Neurodevelopmental risk factors in schizophrenia

The authors review environmental and neurodevelopmental risk factors for schizophrenic disorders, with emphasis on minor physical anomalies, particularly craniofacial anomalies and dermatoglyphic variations. The high prevalence of these anomalies among schizophrenic subjects supports the neurodevelopmental theory of the etiology of schizophrenia, since they suggest either genetically or epigenetically controlled faulty embryonic development of structures of ectodermal origin like brain and skin. This may disturb neurodevelopment that in turn may cause these subjects to be at increased risk for the development of schizophrenia and related disorders. The precise confirmation of this theory, at least in some cases, will provide further understanding of these illnesses, allowing easy and inexpensive identification of subjects at risk and providing guidelines for the development of new pharmacological interventions for early treatment and even for primary prevention of the illness

Perspectives for next generation lithium-ion battery cathode materials

Transitioning to electrified transport requires improvements in sustainability, energy density, power density, lifetime, and approved the cost of lithium-ion batteries, with significant opportunities remaining in the development of next-generation cathodes. This presents a highly complex, multiparameter optimization challenge, where developments in cathode chemical design and discovery, theoretical and experimental understanding, structural and morphological control, synthetic approaches, and cost reduction strategies can deliver performance enhancements required in the near- and longer-term. This multifaceted challenge requires an interdisciplinary approach to solve, which has seen the establishment of numerous academic and industrial consortia around the world to focus on cathode development. One such example is the Next Generation Lithium-ion Cathode Materials project, FutureCat, established by the UK’s Faraday Institution for electrochemical energy storage research in 2019, aimed at developing our understanding of existing and newly discovered cathode chemistries. Here, we present our perspective on persistent fundamental challenges, including protective coatings and additives to extend lifetime and improve interfacial ion transport, the design of existing and the discovery of new cathode materials where cation and cation-plus-anion redox-activity can be exploited to increase energy density, the application of earth-abundant elements that could ultimately reduce costs, and the delivery of new electrode topologies resistant to fracture which can extend battery lifetime

Perspectives for next generation lithium-ion battery cathode materials

Transitioning to electrified transport requires improvements in sustainability, energy density, power density, lifetime, and approved the cost of lithium-ion batteries, with significant opportunities remaining in the development of next-generation cathodes. This presents a highly complex, multiparameter optimization challenge, where developments in cathode chemical design and discovery, theoretical and experimental understanding, structural and morphological control, synthetic approaches, and cost reduction strategies can deliver performance enhancements required in the near- and longer-term. This multifaceted challenge requires an interdisciplinary approach to solve, which has seen the establishment of numerous academic and industrial consortia around the world to focus on cathode development. One such example is the Next Generation Lithium-ion Cathode Materials project, FutureCat, established by the UK’s Faraday Institution for electrochemical energy storage research in 2019, aimed at developing our understanding of existing and newly discovered cathode chemistries. Here, we present our perspective on persistent fundamental challenges, including protective coatings and additives to extend lifetime and improve interfacial ion transport, the design of existing and the discovery of new cathode materials where cation and cation-plus-anion redox-activity can be exploited to increase energy density, the application of earth-abundant elements that could ultimately reduce costs, and the delivery of new electrode topologies resistant to fracture which can extend battery lifetime.</jats:p

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Resuscitation of Newborn Piglets. Short-Term Influence of FiO2 on Matrix Metalloproteinases, Caspase-3 and BDNF

Perinatal hypoxia-ischemia is a major cause of mortality and cerebral morbidity, and using oxygen during newborn resuscitation may further harm the brain. The aim was to examine how supplementary oxygen used for newborn resuscitation would influence early brain tissue injury, cell death and repair processes and the regulation of genes related to apoptosis, neurodegeneration and neuroprotection.Anesthetized newborn piglets were subjected to global hypoxia and then randomly assigned to resuscitation with 21%, 40% or 100% O(2) for 30 min and followed for 9 h. An additional group received 100% O(2) for 30 min without preceding hypoxia. The left hemisphere was used for histopathology and immunohistochemistry and the right hemisphere was used for in situ zymography in the corpus striatum; gene expression and the activity of various relevant biofactors were measured in the frontal cortex. There was an increase in the net matrix metalloproteinase gelatinolytic activity in the corpus striatum from piglets resuscitated with 100% oxygen vs. 21%. Hematoxylin-eosin (HE) staining revealed no significant changes. Nine hours after oxygen-assisted resuscitation, caspase-3 expression and activity was increased by 30-40% in the 100% O(2) group (n = 9/10) vs. the 21% O(2) group (n = 10; p<0.04), whereas brain-derived neurotrophic factor (BDNF) activity was decreased by 65% p<0.03.The use of 100% oxygen for resuscitation resulted in increased potentially harmful proteolytic activities and attenuated BDNF activity when compared with 21%. Although there were no significant changes in short term cell loss, hyperoxia seems to cause an early imbalance between neuroprotective and neurotoxic mechanisms that might compromise the final pathological outcome

Shorter courses of parenteral antibiotic therapy do not appear to influence response rates for children with acute hematogenous osteomyelitis: a systematic review

BACKGROUND: Acute hematogenous osteomyelitis (AHO) occurs primarily in children and is believed to evolve from bacteremia followed by localization of infection to the metaphysis of bones. Currently, there is no consensus on the route and duration of antimicrobial therapy to treat AHO. METHODS: We conducted a systematic review of a short versus long course of treatment for AHO due primarily to Staphylococcus aureus in children aged 3 months to 16 years. We searched Medline, Embase and the Cochrane trials registry for controlled trials. Clinical cure rate at 6 months was the primary outcome variable, and groups receiving less than 7 days of intravenous therapy were compared with groups receiving one week or longer of intravenous antimicrobials. RESULTS: 12 eligible prospective studies, one of which was randomized, were identified. The overall cure rate at 6 months for the short course of intravenous therapy was 95.2% (95% CI = 90.4, 97.7) compared to 98.8% (95% CI = 93.6, 99.8) for the longer course of therapy. There was no significant difference in the duration of oral therapy between the two groups. CONCLUSIONS: Given the potential increased morbidity and cost associated with longer courses of intravenous therapy, this finding should be confirmed through a randomized controlled equivalence trial

Complex c-di-GMP Signaling Networks Mediate Transition between Virulence Properties and Biofilm Formation in Salmonella enterica Serovar Typhimurium

Upon Salmonella enterica serovar Typhimurium infection of the gut, an early line of defense is the gastrointestinal epithelium which senses the pathogen and intrusion along the epithelial barrier is one of the first events towards disease. Recently, we showed that high intracellular amounts of the secondary messenger c-di-GMP in S. typhimurium inhibited invasion and abolished induction of a pro-inflammatory immune response in the colonic epithelial cell line HT-29 suggesting regulation of transition between biofilm formation and virulence by c-di-GMP in the intestine. Here we show that highly complex c-di-GMP signaling networks consisting of distinct groups of c-di-GMP synthesizing and degrading proteins modulate the virulence phenotypes invasion, IL-8 production and in vivo colonization in the streptomycin-treated mouse model implying a spatial and timely modulation of virulence properties in S. typhimurium by c-di-GMP signaling. Inhibition of the invasion and IL-8 induction phenotype by c-di-GMP (partially) requires the major biofilm activator CsgD and/or BcsA, the synthase for the extracellular matrix component cellulose. Inhibition of the invasion phenotype is associated with inhibition of secretion of the type three secretion system effector protein SipA, which requires c-di-GMP metabolizing proteins, but not their catalytic activity. Our findings show that c-di-GMP signaling is at least equally important in the regulation of Salmonella-host interaction as in the regulation of biofilm formation at ambient temperature

Packages of Care for Schizophrenia in Low- and Middle-Income Countries

In the third in a series of six articles on packages of care for mental disorders in low- and middle-income countries, Jair Mari and colleagues discuss the treatment of schizophrenia