Low intensity shockwave treatment modulates macrophage functions beneficial to healing chronic wounds

Acknowledgments: We acknowledge the University of Aberdeen Microscopy and Histology Facility and the qPCR facility for use of facilities and advice. We acknowledge Ehab Husain for scoring the patient wound biopsies. Funding: This research was funded by NHS Grampian Endowments, grant number 17/004 and by personal funding from JSH.Peer reviewedPublisher PD

Management of secondary risk factors in patients with intermittent claudication

Objectives: the first line management of patients with intermittent claudication is "best medical therapy'' i.e., smoking cessation, exercise, antiplatelet therapy and risk factors modification. The aim of this study was to assess the current management of risk factors in primary care and to compare General Practitioner (GP) attitudes and actual management. Design and Methods: postal questionnaire of all 336 GPs in the referral area (Grampian, Scotland). Questionnaire and measurement of serum cholesterol, blood glucose and HbA1c of new clinic patients (n 104) with claudication referred by general practitioners. Results: a 73% GP response rate was obtained. Ninety-five percent of GPs would treat risk factors. The vast majority would prescribe aspirin, yet 28% of patients were on no anti-platelet therapy. Eighty-nine percent of GPs would advise an increase in exercise but only 14% of patients recalled being told to do so. One in seven of the GPs would not check serum cholesterol, 18% considered cholesterol lowering therapy to be primary prevention and 41% would only treat levels above 5.5 mmol/l. Eighty-five percent of patients were on a statin or had a cholesterol above 5 mmol/L. Seventy-seven percent of GPs would check glucose levels, and 14% of patients were found to be previously undiagnosed diabetics. Conclusions: risk factors in claudicants are suboptimally managed. Urgent guidelines for the specific management of claudicants by general practitioners, as well as strategies to ensure their implementation, are required.peer-reviewe

Completing the audit cycle : comparison of cardiac risk factor management in patients with intermittent claudication in two time periods

Aim. The first line treatment of patients with intermittent claudication (IC) is to prolong life via cardiac risk factor management. We aimed to compare current standards of secondary prevention with those in a previously published audit. Methods. Risk factor data was prospectively collated on 304 consecutive new referrals attending the claudication clinic over a 1-year period (2004/2005) and compared to the 104 patients assessed in 2000. Results. In 2004/5 30%, (n=91) of patients did not have a diagnosis of IC confirmed (p < 0.01). The use of antiplatelet therapy remained static at 73%. Statin therapy increased in 2004/5 (62% versus 38%, p < 0.01) but blood pressure control remained poor with 65% failing to achieve the target levels. Smoking cessation therapy continues to be offered to a minority of patients and 17% of patients have previously undiagnosed diabetes in 2004/2005 (p-value 0.353). The number of patients who have been advised to increase physical activity significantly has fallen from 15% to 2% in the 2004/5 (p < 0.01). Conclusions. Difficulties exist in diagnosing intermittent claudication in primary care and cardiac risk factor manage- ment continues to be sub-optimally managed.peer-reviewe

Satellite tracking of leatherback and loggerhead sea turtles on the Southeast African coastline

The waters of southeast Africa contain important habitats for several sea turtle species, including the leatherback Dermochelys coriacea, loggerhead Caretta caretta, hawksbill Eretmochelys imbricata, green Chelonia mydas, and olive ridley turtle Lepidochelys olivacea. Many of these species are of conservation concern (Rakotoniria & Cooke, 1994; Thorson et al., 2012; Nel et al., 2013) and vulnerable to regional threats such as fisheries by-catch or boat-strikes (Bourjea et al., 2008; Grantham et al., 2008; Pusineri & Quillard, 2008). To help in the development of effective conservation plans for these species, many conservation or research organisations have used satellite transmitters to help identify critical habitats for sea turtles (Harris et al., 2015; Robinson et al., 2016). Here, we review the movement patterns of sea turtles that have been tracked through satellite telemetry from their nesting beaches on the east coast of South Africa

Olig2-Regulated Lineage-Restricted Pathway Controls Replication Competence in Neural Stem Cells and Malignant Glioma

Recent studies have identified stem cells in brain cancer. However, their relationship to normal CNS progenitors, including dependence on common lineage-restricted pathways, is unclear. We observe expression of the CNS-restricted transcription factor, OLIG2, in human glioma stem and progenitor cells reminiscent of type C transit-amplifying cells in germinal zones of the adult brain. Olig2 function is required for proliferation of neural progenitors and for glioma formation in a genetically relevant murine model. Moreover, we show p21^(WAF1/CIP1), a tumor suppressor and inhibitor of stem cell proliferation, is directly repressed by OLIG2 in neural progenitors and gliomas. Our findings identify an Olig2-regulated lineage-restricted pathway critical for proliferation of normal and tumorigenic CNS stem cells

DNA double-strand breaks cooperate with loss of Ink4 and Arf tumor suppressors to generate glioblastomas with frequent Met amplification

Glioblastomas (GBM) are highly radioresistant and lethal brain tumors. Ionizing radiation (IR)- induced DNA double-strand breaks (DSBs) are a risk factor for the development of GBM. In this study, we systematically examined the contribution of IR-induced DSBs to GBM development using transgenic mouse models harboring brain-targeted deletions of key tumor suppressors frequently lost in GBM, namely Ink4a, Ink4b, Arf, and/or PTEN. Using low linear energy transfer (LET) X-rays to generate simple breaks or high LET Fe ions to generate complex breaks, we found that DSBs induce high-grade gliomas in these mice which, otherwise, do not develop gliomas spontaneously. Loss of Ink4a and Arf was sufficient to trigger IR-induced glioma development but additional loss of Ink4b significantly increased tumor incidence. We analyzed IR-induced tumors for copy number alterations (CNAs) to identify oncogenic changes that were generated and selected for as a consequence of stochastic DSB events. We found Met amplification to be the most significant oncogenic event in these radiation-induced gliomas. Importantly, Met activation resulted in expression of Sox2, a GBM cancer stem cell (CSC) marker, and was obligatory for tumor formation. In sum, these results indicate that radiation-induced DSBs cooperate with loss of Ink4 and Arf tumor suppressors to generate high-grade gliomas that are commonly driven by Met amplification and activation

Analysis of Tumor Metabolism Reveals Mitochondrial Glucose Oxidation in Genetically Diverse Human Glioblastomas in the Mouse Brain In Vivo

SummaryDysregulated metabolism is a hallmark of cancer cell lines, but little is known about the fate of glucose and other nutrients in tumors growing in their native microenvironment. To study tumor metabolism in vivo, we used an orthotopic mouse model of primary human glioblastoma (GBM). We infused 13C-labeled nutrients into mice bearing three independent GBM lines, each with a distinct set of mutations. All three lines displayed glycolysis, as expected for aggressive tumors. They also displayed unexpected metabolic complexity, oxidizing glucose via pyruvate dehydrogenase and the citric acid cycle, and using glucose to supply anaplerosis and other biosynthetic activities. Comparing the tumors to surrounding brain revealed obvious metabolic differences, notably the accumulation of a large glutamine pool within the tumors. Many of these same activities were conserved in cells cultured ex vivo from the tumors. Thus GBM cells utilize mitochondrial glucose oxidation during aggressive tumor growth in vivo

Spatiotemporal trends in cetacean strandings and response in the southwestern Indian Ocean : 2000–2020

On behalf of SIF, we would like to thank the Seychelles partners (Alphonse Foundation, Desroches Foundation, Island Conservation Society, Farquhar Foundation, Seychelles Islands Foundation, Silhouette Foundation) for providing financial support to acquire and grant use of their data. Collection of data in Reunion was funded by DEAL Reunion and Region-Reunion.The south-western Indian Ocean (SWIO) is a region of global importance for marine mammal biodiversity, but our understanding of most of the species and populations found there is still rudimentary. The Indian Ocean Network for Cetacean Research (IndoCet) was formed in 2014 and is dedicated to the research of all cetacean species across the SWIO. Since 2019, there have been efforts to create a regional network for coordinated response to stranding events as well as training and capacity building in the SWIO region. The present analysis represents a first investigation of stranding data collected by various members and collaborators within the IndoCet network, covering over 14,800km of coastline belonging to nine countries/territories. Between 2000–2020, there were 397 stranding events, representing 1,232 individual animals, 17 genera and 27 species, belonging to six families: four balaenopterids, one balaenid, one physeterid, two kogiids, six ziphiids and 14 delphinids. Seven mass strandings were recorded: two were composed of three to 20 individuals and five composed of > 20 individuals. Spatial analysis of stranding events indicated that local spatio-temporal clusters (excessive number of events in time and geographic space) were present in all countries/territories, except for the Comoros. The only significant cluster was detected on the southwest coast of Mauritius, just west of the village of Souillac. The SWIO region predominantly comprises relatively poor countries/territories, but imminent Ocean Economy developments are prevalent throughout the region. This study highlights the importance of establishing baselines upon which any future potential impact from anthropogenic developments in the region can be measured.Peer reviewe

Lesson learned from early and long-term results of 327 cases of coexisting surgical abdominal diseases and aortic aneurysms treated in open and endovascular surgery

Patients with abdominal aortic aneurysm (AAA) frequently have other abdominal pathologies of surgical interest (other diseases, OD). Out of 1,375 elective open aortic replacements for AAA, 315 cases with OD were subdivided in Group 1 (82 patients with “clean wound” OD) and Group 2 (233 patients with “clean-contaminated wound” OD). The results of the sub-groups in which OD was treated at the same time as AAA were analysed (1a, 66 cases and 2a, 86 cases) and compared with OD not treated at the same time as AAA (1b, 16 cases and 2b, 147 cases). EVAR was done in 12 patients with a infrarenal AAA and concomitant abdominal disease. In this group post-operative complications occured in two patients (endoleaks) and no sign of endograft infection was developed. Mean follow-up was 36 months. Mortality was 0% in Group 1a, 1b, 2b and 5.8% in Group 2a. In Group 1a there were one haemoperitoneum, one ischaemic colitis and one graft infection. In Group 1b there were 4 nefrectomies for renal carcinoma and three emergency hernia repairs within 18 months from AAA operation. In Group 2a the follow-up was uneventful. In Group 2b there was no acute complication of OD and 57.2% of patients were subsequently operated for OD. In the EVAR group the 30-day and late mortality rates were 0 and 25%, respectively and all deaths were cancer-related. Contemporary correction of OD in open surgery for AAA should be performed in clean wound cases, while clean-contaminated operations can be done only in selected cases. EVAR is a valid alternative technique to open vascular surgery for the concomitant treatment of aortic aneurysms and abdominal pathologies

Heart rate variability in non-apneic snorers and controls before and after continuous positive airway pressure

BACKGROUND: We hypothesized that sympathetic nervous system activity (SNSA) is increased and parasympathetic nervous system activity (PNSA) is decreased during non-rapid eye movement (NREM) sleep in non-apneic, otherwise healthy, snoring individuals compared to control. Moreover, we hypothesized that these alterations in snoring individuals would be more evident during non-snoring than snoring when compared to control. METHODS: To test these hypotheses, heart rate variability was used to measure PNSA and SNSA in 11 normotensive non-apneic snorers and 12 control subjects before and 7-days after adapting to nasal continuous positive airway pressure (nCPAP). RESULTS: Our results showed that SNSA was increased and PNSA was decreased in non-apneic snorers during NREM compared to control. However, these changes were only evident during the study in which snoring was eliminated with nCPAP. Conversely, during periods of snoring SNSA and PNSA were similar to measures obtained from the control group. Additionally, within the control group, SNSA and PNSA did not vary before and after nCPAP application. CONCLUSION: Our findings suggest that long-lasting alterations in autonomic function may exist in snoring subjects that are otherwise healthy. Moreover, we speculate that because of competing inputs (i.e. inhibitory versus excitatory inputs) to the autonomic nervous system during snoring, the full impact of snoring on autonomic function is most evident during non-snoring periods