Effect of environmental variables on mercury accumulation in sediments of an anthropogenically impacted tropical estuary (Buenaventura Bay, Colombian Pacific).

Estuaries are the main entry areas of mercury to the marine environment and are important to understand the effect of this contaminant on marine organisms, since it accumulates in the sediments becoming available to enter the food trophic chain. This study aims to determine the environmental variables that mainly influence the spatiotemporal dynamics of total mercury accumulation in sediments of tropical estuaries. Sediment samples were collected from interior and exterior areas of the estuary during the dry and rainy seasons, representing the spatiotemporal gradients of the estuary. The grain size, organic matter content (OM), and total mercury concentration (THg) of the sediment samples were determined. In addition, salinity, temperature, dissolved oxygen, and pH of the water column associated with each sediment sample were assessed. The variations in environmental conditions, OM and THg in sediment were in accordance with a gradient which goes from conditions influenced by fresh water in the inner estuary to conditions influenced by sea water in the outer part of the estuary. The OM and THg in sediments presented similar variation patterns; they were higher in the rainy season than in the dry season and in the interior area of the estuary than in the exterior area. Despite the complex dynamic observed in the distribution and accumulation processes of mercury in sediments, these processes could be modeled from OM and salinity parameters. Due to the correlations found, in the process of accumulation of mercury in sediments the OM could represents the pathway of transport and accumulation of THg, and salinity could represent the influence of the hydroclimatic variations and environmental gradients of the estuary.

Influence of environmental variables on the spatiotemporal dynamics of water quality in Buenaventura Bay, Colombian Pacific.

Tropical estuaries are productive dynamic ecosystems where water quality is mediated by physicochemical and biological processes and by fluvial and anthropogenic discharges. The objective of the study was to determine the influence of environmental variables on the spatiotemporal dynamics of water quality in Buenaventura Bay, which is a highly impacted estuary. Sampling was carried out during the dry and rainy season, at three depths, in four stations that represent the environmental gradient of the bay. Temperature, total dissolved solids, salinity, dissolved oxygen, and pH were determined for each sample. In addition, alkalinity, phosphates, nitrites, and nitrates as indicators of water quality were also measured. The estuary was classified as meso- and polyhaline, with appropriate oxygen and pH conditions and spatiotemporal gradients of temperature and solids mediated by river discharges. Significant variations were found in the physicochemical variables by season, with maximum salinity, pH, and solids in the dry season and oxygen and temperature in the rainy season. Likewise, most of these environmental variables were higher in the outer zone of the estuary and lower in the inner stations. Alkalinity and nitrite values were within the permitted ranges, while phosphates and nitrates indicated low water quality. There was a significant direct influence of temperature and oxygen on alkalinity and nitrites. However, for phosphates, no significant influence of environmental variables was found, suggesting a greater influence by fluvial and anthropogenic discharges, which produce a decrease in the environmental quality of the estuary.

Influence of water quality on the macroinvertebrate community in a tropical estuary (Buenaventura Bay).

The anthropogenic discharges of inorganic nutrients impact water quality, affecting the macroinvertebrate assemblage and food safety. The main objective of this study was to examine the seawater quality and macroinvertebrate dynamics in muddy habitats of Buenaventura Bay, Colombian Pacific. Macroinvertebrates were captured using artisanal trawl nets during different seasons and along four sampling sites. Multivariate analyses (canonical correspondence analysis and generalized additive model) were used to assess the effects of variations in nitrite, nitrates, phosphate concentrations, and physicochemical variables (salinity, pH, dissolved oxygen [DO], temperature, and total dissolved solids [TDS]) of water on the macroinvertebrate assemblage. Richness was the highest at sites with high salinity and temperature and low concentrations of nitrites and TDS. The densities of the commercial shrimp species Xiphopenaeus riveti and Rimapenaeus byrdi were the highest at sites with higher DO and alkalinity, and lower nitrate concentrations. The swimming crab Callinectes arcuatus was dominant at sites with low water quality. In summary, in the transitional season and at the inner sites of Buenaventura Bay, it was observed the lowest water quality due to high nitrate concentration. High nitrate concentration was highlighted as the main anthropogenic factor that could decrease the capture of target macroinvertebrate species for food and livelihoods of artisanal fishermen and their families. Thus, macroinvertebrate communities may be vulnerable to increased inorganic nutrient inputs, which could affect estuarine water quality and ecosystems services. Integr Environ Assess Manag 2022;18:796-812. © 2021 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Sec22b Regulates Inflammatory Responses by Controlling the Nuclear Translocation of NF-κB and the Secretion of Inflammatory Mediators.

Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) regulate the vesicle transport machinery in phagocytic cells. Within the secretory pathway, Sec22b is an endoplasmic reticulum-Golgi intermediate compartment (ERGIC)-resident SNARE that controls phagosome maturation and function in macrophages and dendritic cells. The secretory pathway controls the release of cytokines and may also impact the secretion of NO, which is synthesized by the Golgi-active inducible NO synthase (iNOS). Whether ERGIC SNARE Sec22b controls NO and cytokine secretion is unknown. Using murine bone marrow-derived dendritic cells, we demonstrated that inducible NO synthase colocalizes with ERGIC/Golgi markers, notably Sec22b and its partner syntaxin 5, in the cytoplasm and at the phagosome. Pharmacological blockade of the secretory pathway hindered NO and cytokine release, and inhibited NF-κB translocation to the nucleus. Importantly, RNA interference-mediated silencing of Sec22b revealed that NO and cytokine production were abrogated at the protein and mRNA levels. This correlated with reduced nuclear translocation of NF-κB. We also found that Sec22b co-occurs with NF-κB in both the cytoplasm and nucleus, pointing to a role for this SNARE in the shuttling of NF-κB. Collectively, our data unveiled a novel function for the ERGIC/Golgi, and its resident SNARE Sec22b, in the production and release of inflammatory mediators.

Hábitos alimentarios de tres especies de peces lenguados (Pleuronectiformes: Achiridae) en la Bahía de Buenaventura, Pacífico Colombiano / Feeding habits of three species of sole fish (Pleuronectiformes: Achiridae) in Buenaventura Bay, Colombian Pacific

Resumen Introducción: La dinámica de las condiciones ambientales influencia la variación del alimento disponible para los organismos estuarinos, afectando el consumo de alimento de los organismos bentónicos como los lenguados, esenciales para establecer y monitorear la calidad ambiental en estos ecosistemas. Objetivo: Determinar los hábitos tróficos de tres especies de la familia Achiridae en la Bahía de Buenaventura, Pacífico colombiano. Métodos: Los peces se recolectaron por medio de pesca de arrastre artesanal. Así mismo, en laboratorio se determinó la dieta de cada una de las especies y se calcularon diferentes índices tróficos, registrando diferencias en los hábitos alimentarios entre estas especies. Resultados: Se recolectó un total de 159 peces del género Achirus, siendo la especie más abundante Achirus klunzingeri (98), luego Achirus mazatlanus (44) y finalmente Achirus scutum (17). La dieta de A. scutum se basó en detritos, la de A. mazatlanus en detritos y peces y la de A. klunzingeri en crustáceos y peces. Los individuos de A. klunzingeri presentaron diferencias en su dieta entre la zona interna y externa del estuario, en la zona interna los peces fueron la presa principal y en la zona externa fueron los crustáceos. Las especies A. klunzingeri y A. mazatlanus presentaron ingesta de microplásticos, principalmente fibras alargadas e incoloras presentes en individuos de todas las tallas. La dinámica de los hábitos tróficos de A. klunzingeri, se relacionaron con algunas variables ambientales, como temperatura, trasparencia y oxígeno disuelto. Por ejemplo, estas tres variables presentaron correlaciones negativas con el ítem peces, y positivas para la categoría crustáceos. Conclusión: Se evidenció que estas especies son generalistas y que las condiciones ambientales no solo influenciaron la dinámica del consumo alimentario, sino que también, determinaron la presencia de los microplásticos.

Abstract Introduction: The dynamic of the environmental conditions influences the availability of the food resources for the estuarine organisms, affecting the food consumption of the benthic organism such as the soles, which are essential for establishing and monitoring the environmental quality of these ecosystems. Objective: To determine the trophic habits of three species of the Achiridae family in Buenaventura Bay, Colombian Pacific. Methods: Fish were captured using artisanal trawling. Then, the diet of each species was determined and different trophic indexes were calculated registering differences in alimentary habits among species. Results: It was collected a total of 159 fishes of the genus Achirus, being the most abundant Achirus klunzingeri (98), then Achirus mazatlanus (44) and finally Achirus scutum (17). The diet of A. scutum was based on detritus, the diet of A. mazatlanus was mainly detritus and fish whereas the diet of A. klunzingeri presented a dynamic pattern based mainly on crustaceans and fish. The individuals of Achirus klunzingeri presented differences in the diet between the internal and external area of the estuary, in the internal zone the fish were the main prey while in the external zone were the crustaceans. The species A. klunzingeri and A. mazatlanus presented ingestion of microplastics, mainly elongated and colorless fibers which were present in individuals of all sizes. The dynamic of the trophic habits of A. klunzingeri was related to the environmental variables such as temperature, transparency and dissolved oxygen. For example, these three variables presented negative correlations with the item fishes, and positive for the crustacean category. Conclusions: Despite the generalist nature of the studied species, the environmental conditions, not only influenced the food consumption dynamic, but also determined the presence of microplastics.

First-line haploidentical stem cell transplantation in children and adolescents with severe aplastic anemia using mobilized peripheral blood as source of CD34+: Single-institutional experience in a transplant center from northeast Mexico.

INTRODUCTION: The only curative treatment for severe aplastic anemia in children is an allogeneic stem cell transplant; however, few patients have a matched related or unrelated donor. Haploidentical stem cell transplantation (haplo-SCT) using bone marrow (BM) and peripheral blood stem cells (PBSC) has been recently described as effective and safe. In this study, we retrospectively report the outcome of twelve pediatric patients who underwent haplo-SCT using only PBSC. METHODS: The conditioning regimen consisted on rabbit anti-thymocyte globulin (r-ATG) 2.5 mg/kg/d on days -7, -6,-5, and -4, and cyclophosphamide (Cy) 50 mg/kg/d on days -3 and -2. We used Cy 50 mg/kg/d on days +3 and +4, tacrolimus and mycophenolic acid as graft versus host disease (GVHD) prophylaxis. RESULTS: The median follow-up was 1,099 days (45-1258 days). The overall survival rate up-to-date is 83.3%. In 10 of the 12 patients, a sustained graft was achieved. None of the patients had acute or chronic GVHD. CONCLUSIONS: Haplo-SCT could be established as a first-line treatment when there is no matched related or unrelated donor. According to this short sample and previous reports, PBSC are a feasible option effectively used as the sole source of stem cells. Additionally, post-transplant cyclophosphamide remains a good strategy for GVHD prevention.

Leishmania donovani Metacyclic Promastigotes Impair Phagosome Properties in Inflammatory Monocytes.

Leishmaniasis, a debilitating disease with clinical manifestations ranging from self-healing ulcers to life-threatening visceral pathologies, is caused by protozoan parasites of the Leishmania genus. These professional vacuolar pathogens are transmitted by infected sand flies to mammalian hosts as metacyclic promastigotes and are rapidly internalized by various phagocyte populations. Classical monocytes are among the first myeloid cells to migrate to infection sites. Recent evidence shows that recruitment of these cells contributes to parasite burden and the establishment of chronic disease. However, the nature of Leishmania-inflammatory monocyte interactions during the early stages of host infection has not been well investigated. Here, we aimed to assess the impact of Leishmania donovani metacyclic promastigotes on antimicrobial responses within these cells. Our data showed that inflammatory monocytes are readily colonized by L. donovani metacyclic promastigotes, while infection with Escherichia coli is efficiently cleared. Upon internalization, metacyclic promastigotes inhibited superoxide production at the parasitophorous vacuole (PV) through a mechanism involving exclusion of NADPH oxidase subunits gp91phox and p47phox from the PV membrane. Moreover, we observed that unlike phagosomes enclosing zymosan particles, vacuoles containing parasites acidify poorly. Interestingly, whereas the parasite surface coat virulence glycolipid lipophosphoglycan (LPG) was responsible for the inhibition of PV acidification, impairment of the NADPH oxidase assembly was independent of LPG and GP63. Collectively, these observations indicate that permissiveness of inflammatory monocytes to L. donovani may thus be related to the ability of this parasite to impair the microbicidal properties of phagosomes.

Resultados funcionales a largo plazo de la cirugía abierta de liberación del túnel carpiano / Long-term functional outcomes of open carpal tunnel release surgery

Introducción: El síndrome del túnel carpiano es la neuropatía por atrapamiento más común que genera compresión del nervio mediano. La cirugía de liberación abierta del nervio mediano tiene un papel importante, especialmente, en pacientes que no responden al manejo conservador o con diagnóstico de síndrome del túnel carpiano con criterios de gravedad. El propósito de este estudio fue describir los resultados funcionales, la satisfacción y la fuerza objetiva a mediano (6-24 meses) y largo plazo (>24 meses) con la técnica abierta convencional en la población local. Materiales y métodos: Estudio observacional descriptivo con datos retrospectivos de resultados clínicos funcionales a mediano y largo plazo en pacientes sometidos a cirugía de liberación abierta del nervio mediano como tratamiento del síndrome del túnel carpiano. Se determinaron el nivel funcional según el BCTQ y la FSS, la fuerza de agarre con un dinamómetro electrónico y la satisfacción. Resultados: Se realizaron 100 procedimientos entre mayo de 2012 y septiembre de 2018, con un seguimiento posoperatorio >6 meses. La mayoría eran mujeres (83%) con una mediana de la edad de 59 años. El 97% obtuvo resultados buenos y excelentes a mediano plazo y el 90%, a largo plazo, con una mediana de fuerza de 17 kg (RIC 7,4) y una satisfacción de 90 (RIC 20) a mediano y largo plazo. Conclusiones: La cirugía abierta de liberación del nervio mediano en pacientes con síndrome del túnel carpiano logra resultados buenos y excelentes a mediano y largo plazo en cuanto a funcionalidad, fuerza y satisfacción. Nivel de Evidencia: IV

Introduction: Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy that causes compression of the median nerve. Open median nerve release surgery plays an important role, especially in patients with failed conservative management or with a diagnosis of severe CTS. The purpose of the following study is to describe the functional outcomes, satisfaction, and objective strength in the medium (6 to 24 months) and long term (greater than 24 months) with the conventional open technique in the local population. Materials and methods: Descriptive observational study based on retrospective data of functional clinical outcomes in the medium and long term in patients undergoing open release surgery of the median nerve as a treatment for CTS. Functional level according to the BCTQ and FSS, grip strength with an electronic dynamometer, and satisfaction were determined. Results: 100 procedures were performed between May 2012 and September 2018, with a follow-up of more than 6 months. The majority were women (83%) with a total median age of 59 years showing good to excellent results in the 97% in the medium term and 90% in the long term, with a median strength of 17 kg (Interquartile range: 7.4) and satisfaction of 90 (Interquartile range: 20). Conclusions: Open surgery to release the median nerve in patients with CTS shows good to excellent functional outcomes, satisfaction, and strength in the medium and long term. Level of Evidence: IV

Translational profiling of macrophages infected with Leishmania donovani identifies mTOR- and eIF4A-sensitive immune-related transcripts.

The protozoan parasite Leishmania donovani (L. donovani) causes visceral leishmaniasis, a chronic infection which is fatal when untreated. Herein, we investigated whether in addition to altering transcription, L. donovani modulates host mRNA translation to establish a successful infection. Polysome-profiling revealed that one third of protein-coding mRNAs expressed in primary mouse macrophages are differentially translated upon infection with L. donovani promastigotes or amastigotes. Gene ontology analysis identified key biological processes enriched for translationally regulated mRNAs and were predicted to be either activated (e.g. chromatin remodeling and RNA metabolism) or inhibited (e.g. intracellular trafficking and antigen presentation) upon infection. Mechanistic in silico and biochemical analyses showed selective activation mTOR- and eIF4A-dependent mRNA translation, including transcripts encoding central regulators of mRNA turnover and inflammation (i.e. PABPC1, EIF2AK2, and TGF-ß). L. donovani survival within macrophages was favored under mTOR inhibition but was dampened by pharmacological blockade of eIF4A. Overall, this study uncovers a vast yet selective reprogramming of the host cell translational landscape early during L. donovani infection, and suggests that some of these changes are involved in host defense mechanisms while others are part of parasite-driven survival strategies. Further in vitro and in vivo investigation will shed light on the contribution of mTOR- and eIF4A-dependent translational programs to the outcome of visceral leishmaniasis.

Effect of water quality variation on fish assemblages in an anthropogenically impacted tropical estuary, Colombian Pacific.

In tropical estuaries, fish diversity varies spatially and temporally due to behavioral processes such as reproductive migrations, predator avoidance, and foraging, which are affected by water quality. Eutrophication is one of the main factors affecting water quality in estuaries. The objective of this study was to determine variation in fish assemblage explained by fluctuating water quality in the Buenaventura Bay. Fish were captured using artisanal trawl nets during the wet, dry, and transitional seasons at four sampling sites. Additionally, alkalinity; phosphate, nitrite, and nitrate concentrations; dissolved oxygen; pH; temperature; and suspended solids were measured. Multivariate analysis was used to assess the effect of water quality on fish assemblage. In Buenaventura Bay, the assemblage composition of Pseudupeneus grandisquamis, Daector dowi, and Citharichthys gilberti was affected by nitrate concentration. Moreover, large fish biomasses were associated with high nitrite concentration, intermediate salinity, and low dissolved oxygen, suggesting that these estuaries are dominated by species tolerant to poor water quality. Species richness was associated with low nitrate and phosphate concentrations, more suitable water quality indicators, and intermediate temperatures. These results suggest that the deteriorating water quality of estuaries as a result of the anthropogenic impact could increase dominance and decrease richness, resulting in structural changes of fish assemblages.

Mercury dynamics in macroinvertebrates in relation to environmental factors in a highly impacted tropical estuary: Buenaventura Bay, Colombian Pacific.

The environmental health of Buenaventura Bay, a highly impacted tropical estuary, is influenced by numerous human activities, including mining upstream. Large- and small-scale fishing plays an important role in the local economy, so we investigated the dynamic processes of bioaccumulation of mercury at basal trophic levels. Four samples were taken at each of the four locations in Buenaventura Bay during each of the four seasons of 2015. We measured the total mercury content (T-Hg, dry weight) in sediments and in muscle tissue across 17 macroinvertebrate species. The most abundant were the blue crab (C. arcuatus) and the mantis shrimp (S. aculeata aculeata). Blue crab showed an average muscle T-Hg value ​​exceeding the limit of 0.2 g·g-1, which is the maximum T-Hg level suggested for food consumption by vulnerable humans and populations: pregnant women, children, and the community that feeds from this source of protein on a daily basis. It was found that, 6.22% of individuals exceeded the 0.5 g·g-1 level, which is the maximum T-Hg level suggested for food consumption by the general population: the population that consumes it sporadically. Significantly high values ​​of T-Hg in blue crab and mantis shrimp occurred during low salinity conditions in the estuary, suggesting that Hg mainly originates from river runoff during the rainy season. Nevertheless, the biota-sediment accumulation factor (BSAF) was favored in high salinity, which could mean greater availability of Hg for higher levels of the estuarine food web in the dry season and in marine waters. In general, the T-Hg levels in some samples exceeded 0.2 g·g-1. Therefore this pollutant must be monitored due to its biomagnification potential and as a threat to human health, especially that for the local population of fishermen and their families.

Impact of Obesity on Lumbar Puncture Outcomes in Adults with Acute Lymphoblastic Leukemia and Lymphoma: Experience at an Academic Reference Center.

Background: Lumbar puncture (LP) is a hematology procedure that can require repeated attempts leading to traumatic LP (TLP), which has been related to the central nervous system (CNS) relapse. LP success can depend on the size and anatomy of the patient and the skill of the hematologist. The main objective was to determine the influence of body mass index (BMI) on LP outcomes. Materials and Methods: Adults with lymphoid malignancies requiring LP were included prospectively over one year; hematology residents performed most procedures. A 22-gauge Quincke needle was employed. Comparison between non-traumatic vs. traumatic LPs according to BMI, CNS relapse, and residents' year was performed. Results: Fifty-four patients with a mean age of 31.5±15.57 years were included. Diagnosis was Acute Lymphoblastic Leukemia-B (74%), Acute Lymphoblastic Leukemia-T (13%) and Non-Hodgkin Lymphoma (13%). 227 LPs were performed, 121 (53.3%) successful, 98 (43.2%) traumatic, 11 (11.2%) TLPs were macroscopically detectable and 87 (88%) microscopic; 8 (3.5%) were dry-taps. Median time between punctures was 11 days (1-202). Median BMI was 25 (22.8-39.6). Main indication for LP was prophylactic (74.5%); 39.2% were performed by first-year, 35.2% by second-year, 19.6% by third-year hematology residents. No difference (p = 0.145) for a TLP was found among residents. A BMI ≥30 (p = 0.040), non-palpable intervertebral space (p = 0.001) and more than one attempt (p = 0.001) were significant for TLP. TLP was not associated with CNS relapse (p = 0.962). Conclusion: Obesity predicted a TLP. A traumatic puncture did not increase the risk of CNS relapse at one-year follow-up.

Reduced-dose plerixafor as a mobilization strategy in autologous hematopoietic cell transplantation: a proof of concept study.

BACKGROUND: Autologous stem cell transplantation (ASCT) is an effective treatment for patients with relapsing myeloma or lymphoma, diseases associated with unsuccessful peripheral blood stem cell (PBSC) collection. Plerixafor is a potent mobilizing agent, allowing more CD34+ cells to be obtained; however, the main obstacle for its use is its high cost. Our aim was to demonstrate that of the use of reduced doses of plerixafor (RD-plerixafor) can be sufficient to collect at least 2 × 106 /Kg CD34+ PBSC in patients with multiple myeloma (MM) or lymphoma undergoing ASCT. STUDY DESIGN AND METHODS: Twenty patients were mobilized with filgrastim (10 µg/kg/4 days) plus a single dose of plerixafor 0.12 mg/kg in Day 4. Apheresis collection was performed on Day 5. One vial of plerixafor was used for two patients. Clinicaltrials.gov NCT03244930. RESULTS: Cell mobilization and collection was successful in 85% of patients (≥2 × 106 CD34+ cells per kilogram). The median collected CD34+ cell count was 4.62 × 106 /kg (range, 1.27-24.5). A 4.1-fold-increase in the median CD34+ PBSC pre-count was observed (from 10.4/µl to 42.4/µl) after RD-plerixafor administration. Seven patients had mild to moderate adverse events. CONCLUSION: RD-plerixafor is an effective, safe, and affordable strategy to ensure adequate PBSC mobilization in patients with MM or lymphoma who undergo ASCT.

Leishmania braziliensis: Strain-Specific Modulation of Phagosome Maturation.

Leishmania (Viannia) braziliensis is responsible for the largest number of American tegumentary leishmaniasis (ATL) in Brazil. ATL can present several clinical forms including typical (TL) and atypical (AL) cutaneous and mucocutaneous (ML) lesions. To identify parasite and host factors potentially associated with these diverse clinical manifestations, we first surveyed the expression of two virulence-associated glycoconjugates, lipophosphoglycan (LPG) and the metalloprotease GP63 by a panel of promastigotes of Leishmania braziliensis (L. braziliensis) strains isolated from patients with different clinical manifestations of ATL and from the sand fly vector. We observed a diversity of expression patterns for both LPG and GP63, which may be related to strain-specific polymorphisms. Interestingly, we noted that GP63 activity varies from strain to strain, including the ability to cleave host cell molecules. We next evaluated the ability of promastigotes from these L. braziliensis strains to modulate phagolysosome biogenesis in bone marrow-derived macrophages (BMM), by assessing phagosomal recruitment of the lysosome-associated membrane protein 1 (LAMP-1) and intraphagosomal acidification. Whereas, three out of six L. braziliensis strains impaired the phagosomal recruitment of LAMP-1, only the ML strain inhibited phagosome acidification to the same extent as the L. donovani strain that was used as a positive control. While decreased phagosomal recruitment of LAMP-1 correlated with higher LPG levels, decreased phagosomal acidification correlated with higher GP63 levels. Finally, we observed that the ability to infect and replicate within host cells did not fully correlate with the inhibition of phagosome maturation. Collectively, our results revealed a diversity of strain-specific phenotypes among L. braziliensis isolates, consistent with the high genetic diversity within Leishmania populations.

The host cell secretory pathway mediates the export of Leishmania virulence factors out of the parasitophorous vacuole.

To colonize phagocytes, Leishmania subverts microbicidal processes through components of its surface coat that include lipophosphoglycan and the GP63 metalloprotease. How these virulence glycoconjugates are shed, exit the parasitophorous vacuole (PV), and traffic within host cells is poorly understood. Here, we show that lipophosphoglycan and GP63 are released from the parasite surface following phagocytosis and redistribute to the endoplasmic reticulum (ER) of macrophages. Pharmacological disruption of the trafficking between the ER and the Golgi hindered the exit of these molecules from the PV and dampened the cleavage of host proteins by GP63. Silencing by RNA interference of the soluble N-ethylmaleimide-sensitive-factor attachment protein receptors Sec22b and syntaxin-5, which regulate ER-Golgi trafficking, identified these host proteins as components of the machinery that mediates the spreading of Leishmania effectors within host cells. Our findings unveil a mechanism whereby a vacuolar pathogen takes advantage of the host cell's secretory pathway to promote egress of virulence factors beyond the PV.

Leishmania infantum Lipophosphoglycan-Deficient Mutants: A Tool to Study Host Cell-Parasite Interplay.

Lipophosphoglycan (LPG) is the major surface glycoconjugate of metacyclic Leishmania promastigotes and is associated with virulence in various species of this parasite. Here, we generated a LPG-deficient mutant of Leishmania infantum, the foremost etiologic agent of visceral leishmaniasis in Brazil. The L. infantum LPG-deficient mutant (Δlpg1) was obtained by homologous recombination and complemented via episomal expression of LPG1 (Δlpg1 + LPG1). Deletion of LPG1 had no observable effect on parasite morphology or on the presence of subcellular organelles, such as lipid droplets. While both wild-type and add-back parasites reached late phase in axenic cultures, the growth of Δlpg1 parasites was delayed. Additionally, the deletion of LPG1 impaired the outcome of infection in murine bone marrow-derived macrophages. Although no significant differences were observed in parasite load after 4 h of infection, survival of Δlpg1 parasites was significantly reduced at 72 h post-infection. Interestingly, L. infantum LPG-deficient mutants induced a strong NF-κB-dependent activation of the inducible nitric oxide synthase (iNOS) promoter compared to wild type and Δlpg1 + LPG1 parasites. In conclusion, the L. infantum Δlpg1 mutant constitutes a powerful tool to investigate the role(s) played by LPG in host cell-parasite interactions.

Understanding TGEV-ETEC Coinfection through the Lens of Proteomics: A Tale of Porcine Diarrhea.

Porcine diarrhea and gastroenteritis are major causes of piglet mortality that result in devastating economic losses to the industry. A plethora of pathogens can cause these diseases, with the transmissible gastroenteritis virus (TGEV) and enterotoxigenic Escherichia coli K88 (ETEC) being two of the most salient. In the December 2017 issue of Proteomics Clinical Aplications, Xia and colleagues used comparative proteomics to shed light on how these microbes interact to cause severe disease . The authors discovered that TGEV induces an epithelial-mesenchymal transition-like phenotype that augments cell adhesion proteins mediating the attachment of ETEC to intestinal epithelial cells. Moreover, coinfection was found to modulate several host proteins that could bolster pathogen persistence. Importantly, the authors observed that ETEC suppresses the production of inflammatory cytokines induced by TGEV, which may in turn promote the long-term survival of both microbes.

Danazol as First-Line Therapy for Myelodysplastic Syndrome.

BACKGROUND: Allogeneic stem cell transplantation (ASCT) represents the only option with a potential cure rate of 30% to 50% in myelodysplastic syndrome (MDS); however, < 5% of patients are optimal candidates for this management. Therapeutic options are limited in patients unsuitable for ASCT. Evidence that androgens might be beneficial in MDS is controversial. We aimed to document the clinical outcomes of patients diagnosed with MDS treated with danazol as first-line therapy. PATIENTS AND METHODS: We retrospectively reviewed patients diagnosed in our center with MDS according to the World Health Organization 2008 criteria and treated with danazol between 2005 and 2015. Response was defined according to international working group criteria. RESULTS: We included 42 patients treated exclusively with danazol. Median dose was 400 mg/d (range, 100-600 mg/d). Median follow-up was 12 (range, 3-76) months. Twenty-four of these patients (60%) achieved clinical response. Median overall survival was 24 months (95% confidence interval, 5.1-42). Responders were older than nonresponders (P = .025) and had higher baseline hemoglobin concentration (P = .009). No patients discontinued danazol because of toxicity. Fifteen patients died (35.7%) and 5 progressed to acute myeloid leukemia. CONCLUSION: Danazol as first-line therapy is an acceptable treatment option with low side effects for patients with MDS who cannot receive ASCT.

Encondroma solitario de la mano: seguimiento a largo plazo después del tratamiento quirúrgico. serie de casos / Isolated enchondroma of the hand. long-term follow-up after surgical treatment. case series

Introducción: los encondromas solitarios son los tumores óseos más comunes de la mano. Aproximadamente el 40% compromete esta extremidad, con predilección por los rayos cubitales y las falanges proximales. El riesgo de transformación maligna a condrosarcoma es del 1% y el de recurrencia, del 2-15%. Se describen la experiencia y los resultados de un importante número de pacientes con un seguimiento a largo plazo. Materiales y Métodos: Estudio descriptivo, retrospectivo, de tipo serie de casos. Se seleccionaron pacientes con diagnóstico confirmado de encondroma solitario de la mano, que fueron manejados mediante resección con curetaje del tumor más aplicación de injertos autólogos de cresta ilíaca o radio. Después del tratamiento quirúrgico, se evaluaron la función, mediante la clasificación de Takigawa, los resultados radiográficos y la frecuencia de complicaciones o recidivas. Resultados: Se incluyeron 19 pacientes con un seguimiento posoperatorio promedio de 11 años. De acuerdo con la clasificación de Takigawa, la función fue excelente en 16 pacientes (84,2%) y buena en 3 (15,7%). Un paciente presentó una infección del sitio operatorio incisional superficial, con resolución completa. No hubo recidivas. Conclusiones: En los pacientes evaluados, los resultados funcionales y radiológicos fueron buenos después de la cirugía. Los encondromas plantean el riesgo de fracturas patológicas, recidiva y, en menor proporción, de transformación maligna; sin embargo, esto no ocurrió en ninguno de los casos. Se describe una opción de manejo quirúrgico, sencilla con buenos y excelentes resultados a largo plazo.

Introduction: Isolated enchondromas are the most common tumors of the hand. Approximately 40% affect this upper extremity, with preference for cubital rays and proximal phalanges. Risk of malignant transformation to chondrosarcoma is 1% and the risk of recurrence ranges from 2 to 15%. Our experience and results with a large number of patients with a long-term follow-up are described. Methods: Descriptive, retrospective, case series study. Patients with diagnosis of isolated enchondroma of the hand that were treated with tumor resection, curettage and iliac crest or radius autograft placement were included. After surgical treatment, hand function was assessed using the Takigawa classification, radiological results and frequency of complications or recurrence were evaluated. Results: Nineteen patients with a mean follow-up of 11 years were included. According to the Takigawa classification, function was excellent in 16 patients (84.2%) and good in 3 (15.7%). One patient had an incisional superficial surgical site infection that resolved completely. No cases of recurrence were identified. Conclusions: Good functional and radiological results were obtained after surgical treatment. Enchondromas can pose the risk of pathological fractures, recurrence and, in a lesser degree, malignant transformation; however, none of these complications were identified. The results of a simple surgical treatment option with good and excellent long-term results are described.

Macrophages Tell the Non-Professionals What to Do.

Phagocytosis by professional and non-professional phagocytes plays a critical role in tissue homeostasis and the immune response. Using an airway inflammation model, Han et al. (2016) report in Nature that macrophages secrete IGF-1 to signal epithelial cells to stop ingesting apoptotic cells while increasing the uptake of anti-inflammatory macrophage-derived microvesicles.