How pain is controlled in endodontic therapy.

Endodontic therapy is often of concern to patients, frequently due either to the expectation, or experience of pain. Managing this pain before, throughout and after a procedure is not only beneficial to a patient but reflects upon their dentist. To achieve effective pain relief different methods of pain control, including a pharmacological plan and the use of anaesthetics, must be individually tailored for each patient alongside an appropriate diagnosis and treatment plan.

When is extra-anatomical bypass for the left subclavian artery required to prevent ischaemia after thoracic endovascular stent grafting?

INTRODUCTION: Thoracic endovascular aortic repair (TEVAR) has become an accepted treatment for thoracic aortic disease. However, the principal complications relate to coverage of the thoracic aortic wall and deliberate occlusion of aortic branches over a potentially long segment. Complications include risk of stroke, spinal cord ischaemia (SCI) and arterial insufficiency to the left arm (left arm ischaemia (LAI)). This study specifically scrutinised the development of SCI and LAI after TEVAR for interventions for thoracic aortic disease from 1999 to 2020. In particular, those who underwent extra-anatomical bypass (both immediate and late) were compared to the length of thoracic aortic coverage by the stent graft. MATERIALS AND METHODS: Ninety-eight patients underwent TEVAR. The presenting symptoms, pathology, procedural and follow-up data were collected prospectively with particular evidence of stroke, SCI and LAI both immediate onset and after 48 h of graft placement. RESULTS: Fifty underwent TEVAR for an aneurysm (thoracoabdominal aortic aneurysm), 22 for dissection, 19 for acute transection and 7 for intramural haematoma/pseudoaneurysm of the thoracic aorta. Twenty-nine (30%) required a debranching procedure to increase the proximal landing zone (1 aorto-carotid subclavian bypass, 10 carotid/carotid subclavian bypass and 18 carotid/subclavian bypass). Ten patients (10%) died within 30 days of TEVAR. Twenty-four grafts covered the left subclavian artery origin without a carotid/subclavian bypass. Five required a delayed carotid/subclavian bypass for LAI (4) and SCI (1). Six developed immediate signs of SCI after TEVAR and these 11 (group i) had a mean (SD) length of coverage of the thoracic aorta of 30.2 (10.6) cm compared to 21.5 (11.2) cm (group g) in those who had no LAI or SCI post TEVAR, p < 0.05. CONCLUSIONS: In this series, delayed carotid/subclavian bypass may be required for chronic arm ischaemia and less so for SCI. The length of coverage of thoracic aorta during TEVAR is a factor in the development of delayed SCI and LAI occurrence. Carotid subclavian bypass is required for certain patients undergoing TEVAR (particularly if greater than 20 cm of thoracic aorta is covered).

Tunnelled peritoneal drainage catheter placement for the palliative management of refractory ascites in patients with liver cirrhosis.

OBJECTIVE: Refractory ascites is an established indication for liver transplantation. While transplantation is regarded as the definitive therapy for this condition, many patients are unsuitable due to comorbidity or frailty. Alternatives such as transjugular intrahepatic portosystemic shunt (TIPSS) and large-volume paracentesis can lead to complications, including encephalopathy, circulatory and renal dysfunction, and protein-calorie deficiency that may accelerate sarcopenia. Cost and complication rates limit therapies such as alfapump. While there are data to support the use of indwelling catheters in the management of patients with malignant ascites, there is limited evidence to support their routine use in the context of end-stage liver cirrhosis. Here we describe our centres' experience using indwelling tunnelled ascitic drains over a 6-year period. METHODS: A retrospective review of data (January 2012-May 2018) was undertaken for all patients with refractory ascites who underwent a tunnelled ascitic drain. Demographics, disease aetiology, procedure data and follow-up data were obtained through interrogation of electronic records and reports. RESULTS: Twenty-five drains were placed. All procedures were technically successful with no immediate complications. Six patients were readmitted following their index admission with abdominal pain and suspected infected ascites (although only two had a positive ascitic fluid culture). There were three cases of abdominal wall cellulitis and three of leakage around the tunnel site; all managed conservatively. CONCLUSION: Indwelling drains appear an effective strategy for palliative management of select patients with liver cirrhosis complicated by refractory ascites who are not amenable to undergo TIPSS or transplantation. While complications can occur, these are most usually minor and can be managed on an outpatient basis.

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.

We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10-10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10-14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

Periodontitis and Cognitive Decline in Alzheimer's Disease.

Periodontitis is common in the elderly and may become more common in Alzheimer's disease because of a reduced ability to take care of oral hygiene as the disease progresses. Elevated antibodies to periodontal bacteria are associated with an increased systemic pro-inflammatory state. Elsewhere raised serum pro-inflammatory cytokines have been associated with an increased rate of cognitive decline in Alzheimer's disease. We hypothesized that periodontitis would be associated with increased dementia severity and a more rapid cognitive decline in Alzheimer's disease. We aimed to determine if periodontitis in Alzheimer's disease is associated with both increased dementia severity and cognitive decline, and an increased systemic pro inflammatory state. In a six month observational cohort study 60 community dwelling participants with mild to moderate Alzheimer's Disease were cognitively assessed and a blood sample taken for systemic inflammatory markers. Dental health was assessed by a dental hygienist, blind to cognitive outcomes. All assessments were repeated at six months. The presence of periodontitis at baseline was not related to baseline cognitive state but was associated with a six fold increase in the rate of cognitive decline as assessed by the ADAS-cog over a six month follow up period. Periodontitis at baseline was associated with a relative increase in the pro-inflammatory state over the six month follow up period. Our data showed that periodontitis is associated with an increase in cognitive decline in Alzheimer's Disease, independent to baseline cognitive state, which may be mediated through effects on systemic inflammation.

Etanercept in Alzheimer disease: A randomized, placebo-controlled, double-blind, phase 2 trial.

OBJECTIVES: To determine whether the tumor necrosis factor α inhibitor etanercept is well tolerated and obtain preliminary data on its safety in Alzheimer disease dementia. METHODS: In a double-blind study, patients with mild to moderate Alzheimer disease dementia were randomized (1:1) to subcutaneous etanercept (50 mg) once weekly or identical placebo over a 24-week period. Tolerability and safety of this medication was recorded including secondary outcomes of cognition, global function, behavior, and systemic cytokine levels at baseline, 12 weeks, 24 weeks, and following a 4-week washout period. This trial is registered with EudraCT (2009-013400-31) and ClinicalTrials.gov (NCT01068353). RESULTS: Forty-one participants (mean age 72.4 years; 61% men) were randomized to etanercept (n = 20) or placebo (n = 21). Etanercept was well tolerated; 90% of participants (18/20) completed the study compared with 71% (15/21) in the placebo group. Although infections were more common in the etanercept group, there were no serious adverse events or new safety concerns. While there were some interesting trends that favored etanercept, there were no statistically significant changes in cognition, behavior, or global function. CONCLUSIONS: This study showed that subcutaneous etanercept (50 mg/wk) was well tolerated in this small group of patients with Alzheimer disease dementia, but a larger more heterogeneous group needs to be tested before recommending its use for broader groups of patients. CLASSIFICATION OF EVIDENCE: This study shows Class I evidence that weekly subcutaneous etanercept is well tolerated in Alzheimer disease dementia.

Rhodium catalysed dehydrogenative borylation of vinylarenes and 1,1-disubstituted alkenes without sacrificial hydrogenation--a route to 1,1-disubstituted vinylboronates.

The complex trans-[Rh(Cl)(CO)(PPh3)2] (1) is an efficient catalyst precursor for the dehydrogenative borylation of alkenes without consumption of half the alkene substrate by hydrogenation, giving useful vinylboronate esters including 1,1-disubstituted derviatives that cannot be made by alkyne hydroboration.

Rhodium catalysed dehydrogenative borylation of alkenes: vinylboronates via C-H activation.

We present herein a high yield, highly selective catalytic synthesis of vinylboronate esters (VBEs), including 1,1-disubstituted VBEs, from alkenes without significant hydrogenation or hydroboration, using the simple catalyst precursor, trans-[RhCl(CO)(PPh3)2] (1), and the diboron reagents B2pin2 (2a, pin = pinacolato = OCMe2CMe2O) or B2neop2 (2b, neop = neopentylglycolato = OCH2CMe2CH2O), or the monoboron reagent HBpin, all of which are commercially available. The reactions were conducted at 80 degrees C using conventional heating, or in a microwave reactor at 150 degrees C.

Elements of a cost-benefit analysis for improving salmonid spawning habitat in the River Wye.

Contingent valuation methods were used to derive an economic value for salmonid spawning habitat restoration. Anglers' willingness to pay for such restoration and farmers' willingness to accept compensation for lost productivity due to the restoration were investigated using questionnaire and face-to-face surveys, respectively. These elements were combined with the Wye Habitat Improvement Project (WHIP) budget into a cost-benefit analysis (CBA) based upon direct use values only. The CBA assumed that the WHIP will improve salmonid stock. Different levels of investment were considered and the CBA gave a positive net present value indicating an economically viable project and benefit-to-cost ratios greater than one for minor projects. However, the number of anglers using the Wye would need to double or triple in order to justify the full WHIP budget. Management of an environmental resource must consider users' and stakeholders' needs and opinions. It was found that anglers on the Wye value habitat/scenery in its own right and that this played an important part in the activity. Farmers' agreement regarding involvement in such projects was more likely to be determined by their political and ethical views than receiving an economic compensation.

Formation of metallaboranes from the group IV transition metals and pentaborane(9): crystal and molecular structure of [(Cp(2)Zr)(2)B(5)H(8)][B(11)H(14)].

The reactions between [(C(5)H(5))(2)MCl(2)] (where M = Ti, Zr, Hf) and Li[B(5)H(8)] in a variety of solvents have been investigated. In the case of Zr, a pale orange solid, mu-(Cp(2)ClZr)B(5)H(8) (1), is formed in 70% yield. Compound 1 exists as a B(5)H(9) cage with a Cp(2)ClZr moiety replacing a bridging H atom. The variable temperature NMR spectra of 1 reveal two fluxional processes, one (DeltaG(++) = 54 kJ mol(-1)) which renders a plane of symmetry in the molecule and a higher temperature one (DeltaG(++) = 48 kJ mol(-1)) which renders all the basal B atoms equivalent. Dynamic processes are suggested to account for these observations. Passage of a CH(2)Cl(2) solution of 1 through silica gel affords 2, [(Cp(2)Zr)(2)B(5)H(8)][B(11)H(14)], a yellow, air-stable, crystalline solid, in 14% yield. The cation in 2, [(Cp(2)Zr)(2)B(5)H(8)](+), consists of a distorted spiro[2.2]pentane-like B(5) moiety comprising two B(3) triangles sharing a naked boron vertex. The two triangles are twisted 73 degrees with respect to each other, and the two [Cp(2)Zr] groups bond in a trihapto arrangement to the two opposite B-B-B edges. Each exterior B-Zr edge is H-bridged, and the B atoms possess terminal hydrogens. Reactions of Cp(2)HfCl(2) with Li[B(5)H(8)] lead to the formation of the analogue of 2, [(Cp(2)Hf)(2)B(5)H(8)][B(11)H(14)] (3). The precursor to 3, that is, the Hf analogue of 1, is not observed. Reaction between Li[B(5)H(8)] and Cp(2)TiCl(2) afforded no identifiable products, but reaction with CpTiCl(3) resulted in cage coupling and the formation of B(10)H(14).

Chromium speciation and fractionation in ground and surface waters in the vicinity of chromite ore processing residue disposal sites.

Chromium concentrations of up to 91 mg l(-1) were found by ICP-OES for ground water from nine boreholes at four landfill sites in an area of S.E. Glasgow/S. Lanarkshire where high-lime chromite ore processing residue (COPR) from a local chemical works had been deposited from 1830 to 1968. Surface water concentrations of up to 6.7 mg l(-1) in a local tributary stream fell to 0.11 mg l(-1) in the River Clyde. Two independent techniques of complexation/colorimetry and speciated isotope dilution mass spectrometry (SIDMS) showed that Cr was predominantly (>90%) in hexavalent form (CrVI) as CrO4(2-), as anticipated at the high pH (7.5-12.5) of the sites. Some differences between the implied and directly determined concentrations of dissolved CrIII, however, appeared related to the total organic carbon (TOC) content. This was most significant for the ground water from one borehole that had the highest TOC concentration of 300 mg l(-1) and at which < 3% of Cr was in the form of CrVI. Subsequent ultrafiltration produced significant decreases in Cr concentration with decreasing size fractions, e.g. <0.45 microm, < 100 kDa, <30 kDa and < 1 kDa by the tangential-flow method. As this appeared related more to concentrations of humic substances than of TOC per se, horizontal bed gel electrophoresis of freeze-dried ultrafilter retentates was carried out to further characterise the CrIII-organic complex. This showed for the main Cr-containing fraction, 100 kDa-0.45 microm, that the Cr was associated with a dark brown band characteristic of organic (humic) matter. Comparison of gel electrophoresis and FTIR results for ultrafilter retentates of ground water from this borehole with those for a borehole at another site where CrVI predominated suggested the influence of carboxylate groups, both in reducing CrVI and in forming soluble CrIII-humic complexes. The implications of this for remediation strategies (especially those based on the addition of organic matter) designed to reduce highly mobile and carcinogenic Cr(VI)O4(2-) to the much less harmful CrIII as insoluble Cr(OH)3 are discussed.

Chromium remediation or release? Effect of iron(II) sulfate addition on chromium(VI) leaching from columns of chromite ore processing residue.

Chromite ore processing residue (COPR), derived from the so-called high lime processing of chromite ore, contains high levels of Cr(III) and Cr(VI) and has a pH between 11 and 12. Ferrous sulfate, which is used for remediation of Cr(VI) contamination in wastewater and soils via reduction to Cr(III) and subsequent precipitation of iron(III)/chromium(III) hydroxide, has also been proposed for remediation of Cr(VI) in COPR. Instead, however, addition of FeSO4 to the infiltrating solution in column experiments with COPR greatly increased leaching of Cr(VI). Leached Cr(VI) increased from 3.8 to 12.3 mmol kg(-1) COPR in 25 pore volumes with 20 mM FeSO4, reaching solution concentrations as high as 1.6 mM. Fe(II) was ineffective in reducing Cr(VI) to Cr(III) because it precipitated when it entered the column due to the high pH of COPR, while Cr(VI) in solution was transported away with the infiltrating solution. The large increase in leaching of Cr(VI) upon infiltration of sulfate, either as FeSO4 or Na2SO4, was caused by anion exchange of sulfate for chromate in the layered double hydroxide mineral hydrocalumite, a process for which scanning electron microscopy with energy-dispersive X-ray microanalysis provided direct evidence.