Murine nuclear tyrosyl-tRNA synthetase deficiency leads to fat storage deficiency and hearing loss.

Aminoacyl-tRNA synthetases are fundamental to the translation machinery with emerging roles in transcriptional regulation. Previous cellular studies have demonstrated tyrosyl-tRNA synthetase (YARS1 or TyrRS) as a stress response protein through its cytosol-nucleus translocation to maintain cellular homeostasis. Here, we established a mouse model with a disrupted TyrRS nuclear localization signal, revealing its systemic impact on metabolism. Nuclear TyrRS deficiency (YarsΔNLS) led to reduced lean mass, reflecting a mild developmental defect, and reduced fat mass, possibly due to increased energy expenditure. Consistently, YarsΔNLS mice exhibit improved insulin sensitivity and reduced insulin levels, yet maintain normoglycemia, indicative of enhanced insulin action. Notably, YarsΔNLS mice also develop progressive hearing loss. These findings underscore the crucial function of nuclear TyrRS in the maintenance of fat storage and hearing and suggest that aminoacyl-tRNA synthetases' regulatory roles can affect metabolic pathways and tissue-specific health. This work broadens our understanding of how protein synthesis interconnects metabolic regulation to ensure energy efficiency.

Catechol acetylglucose: a newly identified benzoxazinoid-regulated defensive metabolite in maize.

An enormous diversity of specialized metabolites is produced in the plant kingdom, with each individual plant synthesizing thousands of these compounds. Previous research showed that benzoxazinoids, the most abundant class of specialized metabolites in maize, also function as signaling molecules by regulating the production callose as a defense response. We searched for additional benzoxazinoid-regulated specialized metabolites, characterized them, examined whether they too function in herbivore protection, and determined how Spodoptera frugiperda (fall armyworm), a prominent maize pest, copes with these metabolites. We identified catechol acetylglucose (CAG) as a benzoxazinoid-regulated metabolite that is produced from salicylic acid via catechol and catechol glucoside. Genome-wide association studies of CAG abundance identified a gene encoding a predicted acetyltransferase. Knockout of this gene resulted in maize plants that lack CAG and over-accumulate catechol glucoside. Upon tissue disruption, maize plants accumulate catechol, which inhibits S. frugiperda growth. Analysis of caterpillar frass showed that S. frugiperda detoxifies catechol by glycosylation, and the efficiency of catechol glycosylation was correlated with S. frugiperda growth on a catechol-containing diet. Thus, the success of S. frugiperda as an agricultural pest may depend partly on its ability to detoxify catechol, which is produced as a defensive metabolite by maize.

Extratunical grafting for minimally invasive management of complex Peyronie's disease deformities.

BACKGROUND: Penile deformities due to Peyronie's Disease (PD) often significantly impair men's sexual health and quality of life. AIM: In this article we discuss the extratunical graft (ETG) procedure as a management strategy for PD patients with hourglass or indent penile deformities. METHODS: We compiled descriptions of surgical techniques and performed a review of the literature regarding ETG for PD. OUTCOMES: The ETG procedure appears to have promising results in the management of indent/hourglass deformity of PD. RESULTS: The findings of this review of the literature demonstrate that ETG is a safe and effective reconstructive technique for penile deformity with minimal side effects. CLINICAL IMPLICATIONS: We recommend utilizing ETG with or without plication for PD patients with indent or hourglass deformities. STRENGTHS AND LIMITATIONS: Strengths of ETG are the improvement in patients with tunical indents and hourglass deformities secondary to PD. Additionally, patients who underwent ETG maintained sexual function given no significant change in penile length and intact erectile function. Limitations, however, are that the procedure is relatively new, and data are limited to small cohorts. CONCLUSION: The ETG procedure is a safe and effective for management of complex PD in the short- and intermediate-term follow-up cohort.

Lessons learned from the Sexual Medicine Society of North America fellowship bootcamp.

BACKGROUND: Sexual Medicine Society of North America (SMSNA) fellowships offer variable experience in sexual health domains: erectile dysfunction, Peyronie's disease, male infertility, male hypogonadism (low testosterone), reconstruction (including male incontinence), benign prostatic hyperplasia, gender affirmation surgery, sexual mental health, and female sexual dysfunction. AIM: To evaluate baseline and postbootcamp understanding and trust in these domains. METHODS: In 2023, 28 of 31 urologists currently enrolled in SMSNA-endorsed fellowships participated in a 3.5-day training bootcamp in Minneapolis, Minnesota. Participants were asked to complete pre- and postbootcamp surveys. The bootcamp curriculum offered American Urological Association guidelines and case-based lectures, hands-on clinical training with cadavers (penile surgery) and models (collagenase training), and interaction with industry. OUTCOMES: Changes in knowledge, independence, and trust in performing the procedures, as well as billing issues and feedback for future bootcamps. RESULTS: Prebootcamp surveys revealed vastly varied residency experience. Reported time with an expert faculty member was greatest for benign prostatic hyperplasia and least for female sexual dysfunction, gender affirmation surgery, and low testosterone. The lowest prebootcamp confidence in performing surgery independently was for penile grafting procedures and elevating the neurovascular bundle. Postbootcamp results revealed several areas of significant improvement in confidence (P ≤ .03): intralesional injections for Peyronie's disease, manual modeling, penile plication, penile grafting procedures, and elevating the neurovascular bundle. There was a trend for improved confidence with the insertion of inflatable (P = .05) and semirigid (P = .08) penile prostheses. Nonsignificant improvement occurred in artificial urinary sphincter surgery (P = .12). Participants graded the bootcamp very highly and requested that next year's bootcamp have more content on female sexual dysfunction, male incontinence, and low testosterone, as well as more hands-on skills sessions and case-based lecture formats. CLINICAL IMPLICATIONS: Offering a bootcamp with hands-on instruction could significantly improve urologists' knowledge and confidence. STRENGTHS AND LIMITATIONS: As the main strength, this study was the first specialized bootcamp for urologists in the subject of men's health, taking into account hands-on and cadaver laboratories, as well as highlighting industrial and pharmaceutical products. The small sample size was the major limitation. CONCLUSIONS: Current SMSNA fellows present with varied levels of experience and confidence across sexual health domains. Notable confidence improvements were seen with topics that combined didactic lectures with hands-on trainings.

Does Positioning During Oral and Maxillofacial Surgery Operations Influence the Development of Upper Extremity Peripheral Neuropathy?

BACKGROUND: Controversy exists regarding the role of specific etiology and mitigating factors in perioperative upper extremity peripheral neuropathy (PUN) development during oral and maxillofacial surgery (OMS) procedures. PURPOSE: The purpose of this study was to measure the association between upper extremity (UE) positioning and developing PUN in OMS operations. STUDY DESIGN, SETTING, SAMPLE: The investigators implemented a retrospective cohort study. Patients referred to the Department of Oral and Maxillofacial Surgery at Jefferson Health who underwent orthognathic, telegnathic, or free flap surgery from April 2017 through December 2021 were identified. Exclusion criteria were age less than 13, revision surgery, ablative case without free flap reconstruction, incomplete medical record, pre-existing neuropathy, and UE position other than tucked or abducted. PREDICTOR VARIABLE: The predictor variable was UE position during surgery, which had 2 levels-tucked or abducted. MAIN OUTCOME VARIABLE: The outcome variable was self-reported development of PUN, defined as new sensory and/or motor deficit in a nonoperated extremity diagnosed within 48 hours of surgery. COVARIATES: Demographic covariates included age, gender, and race. Perioperative covariates included American Society of Anesthesiologists physical status and body mass index (BMI). The operative covariate was general anesthesia (GA) duration. ANALYSES: Descriptive statistics were calculated. Shapiro-Wilk test was used to assess normality of the sample. Categorical variables were analyzed with Fisher's exact test. Continuous variables were analyzed with Mann-Whitney U test. Significance was defined at P < .05. RESULTS: Of the 432 patients identified, 342 met inclusion criteria. Median (interquartile range) ages for the abducted and tucked cohorts were 40 (31) and 34 (28) years, respectively (P < .01). Males comprised 55.4% (n = 41) and 54.1% (n = 145) of abducted and tucked groups, respectively (P = .9). PUN frequency was 6.8% (n = 5) for abducted subjects and 3.7% (n = 10) for tucked subjects (relative risk 1.8, 95% confidence interval [0.7, 5.1]; P = .33). PUN was associated with gender (P = .01), American Society of Anesthesiologists status (P = .03), BMI (P = .01), and GA duration (P < .01) on bivariate analysis. When adjusting for covariates, only GA duration (P < .01) and BMI (P = .03) were associated with PUN development. CONCLUSION AND RELEVANCE: The findings suggest that PUN development during OMS procedures was not associated with UE position.

So many toadfish, so little timea).

The oyster toadfish, Opsanus tau, has been a valuable biomedical model for a wide diversity of studies. However, its vocalization ability arguably has attracted the most attention, with numerous studies focusing on its ecology, behavior, and neurophysiology in regard to its sound production and reception. This paper reviews 30 years of research in my laboratory using this model to understand how aquatic animals detect, integrate, and respond to external environment cues. The dual vestibular and auditory role of the utricle is examined, and its ability to integrate multimodal input is discussed. Several suggestions for future research are provided, including in situ auditory recording, interjecting natural relevant ambient soundscapes into laboratory sound studies, adding transparency to the field of acoustic deterrents, and calls for fish bioacoustics teaching modules to be incorporated in K-12 curricula to excite and diversify the next generation of scientists.

Introduction to the special issue on fish bioacoustics: Hearing and sound communicationa).

Fish bioacoustics, or the study of fish hearing, sound production, and acoustic communication, was discussed as early as Aristotle. However, questions about how fishes hear were not really addressed until the early 20th century. Work on fish bioacoustics grew after World War II and considerably in the 21st century since investigators, regulators, and others realized that anthropogenic (human-generated sounds), which had primarily been of interest to workers on marine mammals, was likely to have a major impact on fishes (as well as on aquatic invertebrates). Moreover, passive acoustic monitoring of fishes, recording fish sounds in the field, has blossomed as a noninvasive technique for sampling abundance, distribution, and reproduction of various sonic fishes. The field is vital since fishes and aquatic invertebrates make up a major portion of the protein eaten by a signification portion of humans. To help better understand fish bioacoustics and engage it with issues of anthropogenic sound, this special issue of The Journal of the Acoustical Society of America (JASA) brings together papers that explore the breadth of the topic, from a historical perspective to the latest findings on the impact of anthropogenic sounds on fishes.

Improved Radiosynthesis and Automation of [11C]2-(2,6-Difluoro-4-((2-(N-methylphenylsulfonamido)ethyl)thio)phenoxy)acetamide ([11C]K2) for Positron Emission Tomography of the Glutamate α-Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid (AMPA) Receptor.

A new automated radiosynthesis of [11C]2-(2,6-difluoro-4-((2-(N-methylphenylsulfonamido)ethyl)thio)phenoxy)acetamide ([11C]K2), a radiopharmaceutical for the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, is reported. Although manual syntheses have been described, these are unsuitable for routine production of larger batches of [11C]K2 for (pre)clinical PET imaging applications. To meet demands for the imaging agent from our functional neuroimaging collaborators, herein, we report a current good manufacturing practice (cGMP)-compliant synthesis of [11C]K2 using a commercial synthesis module. The new synthesis is fully automated and has been validated for clinical use. The total synthesis time is 33 min from end of bombardment, and the production method provides 2.66 ± 0.3 GBq (71.9 ± 8.6 mCi) of [11C]K2 in 97.7 ± 0.5% radiochemical purity and 754.1 ± 231.5 TBq/mmol (20,382.7 ± 6256.1 Ci/mmol) molar activity (n = 3). Batches passed all requisite quality control testing confirming suitability for clinical use.

Zinc-Mediated Radiosynthesis of Unprotected Fluorine-18 Labelled α-Tertiary Amides.

This report describes the development of a Zn(OTf)2 -mediated method for converting α-tertiary haloamides to the corresponding fluorine-18 labelled α-tertiary fluoroamides with no-carrier-added [18 F]tetramethylammonium fluoride. 1,5,7-Triazabicyclo[4.4.0]dec-5-ene is an essential additive for achieving high radiochemical conversion. Under the optimised conditions, radiofluorination proceeds at sterically hindered tertiary sites in high radiochemical conversions, yields, and purities. This method has been successfully automated and applied to access >200 mCi (>7.4 GBq) of several model radiofluorides. Mechanistic studies led to the development of a new, nucleophilic C-H radiofluorination process using N-sulphonyloxyamide substrates.

Mechanical indications for inflatable penile prosthesis revision: analysis and implications for revision surgery.

BACKGROUND: Despite technical advancements, inflatable penile prostheses (IPPs) are inherently at risk of mechanical failure given their nature as hydraulic devices. AIM: To characterize IPP component failure location at the time of device revision and stratify by manufacturer: American Medical Systems (Boston Scientific [BSCI]) and Coloplast (CP). METHODS: A retrospective review of penile prosthesis cases from July 2007 to May 2022 was conducted, identifying men who underwent revision surgery. Cases were excluded if documentation did not denote the cause of failure or the manufacturer. Mechanical indications for surgery were categorized by location (eg, tubing, cylinder, or reservoir leak; pump malfunction). Nonmechanical revisions were excluded (component herniation, erosion, or crossover). Categorical variables were assessed with Fisher exact or chi-square analysis; Student t-test and Mann-Whitney U test were used for continuous variables. OUTCOMES: Primary outcomes included specific location of IPP mechanical failure among BSCI and CP devices and time to mechanical failure. RESULTS: We identified 276 revision procedures, 68 of which met inclusion criteria (46 BSCI and 22 CP). Revised CP devices were longer than BSCI devices (median cylinder length, 20 vs 18 cm; P < .001). Log-rank analysis revealed a similar time to mechanical failure between brands (P = .096). CP devices failed most often due to tubing fracture (19/22, 83%). BSCI devices had no predominant site of failure. Between manufacturers, tubing failure was more common in CP devices (19/22 vs 15/46 for BSCI, P < .001), while cylinder failure was more common among BSCI devices (10/46 vs 0/22 for CP, P = .026). CLINICAL IMPLICATIONS: The distribution of mechanical failure is significantly different between BSCI and CP devices; this has implications regarding the approach to revision surgery. STRENGTHS AND LIMITATIONS: This is the first study to directly compare when and where mechanical failure occurs in IPPs and to compare the 2 main manufacturers head-to-head. This study would be strengthened by being repeated in a multi-institutional fashion to provide more robust and objective evaluation. CONCLUSION: CP devices commonly failed at the tubing and rarely elsewhere, while BSCI devices showed no predominant failure site; these findings may inform decision making regarding revision surgery.

Part II: Cutaneous manifestations of peripheral vascular disease.

In this Part 2 of a 2-part continuing medical education series, we review the epidemiology of peripheral vascular disease, its association with cutaneous symptoms, and the diagnosis and evaluation of cutaneous features of vascular disorders. As peripheral vascular disease becomes more prevalent globally, it is essential for dermatologists to become competent at accurately recognizing and diagnosing cutaneous manifestations and directing individuals to receive appropriate care and treatment.

Sound frequencies detectable by grass (Ctenopharyngodon idella) and black (Mylopharyngodon pisceus) carp determined with auditory evoked potentialsa).

Grass (Ctenopharyngodon idella) and black (Mylopharyngodon piceus) carp were imported to the United States as biocontrol agents in aquaculture facilities; however, due to intentional stocking or accidental release, invasive populations have become established. Invasive bigheaded carps display negative phonotaxis to sound, suggesting acoustic deterrents as a potential management tool. Grass and black carp frequency detection in response to 0.2-6 kHz sound was evaluated using auditory evoked potentials (AEPs) and determined for sound pressure level (SPL) and particle acceleration level (PAL). AEPs were detectable in response to pure tone stimuli from 0.2 to 4 kHz. The lowest SPL thresholds for grass carp were at 0.3 kHz (87.0 ± 3.6 dB re 1 µPa SPLrms; mean ± standard deviation), and the lowest PAL thresholds were at 0.4 kHz (-65.8 ± 3.2 dB re 1 ms-2 PALrms). For black carp, the lowest SPL and PAL thresholds were at 0.3 kHz (93.4 ± 3.0 dB re 1 µPa SPLrms, -60.8 ± 1.5 dB re 1 ms-2 PALrms). These results indicate that the ranges of detectable frequencies for grass and black carp overlap with those reported for bigheaded carps. However, behavioral studies are needed to determine potential efficacy of acoustic deterrents for these fish.

Response of toadfish (Opsanus tau) utricular afferents to multimodal inputs.

The inner ear of teleost fishes is composed of three paired multimodal otolithic end organs (saccule, utricle, and lagena), which encode auditory and vestibular inputs via the deflection of hair cells contained within the sensory epithelia of each organ. However, it remains unclear how the multimodal otolithic end organs of the teleost inner ear simultaneously integrate vestibular and auditory inputs. Therefore, microwire electrodes were chronically implanted using a 3-D printed micromanipulator into the utricular nerve of oyster toadfish (Opsanus tau) to determine how utricular afferents respond to conspecific mate vocalizations termed boatwhistles (180 Hz fundamental frequency) during movement. Utricular afferents were recorded while fish were passively moved using a sled system along an underwater track at variable speeds (velocity: 4.0-12.5 cm/s; acceleration: 0.2-2.6 cm/s2) and while fish freely swam (velocity: 3.5-18.6 cm/s; acceleration: 0.8-29.8 cm/s2). Afferent fiber activities (spikes/s) increased in response to the onset of passive and active movements; however, afferent fibers differentially adapted to sustained movements. In addition, utricular afferent fibers remained sensitive to playbacks of conspecific male boatwhistle vocalizations during both passive and active movements. Here, we demonstrate in alert toadfish that utricular afferents exhibit enhanced activity levels (spikes/s) in response to behaviorally relevant acoustic stimuli during swimming.NEW & NOTEWORTHY The inner ear of teleost fishes is composed of three paired multimodal otolithic end organs, which are sensitive to vestibular and auditory inputs. Previous studies investigating inner ear functions have primarily focused on the effects of unimodal stimuli; therefore, it remains unclear how otolithic end organs simultaneously encode multiple stimuli. Here, we show that utricular afferents remain sensitive to behaviorally relevant acoustic stimuli during swimming.

Long-term lower urinary tract sequelae following AUS cuff erosion.

AIMS: To examine the rate of lower urinary tract complications (LUTC) and urinary diversion (UD) after artificial urinary sphincter (AUS) explantation with the acute reconstruction of AUS cuff erosion defects. METHODS: We performed a retrospective study of patients who underwent in-situ urethroplasty (ISU) for AUS cuff erosion from June 2007 to December 2020. Outcomes included LUTC (urethral stricture, diverticulum, fistula), AUS reimplantation, and UD. Defect size was prospectively estimated acutely and a subanalysis was performed to determine the impact of erosion severity (small erosions [<33% circumferential defect] and large erosions [≥33%]) on these outcomes. Kaplan-Meier curves were created to compare survival between the two groups. RESULTS: A total of 40 patients underwent ISU for urethral cuff erosion. The median patient age was 76 years old with a median erosion circumference of 46%. The overall LUTC rate was 30% (12/40) with 35% (14/40) of patients requiring permanent UD. Secondary AUS placement occurred in 24/40 (60%) patients with 11/24 (46%) leading to repeat erosion. On subanalysis, small erosion was associated with improved LUTC-free and UD-free survival but not associated with AUS reimplantation. CONCLUSIONS: Lower urinary tract complications are common after AUS cuff erosion and can lead to the need for permanent UD. Patients with larger erosions are more likely to undergo UD and reach this end-stage condition earlier compared to patients with small erosions.

The Interrelationship of Tinnitus and Hearing Loss Secondary to Age, Noise Exposure, and Traumatic Brain Injury.

OBJECTIVE: Tinnitus has been the No. 1 disability at the Veteran Administration for the last 15 years, yet its interaction with hearing loss secondary to etiologies such as age, noise trauma, and traumatic brain injuries remains poorly characterized. Our objective was to analyze hearing loss and tinnitus, including audiogram data, of the Million Veteran Program within the context of military exposures in an aging population. DESIGN: Health records, questionnaires, audiograms, and military data were aggregated for 758,005 Veteran participants in the Million Veteran Program 2011 to 2020, with relative risks (RR) calculated for ancestries, sex, hearing loss and military exposures such as combat, blast, and military era served. A multivariate model with significant demographic measures and exposures was then analyzed. Next, audiogram data stratified by sex were compared for those with and without tinnitus by two methods: first, mean thresholds at standard frequencies were compared to thresholds adjusted per ISO 7029:2000E age and sex formulae. Second, levels for those ≤40 years of age were compared with those 41 and older. Finally, a proportional hazards model was examined to ascertain the timing between the onset of tinnitus and hearing loss, calculated separately for electronic health record diagnoses (ICD) and self-report. RESULTS: Tinnitus was either self-reported, diagnosed, or both in 37.5% (95% CI, 37.4 to 37.6), mean age 61.5 (95% CI, 61.4 to 61.5), range 18 to 112 years. Those with hearing loss were 4.15 times (95% CI, 4.12 to 4.15) as likely to have tinnitus. Americans of African descent were less likely to manifest tinnitus (RR 0.61, 95% CI, 0.60 to 0.61), as were women (RR 0.65, 95% CI, 0.64 to 0.65). A multivariate model indicated a higher RR of 1.73 for traumatic brain injury (95% CI, 1.71 to 1.73) and daily combat noise exposure (1.17, 95% CI, 1.14 to 1.17) than age (0.998, 95% CI, 0.997 to 0.998). Subjects ≤40 years of age had small but significantly elevated hearing thresholds through all standard frequencies compared to Veterans without tinnitus, and the effect of tinnitus on hearing thresholds diminished with age. In the hazard model, those >40 with new onset of tinnitus were at risk for hearing loss sooner and with greater incidence than those who were younger. The rate of hearing loss following tinnitus approached 100%. In contrast, only approximately 50% of those who self-reported hearing loss initially were at risk for later hearing loss, in contrast to ICD comparison, where those with ICD of hearing loss were more likely to sustain an ICD of tinnitus subsequently. CONCLUSIONS: Evidence suggests that the occurrence of tinnitus in the military is more closely related to environmental exposures than to aging. The finding that tinnitus affects hearing frequencies across the audiogram spectrum suggests an acoustic injury independent of tonotopicity. Particularly for males >40, tinnitus may be a harbinger of audiologic damage predictive of later hearing loss.

Evidence reversals in primary care research: a study of randomized controlled trials.

BACKGROUND: Evidence-Based Medicine is built on the premise that clinicians can be more confident when their decisions are grounded in high-quality evidence. Furthermore, evidence from studies involving patient-oriented outcomes is preferred when making decisions about tests or treatments. Ideally, the findings of relevant and valid trials should be stable over time, that is, unlikely to be reversed in subsequent research. OBJECTIVE: To evaluate the stability of evidence from trials relevant to primary healthcare and to identify study characteristics associated with their reversal. METHODS: We studied synopses of randomized controlled trials (RCTs) published from 2002 to 2005 as "Daily POEMs" (Patient Oriented Evidence that Matters). The initial evidence (E1) from these POEMs (2002-2005) was compared with the updated evidence (E2) on that same topic in a summary resource (DynaMed 2019). Two physician-raters independently categorized each POEM-RCT as (i) reversed when E1 ≠ E2, or as (ii) not reversed, when E1 = E2. For all "Evidence Reversals" (E1 ≠ E2), we assessed the direction of change in the evidence. RESULTS: We evaluated 408 POEMs on RCTs. Of those, 35 (9%; 95% confidence interval [6-12]) were identified as reversed, 359 (88%) were identified as not reversed, and 14 (3%) were indeterminate. On average, this represents about 2 evidence reversals per annum for POEMs about RCTs. CONCLUSIONS: Over 12-17 years, 9% of RCTs summarized as POEMs are reversed. Information alerting services that apply strict criteria for relevance and validity of clinical information are likely to identify RCTs whose findings are stable over time.

We studied the extent to which evidence from randomized controlled trials (RCTs) relevant to primary care is contradicted in subsequent research. When it was, we identified this event as an evidence reversal. In addition, we sought to identify characteristics of RCTs associated with their reversal. From 408 RCTs published during the period 2002­2005, study characteristics such as sample size were identified and extracted. Subsequently, we compared the evidence reported in each of these RCTs with the evidence on that same topic in an online summary resource in 2019. This allowed us to classify each RCT in one of the following 3 categories: evidence confirmed, reversed, or uncertain if this evidence is confirmed or reversed. Over 12­17 years of follow-up time, the findings of about 9 in 10 RCTs summarized as POEMs are stable. We found no statistically significant associations between trial characteristics and their subsequent reversal. This low rate of evidence reversal is good news for the RCTs that are used to inform decision-making.

Otitis media susceptibility and shifts in the head and neck microbiome due to SPINK5 variants.

BACKGROUND: Otitis media (OM) susceptibility has significant heritability; however, the role of rare variants in OM is mostly unknown. Our goal is to identify novel rare variants that confer OM susceptibility. METHODS: We performed exome and Sanger sequencing of >1000 DNA samples from 551 multiethnic families with OM and unrelated individuals, RNA-sequencing and microbiome sequencing and analyses of swabs from the outer ear, middle ear, nasopharynx and oral cavity. We also examined protein localisation and gene expression in infected and healthy middle ear tissues. RESULTS: A large, intermarried pedigree that includes 81 OM-affected and 53 unaffected individuals cosegregates two known rare A2ML1 variants, a common FUT2 variant and a rare, novel pathogenic variant c.1682A>G (p.Glu561Gly) within SPINK5 (LOD=4.09). Carriage of the SPINK5 missense variant resulted in increased relative abundance of Microbacteriaceae in the middle ear, along with occurrence of Microbacteriaceae in the outer ear and oral cavity but not the nasopharynx. Eight additional novel SPINK5 variants were identified in 12 families and individuals with OM. A role for SPINK5 in OM susceptibility is further supported by lower RNA counts in variant carriers, strong SPINK5 localisation in outer ear skin, faint localisation to middle ear mucosa and eardrum and increased SPINK5 expression in human cholesteatoma. CONCLUSION: SPINK5 variants confer susceptibility to non-syndromic OM. These variants potentially contribute to middle ear pathology through breakdown of mucosal and epithelial barriers, immunodeficiency such as poor vaccination response, alteration of head and neck microbiota and facilitation of entry of opportunistic pathogens into the middle ear.

Cold cicadas and hot rocks: Thermal responses and thermoregulation in some New Zealand cicadas (Insecta: Hemiptera: Cicadidae: Cicadettinae: Cicadettini).

We determine the thermal responses for 11 species from four genera of New Zealand cicadas. Thermal responses are remarkably similar regardless of environment or elevation inhabited by the species. The thermal responses of New Zealand cicadas do not show the same variability as cicada species in similarly diverse environments in Africa, Australia, Europe, North America, and South America nor the correlation to elevation as seen in some North American cicadas. Behavioral thermoregulation appears to be the mechanism permitting the distribution of species into specific habitats so that diverging thermal adaptation was not necessary as speciation occurred. The first example of a cicada using conductive heat transfer to thermoregulate is provided. These data show an evolutionary divergence from what otherwise have been convergent thermal adaptation patterns in a variety of cicadas separated by large geographic distances and species phylogeny.

Thermal responses of some Australian cicadas (Insecta: Hemiptera: Cicadidae).

We determine the thermal responses for 22 species from 16 genera, nine tribes and two subfamilies of Australian cicadas. Thermal responses are related to habitat and possibly to behavior. The thermal responses of the Australian species show convergent patterns to the cicadas in similar environments in Africa, Europe, North America, and South America. The study illustrates that similar evolutionary pressures select for similar thermal adaptation regardless of geographic locality or species phylogeny.

Conflicts of Interest in Psychopharmacology Textbooks.

While most medical journals require disclosures of industry payments to authors and editors, there is no requirement for textbooks. In this study we evaluated nine well-known psychopharmacology textbooks to identify payments to their writers and editors. Two-thirds of the textbooks had at least one editor or author who received personal payments from one or more pharmaceutical companies, for a total of 11,021,409 USD paid to 11 of 21 editors/authors over a seven-year period. Much of this money was paid to a single author but 24% of the writers received over 75,000 USD each over this time period. There are several psychopharmacology textbooks authored by writers without apparent financial conflicts of interest. Just as with medical journals, medical textbooks should be transparent about payments made to their authors and editors.