diagnostics of LCHAD/MTP deficiencies. The ratio was demonstrated to increase the sensitivity and specificity of this method and reduce the chances of false-negative results.

Fluorescent Guanidinium-Azacarbazole for Oxoanion Binding in Water.

Oxoanions such as carboxylates, phosphates, and sulfates play important roles in both chemistry and biology and are abundant on the cell surface. We report on the synthesis and properties of a rationally designed guanidinium-containing oxoanion binder, 1-guanidino-8-amino-2,7-diazacarbazole (GADAC). GADAC binds to a carboxylate, phosphate, and sulfate in pure water with affinities of 3.6 × 104, 1.1 × 103, and 4.2 × 103 M-1, respectively. Like 2-azacarbazole, which is a natural product that enables scorpions to fluoresce, GADAC is fluorescent in water (λabs = 356 nm, λem = 403 nm, ε = 13,400 M-1 cm-1). The quantum yield of GADAC is pH-sensitive, increasing from Φ = 0.12 at pH 7.4 to Φ = 0.53 at pH 4.0 as a result of the protonation of the aminopyridine moiety. The uptake of GADAC into live human melanoma cells is detectable in the DAPI channel at low micromolar concentrations. Its properties make GADAC a promising candidate for applications in oxoanion binding and fluorescence labeling in biological (e.g., the delivery of cargo into cells) and other contexts.

Oncolytic Efficacy of a Recombinant Vaccinia Virus Strain Expressing Bacterial Flagellin in Solid Tumor Models.

Oncolytic viral therapy is a promising novel approach to cancer treatment. Oncolytic viruses cause tumor regression through direct cytolysis on the one hand and recruiting and activating immune cells on the other. In this study, to enhance the antitumor efficacy of the thymidine kinase-deficient vaccinia virus (VV, Lister strain), recombinant variants encoding bacterial flagellin (subunit B) of Vibrio vulnificus (LIVP-FlaB-RFP), firefly luciferase (LIVP-Fluc-RFP) or red fluorescent protein (LIVP-RFP) were developed. The LIVP-FLuc-RFP strain demonstrated exceptional onco-specificity in tumor-bearing mice, detected by the in vivo imaging system (IVIS). The antitumor efficacy of these variants was explored in syngeneic murine tumor models (B16 melanoma, CT26 colon cancer and 4T1 breast cancer). After intravenous treatment with LIVP-FlaB-RFP or LIVP-RFP, all mice tumor models exhibited tumor regression, with a prolonged survival rate in comparison with the control mice. However, superior oncolytic activity was observed in the B16 melanoma models treated with LIVP-FlaB-RFP. Tumor-infiltrated lymphocytes and the cytokine analysis of the serum and tumor samples from the melanoma-xenografted mice treated with these virus variants demonstrated activation of the host's immune response. Thus, the expression of bacterial flagellin by VV can enhance its oncolytic efficacy against immunosuppressive solid tumors.

Chemoselective Caging of Carboxyl Groups for On-Demand Protein Activation with Small Molecules.

Tools for on-demand protein activation enable impactful gain-of-function studies in biological settings. Thus far, however, proteins have been chemically caged at primarily Lys, Tyr, and Sec, typically through the genetic encoding of unnatural amino acids. Herein, we report that the preferential reactivity of diazo compounds with protonated acids can be used to expand this toolbox to solvent-accessible carboxyl groups with an elevated pKa value. As a model protein, we employed lysozyme (Lyz), which has an active-site Glu35 residue with a pKa value of 6.2. A diazo compound with a bioorthogonal self-immolative handle esterified Glu35 selectively, inactivating Lyz. The hydrolytic activity of the caged Lyz on bacterial cell walls was restored with two small-molecule triggers. The decaging was more efficient by small molecules than by esterases. This simple chemical strategy was also applied to a hemeprotein and an aspartyl protease, setting the stage for broad applicability.

Modular Diazo Compound for the Bioreversible Late-Stage Modification of Proteins.

We introduce a versatile strategy for the bioreversible modification of proteins. Our strategy is based on a tricomponent molecule, synthesized in three steps, that incorporates a diazo moiety for chemoselective esterification of carboxyl groups, a pyridyl disulfide group for late-stage functionalization with thiolated ligands, and a self-immolative carbonate group for esterase-mediated cleavage. Using cytochrome c (Cyt c) and the green fluorescent protein (GFP) as models, we generated protein conjugates modified with diverse domains for cellular delivery that include a small molecule, targeting and cell-penetrating peptides (CPPs), and a large polysaccharide. As a proof of concept, we used our strategy to effect the delivery of proteins into the cytosol of live mammalian cells in the presence of serum. The cellular delivery of functional Cyt c, which induces apoptosis, highlighted the advantage of bioreversible conjugation on a carboxyl group versus irreversible conjugation on an amino group. The ease and utility of this traceless modification provide new opportunities for chemical biologists.

Application of vibrational spectroscopy and nuclear magnetic resonance methods for drugs pharmacokinetics research.

OBJECTIVES: The development of new methods for determining the concentration of drugs is an actual topic today. The article contains a detailed review on vibrational spectroscopy and nuclear magnetic resonance methods using for pharmacokinetic research. This study is devoted to the possibility of using vibrational spectroscopy and 1H nuclear magnetic resonance spectroscopy to determine the concentration of drugs and the use of these groups of techniques for therapeutic drug monitoring. CONTENT: The study was conducted by using scientific libraries (Scopus, Web of Science Core Collection, Medline, GoogleScholar, eLIBRARY, PubMed) and reference literature. A search was conducted for the period from 2011 to 2021 in Russian and English, by combinations of words: 1H nuclear magnetic resonance (1H NMR), vibrational spectroscopy, Surface-Enhanced Raman spectroscopy, drug concentration, therapeutic drug monitoring. These methods have a number of advantages and are devoid of some of the disadvantages of classical therapeutic drug monitoring (TDM) methods - high performance liquid chromatography and mass spectrometry. This review considers the possibility of using the methods of surface-enhanced Raman scattering (SERS) and 1H NMR-spectroscopy to assess the concentration of drugs in various biological media (blood, urine), as well as to study intracellular metabolism and the metabolism of ophthalmic drugs. 1Н NMR-spectroscopy can be chosen as a TDM method, since it allows analyzing the structure and identifying metabolites of various drugs. 1Н NMR-based metabolomics can provide information on the side effects of drugs, predict response to treatment, and provide key information on the mechanisms of action of known and new drug compounds. SUMMARY AND OUTLOOK: SERS and 1Н NMR-spectroscopy have great potential for further study and the possibility of introducing them into clinical practice, including for evaluating the efficacy and safety of drugs.

Cu, Mg Codoped Bismuth Tantalate Pyrochlores: Crystal Structure, XPS Spectra, Thermal Expansion, and Electrical Properties.

The pyrochlore-type solid-solution formation in a Bi1.6Mg0.8-xCuxTa1.6O7.2-Δ system, synthesized for the first time, is observed at x ≤ 0.56. High-temperature X-ray diffraction showed that the pyrochlore phase exists in air up to 1080 °C, where its thermal decomposition leads to the segregation of (Mg,Cu)Ta2O6. The thermal expansion coefficients of the end member, Bi1.6Mg0.24Cu0.56Ta1.6O7.2-Δ, increase from 3.3 × 10-6 °C-1 at room temperature up to 8.7 × 10-6 °C-1 at 930 °C. Rietveld refinement confirmed that the pyrochlore crystal structure is disordered with space group Fd3̅m:2 (Z = 8, no. 227). Doping with copper results in a modest expansion of the cubic unit cell, promotes sintering of the ceramic materials, and induces their red-brown color. X-ray photoelectron spectroscopy demonstrated that the states of Bi(III) and Mg(II) are not affected by doping, and the effective charge of tantalum cations is lower than +5, while the Cu(II) states coexist with Cu(I). The electron spin resonance spectra display a single line with g = 2.2, ascribed to the dipole-broadened Cu2+ signal. The dielectric permittivity of Bi1.6Mg0.8-xCuxTa1.6O7.2-Δ ceramics may achieve up to ∼105, with the dielectric loss tangent varying in the range from 0.2 up to 12. Multiple dielectric relaxations are found at room temperature and above for all samples.

Clinical relevance of circulating MACC1 and S100A4 transcripts for ovarian cancer.

Metastasis-associated in colon cancer 1 (MACC1) and S100 calcium-binding protein A4 (S100A4) are prominent inducers of tumor progression and metastasis. For the first time, we systematically tracked circulating serum levels of MACC1 and S100A4 transcripts in the course of surgery and chemotherapy and analyzed their clinical relevance for ovarian cancer. MACC1 and S100A4 transcripts were quantified in a total of 318 serum samples from 79 ovarian cancer patients by RT-qPCR and digital droplet PCR, respectively. MACC1 and S100A4 transcripts were significantly elevated in serum of ovarian cancer patients, compared to healthy controls (P = 0.024; P < 0.001). At primary diagnosis, high levels of MACC1 or S100A4 correlated with advanced FIGO stage (P = 0.042; P = 0.008), predicted suboptimal debulking surgery and indicated shorter progression-free survival (PFS; P = 0.003; P = 0.001) and overall survival (OS; P = 0.001; P = 0.002). This is the first study in ovarian cancer to propose circulating MACC1 and S100A4 transcripts as potential liquid biopsy markers.

Two new cestode species of the family Hymenolepididae Perrier, 1897 (Cyclophyllidea) from passerine birds in Ethiopia, with the erection of Citrilolepis n. g.

Two new cestode species of the family Hymenolepididae Perrier, 1897 are described from birds of the order Passeriformes at Wondo Genet, Ethiopia. Passerilepis zimbebel n. sp., a parasite of Terpsiphone viridis (Müller) (Monarchidae), is distinguished from its most similar congeners by its diorchoid rostellar hooks with length 37-38 µm, its median ovary consisting of three compact lobes, its compact vitellarium and the variable position of the terminal genital ducts passing mostly dorsally to the poral osmoregulatory canals. Citrilolepis n. g. is erected as monotypic for C. citrili n. sp., a parasite of Crithagra citrinelloides (Rüpell) (Fringillidae). The new genus is distinguished from the remaining avian and mammalian genera of the family Hymenolepididae by the presence of numerous (18) rostellar hooks, unilateral sinistral genital pores, ventral osmoregulatory canals with transverse anastomoses, 3 (rarely 4, in c.10% of proglottides) testes in number with variable positions in the proglottis and the sac-like uterus not extending beyond the osmoregulatory canals.

Antioxidant and prooxidant effects of Piptadeniastrum africanum as the possible rationale behind its broad scale application in African ethnomedicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Piptadeniastrum africanum is widely used in treating oxidative stress related diseases. Oxidative stress, defined as the disturbance in the balance between the production of free radicals and antioxidant defenses, is the root cause of many pathophysiological conditions. Based on the dual properties of prooxidants as toxic and beneficial compounds, both prooxidants and antioxidants may be effective in the treatment of these conditions when the right dose is given to the right subject at the right time for the right duration. AIM OF THE STUDY: This study was aimed at investigating the in vitro and ex vivo anti- and pro-oxidative effects of P. africanum. MATERIALS AND METHODS: Total phenolic and flavonoid contents of methanol and aqueous extracts of P. africanum stem back were quantified spectrophotometrically. The methanol extract, ascorbate radicals and reactive oxygen species in brain and liver homogenates of mice treated with the methanol stem bark extract were analyzed by electron paramagnetic resonance (EPR) spectroscopy. Free radical scavenging of DPPH was determined by spectrophotometric and EPR assays. RESULTS: The methanol extract was richer in both phenolic and flavonoid contents compared to the aqueous extracts and also showed better DPPH radical scavenging capacity. The EPR spectroscopy in vitro analysis exhibited high DPPH scavenging capacity before and after UV irradiation (99.5% and 98.76%) at 40 µg/ml extract. The ex vivo EPR spectroscopy studies demonstrated increased levels of ascorbate radicals (•Asc) in liver and brain homogenates of healthy mice treated with P. africanum in comparison with those of the non treated controls (0.6141 ±â€¯0.026 vs 0.1800 ±â€¯0.0073 arb. units for liver homogenates and 0.9605 ±â€¯0.0492 vs 0.3375 ±â€¯0.0062 arb. units for brain homogenates, correspondingly). Considerably, higher levels of reactive oxygen species (ROS) were measured in mice liver and brain homogenates after treatment with P. africanum extract compared to the control group, as well (1.9402 ±â€¯0.1200 vs 0.6699 ±â€¯0.062 arb. units for liver homogenates and 1.7325 ±â€¯01503 vs 0.3167 ±â€¯0.0403 arb.units, respectively). CONCLUSION: Therefore, P. africanum exhibited antioxidant and pro-oxidant properties which may explain its broad spectrum use in a wide variety of ailments.

Xantogranuloma juvenil com múltiplas lesões / Juvenile xanthogranuloma with multiple skin lesions

Objetivo: O xantogranuloma juvenil é uma histiocitose não Langerhans que geralmente surge no primeiro ano de vida e que em 82% dos casos se manifesta como lesão única. Sendo assim, justifica-se a relevância deste relato, posto que apresentamos uma variante clínica incomum, com multiplicidade de lesões. Descrição do caso: Paciente do sexo feminino, dez meses de idade, apresenta pápulas assintomáticas iniciadas aos 4 meses de vida, localizadas no couro cabeludo, face, pescoço, tronco e extremidades. As pápulas se apresentavam não confluentes, de superfície lisa, contornos regulares e margens bem definidas. Algumas normocrômicas, outras eritematosas, de consistência firme e indolores a palpação. Ao exame oftalmológico não foram encontradas alterações e a biópsia de uma lesão no dorso apresentou análise histopatológica compatível com o diagnóstico. Conclusão: Pacientes com xantogranuloma juvenil devem ser avaliados de forma multidisciplinar posto que foram relatados associações da patologia com neurofibromatose tipo I e LMC juvenil. Esta condição clínica é considerada indicativa da necessidade de investigação de possível leucemia subjacente e pesquisa de história familiar de neurofibromatose. A investigação oftalmológica também se faz necessária, pois é relatado como sendo o acometimento mais frequente, embora incomum. Diante disso, pacientes com múltiplas lesões, crianças menores de dois anos e sintomas oculares são considerados fatores de risco para acometimento ocular e necessitam de investigação especializada para essa manifestação extradermatológica.

Pseudangularia gonzalezi n. sp. and Gibsonilepis swifti (Singh, 1952) n. g., n. comb. (Cestoda, Dilepididae) from the House Swift, Apus affinis (J.E. Gray) (Aves, Apodiformes) from Franceville, Republic of Gabon.

Nine specimens of Apus affinis (J.E. Gray) were studied at Franceville, Haut-Ogooué Province, Republic of Gabon, for the presence of helminth parasites. Two cestode species of the family Dilepididae were recorded. Pseudangularia gonzalezi n. sp. is distinguished from the most similar species P. europaea Georgiev & Murai, 1993 by having elliptical cirrus-sac, longer vagina, longer rostellar sheath and greater diameter of suckers. An identification key to the species of the genus Pseudangularia Burt, 1938 is proposed. The present study is the first record of the genus Pseudangularia in the Afrotropical Region. Our study confirms that, in dilepidids with vaginal sclerites from swifts, breaking off the cirrus after copulation is a frequent phenomenon. The genus Gibsonilepis n. g. is erected as monotypic for Vitta swifti Singh, 1952 (originally described from the same host species in India) and Gibsonilepis swifti n. comb. is proposed. Gibsonilepis n. g. is distinguished from Vitta Burt, 1938 by its highly elongate rostellum, rostellar sheath much bigger than rostellum, relatively small rostellar hooks possessing strongly developed guard, disc-shaped suckers with weak peripheral musculature and flat or convex central part, long and well-expressed neck, highly lobed two-winged ovary (lobes rounded) and presence of a band consisting of rows of spine-like microtriches along posterior margin of each proglottis. This is the first record of G. swifti in the Afrotropical Region. The separation of G. swifti from the genus Vitta (parasites of swallows) suggests that, contrary to previous opinions, no dilepidid genera are shared by Apodidae (swifts) and Hirundinidae (swallows).

Perceptual assimilation of American English vowels by inexperienced Russian listeners.

In a perceptual assimilation task, 16 Russian speakers categorized American English (AE) vowels [i[see text], I, epsilon, ae[see tedxt], a[see text], u[see text]] in /Vp/ disyllables into Russian (RU) response categories and rated their perceived goodness on a 9-point Likert scale. Cross-language discriminant analysis established acoustic similarities to Russian vowels. For all but AE [epsilon], acoustic similarity predicted modal assimilation responses. Russian listeners consistently assimilated AE point vowels to their Russian counterparts, whereas assimilation of the remaining vowels was less consistent. These acoustic and perceptual similarity patterns provide a baseline for future studies of AE vowel discrimination by Russian learners of English.

[Fungal keratitis in the State of Paraná-Brazil: clinical, epidemiological and diagnostic findings]. / Ceratite fúngica no estado do Paraná-Brasil: aspectos epidemiológicos, etiológicos e diagnósticos.

Fungal keratites is more prevalent in tropical and subtropical regions, such as Brazil, and causes high morbidity. Usually, it is preceded by underlying conditions like ocular trauma or immunosuppression. The diagnosis is confirmed by the demonstration of the etiologic agent in the clinical specimen. Data were analysed from 49 patients with fungal keratitis observed in Ophthalmologic Division of Hospital de Clinicas, Federal University of Parana, from 1983 to 1997. The diagnosis was confirmed by culture and/ or direct examination. Of the cases studied, 22% were diagnosed only by direct examination; 50% by isolation in culture and 26% by the association of the both methods. The most prevalent etiologic agents were: Fusarium sp. (32%), Aspergillus sp. (16,5%) and Penicillium sp. (10%).