Zika virus has acquired worldwide concern after a recent outbreak in Latin America that started in Brazil, with associated neurological conditions such as microcephaly in newborns from infected ...mothers. The virus is transmitted mainly by
Aedes aegypti
mosquitoes, but direct (sexual) transmission has been documented. We formulate a reaction diffusion model that considers spatial movement of humans and vectors, with local contact transmission of Zika virus. Vaccination is introduced as a control variable, giving immunity to susceptible humans, in order to characterize an optimal vaccination strategy that minimizes the costs associated with infections and vaccines. The optimal control characterization is obtained in terms of state and adjoint equations. Parameter estimation and numerical simulations are carried out using data for the initial 2015 Zika outbreak in the state of Rio Grande do Norte in Brazil. Several scenarios are considered and analyzed in terms of number of new infections and costs, showing that the optimal control application is successful, significantly reducing these quantities.
The kidney plays a key role in the correction of systemic acid-base imbalances. Central for this regulation are the intercalated cells in the distal nephron, which secrete acid or base into the ...urine. How these cells sense acid-base disturbances is a long-standing question. Intercalated cells exclusively express the Na
-dependent Cl
/HCO
exchanger AE4 (Slc4a9). Here we show that AE4-deficient mice exhibit a major dysregulation of acid-base balance. By combining molecular, imaging, biochemical and integrative approaches, we demonstrate that AE4-deficient mice are unable to sense and appropriately correct metabolic alkalosis and acidosis. Mechanistically, a lack of adaptive base secretion via the Cl
/HCO
exchanger pendrin (Slc26a4) is the key cellular cause of this derailment. Our findings identify AE4 as an essential part of the renal sensing mechanism for changes in acid-base status.
Understanding of the taxonomy and phylogeny of Cryptococcus gattii has been advanced by modern molecular techniques. C. gattii probably diverged from Cryptococcus neoformans between 16 million and ...160 million years ago, depending on the dating methods applied, and maintains diversity by recombining in nature. South America is the likely source of the virulent C. gattii VGII molecular types that have emerged in North America. C. gattii shares major virulence determinants with C. neoformans, although genomic and transcriptomic studies revealed that despite similar genomes, the VGIIa and VGIIb subtypes employ very different transcriptional circuits and manifest differences in virulence phenotypes. Preliminary evidence suggests that C. gattii VGII causes severe lung disease and death without dissemination, whereas C. neoformans disseminates readily to the central nervous system (CNS) and causes death from meningoencephalitis. Overall, currently available data indicate that the C. gattii VGI, VGII, and VGIII molecular types more commonly affect nonimmunocompromised hosts, in contrast to VGIV. New, rapid, cheap diagnostic tests and imaging modalities are assisting early diagnosis and enabling better outcomes of cerebral cryptococcosis. Complications of CNS infection include increased intracranial pressure, severe neurological sequelae, and development of immune reconstitution syndrome, although the mortality rate is low. C. gattii VGII isolates may exhibit higher fluconazole MICs than other genotypes. Optimal therapeutic regimens are yet to be determined; in most cases, initial therapy with amphotericin B and 5-flucytosine is recommended.
Iridium‐catalyzed electrochemical C−H activation was accomplished within a cooperative catalysis manifold, setting the stage for electrooxidative C−H alkenylations through weak O‐coordination. The ...iridium‐electrocatalyzed C−H activation featured high functional‐group tolerance through assistance of a metal‐free redox mediator through indirect electrolysis. Detailed mechanistic insights provided strong support for an organometallic C−H cleavage and a synergistic iridium(III/I)/redox catalyst regime, enabling the use of sustainable electricity as the terminal oxidant with improved selectivity features.
Cooperation: Electrooxidative twofold C−H alkenylation by weak O‐assistance was accomplished by synergistic indirect iridium‐catalyzed electrolysis, enabling unique levels of chemoselectivity.
Summary
This study examines the association between the ASA physical status classification score at hip fracture surgery and severe postoperative complications in patients aged 60 and older. Among ...both men and women, ASA scores consistently predict a wide range of complications including infections, cardiovascular complications, hospital readmissions, and death.
Introduction
Hip fractures are common in aging populations and associated with poor prognosis. This study examines how the American Society of Anaesthesiologists (ASA) physical status classification is related to severe complications among hip fracture patients including infections, cardiovascular diseases, hospital readmissions, and death.
Methods
Based on a linkage of the Swedish National Inpatient Register with the Swedish National Registry for Hip Fractures (RIKSHÖFT), this study includes patients aged 60+ with first hip fracture between 1998 and 2017. We estimated associations between ASA score and complications during the hospital stay and during 1 year after hip fracture using multivariable-adjusted logistic regression and Cox proportional hazard regression.
Results
The study population included 170,193 hip fracture patients of which 24% died and 39% were readmitted to hospital within 1 year. The most common complications were urinary tract infections, pneumonia, second hip fractures, and heart failure. Among both men and women, higher ASA scores were consistently associated with higher risks for all complications included in this study. The strongest associations were observed for heart failure, myocardial infarction, pneumonia, and death.
Conclusion
ASA scores are routinely assessed in clinical practice and predict a wide range of postoperative complications among hip fracture patients. Since many complications may be preventable through adequate drug treatment, rehabilitation, and risk awareness, future studies should examine the mechanisms linking ASA scores to complication risk in order to improve preventive strategies. Particularly, the high risk of cardiovascular complications among patients with high ASA scores deserves clinical and scientific attention.
A significant fraction of OB-type, main-sequence massive stars are classified as runaway and move supersonically through the interstellar medium (ISM). Their strong stellar winds interact with their ...surroundings, where the typical strength of the local ISM magnetic field is about 3.5-7 ...G, which can result in the formation of bow shock nebulae. We investigate the effects of such magnetic fields, aligned with the motion of the flow, on the formation and emission properties of these circumstellar structures. Our axisymmetric, magneto-hydrodynamical simulations with optically thin radiative cooling, heating and anisotropic thermal conduction show that the presence of the background ISM magnetic field affects the projected optical emission of our bow shocks at H... and Oiii ...5007 which become fainter by about 1-2 orders of magnitude, respectively. Radiative transfer calculations against dust opacity indicate that the magnetic field slightly diminishes their projected infrared emission and that our bow shocks emit brightly at 60 ...m. This may explain why the bow shocks generated by ionizing runaway massive stars are often difficult to identify. Finally, we discuss our results in the context of the bow shock of ... Ophiuchi and we support the interpretation of its imperfect morphology as an evidence of the presence of an ISM magnetic field not aligned with the motion of its driving star. (ProQuest: ... denotes formulae/symbols omitted.)
Catalyst‐ and chemical oxidant‐free electrochemical azole C−H aminations were accomplished via cross‐dehydrogenative C−H/N−H functionalization. The catalyst‐free electrochemical C−H amination proved ...feasible on azoles with high levels of efficacy and selectivity, avoiding the use of stoichiometric oxidants under ambient conditions. Likewise, the C(sp3)−H nitrogenation proved viable under otherwise identical conditions. The dehydrogenative C−H amination featured ample scope, including cyclic and acyclic aliphatic amines as well as anilines, and employed sustainable electricity as the sole oxidant.
Set them free: Catalyst‐free electrochemical C−H aminations were accomplished by oxidative C−H/N−H functionalizations with electricity as the sole oxidant.
Coronal jets represent important manifestations of ubiquitous solar transients, which may be the source of significant mass and energy input to the upper solar atmosphere and the solar wind. While ...the energy involved in a jet-like event is smaller than that of "nominal" solar flares and coronal mass ejections (CMEs), jets share many common properties with these phenomena, in particular, the explosive magnetically driven dynamics. Studies of jets could, therefore, provide critical insight for understanding the larger, more complex drivers of the solar activity. On the other side of the size-spectrum, the study of jets could also supply important clues on the physics of transients close or at the limit of the current spatial resolution such as spicules. Furthermore, jet phenomena may hint to basic process for heating the corona and accelerating the solar wind; consequently their study gives us the opportunity to attack a broad range of solar-heliospheric problems.
To assess the benefit of Enhanced Recovery After Surgery (ERAS) on length of stay (LOS), postoperative complications, 30-day readmission, and cost in gynecologic oncology.
A systematic literature ...search was performed in MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and Web of Science for all peer-reviewed cohort studies and controlled trials on ERAS involving gynecologic oncology patients. Abstracts, commentaries, non-controlled studies, and studies without specific data on gynecologic oncology patients were excluded. Meta-analysis was performed on the primary endpoint of LOS. Subgroup analyses were performed based on risk of bias of the studies included, number of ERAS elements, and ERAS compliance. Secondary endpoints were readmission rate, complications, and cost.
A total of 31 studies (6703 patients) were included: 5 randomized controlled trials, and 26 cohort studies. Meta-analysis of 27 studies (6345 patients) demonstrated a decrease in LOS of 1.6 days (95% confidence interval, CI 1.2–2.1) with ERAS implementation. Meta-analysis of 21 studies (4974 patients) demonstrated a 32% reduction in complications (OR 0.68, 95% CI 0.55–0.83) and a 20% reduction in readmission (OR 0.80, 95% CI 0.64–0.99) for ERAS patients. There was no difference in 30-day postoperative mortality (OR 0.61, 95% CI 0.23–1.6) for ERAS patients compared to controls. No difference in the odds of complications or reduction in LOS was observed based on number of included ERAS elements or reported compliance with ERAS interventions. The mean cost savings for ERAS patients was $2129 USD (95% CI $712 - $3544).
ERAS protocols decrease LOS, complications, and cost without increasing rates of readmission or mortality in gynecologic oncology surgery. This evidence supports implementation of ERAS as standard of care in gynecologic oncology.
•Enhanced Recovery After Surgery (ERAS) is a global surgical quality improvement initiative.•ERAS protocols decrease length of stay, complications, and cost without increasing readmission in gynecologic oncology.•Meta-analysis of evidence supports implementation of ERAS as standard of care in gynecologic oncology.
Positron emission tomography (PET) imaging with radiotracers that target translocator protein 18 kDa (TSPO) has become a popular approach to assess putative neuroinflammatory processes and associated ...microglia activation in psychotic illnesses. It remains unclear, however, whether TSPO imaging can accurately capture low-grade inflammatory processes such as those present in schizophrenia and related disorders. Therefore, we evaluated the validity of TSPO as a disease-relevant marker of inflammation using a translational approach, which combined neurodevelopmental and neurodegenerative mouse models with PET imaging in patients with recent-onset schizophrenia and matched controls. Using an infection-mediated neurodevelopmental mouse model, we show that schizophrenia-relevant behavioral abnormalities and increased inflammatory cytokine expression are associated with reduced prefrontal TSPO levels. On the other hand, TSPO was markedly upregulated in a mouse model of acute neurodegeneration and reactive gliosis, which was induced by intrahippocampal injection of kainic acid. In both models, the changes in TSPO levels were not restricted to microglia but emerged in various cell types, including microglia, astrocytes and vascular endothelial cells. Human PET imaging using the second-generation TSPO radiotracer
CDPA-713 revealed a strong trend towards reduced TSPO binding in the middle frontal gyrus of patients with recent-onset schizophrenia, who were previously shown to display increased levels of inflammatory cytokines in peripheral and central tissues. Together, our findings challenge the common assumption that central low-grade inflammation in schizophrenia is mirrored by increased TSPO expression or ligand binding. Our study further underscores the need to interpret altered TSPO binding in schizophrenia with caution, especially when measures of TSPO are not complemented with other markers of inflammation. Unless more selective microglial markers are available for PET imaging, quantification of cytokines and other inflammatory biomarkers, along with their molecular signaling pathways, may be more accurate in attempts to characterize inflammatory profiles in schizophrenia and other mental disorders that lack robust reactive gliosis.
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