Incidence of gallbladder lithiasis after ceftriaxone treatment

Ceftriaxone has potent activity against a broad range of Gram-positive and Gram-negative bacteria. While it is eliminated mainly by the kidney, 10-20% of the drug is eliminated in the bile and ceftriaxone salt precipitates have been described in the gallbladder of animals dosed with ceftriaxone. The purpose of the present study was to investigate the incidence of biliary lithiasis 6 and 12 months after treatment with ceftriaxone and to compare it with that in patients treated with amoxycillin/clavulanate. Biliary ultrasonography was performed at the start of treatment, at 6 months and at 12 months after the beginning of the study. One hundred patients were randomized and 74 were evaluable: 34 were given amoxycillin/clavulanate, 40 ceftriaxone. Gallbladder lithiasis developed in one patient 12 months after the amoxycillin/clavulanate treatment and in none in the ceftriaxone treatment arm. Biliary precipitate during ceftriaxone treatment was not looked for because this phenomenon was not known at the beginning of the study, but gallbladder precipitation that was seen in two patients given ceftriaxone during and at the end of treatment, respectively, resolved spontaneously. In conclusion, ceftriaxone treatment does not appear to lead to gallstone formation more often than an antibiotic that is not eliminated through the bil

Transcriptional Basis of Mouse and Human Dendritic Cell Heterogeneity

Dendritic cells (DCs) play a critical role in orchestrating adaptive immune responses due to their unique ability to initiate T cell responses and direct their differentiation into effector lineages. Classical DCs have been divided into two subsets, cDC1 and cDC2, based on phenotypic markers and their distinct abilities to prime CD8 and CD4 T cells. While the transcriptional regulation of the cDC1 subset has been well characterized, cDC2 development and function remain poorly understood. By combining transcriptional and chromatin analyses with genetic reporter expression, we identified two principal cDC2 lineages defined by distinct developmental pathways and transcriptional regulators, including T-bet and RORgt, two key transcription factors known to define innate and adaptive lymphocyte subsets. These novel cDC2 lineages were characterized by distinct metabolic and functional programs. Extending our findings to humans revealed conserved DC heterogeneity and the presence of the newly defined cDC2 subsets in human cancer

Cystamine/cysteamine rescues the dopaminergic system and shows neurorestorative properties in an animal model of Parkinson's disease.

The neuroprotective properties of cystamine identified in pre-clinical studies have fast-tracked this compound to clinical trials in Huntington's disease, showing tolerability and benefits on motor symptoms. We tested whether cystamine could have such properties in a Parkinson's disease murine model and now provide evidence that it can not only prevent the neurodegenerative process but also can reverse motor impairments created by a 6-hydroxydopamine lesion 3weeks post-surgery. Importantly, we report that cystamine has neurorestorative properties 5weeks post-lesion as seen on the number of nigral dopaminergic neurons which is comparable with treatments of cysteamine, the reduced form of cystamine used in the clinic, as well as rasagiline, increasingly prescribed in early parkinsonism. All three compounds induced neurite arborization of the remaining dopaminergic cells which was further confirmed in ex vivo dopaminergic explants derived from Pitx3-GFP mice. The disease-modifying effects displayed by cystamine/cysteamine would encourage clinical testing

Incidence of gallbladder lithiasis after ceftriaxone treatment.

Ceftriaxone has potent activity against a broad range of Gram-positive and Gram-negative bacteria. While it is eliminated mainly by the kidney, 10-20% of the drug is eliminated in the bile and ceftriaxone salt precipitates have been described in the gallbladder of animals dosed with ceftriaxone. The purpose of the present study was to investigate the incidence of biliary lithiasis 6 and 12 months after treatment with ceftriaxone and to compare it with that in patients treated with amoxycillin/clavulanate. Biliary ultrasonography was performed at the start of treatment, at 6 months and at 12 months after the beginning of the study. One hundred patients were randomized and 74 were evaluable: 34 were given amoxycillin/clavulanate, 40 ceftriaxone. Gallbladder lithiasis developed in one patient 12 months after the amoxycillin/clavulanate treatment and in none in the ceftriaxone treatment arm. Biliary precipitate during ceftriaxone treatment was not looked for because this phenomenon was not known at the beginning of the study, but gallbladder precipitation that was seen in two patients given ceftriaxone during and at the end of treatment, respectively, resolved spontaneously. In conclusion, ceftriaxone treatment does not appear to lead to gallstone formation more often than an antibiotic that is not eliminated through the bile

Biopedagogies and Indigenous knowledge: examining sport for development and peace for urban Indigenous young women in Canada and Australia

This paper uses transnational postcolonial feminist participatory action research (TPFPAR) to examine two sport for development and peace (SDP) initiatives that focus on Indigenous young women residing in urban areas, one in Vancouver, Canada, and one in Perth, Australia. We examine how SDP programs that target urban Indigenous young women and girls reproduce the hegemony of neoliberalism by deploying biopedagogies of neoliberalism to \u27teach\u27 Indigenous young women certain education and employment skills that are deemed necessary to participate in competitive capitalism. We found that activities in both programs were designed to equip the Indigenous girls and young women with individual attributes that would enhance their chances of future success in arenas valued by neoliberal capitalism: Eurocentric employment, post-secondary education and healthy active living. These forms of \u27success\u27 fall within neoliberal logic, where the focus is on the individual being able to provide for oneself. However, the girls and young women we interviewed argued that their participation in the SDP programs would help them change racist and sexist stereotypes about their communities and thereby challenged negative stereotypes. Thus, it is possible that these programs, despite their predominant use of neoliberal logic and biopedagogies, may help to prepare the participants to more successfully negotiate Eurocentric institutions, and through this assist them participants in contributing to social change. Nevertheless, based on our findings, we argue that SDP programs led by Indigenous peoples that are fundamentally shaped by Indigenous voices, epistemologies, concerns and standpoints would provide better opportunities to shake SDP\u27s current biopedagogical foundation. We conclude by suggesting that a more radical approach to SDP, one that fosters Indigenous self-determination and attempts to disrupt dominant relations of power, could have difficulty in attracting the sort of corporate donors who currently play such important roles in the current SDP landscape

Patient-reported outcome measures in dermatology: a systematic review

By relying on data from existing patient-reported outcome measures of quality of life, the true impact of skin conditions on patients’ lives may be underestimated. This study systematically reviewed all dermatology-specific (used across skin conditions) patient-reported outcome measures and makes evidence-based recommendations for their use. The study protocol is registered on PROSPERO (CRD42018108829). PubMed, PsycInfo and CINAHL were searched from inception to 25 June 2018. The Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) criteria were used to assess the measurement properties and methodological quality of studies. A total of 12,925 abstracts were identified. Zero patient-reported outcome measures were assigned to category A (ready for use without further validation), 31 to category B (recommended for use, but only with further validation) and 5 to category C (not recommended for use). There is no gold-standard dermatology-specific patient-reported outcome measure that can be recommended or used without caution. A new measure that can comprehensively capture the impact of dermatological conditions on the patient’s life is needed

Postcolonial healing landscapes and mental health in a remote Indigenous community in subarctic Ontario, Canada

The concept of therapeutic landscape is concerned with a holistic, socio-ecological model of health, but most studies have attempted to explore land-health links from a Western perspective. On an Indigenous reserve in Northern Ontario, part of the Canadian subarctic, we explore the importance of spaces and places in creating postcolonial therapeutic landscapes to treat the wounds inflicted by colonialism. The aim of this research is to gain insight from views and experiences of First Nations residents living on reservations that are undergoing a process of regaining traditional spiritual beliefs and teachings to construct therapeutic spaces to face mental health problems caused by legal opioid analgesic abuse. This qualitative study used semi-structured interviews with Cree and Ojibwe participants to understand how they are reconnecting with earth, spirituality and traditional animist beliefs on their way to recovery. We find that practices such as taking part in ceremonies and ritual spaces, and seeking knowledge and advice from Elders assist with personal healing and enable Indigenous people to be physically and mentally healthy. Our research findings provide important insights into the relationship between space, healing and culture as determinants of health and well-being and document some key factors that contribute to substance abuse recovery.This work was supported by the Ministry of Education and Science (Spain) [I + D+i SEJ2005-09344/SOCI]; Social Sciences and Humanities Research Council (Canada) [I + D+i CURA/NORTHERN]

Quantifying Microstructural Evolution in Moving Magma

Many of the grand challenges in volcanic and magmatic research are focused on understanding the dynamics of highly heterogeneous systems and the critical conditions that enable magmas to move or eruptions to initiate. From the formation and development of magma reservoirs, through propagation and arrest of magma, to the conditions in the conduit, gas escape, eruption dynamics, and beyond into the environmental impacts of that eruption, we are trying to define how processes occur, their rates and timings, and their causes and consequences. However, we are usually unable to observe the processes directly. Here we give a short synopsis of the new capabilities and highlight the potential insights that in situ observation can provide. We present the XRheo and Pele furnace experimental apparatus and analytical toolkit for the in situ X-ray tomography-based quantification of magmatic microstructural evolution during rheological testing. We present the first 3D data showing the evolving textural heterogeneity within a shearing magma, highlighting the dynamic changes to microstructure that occur from the initiation of shear, and the variability of the microstructural response to that shear as deformation progresses. The particular shear experiments highlighted here focus on the effect of shear on bubble coalescence with a view to shedding light on both magma transport and fragmentation processes. The XRheo system is intended to help us understand the microstructural controls on the complex and non-Newtonian evolution of magma rheology, and is therefore used to elucidate the many mobilization, transport, and eruption phenomena controlled by the rheological evolution of a multi-phase magmatic flows. The detailed, in situ characterization of sample textures presented here therefore represents the opening of a new field for the accurate parameterization of dynamic microstructural control on rheological behavior

Molecular synergy underlies the co-occurrence patterns and phenotype of NPM1-mutant acute myeloid leukemia

NPM1 mutations define the commonest subgroup of acute myeloid leukemia (AML) and frequently co-occur with FLT3 internal tandem duplications (ITD) or, less commonly, NRAS or KRAS mutations. Co-occurrence of mutant NPM1 with FLT3-ITD carries a significantly worse prognosis than NPM1-RAS combinations. To understand the molecular basis of these observations, we compare the effects of the 2 combinations on hematopoiesis and leukemogenesis in knock-in mice. Early effects of these mutations on hematopoiesis show that compound Npm1cA/+;NrasG12D/+ or Npm1cA;Flt3ITD share a number of features: Hox gene overexpression, enhanced self-renewal, expansion of hematopoietic progenitors, and myeloid differentiation bias. However, Npm1cA;Flt3ITD mutants displayed significantly higher peripheral leukocyte counts, early depletion of common lymphoid progenitors, and a monocytic bias in comparison with the granulocytic bias in Npm1cA/+;NrasG12D/+ mutants. Underlying this was a striking molecular synergy manifested as a dramatically altered gene expression profile in Npm1cA;Flt3ITD, but not Npm1cA/+;NrasG12D/+, progenitors compared with wild-type. Both double-mutant models developed high-penetrance AML, although latency was significantly longer with Npm1cA/+;NrasG12D/+. During AML evolution, both models acquired additional copies of the mutant Flt3 or Nras alleles, but only Npm1cA/+;NrasG12D/+ mice showed acquisition of other human AML mutations, including IDH1 R132Q. We also find, using primary Cas9-expressing AMLs, that Hoxa genes and selected interactors or downstream targets are required for survival of both types of double-mutant AML. Our results show that molecular complementarity underlies the higher frequency and significantly worse prognosis associated with NPM1c/FLT3-ITD vs NPM1/NRAS-G12D-mutant AML and functionally confirm the role of HOXA genes in NPM1c-driven AML

Multifractal Spatial Patterns and Diversity in an Ecological Succession

We analyzed the relationship between biodiversity and spatial biomass heterogeneity along an ecological succession developed in the laboratory. Periphyton (attached microalgae) biomass spatial patterns at several successional stages were obtained using digital image analysis and at the same time we estimated the species composition and abundance. We show that the spatial pattern was self-similar and as the community developed in an homogeneous environment the pattern is self-organized. To characterize it we estimated the multifractal spectrum of generalized dimensions Dq. Using Dq we analyze the existence of cycles of heterogeneity during succession and the use of the information dimension D1 as an index of successional stage. We did not find cycles but the values of D1 showed an increasing trend as the succession developed and the biomass was higher. D1 was also negatively correlated with Shannon's diversity. Several studies have found this relationship in different ecosystems but here we prove that the community self-organizes and generates its own spatial heterogeneity influencing diversity. If this is confirmed with more experimental and theoretical evidence D1 could be used as an index, easily calculated from remote sensing data, to detect high or low diversity areas