Electrospray ionization mass spectrometry of platinum anticancer agents.

Quantification and identification of platinum drugs and their metabolites in biological samples has always been difficult because these compounds are thermally unstable, non-volatile and insoluble. We have demonstrated that electrospray ionization mass spectrometry can be a valuable technique for direct mass spectral analysis of platinum anticancer agents and for obtaining structural information as a result of fragmentation. Full-scan spectra were obtained with approximately 10 pmol samples. These results show the potential of applying this technique in pharmacokinetic studies of platinum anticancer drugs.     

Effects of inspiratory elastic load on respiratory control in hypercapnia and exercise

Five healthy young men underwent two separate steady-state incremental exercise runs within the aerobic range on a treadmill with alternating periods of breathing with no load (NL) and with a discontinuous inspiratory elastic load (IEL) of approximately 10 cmH2O/l. End-tidal PCO2 was maintained constant throughout each run at the eucapnic or a constant hypercapnic level by adding 0-5% CO2 to the inspired O2. Hypercapnia caused a steepening, as well as upward shift, relative to the corresponding eucapnic ventilation-CO2 output (VE-VCO2) relationship in NL and IEL. Compared with NL, the VE-VCO2 slope was depressed by IEL, more so in hypercapnic [-28.7 +/- 7.2 (SE) %] than in eucapnic exercise (-16.0 +/- 2.8%). The steady-state hypercapnic ventilatory response at rest was also markedly depressed (-32.1 +/- 11.2%). Occlusion pressure response was augmented in response to IEL during eucapnic exercise (88.7 +/- 13.3%) but not during CO2 inhalation at rest or during exercise. Breathing pattern characteristics were similar regardless of the type of stimulus input and the level of inspiratory load. Results are consistent with the notion that the control of VE and breathing pattern may both be influenced by a balance between the prevailing chemical drive and a propensity of the controller to reduce respiratory effort.     

Ventilatory control in hypercapnia and exercise: optimization hypothesis

A model of the respiratory control system incorporating both chemical and respiratory neuromechanical feedbacks is proposed to describe the steady-state ventilatory responses to CO2 inhalation and exercise. It is postulated that ventilatory output (VE) is set by the respiratory center to minimize a net operating cost representing the conflicting challenges of arterial chemical imbalance and respiratory-mechanical discomfort (intolerance of effort), given, respectively, by a quadratic function of arterial PCO2 and a logarithmic function of VE. In addition, the system is assumed to be mechanically limited at maximum VE (Vmax). The predicted responses in VE during moderate hypercapnia, exercise, and ventilatory loading closely mimic those normally observed, even though no separate signal unique to exercise is assumed. As a quantitative validation, the model yielded good fits to ventilatory response data obtained in eight healthy subjects during eucapnic and hypercapnic exercise; the predicted Vmax averaged approximately 77% of the maximum voluntary ventilation in all subjects. The results demonstrate the plausibility of the proposed optimization mechanism and suggest an important role for respiratory-mechanical factors in the control of VE.     

Full‐field swept‐source optical coherence tomography and neural tissue classification for deep brain imaging

Optical coherence tomography can differentiate brain regions with intrinsic contrast and at a micron scale resolution. Such a device can be particularly useful as a real‐time neurosurgical guidance tool. We present, to our knowledge, the first full‐field swept‐source optical coherence tomography system operating near a wavelength of 1310 nm. The proof‐of‐concept system was integrated with an endoscopic probe tip, which is compatible with deep brain stimulation keyhole neurosurgery. Neuroimaging experiments were performed on ex vivo brain tissues and in vivo in rat brains. Using classification algorithms involving texture features and optical attenuation, images were successfully classified into three brain tissue types.     

Identification of hemopexin in tear film

Human tear fluid is a complex mixture of aqueous lipids, proteins, enzymes, and other biochemical and cellular elements. By conventional comparative proteomic approaches, we investigated the proteome in human tear fluid and compared the tear protein profile of normal control subjects with that of patients suffering from the ocular inflammatory disease vernal keratoconjunctivitis (VKC). Collected tear samples were directed to two-dimensional polyacrylamide gel electrophoresis protein separation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry peptide identification. Six differentially expressed proteins—interleukin 4, phospholipase A2, albumin, lactoferrin, hemopexin, and lipocalin—were displayed. Hemopexin had not been reported previously in tear film. Enzyme-linked immunosorbent assay confirmed that hemopexin concentrations were significantly higher in VKC tear samples and increased with disease stages. The results implied clinical interest of hemopexin in the tear proteome and eye diseases.     

Postoperative outcomes for Indigenous Peoples in Canada: a systematic review

Background:Substantial health inequities exist for Indigenous Peoples in Canada. The remote and distributed population of Canada presents unique challenges for access to and use of surgery. To date, the surgical outcome data for Indigenous Peoples in Canada have not been synthesized.Methods:We searched 4 databases to identify studies comparing surgical outcomes and utilization rates of adults of First Nations, Inuit or Métis identity with non-Indigenous people in Canada. Independent reviewers completed all stages in duplicate. Our primary outcome was mortality; secondary outcomes included utilization rates of surgical procedures, complications and hospital length of stay. We performed meta-analysis of the primary outcome using random effects models. We assessed risk of bias using the ROBINS-I tool.Results:Twenty-eight studies were reviewed involving 1 976 258 participants (10.2% Indigenous). No studies specifically addressed Inuit or Métis populations. Four studies, including 7 cohorts, contributed adjusted mortality data for 7135 participants (5.2% Indigenous); Indigenous Peoples had a 30% higher rate of death after surgery than non-Indigenous patients (pooled hazard ratio 1.30, 95% CI 1.09–1.54; I² = 81%). Complications were also higher for Indigenous Peoples, including infectious complications (adjusted OR 1.63, 95% CI 1.13–2.34) and pneumonia (OR 2.24, 95% CI 1.58–3.19). Rates of various surgical procedures were lower, including rates of renal transplant, joint replacement, cardiac surgery and cesarean delivery.Interpretation:The currently available data on postoperative outcomes and surgery utilization rates for Indigenous Peoples in Canada are limited and of poor quality. Available data suggest that Indigenous Peoples have higher rates of death and adverse events after surgery, while also encountering barriers accessing surgical procedures. These findings suggest a need for substantial re-evaluation of surgical care for Indigenous Peoples in Canada to ensure equitable access and to improve outcomes. Protocol registration:PROSPERO-CRD42018098757

Safe, timely and affordable access to surgical care is essential to overall population health, as conditions amenable to surgical intervention account for one-third of the global burden of disease.^1,2 Surgery is responsible for 65% of cancer cure and control, it is key to trauma management, and access to cesarean delivery reduces neonatal deaths by up to 70%.¹ The magnitude and ubiquity of surgical conditions makes tracking their prevalence and treatment within local and national monitoring systems essential to fully capture the health and welfare of populations in Canada, including Indigenous Peoples.About 1.67 million people in Canada are Indigenous, representing 4.9% of the total population (58% First Nations, 4% Inuit, 35% Métis).³ Health inequities exist for the Indigenous population; life expectancy at birth is 5–11 years shorter than for non-Indigenous Peoples^4,5 and higher rates of communicable and noncommunicable diseases, unintentional injury and suicide are well documented.^4,6–14 These health inequities are direct impacts of the social determinants of health, which are in turn effects of colonialism and government policies, including the Indian residential school system.^8,11 People living in remote regions have less access to publicly funded health care than other people in Canada, with worse outcomes.¹⁵Given the substantial impact of surgical disease on population health and the recognized disparities in health care access for Indigenous Peoples in Canada, understanding access to surgical services and subsequent outcomes is a key step to addressing health inequities. To date, limited research has been conducted on surgical and postoperative care involving Indigenous Peoples in Canada and the available literature has not been synthesized. Our objective was to systematically review studies comparing postoperative outcomes between Indigenous and non-Indigenous Peoples in Canada.     

Quantification of perfusion and metabolism in an autism mouse model assessed by diffuse correlation spectroscopy and near-infrared spectroscopy

There is a need for quantitative biomarkers for early diagnosis of autism. Cerebral blood flow and oxidative metabolism parameters may show superior contrasts for improved characterization. Diffuse correlation spectroscopy (DCS) has been shown to be reliable method to obtain cerebral blood flow contrast in animals and humans. Thus, in this study, we evaluated the combination of DCS and fNIRS in an established autism mouse model. Our results indicate that autistic group had significantly (P = .001) lower (~40%) blood flow (1.16 ± 0.26) × 10⁻⁸ cm²/s), and significantly (P = .015) lower (~70%) oxidative metabolism (52.4 ± 16.6 μmol/100 g/min) compared to control group ([1.93 ± 0.74] × 10⁻⁸ cm²/s, 177.2 ± 45.8 μmol/100 g/min, respectively). These results suggest that the combination of DCS and fNIRS can provide hemodynamic and metabolic contrasts for in vivo assessment of autism pathological conditions noninvasively.