Continuous real-time monitoring of the adequacy of cerebral perfusion can provide important therapeutic information in a variety of clinical settings. The current clinical availability of several ...non-invasive near-infrared spectroscopy (NIRS)-based cerebral oximetry devices represents a potentially important development for the detection of cerebral ischaemia. In addition, a number of preliminary studies have reported on the application of cerebral oximetry sensors to other tissue beds including splanchnic, renal, and spinal cord. This review provides a synopsis of the mode of operation, current limitations and confounders, clinical applications, and potential future uses of such NIRS devices.
Climate change models predict that future precipitation patterns will entail lower-frequency but larger rainfall events, increasing the duration of dry soil conditions. Resulting shifts in microbial ...C cycling activity could affect soil C storage. Further, microbial response to rainfall events may be constrained by the physiological or nutrient limitation stress of extended drought periods; thus seasonal or multi-annual precipitation regimes may influence microbial activity following soil wet-up. We quantified rainfall-driven dynamics of microbial processes that affect soil C loss and retention, and microbial community composition, in soils from a long-term (14-y) field experiment contrasting "Ambient" and "Altered" (extended intervals between rainfalls) precipitation regimes. We collected soil before, the day following, and five days following 2.5-cm rainfall events during both moist and dry periods (respectively: June and September 2011, soil water potential = -0.01 and -0.83 MPa), and measured microbial respiration, microbial biomass, organic matter decomposition potential (extracellular enzyme activities), and microbial community composition (phospholipid fatty acids). The equivalent rainfall events caused equivalent microbial respiration responses in both treatments. In contrast, microbial biomass was higher and increased after rainfall in Altered treatment soils only, thus microbial C-use efficiency (CUE) was higher in Altered than Ambient treatments (0.70 ± 0.03 > 0.46 ± 0.10). CUE was also higher in dry (September) soils. C-acquiring enzyme activities (β-glucosidase, cellobiohydrolase and phenol oxidase) increased after rainfall in moist (June), but not dry (September) soils. Both microbial biomass C:N ratios and fungal:bacterial ratios were higher at lower soil water contents, suggesting a functional and/or population-level shift in the microbiota at low soil water contents, and microbial community composition also differed following wet-up and between seasons and treatments. Overall, microbial activity may directly (C respiration) and indirectly (enzyme potential) reduce soil organic matter pools less in drier soils, and soil C sequestration potential (CUE) may be higher in soils with a history of extended dry periods between rainfall events. The implications include that soil C loss may be reduced or compensated for via different mechanisms at varying time scales, and that microbial taxa with better stress tolerance or growth efficiency may be associated with these functional shifts.
Focal adhesion kinase (FAK) is considered intimately involved in cancer progression. Our previous research has demonstrated that overexpression of FAK is an early and frequent event in squamous cell ...carcinomas of the supraglottic larynx, and it is associated with the presence of metastases in cervical lymph nodes. The purpose of this study was to examine the functional role of FAK in the progression of head and neck squamous cell carcinomas (HNSCC). To this end, expression of FAK-related nonkinase (FRNK) or small interfering RNA (siRNA) against FAK was used to disrupt the FAK-induced signal transduction pathways in the HNSCC-derived SCC40 and SCC38 cell lines. Similar phenotypic effects were observed with the two methodological approaches in both cell lines. Decreased cell attachment, motility and invasion were induced by FRNK and FAK siRNA, whereas cell proliferation was not impaired. In addition, increased cell invasion was observed upon FAK overexpression in SCC cells. FRNK expression resulted in a downregulation of MMP-2 and MMP-9 expression. Interestingly, MMP-2 overexpression in FRNK-expressing cells rescued FRNK inhibition of cell invasion. This is the first demonstration of a direct rescue of impaired cell invasion by the re-expression of MMP-2 in a tumour cell type with decreased expression of functional FAK. Collectively, these data reported here support the conclusion that FAK enhances invasion of HNSCC by promoting both increased cell motility and MMP-2 production, thus providing new insights into possible therapeutic intervention strategies.
To evaluate the impact of a curricular intervention to promote health-related fitness (HRF) among medical students in Bogota, Colombia.
The study was conducted between May 2014 and December 2015 as ...part of the medical physiology course, in which 208 medical students were enrolled.The curricular intervention included two lectures on physical activity (PA) and student-led group presentations on the physiological effects of exercise on human physiology. An academic incentive (10% of final grade) was given to students who reported and documented regular PA practice during the semester. This study assessed students' HRF variables, perceptions of the curriculum intervention, and PA practices using quantitative and qualitative approaches.
55% of the students were female, with a mean age of 19.5 years. Body fat, estimated maximum oxygen consumption (VO2max), handgrip, and sit-up strength showed statistically significant improvements at the end of the intervention. Students reported that PA practice was positively influenced by the curriculum intervention, particularly the academic incentive and the HRF tests. Students reported a wide variety of PA practices, which were mainly done with friends, classmates, or family members. Lack of time was the main reported barrier to PA practice.
The curricular intervention was effective in improving HRF and promoting PA. It remains to be investigated whether these gains are sustained over time.
Nature-inspired processing of complex reticular/cellular architected materials by selectively incorporating multiphase materials in emulsions with targeted interactions is reported in this work. In ...particular, structuring of TiO
2
foams at different scales is realized by combining colloidal processing and 3D printing with fundamental understanding of the TiO
2
nanoparticle system. Specifically, hybrid TiO
2
/Ti-organic aqueous suspensions are emulsified with bio-compatible and naturally synthesized oil stabilizers where air bubbles are trapped, forming the cells of the wet foams, which are subsequently directly written as planar and three-dimensional free-standing and spanning structures. Variations in the formulation of these emulsions are implemented to tune their viscosity and render diverse cell morphologies (i.e., open- or closed-cell foam configurations) while controlling their micro-, meso- and macro-porosity. Investigation of the foams’ curing using heat versus UV light indicates differences in the emulsion’s oil-phase elimination mechanism with effects in their microstructure, which, added to the characteristic relationships between the foams’ microstructures and their photocatalytic activity, can be used to target specific properties. Our synthesis method, adjusted from the cosmetics industry, combines inorganic processing with emulsion systems of non-toxic and abundant material precursors to realize hierarchically ordered mesoporous titania foams. This method can be further exploited with other metal-oxide materials systems and even more complex emulsions to meet the needs of the currently growing technologic application fields. Moreover, we anticipate our family of foams to be readily relevant for a plethora of applications including catalysis, energy harvesting and recovery, and biomedical. Designed to be safe and water-compatible, our multi-phase emulsion systems marry high control over the materials’ microstructure and interfaces with scalable, affordable and responsible manufacturing.
Plasmodium vivax infects a hundred million people annually and endangers 40% of the world's population. Unlike Plasmodium falciparum, P. vivax parasites can persist as a dormant stage in the liver, ...known as the hypnozoite, and these dormant forms can cause malaria relapses months or years after the initial mosquito bite. Here we analyze whole genome sequencing data from parasites in the blood of a patient who experienced consecutive P. vivax relapses over 33 months in a non-endemic country. By analyzing patterns of identity, read coverage, and the presence or absence of minor alleles in the initial polyclonal and subsequent monoclonal infections, we show that the parasites in the three infections are likely meiotic siblings. We infer that these siblings are descended from a single tetrad-like form that developed in the infecting mosquito midgut shortly after fertilization. In this natural cross we find the recombination rate for P. vivax to be 10 kb per centimorgan and we further observe areas of disequilibrium surrounding major drug resistance genes. Our data provide new strategies for studying multiclonal infections, which are common in all types of infectious diseases, and for distinguishing P. vivax relapses from reinfections in malaria endemic regions. This work provides a theoretical foundation for studies that aim to determine if new or existing drugs can provide a radical cure of P. vivax malaria.
Pulmonary hypertension (PH) conveys a worse prognosis in heart failure (HF), in particular when right ventricular (RV) dysfunction ensues. Cardiovascular magnetic resonance (CMR) non-invasively ...estimates pulmonary vascular resistance (PVR), which has shown prognostic value in HF. Importantly, RV to pulmonary artery (PA) coupling is altered early in HF, before significant rise in PV resistance occurs. The aim of this study was to assess the prognostic value of mean velocity at the pulmonary artery (mvPA), a novel non-invasive parameter determined by CMR, in HF with reduced ejection fraction (HFrEF) with and without associated PH.
Prospective inclusion of 238 patients admitted for new-onset HFrEF. MvPA was measured with CMR during index admission. The primary endpoint was defined as a composite of HF readmissions and all-cause mortality.
During a median follow-up of 25 months, 91 patients presented with the primary endpoint. Optimal cut-off value of mvPA calculated by the receiver operator curve for the prediction of the primary endpoint was 9 cm/s. The primary endpoint occurred more frequently in patients with mvPA≤9 cm/s, as indicated by Kaplan-Meier survival curves; Log Rank 16.0, p < 0.001. Importantly, mvPA maintained its prognostic value regardless of RV function and also when considering mortality and HF readmissions separately. On Cox proportional hazard analysis, reduced mvPA≤9 cm/s emerged as an independent prognostic marker, together with NYHA III-IV/IV class, stage 3-4 renal failure and ischemic cardiomyopathy.
In our HFrEF cohort, mvPA emerged as an independent prognostic indicator independent of RV function, allowing identification of a higher-risk population before structural damage onset. Moreover, mvPA emerged as a surrogate marker of the RV-PA unit coupling status.
Deep brain stimulation targeting the posterior hypothalamus (pHyp-DBS) is being investigated as a treatment for refractory aggressive behavior, but its mechanisms of action remain elusive. We ...conducted an integrated imaging analysis of a large multi-centre dataset, incorporating volume of activated tissue modeling, probabilistic mapping, normative connectomics, and atlas-derived transcriptomics. Ninety-one percent of the patients responded positively to treatment, with a more striking improvement recorded in the pediatric population. Probabilistic mapping revealed an optimized surgical target within the posterior-inferior-lateral region of the posterior hypothalamic area. Normative connectomic analyses identified fiber tracts and functionally connected with brain areas associated with sensorimotor function, emotional regulation, and monoamine production. Functional connectivity between the target, periaqueductal gray and key limbic areas - together with patient age - were highly predictive of treatment outcome. Transcriptomic analysis showed that genes involved in mechanisms of aggressive behavior, neuronal communication, plasticity and neuroinflammation might underlie this functional network.
Abstract Purpose The aim of the study was to determine whether C-reactive protein (CRP), procalcitonin (PCT), and d -dimer (DD) are markers of mortality in patients admitted to the emergency ...department (ED) with suspected infection and sepsis. Basic Procedures We conducted a prospective cohort in a university hospital in Medellín, Colombia. Patients were admitted between August 1, 2007, and January 30, 2009. Clinical and demographic data and Acute Physiology and Chronic Health Evaluation II and Sepsis Organ Failure Assessment scores as well as blood samples for CRP, PCT, and DD were collected within the first 24 hours of admission. Survival was determined on day 28 to establish its association with the proposed biomarkers using logistic regression and receiver operating characteristic curves. Main Findings We analyzed 684 patients. The median Acute Physiology and Chronic Health Evaluation II and Sepsis Organ Failure Assessment scores were 10 (interquartile range IQR, 6-15) and 2 (IQR, 1-4), respectively. The median CRP was 9.6 mg/dL (IQR, 3.5-20.4 mg/dL); PCT, 0.36 ng/mL (IQR, 0.1-3.7 ng/mL); and DD, 1612 ng/mL (IQR, 986-2801 ng/mL). The median DD in survivors was 1475 ng/mL (IQR, 955-2627 ng/mL) vs 2489 ng/mL (IQR, 1698-4573 ng/mL) in nonsurvivors ( P = .0001). The discriminatory ability showed area under the curve–receiver operating characteristic for DD, 0.68; CRP, 0.55; and PCT, 0.59. After multivariate analysis, the only biomarker with a linear relation with mortality was DD, with an odds ratio of 2.07 (95% confidence interval, 0.93-4.62) for values more than 1180 and less than 2409 ng/mL and an odds ratio of 3.03 (95% confidence interval, 1.38-6.62) for values more than 2409 ng/mL. Principal Conclusions Our results suggest that high levels of DD are associated with 28-day mortality in patients with infection or sepsis identified in the emergency department.
5α,8α-peroxyergosteryl divaricatinate (
) is isolated for the first time from acetone extract of the thallus of
cf.
together with condidymic (
), isodidymic (
) and barbatic (
) acids. Their UVB/UVA ...photoprotective and antioxidant activities were determined along with their cyto- and DNA-protecting actions against OH• damage. Compound
showed high UVA, cyto- (%cell viability
82 at 15 µM
71 for OH•) and DNA (%DNA-integrity
74 at 100 µM
22 for OH•) protecting properties. Compounds
and
exhibited high UVB (SPF
40) and antioxidant activities (free radical scavenging potency EC
= 0.6694 and 1.700 mol compound/mol DPPH•; ferric reducing power 0.392 and 0.546, at 500 ppm and inhibited lipid peroxidation); protecting cells (%cell viability
76 at 15 µM) and DNA (%DNA-integrity
57 at 100 µM). Compounds
to
fulfilled some physicochemical properties to act topically on the skin.