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Gerwyn Jones and colleagues describe how service users were encouraged and supported by mental health staff and partner organisations to tell their personal stories about recovery from psychosis. The project culminated in a joint conference presentation. [ABSTRACT FROM AUTHOR]

Background: Fatigue is a multidimensional condition that may overlap with depression. Initial studies found that fatigue responds in only a limited way to standard monoaminergic antidepressants and mood stabilizers but does respond positively to intravenous (IV) racemic (R,S)-ketamine (ketamine). However, IV ketamine's use is limited by cost and access barriers. To date, no study has evaluated intranasal (IN) ketamine in individuals with fatigue. This study sought to evaluate the anti-fatigue effects of a single 50 mg dose of IN ketamine in individuals with major depressive disorder (MDD) or bipolar depression (BDep), both with and without comorbid alcohol use disorder (AUD)., Methods: Twenty-eight individuals with primary diagnoses of MDD or BDep I/II currently experiencing a depressive episode with active suicidality were enrolled; approximately 60 % had comorbid AUD. Changes in the NIH-Brief Fatigue Inventory (NIH-BFI) were assessed at baseline and at 4, 24, and 48 h post-treatment., Results: The group x time interaction for NIH-BFI score was significant (F = 3.44, p = 0.022), favoring IN ketamine over placebo. IN ketamine was well-tolerated with minimal adverse effects., Limitations: Limitations include the limited sample size, short duration, and single, fixed dose., Conclusions: IN ketamine appears to induce rapid anti-fatigue effects in individuals with severe MDD and BDep both with and without comorbid AUD. This suggests that IN ketamine holds potential as an alternative, rapid-acting, anti-fatigue option for different medical conditions., Competing Interests: Declaration of competing interest Dr. Machado-Vieira has received consulting fees from Eurofarma Pharmaceuticals, Abbott, and BioStrategies group; has research contracts with Boerhinger Ingelheim and Janssen Pharmaceuticals; has received speaker fees from Otsuka, EMS, and Cristalia; and is a member of the scientific boards of Symbinas Pharmaceuticals and Allergan. Dr. Machado-Vieira is also the PI for the following grants: NIH (R21HD106779 and R21MH129888), Milken Institute (BD-0000000081), Dr Machado-Vieira was PI for the Janssen 54135419TRD4005 study. Dr. Soares has served on the Advisory Board of Alkermes; as a Consultant for Boehringer, Johnson and Johnson, Livanova, and Sunovian; and received research grants from Compass Pathways, Mind Med, and Relmada. Dr. Zarate is listed as a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation; as a co-inventor on a patent for the use of (2R,6R)-hydroxynorketamine, (S)-dehydronorketamine, and other stereoisomeric dehydroxylated and hydroxylated metabolites of (R,S)-ketamine metabolites in the treatment of depression and neuropathic pain; and as a co-inventor on a patent application for the use of (2R,6R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorder. He has assigned his patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. All other authors have no conflict of interest to disclose, financial or otherwise., (Copyright © 2024. Published by Elsevier B.V.)

Meniere's disease (MD) is a complex inner ear disease related to endolymphatic hydrops and with multiple other etiologies suggested including autoimmunity and vascular insufficiency. Statins are lipid-lowering medications with additional effects including reduction of oxidative stress and inflammation. We performed a cross-sectional study comparing patients with MD on statins to those not on statins to see if there is any difference in disease activity (major vertigo spells) and hearing stage utilizing linear and logistic regression. Our analysis showed no difference in the average number of major vertigo spells per month ( β  = .07, P  = .9) between statin users and nonusers; however, statin users were found to have lower odds of worse hearing (odds ratio = 0.46, P  = .047). Further studies are needed to confirm our results., Competing Interests: None., (© 2024 The Author(s). OTO Open published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Objective: Although individuals with a family history of alcohol use disorder (AUD) have a superior antidepressant response to ketamine, outcomes in patients with current AUD remain unclear. This study sought to investigate whether intranasal (IN) racemic ( R,S )-ketamine had antisuicidal and antidepressant effects in unipolar and bipolar depression and whether comorbid AUD conferred superior antisuicidal outcomes for patients., Methods: This was a double-blind, randomized, placebo-controlled trial (May 2018 to January 2022) of single administration, fixed-dose (50 mg) IN ( R,S )-ketamine (or saline comparator) in unmedicated inpatients meeting Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition, Text Revision, criteria for a current major depressive episode (bipolar or unipolar), with current suicidal ideation (SI) and past attempt. Patients with and without comorbid AUD were enrolled. Change in Scale for Suicide Ideation score was the primary outcome measure, and change in Montgomery-Åsberg Depression Rating Scale score was the secondary outcome measure., Results: No significant group × time effect was noted for SI ( F = 1.1, P = .36). A statistical trend toward superior improvement in suicidality was observed in participants with comorbid AUD. The group × time interaction was significant for improvements in depression ( F = 3.06, P = .03) and largely unaffected by comorbid AUD or primary mood disorder type. Within the ketamine group, a significant correlation was observed between improvement in depressive symptoms and SI for patients without comorbid AUD ( r =0.927, P = .023) that was absent in patients with AUD ( r = 0.39, P = .44)., Conclusion: IN ketamine induced rapid antidepressant effects compared to placebo but did not significantly alter SI scores. The treatment was well tolerated. Continued investigation with IN ketamine as a practical alternative to current formulations is warranted., Trial Registration: ClinicalTrials.gov identifier: NCT03539887., (© Copyright 2024 Physicians Postgraduate Press, Inc.)

Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA's F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600  ms - 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes - B1, provided by the Japanese space agency, JAXA, and B2 - that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission's science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule., Competing Interests: Competing InterestsThe authors declare no competing interests., (© The Author(s) 2024.)

Sulfur oxide species (RSO x ) play a critical role in many fields, ranging from biology to atmospheric chemistry. Chlorine-containing sulfur oxides may play a key role in sulfate aerosol formation in Venus' cloud layer by catalyzing the oxidation of SO to SO 2 via sulfinyl radicals (RSO). We present results from the gas-phase UV-vis transient absorption spectroscopy study of the simplest sulfinyl radical, ClSO, generated from the pulsed-laser photolysis of thionyl chloride at 248 nm (at 40 Torr of N 2 and 292 K). A weak absorption spectrum from 350 to 480 nm with a peak at 385 nm was observed, with partially resolved vibronic bands (spacing = 226 cm -1 ), and a peak cross section σ(385 nm) = (7.6 ± 1.9) × 10 -20 cm 2 . From ab initio calculations at the EOMEE-CCSD/ano-pVQZ level, we assigned this band to 1 2 A' ← X 2 A″ and 2 2 A' ← X 2 A″ transitions. The spectrum was modeled as a sum of a bound-to-free transition to the 1 2 A' state and a bound-to-bound transition to the 2 2 A' state with similar oscillator strengths; the prediction agreed well with the observed spectrum. We attributed the vibronic structure to a progression in the bending vibration of the 2 2 A' state. Further calculations at the XDW-CASPT2 level predicted a conical intersection between the excited 1 2 A' and 2 2 A' potential energy surfaces near the Franck-Condon region. The geometry of the minimum-energy conical intersection was similar to that of the ground-state geometry. The lack of structure at shorter wavelengths could be evidence of a short excited-state lifetime arising from strong vibronic coupling. From simplified molecular orbital analysis, we attributed the ClSO spectrum to transitions involving the out-of-plane π/π * orbitals along the S-O bond and the in-plane orbital possessing a σ/σ * character along the S-Cl bond. We hypothesize that these orbitals are common to other sulfinyl radicals, RSO, which would share a combination of a strong and a weak transition in the UV (near 300 nm) and visible (400-600 nm) regions.

Bipolar disorder is a decidedly heterogeneous and multifactorial disease, with significant psychosocial and medical disease burden. Much difficulty has been encountered in developing novel therapeutics and objective biomarkers for clinical use in this population. In that regard, gut-microbial homeostasis appears to modulate several key pathways relevant to a variety of psychiatric, metabolic, and inflammatory disorders. Microbial impact on immune, endocrine, endocannabinoid, kynurenine, and other pathways are discussed throughout this review. Emphasis is placed on this system's relevance to current pharmacology, diet, and comorbid illness in bipolar disorder. Despite the high level of optimism promoted in many reviews on this topic, substantial obstacles exist before any microbiome-related findings can provide meaningful clinical utility. Beyond a comprehensive overview of pathophysiology, this review hopes to highlight several key areas where progress is needed. As well, novel microbiome-associated suggestions are presented for future research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The concentration of formic acid in Earth's troposphere is underestimated by detailed chemical models compared to field observations. Phototautomerization of acetaldehyde to its less stable tautomer vinyl alcohol, followed by the OH-initiated oxidation of vinyl alcohol, has been proposed as a missing source of formic acid that improves the agreement between models and field measurements. Theoretical investigations of the OH + vinyl alcohol reaction in excess O 2 conclude that OH addition to the α carbon of vinyl alcohol produces formaldehyde + formic acid + OH, whereas OH addition to the β site leads to glycoaldehyde + HO 2 . Furthermore, these studies predict that the conformeric structure of vinyl alcohol controls the reaction pathway, with the anti -conformer of vinyl alcohol promoting α OH addition, whereas the syn -conformer promotes β addition. However, the two theoretical studies reach different conclusions regarding which set of products dominate. We studied this reaction using time-resolved multiplexed photoionization mass spectrometry to quantify the product branching fractions. Our results, supported by a detailed kinetic model, conclude that the glycoaldehyde product channel (arising mostly from syn -vinyl alcohol) dominates over formic acid production with a 3.6:1.0 branching ratio. This result supports the conclusion of Lei et al. that conformer-dependent hydrogen bonding at the transition state for OH-addition controls the reaction outcome. As a result, tropospheric oxidation of vinyl alcohol creates less formic acid than recently thought, increasing again the discrepancy between models and field observations of Earth's formic acid budget.

Streptomyces are soil dwelling bacteria that are notable for their ability to sporulate and to produce antibiotics and other secondary metabolites. Antibiotic biosynthesis is controlled by a variety of complex regulatory networks, involving activators, repressors, signaling molecules and other regulatory elements. One group of enzymes that affects antibiotic synthesis in Streptomyces is the ribonucleases. In this review, the function of five ribonucleases, RNase E, RNase J, polynucleotide phosphorylase, RNase III and oligoribonuclease, and their impact on antibiotic production will be discussed. Mechanisms for the effects of RNase action on antibiotic synthesis are proposed., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jones.)

Background: In adults, the solitary lateral cystic neck mass remains a diagnostic challenge with little solid material to target for cytology and few clues on imaging modalities to suggest underlying malignancy., Method: This study was a retrospective review of patients presenting with a lateral cystic neck mass to a tertiary academic head and neck centre over a 10-year period., Results: A total of 25 of 157 cystic lesions were subsequently malignant on paraffin section histopathology, with the youngest patient being 42 years. In the age cohort over 40 years, 30 per cent of males and 10 per cent of females were diagnosed with malignancy. The ipsilateral palatine tonsil was the most common primary site (50 per cent). A total of 85 per cent of cases demonstrated integrated human papillomavirus infection. Age, male sex and alcohol were significant risk factors on univariate analysis. Ultrasound-guided fine needle aspiration cytology and magnetic resonance imaging represented the most accurate pre-open biopsy tests., Conclusion: The authors of this study advocate for a risk-stratified, evidence-based workup in patients with solitary lateral cystic neck mass in order to optimise timely diagnosis.

We analyze observations of a solar energetic particle (SEP) event at Rosetta's target comet 67P/Churyumov-Gerasimenko during 6-10 March 2015. The comet was 2.15 AU from the Sun, with the Rosetta spacecraft approximately 70 km from the nucleus placing it deep inside the comet's coma and allowing us to study its response. The Eastern flank of an interplanetary coronal mass ejection (ICME) also encountered Rosetta on 6 and 7 March. Rosetta Plasma Consortium data indicate increases in ionization rates, and cometary water group pickup ions exceeding 1 keV. Increased charge exchange reactions between solar wind ions and cometary neutrals also indicate increased upstream neutral populations consistent with enhanced SEP induced surface activity. In addition, the most intense parts of the event coincide with observations interpreted as an infant cometary bow shock, indicating that the SEPs may have enhanced the formation and/or intensified the observations. These solar transient events may also have pushed the cometopause closer to the nucleus. We track and discuss characteristics of the SEP event using remote observations by SOHO, WIND, and GOES at the Sun, in situ measurements at Solar Terrestrial Relations Observatory Ahead, Mars and Rosetta, and ENLIL modeling. Based on its relatively prolonged duration, gradual and anisotropic nature, and broad angular spread in the heliosphere, we determine the main particle acceleration source to be a distant ICME which emerged from the Sun on 6 March 2015 and was detected locally in the Martian ionosphere but was never encountered by 67P directly. The ICME's shock produced SEPs for several days which traveled to the in situ observation sites via magnetic field line connections., (©2022. The Authors.)

Thionyl chloride (Cl 2 SO) serves as a common Cl atom source in widespread applications of chlorine chemistry though little is known about the reactivity and spectroscopy of the ClSO radical after a Cl-S bond cleavage. We performed a Pulsed Laser Photolysis experiment to detect ClSO from Cl 2 SO photolysis at 248 nm in a gas-flow reactor by time-resolved UV-vis transient absorption spectroscopy. A few chemical tests, using I 2 and NO 2 , suggested the structured absorption band between 260 and 320 nm belonged to ClSO radical and that the termolecular ClSO + Cl + M → Cl 2 SO association reaction occurred. From EOMIP-CCSD/ano-pVQZ calculations, the ClSO band was assigned to the 1 2 A″ ← X 2 A″ transition involving the π* ← π transition of the SO bond and the vibrational progression to the SO stretching mode of the 1 2 A″ state, with a maximum cross-section = (2.0 ± 0.5) × 10 -18 cm 2 near 286 nm (1σ uncertainty) and an average spacing of vibrational structure of 658 cm -1 . The rapid decay of the ClSO signal monitored near 303 nm could be fit to a second-order kinetic model over 10-90 Torr, which yields an effective bimolecular rate coefficient k Cl+ClSO = (1.48 ± 0.42) × 10 -11 cm 3 molecule -1 s -1 at 292 K and 90 Torr (1σ uncertainty). This fast recombination reaction suggests that Cl-containing SO x species might act as significant Cl atom reservoirs in sulfur oxide-rich environments such as Venus' atmosphere. Moreover, the reported UV spectrum provides a new means for monitoring the ClSO radicals.

Objective: To evaluate whether a history of suicide attempt increases the odds of receiving clozapine treatment in veterans with schizophrenia or schizoaffective disorder., Methods: Electronic health record data were obtained for veterans with schizophrenia or schizoaffective disorder treated at any US Veterans Affairs Medical Center between January 1, 2000, and January 31, 2021 (N = 134,692). Logistic regression (adjusted and unadjusted) was applied to estimate odds ratios (ORs) for clozapine treatment in suicide attempters relative to nonattempters., Results: 3,407 patients had a documented history of suicide attempt, while 6,867 patients had received clozapine treatment. Also, 9.4% (n = 321) of suicide attempters versus 5.0% (n = 6546) of nonattempters had received clozapine treatment. The odds of being treated with clozapine was approximately 2-fold in patients with a history of suicide attempt in unadjusted (OR = 1.98, 95% CI, 1.76-2.22) and adjusted (OR = 1.91, 95% CI, 1.67-2.15) analyses., Conclusions: Despite the higher odds of clozapine treatment in suicide attempters with schizophrenia or schizoaffective disorder, clozapine was underutilized in the current sample of veterans. Concerted efforts should be made to expand the use of clozapine in patients with schizophrenia or schizoaffective disorder, especially those with a history of suicide attempt., (© Copyright 2022 Physicians Postgraduate Press, Inc.)

Chili powder is the most frequently consumed spice in Mexican diets. Thus, the dissemination of microorganisms associated with chili powder derived from Capsicum annuum L. is significant during microbial quality analysis, with special attention on detection of potential pathogens. The results presented here describe the initial characterization of bacterial community structure in commercial chili powder samples. Our results demonstrate that, within the domain Bacteria, the most abundant family was Bacillaceae , with a relative abundance of 99% in 71.4% of chili powder samples, while 28.6% of samples showed an average relative abundance of 60% for the Enterobacteriaceae family. Bacterial load for aerobic mesophilic bacteria (AMB) ranged from 10 4 to 10 6 cfu/g, while for sporulated mesophilic bacteria (SMB), the count ranged from 10 2 to 10 5 cfu/g. Bacillus cereus sensu lato ( s.l. ) was observed at ca. ˂600 cfu/g, while the count for Enterobacteriaceae ranged from 10 3 to 10 6 cfu/g, Escherichia coli and Salmonella were not detected. Fungal and yeast counts ranged from 10 2 to 10 5 cfu/g. Further analysis of the opportunistic pathogens isolated, such as B. cereus s.l. and Kosakonia cowanii, using antibiotic-resistance profiles and toxinogenic characteristics, revealed the presence of extended-spectrum β-lactamases (ESBLs) and Metallo-β-lactamases (MBLs) in these organisms. These results extend our knowledge of bacterial diversity and the presence of opportunistic pathogens associated with Mexican chili powder and highlight the potential health risks posed by its use through the spread of antibiotic-resistance and the production of various toxins. Our findings may be useful in developing procedures for microbial control during chili powder production.

Objectives: To explore the impact of COVID-19 on the management and outcomes of acute paediatric mastoiditis across the UK., Design: National retrospective and prospective audit., Setting: 48 UK secondary care ENT departments., Participants: Consecutive children aged 18 years or under, referred to ENT with a clinical diagnosis of mastoiditis., Main Outcome Measures: Cases were divided into Period 1 (01/11/19-15/03/20), before the UK population were instructed to reduce social contact, and Period 2 (16/03/20-30/04/21), following this. Periods 1 and 2 were compared for population variables, management and outcomes. Secondary analyses compared outcomes by primary treatment (medical/needle aspiration/surgical)., Results: 286 cases met criteria (median 4 per site, range 0-24). 9.4 cases were recorded per week in period 1 versus 2.0 in period 2, with no winter increase in cases in December 2020-Febraury 2021. Patient age differed between periods 1 and 2 (3.2 vs 4.7 years respectively, p < 0.001). 85% of children in period 2 were tested for COVID-19 with a single positive test. In period, 2 cases associated with P. aeruginosa significantly increased. 48.6% of children were scanned in period 1 vs 41.1% in period 2. Surgical management was used more frequently in period 1 (43.0% vs 24.3%, p = 0.001). Treatment success was high, with failure of initial management in 6.3%, and 30-day re-admission for recurrence in 2.1%. The adverse event rate (15.7% overall) did not vary by treatment modality or between periods 1& 2., Conclusion: The COVID-19 pandemic led to a significant change in the presentation and case mix of acute paediatric mastoiditis in the UK., (© 2021 John Wiley & Sons Ltd.)

The goal of Project GAUSS (Genesis of Asteroids and evolUtion of the Solar System) is to return samples from the dwarf planet Ceres. Ceres is the most accessible candidate of ocean worlds and the largest reservoir of water in the inner Solar System. It shows active volcanism and hydrothermal activities in recent history. Recent evidence for the existence of a subsurface ocean on Ceres and the complex geochemistry suggest past habitability and even the potential for ongoing habitability. GAUSS will return samples from Ceres with the aim of answering the following top-level scientific questions: What is the origin of Ceres and what does this imply for the origin of water and other volatiles in the inner Solar System?What are the physical properties and internal structure of Ceres? What do they tell us about the evolutionary and aqueous alteration history of dwarf planets?What are the astrobiological implications of Ceres? Is it still habitable today?What are the mineralogical connections between Ceres and our current collections of carbonaceous meteorites?, (© The Author(s) 2021.)

The environment of a comet is a fascinating and unique laboratory to study plasma processes and the formation of structures such as shocks and discontinuities from electron scales to ion scales and above. The European Space Agency's Rosetta mission collected data for more than two years, from the rendezvous with comet 67P/Churyumov-Gerasimenko in August 2014 until the final touch-down of the spacecraft end of September 2016. This escort phase spanned a large arc of the comet's orbit around the Sun, including its perihelion and corresponding to heliocentric distances between 3.8 AU and 1.24 AU. The length of the active mission together with this span in heliocentric and cometocentric distances make the Rosetta data set unique and much richer than sets obtained with previous cometary probes. Here, we review the results from the Rosetta mission that pertain to the plasma environment. We detail all known sources and losses of the plasma and typical processes within it. The findings from in-situ plasma measurements are complemented by remote observations of emissions from the plasma. Overviews of the methods and instruments used in the study are given as well as a short review of the Rosetta mission. The long duration of the Rosetta mission provides the opportunity to better understand how the importance of these processes changes depending on parameters like the outgassing rate and the solar wind conditions. We discuss how the shape and existence of large scale structures depend on these parameters and how the plasma within different regions of the plasma environment can be characterised. We end with a non-exhaustive list of still open questions, as well as suggestions on how to answer them in the future., Competing Interests: Competing InterestsThe authors declare no competing interests., (© The Author(s) 2022.)

The potential presence of spore-forming bacteria related to the Bacillus cereus group in Mexican chili powder elaborated from Capsicum annuum L. is of commercial and clinical interest, because chili powder is an essential spice in the Mexican diet and in diets around the globe. To facilitate detection and isolation of members of this group of spore-forming bacteria from Mexican chili powder samples, we identified colonies that grew on agar medium selective for Bacillus cereus sensu lato, supplemented with polymyxin B (10 µg/mL) and ampicillin (10 to 100 µg/mL). The presumptive B. cereus ( s.l. ) isolates were tested using a tRNA Cys -PCR-based approach and the results identified species related phylogenetically to B. cereus , B. thuringiensis, and B. toyonensis . Their toxigenic potential was assessed by serological tests to detect enterotoxins (Nhe and Hbl) and by PCR targeting the hemolysin BL ( hbl ) component C ( hblC ) and non-hemolytic enterotoxin component A ( nheA ). The antibiotic profiles of the isolates showed a high resistance to β-lactams (100% of the isolates), trimethoprim-sulfamethoxazole (100%), tetracycline (90%), erythromycin (77%), clindamycin (74%), and chloramphenicol (42%). Our results indicate the presence of B. cereus s.l. with toxigenic characteristics in Mexican chili powder. Because of the potential for these organisms to cause disease through their production of various toxins, and resistance to antibiotics, we recommend that a microbiological risk assessment must be considered in the Mexican regulatory requirements.

Bipolar disorder is a decidedly heterogeneous and multifactorial disease, with a high individual and societal burden. While not all patients display overt markers of elevated inflammation, significant evidence suggests that aberrant immune signaling contributes to all stages of the disease, and likely explains the elevated rates of comorbid inflammatory illnesses seen in this population. While individual systems have been intensely studied and targeted, a relative paucity of attention has been given to the interconnecting role of inflammatory signals therein. This review presents an updated overview of some of the most prominent pathophysiologic mechanisms in bipolar disorder, from mitochondrial, endoplasmic reticular, and calcium homeostasis, to purinergic, kynurenic, and hormonal/neurotransmitter signaling, showing inflammation to act as a powerful nexus between these systems. Several areas with a high degree of mechanistic convergence within this paradigm are highlighted to present promising future targets for therapeutic development and screening.

Objective: Evidence for the management of acute otitis externa (AOE) is limited, with unclear diagnostic criteria and variably reported outcome measures that may not reflect key stakeholder priorities. We aimed to develop 1) a definition, 2) diagnostic criteria and 3) a core outcome set (COS) for AOE., Study Design: COS development according to Core Outcome Measures in Effectiveness Trials (COMET) methodology and parallel consensus selection of diagnostic criteria/definition., Setting: Stakeholders from the United Kingdom., Subjects and Methods: Comprehensive literature review identified candidate items for the COS, definition and diagnostic criteria. Nine individuals with past AOE generated further patient-centred candidate items. Candidate items were rated for importance by patient and professional (ENT doctors, general practitioners, microbiologists, nurses, audiologists) stakeholders in a three-round online Delphi exercise. Consensus items were grouped to form the COS, diagnostic criteria, and definition., Results: Candidate COS items from patients (n = 28) and literature (n = 25) were deduplicated and amalgamated to a final candidate list (n = 46). Patients emphasised quality-of-life and the impact on daily activities/work. Via the Delphi process, stakeholders agreed on 31 candidate items. The final COS covered six outcomes: pain; disease severity; impact on quality-of-life and daily activities; patient satisfaction; treatment-related outcome; and microbiology. 14 candidate diagnostic criteria were identified, 8 reaching inclusion consensus. The final definition for AOE was 'diffuse inflammation of the ear canal skin of less than 6 weeks duration'., Conclusion: The development and adoption of a consensus definition, diagnostic criteria and a COS will help to standardise future research in AOE, facilitating meta-analysis. Consulting former patients throughout development highlighted deficiencies in the outcomes adopted previously, in particular concerning the impact of AOE on daily life., Competing Interests: The authors have declared that no competing interests exist.

Poly(A) polymerases (PAPs) and tRNA nucleotidyltransferases belong to a superfamily of nucleotidyltransferases and modify RNA 3'-ends. The product of the pcnB gene, PAP I, has been characterized in a few β-, γ- and δ- Proteobacteria . Using the PAP I signature sequence, putative PAPs were identified in bacterial species from the α- and ε- Proteobacteria and from four other bacterial phyla ( Firmicutes , Actinobacteria , Bacteroidetes and Aquificae ). Phylogenetic analysis, alien index and G+C content calculations strongly suggest that the PAPs in the species identified in this study arose by horizontal gene transfer from the β- and γ- Proteobacteria .

Bipolar spectrum disorders carry a significant public health burden. Disproportionately high rates of suicide, incarceration, and comorbid medical conditions necessitate an extraordinary focus on understanding the intricacies of this disease. Elucidating granular, intracellular details seems to be a necessary preamble to advancing promising therapeutic opportunities. In this chapter, we review a wide range of intracellular mechanisms including mitochondrial energetics, calcium signaling, neuroinflammation, the microbiome, neurotransmitter metabolism, glycogen synthase kinase 3-beta (GSK3β), protein kinase C (PKC) and diacylglycerol (DAG), and neurotrophins (especially BDNF), as well as the glutamatergic, dopaminergic, purinergic, and neurohormonal systems. Owing to the relative lack of understanding and effective therapeutic options compared to the rest of the spectrum, special attention is paid in the chapter to the latest developments in bipolar depression. Likewise, from a therapeutic standpoint, special attention should be paid to the pervasive mechanistic actions of lithium as a means of amalgamating numerous, disparate cascades into a digestible cognitive topology.

Background: There are sparse data on the outcomes of endoscopic stapling of pharyngeal pouches. The Mersey ENT Trainee Collaborative compared regional practice against published benchmarks., Methods: A 10-year retrospective analysis of endoscopic pharyngeal pouch surgery was conducted and practice was assessed against eight standards. Comparisons were made between results from the tertiary centre and other sites., Results: A total of 225 procedures were performed (range of 1.2-9.2 cases per centre per year). All centres achieved 90 per cent resumption of oral intake within 2 days. All centres achieved less than 2-day hospital stays. Primary success (84 per cent (i.e. abandonment of endoscopic stapling in 16 per cent)), symptom resolution (83 per cent) and recurrence rates (13 per cent) failed to meet the standard across the non-tertiary centres., Conclusion: Endoscopic pharyngeal pouch stapling is a procedure with a low mortality and brief in-patient stay. There was significant variance in outcomes across the region. This raises the question of whether this service should become centralised and the preserve of either tertiary centres or sub-specialist practitioners.

Background: In spore-forming bacteria, the molecular mechanisms of accumulation of transfer RNA (tRNA) during sporulation must be a priority as tRNAs play an essential role in protein synthesis during spore germination and outgrowth. However, tRNA processing has not been extensively studied in these conditions, and knowledge of these mechanisms is important to understand long-term stress survival.    Methods: To gain further insight into tRNA processing during spore germination and outgrowth, the expression of the single copy tRNA Cys gene was analyzed in the presence and absence of 1.2 M NaCl in Bacillus subtilis using RNA-Seq data obtained from the Gene Expression Omnibus (GEO) database. The CLC Genomics work bench 12.0.2 (CLC Bio, Aarhus, Denmark, https://www.qiagenbioinformatics.com/) was used to analyze reads from the tRNA Cys gene.  Results: The results show that spores store different populations of tRNA Cys -related molecules.  One such population, representing 60% of total tRNA Cys , was composed of tRNA Cys fragments.  Half of these fragments (3´-tRF) possessed CC, CCA or incorrect additions at the 3´end. tRNA Cys with correct CCA addition at the 3´end represented 23% of total tRNA Cys , while with CC addition represented 9% of the total and with incorrect addition represented 7%. While an accumulation of tRNA Cys precursors was induced by upregulation of the rrnD operon under the control of  σ A -dependent promoters under both conditions investigated, salt stress produced only a modest effect on tRNA Cys expression and the accumulation of tRNA Cys related species. Conclusions :The results demonstrate that tRNA Cys molecules resident in spores undergo dynamic processing to produce functional molecules that may play an essential role during protein synthesis., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Arvizu Hernández I et al.)

Objectives: This study aimed to estimate how many patients with asthma in England met the referral eligibility criteria using national asthma guidelines, identify what proportion were referred and determine the average waiting time to referral., Design: This is an observational cohort study., Setting/data Sources: Routinely collected healthcare data were provided by Clinical Practice Research Datalink records and Hospital Episode Statistics records from January 2007 to December 2015., Participants: Patients with asthma aged 18-80 years participated in this study., Main Outcome Measures: Eligibility for referral by the British Thoracic Society/Scottish Intercollegiate Guidelines Network (BTS/SIGN) 2016 guidelines, determined after a 3-month pharmacological therapy exposure assessment, was classed by either 'high-dose therapies', 'continuous or frequent use of oral steroids' or 'incident eligibility' during follow-up (continuous oral corticosteroids for more than 3 months, or ≥800 µg/day inhaled corticosteroids/long-acting β 2 -agonist (or three controllers) and ≥2 asthma attacks/year)., Results: From the final cohort (n=23293), 19837 patients were eligible for specialist referral during follow-up based on the BTS/SIGN guideline recommendations. Among eligible patients without any previously recorded referral, 4% were referred during follow-up, with a median waiting time of 880 days (IQR=1428 days) between eligibility and referral., Conclusions: A large number of patients with asthma were eligible for specialist referral, of which a small proportion were referred, and many experienced a long waiting time before referral. The results indicate a major unmet need in asthma referral, which is a potential source of preventable harm and are likely to have implications regarding how services are organised to address this unmet need., Competing Interests: Competing interests: In the last three years, JDB has received personal fees and non-financial support from Napp, AstraZeneca and Boehringer Ingelheim, and personal fees from Novartis and Teva, outside the submitted work. GHJ has received personal fees from Pfizer, AstraZeneca, Chiesi and GlaxoSmithKline, and non-financial support from Napp, outside the submitted work. AG was an employee of Boehringer Ingelheim at the time the study was carried out. MGS and MB are employees of Boehringer Ingelheim., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To investigate the incretin axis in people with cystic fibrosis., Methods: Adults with cystic fibrosis-related diabetes, cystic fibrosis without diabetes, and controls (adults without cystic fibrosis and without diabetes) underwent an oral glucose tolerance test and then a closely matched isoglycaemic i.v. glucose infusion. On each occasion, glucose, insulin, C-peptide, total and active glucagon-like peptide-1 and gastric inhibitory polypeptide responses were recorded and incremental areas under curves were calculated for 60 and 240 min., Results: Five adults with cystic fibrosis-related diabetes, six with cystic fibrosis without diabetes and six controls, matched for age and BMI, completed the study. Glucose during oral glucose tolerance test closely matched those during isoglycaemic i.v. glucose infusion. The calculated incretin effect was similar in the control group and the cystic fibrosis without diabetes group (28% and 29%, respectively), but was lost in the cystic fibrosis-related diabetes group (cystic fibrosis-related diabetes vs control group: -6% vs 28%; p=0.03). No hyposecretion of glucagon-like peptide-1 or gastric inhibitory polypeptide was observed; conversely, 60-min incremental area under the curve for total glucagon-like peptide-1 was significantly higher in the cystic fibrosis-related diabetes group than in the control group [1070.4 (254.7) vs 694.97 (308.1); p=0.03] CONCLUSIONS: The incretin effect was lost in cystic fibrosis-related diabetes despite adequate secretion of the incretin hormones. These data support the concept that reduced incretin hormone insulinotropic activity contributes significantly to postprandial hyperglycaemia in cystic fibrosis-related diabetes., (© 2019 Diabetes UK.)

The tRNA nucleotidyltransferases and poly(A) polymerases belong to a superfamily of nucleotidyltransferases. The amino acid sequences of a number of bacterial tRNA nucleotidyltransferases and poly(A) polymerases have been used to construct a rooted, neighbor-joining phylogenetic tree. Using information gleaned from that analysis, along with data from the rRNA-based phylogenetic tree, structural data available on a number of members of the superfamily and other biochemical information on the superfamily, it is possible to suggest a scheme for the evolution of the bacterial tRNA nucleotidyltransferases and poly(A) polymerases from ancestral species. Elements of that scheme are discussed along with questions arising from the scheme which can be explored experimentally.

In Bacillus subtilis, the tRNA Cys lacks an encoded CCA 3' end. To gain insight into the role of CCAase and RNases in tRNA Cys processing, several mutant strains were generated. Northern blot and RT-PCR results suggest that enzymes other than CCAase can participate in CCA addition at the 3' end of the immature tRNA Cys .

Saturn's main ring system is associated with a set of small moons that either are embedded within it or interact with the rings to alter their shape and composition. Five close flybys of the moons Pan, Daphnis, Atlas, Pandora, and Epimetheus were performed between December 2016 and April 2017 during the ring-grazing orbits of the Cassini mission. Data on the moons' morphology, structure, particle environment, and composition were returned, along with images in the ultraviolet and thermal infrared. We find that the optical properties of the moons' surfaces are determined by two competing processes: contamination by a red material formed in Saturn's main ring system and accretion of bright icy particles or water vapor from volcanic plumes originating on the moon Enceladus., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Biofilms are structures that confer adaptive ability to and facilitate the virulence of fungal pathogens. Certain multi-functional proteins have been shown to be involved in fungal pathogenesis and these proteins may also be implicated in biofilm formation. The aim of this study was to identify a fungal agent isolated from the human cornea, to analyze the ability of this organism to form biofilms in vitro and to investigate protein expression in this condition. The fungus was identified by phylogenetic inference analysis. Biofilm formation and structure were evaluated by colorimetric methods and by optical and electron microscopy. We also resolved proteins obtained from biofilms and planktonic cultures by two-dimensional gel electrophoresis and identified those proteins by mass spectrometry. The fungus was identified as Fusarium falciforme. Colorimetric analysis and microscopy revealed that the highest level of biofilm formation was obtained at a concentration of 1 × 10 6 conidia/mL with 96 h of incubation at 28 °C. The biofilm architecture consisted of an extracellular matrix that embedded fungal filaments. We found nineteen proteins that were over-expressed in biofilms, as compared with planktonic cultures, and six proteins with unique expression in biofilms. Among the more abundant proteins identified were: transketolase, a putative antigen 1, enolase, phosphoglycerate kinase and ATP-citrate synthase. Some of these proteins are involved in basal metabolism, function as multi-functional proteins or have been described as potential virulence factors. We focused on the expression in biofilm of the enzyme, enolase, which was determined by real-time PCR. Our findings provide a perspective on the proteins associated with the formation of biofilms in vitro by an F. falciforme keratitis isolate., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

American foulbrood (AFB) caused by Paenibacillus larvae is the most destructive honeybee bacterial disease and its dissemination via commercial bee pollen is an important mechanism for the spread of this bacterium. Because Mexico imports bee pollen from several countries, we developed a tRNA Cys -PCR strategy and complemented that strategy with MALDI-TOF MS and amplicon-16S rRNA gene analysis to evaluate the presence of P. larvae in pollen samples. P. larvae was not detected when the tRNA Cys -PCR approach was applied to spore-forming bacterial colonies obtained from three different locations and this result was validated by bacterial identification via MALDI-TOF MS. The genera identified in the latter analysis were Bacillus (fourteen species) and Paenibacillus (six) species. However, amplicon-16S rRNA gene analysis for taxonomic composition revealed a low presence of Paenibacillaceae with 0.3 to 16.2% of relative abundance in the commercial pollen samples analyzed. Within this family, P. larvae accounted for 0.01% of the bacterial species present in one sample. Our results indicate that the tRNA Cys -PCR, combined with other molecular tools, will be a useful approach for identifying P. larvae in pollen samples and will assist in controlling the spread of the pathogen.

In the article mentioned above an author's name was misspelled.

Little is known about extremophilic microorganisms from glaciers found in subtropical regions, and to our knowledge, no reports have identified glacial bacteria in this ecosystem in Mexico. Herein, we report a 16S rRNA gene amplicon data set demonstrating bacterial diversity of three samples from the Iztaccihuatl volcanic complex (Mexico) with a total of 115,701 to 138,805 high-quality reads. The bacterial population was classified at the phylum level in all samples., (Copyright © 2019 Calvillo-Medina et al.)

Background: In recent years, human keratitis caused by fungal plant pathogens has become more common. Biofilm is a structure that confers adaptations and virulence to fungi in keratitis. Neoscytalidium spp. are phytopathogenic and recently have been recognised as a human pathogen, using biofilm formation as a virulence factor., Objectives: The aim of this study was isolation, identification (at the species level) and characterisation of a new fungal keratitis agent., Patients/methods: The fungus was isolated from a 67-year-old male patient with a corneal ulcer. Biofilm formation and structure were evaluated by colorimetric methods and microscopy. To identify the fungus, morphological characteristics were examined and a phylogenetic analysis was performed., Results and Conclusions: We report the identification of a fungus, a member of the genus Neoscytalidium which is associated with human keratitis. Phylogenetic analysis and morphological observations on conidiogenous cells, which occur only in arthric chains in aerial mycelium and the coelomycetous synasexual morph is absent, identified a new species, Neoscytalidium oculus sp. nov. The fungus formed biofilm at a concentration of 1 × 10 6  conidia/mL, during 96 hours of incubation at 37°C, and also manifested haemolysis and melanin production. This is the first report in Latin America of a new species of Neoscytalidium from a clinical isolate has been identified., (© 2018 Blackwell Verlag GmbH.)

Saturn's main rings are composed of >95% water ice, and the nature of the remaining few percent has remained unclear. The Cassini spacecraft's traversals between Saturn and its innermost D ring allowed its cosmic dust analyzer (CDA) to collect material released from the main rings and to characterize the ring material infall into Saturn. We report the direct in situ detection of material from Saturn's dense rings by the CDA impact mass spectrometer. Most detected grains are a few tens of nanometers in size and dynamically associated with the previously inferred "ring rain." Silicate and water-ice grains were identified, in proportions that vary with latitude. Silicate grains constitute up to 30% of infalling grains, a higher percentage than the bulk silicate content of the rings., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Saturn has a sufficiently strong dipole magnetic field to trap high-energy charged particles and form radiation belts, which have been observed outside its rings. Whether stable radiation belts exist near the planet and inward of the rings was previously unknown. The Cassini spacecraft's Magnetosphere Imaging Instrument obtained measurements of a radiation belt that lies just above Saturn's dense atmosphere and is decoupled from the rest of the magnetosphere by the planet's A- to C-rings. The belt extends across the D-ring and comprises protons produced through cosmic ray albedo neutron decay and multiple charge-exchange reactions. These protons are lost to atmospheric neutrals and D-ring dust. Strong proton depletions that map onto features on the D-ring indicate a highly structured and diverse dust environment near Saturn., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Despite intensive research and clinical trials with numerous therapeutic treatments, traumatic brain injury (TBI) is a serious public health problem in the United States. There is no effective FDA-approved treatment to reduce morbidity and mortality associated with TBI. Inflammation plays a pivotal role in the pathogenesis of TBI. We looked to re-purpose existing drugs that reduce immune activation without broad immunosuppression. Teriflunomide, an FDA-approved drug, has been shown to modulate immunological responses outside of its ability to inhibit pyrimidine synthesis in rapidly proliferating cells. In this study, we tested the efficacy of teriflunomide to treat two different injury intensities in rat models of TBI. Our results show that teriflunomide restores blood-brain barrier integrity, decreases inflammation, and increases neurogenesis in the subgranular zone of the hippocampus. While we were unable to detect neurocognitive effects of treatment on memory and special learning abilities after treatment, a 2-week treatment following injury was sufficient to reduce neuroinflammation up to 120 days later., (Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Introduction: Diagnostic tonsillectomy is performed to exclude malignancy. It is associated with a post-operative hemorrhage rate of 3.5%, (1) which is more dangerous in small children. No previous case series for asymmetrical tonsils have detected tonsil lymphoma.(2-6) We aimed to review our local diagnostic tonsillectomy practice., Method: The authors reviewed the clinical notes and histological results for all diagnostic tonsillectomies carried out from June 2013 to June 2016., Results: We recorded data for 168 patients. There were four post-operative bleeds and one return to theatre. Bilateral tonsillectomies accounted for 152 operations (90.5%). Lymphoid hyperplasia accounted for 95% of histological diagnosis with no malignancies found. Pre-operative tonsil grading demonstrated no statistically significant association with histological tonsil weight difference (ANOVA p = 0.10). Actinomyces colonisation had little affect on tonsil weight difference when we compared patients with bilateral colonisation and no colonisation (t-test p = 0.540) and between tonsils in patients with unilateral tonsil Actinomyces colonisation (paired t-test p = 0.448). Recurrent tonsillitis was more prevalent in patients with Actinomyces colonisation than OSA/sleep disordered breathing (39% vs 15%)., Conclusion: A literature search yielded five smaller case series of palatine tonsil asymmetry in children with no malignancy found.(2-6) Case-control studies report tonsillar asymmetry as the most common presenting symptom (73%) in tonsillar lymphoma.(7) This enlargement usually occurs rapidly within 6 weeks with new obstructive or systemic B-type symptoms.(3) A Turkish epidemiological study found asymmetrical tonsils in 1.7% of the healthy paediatric population.(8) We therefore estimate there to be over 210,000 children with asymmetrical tonsils in the UK. With an unreliable grading system, we believe asymmetrical tonsils in isolation, unchanged for over 6 weeks may not warrant tonsillectomy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Bee pollen is a highly nutritive natural foodstuff. Because of its use as a comestible, the association of bacteria with bee pollen is commercially and biologically important. We report here the bacterial diversity of seven bee pollen samples (five from Europe, one from Chile, and one from Mexico) based on 16S rRNA gene amplicon metagenome sequencing., (Copyright © 2018 Moreno Andrade et al.)