Summary
This pilot and feasibility study evaluated wrist‐worn accelerometers to measure recovery from day‐case surgery in comparison with daily quality of recovery‐15 scores. The protocol was ...designed with extensive patient and public involvement and engagement, and delivered by a research network of anaesthesia trainees. Forty‐eight patients recruited through pre‐operative assessment clinics wore wrist accelerometers for 7 days before (pre‐operative) and immediately after elective surgery (early postoperative), and again at 3 months (late postoperative). Validated activity and quality of recovery questionnaires were administered. Raw accelerometry data were archived and analysed using open source software. The mean (SD) number of valid days of accelerometer wear per participant in the pre‐operative, early and late postoperative periods were 5.4 (1.7), 6.6 (1.1) and 6.6 (1.0) days, respectively. On the day after surgery, Euclidian norm minus one (a summary measure of raw accelerations), step count, light physical activity and moderate/vigorous physical activity decreased to 57%, 47%, 59% and 35% of baseline values, respectively. Activity increased progressively on a daily basis but had not returned to baseline values by 7 days. Patient questionnaires suggested subjective recovery by postoperative day 3 to 4; however, accelerometry data showed that activity levels had not returned to baseline at this point. All activity measures had returned to baseline by 3 months. Wrist‐worn accelerometery is acceptable to patients and feasible as a surrogate measure for monitoring postoperative recovery from day‐case surgery. Our results suggest that patients may overestimate their rate of recovery from day‐case surgery, which has important implications for future research.
The lymphatic microvasculature is uniquely adapted for the continuous removal of interstitial fluid and proteins and is an important entry point for leukocytes and tumor cells. Specialized functions ...of lymphatics suggest differences in the molecular composition of the lymphatic and blood vascular endothelium. However, the extent to which the two cell types differ is still unclear, and few molecules that are truly specific to lymphatic endothelial cells have been identified to date. We have isolated primary lymphatic and blood microvascular endothelial cells from human skin by immunoselection with the lymphatic marker LYVE-1 and demonstrate that the two cell lineages express distinct sets of vascular markers and respond differently to growth factors and extracellular matrix. Comparative microarray analysis of gene-expression profiles revealed a number of unique molecular properties that distinguish lymphatic and blood vascular endothelium. The molecular profile of lymphatic endothelium seems to reflect characteristic functional and structural features of the lymphatic capillaries. Classification of the differentially expressed genes into functional groups revealed particularly high levels of genes implicated in protein sorting and trafficking, indicating a more active role of lymphatic endothelium in uptake and transport of molecules than previously anticipated. The identification of a large number of genes selectively expressed by lymphatic endothelium should facilitate the discovery of hitherto unknown lymphatic vessel markers and provide a basis for the analysis of the molecular mechanisms accounting for the characteristic functions of lymphatic capillaries.
Acute mountain sickness (AMS) is a common problem among visitors at high altitude, and may progress to life-threatening pulmonary and cerebral oedema in a minority of cases. International consensus ...defines AMS as a constellation of subjective, non-specific symptoms. Specifically, headache, sleep disturbance, fatigue and dizziness are given equal diagnostic weighting. Different pathophysiological mechanisms are now thought to underlie headache and sleep disturbance during acute exposure to high altitude. Hence, these symptoms may not belong together as a single syndrome. Using a novel visual analogue scale (VAS), we sought to undertake a systematic exploration of the symptomatology of AMS using an unbiased, data-driven approach originally designed for analysis of gene expression. Symptom scores were collected from 292 subjects during 1110 subject-days at altitudes between 3650 m and 5200 m on Apex expeditions to Bolivia and Kilimanjaro. Three distinct patterns of symptoms were consistently identified. Although fatigue is a ubiquitous finding, sleep disturbance and headache are each commonly reported without the other. The commonest pattern of symptoms was sleep disturbance and fatigue, with little or no headache. In subjects reporting severe headache, 40% did not report sleep disturbance. Sleep disturbance correlates poorly with other symptoms of AMS (Mean Spearman correlation 0.25). These results challenge the accepted paradigm that AMS is a single disease process and describe at least two distinct syndromes following acute ascent to high altitude. This approach to analysing symptom patterns has potential utility in other clinical syndromes.
The quest for effective treatments of oxidative stress has concentrated over the years on new nanomaterials with improved antioxidant and antiradical activity, thereby attracting broad research ...interest. In that regard, research efforts in our lab were launched to pursue such hybrid materials involving a) synthesis of silica gel matrices, b) evaluation of the suitability of atoxic matrices as potential carriers for the controlled release of V(IV)(VOSO4), V(V)(NaVO3) compounds and a newly synthesized heterometallic lithium-vanadium(IV,V) tetranuclear compound containing vanadium-bound hydroxycarboxylic 1,3-diamine-2-propanol-N,N,N′,N′-tetraacetic acid (DPOT), and c) investigation of structural and textural properties of silica nanoparticles (NPs) by different and complementary characterization techniques, inquiring into the nature of the encapsulated vanadium species and their interaction with the siloxane matrix, collectively targeting novel antioxidant and antiradical nanomaterials biotechnology. The physicochemical characterization of the vanadium-loaded SiO2 NPs led to the formulation of optimized material configuration linked to the delivery of the encapsulated antioxidant-antiradical load. Entrapment and drug release studies showed a) the competence of hybrid nanoparticles with respect to encapsulation efficiency of the vanadium compound (concentration dependence), b) congruence with the physicochemical features determined, and c) a well-defined release profile of NP load. Antioxidant properties and the free radical scavenging capacity of the new hybrid materials (containing VOSO4, NaVO3, and V-DPOT) were demonstrated through a) 2-diphenyl-1-picrylhydrazyl (DPPH) free radical, and b) intracellular-extracellular reactive oxygen species (ROS) assays, through UV–Visible spectroscopy techniques, collectively showing that the hybrid silica NPs (empty-loaded) could serve as an efficient platform for nanodrug formulations counteracting oxidative stress.
Efforts targeting development of antioxidant and antiradical nanotechnology led to new silica nanoparticles bearing V(IV), V(V), and a new synthetic V(IV,V)-DPOT compound. The emerging hybrid materials exhibit well-defined optimized physicochemical properties, decreased cytotoxicity, and improved radical scavenging capacity, as a result of high structure-specific vanadium encapsulation efficiency and release rates. Display omitted
•Synthesis and characterization of V(IV), V(V), V(IV,V)-loaded silica nanoparticles•Vanadium encapsulation and release profiling enhance radical scavenging capacity.•Development of antioxidant and antiradical nanotechnology based on vanadium species•Efficient hybrid vanadium-complex inorganic nanocarriers countering oxidative stress•Nanoparticulate vanadium oxidation state, structure- and cell-specific bioactivity
VEGF and Angiopoietin-1 requisitely collaborate during blood vessel development. While Angiopoietin-1 obligately activates its Tie2 receptor, Angiopoietin-2 can activate Tie2 on some cells, while it ...blocks Tie2 activation on others. Our analysis of mice lacking Angiopoietin-2 reveals that Angiopoietin-2 is dispensable for embryonic vascular development but is requisite for subsequent angiogenic remodeling. Unexpectedly, mice lacking Angiopoietin-2 also exhibit major lymphatic vessel defects. Genetic rescue with Angiopoietin-1 corrects the lymphatic, but not the angiogenesis, defects, suggesting that Angiopoietin-2 acts as a Tie2 agonist in the former setting, but as an antagonist in the latter setting. Our studies define a vascular growth factor whose primary role is in postnatal angiogenic remodeling and also demonstrate that members of the VEGF and Angiopoietin families collaborate during development of the lymphatic vasculature.
Metastasis is a frequent and lethal complication of cancer. Vascular endothelial growth factor‐C (VEGF‐C) is a recently described lymphangiogenic factor. Increased expression of VEGF‐C in primary ...tumours correlates with dissemination of tumour cells to regional lymph nodes. However, a direct role for VEGF‐C in tumour lymphangiogenesis and subsequent metastasis has yet to be demonstrated. Here we report the establishment of transgenic mice in which VEGF‐C expression, driven by the rat insulin promoter (Rip), is targeted to β‐cells of the endocrine pancreas. In contrast to wild‐type mice, which lack peri‐insular lymphatics, RipVEGF‐C transgenics develop an extensive network of lymphatics around the islets of Langerhans. These mice were crossed with Rip1Tag2 mice, which develop pancreatic β‐cell tumours that are neither lymphangiogenic nor metastatic. Double‐transgenic mice formed tumours surrounded by well developed lymphatics, which frequently contained tumour cell masses of β‐cell origin. These mice frequently developed pancreatic lymph node metastases. Our findings demonstrate that VEGF‐C‐induced lymphangiogenesis mediates tumour cell dissemination and the formation of lymph node metastases.
We used proton magnetic resonance spectroscopy (1H MRS) to investigate the temporal lobes of 25 patients with temporal lobe epilepsy. Spectra were obtained from 2 x 2 x 2 cm cubes in the medial ...region of the temporal lobe, and were analyzed on the basis of signals from N-acetylaspartate (NAA), creatine + phosphocreatine (Cr), and choline-containing compounds (Cho). In comparison with control subjects, the temporal lobes ipsilateral to the seizure focus showed a mean reduction of 22% in the NAA signal, with a 15% increase in the Cr signal and a 25% increase in the Cho signal. There were smaller effects in the contralateral temporal lobes. These spectral abnormalities may reflect neuronal loss or damage, together with reactive astrocytosis. The NAA/Cho+Cr ratio was abnormally low in 88% of the patients, 40% showing bilateral effects. On the basis of the NAA/Cho+Cr ratio, we correctly achieved lateralization in 15 cases, with three incorrect. Two of the incorrect lateralizations also had imaging abnormalities on the contralateral side, and the other had severe bilateral abnormalities on MRS. We conclude that 1H MRS provides useful information in the preoperative investigation of patients with temporal lobe epilepsy, contributing to lateralization and detecting bilateral abnormalities.
Germ-line truncating mutations in the E-cadherin (CDH1) gene have been found in families with hereditary diffuse gastric cancer. These families are characterized by a highly penetrant susceptibility ...to diffuse gastric cancer with an autosomal dominant pattern of inheritance, predominantly in young persons. We describe genetic screening, surgical management, and pathological findings in young persons with truncating mutations in CDH1 from two unrelated families with hereditary diffuse gastric cancer.
Mutation-specific predictive genetic testing was performed by polymerase-chain-reaction amplification, followed by restriction-enzyme digestion and DNA sequencing in Family 1 and by heteroduplex analysis in Family 2. A total gastrectomy was performed prophylactically in five carriers of mutations who were between 22 and 40 years old. In each case, the entire mucosa of the stomach was extensively sampled for microscopical analysis.
Superficial infiltrates of malignant signet-ring cells were identified in the surgical samples from all five persons who underwent gastrectomy. These early diffuse gastric cancers were multifocal in three of the five cases, and in one person infiltrates of malignant signet-ring cells were present in 65 of the 140 tissue blocks analyzed, representing in aggregate less than 2 percent of the gastric mucosa.
We recommend genetic counseling and consideration of prophylactic gastrectomy in young, asymptomatic carriers of germ-line truncating CDH1 mutations who belong to families with highly penetrant hereditary diffuse gastric cancer.
Coconut production in the Pacific Islands is threatened by coconut rhinoceros beetle (CRB). Distinctive feeding damage caused by adults is often the first indicator of CRB activity in a new location. ...Multiple approaches to damage assessment have been used, reflecting observers' experience. The lack of standardisation makes it difficult to compare CRB impacts on coconut palms over time. We examine damage assessment from three perspectives: participants, power and purpose. Participants applied binary, 3-point and 5-point damage scales consecutively to photographs of damaged palms. Participant responses were more accurate using the binary scale compared with the 5-point scale. Experience with CRB improved accuracy, but this did not wholly compensate for the effect of scale complexity. Calculations of statistical power determined minimum sample sizes to detect a 20% change in palm damage was 50 palms for the binary scale, 150 palms for the 3-point scale and > 200 palms for the 5-point scale, when the change in damage was spread across damage categories. More complex damage scales did not increase the likelihood of detecting significant changes in palm damage. With real-world examples, including detecting new outbreaks and managing established populations, recommendations were developed to standardise damage assessment for CRB on coconut palms.
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