miR-375 gene dosage in pancreatic β-cells: implications for regulation of β-cell mass and biomarker development

MicroRNAs play a crucial role in the regulation of cell growth and differentiation. Mice with genetic deletion of miR-375 exhibit impaired glycemic control due to decreased β-cell and increased α-cell mass and function. The relative importance of these processes for the overall phenotype of miR-375KO mice is unknown. Here, we show that mice overexpressing miR-375 exhibit normal β-cell mass and function. Selective re-expression of miR-375 in β-cells of miR-375KO mice normalizes both, α- and β-cell phenotypes as well as glucose metabolism. Using this model, we also analyzed the contribution of β-cells to the total plasma miR-375 levels. Only a small proportion (≈1 %) of circulating miR-375 originates from β-cells. Furthermore, acute and profound β-cell destruction is sufficient to detect elevations of miR-375 levels in the blood. These findings are supported by higher miR-375 levels in the circulation of type 1 diabetes (T1D) subjects but not mature onset diabetes of the young (MODY) and type 2 diabetes (T2D) patients. Together, our data support an essential role for miR-375 in the maintenance of β-cell mass and provide in vivo evidence for release of miRNAs from pancreatic β-cells. The small contribution of β-cells to total plasma miR-375 levels make this miRNA an unlikely biomarker for β-cell function but suggests a utility for the detection of acute β-cell death for autoimmune diabetes

Early results in the treatment of proximal humeral fractures with a polyaxial locking plate

Objectives: We report early results using a second generation locking plate, non-contact bridging plate (NCB PH®, Zimmer Inc. Warsaw, IN, USA), for the treatment of proximal humeral fractures. The NCB PH® combines conventional plating technique with polyaxial screw placement and angular stability. Design: Prospective case series. Setting: A single level-1 trauma center. Patients: A total of 50 patients with proximal humeral fractures were treated from May 2004 to December 2005. Intervention: Surgery was performed in open technique in all cases. Main outcome measures: Implant-related complications, clinical parameters (duration of surgery, range of motion, Constant-Murley Score, subjective patient satisfaction, complications) and radiographic evaluation [union, implant loosening, implant-related complications and avascular necrosis (AVN) of the humeral head] at 6, 12 and 24weeks. Results: All fractures available to follow-up (48 of 50) went to union within the follow-up period of 6months. One patient was lost to follow-up, one patient died of a cause unrelated to the trauma, four patients developed AVN with cutout, one patient had implant loosening, three patients experienced cutout and one patient had an axillary nerve lesion (onset unknown). The average age- and gender-related Constant Score (n=35) was 76. Conclusions: The NCB PH® combines conventional plating technique with polyaxial screw placement and angular stability. Although the complication rate was 19%, with a reoperation rate of 12%, the early results show that the NCB PH® is a safe implant for the treatment of proximal humeral fracture

Schmerzmanagement bei Kindern in der Schweiz

Zusammenfassung: Hintergrund: Schmerzen bei stationär aufgenommenen Kindern werden häufig unzureichend behandelt. Bisher gab es keine Informationen zum Schmerzmanagement von Kinderkrankenhäusern in der Schweiz. Ziel der vorliegenden Studie war, den aktuellen Stand der Schmerzerfassung, -interpretation und -behandlung zu bestimmen. Studiendesign: Ein Fragebogen wurde an alle pädiatrischen Krankenhäuser in der Schweiz gesendet. Ergebnisse: Insgesamt antworteten 27 von 45Einheiten (Antwortrate: 60%). Die meisten Abteilungen verwenden Schmerzerfassungstools (96%) und führten diesbezügliche Leitlinien ein (78%). Die Behandlung von Schmerzen erfolgt ebenfalls meist nach hausinterner Leitlinie (78%). Prozedurale und postoperative Schmerzen werden stets (100%) analgetisch behandelt. Bei Frühgeborenen und Kindern auf Intensivpflegestationen werden bei invasiven Eingriffen häufig Analgetika (> 87%) verwendet. Auf Intensivstationen liegen in 44% diesbezügliche Leitlinien vor. Resümee: Der Nutzen eines effektiven Schmerzmanagements bei Kindern ist eindeutig belegt. Viele Ansätze zur Verbesserung werden in der Schweiz gut umgesetzt. Vor allem im internationalen Vergleich verbesserte sich das Schmerzmanagement. Es gibt aber noch Optimierungsmöglichkeiten. Beispielsweise besitzen weniger als die Hälfte aller schweizerischen Intensivstationen eine Leitlinie für die Behandlung von Schmerzen bei invasiven Eingriffe

Antimatter and Matter Production in Heavy Ion Collisions at CERN (The NEWMASS Experiment NA52)

Besides the dedicated search for strangelets NA52 measures light (anti)particle and (anti)nuclei production over a wide range of rapidity. Compared to previous runs the statistics has been increased in the 1998 run by more than one order of magnitude for negatively charged objects at different spectrometer rigidities. Together with previous data taking at a rigidity of -20 GeV/c we obtained 10^6 antiprotons 10^3 antideuterons and two antihelium3 without centrality requirements. We measured nuclei and antinuclei (p,d,antiprotons, antideuterons) near midrapidity covering an impact parameter range of b=2-12 fm. Our results strongly indicate that nuclei and antinuclei are mainly produced via the coalescence mechanism. However the centrality dependence of the antibaryon to baryon ratios show that antibaryons are diminished due to annihilation and breakup reactions in the hadron dense environment. The volume of the particle source extracted from coalescence models agrees with results from pion interferometry for an expanding source. The chemical and thermal freeze-out of nuclei and antinuclei appear to coincide with each other and with the thermal freeze-out of hadrons.Comment: 12 pages, 8 figures, to appear in the proceedings of the conference on 'Fundamental Issues in Elementary Matter' Bad Honnef, Germany, Sept. 25-29, 200

Coupled insights from the palaeoenvironmental, historical and archaeological archives to support social-ecological resilience and the sustainable development goals

Many governments and organisations are currently aligning many aspects of their policies and practices to the sustainable development goals (SDGs). Achieving the SDGs should increase social-ecological resilience to shocks like climate change and its impacts. Here, we consider the relationship amongst the three elements�the SDGs, social-ecological resilience and climate change�as a positive feedback loop. We argue that long-term memory encoded in historical, archaeological and related �palaeo-data� is central to understanding each of these elements of the feedback loop, especially when long-term fluctuations are inherent in social-ecological systems and their responses to abrupt change. Yet, there is scant reference to the valuable contribution that can be made by these data from the past in the SDGs or their targets and indicators. The historical and archaeological records emphasise the importance of some key themes running through the SDGs including how diversity, inclusion, learning and innovation can reduce vulnerability to abrupt change, and the role of connectivity. Using paleo-data, we demonstrate how changes in the extent of water-related ecosystems as measured by indicator 6.6.1 may simply be related to natural hydroclimate variability, rather than reflecting actual progress towards Target 6.6. This highlights issues associated with using SDG indicator baselines predicated on short-term and very recent data only. Within the context of the contributions from long-term data to inform the positive feedback loop, we ask whether our current inability to substantively combat anthropogenic climate change threatens achieving both the SDGS and enhanced resilience to climate change itself. We argue that long-term records are central to understanding how and what will improve resilience and enhance our ability to both mitigate and adapt to climate change. However, for uptake of these data to occur, improved understanding of their quality and potential by policymakers and managers is required

Striking Decrease of Enteroviral Meningitis in Children During the COVID-19 Pandemic.

We report the unprecedented complete absence of pediatric enteroviral meningitis in 2020 in the area of Bern, Switzerland. Presumably an unintended effect of coronavirus disease 2019 public health measures, this finding highlights the potential of community-wide nonpharmaceutical interventions for controlling the circulation of a major pediatric pathogen, which is mainly transmitted by the fecal-oral route

Early sexual dimorphism in the developing gut microbiome of northern elephant seals

The gut microbiome is an integral part of a species’ ecology, but we know little about how host characteristics impact its development in wild populations. Here, we explored the role of such intrinsic factors in shaping the gut microbiome of northern elephant seals during a critical developmental window of six weeks after weaning, when the pups stay ashore without feeding. We found substantial sex-differences in the early-life gut microbiome, even though males and females could not yet be distinguished morphologically. Sex and age both explained around 15% of the variation in gut microbial beta diversity, while microbial communities sampled from the same individual showed high levels of similarity across time, explaining another 40% of the variation. Only a small proportion of the variation in beta diversity was explained by health status, assessed by full blood counts, but clinically healthy individuals had a greater microbial alpha diversity than their clinically abnormal peers. Across the post-weaning period, the northern elephant seal gut microbiome was highly dynamic. We found evidence for several colonisation and extinction events as well as a decline in Bacteroides and an increase in Prevotella, a pattern that has previously been associated with the transition from nursing to solid food. Lastly, we show that genetic relatedness was correlated with gut microbiome similarity in males but not females, again reflecting early sex-differences. Our study represents a naturally diet-controlled and longitudinal investigation of how intrinsic factors shape the early gut microbiome in a species with extreme sex differences in morphology and life history

Domain analysis of lipoprotein LppQ in Mycoplasma mycoides subsp. mycoides SC

The lipoprotein LppQ is the most prominent antigen of Mycoplasma mycoides subsp. mycoides small colony type (SC) during infection of cattle. This pathogen causes contagious bovine pleuropneumonia (CBPP), a devastating disease of considerable socio-economic importance in many countries worldwide. The dominant antigenicity and high specificity for M. mycoides subsp. mycoides SC of lipoprotein LppQ have been exploited for serological diagnosis and for epidemiological investigations of CBPP. Scanning electron microscopy and immunogold labelling were used to provide ultrastructural evidence that LppQ is located to the cell membrane at the outer surface of M. mycoides subsp. mycoides SC. The selectivity and specificity of this method were demonstrated through discriminating localization of extracellular (i.e., in the zone of contact with host cells) vs. integral membrane domains of LppQ. Thus, our findings support the suggestion that the accessible N-terminal domain of LppQ is surface exposed and such surface localization may be implicated in the pathogenesis of CBPP

Erratum: Author Correction: System immunology-based identification of blood transcriptional modules correlating to antibody responses in sheep.

[This corrects the article DOI: 10.1038/s41541-018-0078-0.]