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Viruses interact with numerous host factors to facilitate viral replication and to dampen antiviral defense mechanisms. We currently have a limited mechanistic understanding of how SARS-CoV-2 binds host factors and the functional role of these interactions. Here, we uncover a novel interaction between the viral NSP3 protein and the fragile X mental retardation proteins (FMRPs: FMR1, FXR1-2). SARS-CoV-2 NSP3 mutant viruses preventing FMRP binding have attenuated replication in vitro and reduced levels of viral antigen in lungs during the early stages of infection. We show that a unique peptide motif in NSP3 binds directly to the two central KH domains of FMRPs and that this interaction is disrupted by the I304N mutation found in a patient with fragile X syndrome. NSP3 binding to FMRPs disrupts their interaction with the stress granule component UBAP2L through direct competition with a peptide motif in UBAP2L to prevent FMRP incorporation into stress granules. Collectively, our results provide novel insight into how SARS-CoV-2 hijacks host cell proteins and provides molecular insight into the possible underlying molecular defects in fragile X syndrome.

Viruses interact with numerous host factors to facilitate viral replication and to dampen antiviral defense mechanisms. We currently have a limited mechanistic understanding of how SARS-CoV-2 binds host factors and the functional role of these interactions. Here, we uncover a novel interaction between the viral NSP3 protein and the fragile X mental retardation proteins (FMRPs: FMR1, FXR1-2). SARS-CoV-2 NSP3 mutant viruses preventing FMRP binding have attenuated replication in vitro and reduced levels of viral antigen in lungs during the early stages of infection. We show that a unique peptide motif in NSP3 binds directly to the two central KH domains of FMRPs and that this interaction is disrupted by the I304N mutation found in a patient with fragile X syndrome. NSP3 binding to FMRPs disrupts their interaction with the stress granule component UBAP2L through direct competition with a peptide motif in UBAP2L to prevent FMRP incorporation into stress granules. Collectively, our results provide novel insight into how SARS-CoV-2 hijacks host cell proteins and provides molecular insight into the possible underlying molecular defects in fragile X syndrome.

Viruses interact with numerous host factors to facilitate viral replication and to dampen antiviral defense mechanisms. We currently have a limited mechanistic understanding of how SARS-CoV-2 binds host factors and the functional role of these interactions. Here, we uncover a novel interaction between the viral NSP3 protein and the fragile X mental retardation proteins (FMRPs: FMR1, FXR1-2). SARS-CoV-2 NSP3 mutant viruses preventing FMRP binding have attenuated replication in vitro and reduced levels of viral antigen in lungs during the early stages of infection. We show that a unique peptide motif in NSP3 binds directly to the two central KH domains of FMRPs and that this interaction is disrupted by the I304N mutation found in a patient with fragile X syndrome. NSP3 binding to FMRPs disrupts their interaction with the stress granule component UBAP2L through direct competition with a peptide motif in UBAP2L to prevent FMRP incorporation into stress granules. Collectively, our results provide novel insight into how SARS-CoV-2 hijacks host cell proteins and provides molecular insight into the possible underlying molecular defects in fragile X syndrome.

Viruses interact with numerous host factors to facilitate viral replication and to dampen antiviral defense mechanisms. We currently have a limited mechanistic understanding of how SARS-CoV-2 binds host factors and the functional role of these interactions. Here, we uncover a novel interaction between the viral NSP3 protein and the fragile X mental retardation proteins (FMRPs: FMR1, FXR1-2). SARS-CoV-2 NSP3 mutant viruses preventing FMRP binding have attenuated replication in vitro and reduced levels of viral antigen in lungs during the early stages of infection. We show that a unique peptide motif in NSP3 binds directly to the two central KH domains of FMRPs and that this interaction is disrupted by the I304N mutation found in a patient with fragile X syndrome. NSP3 binding to FMRPs disrupts their interaction with the stress granule component UBAP2L through direct competition with a peptide motif in UBAP2L to prevent FMRP incorporation into stress granules. Collectively, our results provide novel insight into how SARS-CoV-2 hijacks host cell proteins and provides molecular insight into the possible underlying molecular defects in fragile X syndrome.

Viruses interact with numerous host factors to facilitate viral replication and to dampen antiviral defense mechanisms. We currently have a limited mechanistic understanding of how SARS-CoV-2 binds host factors and the functional role of these interactions. Here, we uncover a novel interaction between the viral NSP3 protein and the fragile X mental retardation proteins (FMRPs: FMR1, FXR1-2). SARS-CoV-2 NSP3 mutant viruses preventing FMRP binding have attenuated replication in vitro and reduced levels of viral antigen in lungs during the early stages of infection. We show that a unique peptide motif in NSP3 binds directly to the two central KH domains of FMRPs and that this interaction is disrupted by the I304N mutation found in a patient with fragile X syndrome. NSP3 binding to FMRPs disrupts their interaction with the stress granule component UBAP2L through direct competition with a peptide motif in UBAP2L to prevent FMRP incorporation into stress granules. Collectively, our results provide novel insight into how SARS-CoV-2 hijacks host cell proteins and provides molecular insight into the possible underlying molecular defects in fragile X syndrome.

Viruses interact with numerous host factors to facilitate viral replication and to dampen antiviral defense mechanisms. We currently have a limited mechanistic understanding of how SARS-CoV-2 binds host factors and the functional role of these interactions. Here, we uncover a novel interaction between the viral NSP3 protein and the fragile X mental retardation proteins (FMRPs: FMR1, FXR1-2). SARS-CoV-2 NSP3 mutant viruses preventing FMRP binding have attenuated replication in vitro and reduced levels of viral antigen in lungs during the early stages of infection. We show that a unique peptide motif in NSP3 binds directly to the two central KH domains of FMRPs and that this interaction is disrupted by the I304N mutation found in a patient with fragile X syndrome. NSP3 binding to FMRPs disrupts their interaction with the stress granule component UBAP2L through direct competition with a peptide motif in UBAP2L to prevent FMRP incorporation into stress granules. Collectively, our results provide novel insight into how SARS-CoV-2 hijacks host cell proteins and provides molecular insight into the possible underlying molecular defects in fragile X syndrome.

Introduction: Italy is one of the high-income countries hit hardest by Covid-19. During the first months of the pandemic, Italian healthcare workers were praised by media and the public for their efforts to face the emergency, although with limited knowledge and resources. However, healthcare workers soon had to face new challenges at a time when the national health system was working hard to recover. This study focuses on this difficult period to assess the impact of the COVID-19 pandemic on the mental health of Italian healthcare workers. Materials and Methods: Healthcare workers from all Italian regions [n = 5,502] completed an online questionnaire during the reopening phase after the first wave lockdown. We assessed a set of individual-level factors (e.g., stigma and violence against HCWs) and a set of workplace-level factors (e.g., trust in the workplace capacity to handle COVID-19) that were especially relevant in this context. The primary outcomes assessed were score ≥15 on the Patient Health Questionnaire-9 and score ≥4 on the General Health Questionnaire-12, indicators of clinically significant depressive symptoms and psychological distress, respectively. Logistic regression analyses were performed on depressive symptoms and psychological distress for each individual- and workplace-level factor adjusting for gender, age, and profession. Results: Clinically significant depressive symptoms were observed in 7.5% and psychological distress in 37.9% of HCWs. 30.5% of healthcare workers reported having felt stigmatized or discriminated, while 5.7% reported having experienced violence. Feeling stigmatized or discriminated and experiencing violence due to being a healthcare worker were strongly associated with clinically significant depressive symptoms [OR 2.98, 95%CI 2.36–3.77 and OR 4.72 95%CI 3.41–6.54] and psychological distress [OR 2.30, 95%CI 2.01–2.64 and OR 2.85 95%CI 2.16–3.75]. Numerous workplace-level factors, e.g., trust in the workplace capacity to han

The widespread cancelation of cultural events during the early 2020 stages of the COVID-19 pandemic led professional performing musicians across the world to experience an increasing economic fragility that threatened their health and wellbeing. Within this "new normal," developing countries have been at a higher risk due to their vulnerable health systems and cultural policies. Even in such difficult times, the music profession requires musicians to keep up their practicing routines, even if they have no professional commitments. This is because high level technical and expressive skills are crucial to sustaining a music career at a high performance level. However, it could be expected that not all musicians might have had the same engagement with music practice during lockdowns. In this study, we studied the experiences of 309 professional classical musicians based in European and Latin American countries with different levels of performing experience to examine their passionate (or lack thereof) engagement with music practice. Through the mixed methods combination of multigroup invariance and narrative analyses, we identified distinct profiles of musicians who displayed more harmonious or more obsessive passion orientations before and at the peak of the pandemic. We observed that musicians with higher levels of harmonious passion in particular were more capable of sustaining their practice at the peak of the pandemic and that these musicians were mostly located in Latin America-a paradox, considering that cultural politics supporting the careers of professional performing musicians and entrepreneurial education in Latin America are lacking to a great extent, especially in comparison with the European context. We explain this in terms of the "forced" self-management embraced by musicians in Latin American countries who want to engage with music practice both before and during the COVID-19 pandemic even if the music profession does not generate enough revenue for t

BACKGROUND: Among all psychoactive substances, alcohol consumption presents the most significant public health problem and is a leading risk factor for overall disease burden in Latin America. However, most people who meet criteria for a substance use disorder do not receive treatment in primary or secondary care sources. Community members can play a role in helping people to seek help as they are likely to encounter people experiencing problem drinking and recognize the signs. However, many do not have adequate mental health first aid knowledge or skills to provide help. We aimed to culturally adapt the existing English-language mental health first aid guidelines for helping someone with problem drinking for Argentina and Chile. METHODS: The Delphi consensus method was used to determine the importance of helping actions translated from the English-language guidelines and to add new actions suggested by expert panellists. The importance of each statement was rated by two expert panels. Panel one included people with lived experience (either their own or as a support person, n = 23) recruited in Argentina and panel two included health professionals (n = 31) recruited in Argentina and Chile. RESULTS: Overall, 165 helping actions were endorsed by panellists across two consecutive survey rounds. Endorsed items included 132 of the 182 items translated into Spanish from the English-language guidelines and 33 of the 61 new items generated from panellists' comments in the first survey round. CONCLUSIONS: While there were some similarities in recommended helping actions between English-speaking countries, and Argentina and Chile, key differences were seen in attitudes to low-risk drinking. While there was a relatively high level of agreement between health professionals and people with lived experience, some divergence of opinion was seen, particularly in the area of commitment to recovery as a condition for help. Future research should explore the implementation of the guid

Coastal aquatic ecosystems such as estuaries and coastal lagoons are important atmospheric methane sources that must be better constrained. This work presents a detailed characterization of the methane cycle in a tropical coastal lagoon (La Mancha, Veracruz, Mexico) and its tributary river over three distinct seasons, along a transect from the river to the sea connection. In addition to several physicochemical parameters, the dissolved methane, carbon dioxide, and oxygen concentrations were measured with high resolution in the sediments and the water column, combined with production/uptake rates. Methane and carbon dioxide cycles were further constrained by determining atmospheric flux over the entire river and lagoon sections. The results indicate that La Mancha is a highly contrasted ecosystem. The river section is characterized by a strong pycnocline, relatively high methane concentration, and active methanogenesis and methanotrophy, discharging into a relatively homogeneous lagoon section where the methane and carbon cycles are less active. Overall, both the river and the lagoon were a net source of methane and carbon dioxide, with an annual emission of 2.9 metric tons of methane and 2757 metric tons of carbon dioxide. The spatial structure of the main components of the methane, carbon dioxide, and oxygen cycles was established, and it was observed that depthwise heterogeneities predominated in the river section. In contrast, lengthwise heterogeneities dominated in the lagoon section.

Coastal aquatic ecosystems such as estuaries and coastal lagoons are important atmospheric methane sources that must be better constrained. This work presents a detailed characterization of the methane cycle in a tropical coastal lagoon (La Mancha, Veracruz, Mexico) and its tributary river over three distinct seasons, along a transect from the river to the sea connection. In addition to several physicochemical parameters, the dissolved methane, carbon dioxide, and oxygen concentrations were measured with high resolution in the sediments and the water column, combined with production/uptake rates. Methane and carbon dioxide cycles were further constrained by determining atmospheric flux over the entire river and lagoon sections. The results indicate that La Mancha is a highly contrasted ecosystem. The river section is characterized by a strong pycnocline, relatively high methane concentration, and active methanogenesis and methanotrophy, discharging into a relatively homogeneous lagoon section where the methane and carbon cycles are less active. Overall, both the river and the lagoon were a net source of methane and carbon dioxide, with an annual emission of 2.9 metric tons of methane and 2757 metric tons of carbon dioxide. The spatial structure of the main components of the methane, carbon dioxide, and oxygen cycles was established, and it was observed that depthwise heterogeneities predominated in the river section. In contrast, lengthwise heterogeneities dominated in the lagoon section.

Objectives: Selectively reported results from only well-performing cutoffs in diagnostic accuracy studies may bias estimates in meta-analyses. We investigated cutoff reporting patterns for the Patient Health Questionnaire-9 (PHQ-9; standard cutoff 10) and Edinburgh Postnatal Depression Scale (EPDS; no standard cutoff, commonly used 10–13) and compared accuracy estimates based on published cutoffs versus all cutoffs. Methods: We conducted bivariate random effects meta-analyses using individual participant data to compare accuracy from published versus all cutoffs. Results: For the PHQ-9 (30 studies, N = 11,773), published results underestimated sensitivity for cutoffs below 10 (median difference: −0.06) and overestimated for cutoffs above 10 (median difference: 0.07). EPDS (19 studies, N = 3637) sensitivity estimates from published results were similar for cutoffs below 10 (median difference: 0.00) but higher for cutoffs above 13 (median difference: 0.14). Specificity estimates from published and all cutoffs were similar for both tools. The mean cutoff of all reported cutoffs in PHQ-9 studies with optimal cutoff below 10 was 8.8 compared to 11.8 for those with optimal cutoffs above 10. Mean for EPDS studies with optimal cutoffs below 10 was 9.9 compared to 11.8 for those with optimal cutoffs greater than 10. Conclusion: Selective cutoff reporting was more pronounced for the PHQ-9 than EPDS.

As irrigation water decreases, crop transpiration also decreases, resulting in an increase in leaf temperature and an increase of the crop water stress index (CWSI). Therefore, in the study, the response of Capsicum to different irrigation regimes was evaluated with periodic measurements of leaf temperature, stomatal conductance and estimation of the CWSI. The treatments consisted of a complete drip irrigation (RO) and deficit irrigation (RD-78 and RD-58) that received 78% and 58% of the complete irrigation, applying a total volume of water of 3363, 2618 and 1956 m3 ha-1 for RO, RD-78 and RD-58, respectively; and obtaining maximum yields of 30.2, 13.9 and 12.9 t ha-1 with CWSI of 0.50, 0.62 and 0.54 in C. bacatum, C. annumm and C. chinense, respectively. The highest stomatal conductance values ​​ranged from 724 to 887 mmol s-1 m-2, with CWSI from 0.1 to 0.3. The CWSI value of 0.3 (soil moisture from 25 to 33%) results in a good indicator of the time of irrigation, and it might be a criterion to be incorporated to save water and improve the management of Capsicum irrigation programs., A medida que disminuye el agua de riego, la transpiración del cultivo disminuye, resultando en un incremento de la temperatura foliar y un aumento del índice de estrés hídrico del cultivo (IEHC). Por ello, en el estudio, se evaluó la respuesta del Capsicum a diferentes regímenes de riego, con mediciones periódicas de la temperatura de la hoja, la conductancia estomática y la estimación del IEHC. Los tratamientos consistieron en un riego por goteo completo (RO) y riego con déficit (RD-78 y RD-58) que recibieron el 78% y 58% del riego completo, aplicándose un volumen total de agua de 3363, 2618 y 1956 m3 ha-1 para RO, RD-78 y RD-58, respectivamente; and obteniéndose rendimientos máximos de 30,2, 13,9 y 12,9 t ha-1 con IEHC de 0,50, 0,62 y 0,54 en C. bacatum, C. annumm y C. chinense, respectivamente. Los mayores valores de conductancia estomática variaron de 724 a 887 mmol s-1 m-2, con IEHC de 0,1 a 0,3. El valor IEHC de 0,3 (humedad del suelo del 25% al 33%), resulta en un buen indicador del momento del riego, criterio a incorporar con la finalidad de ahorrar agua y mejorar la gestión de programas de riego del Capsicum.

Introduction: Three previous individual participant data meta-analyses (IPDMAs) reported that, compared to the Structured Clinical Interview for the DSM (SCID), alternative reference standards, primarily the Composite International Diagnostic Interview (CIDI) and the Mini International Neuropsychiatric Interview (MINI), tended to misclassify major depression status, when controlling for depression symptom severity. However, there was an important lack of precision in the results. Objective: To compare the odds of the major depression classification based on the SCID, CIDI, and MINI. Methods: We included and standardized data from 3 IPDMA databases. For each IPDMA, separately, we fitted binomial generalized linear mixed models to compare the adjusted odds ratios (aORs) of major depression classification, controlling for symptom severity and characteristics of participants, and the interaction between interview and symptom severity. Next, we synthesized results using a DerSimonian-Laird random-effects meta-analysis. Results: In total, 69,405 participants (7,574 [11%] with major depression) from 212 studies were included. Controlling for symptom severity and participant characteristics, the MINI (74 studies; 25,749 participants) classified major depression more often than the SCID (108 studies; 21,953 participants; aOR 1.46; 95% confidence interval [CI] 1.11-1.92]). Classification odds for the CIDI (30 studies; 21,703 participants) and the SCID did not differ overall (aOR 1.19; 95% CI 0.79-1.75); however, as screening scores increased, the aOR increased less for the CIDI than the SCID (interaction aOR 0.64; 95% CI 0.52-0.80). Conclusions: Compared to the SCID, the MINI classified major depression more often. The odds of the depression classification with the CIDI increased less as symptom levels increased. Interpretation of research that uses diagnostic interviews to classify depression should consider the interview characteristics. © 2020

BACKGROUND: Sm16, also known as SPO-1 and SmSLP, is a low molecular weight protein (~16kDa) secreted by the digenean trematode parasite Schistosoma mansoni, one of the main causative agents of human schistosomiasis. The molecule is secreted from the acetabular gland of the cercariae during skin invasion and is believed to perform an immune-suppressive function to protect the invading parasite from innate immune cell attack. METHODOLOGY/PRINCIPAL FINDINGS: We show that Sm16 homologues of the Schistosomatoidea family are phylogenetically related to the helminth defence molecule (HDM) family of immunomodulatory peptides first described in Fasciola hepatica. Interrogation of 69 helminths genomes demonstrates that HDMs are exclusive to trematode species. Structural analyses of Sm16 shows that it consists predominantly of an amphipathic alpha-helix, much like other HDMs. In S. mansoni, Sm16 is highly expressed in the cercariae and eggs but not in adult worms, suggesting that the molecule is of importance not only during skin invasion but also in the pro-inflammatory response to eggs in the liver tissues. Recombinant Sm16 and a synthetic form, Sm16 (34-117), bind to macrophages and are internalised into the endosomal/lysosomal system. Sm16 (34-117) elicited a weak pro-inflammatory response in macrophages in vitro but also suppressed the production of bacterial lipopolysaccharide (LPS)-induced inflammatory cytokines. Evaluation of the transcriptome of human macrophages treated with a synthetic Sm16 (34-117) demonstrates that the peptide exerts significant immunomodulatory effects alone, as well as in the presence of LPS. Pathways most significantly influenced by Sm16 (34-117) were those involving transcription factors peroxisome proliferator-activated receptor (PPAR) and liver X receptors/retinoid X receptor (LXR/RXR) which are intricately involved in regulating the cellular metabolism of macrophages (fatty acid, cholesterol and glucose homeostasis) and are central to infla

BACKGROUND: Sm16, also known as SPO-1 and SmSLP, is a low molecular weight protein (~16kDa) secreted by the digenean trematode parasite Schistosoma mansoni, one of the main causative agents of human schistosomiasis. The molecule is secreted from the acetabular gland of the cercariae during skin invasion and is believed to perform an immune-suppressive function to protect the invading parasite from innate immune cell attack. METHODOLOGY/PRINCIPAL FINDINGS: We show that Sm16 homologues of the Schistosomatoidea family are phylogenetically related to the helminth defence molecule (HDM) family of immunomodulatory peptides first described in Fasciola hepatica. Interrogation of 69 helminths genomes demonstrates that HDMs are exclusive to trematode species. Structural analyses of Sm16 shows that it consists predominantly of an amphipathic alpha-helix, much like other HDMs. In S. mansoni, Sm16 is highly expressed in the cercariae and eggs but not in adult worms, suggesting that the molecule is of importance not only during skin invasion but also in the pro-inflammatory response to eggs in the liver tissues. Recombinant Sm16 and a synthetic form, Sm16 (34-117), bind to macrophages and are internalised into the endosomal/lysosomal system. Sm16 (34-117) elicited a weak pro-inflammatory response in macrophages in vitro but also suppressed the production of bacterial lipopolysaccharide (LPS)-induced inflammatory cytokines. Evaluation of the transcriptome of human macrophages treated with a synthetic Sm16 (34-117) demonstrates that the peptide exerts significant immunomodulatory effects alone, as well as in the presence of LPS. Pathways most significantly influenced by Sm16 (34-117) were those involving transcription factors peroxisome proliferator-activated receptor (PPAR) and liver X receptors/retinoid X receptor (LXR/RXR) which are intricately involved in regulating the cellular metabolism of macrophages (fatty acid, cholesterol and glucose homeostasis) and are central to infla

Objectives: A previous individual participant data meta-analysis (IPDMA) identified differences in major depression classification rates between different diagnostic interviews, controlling for depressive symptoms on the basis of the Patient Health Questionnaire-9. We aimed to determine whether similar results would be seen in a different population, using studies that administered the Edinburgh Postnatal Depression Scale (EPDS) in pregnancy or postpartum. Methods: Data accrued for an EPDS diagnostic accuracy IPDMA were analysed. Binomial generalised linear mixed models were fit to compare depression classification odds for the Mini International Neuropsychiatric Interview (MINI), Composite International Diagnostic Interview (CIDI), and Structured Clinical Interview for DSM (SCID), controlling for EPDS scores and participant characteristics. Results: Among fully structured interviews, the MINI (15 studies, 2,532 participants, 342 major depression cases) classified depression more often than the CIDI (3 studies, 2,948 participants, 194 major depression cases; adjusted odds ratio [aOR] = 3.72, 95% confidence interval [CI] [1.21, 11.43]). Compared with the semistructured SCID (28 studies, 7,403 participants, 1,027 major depression cases), odds with the CIDI (interaction aOR = 0.88, 95% CI [0.85, 0.92]) and MINI (interaction aOR = 0.95, 95% CI [0.92, 0.99]) increased less as EPDS scores increased. Conclusion: Different interviews may not classify major depression equivalently.

OBJECTIVES: A previous individual participant data meta-analysis (IPDMA) identified differences in major depression classification rates between different diagnostic interviews, controlling for depressive symptoms on the basis of the Patient Health Questionnaire-9. We aimed to determine whether similar results would be seen in a different population, using studies that administered the Edinburgh Postnatal Depression Scale (EPDS) in pregnancy or postpartum. METHODS: Data accrued for an EPDS diagnostic accuracy IPDMA were analysed. Binomial generalised linear mixed models were fit to compare depression classification odds for the Mini International Neuropsychiatric Interview (MINI), Composite International Diagnostic Interview (CIDI), and Structured Clinical Interview for DSM (SCID), controlling for EPDS scores and participant characteristics. RESULTS: Among fully structured interviews, the MINI (15 studies, 2,532 participants, 342 major depression cases) classified depression more often than the CIDI (3 studies, 2,948 participants, 194 major depression cases; adjusted odds ratio [aOR] = 3.72, 95% confidence interval [CI] [1.21, 11.43]). Compared with the semistructured SCID (28 studies, 7,403 participants, 1,027 major depression cases), odds with the CIDI (interaction aOR = 0.88, 95% CI [0.85, 0.92]) and MINI (interaction aOR = 0.95, 95% CI [0.92, 0.99]) increased less as EPDS scores increased. CONCLUSION: Different interviews may not classify major depression equivalently.

Background: Rhinovirus, airborne pollution, and allergens are thought to contribute to epithelial dysfunction in chronic airway disease. Objectives were to determine whether these factors act in synergism to induce inflammation and chronic airway disease. Methods: Respiratory mucosa from chronic rhinosinusitis with nasal polyps (CRSwNP) (n=7) or healthy (n=6) patients were cultured at air-liquid interface (ALI) (culture wells n=204). Cells were infected with rhinovirus, then exposed to combinations of vehicle, diesel particulate matter (DPM), and house dust mite (HDM). Ciliary beating frequency (CBF), interleukin (IL)-6 release, and cytotoxicity were assessed by Sisson-Ammons Video Analysis (SAVA) software, flow cytometry, and LDH assays. Results: Compared with healthy cultures, CRSwNP culture groups had lower baseline CBF. The CBF of virally infected ALI cultures was higher than healthy cultures. Challenges tended to impair CBF more in cells that were also virally infected. There was an elevation in IL-6 with viral infection. Challenge combinations did not cause a different IL-6 or CBF response within groups. Conclusions: An inherent mucosal dysfunction and environmental exposures can worsen sinus disease. Synergism in CBF impairment or IL-6 release was not seen.

Background: Rhinovirus, airborne pollution, and allergens are thought to contribute to epithelial dysfunction in chronic airway disease. Objectives were to determine whether these factors act in synergism to induce inflammation and chronic airway disease. Methods: Respiratory mucosa from chronic rhinosinusitis with nasal polyps (CRSwNP) (n=7) or healthy (n=6) patients were cultured at air-liquid interface (ALI) (culture wells n=204). Cells were infected with rhinovirus, then exposed to combinations of vehicle, diesel particulate matter (DPM), and house dust mite (HDM). Ciliary beating frequency (CBF), interleukin (IL)-6 release, and cytotoxicity were assessed by Sisson-Ammons Video Analysis (SAVA) software, flow cytometry, and LDH assays. Results: Compared with healthy cultures, CRSwNP culture groups had lower baseline CBF. The CBF of virally infected ALI cultures was higher than healthy cultures. Challenges tended to impair CBF more in cells that were also virally infected. There was an elevation in IL-6 with viral infection. Challenge combinations did not cause a different IL-6 or CBF response within groups. Conclusions: An inherent mucosal dysfunction and environmental exposures can worsen sinus disease. Synergism in CBF impairment or IL-6 release was not seen.

[EN] In some Western countries, the generalist teachers’ initial training programmes are ceding to trainee teachers the responsibility for articulating musical and pedagogical knowledge. In a same education system, therefore, would arise many representations about the music education. This study aims to determine the pedagogical and musical training that Chilean accredited universities are imparting on their Primary Education Degree’s programmes, in accordance with the Chilean education policy for the music education enacted by the Chile’s Ministry of Education. The Holistic Architecture for Music Education is used as the research approach. Results show the Chilean reality is not different to other Western contexts because the relevance that universities assign didactics of music during initial teacher training is in scrutiny. Conclusions indicate inconsistencies between ministerial interests for music subject and universities’ epistemic responses. It is imperative that college programmes are in line with the Chilean education policy. That is, the initial teacher training should be oriented toward the specialised training in “music education”, which implies to domain both musical and pedagogical competences for carrying out didactics of music., [ES] En algunos países occidentales, los programas de formación inicial del profesorado generalista están relegando la responsabilidad de articular los conocimientos musicales con los pedagógicos a los estudiantes de magisterio. Por lo tanto, en un mismo sistema educativo se estaría generando una multiplicidad de representaciones sobre la educación musical. El objetivo de este estudio es determinar la formación pedagógica y musical que imparten las universidades acreditadas chilenas en sus carreras profesionales de Pedagogía General Básica, conforme al currículo nacional para la asignatura de música que establece el Ministerio de Educación de Chile. La Arquitectura Holística para la Educación Musical se emplea como enfoque de investigación. Los resultados muestran que la realidad chilena no es distinta de otros contextos de occidente debido a que se ha puesto en tela de juicio la relevancia que las mismas universidades asignan a la didáctica de la música durante la formación inicial docente. Las conclusiones hacen notar que existirían inconsistencias entre los intereses ministeriales para la asignatura de música y las respuestas epistémicas de las universidades chilenas. Es imperioso entonces que los programas universitarios se ajusten al currículo nacional chileno. Es decir, la formación inicial del profesorado generalista se debería orientar hacia la formación especializada en “educación musical”, lo que implica dominar tanto competencias musicales como pedagógicas para llevar a cabo la didáctica de la música.

[EN] In some Western countries, the generalist teachers’ initial training programmes are ceding to trainee teachers the responsibility for articulating musical and pedagogical knowledge. In a same education system, therefore, would arise many representations about the music education. This study aims to determine the pedagogical and musical training that Chilean accredited universities are imparting on their Primary Education Degree’s programmes, in accordance with the Chilean education policy for the music education enacted by the Chile’s Ministry of Education. The Holistic Architecture for Music Education is used as the research approach. Results show the Chilean reality is not different to other Western contexts because the relevance that universities assign didactics of music during initial teacher training is in scrutiny. Conclusions indicate inconsistencies between ministerial interests for music subject and universities’ epistemic responses. It is imperative that college programmes are in line with the Chilean education policy. That is, the initial teacher training should be oriented toward the specialised training in “music education”, which implies to domain both musical and pedagogical competences for carrying out didactics of music., [ES] En algunos países occidentales, los programas de formación inicial del profesorado generalista están relegando la responsabilidad de articular los conocimientos musicales con los pedagógicos a los estudiantes de magisterio. Por lo tanto, en un mismo sistema educativo se estaría generando una multiplicidad de representaciones sobre la educación musical. El objetivo de este estudio es determinar la formación pedagógica y musical que imparten las universidades acreditadas chilenas en sus carreras profesionales de Pedagogía General Básica, conforme al currículo nacional para la asignatura de música que establece el Ministerio de Educación de Chile. La Arquitectura Holística para la Educación Musical se emplea como enfoque de investigación. Los resultados muestran que la realidad chilena no es distinta de otros contextos de occidente debido a que se ha puesto en tela de juicio la relevancia que las mismas universidades asignan a la didáctica de la música durante la formación inicial docente. Las conclusiones hacen notar que existirían inconsistencias entre los intereses ministeriales para la asignatura de música y las respuestas epistémicas de las universidades chilenas. Es imperioso entonces que los programas universitarios se ajusten al currículo nacional chileno. Es decir, la formación inicial del profesorado generalista se debería orientar hacia la formación especializada en “educación musical”, lo que implica dominar tanto competencias musicales como pedagógicas para llevar a cabo la didáctica de la música.

[EN] In some Western countries, the generalist teachers’ initial training programmes are ceding to trainee teachers the responsibility for articulating musical and pedagogical knowledge. In a same education system, therefore, would arise many representations about the music education. This study aims to determine the pedagogical and musical training that Chilean accredited universities are imparting on their Primary Education Degree’s programmes, in accordance with the Chilean education policy for the music education enacted by the Chile’s Ministry of Education. The Holistic Architecture for Music Education is used as the research approach. Results show the Chilean reality is not different to other Western contexts because the relevance that universities assign didactics of music during initial teacher training is in scrutiny. Conclusions indicate inconsistencies between ministerial interests for music subject and universities’ epistemic responses. It is imperative that college programmes are in line with the Chilean education policy. That is, the initial teacher training should be oriented toward the specialised training in “music education”, which implies to domain both musical and pedagogical competences for carrying out didactics of music., [ES] En algunos países occidentales, los programas de formación inicial del profesorado generalista están relegando la responsabilidad de articular los conocimientos musicales con los pedagógicos a los estudiantes de magisterio. Por lo tanto, en un mismo sistema educativo se estaría generando una multiplicidad de representaciones sobre la educación musical. El objetivo de este estudio es determinar la formación pedagógica y musical que imparten las universidades acreditadas chilenas en sus carreras profesionales de Pedagogía General Básica, conforme al currículo nacional para la asignatura de música que establece el Ministerio de Educación de Chile. La Arquitectura Holística para la Educación Musical se emplea como enfoque de investigación. Los resultados muestran que la realidad chilena no es distinta de otros contextos de occidente debido a que se ha puesto en tela de juicio la relevancia que las mismas universidades asignan a la didáctica de la música durante la formación inicial docente. Las conclusiones hacen notar que existirían inconsistencias entre los intereses ministeriales para la asignatura de música y las respuestas epistémicas de las universidades chilenas. Es imperioso entonces que los programas universitarios se ajusten al currículo nacional chileno. Es decir, la formación inicial del profesorado generalista se debería orientar hacia la formación especializada en “educación musical”, lo que implica dominar tanto competencias musicales como pedagógicas para llevar a cabo la didáctica de la música.

[EN] In some Western countries, the generalist teachers’ initial training programmes are ceding to trainee teachers the responsibility for articulating musical and pedagogical knowledge. In a same education system, therefore, would arise many representations about the music education. This study aims to determine the pedagogical and musical training that Chilean accredited universities are imparting on their Primary Education Degree’s programmes, in accordance with the Chilean education policy for the music education enacted by the Chile’s Ministry of Education. The Holistic Architecture for Music Education is used as the research approach. Results show the Chilean reality is not different to other Western contexts because the relevance that universities assign didactics of music during initial teacher training is in scrutiny. Conclusions indicate inconsistencies between ministerial interests for music subject and universities’ epistemic responses. It is imperative that college programmes are in line with the Chilean education policy. That is, the initial teacher training should be oriented toward the specialised training in “music education”, which implies to domain both musical and pedagogical competences for carrying out didactics of music., [ES] En algunos países occidentales, los programas de formación inicial del profesorado generalista están relegando la responsabilidad de articular los conocimientos musicales con los pedagógicos a los estudiantes de magisterio. Por lo tanto, en un mismo sistema educativo se estaría generando una multiplicidad de representaciones sobre la educación musical. El objetivo de este estudio es determinar la formación pedagógica y musical que imparten las universidades acreditadas chilenas en sus carreras profesionales de Pedagogía General Básica, conforme al currículo nacional para la asignatura de música que establece el Ministerio de Educación de Chile. La Arquitectura Holística para la Educación Musical se emplea como enfoque de investigación. Los resultados muestran que la realidad chilena no es distinta de otros contextos de occidente debido a que se ha puesto en tela de juicio la relevancia que las mismas universidades asignan a la didáctica de la música durante la formación inicial docente. Las conclusiones hacen notar que existirían inconsistencias entre los intereses ministeriales para la asignatura de música y las respuestas epistémicas de las universidades chilenas. Es imperioso entonces que los programas universitarios se ajusten al currículo nacional chileno. Es decir, la formación inicial del profesorado generalista se debería orientar hacia la formación especializada en “educación musical”, lo que implica dominar tanto competencias musicales como pedagógicas para llevar a cabo la didáctica de la música.

[EN] In some Western countries, the generalist teachers’ initial training programmes are ceding to trainee teachers the responsibility for articulating musical and pedagogical knowledge. In a same education system, therefore, would arise many representations about the music education. This study aims to determine the pedagogical and musical training that Chilean accredited universities are imparting on their Primary Education Degree’s programmes, in accordance with the Chilean education policy for the music education enacted by the Chile’s Ministry of Education. The Holistic Architecture for Music Education is used as the research approach. Results show the Chilean reality is not different to other Western contexts because the relevance that universities assign didactics of music during initial teacher training is in scrutiny. Conclusions indicate inconsistencies between ministerial interests for music subject and universities’ epistemic responses. It is imperative that college programmes are in line with the Chilean education policy. That is, the initial teacher training should be oriented toward the specialised training in “music education”, which implies to domain both musical and pedagogical competences for carrying out didactics of music., [ES] En algunos países occidentales, los programas de formación inicial del profesorado generalista están relegando la responsabilidad de articular los conocimientos musicales con los pedagógicos a los estudiantes de magisterio. Por lo tanto, en un mismo sistema educativo se estaría generando una multiplicidad de representaciones sobre la educación musical. El objetivo de este estudio es determinar la formación pedagógica y musical que imparten las universidades acreditadas chilenas en sus carreras profesionales de Pedagogía General Básica, conforme al currículo nacional para la asignatura de música que establece el Ministerio de Educación de Chile. La Arquitectura Holística para la Educación Musical se emplea como enfoque de investigación. Los resultados muestran que la realidad chilena no es distinta de otros contextos de occidente debido a que se ha puesto en tela de juicio la relevancia que las mismas universidades asignan a la didáctica de la música durante la formación inicial docente. Las conclusiones hacen notar que existirían inconsistencias entre los intereses ministeriales para la asignatura de música y las respuestas epistémicas de las universidades chilenas. Es imperioso entonces que los programas universitarios se ajusten al currículo nacional chileno. Es decir, la formación inicial del profesorado generalista se debería orientar hacia la formación especializada en “educación musical”, lo que implica dominar tanto competencias musicales como pedagógicas para llevar a cabo la didáctica de la música.

[EN] In some Western countries, the generalist teachers’ initial training programmes are ceding to trainee teachers the responsibility for articulating musical and pedagogical knowledge. In a same education system, therefore, would arise many representations about the music education. This study aims to determine the pedagogical and musical training that Chilean accredited universities are imparting on their Primary Education Degree’s programmes, in accordance with the Chilean education policy for the music education enacted by the Chile’s Ministry of Education. The Holistic Architecture for Music Education is used as the research approach. Results show the Chilean reality is not different to other Western contexts because the relevance that universities assign didactics of music during initial teacher training is in scrutiny. Conclusions indicate inconsistencies between ministerial interests for music subject and universities’ epistemic responses. It is imperative that college programmes are in line with the Chilean education policy. That is, the initial teacher training should be oriented toward the specialised training in “music education”, which implies to domain both musical and pedagogical competences for carrying out didactics of music., [ES] En algunos países occidentales, los programas de formación inicial del profesorado generalista están relegando la responsabilidad de articular los conocimientos musicales con los pedagógicos a los estudiantes de magisterio. Por lo tanto, en un mismo sistema educativo se estaría generando una multiplicidad de representaciones sobre la educación musical. El objetivo de este estudio es determinar la formación pedagógica y musical que imparten las universidades acreditadas chilenas en sus carreras profesionales de Pedagogía General Básica, conforme al currículo nacional para la asignatura de música que establece el Ministerio de Educación de Chile. La Arquitectura Holística para la Educación Musical se emplea como enfoque de investigación. Los resultados muestran que la realidad chilena no es distinta de otros contextos de occidente debido a que se ha puesto en tela de juicio la relevancia que las mismas universidades asignan a la didáctica de la música durante la formación inicial docente. Las conclusiones hacen notar que existirían inconsistencias entre los intereses ministeriales para la asignatura de música y las respuestas epistémicas de las universidades chilenas. Es imperioso entonces que los programas universitarios se ajusten al currículo nacional chileno. Es decir, la formación inicial del profesorado generalista se debería orientar hacia la formación especializada en “educación musical”, lo que implica dominar tanto competencias musicales como pedagógicas para llevar a cabo la didáctica de la música.

[EN] In some Western countries, the generalist teachers’ initial training programmes are ceding to trainee teachers the responsibility for articulating musical and pedagogical knowledge. In a same education system, therefore, would arise many representations about the music education. This study aims to determine the pedagogical and musical training that Chilean accredited universities are imparting on their Primary Education Degree’s programmes, in accordance with the Chilean education policy for the music education enacted by the Chile’s Ministry of Education. The Holistic Architecture for Music Education is used as the research approach. Results show the Chilean reality is not different to other Western contexts because the relevance that universities assign didactics of music during initial teacher training is in scrutiny. Conclusions indicate inconsistencies between ministerial interests for music subject and universities’ epistemic responses. It is imperative that college programmes are in line with the Chilean education policy. That is, the initial teacher training should be oriented toward the specialised training in “music education”, which implies to domain both musical and pedagogical competences for carrying out didactics of music., [ES] En algunos países occidentales, los programas de formación inicial del profesorado generalista están relegando la responsabilidad de articular los conocimientos musicales con los pedagógicos a los estudiantes de magisterio. Por lo tanto, en un mismo sistema educativo se estaría generando una multiplicidad de representaciones sobre la educación musical. El objetivo de este estudio es determinar la formación pedagógica y musical que imparten las universidades acreditadas chilenas en sus carreras profesionales de Pedagogía General Básica, conforme al currículo nacional para la asignatura de música que establece el Ministerio de Educación de Chile. La Arquitectura Holística para la Educación Musical se emplea como enfoque de investigación. Los resultados muestran que la realidad chilena no es distinta de otros contextos de occidente debido a que se ha puesto en tela de juicio la relevancia que las mismas universidades asignan a la didáctica de la música durante la formación inicial docente. Las conclusiones hacen notar que existirían inconsistencias entre los intereses ministeriales para la asignatura de música y las respuestas epistémicas de las universidades chilenas. Es imperioso entonces que los programas universitarios se ajusten al currículo nacional chileno. Es decir, la formación inicial del profesorado generalista se debería orientar hacia la formación especializada en “educación musical”, lo que implica dominar tanto competencias musicales como pedagógicas para llevar a cabo la didáctica de la música.

© 2016 cThe Author(s). Helminth parasites secrete molecules that potently modulate the immune responses of their hosts and, therefore, have potential for the treatment of immune-mediated human diseases. FhHDM-1, a 68-mer peptide secreted by the helminth parasite Fasciola hepatica, ameliorated disease in two different murine models of autoimmunity, type 1 diabetes and relapsing-remitting immune-mediated demyelination. Unexpectedly, FhHDM-1 treatment did not affect the proliferation of auto-antigen specific T cells or their production of cytokines. However, in both conditions, the reduction in clinical symptoms was associated with the absence of immune cell infiltrates in the target organ (islets and the brain tissue). Furthermore, after parenteral administration, the FhHDM-1 peptide interacted with macrophages and reduced their capacity to secrete pro-inflammatory cytokines, such as TNF and IL-6. We propose this inhibition of innate pro-inflammatory immune responses, which are central to the initiation of autoimmunity in both diseases, prevented the trafficking of autoreactive lymphocytes from the periphery to the site of autoimmunity (as opposed to directly modulating their function per se), and thus prevented tissue destruction. The ability of FhHDM-1 to modulate macrophage function, combined with its efficacy in disease prevention in multiple models, suggests that FhHDM-1 has considerable potential as a treatment for autoimmune diseases.

© 2016 cThe Author(s). Helminth parasites secrete molecules that potently modulate the immune responses of their hosts and, therefore, have potential for the treatment of immune-mediated human diseases. FhHDM-1, a 68-mer peptide secreted by the helminth parasite Fasciola hepatica, ameliorated disease in two different murine models of autoimmunity, type 1 diabetes and relapsing-remitting immune-mediated demyelination. Unexpectedly, FhHDM-1 treatment did not affect the proliferation of auto-antigen specific T cells or their production of cytokines. However, in both conditions, the reduction in clinical symptoms was associated with the absence of immune cell infiltrates in the target organ (islets and the brain tissue). Furthermore, after parenteral administration, the FhHDM-1 peptide interacted with macrophages and reduced their capacity to secrete pro-inflammatory cytokines, such as TNF and IL-6. We propose this inhibition of innate pro-inflammatory immune responses, which are central to the initiation of autoimmunity in both diseases, prevented the trafficking of autoreactive lymphocytes from the periphery to the site of autoimmunity (as opposed to directly modulating their function per se), and thus prevented tissue destruction. The ability of FhHDM-1 to modulate macrophage function, combined with its efficacy in disease prevention in multiple models, suggests that FhHDM-1 has considerable potential as a treatment for autoimmune diseases.

Jatropha curcas L., known in Mexico as "piñoncillo", is an oil producing species, which has received much attention in recent years as a source for biodiesel production because their seed yield from 46 to 64% oil. However, Jatropha production has shown limited success due to heterogeneous seed yield and oil content. For this reason, the selection of genotypes with superior performance characteristics to be propagated on a large scale has increased. Therefore, clonal propagation by plant tissue technique offers an alternative for genetic omogeneity. So, in this research, the organogenic induction from young leaves of a Mexican Jatroppha genotype was studied. The establishment of in vitro asceptic explants in Murashige & Skoog 1962 (MS) culture media was accomplished after 14 days with 70% asceptic explants. With respect to the induction of buds, greater response was achieved in treatment one, using the same basic media supplemented with 1.0 mg L-1 6-benzyl-aminopurine (BA) and 0.5 mg L-1 indole-3-butyric acid (IBA), achieving bud formation after 60 days, viability was 37.5%, while the number of adventitious buds was 2.2, all treatments showed callus association. In bud proliferation, the greatest response was in treatment two, with the addition of 0.5 mg L-1 BA, with an average of 5.14 shoots per explants after four weeks., Jatropha curcas L., conocida en México como piñoncillo, es una especie productora de aceite, la cual ha recibido gran atención en recientes años al ser utilizada como fuente para la elaboración de biodiesel debido que sus semillas llegan a producir de 46 a 64% de aceite. Sin embargo, la producción de Jatropha ha demostrado limitado éxito debido al heterogéneo rendimiento de semillas y contenido de aceite. Por tal motivo, se ha impulsado la selección de genotipos con características de rendimiento superiores para ser propagados a gran escala. Por esta razón, la propagación clonal mediante la técnica de cultivo de tejidos vegetales ofrece una alternativa de homogeneidad genética. Por lo que, en esta investigación se estudió la inducción organogénica a partir de hojas jóvenes de piñoncillo de un genotipo mexicano. Logrando el establecimiento aséptico de los explantes en el medio de cultivo Murashige & Skoog 1962 (MS), después de 14 días del establecimiento in vitro, existiendo un 70% de explantes asépticos. Con respecto a la inducción de yemas la mayor respuesta se logro en el tratamiento uno, utilizando el mismo medio básico de (MS) suplementado con 1.0 mg L-1 de 6-bencil-aminopurina (BA) y 0.5 mg L-1 de ácido indol-3-butírico (AIB), logrando la formación de yemas después de 60 días, el porcentaje de viabilidad se presentó en un 37.5%, mientras que el número de yemas adventicias fue de 2.2, todos los tratamientos presentaron la asociación de callo. Mientras que en la proliferación de brotes, la mayor respuesta se presento en el tratamiento dos, mas la adición de 0.5 mg L-1 de BA, con un promedio de 5.14 brotes por explante después de cuatro semanas.

The ability of tissue dwelling helminth parasites to induce chronic long term infections, is enabled by the establishment of T helper 2/ regulatory T cell (Th2/Treg) immune responses within their mammalian hosts. Such responses prevent the expulsion of the parasites, whilst simultaneously avoiding excessive inflammation/fibrosis arising within the host, as a consequence of tissue damage induced by helminth migration. Importantly, helminths excrete and secrete a series of molecules (collectively known as ES products), which not only play major roles in parasite biology, but also exert direct immune modulatory functions, promoting the establishment of Th2/Treg immunity. The trematode, Fasciola hepatica, is an excellent model of helminth-mediated immune modulation, because it induces a very rapid switch towards Th2 responses in its mammalian hosts and inhibits Th1 immunity. Fractionation of the ES products of F. hepatica has identified three major immune modulatory components: the protease cathepsin L1, the antioxidant peroxiredoxin, and a previously uncharacterised peptide, FhHDM-1. Structural analysis of FhHDM-1 revealed a close resemblance to the cathelicidin, LL-37, a well characterised mammalian immune-modulating peptide. Therefore, a putative immune modulatory role for FhHDM-1 was explored in this project. Immunofluorescent confocal microscopy demonstrated that FhHDM-1 interacted with macrophage lipid rafts, prior to being actively internalised by cholesterol- and cytoskeletal network-dependent endocytosis, with progressive compartmentalisation of the peptide into early endosomes and endolysosomal vesicles. Flow cytometry studies indicated that, once internalised, FhHDM-1 enhanced the rate of endocytosis of dextran by macrophages. Despite this, FhHDM-1 was found to impair the acidification of macrophage endolysosomes and as a consequence, the efficient processing and subsequent presentation of ovalbumin to T cells was prevented, as assessed by decreased detection

The ability of tissue dwelling helminth parasites to induce chronic long term infections, is enabled by the establishment of T helper 2/ regulatory T cell (Th2/Treg) immune responses within their mammalian hosts. Such responses prevent the expulsion of the parasites, whilst simultaneously avoiding excessive inflammation/fibrosis arising within the host, as a consequence of tissue damage induced by helminth migration. Importantly, helminths excrete and secrete a series of molecules (collectively known as ES products), which not only play major roles in parasite biology, but also exert direct immune modulatory functions, promoting the establishment of Th2/Treg immunity. The trematode, Fasciola hepatica, is an excellent model of helminth-mediated immune modulation, because it induces a very rapid switch towards Th2 responses in its mammalian hosts and inhibits Th1 immunity. Fractionation of the ES products of F. hepatica has identified three major immune modulatory components: the protease cathepsin L1, the antioxidant peroxiredoxin, and a previously uncharacterised peptide, FhHDM-1. Structural analysis of FhHDM-1 revealed a close resemblance to the cathelicidin, LL-37, a well characterised mammalian immune-modulating peptide. Therefore, a putative immune modulatory role for FhHDM-1 was explored in this project. Immunofluorescent confocal microscopy demonstrated that FhHDM-1 interacted with macrophage lipid rafts, prior to being actively internalised by cholesterol- and cytoskeletal network-dependent endocytosis, with progressive compartmentalisation of the peptide into early endosomes and endolysosomal vesicles. Flow cytometry studies indicated that, once internalised, FhHDM-1 enhanced the rate of endocytosis of dextran by macrophages. Despite this, FhHDM-1 was found to impair the acidification of macrophage endolysosomes and as a consequence, the efficient processing and subsequent presentation of ovalbumin to T cells was prevented, as assessed by decreased detection

The Spondylodiscitis is the primary infection of the nucleus pulposous in the intervertebral space, uncommon condition that can begin in the endplate cartilage and extend to the disk and adjacent vertebrae. It can occur after surgical procedures or spontaneously, the latter is the most common. Generally for the treatment of spondylodiscitis it has always been resorted to antibiotics along with corsets or immobilization with orthopedic belts fortwo to three months, and a considerable percentage of 25 to 30% are invasive treatments, surgery is indicated, laminectomy or anterior retroperitoneal approach with instrumentation. I present the pioneering experience in the primary treatment of 13 cases of vertebral spondylodiscitis treated with the administration of oxygen-ozone mixture, from 2004 to 2011. Thirteen cases of infection of the intervertebral space were observed; it was determined that 9 cases were a spontaneous evolution and three post-surgical cases of herniated discs. The results after treatment with ozon e discolysis paraverte bral puncture followed by ozone have been very satisfactory. It can be concluded that primary treatment of ozone is showing excellent results obviating the use of corsets, especially antibiotics and surgery, La Espondilodiscitis es la infección primaria del núcleo pulposo en el espacio intervertebral, patología poco frecuente, que puede empezar en el cartílago del platillo vertebral y ext enderse al disco y las vert ebras adyacentes, puede ocurri r se r de quirúrgicos como puede ser espontanea, esta última es la más común. Para el tratamiento de la E spondilodiscitis se ha recu rrido a la administración de antibióticos junto con la inmovilización con corsés o fajas ortopédicas durante dos a tres meses y en un porcentaje no despreciable de 25 a 30% tratamientos invasivos, la interven ción quirúrgica co mo la laminectomia o un abordaje retroperitoneal con instrumentación anterior. Se Pr esenta la experienci a p i onera en el tratamiento pr i mario de 13 ca sos de Espondilodiscitis intervertebral, tratada con la administración de mezcla de oxigenoozono , desde el año 2004 al 2011 se observo 13 cas os de in fección del espacio intervertebral, se pudo determinar que 9 casos fueron de una evolución espontanea y tres casos p osterior es a intervenciones quirúrgicas d e hernias d i scales. Los resultados después del tratamiento con discolisis con ozono seguidos de punciones paravertebrales de ozonoterapia han sido muy satisfactorios. Se puede concluir que el tratamiento primario de la ozonoterapia está demostrando excelentes resultados obviando la utilización de corsés, antibióticos y sobre todo la intervención quirúrgica

The Spondylodiscitis is the primary infection of the nucleus pulposous in the intervertebral space, uncommon condition that can begin in the endplate cartilage and extend to the disk and adjacent vertebrae. It can occur after surgical procedures or spontaneously, the latter is the most common. Generally for the treatment of spondylodiscitis it has always been resorted to antibiotics along with corsets or immobilization with orthopedic belts fortwo to three months, and a considerable percentage of 25 to 30% are invasive treatments, surgery is indicated, laminectomy or anterior retroperitoneal approach with instrumentation. I present the pioneering experience in the primary treatment of 13 cases of vertebral spondylodiscitis treated with the administration of oxygen-ozone mixture, from 2004 to 2011. Thirteen cases of infection of the intervertebral space were observed; it was determined that 9 cases were a spontaneous evolution and three post-surgical cases of herniated discs. The results after treatment with ozon e discolysis paraverte bral puncture followed by ozone have been very satisfactory. It can be concluded that primary treatment of ozone is showing excellent results obviating the use of corsets, especially antibiotics and surgery, La Espondilodiscitis es la infección primaria del núcleo pulposo en el espacio intervertebral, patología poco frecuente, que puede empezar en el cartílago del platillo vertebral y ext enderse al disco y las vert ebras adyacentes, puede ocurri r se r de quirúrgicos como puede ser espontanea, esta última es la más común. Para el tratamiento de la E spondilodiscitis se ha recu rrido a la administración de antibióticos junto con la inmovilización con corsés o fajas ortopédicas durante dos a tres meses y en un porcentaje no despreciable de 25 a 30% tratamientos invasivos, la interven ción quirúrgica co mo la laminectomia o un abordaje retroperitoneal con instrumentación anterior. Se Pr esenta la experienci a p i onera en el tratamiento pr i mario de 13 ca sos de Espondilodiscitis intervertebral, tratada con la administración de mezcla de oxigenoozono , desde el año 2004 al 2011 se observo 13 cas os de in fección del espacio intervertebral, se pudo determinar que 9 casos fueron de una evolución espontanea y tres casos p osterior es a intervenciones quirúrgicas d e hernias d i scales. Los resultados después del tratamiento con discolisis con ozono seguidos de punciones paravertebrales de ozonoterapia han sido muy satisfactorios. Se puede concluir que el tratamiento primario de la ozonoterapia está demostrando excelentes resultados obviando la utilización de corsés, antibióticos y sobre todo la intervención quirúrgica

We previously reported the identification of a novel family of immunomodulatory proteins, termed helminth defense molecules (HDMs), that are secreted by medically important trematode parasites. Since HDMs share biochemical, structural, and functional characteristics with mammalian cathelicidin-like host defense peptides (HDPs), we proposed that HDMs modulate the immune response via molecular mimicry of host molecules. In the present study, we report the mechanism by which HDMs influence the function of macrophages. We show that the HDM secreted by Fasciola hepatica (FhHDM-1) binds to macrophage plasma membrane lipid rafts via selective interaction with phospholipids and/or cholesterol before being internalized by endocytosis. Following internalization, FhHDM-1 is rapidly processed by lysosomal cathepsin L to release a short C-terminal peptide (containing a conserved amphipathic helix that is a key to HDM function), which then prevents the acidification of the endolysosomal compartments by inhibiting vacuolar ATPase activity. The resulting endolysosomal alkalization impedes macrophage antigen processing and prevents the transport of peptides to the cell surface in conjunction with MHC class II for presentation to CD4+ T cells. Thus, we have elucidated a novel mechanism by which helminth pathogens alter innate immune cell function to assist their survival in the host.

We previously reported the identification of a novel family of immunomodulatory proteins, termed helminth defense molecules (HDMs), that are secreted by medically important trematode parasites. Since HDMs share biochemical, structural, and functional characteristics with mammalian cathelicidin-like host defense peptides (HDPs), we proposed that HDMs modulate the immune response via molecular mimicry of host molecules. In the present study, we report the mechanism by which HDMs influence the function of macrophages. We show that the HDM secreted by Fasciola hepatica (FhHDM-1) binds to macrophage plasma membrane lipid rafts via selective interaction with phospholipids and/or cholesterol before being internalized by endocytosis. Following internalization, FhHDM-1 is rapidly processed by lysosomal cathepsin L to release a short C-terminal peptide (containing a conserved amphipathic helix that is a key to HDM function), which then prevents the acidification of the endolysosomal compartments by inhibiting vacuolar ATPase activity. The resulting endolysosomal alkalization impedes macrophage antigen processing and prevents the transport of peptides to the cell surface in conjunction with MHC class II for presentation to CD4+ T cells. Thus, we have elucidated a novel mechanism by which helminth pathogens alter innate immune cell function to assist their survival in the host.

An investigation was carried out with the aim of improving recycling efficiency and, in particular, Mn recovery. Slag-metal equilibrium experiments were conducted in a closed MoSi2 resistance furnace in an argon atmosphere using four synthetic slag series, CaO-SiO2, CaO-SiO2- Al2O3, CaO-SiO2-MgO and CaO-SiO2-Al2O3-MgO. The slags were brought into contact with two Fe-Mn alloys containing 50 and 90 wt% Mn, respectively, using alumina crucibles at 1 470 degrees C. Equilibrium computations were carried out using FactSage software. The theoretical and experimental results showed acceptable agreement. The results showed that five of the slag systems yielded Mn contents of more than 80 wt% in the alloy. The most important factor for increasing Mn content was the CaO content in the slag. In addition, the presence of MgO improved the basicity of the slag. Optimum results were obtained using a slag composition of 54 wt% CaO, 6 wt% SiO2, 37 wt% Al2O3 and 3 wt% MgO, when Mn recovery of more than 90 wt% in the alloy was achieved., An investigation was carried out with the aim of improving recycling efficiency and, in particular, Mn recovery. Slag-metal equilibrium experiments were conducted in a closed MoSi2 resistance furnace in an argon atmosphere using four synthetic slag series, CaO-SiO2, CaO-SiO2- Al2O3, CaO-SiO2-MgO and CaO-SiO2-Al2O3-MgO. The slags were brought into contact with two Fe-Mn alloys containing 50 and 90 wt% Mn, respectively, using alumina crucibles at 1 470 degrees C. Equilibrium computations were carried out using FactSage software. The theoretical and experimental results showed acceptable agreement. The results showed that five of the slag systems yielded Mn contents of more than 80 wt% in the alloy. The most important factor for increasing Mn content was the CaO content in the slag. In addition, the presence of MgO improved the basicity of the slag. Optimum results were obtained using a slag composition of 54 wt% CaO, 6 wt% SiO2, 37 wt% Al2O3 and 3 wt% MgO, when Mn recovery of more than 90 wt% in the alloy was achieved.

25-34, BACKGROUND: Prompt surgical intervention supplemented by appropriate antimicrobial therapy is usually required for successful treatment of complicated intra-abdominal infections. The objective of this study was to further evaluate the efficacy and safety of ertapenem relative to ceftriaxone/metronidazole as treatment for complicated intra-abdominal infections. METHODS: Adult patients with intra-abdominal infections requiring surgery were eligible for this open-label randomized trial comparing ertapenem 1 g daily with ceftriaxone 2 g daily plus metronidazole 30 mg/kg/day. The primary efficacy outcome was the clinical response rate in clinically and microbiologically evaluable participants at the test-of-cure (TOC) visit 2 weeks after discontinuation of therapy. All treated patients were included in the safety analysis. RESULTS: Participant demographics, disease characteristics, and duration of therapy in both treatment groups were generally similar. Escherichia coli was the most commonly isolated baseline pathogen, recovered in 52% of cases in each treatment group. Favorable clinical responses were achieved at TOC in 143 (96.6%) of 148 ertapenem recipients and in 146 (96.7%) of 151 ceftriaxone/metronidazole recipients. The frequencies of drug-related adverse events, most commonly nausea, diarrhea, vomiting, and elevated platelet count, were generally comparable in both treatment arms. Four ertapenem recipients (1.8%) and one ceftriaxone/metronidazole recipient (0.4%) experienced serious drug-related adverse events. CONCLUSIONS: In this study, ertapenem and ceftriaxone/metronidazole were comparably effective treatments for adult patients with complicated intra-abdominal infections.

In surveys of office environments that measure occupants’ satisfaction with their workspace, the intrusion of unwanted sound—noise—vies with temperature as the leading source of dissatisfaction (Harris, 1978, 1991, Sundstrom, 1994, Brill, 2001). Recent research by the Center for the Built Environment supports this finding, with more than 40% of employees responding to CBE’s occupant satisfaction survey reporting that workplace acoustics make it harder for them to do their job (CBE, 2001). Moreover, an elevated level of workplace noise has been shown to increase stress, decrease motivation and is associated with risk factors for musculoskeletal disorder (Evans, 2000).To improve this situation, architects, interior designers, and facilities management professionals need to be able to translate a proposed design into a specific prediction of acoustical satisfaction with the resulting workspace. Over the past 40 years, acoustical consultants have in fact developed such a method. In the late 1950’s, engineers at Bolt, Beranek & Newman recognized that a majority of acoustical complaints in offices were related to speech privacy—overhearing unwanted conversations or feeling that one is overheard. Building on research at Bell Labs that correlated a listener’s ability to understand words with the ratio between the loudness of a person’s voice and the loudness of the background noise, these engineers demonstrated that a listener’s inability to understand words in a workplace setting is part of this same continuum of signal to noise. They then showed that that a series of objective measurements can establish this ratio and accurately predict an occupant’s satisfaction with their speech privacy (Cavanaugh 1962). Over the past forty years, this method for predicting speech privacy satisfaction with has been simplified (Young, 1965), adapted for use in open plan environments (Pirn, 1971) and consolidated into worksheet formats for both open and closed office environments (Ega

In surveys of office environments that measure occupants’ satisfaction with their workspace, the intrusion of unwanted sound—noise—vies with temperature as the leading source of dissatisfaction (Harris, 1978, 1991, Sundstrom, 1994, Brill, 2001). Recent research by the Center for the Built Environment supports this finding, with more than 40% of employees responding to CBE’s occupant satisfaction survey reporting that workplace acoustics make it harder for them to do their job (CBE, 2001). Moreover, an elevated level of workplace noise has been shown to increase stress, decrease motivation and is associated with risk factors for musculoskeletal disorder (Evans, 2000).To improve this situation, architects, interior designers, and facilities management professionals need to be able to translate a proposed design into a specific prediction of acoustical satisfaction with the resulting workspace. Over the past 40 years, acoustical consultants have in fact developed such a method. In the late 1950’s, engineers at Bolt, Beranek & Newman recognized that a majority of acoustical complaints in offices were related to speech privacy—overhearing unwanted conversations or feeling that one is overheard. Building on research at Bell Labs that correlated a listener’s ability to understand words with the ratio between the loudness of a person’s voice and the loudness of the background noise, these engineers demonstrated that a listener’s inability to understand words in a workplace setting is part of this same continuum of signal to noise. They then showed that that a series of objective measurements can establish this ratio and accurately predict an occupant’s satisfaction with their speech privacy (Cavanaugh 1962). Over the past forty years, this method for predicting speech privacy satisfaction with has been simplified (Young, 1965), adapted for use in open plan environments (Pirn, 1971) and consolidated into worksheet formats for both open and closed office environments (Ega

Over the past century, the company direction and management of smelters in Chile has evolved from one characterised by a paternalistic, autocratic style to one which empowers the local management team and workforce to run the smelter as a successful business. There are now seven copper smelters, treating around 5 000 000 tonnes of copper concentrate each year to produce around 1 500 000 tonnes of copper. Chuquicamata, Potrerillos, Caletones and Chagres belong to primary producers while Paipote, Ventanas and Altonorte are custom smelters. There is a wide range of plant capacities, feed types, technologies and management styles. Average, maximum and minimum parameters for production, concentrates, efficiency, accidents and labour in 1998 are presented and the challenges faced by management since the 1960s are discussed, together with changes in corporate culture and management values, principles and policies., Over the past century, the company direction and management of smelters in Chile has evolved from one characterised by a paternalistic, autocratic style to one which empowers the local management team and workforce to run the smelter as a successful business. There are now seven copper smelters, treating around 5 000 000 tonnes of copper concentrate each year to produce around 1 500 000 tonnes of copper. Chuquicamata, Potrerillos, Caletones and Chagres belong to primary producers while Paipote, Ventanas and Altonorte are custom smelters. There is a wide range of plant capacities, feed types, technologies and management styles. Average, maximum and minimum parameters for production, concentrates, efficiency, accidents and labour in 1998 are presented and the challenges faced by management since the 1960s are discussed, together with changes in corporate culture and management values, principles and policies.

Following a pre-feasibility study, measures were proposed for developing the Chilean copper smelter so as to maintain capacity while achieving full environmental compliance. The processing capacity of the Teniente converters will be increased to 2 400 t/d of chalcopyrite-based concentrates containing 30% Cu, by more intensive use of oxygen and improved stabilisation of the overall operation. Productivity increases are also planned for the conversion of white metal, the pyrometallurgical treatment of slags and the capacity of supporting facilities such as the sulphuric acid plants. An intensive and well-designed scheme for upgrading the labour force will aim to drive technical development by transforming all workers into experts in their particular fields., Following a pre-feasibility study, measures were proposed for developing the Chilean copper smelter so as to maintain capacity while achieving full environmental compliance. The processing capacity of the Teniente converters will be increased to 2 400 t/d of chalcopyrite-based concentrates containing 30% Cu, by more intensive use of oxygen and improved stabilisation of the overall operation. Productivity increases are also planned for the conversion of white metal, the pyrometallurgical treatment of slags and the capacity of supporting facilities such as the sulphuric acid plants. An intensive and well-designed scheme for upgrading the labour force will aim to drive technical development by transforming all workers into experts in their particular fields.