Direct and Inverse Results on Bounded Domains for Meshless Methods via Localized Bases on Manifolds

This article develops direct and inverse estimates for certain finite dimensional spaces arising in kernel approximation. Both the direct and inverse estimates are based on approximation spaces spanned by local Lagrange functions which are spatially highly localized. The construction of such functions is computationally efficient and generalizes the construction given by the authors for restricted surface splines on $\mathbb{R}^d$. The kernels for which the theory applies includes the Sobolev-Mat\'ern kernels for closed, compact, connected, $C^\infty$ Riemannian manifolds.Comment: 29 pages. To appear in Festschrift for the 80th Birthday of Ian Sloa

The Vesicle Priming Factor CAPS Functions as a Homodimer via C2 Domain Interactions to Promote Regulated Vesicle Exocytosis.

Neurotransmitters and peptide hormones are secreted by regulated vesicle exocytosis. CAPS (also known as CADPS) is a 145-kDa cytosolic and peripheral membrane protein required for vesicle docking and priming steps that precede Ca2+-triggered vesicle exocytosis. CAPS binds phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and SNARE proteins and is proposed to promote SNARE protein complex assembly for vesicle docking and priming. We characterized purified soluble CAPS as mainly monomer in equilibrium with small amounts of dimer. However, the active form of CAPS bound to PC12 cell membranes or to liposomes containing PI(4,5)P2 and Q-SNARE proteins was mainly dimer. CAPS dimer formation required its C2 domain based on mutation or deletion studies. Moreover, C2 domain mutations or deletions resulted in a loss of CAPS function in regulated vesicle exocytosis, indicating that dimerization is essential for CAPS function. Comparison of the CAPS C2 domain to a structurally defined Munc13-1 C2A domain dimer revealed conserved residues involved in CAPS dimerization. We conclude that CAPS functions as a C2 domain-mediated dimer in regulated vesicle exocytosis. The unique tandem C2-PH domain of CAPS may serve as a PI(4,5)P2-triggered switch for dimerization. CAPS dimerization may be coupled to oligomeric SNARE complex assembly for vesicle docking and priming

Assessment of potential cardiotoxic side effects of mitoxantrone in patients with multiple sclerosis

Previous studies showed that mitoxantrone can reduce disability progression in patients with multiple sclerosis (MS). There is, however, concern that it may cause irreversible cardiomyopathy with reduced left ventricular (LV) ejection fraction (EF) and congestive heart failure. The aim of this prospective study was to investigate cardiac side effects of mitoxantrone by repetitive cardiac monitoring in MS patients. The treatment protocol called for ten courses of a combined mitoxantrone (10 mg/m(2) body surface) and methylprednisolone therapy. Before each course, a transthoracic echocardiogram was performed to determine the LV end-diastolic diameter, the end-systolic diameter and the fractional shortening; the LV-EF was calculated. Seventy-three patients participated (32 males; age 48 +/- 12 years, range 20-75 years; 25 with primary progressive, 47 with secondary progressive and 1 with relapsing-remitting MS) who received at least four courses of mitoxantrone. Three of the 73 patients were excluded during the study (2 patients discontinued therapy; 1 patient with a previous history of ischemic heart disease developed atrial fibrillation after the second course of mitoxantrone). The mean cumulative dose of mitoxantrone was 114.0 +/- 33.8 mg. The mean follow-up time was 23.4 months (range 10-57 months). So far, there has been no significant change in any of the determined parameters (end-diastolic diameter, end-systolic diameter, fractional shortening, EF) over time during all follow-up investigations. Mitoxantrone did not cause signs of congestive heart failure in any of the patients. Further cardiac monitoring is, however, needed to determine the safety of mitoxantrone after longer follow-up times and at higher cumulative doses. Copyright (C) 2005 S. Karger AG, Basel

Cardiopulmonary exercise testing before and after intravenous iron in preoperative patients: a prospective clinical study

Background: Anemia is associated with impaired physical performance and adverse perioperative outcomes. Iron-deficiency anemia is increasingly treated with intravenous iron before elective surgery. We explored the relationship between exercise capacity, anemia, and total hemoglobin mass (tHb-mass) and the response to intravenous iron in anemic patients prior to surgery.// Methods: A prospective clinical study was undertaken in patients having routine cardiopulmonary exercise testing (CPET) with a hemoglobin concentration ([Hb]) < 130 g.l⁻¹ and iron deficiency/depletion. Patients underwent CPET and tHb-mass measurements before and a minimum of 14 days after receiving intravenous (i.v.) Ferric derisomaltose (Monofer®) at the baseline visit. Comparative analysis of hematological and CPET variables was performed pre and post-iron treatment.// Results: Twenty-six subjects were recruited, of whom 6 withdrew prior to study completion. The remaining 20 (9 [45%] male; mean ± SD age 68 ± 10 years) were assessed 25 ± 7 days between baseline and the final visit. Following i.v. iron, increases were seen in [Hb] (mean ± SD) from 109 ± 14 to 116 ± 12 g l⁻¹ (mean rise 6.4% or 7.3 g l⁻¹, p =  < 0.0001, 95% CI 4.5–10.1); tHb-mass from 497 ± 134 to 546 ± 139 g (mean rise 9.3% or 49 g, p =  < 0.0001, 95% CI 29.4–69.2). Oxygen consumption at anerobic threshold (V˙O2 AT) did not change (9.1 ± 1.7 to 9.8 ± 2.5 ml kg⁻¹ min⁻¹, p = 0.09, 95% CI − 0.13 − 1.3). Peak oxygen consumption (V˙O2 peak) increased from 15.2 ± 4.1 to 16 ± 4.4 ml.kg.⁻¹ min⁻¹, p = 0.02, 95% CI 0.2–1.8) and peak work rate increased from 93 [67–112] watts to 96 [68–122] watts (p = 0.02, 95% CI 1.3–10.8).// Conclusion: Preoperative administration of intravenous iron to iron-deficient/deplete anemic patients is associated with increases in [Hb], tHb-mass, peak oxygen consumption, and peak work rate. Further appropriately powered prospective studies are required to ascertain whether improvements in tHb-mass and performance in turn lead to reductions in perioperative morbidity

A behavioural intervention increases physical activity in people with subacute spinal cord injury: a randomised trial

AbstractQuestions: For people with subacute spinal cord injury, does rehabilitation that is reinforced with the addition of a behavioural intervention to promote physical activity lead to a more active lifestyle than rehabilitation alone? Design: Randomised, controlled trial with concealed allocation, intention-to-treat analysis, and blinded assessors. Participants: Forty-five adults with subacute spinal cord injury who were undergoing inpatient rehabilitation and were dependent on a manual wheelchair. The spinal cord injuries were characterised as: tetraplegia 33%; motor complete 62%; mean time since injury 150 days (SD 74). Intervention: All participants received regular rehabilitation, including handcycle training. Only the experimental group received a behavioural intervention promoting an active lifestyle after discharge. This intervention involved 13 individual sessions delivered by a coach who was trained in motivational interviewing; it began 2 months before and ended 6 months after discharge from inpatient rehabilitation. Outcome measures: The primary outcome was physical activity, which was objectively measured with an accelerometer-based activity monitor 2 months before discharge, at discharge, and 6 and 12 months after discharge from inpatient rehabilitation. The accelerometry data were analysed as total wheeled physical activity, sedentary time and motility. Self-reported physical activity was a secondary outcome. Results: The behavioural intervention significantly increased wheeled physical activity (overall between-group difference from generalised estimating equation 21minutes per day, 95% CI 8 to 35). This difference was evident 6 months after discharge (28minutes per day, 95% CI 8 to 48) and maintained at 12 months after discharge (25minutes per day, 95% CI 1 to 50). No significant intervention effect was found for sedentary time or motility. Self-reported physical activity also significantly improved. Conclusion: The behavioural intervention was effective in eliciting a behavioural change toward a more active lifestyle among people with subacute spinal cord injury. Trial registration: NTR2424. [Nooijen CFJ, Stam H, Bergen MP, Bongers-Janssen HMH, Valent L, van Langeveld S, Twisk J, Act-Active Research Group, van den Berg-Emons RJG (2016) A behavioural intervention increases physical activity in people with subacute spinal cord injury: a randomised trial. Journal of Physiotherapy 62: 35–41

Bacterial porin disrupts mitochondrial membrane potential and sensitizes host cells to apoptosis

The bacterial PorB porin, an ATP-binding beta-barrel protein of pathogenic Neisseria gonorrhoeae, triggers host cell apoptosis by an unknown mechanism. PorB is targeted to and imported by host cell mitochondria, causing the breakdown of the mitochondrial membrane potential (delta psi m). Here, we show that PorB induces the condensation of the mitochondrial matrix and the loss of cristae structures, sensitizing cells to the induction of apoptosis via signaling pathways activated by BH3-only proteins. PorB is imported into mitochondria through the general translocase TOM but, unexpectedly, is not recognized by the SAM sorting machinery, usually required for the assembly of beta-barrel proteins in the mitochondrial outer membrane. PorB integrates into the mitochondrial inner membrane, leading to the breakdown of delta psi m. The PorB channel is regulated by nucleotides and an isogenic PorB mutant defective in ATP-binding failed to induce delta psi m loss and apoptosis, demonstrating that dissipation of delta psi m is a requirement for cell death caused by neisserial infection

Perceptions, Barriers, and Enablers on Salt Reduction in the Out-of-Home Sectors in Malaysia (MySaltOH) from the Perspective of Street Food Vendors, Caterers, and Consumers.

OBJECTIVE: To explore the perspectives, barriers, and enablers on salt reduction in out-of-home sectors in Malaysia among street food vendors, caterers, and consumers. DESIGN: A qualitative study involving 22 focus group discussions and six in-depth interviews was conducted, recorded and transcribed verbatim. An inductive thematic analysis approach was employed to analyze the data. SETTING: Two in-depth interviews and 22 focus group discussions were conducted face-to-face. Four in-depth interviews were conducted online. PARTICIPANTS: Focus group discussions were conducted among 23 street food vendors, 21 caterers, and 76 consumers of various eateries. In-depth interviews were conducted among two street food vendors, and four caterers, individually. RESULTS: Consumers and food operators perceived a high salt intake within Malaysia's out-of-home food sectors. Food operators emphasized the necessity for a comprehensive salt reduction policy in the out-of-home sector involving all stakeholders. Consumers faced limited awareness and knowledge, counterproductive practices among food operators, and challenges in accessing affordable low-sodium food products; whereas food operators faced the lack of standardized guidelines and effective enforcement mechanisms, and uncooperative consumer practices. Both groups expressed that food quality and price of salt were also the barriers, and they advocated for awareness promotion, enhanced regulation of manufactured food products, and stricter enforcement targeting vendors. Consumers also suggested promoting and recognizing health-conscious food premises; whereas food operators suggested on knowledge enhancement tailored to them, strategies for gaining consumers acceptance, and maintaining food quality. CONCLUSIONS: These findings provide valuable insights that serve as foundational evidence for developing and implementing salt reduction policies within Malaysia's out-of-home sectors

Contemporary Evolutionary Divergence for a Protected Species following Assisted Colonization

Contemporary evolution following assisted colonization may increase the probability of persistence for refuge populations established as a bet-hedge for protected species. Such refuge populations are considered "genetic replicates" that might be used for future re-colonization in the event of a catastrophe in the native site. Although maladaptive evolutionary divergence of captive populations is well recognized, evolutionary divergence of wild refuge populations may also occur on contemporary time scales. Thus, refuge populations may lose their "value" as true genetic replicates of the native population. Here, we show contemporary evolutionary divergence in body shape in an approximately 30-year old refuge population of the protected White Sands pupfish (Cyprinodon tularosa) resulting in a body-shape mismatch with its native environment.Geometric morphometic data were collected from C. tularosa cultures raised in experimental mesocosms. Cultures were initiated with fish from the two native populations, plus hybrids, in high or low salinity treatments representing the salinities of the two native habitats. We found that body shape was heritable and that shape variation due to phenotypic plasticity was small compared to shape variation due to population source. C. tularosa from the high salinity population retained slender body shapes and fish from the low salinity population retained deep body shapes, irrespective of mesocosm salinity. These data suggest that the observed divergence of a recently established pupfish population was not explained by plasticity. An analysis of microsatellite variation indicated that no significant genetic drift occurred in the refuge population, further supporting the adaptive nature of changes in body shape. These lines of evidence suggest that body shape divergence of the refuge population reflects a case of contemporary evolution (over a 30-year period).These results suggest assisted colonization can introduce novel, and/or relaxed selection, and lead to unintended evolutionary divergence

Placement of an aortomonoiliac stent graft without femorofemoral revascularization in endovascular aneurysm repair: a case report

<p>Abstract</p> <p>Introduction</p> <p>Endovascular aortic repair, if technically feasible, is the treatment of choice for patients with a contained ruptured aortic aneurysm who are unfit for open surgery.</p> <p>Case presentation</p> <p>We report the case of an 80-year-old Caucasian man who presented with an unusually configured, symptomatic infrarenal aortic aneurysm. His aneurysm showed an erosion of the fourth lumbar vertebra and a severely arteriosclerotic pelvic axis. A high thigh amputation of his right leg had been performed 15 months previously. On his right side, occlusion of his external iliac artery, common femoral artery, and deep femoral artery had occurred. His aneurysm was treated by a left-sided aortomonoiliac stent graft without femorofemoral revascularization, resulting in occlusions of both internal iliac arteries. No ischemic symptoms appeared, although perfusion of his right side was maintained only over epigastric collaterals.</p> <p>Conclusions</p> <p>The placement of aortomonoiliac stent grafts for endovascular treatment of infrarenal aortic aneurysms without contralateral revascularization is a feasible treatment option in isolated cases. In this report, access problems and revascularization options in endovascular aneurysm repair are discussed.</p