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Photocatalysis provides a sustainable approach for on‐site production of H2O2, yet single‐phase systems generally display unsatisfactory efficiency and low concentration of H2O2 due to rapid reverse reactions and dissociation of H2O2. Multiphase systems are developed to yield aqueous H2O2 via oxygen reduction by employing hydrophobic photocatalysts, however, the low solubility of oxygen and the possible dissociation of generated H2O2 result in a limited improvement in catalytic performances. Herein, a lauric acid (LA)‒n‐dodecyltrimethoxysilane (DTMS) dual‐emulsifier coated Pd/TiO2 (LD‐Pd/TiO2) is constructed for the synthesis of H2O2 in a water‐nonane system via water oxidation with quintozene as an insoluble hydrogen acceptor in water. While DTMS in the composite coating quenches the decomposition of H2O2, LA facilitates the enrichment of quintozene near the Pd/TiO2 for a rapid consumption of hydrogen atoms. The LD‐Pd/TiO2 leads to a remarkable H2O2 concentration of 133 mM with decent stability and a high quantum efficiency (6.5% at 365 nm). Additionally, the system can be demulsified gently after reaction, obtaining aqueous H2O2 solution and oil phase with hydrogenated products for simple separation and collection. A dual‐emulsifier coated photocatalyst facilitates efficient synthesis of H2O2 in water and the hydrogenation in oil via water dissociation.

BACKGROUND: Congenital cholesteatomas account for just up to 5% of all cholesteatomas and most commonly arise in the petrous apex and middle ear. Congenital cholesteatomas arising in the mastoid are rare and typically present late. METHODS: In this study, we report a case series of 3 cases managed in our department between 2006 and 2021 and present a summary of the current literature. RESULTS: Congenital cholesteatomas arising in the mastoid is a rare finding and even among reported cases, not all are clearly mastoid in origin. Their location allows for considerable growth before symptoms develop. Pain and localized swelling in the temporal area are the most common presenting symptoms which can lead to diagnostic challenges. Our cases show that although surgery is often appropriate, conservative management may be suitable in certain situations. CONCLUSION: Congenital cholesteatoma of mastoid origin is rare and can present a diagnostic challenge. Greater awareness is important to facilitate early detection. A high index of suspicion is needed in those presenting with retro-auricular pain and swelling in the context of a normal ontological examination. KEYWORDS: Congenital cholesteatoma, ear surgery, otology, temporal bone

Hydrogen peroxide (H2O2) is an important chemical in synthetic chemistry with huge demands. Photocatalytic synthesis of H2O2 via oxygen reduction and water oxidation reactions (ORR and WOR) is considered as a promising and desirable solution for on‐site applications. However, the efficiency of such a process is low due to the poor solubility of molecular oxygen and the rapid reverse reaction of hydroxyl radicals (•OH) with hydrogen atoms (H). Here, a strategy is proposed to boost the H2O2 evolution via oxidation of water by employing a H acceptor (A, nitrocyclohexane), an •OH mediator (M, dioxane), and a photocatalyst (CdS nanosheets). While •OH radicals are stabilized by dioxane to produce ketyl radicals prior to the formation of H2O2, H atoms are effectively utilized in the generation of cyclohexanone oxime, an important intermediate in the production of Nylon 6. The system displays a rapid kinetic accumulation of H2O2 (0.13 min−1) to a high concentration (6.6 mM). At optimum reaction conditions, a high quantum efficiency (16.6%) and light‐to‐chemical conversion efficiency (4.9%) can be achieved under 410 nm irradiation. Photocatalytic partial water oxidation promoted by a hydrogen acceptor (A) and a hydroxyl mediator (M) couple on CdS nanosheets. While the photogenerated •OH radicals can be stabilized by M to produce ketyl radicals prior to the formation of H2O2, H atoms are transferred to A. This strategy enables a rapid evolution of H2O2 with a high quantum efficiency (16.6%) under visible light irradiation.

Background The symptoms of Clostridium difficile infection are mediated primarily by two toxins, TcdA and TcdB, the expression of which is governed by a multitude of factors including nutrient availability, growth phase and cell stress. Several global regulators have been implicated in the regulation of toxin expression, such as CcpA and CodY. Results During attempts to insertionally inactivate a putative secondary cell wall polysaccharide synthesis gene, we obtained several mutants containing off-target insertions. One mutant displayed an unusual branched colony morphology and was investigated further. Marker recovery revealed an insertion in mfd, a gene encoding a transcription-coupled repair factor. The mfd mutant exhibited pleiotropic effects, in particular increased expression of both toxin A and B (TcdA and TcdB) compared to the parental strain. Western blotting and cellular cytotoxicity assays revealed increased expression across all time points over a 24 h period, with inactivation of mfd resulting in at least a 10 fold increase in cell cytotoxicity. qRT-PCR demonstrated the upregulation of both toxins occurred on a transcriptional level. All effects of the mfd mutation were complemented by a plasmid-encoded copy of mfd , showing the effects are not due to polar effects of the intron insertion or to second site mutations. Conclusions This study adds Mfd to the repertoire of factors involved in regulation of toxin expression in Clostridium difficile . Mfd is known to remove RNA polymerase molecules from transcriptional sites where it has stalled due to repressor action, preventing transcriptional read through. The consistently high levels of toxin in the C. difficile mfd mutant indicate this process is inefficient leading to transcriptional de-repression.

Age-related decline in information processing can have a substantial impact on activities such as driving. However, the assessment of these changes is often carried out using cognitive tasks that do not adequately represent the dynamic process of updating environmental stimuli. Equally, traditional tests are often static in their approach to task complexity, and do not assess difficulty within the bounds of an individual’s capability. To address these limitations, we used a more ecologically valid measure, the Swansea Test of Attentional Control (STAC), in which a threshold for information processing speed is established at a given level of accuracy. We aimed to delineate how older, compared to younger, adults varied in their performance of the task, while also assessing relationships between the task outcome and gender, general cognition (MoCA), perceived memory function (MFQ), cognitive reserve (NART), and aspects of mood (PHQ-9, GAD-7). The results indicate that older adults were significantly slower than younger adults but no less precise, irrespective of gender. Age was negatively correlated with the speed of task performance. Our measure of general cognition was positively correlated with the task speed threshold but not with age per se. Perceived memory function, cognitive reserve, and mood were not related to task performance. The findings indicate that while attentional control is less efficient in older adulthood, age alone is not a defining factor in relation to accuracy. In a real-life context, general cognitive function, in conjunction with dynamic measures such as STAC, may represent a far more effective strategy for assessing the complex executive functions underlying driving ability.

Workshops using arts and board games are forms of non-pharmacological intervention widely employed in seniors with neurocognitive disorders. However, clear guidelines on how to conduct these workshops are missing. The objective of the Art and Game project (AGAP) was to draft recommendations on the structure and content of workshops for elderly people with neurocognitive disorders and healthy seniors, with a particular focus on remote/hybrid workshops, in which at least a part of the participants is connected remotely. Recommendations were gathered using a Delphi methodology. The expert panel (N= 18) included experts in the health, art and/or board games domains. They answered questions via two rounds of web-surveys, and then discussed the results in a plenary meeting. Some of the questions were also shared with the general public (N=101). Both the experts and the general public suggested that organizing workshops in a hybrid format (some face-to-face sessions, some virtual session) is feasible and interesting for people with neurocognitive disorders. We reported guidelines on the overall structure of workshops, practical tips on how to organize remote workshops, and a SWOT analysis of the use of remote/hybrid workshops. The guidelines may be employed by clinicians to decide, based on their needs and constraints, what interventions and what kind of workshop format to employ, as well as by researchers to standardize procedures to assess the effectiveness of non-pharmacological treatments for people with neurocognitive disorders.

Temporal bone osteoradionecrosis is a rare but significant complication of radiation for head and neck malignancies. Various management techniques have been described, but no clear protocol exists. A retrospective case review of patients with temporal bone osteoradionecrosis managed over 15 years was carried out to highlight multidisciplinary team (MDT) management. The review findings were compared with the published literature and a protocol was derived for the management of future cases. A total of 20 patients were included. The sites of osteoradionecrosis included the external auditory canal, the middle ear and the lateral skull base, presenting with features including recalcitrant pain, infection, neuropathies and intracranial sepsis. Treatments included hyperbaric oxygen, antibiotics, debridement and, in advanced cases, lateral temporal bone resection with vascularised tissue transfer. Post-operative and long-term outcomes were discussed. Early temporal bone osteoradionecrosis may be managed conservatively. Refractory osteoradionecrosis can be life-threatening because of intracranial complications and sepsis. Such cases need an MDT approach with radical skull-base surgery for removal of necrotic foci and reconstruction using vascularised tissue transfer.

ObjectiveTo assess the perceived benefits of a novel educational approach for otolaryngology trainees: a virtual reality temporal bone simulator drilling competition.MethodsRegional otolaryngology trainees participated in the competition. Drilling activities using the Voxel-Man TempoSurg simulator were scored by experts. Questionnaires that contained questions covering motivators for attending, perceived learning and enjoyment were sent to participants. Agreement with statements was measured on a 10-point Likert scale (1 = strongly disagree, 10 = strongly agree).ResultsEighteen trainees participated. The most cited reason for attending was for learning and/or education (61 per cent), with most attendees (72 per cent) believing that competition encourages more reading and/or practice. Seventeen attendees (94 per cent) believed Voxel-Man TempoSurg-based simulation would help to improve intra-operative performance in mastoidectomy (mean 7.83 ± 1.47, p < 0.001) and understanding of anatomy (mean 8.72 ± 1.13, p < 0.001). All participants rated the competition as ‘fun’ and 83 per cent believed the competitive element added to this.ConclusionThe virtual reality temporal bone competition is a novel educational approach within otolaryngology that was positively received by otolaryngology trainees.

Cerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack. Our observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316. Between Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0–20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1–5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27–10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29–0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53–0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60–0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07–0·43, p=0·0065; and 0·33, 0·14–0·51, p=0·00059, respectively). In patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from oral anticoagulation. The Stroke Association and the British Heart Foundation.

Oral anticoagulation reduces the rate of systemic embolism for patients with atrial fibrillation by two-thirds, but its benefits for patients with previous intracranial haemorrhage are uncertain. In the Start or STop Anticoagulants Randomised Trial (SoSTART), we aimed to establish whether starting is non-inferior to avoiding oral anticoagulation for survivors of intracranial haemorrhage who have atrial fibrillation. SoSTART was a prospective, randomised, open-label, assessor-masked, parallel-group, pilot phase trial done at 67 hospitals in the UK. We recruited adults (aged ≥18 years) who had survived at least 24 h after symptomatic spontaneous intracranial haemorrhage, had atrial fibrillation, and had a CHA2DS2-VASc score of at least 2. Web-based computerised randomisation incorporating a minimisation algorithm allocated participants (1:1) to start or avoid long-term (≥1 year) full treatment dose open-label oral anticoagulation. The participants assigned to start oral anticoagulation received either a direct oral anticoagulant or vitamin K antagonist, and the group assigned to avoid oral anticoagulation received standard clinical practice (antiplatelet agent or no antithrombotic agent). The primary outcome was recurrent symptomatic spontaneous intracranial haemorrhage, and was adjudicated by an individual masked to treatment allocation. All outcomes were ascertained for at least 1 year after randomisation and assessed in the intention-to-treat population of all randomly assigned participants, using Cox proportional hazards regression adjusted for minimisation covariates. We planned a sample size of 190 participants (one-sided p=0·025, power 90%, allowing for non-adherence) based on a non-inferiority margin of 12% (or adjusted hazard ratio [HR] of 3·2). This trial is registered with ClinicalTrials.gov (NCT03153150) and is complete. Between March 29, 2018, and Feb 27, 2020, consent was obtained at 61 sites for 218 participants, of whom 203 were randomly assigned at a median of 115 days (IQR 49–265) after intracranial haemorrhage onset. 101 were assigned to start and 102 to avoid oral anticoagulation. Participants were followed up for median of 1·2 years (IQR 0·97–1·95; completeness 97·2%). Starting oral anticoagulation was not non-inferior to avoiding oral anticoagulation: eight (8%) of 101 in the start group versus four (4%) of 102 in the avoid group had intracranial haemorrhage recurrences (adjusted HR 2·42 [95% CI 0·72–8·09]; p=0·152). Serious adverse events occurred in 17 (17%) participants in the start group and 15 (15%) in the avoid group. 22 (22%) patients in the start group and 11 (11%) patients in the avoid group died during the study. Whether starting oral anticoagulation was non-inferior to avoiding it for people with atrial fibrillation after intracranial haemorrhage was inconclusive, although rates of recurrent intracranial haemorrhage were lower than expected. In view of weak evidence from analyses of three composite secondary outcomes, the possibility that oral anticoagulation might be superior for preventing symptomatic major vascular events should be investigated in adequately powered randomised trials. British Heart Foundation, Medical Research Council, Chest Heart & Stroke Scotland.