Explosive nosocomial outbreak of SARS-CoV-2 in a rehabilitation clinic: the limits of genomics for outbreak reconstruction.

BACKGROUND: Nosocomial outbreaks of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are frequent despite implementation of conventional infection control measures. An outbreak investigation was undertaken using advanced genomic and statistical techniques to reconstruct likely transmission chains and assess the role of healthcare workers (HCWs) in SARS-CoV-2 transmission. METHODS: A nosocomial SARS-CoV-2 outbreak in a university-affiliated rehabilitation clinic was investigated, involving patients and HCWs, with high coverage of pathogen whole-genome sequences (WGS). The time-varying reproduction number from epidemiological data (Rt) was estimated, and maximum likelihood phylogeny was used to assess genetic diversity of the pathogen. Genomic and epidemiological data were combined into a Bayesian framework to model the directionality of transmission, and a case-control study was performed to investigate risk factors for nosocomial SARS-CoV-2 acquisition in patients. FINDINGS: The outbreak lasted from 14th March to 12th April 2020, and involved 37 patients (31 with WGS) and 39 employees (31 with WGS), 37 of whom were HCWs. Peak Rt was estimated to be between 2.2 and 3.6. The phylogenetic tree showed very limited genetic diversity, with 60 of 62 (96.7%) isolates forming one large cluster of identical genomes. Despite the resulting uncertainty in reconstructed transmission events, the analyses suggest that HCWs (one of whom was the index case) played an essential role in cross-transmission, with a significantly greater fraction of infections (P<2.2e-16) attributable to HCWs (70.7%) than expected given the number of HCW cases (46.7%). The excess of transmission from HCWs was higher when considering infection of patients [79.0%; 95% confidence interval (CI) 78.5-79.5%] and frail patients (Clinical Frailty Scale score >5; 82.3%; 95% CI 81.8-83.4%). Furthermore, frail patients were found to be at greater risk for nosocomial COVID-19 than other patients (adjusted odds ratio 6.94, 95% CI 2.13-22.57). INTERPRETATION: This outbreak report highlights the essential role of HCWs in SARS-CoV-2 transmission dynamics in healthcare settings. Limited genetic diversity in pathogen genomes hampered the reconstruction of individual transmission events, resulting in substantial uncertainty in who infected whom. However, this study shows that despite such uncertainty, significant transmission patterns can be observed.

Lack of health insurance among juvenile offenders: a predictor of inappropriate healthcare use and reincarceration?

OBJECTIVES: Relationships between the health insurance status and healthcare use among justice-involved youths transitioning into adulthood is an underexplored topic, even if transition to adulthood is a crucial time period for healthcare outcomes. To fill in these knowledge gaps, this study had two aims: (1) to examine trajectories of health insurance coverage and healthcare use among serious juvenile offenders transitioning into adulthood; and (2) to explore associations between the lack of health insurance, healthcare use and reincarceration. STUDY DESIGN: We conducted a secondary analysis on the data of the US longitudinal Pathways to Desistance study between ages 20 and 23 years (2000-2010). METHODS: Participant data on health insurance coverage, healthcare use, reincarceration and sociodemographic variables (n = 1215) were extracted and analysed using descriptive statistics, generalized linear regressions and cross-lagged panel models. RESULTS: About half of the young offenders had no health insurance coverage or intermittent coverage between the age of 20 and 23 years. Emergency services were used (≥17.4%), notably more by insured participants and were increasingly used over time. Being uninsured at the age of 20 years was associated with reincarceration at the age of 23 years (b = -0.052, p = 0.014, odd-ratio = 0.95), but incarceration at the age of 20 years did not predict the insurance status at the age of 23 years (b = 0.009, p = 0.792). CONCLUSIONS: Serious juvenile offenders, especially if uninsured, faced major barriers to accessing health care and often reported an inappropriate healthcare use. This likely led to reincarceration. The lack of continuity of care and of access to health care may, therefore, increase health disparities, and efforts are needed to mitigate detrimental outcomes, by effective in and out of detention coordination of health insurance coverage and among health services.

Chemical characterization and complement modulating activities of an arabinogalactan-protein-rich fraction from an aqueous extract of avocado leaves.

The aim of this study was to chemically characterize an arabinogalactan-protein-rich fraction (FRAGP) obtained from an aqueous extract of avocado leaves and investigate its effects on the classical pathway of the complement system. The FRAGP contained 4.6% ±â€¯1.8%, 22.5% ±â€¯4.9%, and 76.7% ±â€¯8.8% of total protein, arabinogalactan-protein, and carbohydrates, respectively. Arabinose and galactose were the main monosaccharide constituents. FT-IR and NMR data, together with linkage analyses, indicated the presence of a structure that included a (1 → 3)-linked ß-D-Galp main chain, mainly substituted at O-6 by Gal and Ara residues, which was characteristic of a type II arabinogalactan. The effect of FRAGP on the classical pathway of complement system was examined by a hemolytic fixation test and comparing with heparin, which was used as a control for inhibition. With pre-incubation, the IC50 of FRAGP was 1.90 ±â€¯1.1 µg/mL, which was similar to that of heparin (IC50 = 2.90 ±â€¯0.3 µg/mL). Without pre-incubation, the IC50 values were 18.6 ±â€¯3.7 and 8.0 ±â€¯4.1 µg/mL for FRAGP and heparin, respectively. Collectively, these results suggested that FRAGP has an inhibitory effect on the classical pathway of the complement system.

Substance use capital: Social resources enhancing youth substance use.

BACKGROUND: Social capital is described as a protective factor against youth substance use, but it may also be associated with behaviours that do not enhance health. The present study hypothesized that 'substance use capital', i.e. resources favourable to substance use, is a risk factor for substance use and misuse. METHODS: We used baseline data from the ongoing Cohort Study on Substance Use Risk Factors (C-SURF) that included a representative sample of young Swiss men (n=5623). Substance use (alcohol, cannabis, 15 illicit drugs, lifetime use, hazardous use and dependence), substance use capital (parental and peer attitudes towards substance use, parental and peer drug use, perceived norms of substance use) and aspects of social capital (relationships with parents and peers) were assessed. Logistic regressions were used to examine the associations between substance-related resources and social resources, and substance use. RESULTS: Results showed that substance-related resources were associated with an increased risk of substance use (OR between 1.25 and 4.67), whereas social resources' associations with substance use were commonly protective but weaker than substance-related resources. Thus, a drug-friendly environment facilitated substance use and misuse. Moreover, the results showed that peer environments were more drug-friendly than familial environments. CONCLUSION: In conclusion, this study highlighted a concept of 'substance use capital', which may be useful for advancing both theoretical and applied knowledge of substance use. Indeed, substance use is not only associated with a lack of social resources, but also with specific drug-friendly social resources coming from environment and background.

Modulating Effects of Arabinogalactans from Plant Gum Exudates on Human Complement System.

Gum arabic and cashew nut tree gum exudate polysaccharide (CNTG) are plant polysaccharides composed of galactose and arabinose known as arabinogalactans (AGs). Although these fractions are used in food and pharmaceutical industry, cases of allergic reactions were described in clinical reports. As AGs were reported as modulators of the classical (CP) and alternative pathways (AP) of complement system (CS), in the present work, we investigate whether gum arabic and CNTG have an effect on both CS pathways. The complement fixation tests were performed with (CP-30 and AP-30) and without pre-incubation (CP-0 and AP-0). For CP-30, CNTG and gum arabic (833 µg/ml) showed a reduction of 28.0% (P = 0.000174) and 48.5% (P = 0.000143), respectively, on CP-induced haemolysis. However, no effect was observed for CP-0 in the CP-induced haemolysis. For AP-30, both CNTG and gum arabic (833 µg/ml) showed 87% reduction on the CP-induced haemolysis, with IC50 values of 100 and 7 µg/ml, respectively. For AP-0, a reduction of 11.3% for gum arabic and no effect for the CNTG on the CP-induced haemolysis were observed. These results suggested that gum arabic and CNTG could be acting as activators of the CS. Thus, this effect on the CS, especially on the AP, which accounts for up to 80-90% of total CS activation, indicates that both fractions may be harmful because of their potential pro-inflammatory action. Considering that CS activation induces inflammatory response, further studies confirming this immunomodulatory effect of these fractions are required to insure their safe use.

Pectinas de plantas medicinais: características estruturais e atividades imunomoduladoras / Pectins of medicinal plants: structural characteristics and immunomodulatory activities

RESUMO As plantas medicinais apresentam várias propriedades terapêuticas, as quais estão relacionadas com a presença de compostos bioativos. Dentre os compostos, destacam-se as pectinas, que compreendem um grupo de polissacarídeos ácidos de relevante importância medicinal e nutracêutica. As pectinas são formadas por unidades de ácido galacturônico, unidas por ligação do tipo α-(1→4), sendo classificadas em homogalacturonanas e ramnogalacturonanas tipo I (RG-I) e tipo II (RG-II). Outros polissacarídeos constituídos por arabinose e/ou galactose têm sido isolados em associação com polissacarídeos pécticos, como as arabinogalactanas (AG) (tipo I e tipo II). As AG-II podem estar associadas a proteínas, denominadas de arabinogalactana-proteínas (AGPs). Inúmeros relatos demonstram que as pectinas, bem como as AG e AGPs, podem atuar como moduladores do sistema imunológico, sendo, por isso, consideradas modificadores da resposta biológica. A imunomodulação pode estar relacionada tanto com a atividade de macrófagos quanto com as vias do sistema complemento. Em geral, os polissacarídeos provocam um estímulo da atividade fagocitária; no aumento da produção de espécies reativas de oxigênio e da secreção de citocinas pró-inflamatórias. Em relação ao sistema complemento, os polissacarídeos podem modular tanto a via clássica como a via alternativa. A presente revisão tem como objetivo principal descrever os aspectos estruturais de pectinas e suas atividades biológicas relacionadas à modulação do sistema imune. Utilizando literatura específica, estão descritas informações de 29 espécies de plantas medicinais, que apresentam como constituintes pectinas, arabinogalactanas e/ou AGPs, correlacionando suas propriedades terapêuticas com as atividades biológicas associadas ao sistema imune. Na maioria dos casos descritos na literatura, é difícil determinar como as características estruturais específicas podem estar envolvidas na modulação da atividade de macrófagos. Porém, em relação à modulação da atividade do sistema complemento fica sugerido que a presença de estruturas tipo AG-II contribuiria mais significativamente para esta atividade. Entretanto, os possíveis mecanismos de modulação de pectinas, AGs e AGPs sobre a atividade de macrófagos e/ou sobre o sistema complemento ainda não estão totalmente esclarecidos, mesmo assim, estes polímeros podem ser considerados potenciais candidatos para estudos que visam ao desenvolvimento de novos agentes terapêuticos com propriedades moduladoras benéficas para o sistema imunológico.

ABSTRACT Medicinal plants have many therapeutic properties that are related to the presence of biologically active compounds. Pectins, a group of acid polysaccharides that have relevant medicinal and nutraceutical properties, are an example of such biological compounds. Pectins contain a main chain with galacturonic acid units that are α-(1→4) linked; they can be classified into homogalacturonans and type I and type II rhamnogalacturonans (RG-I and RG-II). Other polysaccharides containing arabinose, galactose, or both have been isolated in association with pectin-type polysaccharides are known as arabinogalactans (AGs, type I and type II). Arabinogalactan-proteins (AGPs) comprise AG-II associated with proteins. Several studies have reported that pectins, as well as AG and AGPs, can act as modulators of the immune system and can therefore be considered biological response modifiers. The immunomodulation is related to the activity of macrophages as on the complement system pathways. In general, polysaccharides cause stimulation of phagocytic activity, increase production of reactive oxygen species and secretion of pro-inflammatory cytokines. Polysaccharides can modulate the classical and alternative complement pathways. The aim of this review has to describe the structural aspects of pectins and their biological activities related to the modulation of the immune system. Using literature, we reported data of 29 medicinal plant species, which present as constituents pectins, arabinogalactan and/or AGPs, correlating their therapeutic properties with biological activities associated to the immune system. In most cases described in the literature, it is difficult to determine how the specific structural characteristics can be involved in modulation of macrophage activity. However, with respect to the modulation of the activity of the complement system is proposed that the presence of AG-II-type structures would contribute most significantly to this activity. The possible mechanisms of modulation of pectins, AGs and AGPs on macrophage activity and/or the complement system are not yet fully clear, even if, these polymers can be considered potential candidates for studies aimed at the development of new therapeutic agents with modulatory properties beneficial to the immune system.

Effect of the native polysaccharide of cashew-nut tree gum exudate on murine peritoneal macrophage modulatory activities.

The native polysaccharide of cashew-nut tree gum exudate (CNTG) and its arabinogalactan-protein component (CNTG-AGP) were tested by using immuno-stimulant and anti-inflammatory in vitro assays of murine peritoneal macrophage activities. In the assay for immuno-stimulant activity (without previous treatment with lipopolysaccharide; LPS), CNTG increased the production of interleukin (IL)-10 and both CNTG and CNTG-AGP decreased the concentrations of IL6. When the macrophages were incubated in the presence of LPS and CNTG a decrease in the levels of nitric oxide (NO(·)) and IFN-γ was observed. The results could explain the popular use of CNTG as an anti-inflammatory. In addition, CNTG is the main component of the cashew-nut tree gum exudate, which has been considered a versatile polymer with potential pharmaceutical and food industry applications. These data may contribute to the study of the immunomodulation activity of plant polysaccharides, as well as encourage future experiments in the field of cashew-nut tree gum exudate applications.

Atividade ovicida e larvicida do extrato hidroalcoólico de Artemisia annua sobre parasitas gastrintestinais de bovinos / Ovicidal and larvicidal activity of Artemisia annua hydroalcoholic extract against gastrointestinal parasites in cattle

Os parasitas gastrintestinais causam enorme prejuízo econômico na bovinocultura, tanto nacional como mundial, ocasionado principalmente por Bunostumom sp., Cooperia sp. e Trichostrongylus sp. O objetivo deste trabalho foi determinar a eficácia in vitro do extrato hidroalcoólico de Artemisia annua (H.7) frente a esses endoparasitas. O H.7 foi produzido com sete dias de percolação a 4ºC e posteriormente liofilizado. Com esse fitoterápico, realizaram-se testes de eclodibilidade de ovos (TEO) e de migração larvar em ágar (TMLA), com seis repetições, com concentrações crescentes (0,78 a 50mg/mL). Para analisar a composição química do fitoterápico, procedeu-se à marcha fitoquímica completa. No TEO, a eficácia variou de 94,08±2,58% na maior concentração a 15,67±0,97% na menor concentração. Já no TMLA os valores encontrados variaram de 90,05±0,55% a 4,12±0,46%. Nas análises fitoquímicas, foram encontrados diversos compostos com propriedades de combater os nematódeos, tanto direta como indiretamente. Os resultados obtidos nos testes in vitro evidenciam que o extrato produzido possui potencial de combater nematódeos gastrintestinais de bovinos. Novos estudos devem ser realizados buscando maximizar a eficácia do H.7 e de outras extrações obtidas a partir de A. annua, uma vez que foram demonstrados excelentes resultados em ambos os experimentos.

Gastrointestinal parasites cause economic losses to the cattle production, in Brazil and worldwide, mainly caused by Bunostumom sp., Cooperia sp. and Trichostrongylus sp. The aim of this study was to determine the in vitro efficacy of hydroalcoholic extract of Artemisia annua (H.7) against these parasites. The H.7 was produced after 7 days of storage at 4°C and then lyophilized. With this herbal the egg hatch test (EHT) and larval migration inhibition (LMI) were performed,in six replicates with different concentrations (0.78 to 50mg/mL). To analyze the chemistry composition the complete phytochemical screening was done. In EHT efficiency ranged from 94.08±2.58% at the highest concentration to 15.67± 0.97% in the lowest concentration. In LMI test the values ranged from 90.05±0.55% to 4.12±0.46%. Phytochemical tests showed many chemical compounds with anthelmintic properties. The results obtained in biochemical tests together with those found in in vitro tests showed that the extract produced has the potential to combat intestinal nematodes of cattle. Further studies should be conducted to maximize the effectiveness of H.7 and other extractions from A. annua, because it demonstrated excellent results in both experiments.

[Adaptation of a peer pressure scale in French and German: the Peer Pressure Inventory]. / Adaptation en français et en allemand d'une échelle de pression des pairs pour jeunes adultes : le Peer Pressure Inventory.

BACKGROUND: Peer pressure is regarded as an important determinant of substance use, sexual behavior and juvenile delinquency. However, few peer pressure scales are validated, especially in French or German. Little is known about the factor structure of such scales or the kind of scale needed: some scales takes into account both peer pressure to do and peer pressure not to do, while others consider only peer pressure to do. The aim of the present study was to adapt French and German versions of the Peer Pressure Inventory, which is one of the most widely used scales in this field. We considered its factor structure and concurrent validity. METHODS: Five thousand eight hundred and sixty-seven young Swiss men filled in a questionnaire on peer pressure, substance use, and other variables (conformity, involvement) in a cohort study. RESULTS: We identified a four-factor structure, with the three factors of the initial Peer Pressure Inventory (involvement, conformity, misconduct) and adding a new one (relationship with girls). A non-valued scale (from no peer pressure to peer pressure to do only) showed stronger psychometric qualities than a valued scale (from peer pressure not to do to peer pressure to do). Concurrent validity was also good. Each behavior or attitude was significantly associated with peer pressure. CONCLUSION: Peer pressure seems to be a multidimensional concept. In this study, peer pressure to do showed the strongest influence on participants. Indeed, peer pressure not to do did not add anything useful. Only peer pressure to do affected young Swiss men's behaviors and attitudes and was reliable.

Bis(2,2':6',2"-terpyridine-kappa3N)manganese(II) tetrathionate trihydrate.

The structure of the title compound, [Mn(tpy)2](S4O6)*3H2O (tpy is 2,2':6',2"-terpyridine, C15H11N3), consists of monomeric [Mn(tpy)2]2+ units embedded in a complex anionic network made up of tetrathionate ions and hydration water molecules connected via a complex hydrogen-bonding scheme.

trans-Diaqua(2,2'-biquinoline-N,N')(nitrato-O,O')nickel(II) nitrate hydrate.

The structure of the title compound, [Ni(NO(3))(C(18)H(12)N(2))(H(2)O)(2)]NO(3) x H(2)O, is composed of monomers with the nickel ion octahedrally coordinated to a bidentate biquinoline ligand, a bidentate nitrate anion and two water molecules, and is stabilized by a nitrate counter-ion and a hydrate water molecule. There is a fairly complex hydrogen-bonding scheme involving all the water H atoms and five different nitrate O atoms.

Comparative X-ray study of three nickel(II)-thiocyanate compounds.

Three cis nickel-dithiocyanate (SCN) complexes with different N,N'-bidentate bases have been prepared and their crystal structures determined: bis(2,2'-bipyridine-N,N')bis(-ato-N)nickel(II), [Ni(SCN)(2)(C(10)H(8)N(2))(2)], bis(1,10-phenanthroline-N,N')bis(thiocyanato-N)nickel(II), [Ni(SCN)(2)(C(12)H(8)N(2))(2)], and bis(2,9-dimethyl-1,10-phenanthroline-N,N')bis(thiocyanato-N)nickel(II) monohydrate, [Ni(SCN)(2)(C(12)H(8)N(2))(2)].H(2)O. Distortions due to ligand size are discussed.

Antiulcer effectiveness of Maytenus aquifolium spray dried extract.

The antiulcer activity of Maytenus aquifolium spray dried extract was studied in rats. Ulcers were induced by means of three experimental models: acidified-ethanol, indomethacin and acute stress. The extract was found to have significant antiulcer activity against all the models studied. These results show that preparation of the extract by means of the spray dried technique does not alter the biological activity of Maytenus aquifolium.

Bis(1,10-phenanthroline-N,N')(thiosulfato-O, S)nickel(II)-water-methanol (1/0.92/1.4) and bis(2,2'-bipyridyl-N, N')(thiosulfato-O,S)nickel(II)-water-methanol (1/2/0.55)

The title compounds, [Ni(S(2)O(3))(C(12)H(8)N(2))(2)].0.92H(2)O.1. 4CH(4)O and [Ni(S(2)O(3))(C(10)H(8)N(2))(2)].2H(2)O.0.55CH(4)O, are monomeric, containing nickel(II) in a distorted octahedral coordination environment provided by the four N atoms of two bidentate bipy or phen groups and one S and one O atom from a chelating thiosulfate anion. The crystals are highly unstable outside their mother liquors and are stabilized in solution by a not fully determined number of water and methanol solvate molecules. The phenanthroline structure includes two independent moieties related by a non-crystallographic inversion center. The thiosulfate anions display the usual S-O lengthening found when the anion acts in a bidentate mode.

[Efficacy and tolerance of LA 50 mg nicardipine in hypertensive athletes]. / Efficacité et tolérance de la nicardipine LP 50 mg dans l'hypertension artérielle du sportif.

The beneficial effects of physical exercise on the blood pressure are widely recognised. Nevertheless, some athletes remain hypertensive and the treatment of this population makes special demands with respect to treatment efficacy and tolerability, the respect of athletic performance and problems of proscribed substances. For example, the Athletic Boards have prohibited betablockers and diuretics in competitive athletes. The aim of this study was to assess nicardipine LA 50 mg administered twice daily in the special context of hypertensive athletes. Thirty-eight athletes with mild or moderate hypertension undergoing endurance training were included in this double blind trial versus placebo. After two months treatment, the systolic and diastolic blood pressures were significantly lower at rest in the nicardipine than in the placebo group (delta SBP = -18.9 vs -4.1 mmHg, p less than 0.001; delta DBP = -15.7 vs -4.1 mmHg, p less than 0.01). In addition the maximum SBP on effort was significantly lower in the nicardipine group (200 vs 215 mmHg, p less than 0.05). On the other hand, no difference was observed between the two groups as regards the maximum oxygen consumption (delta VO2 max = 6.2 vs -0.4 ml/min/kg, NS) and duration of effort (13.75 vs 12.32 min, NS), showing that athletic performance was unchanged in the group treated by nicardipine LA. These results suggest that treatment with nicardipine LA fulfills the special criteria of hypertensive athletes.