Depressive Symptoms, Systemic Inflammation, and Survival Among Patients With Head and Neck Cancer.

Importance: Patients with head and neck cancer experience high rates of depression. Depression and systemic inflammation have been found to be associated in numerous cancer types, often independently from disease status. Depression-related inflammation may elevate the risks for poor tumor response to treatment and early mortality, and comprises a mechanism by which depression is associated with survival in head and neck cancer. Objective: To assess mediation pathways incorporating pretreatment depressive symptoms, pretreatment inflammation, and tumor response posttreatment on overall survival among patients with head and neck cancer. Design, Setting, and Participants: This was a prospective observational cohort study of patients with head and neck cancer treated in a single multidisciplinary head and neck cancer clinic from May 10, 2013, to December 30, 2019, and followed up for 2 years. Data analysis was performed from June 29, 2022, to June 23, 2023. Exposures: Patient-reported depressive symptoms using the Patient Health Questionnaire-9 item (PHQ-9) at treatment planning; pretreatment hematology workup for systemic inflammation index (SII) score; and clinical data review for tumor response (complete vs incomplete) and overall survival. Main Outcomes: Two-year overall survival. Results: The total study cohort included 394 patients (mean [SD] age, 62.5 [11.5] years; 277 [70.3%] males) with head and neck cancer. Among 285 patients (72.3%) who scored below the clinical cutoff for depression on the PHQ-9, depressive symptoms were significantly associated with inflammation (partial r, 0.168; 95% CI, 0.007-0.038). In addition, both depression and inflammation were associated with early mortality (PHQ-9: hazard ratio [HR], 1.04; 95% CI, 1.02-1.07; SII: HR, 1.36; 95% CI, 1.08-1.71). The depression-survival association was fully mediated by inflammation (HR, 1.28; 95% CI, 1.00-1.64). Depressive symptoms were also associated with poorer tumor response (odds ratio, 1.05; 95% CI, 1.01-1.08), and the depression-survival association was partially mediated by tumor response (HR, 9.44; 95% CI, 6.23-14.32). Systemic inflammation was not associated with tumor response. Conclusions: In this cohort study, systemic inflammation emerged as a novel candidate mechanism of the association of depression with mortality. Tumor response partially mediated effects of depression on mortality, replicating prior work. Thus, depression stands out as a highly feasible target for renewed clinical attention. Even mild symptoms of depression during the treatment-planning phase may be associated with higher systemic inflammation in addition to poorer tumor response to treatment and survival outcomes; therefore, depression should be clinically addressed.

Reference genome of the bicolored carpenter ant, Camponotus vicinus.

Carpenter ants in the genus Camponotus are large, conspicuous ants that are abundant and ecologically influential in many terrestrial ecosystems. The bicolored carpenter ant, Camponotus vicinus Mayr, is distributed across a wide range of elevations and latitudes in western North America, where it is a prominent scavenger and predator. Here, we present a high-quality genome assembly of C. vicinus from a sample collected in Sonoma County, California, near the type locality of the species. This genome assembly consists of 38 scaffolds spanning 302.74 Mb, with contig N50 of 15.9 Mb, scaffold N50 of 19.9 Mb, and BUSCO completeness of 99.2%. This genome sequence will be a valuable resource for exploring the evolutionary ecology of C. vicinus and carpenter ants generally. It also provides an important tool for clarifying cryptic diversity within the C. vicinus species complex, a genetically diverse set of populations, some of which are quite localized and of conservation interest.

Development and validation of a product acceptability questionnaire for intranasal Q-Griffithsin COVID-19 prophylaxis (SPRAY PAL).

OBJECTIVES: Patient experiences are critical when determining the acceptability of novel interventional pharmaceuticals. Here, we report the development and validation of a product acceptability questionnaire (SPRAY PAL) assessing feasibility, acceptability and tolerability of an intranasal Q-Griffithsin (Q-GRFT) drug product designed for COVID-19 prophylaxis. DESIGN: SPRAY PAL validation was undertaken as part of an ongoing phase 1 clinical trial designed to test the safety, pharmacokinetics and tolerability of intranasally administered Q-GRFT for the prevention of SARS-CoV-2 infection. SETTING: The phase 1 clinical trial took place at a University Outpatient Clinical Trials Unit from November 2021 to September 2023. PARTICIPANTS: The initial SPRAY PAL questionnaire was piloted among healthy volunteers ages 25 to 55 in phase 1a of the clinical trial (N=18) and revised for administration in phase 1b for participants ages 24-59 (N=22). RESULTS: Spearman correlations tested convergent and discriminant validity. Internal consistency was assessed using Cronbach's alpha, and test-retest reliability was assessed using intraclass correlation coefficients of responses collected from three repeated questionnaire administrations. The initial version demonstrated excellent internal consistency. The revised version demonstrated very good internal consistency after removal of one item (alpha=0.739). Excellent test-retest reliability (intraclass coefficient=0.927) and adequate convergent (r's=0.208-0.774) and discriminant (r's=0.123-0.392) validity were achieved. Subscales adequately distinguished between the constructs of acceptability, feasibility and tolerability. CONCLUSIONS: The SPRAY PAL product acceptability questionnaire is a valid and reliable patient-reported outcomes measure that can be considered a credible tool for assessing patient-reported information about product acceptability, feasibility of use, tolerability of product and side effects and cost of product for novel intranasal drug formulations. The SPRAY PAL is generalisable, and items may be readily adapted to assess other intranasal formulations. TRIAL REGISTRATION NUMBERS: NCT05122260 and NCT05437029.

International e-Delphi Consensus Recommendations for the Assessment and Diagnosis of Circadian rest-Activity Rhythm Disorders (CARDs) in Patients with Cancer.

PURPOSE: Circadian rest-Activity Rhythm Disorders (CARDs) are common in patients with cancer, particularly in advanced disease. CARDs are associated with increased symptom burden, poorer quality of life, and shorter survival. Research and reporting practices lack standardization, and formal diagnostic criteria do not exist. This electronic Delphi (e-Delphi) study aimed to formulate international recommendations for the assessment and diagnosis of CARDs in patients with cancer. METHODS: An international e-Delphi was performed using an online platform (Welphi). Round 1 developed statements regarding circadian rest-activity rhythms, diagnostic criteria, and assessment techniques. Rounds 2 and 3 involved participants rating their level of agreement with the statements and providing comments until consensus (defined internally as 67%) and stability between rounds were achieved. Recommendations were then created and distributed to participants for comments before being finalized. RESULTS: Sixteen participants from nine different clinical specialties and seven different countries, with 5-35 years of relevant research experience, were recruited, and thirteen participants completed all three rounds. Of the 164 generated statements, 66% achieved consensus, and responses were stable between the final two rounds. CONCLUSIONS: The e-Delphi resulted in international recommendations for assessing and diagnosing CARDs in patients with cancer. These recommendations should ensure standardized research and reporting practices in future studies.

The role of body size and cuticular hydrocarbons in the desiccation resistance of invasive Argentine ants (Linepithema humile).

An insect's cuticle is typically covered in a layer of wax prominently featuring various hydrocarbons involved in desiccation resistance and chemical communication. In Argentine ants (Linepithema humile), cuticular hydrocarbons (CHCs) communicate colony identity, but also provide waterproofing necessary to survive dry conditions. Theory suggests different CHC compound classes have functional trade-offs, such that selection for compounds used in communication would compromise waterproofing, and vice versa. We sampled sites of invasive L. humile populations from across California to test whether CHC differences between them can explain differences in their desiccation survival. We hypothesized that CHCs whose abundance was correlated with environmental factors would determine survival during desiccation, but our regression analysis did not support this hypothesis. Interestingly, we found the abundance of most CHCs had a negative correlation with survival, regardless of compound class. We suggest that the CHC differences between L. humile nests in California are insufficient to explain their differential survival against desiccation, and that body mass is a better predictor of desiccation survival at this scale of comparison.

A Throwing Knife Injury to the Neck: Management of a Unique Airway Situation.

Penetrating neck injuries (PNIs) can present as a simple wound or can be complicated by a disruption of the airway or associated vasculature. As such, stabilization of the vasculature and the airway is paramount. Here we present a case in which a hemodynamically stable 28-year-old female presents with a PNI involving the oropharynx and laryngopharynx.

Near-Field LED Illumination Strategies for Tonsillectomy and Adenoid Surgery.

Objective: Perform a pilot feasibility study to demonstrate viability, quality, and safety advantages of light-emitting diode (LED) illumination when performing tonsillectomy. Study Design: Prospective cohort. Setting: Children's Hospital and Community Multispecialty Hospital. Methods: We tested a commercially available LED light, held in position with a minimally modified mouth gag, for off-label use in a "cavernous wound." We assessed surgeons', residents', and nurses' perceptions of function, safety, as well as preferences compared to headlights. Results: The light was used in 30 cases. Noted advantages over traditional lighting methods included superior brightness, stability and consistency of illumination, and the ability for others to assist more quickly. The inability to adjust brightness and/or the angle of light was an observed disadvantage. A small oral cavity or large tonsillar pillars creating a shadow required the temporary addition of a headlight. However, LED light use was not discontinued. Surgeons and residents reported a preference for not wearing a headlight, and nurses expressed concerns about headlight cleanliness. Conclusion: LED lighting technology demonstrated utility for teaching surgeons, residents, and nurses, and was perceived as safe. Additional specifications may make the light applicable to a wider variety of cases and could potentially mitigate headlight use during procedures of the oral cavity and oropharynx.Level of Evidence: 4.

Depressive symptoms and shorter survival in lung cancer: the role of leukocyte telomere length.

OBJECTIVE: To examine the association between depressive symptoms, leukocyte telomere length-a marker of cellular ageing, and survival amongst lung cancer patients. DESIGN: Patients with non-small cell lung cancer were recruited from a university-affiliated cancer center clinic. MAIN OUTCOME: Patients (N = 67) reported on depressive symptoms and provided a blood sample for leukocyte telomere length assessment at baseline and at a 3-month follow-up. Survival status was tracked over 3 years. RESULTS: Age at diagnosis and depressive symptoms, as measured by the CES-D, were associated with shorter leukocyte telomere length (p < .05), although only age at diagnosis contributed statistical significance to the model. Depressive symptoms predicted shorter survival from date of diagnosis (p < .01). Patients who reported experiencing clinically meaningful levels of depressive symptoms (CES-D scores ≥ 16) demonstrated shorter survival than those who reported sub-clinical levels of depressive symptoms (p < .05). Leukocyte telomere length did not emerge as a predictor of shorter survival. CONCLUSION: Clinically meaningful levels of depressive symptoms are associated with shorter survival amongst lung cancer patients. These findings support the on-going efforts to screen all cancer patients for low mood and to investigate mechanisms linking depressive symptoms and shorter survival in cancer contexts.

Trends in Emergency Department Computed Tomography Usage for Diagnosis of Peritonsillar Abscess.

OBJECTIVES: Peritonsillar abscess (PTA) is the most common deep neck space infection and a frequent cause for otolaryngology consultation. Patients often undergo computed tomography (CT) scan for confirmation in addition to physical examination. Our aims were to determine whether patients unnecessarily undergo CT scans in the emergency department (ED) when presenting with sore throat and identify physical examination characteristics that predict PTA. METHODS: The electronic medical records of all patients (>18 years) presenting to an ED between June 2014 and June 2015 with a primary diagnosis of acute pharyngitis, acute tonsillitis, or PTA were reviewed for presenting symptoms and diagnostic imaging use. RESULTS: Four hundred eight patients met inclusion criteria; 21 were diagnosed with PTA, including 13 based on history and physical alone. A total of 21 CT scans were ordered, 11 (52.3%) of which did not demonstrate abscess. Soft palatal fullness, uvular deviation, drooling, and muffled voice were all significantly associated with increased CT usage (all P values <.02). Rising subjective pain scores were associated with increased use of CT imaging (P = .029). Multivariable analyses revealed that soft palatal fullness, uvular deviation, and drooling were all significant predictors of PTA (all P values <.001). CONCLUSIONS: Patients with severe symptoms of PTA, including uvular deviation, drooling, and soft palatal fullness, were most likely to undergo CT imaging. Given the high likelihood of PTA, patients presenting with these symptoms could forego CT imaging, reducing exposure to ionizing radiation.

The Inclusion of Voice Assessments to Aid Diagnostic and Surgical Decision Making for Patients With Laryngopharyngeal Reflux.

OBJECTIVE: Patients with suspected laryngopharyngeal reflux (LPR) present with a variety of symptoms, such as cough, hoarseness, and globus sensation, and often do not have the classic features associated with gastroesophageal reflux disease. STUDY DESIGN: To achieve greater clarity in the symptom presentation, response to treatment, and the impact on vocal function among patients presenting with signs and symptoms consistent with LPR, we prospectively evaluated initial assessments and outcomes after medication or surgical management. METHODS: A sample of 109 patients completed self-report measures of reflux symptoms, voice handicap, and underwent diagnostic workup by both laryngologist and foregut surgeon to include laryngoscopy, esophagogastroduodenoscopy, manometry and pH monitoring. Patients were then followed for at least 3 months, and outcomes of therapy were recorded. RESULTS: The most common indicators on initial workup were reflux symptom inventory score ≥ 13 and at least one abnormality on manometry. Male patients were significantly more likely to demonstrate esophagitis on biopsy, abnormal upper esophageal sphincter mean pressure, and acid (vs nonacid) reflux. Older patients were more likely to have normal esophageal distal contractile integral activity. Significantly higher voice handicap ratings were observed among patients with a positive reflux indicator score in addition to abnormal upper esophageal sphincter mean basal pressure and contractile front velocity. Patients with acid versus nonacid reflux were equally as likely to report non-responsivity to antisecretory medications. Among a subset of patients with 3-month follow-up data (N = 39), reflux scores were significantly lower irrespective of treatment modality (surgical vs pharmacological intervention). CONCLUSION: Extensive comprehensive workup did not reveal a single predictive indicator for LPR. Voice assessments may be more sensitive to upper esophageal symptomatology or dysfunction compared to reflux assessments, which may be better indicators of inflammation. Our collaborative data confirms the value of assessing vocal quality and impairment, especially in the presence of equivocal reflux indicators, as together these measures may achieve greater sensitivity to reflux issues and may aid in surgical decision making.

An Unexpected Role for Cell Density Rather than IgM in Cell-Surface Display of the Fc Receptor for IgM on Human Lymphocytes.

The Fc receptor for IgM, FcMR, is unusual in that it is preferentially expressed by cells of the adaptive immune system. It is, moreover, the only constitutively expressed Fc receptor on human T cells. Efforts to decipher the normal functions of FcMR have been complicated by species-specific expression patterns in lymphocytes from mice (B cells) versus humans (B, NK, and T cells). In human cells, FcMR cell-surface expression has been reported to be low at baseline ex vivo, with one suggested contribution being ligand-induced internalization by serum IgM. Indeed, preincubation overnight in IgM-free culture medium is recommended for studies of FcMR because surface display is increased under these conditions. We investigated FcMR display on human lymphocytes in PBMCs and found that, surprisingly, cell-surface FcMR was unaffected by IgM abundance and was instead downregulated in high-cell density cultures by a yet undefined mechanism. We further found that ex vivo processing of whole blood decreased surface FcMR, supporting the idea that FcMR expression is likely to be greater on circulating lymphocytes than previously appreciated. Collectively, these findings prompt new predictions of where and when FcMR might be available for functional interactions in vivo.

Association of Stress-Health Factors among Parkinson's Disease Patient/Caregiving-Partner Dyads.

OBJECTIVE: Few studies have explored the shared effects of Parkinson's disease (PD) within patient/caregiver dyads. To fill this gap, we compared stress-health outcomes of patients with those of caregiving-partners, examined individual stress-health associations, and explored stress-health associations within dyads. METHOD: A total of 18 PD patient/caregiving-partner dyads (N = 36) reported on disease-specific distress, anxiety, quality of life (QOL), and provided saliva samples for cortisol assessment. This cross-sectional, secondary analysis of a prospective pilot study used Actor-Partner Interdependence Models to test aims. RESULTS: Patients reported greater anxiety, poorer QOL, and demonstrated flatter cortisol slopes and higher mean bedtime cortisol compared to caregiving-partners. Both patients and caregiving-partners with greater anxiety had elevated bedtime cortisol and poorer QOL. Greater disease-specific distress in an individual was associated with higher diurnal mean cortisol in their partner. CONCLUSIONS: Findings highlight the potential for psychosocial interventions at the dyadic level to reduce shared burden and promote coping among PD patient/caregiving-partner dyads.

Bactericidal effects of high-energy visible light on common otitis media pathogens.

AIMS: This study assessed the use of high-energy, visible light on the survival rates of three bacteria commonly found in middle ear infections (i.e. otitis media; Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae). METHOD AND RESULTS: Bacteria were cultured and then subjected to a single, 4-h treatment of 405 nm wavelength light at two different intensities. All three bacteria species were susceptible to the light at clinically significant rates (>99.9% reduction). Bacteria were susceptible to the high-energy visible (HEV) light in a dose-dependent manner (lower survival rates with increased intensity and duration of exposure). CONCLUSIONS: The results suggest that HEV light may provide a non-surgical, non-pharmaceutical approach to the therapeutic treatment of otitis media. SIGNIFICANCE AN IMPACT OF THE STUDY: Given the growing concerns surrounding antibiotic resistance, this study demonstrates a rapid, alternative method for effective inactivation of bacterial pathogens partly responsible for instances of otitis media.

Reviewers on Reviewing for Psychological, Health and Medical Journals.

Being a reviewer is an honor and it continues to be a very rewarding experience throughout a career. Reviewers get the opportunity to maintain scientific standards and assist in growing the scientific psychological literature. Being a reviewer enhances and integrates scientific values and clinical skills following the scientist-practitioner model. However, for the inexperienced reviewer, the experience can be very scary and intimidating. Everyone's experience with reviewing is highly personal and at the same time, the activity is both common and universal for academic psychologists. In this interview article, three seasoned reviewers respond to questions about their experience as journal reviewers reflecting in their answers their collective wisdom and knowledge in this area.

Patterns of Psychologists' Interprofessional Collaboration Across Clinical Practice Settings.

Healthcare increasingly emphasizes collaborative treatment by multidisciplinary teams. This is the first research focusing on psychologists' participation in team-based care, the mix of professionals with whom psychologists collaborate, and how these collaborations vary across practice settings. Data are from 1607 respondents participating in the American Psychological Association Center for Workforce Studies' 2015 on-line Survey of Psychology Health Service Providers. Practice settings differed markedly in systemic organizational support for interprofessional collaboration and in psychologists' participation in collaborative activities. Psychologists in individual private practice reported least support for and least occurrence of interprofessional collaboration. Psychologists' collaboration with non-behavioral health professionals, such as non-psychiatrist physicians and nurses, was more frequent in general hospitals and VA medical centers. Across settings, greater contact with another health profession was generally associated with psychologists being more confident about working with that profession. However, for work with psychiatrists, that association was attenuated. A collaborative practice model is presented for psychotherapy patients also treated by physicians or other professionals who manage a patient's psychotropic medication.

Developmental, cellular and biochemical basis of transparency in clearwing butterflies.

The wings of butterflies and moths (Lepidoptera) are typically covered with thousands of flat, overlapping scales that endow the wings with colorful patterns. Yet, numerous species of Lepidoptera have evolved highly transparent wings, which often possess scales of altered morphology and reduced size, and the presence of membrane surface nanostructures that dramatically reduce reflection. Optical properties and anti-reflective nanostructures have been characterized for several 'clearwing' Lepidoptera, but the developmental processes underlying wing transparency are unknown. Here, we applied confocal and electron microscopy to create a developmental time series in the glasswing butterfly, Greta oto, comparing transparent and non-transparent wing regions. We found that during early wing development, scale precursor cell density was reduced in transparent regions, and cytoskeletal organization during scale growth differed between thin, bristle-like scale morphologies within transparent regions and flat, round scale morphologies within opaque regions. We also show that nanostructures on the wing membrane surface are composed of two layers: a lower layer of regularly arranged nipple-like nanostructures, and an upper layer of irregularly arranged wax-based nanopillars composed predominantly of long-chain n-alkanes. By chemically removing wax-based nanopillars, along with optical spectroscopy and analytical simulations, we demonstrate their role in generating anti-reflective properties. These findings provide insight into morphogenesis and composition of naturally organized microstructures and nanostructures, and may provide bioinspiration for new anti-reflective materials.

The role of the circadian clock in cancer hallmark acquisition and immune-based cancer therapeutics.

The circadian system temporally regulates physiology to maintain homeostasis. Co-opting and disrupting circadian signals appear to be distinct attributes that are functionally important for the development of a tumor and can enable or give rise to the hallmarks that tumors use to facilitate their initiation, growth and progression. Because circadian signals are also strong regulators of immune cell proliferation, trafficking and exhaustion states, they play a role in how tumors respond to immune-based cancer therapeutics. While immuno-oncology has heralded a paradigm shift in cancer therapeutics, greater accuracy is needed to increase our capability of predicting who will respond favorably to, or who is likely to experience the troubling adverse effects of, immunotherapy. Insights into circadian signals may further refine our understanding of biological determinants of response and help answer the fundamental question of whether certain perturbations in circadian signals interfere with the activity of immune checkpoint inhibitors. Here we review the body of literature highlighting circadian disruption as a cancer promoter and synthesize the burgeoning evidence suggesting circadian signals play a role in how tumors respond to immune-based anti-cancer therapeutics. The goal is to develop a framework to advance our understanding of the relationships between circadian markers, cancer biology, and immunotherapeutics. Bolstered by this new understanding, these relationships may then be pursued in future clinical studies to improve our ability to predict which patients will respond favorably to, and avoid the adverse effects of, traditional and immune-based cancer therapeutics.

Postoperative Recurrent Cholesteatoma in Rural Versus Urban Populations.

OBJECTIVE: Chronic ear disease presents a unique challenge to otolaryngologists in both rural and urban settings. Cholesteatoma remains a difficult disease to treat in rural populations due to limited healthcare access and high risk of recurrence. The purpose of this study was to determine if there are differences in surgical outcomes among patients with acquired cholesteatoma residing in rural versus urban settings. STUDY DESIGN: Single-surgeon retrospective case series with chart review. SETTING: Tertiary care private otolaryngology practice. PATIENTS: One hundred twenty-two patients presenting to the Kentuckiana ENT otology and neurotology practice from January 2011 to May 2017. MAIN OUTCOME MEASURES: Surgical outcomes including recurrence, air-bone gap improvement, ossicular integrity, and complications were reviewed and compared between the rural and urban cohorts. RESULTS: Presence of postoperative residual cholesteatoma (OR = 8.667, 95% CI = 2.022-37.141, p = 0.008) and number of surgeries per patient (OR = 5.185, 95% CI = 1.086-24.763, p = 0.024) were significantly increased among patients in rural nonmetropolitan areas. No significant differences were found when comparing risk of recurrence, size of cholesteatoma, presence of complications, air-bone gap improvement, and ossicular chain integrity. There were significantly more second-look surgeries performed in privately insured patients (OR = 8.582, 95% CI = 1.937-38.017, p = 0.001). CONCLUSIONS: Patients in rural communities have an increased number of surgeries and postoperative risk for residual cholesteatoma compared to patients residing in urban settings. This study provides the basis for larger, multicenter, prospective examinations of outcomes among urban versus rural patients, which would enable a better understanding of difference in surgical outcomes between rural and urban cohorts.Level of Evidence: IV.

Temporal Bone Fractures Caused by Ballistic Projectiles: A Systematic Review.

OBJECTIVE: Ballistic injuries to the temporal bone are uncommon but devastating injuries that damage critical neurovascular structures. This review describes outcomes after ballistic injuries to the temporal bone and offers initiatives for standardized high-quality future research. DATA SOURCES: A systematic search of PubMed, Embase, and Cochrane. REVIEW METHODS: Studies in the review included adults who experienced temporal bone fractures due to gunshot wounds and survived longer than 48 hours. Individual case reports were excluded. The various searches returned 139 results, of which 6 met inclusion criteria. RESULTS: Most of the included studies are case series with low-level evidence that report a wide range of outcomes and follow-up. Outcomes include demographic patient information, audiologic outcomes, vascular injuries, intracranial complications, facial nerve function, and surgical indications. CONCLUSION: This review is the first to characterize the nature and progression of patients who experienced gunshot wounds to the temporal bone. Although all patients share an etiology of injury, they often have vastly different hospital courses and outcomes. This review provides a basis for future studies to guide care for these injuries, as most of the existing literature includes small dated case series.