Search

Objective: Head and neck cancer is a significant contributor to global otolaryngologic disease burden, with a disproportionate impact on low- and middle-income countries. This study investigates the factors contributing to delays in head and neck cancer diagnosis at the University Teaching Hospital of Kigali (CHUK)., Methods: Cross-sectional study of all patients with a pathologic diagnosis of head and neck cancer presenting to CHUK between January 2021 and June 2022. Sociodemographic data, tumor characteristics, and reasons for delay were collected. Univariate and multivariable analyses were undertaken to evaluate risk factors for delays., Results: Eighty-one patients met criteria for inclusion. Median duration from patient first reported symptoms to initial medical consultation was 52 weeks, from initial medical consultation to referral to CHUK was 4 weeks, and from referral to final pathologic diagnosis was 6 weeks. The most common reason for delay to referral to CHUK was financial (37.04%). Patients who visited traditional healers had higher odds of delay between symptom onset and medical consultation (OR 3.51, CI 1.05-11.70). Delays in final diagnosis after referral were most commonly due to OR availability for biopsy (37.04%) and time for pathology results after biopsy (35.80%). OR availability had a significant impact on duration to final diagnosis (OR 59.48, CI 7.17-493.67). Stage 4 disease had the shortest time to final diagnosis (OR 0.05, CI 0.01-0.45)., Conclusion: Understanding the reasons for delayed diagnosis of head and neck cancer may help guide improvements in care, with the goal of reducing global head and neck burden of disease., Level of Evidence: 3; prospective non-random follow-up study Laryngoscope, 134:1663-1669, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: To evaluate the impact of different techniques of microvascular venous anastomosis on the outcome of free tissue transfer to the head and neck. Methods: Retrospective case series of patients undergoing microvascular free tissue transfer (MFTT) from January 2006 to September 2021. Chi-square tests and t -tests were utilized to identify differences in flap outcomes by technique, and log-binomial regression analyses were utilized to identify differences in flap outcomes by technique. Results: A total of 1055 consecutive MFTTs were analyzed. One hundred four cases required a return to the operating room for any reason, and 19 were attributed to venous compromise (18.0%). Ultimately, there were 22 FTT failures requiring complete revision (2.1%). In total, 1055 MFTTs involved 1352 venous anastomoses, ranging from 1 to 3 anastomoses in each case. End-to-end (ETE) was used 1040 times (76.9%) and end-to-side (ETS) 204 times (15.0%). The calculated risk ratio for venous complication for ETS compared with ETE was 1.17 (0.34-3.98). A microvascular coupler was used in 355 cases (33.6%). The calculated risk ratio for coupler compared with suture anastomoses was 0.92 (0.35-2.39). Conclusions: There were no significant difference in regard to outcomes of MFTT when comparing ETE with ETS, nor when comparing coupler with suture anastomoses.

Fifty years ago, in July 1973, providing care to patients with end stage kidney disease changed dramatically with the implementation of legislation (PL 92-603) that deemed chronic renal disease to be a disability and provided coverage under Medicare for the treatment of the disease. In this article, we discuss the impact of the implementation of PL 92-603., (Copyright© by the American Nephrology Nurses Association.)

Importance: Research in facial plastic and reconstructive surgery (FPRS) in the global health setting, especially in low- and middle-income countries (LMICs), is increasing year by year. As this work progresses, it will be crucial to include voices and perspectives of individuals living in the LMICs being studied., Objective: To characterize and understand international collaborations in published literature on FPRS care in a global health setting and report patterns in whether these articles included authors from the LMICs in which the studies took place., Evidence Review: A systematic bibliometric scoping review of articles in Scopus from 1971 to 2022 was performed using a set list of search terms; studies were included using predetermined inclusion and exclusion criteria. Studies met criteria for inclusion if the abstract or text contained information regarding surgeons from a different country performing surgery or conducting research in an LMIC within the domain of FPRS. Exclusion criteria were studies that did not mention a facial plastic or reconstructive surgery and studies where both an HIC and LMIC were not mentioned., Findings: A total of 286 studies met criteria for inclusion. The highest percentage of studies (n = 72, 25.2%) were conducted across multiple countries. A total of 120 studies (41.9%) discussed cleft lip/palate. Overall, 141 studies (49.5%) included at least 1 author from the host LMIC; 89 (31.1%) had first authors from LMICs, and 72 (25.2%) had senior authors from LMICs. A total of 79 studies (27.6%) described humanitarian clinical service trips without mentioning research or education in the text. The remaining studies described research, education projects, or a combination. The published literature on humanitarian service trips had the lowest rate of inclusion of a first or senior author from the host LMICs., Conclusions and Relevance: In this systematic bibliometric scoping review, findings showed a general trend of increased international work in the field of FPRS. However, there continues to be a paucity of inclusive authorship trends, with the majority of studies not including first or senior authors from LMICs. The findings presented here encourage new collaborations worldwide, as well as the improvement of existing efforts.

Objectives: Parotidectomy defects can leave patients with considerable functional and cosmetic deformities. We aim to compare the success rates and complications associated with vascularized versus nonvascularized adipofascial grafts for reconstruction, including flap failure, return to surgery, infection, and delay to adjuvant treatment. Methods: Retrospective case series of patients undergoing either adipofascial anterolateral thigh (AFALT) free tissue transfer or free fat transfer (FFT) after parotidectomy from January 2010 to January 2020. Group comparisons and logistic regression were used to determine predictors of outcome measures. Results: Seventy-six patients underwent AFALT reconstruction, and 73 patients underwent FFT reconstruction. Patients treated with AFALT reconstruction had more aggressive tumor characteristics and underwent more complex resections, most commonly radical parotidectomy ( n  = 55, 72.4%). Postoperative complications at both the donor and recipient sites were more common in the FFT group ( N  = 20, 27.4% in FFT vs. N  = 11, 14.5% in AFALT, odds ratio = 0.45, 95% confidence interval = 0.20-1.02, p  = 0.052). Conclusions: Although used in more advanced disease and in a more heavily treated wound bed, the AFALT free flap was safe and associated with fewer infectious complications than that offered by FFT.

Objectives: Craniomaxillofacial (CMF) trauma represents a significant proportion of global surgical disease burden, disproportionally affecting low- and middle-income countries where care is often delayed. We investigated risk factors for delays to care for patients with CMF trauma presenting to the highest-volume trauma hospital in Rwanda and the impact on complication rates., Study Design: This prospective cohort study comprised all patients with CMF trauma presenting to the University Teaching Hospital of Kigali, Rwanda, between June 1 and October 1, 2020., Setting: Urban referral center in resource-limited setting., Methods: Epidemiologic data were collected, and logistic regression analysis was undertaken to explore risk factors for delays in care and complications., Results: Fifty-four patients (94.4% men) met criteria for inclusion. The mean age was 30 years. A majority of patients presented from a rural setting (n = 34, 63%); the most common cause of trauma was motor vehicle accident (n = 18, 33%); and the most common injury was mandibular fracture (n = 28, 35%). An overall 78% of patients had delayed treatment of the fracture after arrival to the hospital, and 81% of these patients experienced a complication (n = 34, P = .03). Delay in treatment was associated with 4-times greater likelihood of complication (odds ratio, 4.25 [95% CI, 1.08-16.70]; P = .038)., Conclusion: Delay in treatment of CMF traumatic injuries correlates with higher rates of complications. Delays most commonly resulted from a lack of surgeon and/or operating room availability or were related to transfers from rural districts. Expansion of the CMF trauma surgical workforce, increased operative capacity, and coordinated transfer care efforts may improve trauma care., Competing Interests: Disclosures: Competing interests: None. Sponsorships: None. Funding source: None., (© The Authors 2022.)

Objective: To better understand the impact of the otolaryngology-specific workforce on the burden of related diseases., Study Design: Retrospective analysis of existing workforce density data as compared with the incidence, mortality, and morbidity data for 4 otolaryngologic diseases., Setting: An overall 138 countries with known otolaryngology-head and neck surgery workforce and epidemiologic data., Methods: We obtained raw data on workforce estimates of ear, nose, and throat surgical specialists from the World Health Organization. Disease burdens for 4 conditions were estimated via 2 ratios, the mortality:incidence ratio (MIR) and YLD:incidence ratio (years lost to disability), as specified in the Global Burden of Disease database. These were correlated to country-specific otolaryngologist density data in univariate and multivariate analyses., Results: Increased density of the ear, nose, and throat workforce correlated with better outcomes for otolaryngologic-treated surgical diseases. A 10% increase in otolaryngology workforce density was associated with a 0.27% reduction in YLD:incidence ratio for chronic otitis media, a 0.94% reduction in MIR for lip and oral cavity cancer, a 1.46% reduction in MIR for laryngeal cancer, and a 1.34% reduction in MIR for pharyngeal cancer (all P < .001)-an effect that remained after adjustment for health systems factors for all conditions but chronic otitis media., Conclusion: The density of the surgical workforce is assumed to affect disease outcomes, but ours is the first analysis to show that increased workforce density for a specific surgical specialty correlates with improved disease outcomes. While there is a consensus to increase access to health care providers, quantifying the effect on disease outcomes is an important metric for those performing health economics modeling, particularly where resources are limited., Competing Interests: Disclosures: Competing interests: None. Sponsorships: None. Funding source: None., (© The Authors 2022.)

Objective: The prognostic significance of bone invasion in oral cavity squamous cell carcinoma (OCSCC) after accounting for tumor size, nodal spread, and surgical margins is controversial. The aim of this study is to determine whether patients with pT4aN0 oral cavity squamous cell carcinoma with bone invasion have improved overall and disease-free survival with adjuvant treatment., Methods: We conducted a retrospective review of medical records from 64 patients with stage pT4aN0 due to mandibular involvement who underwent surgery from 2000 to 2020. Kaplan-Meier analysis compared disease-free survival and overall survival between groups who underwent surgery only versus surgery and adjuvant therapy. The prognostic impact of adjuvant therapy was assessed using multivariate analysis and reported as hazard ratios., Results: There were no statistically significant differences in clinicopathologic features or mean follow-up between patients who received surgery only and patients who received surgery with RT/CCRT (radiotherapy/concurrent chemoradiation therapy). 5-year disease-free (42.5% versus 65.9%, p = 0.02) and overall survival (43.6% versus 69.0%, p = 0.014) were improved in groups who received surgery and RT/CCRT. Regression analysis controlling for clinicopathologic characteristics, including tumor size, identified radiation as an independent predictor of improved disease-free survival (HR: 0.04, p < 0.001) and overall survival (HR: 0.10, p < 0.001)., Conclusion: Adjuvant RT/CCRT in patients with pT4N0 OCSCC with mandibular bone involvement is associated with improved disease-free and overall survival. This association was significant regardless of tumor pathologic features such as size or margin status. These findings may help guide physicians in counseling patients regarding risks and benefits of adjuvant RT/CCRT and inform practice guidelines., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is rising in prevalence and is associated with better survival than HPV-negative OPSCC. In surgically treated HPV-negative OPSCCs, adverse pathologic features such as positive surgical margins, extra-nodal extension (ENE) and perineural invasion are well described to portend worse clinical outcomes. These adverse pathological features, however, are not validated prognostic markers among surgically treated HPV-positive OPSCCs. To that end, we pooled all available evidence to address the prognostic significance of these histologic features., Patients and Methods: This meta-analysis was performed according to PRISMA guidelines. PubMed, Web of Science and Embase databases were systematically searched for articles evaluating 13 known adverse histopathological prognostic factors of surgically treated HPV-associated OPSCC. Data analysis was done using R v4.0.5., Results: A total of 32 studies (n = 31,535) fulfilled the inclusion criteria. ENE and advanced pT stage were associated with poorer overall survival (OS) [hazard ratio (HR):1.80, 95% confidence interval (CI) [1.59-2.03], p < 0.0001, HR: 3.28, 95% CI [2.20-4.87], p = 0.0025]; disease-specific survival (DSS) (HR: 3.14, 95% CI [1.20-8.26], p = 0.0327, HR: 3.49, 95% CI [2.45-4.96], p = 0.0043) and disease-free survival (DFS) (HR: 2.03, 95% CI [1.05-3.94], p = 0.0397, HR: 3.66, 95% CI [2.81-4.77], p = 0.0001) respectively. The presence of lymphovascular invasion (HR: 1.46, 95% CI [1.22-1.75], p = 0.0018) and positive margins (HR: 1.50, 95% CI [1.185-1.899], p = 0.0069) significantly worsen OS., Conclusion: ENE, advanced pT stage, positive margins and lymphovascular invasion were adverse histologic prognostic marker among surgically treated HPV-positive OPSCC. The presence of these factors should be carefully evaluated in order to select the optimal patients for surgical treatment., (© 2024. Society of Surgical Oncology.)

Dysregulation of skeletal muscle morphology and metabolism is associated with chronic diseases such as obesity and type 2 diabetes. The enzyme glycogen synthase kinase 3 (GSK3) is highly involved in skeletal muscle physiology and metabolism, acting as a negative regulator of muscle size, strength, adaptive thermogenesis, and glucose homeostasis. Correspondingly, we have shown that partial knockdown (~40%) of GSK3 specifically in skeletal muscle increases lean mass, reduces fat mass, and activates muscle-based adaptive thermogenesis via sarco(endo)plasmic reticulum Ca2+ (SERCA) uncoupling in male mice. However, the effects of GSK3 knockdown in female mice have yet to be investigated. Here, we examined the effects of muscle-specific GSK3 knockdown on body composition, muscle size and strength, and whole body metabolism in female C57BL/6J mice. Our results show that GSK3 content is higher in the female soleus versus the male soleus; however, there were no differences in the extensor digitorum longus (EDL). Furthermore, muscle-specific GSK3 knockdown did not alter body composition in female mice, nor did it alter daily energy expenditure, glucose/insulin tolerance, mitochondrial respiration, or the expression of the SERCA uncouplers sarcolipin and neuronatin. We also did not find any differences in soleus muscle size, strength, or fatigue resistance. In the EDL, we found that an increase in absolute and specific force production, but there were no differences in fatigability. Therefore, our study highlights sex differences in the response to genetic reduction of gsk3, with most of the effects previously observed in male mice being absent in females. [ABSTRACT FROM AUTHOR]

Background: Despite the important role of the Aesthetic Plastic Surgery (APS) journal in the field of aesthetic plastic surgery, there is a notable absence of literature that focuses exclusively on the bibliometric analysis of this journal. In recognition of APS's 48 years of publishing, this study aims to perform a bibliometric analysis of the articles published in the APS (1976-2023)., Methods: Articles published in the APS were extracted from the Web of Science Core Collection database. VOSviewer was employed to perform bibliometric analyses. Microsoft Excel was utilized to analyse the publication and citation trends., Results: From 1976 to 2023, 5134 articles were published in the APS. These articles were contributed by 12,963 researchers from 3354 institutions across 91 countries. The USA and China were the leading contributors. The most prolific author is Luan Jie from China. The co-citation networks highlighted the influence of the journal Plastic and Reconstructive Surgery. We categorized the articles into four groups, and the results show that articles with the highest publications and citations in the APS are related to facial cosmetic surgery. In terms of specific surgical procedures, breast augmentation surgery has garnered consistent attention from researchers over the past 48 years, ranking first in both the number of publications and citations., Conclusion: The findings of this study indicate that the APS is a significant scientific journal, is widely utilized by global researchers in the field of aesthetic plastic surgery, and spans diverse knowledge domains., Level of Evidence V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Background and Objectives: Dual amylin and calcitonin receptor agonists (DACRAs) are therapeutic candidates in the treatment of obesity with beneficial effects on weight loss superior to suppression of food intake. Hence, suggesting effects on energy expenditure by possibly targeting mitochondria in metabolically active tissue., Methods: Male rats with HFD-induced obesity received a DACRA, KBP-336, every third day for 8 weeks. Upon study end, mitochondrial respiratory capacity (MRC), - enzyme activity, - transcriptional factors, and -content were measured in perirenal (pAT) and inguinal adipose tissue. A pair-fed group was included to examine food intake-independent effects of KBP-336., Results: A vehicle-corrected weight loss (23.4 ± 2.8%) was achieved with KBP-336, which was not observed to the same extent with the food-restricted weight loss (12.4 ± 2.8%) (P < 0.001). Maximal coupled respiration supported by carbohydrate and lipid-linked substrates was increased after KBP-336 treatment independent of food intake in pAT (P < 0.01). Moreover, oligomycin-induced leak respiration and the activity of citrate synthase and β-hydroxyacetyl-CoA-dehydrogenase were increased with KBP-336 treatment (P < 0.05). These effects occurred without changes in mitochondrial content in pAT., Conclusions: These findings demonstrate favorable effects of KBP-336 on MRC in adipose tissue, indicating an increased energy expenditure and capacity to utilize fatty acids. Thus, providing more mechanistic insight into the DACRA-induced weight loss., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

In inclusive education, students with different needs learn in the same context. With the advancement of artificial intelligence (AI) technologies, it is expected that they will contribute further to an inclusive learning environment that meets the individual needs of diverse learners. However, in Japan, we did not find any studies exploring current needs in an actual special needs context. In this study, we used the learning and evidence analysis framework (LEAF) as a learning analytics-enhanced learning environment and employed Active Reading as an example learning task to investigate the challenges and possibilities of applying AI to inclusive education in the future. Two students who attended a resource room formed the context. We investigated learning logs in the LEAF system while each student executed a given learning task. We detected specific learning behaviors from the logs and explored the challenges and future potential of learning with AI technology, considering human involvement in orchestrating inclusive educational practices. [ABSTRACT FROM AUTHOR]

Migraine is a debilitating disorder that afflicts over 1 billion people worldwide, involving attacks that result in a throbbing and pulsating headache. Migraine is thought to be a neurovascular event associated with vasoconstriction, vasodilation, and neuronal activation. Understanding signaling in migraine pathology is central to the development of therapeutics for migraine prophylaxis and for mitigation of migraine in the prodrome phase before pain sets in. The fact that both vasoactivity and neural sensitization are involved in migraine indicates that agonists which promote these phenomena may very well be involved in migraine pathology. One such group of agonists is the purines, in particular, adenosine phosphates and their metabolites. This manuscript explores what is known about the relationship between these metabolites and migraine pathology and explores the potential for such relationships through their known signaling pathways. [ABSTRACT FROM AUTHOR]

Objective: To survey members of the otolaryngology community about their personal and observed experiences of being treated differently because of one's physical attributes, cultural norms, or preferences in the workplace. Study Design: Cross‐sectional survey. Setting: International Electronic Survey. Methods: We invited members of the international otolaryngology community including 3 European or American otorhinolaryngological Societies to complete a survey about personal/observed experience of differential treatment in the workplace related to age, biological sex; disability, gender identity, language proficiency, military experience, citizenship, ethnicity/race, political belief, and sexual orientation. Results were analyzed according to participant ethnicity/race (white vs non‐white) and gender (male vs female) Results: Four hundred seven participants completed the evaluations: 301 white (74%) and 106 non‐white (26%) participants. Non‐white participants reported significantly more experiences of differential treatment (microaggressions) than white participants (p <.05). Non‐white participants more frequently felt that they needed to work harder for the same opportunities as their peers and were more likely to consider leaving a position because of an unsupportive environment. In general, females reported more frequent experiences with differential treatment related to sexual orientation, biological sex, and gender identity than males. Conclusion: We recognized reports of differential treatment as a proxy for microaggressions. Non‐white members of the otolaryngology community self‐report experiencing or observing more microaggressions than white members in the workplace. Acknowledging the existence and impact of microaggressions in the field of Otolaryngology is the first step towards cultivating an inclusive, diverse workforce where all members feel supported, validated, and welcomed. [ABSTRACT FROM AUTHOR]

Long-term high-fat feeding results in intramyocellular lipid accumulation, leading to insulin resistance. Intramyocellular lipid accumulation is related to an energy imbalance between excess fat intake and fatty acid consumption. Alternating current electromagnetic field exposure has been shown to enhance mitochondrial metabolism in the liver and sperm. Therefore, we hypothesized that alternating current electromagnetic field exposure would ameliorate high-fat diet-induced intramyocellular lipid accumulation via activation of fatty acid consumption. C57BL/6J mice were either fed a normal diet (ND), a normal diet and exposed to an alternating current electromagnetic field (ND+EMF), a high-fat diet (HFD), or a high-fat diet and exposed to an alternating current electromagnetic field (HFD+EMF). Electromagnetic field exposure was administered 8 hrs/day for 16 weeks using an alternating current electromagnetic field device (max.180 mT, Hokoen, Utatsu, Japan). Tibialis anterior muscles were collected for measurement of intramyocellular lipids, AMPK phosphorylation, FAT/CD-36, and carnitine palmitoyltransferase (CPT)-1b protein expression levels. Intramyocellular lipid levels were lower in the HFD + EMF than in the HFD group. The levels of AMPK phosphorylation, FAT/CD-36, and CPT-1b protein levels were higher in the HFD + EMF than in the HFD group. These results indicate that alternating current electromagnetic field exposure decreases intramyocellular lipid accumulation via increased fat consumption. [ABSTRACT FROM AUTHOR]

Background: Injuries remain one of the leading causes of death globally. These disproportionately affect young adults and are particularly prevalent in sub-Saharan Africa (SSA). Maxillofacial injuries (MI) pose significant challenges to public health systems. However, much remains unknown regarding the epidemiology and extent of the financial burden in resource-limited areas, such as SSA, further necessitating more research and support. This scoping review aims to investigate the mechanism, distribution, and financial impact of MI in adults aged ≥ 18 years in SSA. Main body: The scoping review was guided by the methodological frameworks of Arksey and O'Malley and Levac. An electronic literature search for English-published articles on maxillofacial injuries in adults ≥ 18 years was conducted in Scopus, Medline, PubMed, Science Direct, CINAHL, Health Source: Nursing/Academic Edition, and grey literature. The PRISMA chart was used to document database searches and screening outcomes while reporting was guided by PRISMA-ScR. The data extraction process revolved around the predefined study outcomes, which encompassed the study characteristics and epidemiological parameters. The review used a narrative approach to report findings and evaluate publication quality using the STROBE checklist. The database search yielded 8246 studies, of which 30 met the inclusion criteria. A total of 7317 participants were included, 79.3% of whom were males. The peak age range for incidence was between 18 and 40 years. Road traffic collision (RTC) was the leading cause of MI, 59% of which resulted from motorcycle collisions. Assault/interpersonal violence ranked as the second leading cause of MI. The mandible was MI's most frequently affected hard tissue, followed by the midface. Factors such as alcohol/illicit drug use, poor knowledge of traffic regulations, and non-observance of these regulations were associated with MI. In our study, the cost range for mandibular fractures was $200-$468.6, borne by victims and their families. Conclusions: Maxillofacial injuries are predominantly caused by road traffic collisions and assaults in SSA. The findings can provide valuable insights into policy decisions and prevention strategies aimed at reducing injury burden. Further research is warranted to explore the psychological impact of MI, including PTSD, for tailored support and intervention. Scoping Review Registration The protocol has been registered on the Open Science Framework. Registration DOI: https://doi.org/10.17605/OSF.IO/BWVDK. [ABSTRACT FROM AUTHOR]

Aim- Metabolic fuel detectors regulate energy balance at peripheral and central levels. The aim of this study is to assess association of serum Orexin levels with Metabolic risk markers in women of reproductive age group. Material And Methods- The study was conducted in campus of King George Medical University (KGMU), Uttar Pradesh Lucknow, INDIA. 150 apparently healthy women of reproductive age group i.e. 20-40 years of age were randomly selected. Fasting serum orexin and Serum insulin levels were measured using ELISA and weight, Body mass index, Fasting blood glucose, Lipid prole and Blood pressure were estimated in women. Result- The results show that Serum orexin levels has signicant positive correlation with fasting blood glucose, weight, BMI and waist circumference along with a weak negative correlation with serum Insulin level. Conclusion- In present study Serum orexin levels signicantly correlate with weight, BMI, Fasting blood glucose and weak negative correlation with serum Insulin levels. serum orexin levels did not correlate with lipid prole of women of reproductive age group. [ABSTRACT FROM AUTHOR]

Allergic airway inflammation (AAI) is a chronic respiratory disease that is considered a severe restriction in daily life and is accompanied by a constant risk of acute aggravation. It is characterized by IgE-dependent activation of mast cells, infiltration of eosinophils, and activated T-helper cell type 2 (Th2) lymphocytes into airway mucosa. Purinergic receptor signaling is known to play a crucial role in inducing and maintaining allergic airway inflammation. Previous studies in an ovalbumin (OVA)-alum mouse model demonstrated a contribution of the P2Y2 purinergic receptor subtype (P2RY2) in allergic airway inflammation. However, conflicting data concerning the mechanism by which P2RY2 triggers AAI has been reported. Thus, we aimed at elucidating the celltype-specific role of P2RY2 signaling in house dust mite (HDM)-driven model of allergic airway inflammation. Thereupon, HDM-driven AAI was induced in conditional knockout mice, deficient or intact for P2ry2 in either alveolar epithelial cells, hematopoietic cells, myeloid cells, helper T cells, or dendritic cells. To analyze the functional role of P2RY2 in these mice models, flow cytometry of bronchoalveolar lavage fluid (BALF), cytokine measurement of BALF, invasive lung function measurement, HDM re-stimulation of mediastinal lymph node (MLN) cells, and lung histology were performed. Mice that were subjected to an HDM-based model of allergic airway inflammation resulted in reduced signs of acute airway inflammation including eosinophilia in BALF, peribronchial inflammation, Th2 cytokine production, and bronchial hyperresponsiveness in mice deficient for P2ry2 in alveolar epithelial cells, hematopoietic cells, myeloid cells, or dendritic cells. Furthermore, the migration of bone-marrow-derived dendritic cells and bone-marrow-derived monocytes, both deficient in P2ry2, towards ATP was impaired. Additionally, we found reduced levels of MCP-1/CCL2 and IL-8 homologues in the BALF of mice deficient in P2ry2 in myeloid cells and lower concentrations of IL-33 in the lung tissue of mice deficient in P2ry2 in alveolar epithelial cells. In summary, our results show that P2RY2 contributes to HDM-induced airway inflammation by mediating proinflammatory cytokine production in airway epithelial cells, monocytes, and dendritic cells and drives the recruitment of lung dendritic cells and monocytes. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a common condition in reproductive-aged women that induces reproductive and metabolic derangements. Women with PCOS seem to have disturbances in lipid metabolism in the adipose tissue. Nevertheless, gene expression in adipose tissue of PCOS women and its relation to other disturbances have been fragmentarily investigated. We utilized microarray data to identify the most important up- and down-regulated candidate genes in adipose tissue of PCOS women in contrast to healthy women using the meta-analysis technique. Microarray data produced from three independent experiments (n = 3) conducted on adipose tissue in women with PCOS were retrieved from ArrayExpress. Then, the datasets were merged using the metaSeq package in Rstudio and differentially expressed genes (DEGs) were selected in the studies. The integrative bioinformatics analyses of candidate genes were performed by gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and protein–protein interaction (PPI) network construction. Of these, 12 up-regulated genes and 12 down-regulated genes were identified and assessed as the most highly up-regulated and down-regulated genes in adipose tissue of women with PCOS. These DEGs that were annotated by KEGG analysis were mainly involved in PI3K-Akt, MAPK, Rap1, and Ras signaling pathways, and pathways in cancer such as hepatocellular carcinoma and gastric cancer, as well as metabolic pathways, and brain disorder pathways such as Alzheimer's disease and Huntington disease pathways. In the PPI networks, PRDM10, FGFR2, IGF1R, and FLT1 were the key nodes in the up-regulated networks, while the NDUFAB1 and NME2 proteins were key in the down-regulated networks. Overall, these findings provide insight into the gene expression in adipose tissue of PCOS women and its relation to other disturbances. [ABSTRACT FROM AUTHOR]

Aim: MC903 is a synthetic derivative of vitamin D3 that has been designed to diminish its impact on calcium metabolism and is clinically used as a transdermal reagent for psoriasis. Animal studies showed that an oral or intraperitoneal vitamin D3 treatment prevented the development of obesity. In contrast, the bioavailability of orally administered vitamin D3 is reported to be low in obese patients. In the current study, we aimed to investigate the impact of a transdermal treatment with MC903 in established obese mice. We further studied the underlying mechanisms of MC903-mediated metabolic improvement. Materials and methods: Male C57BL/6 J mice were fed standard chow or a 60% high-fat diet (HFD) for 7 weeks, and a transdermal treatment with MC903 on the ear auricle was initiated thereafter. The metabolic profiles of mice were analyzed during 4 weeks of treatment, and mice were dissected for histological and gene expression analyses. The direct impacts of MC903 and vitamin D3 were investigated using 3T3-L1 adipocytes and C2C12 myotubes in vitro. Results: HFD-fed mice showed significant increases in body and epididymal white adipose tissue (eWAT) weights with enlarged adipocytes. They exhibited glucose intolerance, decreased oxygen consumption, and chronic inflammation in eWAT. The transdermal treatment with MC903 significantly ameliorated these metabolic abnormalities in HFD-fed mice without affecting food consumption. In accordance with enhanced energy metabolism, myofiber diameters and the expression of uncoupling protein 3 (UCP3) in the gastrocnemius and soleus muscle were significantly increased in MC903-treated HFD mice. In addition, vitamin D3 and MC903 both suppressed adipogenic differentiation and enhanced lipolysis in 3T3-L1 adipocytes, and increased UCP3 expression in cultured C2C12 myotubes. Furthermore, MC903 increased oxygen consumption and UCP3 knockdown significantly decreased them in C2C12 myotubes. Conclusions: A transdermal treatment with MC903 increased myofiber diameter and energy metabolism and decreased visceral fat accumulation, thereby improving obesity and glucose intolerance in mice. [ABSTRACT FROM AUTHOR]

Background: Understanding of nodal metastasis in patients with HPV+ oropharyngeal squamous cell carcinoma (OPSCC) is warranted. Methods: Patients with HPV+ OPSCC who underwent neck dissection (ND) between 2016 and 2021 were reviewed. Pathology reports were reviewed for lymph node (LN) metastases. Noncontiguous metastases were defined as pathologic evidence of level II disease with another involved LN in a noncontiguous neck level. Skip metastases were defined as pathologic lymph node(s) in the neck without disease in level II. Results: One hundred and thirty‐one patients underwent levels II–IV ND with a mean (SD) LN yield of 33.3 (±13.5). The rate of atypical metastases in both the therapeutic and elective ND cohort was 5%. The noncontiguous and skip metastases were in level IV (n = 2) and level III (n = 4), respectively. Conclusions: Skip and noncontiguous metastases were rare in patients with HPV+ OPSCC undergoing surgical treatment. Surgeons may consider a selective ND omitting Level IV in select patients with HPV+ OPSCC undergoing surgery. [ABSTRACT FROM AUTHOR]

Uncoupling protein‐3 (UCP3) is a mitochondrial transmembrane protein highly expressed in the muscle that has been implicated in regulating the efficiency of mitochondrial oxidative phosphorylation. Increasing UCP3 expression in skeletal muscle enhances proton leak across the inner mitochondrial membrane and increases oxygen consumption in isolated mitochondria, but its precise function in vivo has yet to be fully elucidated. To examine whether muscle‐specific overexpression of UCP3 modulates muscle mitochondrial oxidation in vivo, rates of ATP synthesis were assessed by 31P magnetic resonance spectroscopy (MRS), and rates of mitochondrial oxidative metabolism were measured by assessing the rate of [2‐13C]acetate incorporation into muscle [4‐13C]‐, [3‐13C]‐glutamate, and [4‐13C]‐glutamine by high‐resolution 13C/1H MRS. Using this approach, we found that the overexpression of UCP3 in skeletal muscle was accompanied by increased muscle mitochondrial inefficiency in vivo as reflected by a 42% reduction in the ratio of ATP synthesis to mitochondrial oxidation. [ABSTRACT FROM AUTHOR]

Rationale: The female menstrual or estrous cycle and its associated fluctuations in circulating estradiol (E2), progesterone, and other gonadal hormones alter orexin or hypocretin peptide production and receptor activity. Depending on the estrous cycle phase, the transcription of prepro-orexin mRNA, post-translational modification of orexin peptide, and abundance of orexin receptors change in a brain region-specific manner. The most dramatic changes occur in the hypothalamus, which is considered the starting point of the hypothalamic-pituitary–gonadal axis as well as the hub of orexin-producing neurons. Thus, hypothalamus-regulated behaviors, including arousal, feeding, reward processing, and the stress response depend on coordinated efforts between E2, progesterone, and the orexin system. Given the rise of orexin therapeutics for various neuropsychiatric conditions including insomnia and affective disorders, it is important to delineate the behavioral outcomes of this drug class in both sexes, as well as within different time points of the female reproductive cycle. Objectives: Summarize how the menstrual or estrous cycle affects orexin system functionality in animal models in order to predict how orexin pharmacotherapies exert varying degrees of behavioral effects across the dynamic hormonal milieu. [ABSTRACT FROM AUTHOR]

The purpose of the study was to assess and compare the quality of speech and swallowing between three reconstruction options (primary closure—group A, secondary intention healing—group B and flap reconstruction—group C), in small to moderate sized onco-surgical defects of oral tongue. 47 patients fulfilled the eligibility criteria during the study period, of which, 15 belonged to group A, 16 belonged to group B, 16 were in group C. Speech and swallowing assessment was done using Speech Intelligibility Assessment score and MD Anderson Dysphagia Inventory, respectively. The above tests were administered pre-operatively, 1 month and 6 months post-operativey in all the study participants. The average scores of speech intelligibility at 1 month were 66.13% (±19.96), 70.04% (±12.28) and 37.31% (±11.29) for groups A, B and C respectively. Similarly, average long term scores for speech intelligibility in these three groups were 72.7% (±17.72), 83.3% (±12.78) and 52.8% (±11.74) respectively. With regards to swallowing the composite scores at 1 month were 73.67 (±13.69), 68.31 (±16.06) and 41.81 (±5.44), and at 6 months were 83.2 (±10.24), 79.31 (±12.29) and 57.88 (±7.37), respectively for groups A, B and C. All the differences were statistically significant (p < 0.05). Healing by secondary intention offered the best functional outcome in terms of speech intelligibility, and primary closure offered best swallowing outcomes in operated cases of oral tongue. This trial has been registered with the Clinical Trials Registry—India in December 2018 (CTRI Reg. No: CTRI/2018/12/016803). [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma (LUAD) is the most common respiratory globallywith a poor prognosis. Lipid metabolism is extremely important for the occurrence and development of cancer. However, the role of genes involved in lipid metabolism in LUAD development is unclear. We aimed to identify the abnormal lipid metabolism pathway of LUAD, construct a novel prognostic model of LUAD, and discover novel biomarkers involved in lipid metabolism in LUAD. Methods: Based on differentially expressed genes involved in lipid metabolism in LUAD samples from The Cancer Genome Atlas (TCGA), abnormal lipid metabolism pathways in LUAD were analyzed. The lasso penalized regression analysis was performed on the TCGA cohort (training set) to construct a risk score formula. The predictive ability of the risk score was validated in the Gene Expression Omnibus (GEO) dataset (validation set) using Kaplan-Meier analysis and ROC curves. Finally, based on CRISPR gene editing technology, hematopoietic prostaglandin D synthase (HPGDS) was knocked out in A549 cell lines, the changes in lipid metabolism-related markers were detected by western blotting, and the changes in cell migration were detected by transwell assay. Results: Based on the differential genes between lung cancer tissue and normal tissue, we found that the arachidonic acid metabolism pathway is an abnormal lipid metabolism pathway in both lung adenocarcinoma and lung squamous cell carcinoma. Based on the sample information of TCGA and abnormally expressed lipid metabolism-related genes, a 9-gene prognostic risk score was successfully constructed and validated in the GEO dataset. Finally, we found that knockdown of HPGDS in A549 cell lines promoted lipid synthesis and is more invasive than in control cells. Rescue assays showed that ACSL1 knockdown reversed the pro-migration effects of HPGDS knockdown. The knockdown of HPGDS promoted migration response by upregulating the expression of the lipid metabolism key enzymes ACSL1 and ACC. Conclusion: The genes involved in lipid metabolism are associated with the occurrence and development of LUAD. HPGDS can be a therapeutic target of a potential lipid metabolism pathway in LUAD, and the therapeutic target of lipid metabolism genes in LUAD should be studied further. [ABSTRACT FROM AUTHOR]

The action of protein kinases and protein phosphatases is essential for multiple physiological responses. Each protein kinase displays its own unique substrate specificity and a regulatory mechanism that may be modulated by association with other proteins. Protein kinases are classified as dual-specificity kinases and dual-specificity phosphatases. Dual-specificity phosphatases are important signal transduction enzymes that regulate various cellular processes in coordination with protein kinases and play an important role in obesity. Impairment of insulin signaling in obesity is largely mediated by the activation of the inhibitor of kappa B-kinase beta and the c-Jun N-terminal kinase (JNK). Oxidative stress and endoplasmic reticulum (ER) stress activate the JNK pathway which suppresses insulin biosynthesis. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) are important for proper regulation of glucose metabolism in mammals at both the hormonal and cellular levels. Additionally, obesity-activated calcium/calmodulin dependent-protein kinase II/p38 suppresses insulin-induced protein kinase B phosphorylation by activating the ER stress effector, activating transcription factor-4. To alleviate lipotoxicity and insulin resistance, promising targets are pharmacologically inhibited. Nifedipine, calcium channel blocker, stimulates lipogenesis and adipogenesis by downregulating AMPK and upregulating mTOR, which thereby enhances lipid storage. Contrary to the nifedipine, metformin activates AMPK, increases fatty acid oxidation, suppresses fatty acid synthesis and deposition, and thus alleviates lipotoxicity. Obese adults with vascular endothelial dysfunction have greater endothelial cells activation of unfolded protein response stress sensors, RNA-dependent protein kinase-like ER eukaryotic initiation factor-2 alpha kinase (PERK), and activating transcription factor-6. The transcriptional regulation of adipogenesis in obesity is influenced by AGC (protein kinase A (PKA), PKG, PKC) family signaling kinases. Obesity may induce systemic oxidative stress and increase reactive oxygen species in adipocytes. An increase in intracellular oxidative stress can promote PKC-β activation. Activated PKC-β induces growth factor adapter Shc phosphorylation. Shc-generated peroxides reduce mitochondrial oxygen consumption and enhance triglyceride accumulation and lipotoxicity. Liraglutide attenuates mitochondrial dysfunction and reactive oxygen species generation. Co-treatment of antiobesity and antidiabetic herbal compound, berberine with antipsychotic drug olanzapine decreases the accumulation of triglyceride. While low-dose rapamycin, metformin, amlexanox, thiazolidinediones, and saroglitazar protect against insulin resistance, glucagon-like peptide-1 analog liraglutide inhibits palmitate-induced inflammation by suppressing mTOR complex 1 (mTORC1) activity and protects against lipotoxicity., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Objective: To determine the cost-effectiveness of surveillance imaging with PET/CT scan among patients with human papillomavirus-positive oropharyngeal squamous cell carcinoma., Study Design: Cost-effectiveness analysis., Setting: Oncologic care centers in the United States with head and neck oncologic surgeons and physicians., Methods: We compared the cost-effectiveness of 2 posttreatment surveillance strategies: clinical surveillance with the addition of PET/CT scan versus clinical surveillance alone in human papillomavirus-positive oropharyngeal squamous cell carcinoma patients. We constructed a Markov decision model which was analyzed from a third-party payer's perspective using 1-year Markov cycles and a 30-year time horizon. Values for transition probabilities, costs, health care utilities, and their studied ranges were derived from the literature., Results: The incremental cost-effectiveness ratio for PET/CT with clinical surveillance versus clinical surveillance alone was $89,850 per quality-adjusted life year gained. Flexible fiberoptic scope exams during clinical surveillance would have to be over 51% sensitive or PET/CT scan cost would have to exceed $1678 for clinical surveillance alone to be more cost-effective. The willingness-to-pay threshold at which imaging surveillance was equally cost-effective to clinical surveillance was approximately $80,000/QALY., Conclusion: Despite lower recurrence rates of human papillomavirus-positive oropharyngeal cancer, a single PET/CT scan within 6 months after primary treatment remains a cost-effective tool for routine surveillance when its cost does not exceed $1678. The cost-effectiveness of this strategy is also dependent on the clinical surveillance sensitivity (flexible fiberoptic pharyngoscopy), and willingness-to-pay thresholds which vary by country., (© 2023 The Authors. Otolaryngology-Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Background: As opposed to observation of the neck, elective neck dissection has a survival benefit for cN0 oropharyngeal squamous cell carcinoma (OPSCC). However, there are limited date on level IV neck dissection in human papillomavirus (HPV)-negative OPSCC because most earlier studies did not stratify by P16 or HPV status. Thus, whether to exclude level IV from selective dissection (SND) of cN0 HPV-negative OPSCC remains controversial.Methods: In this single-center retrospective cohort study, disease-free survival (DFS) was estimated as the primary endpoint for 124 cN0 HPV-negative OPSCC patients who received SND of levels I-III (Group A) and I-IV (Group B). Overall survival (OS) and disease-specific survival (DSS) were considered secondary endpoints.Results: For the entire cohort, the 5-year DFS rates of Groups A and B were 55.0% and 60.1%, respectively. Five-year OS rates were 58.9% and 61.5%, and 5-year DSS rates were 74.0% and 64.8%, respectively. Group B did not show higher 5-year DFS, OS, or DSS than Group A.Conclusions: This retrospective cohort study validated that in cN0 HPV-negative OPSCC, SND including level IV does not have substantial benefits regarding DFS, OS or DSS. [ABSTRACT FROM AUTHOR]

Objective: To analyze the oncologic outcomes and risk factors for recurrence in patients who underwent surgery for oropharyngeal squamous cell carcinoma (OPSCC), and in whom adjuvant therapy was not recommended or was declined. Methods: Retrospective cohort study of patients with OPSCC who were treated with transoral surgery only at a tertiary care academic medical center from April 2010 to March 2019. Results: Seventy-four patients met inclusion criteria. In 16, adjuvant therapy was recommended but declined. There were 8 recurrences, of which 6 had been given recommendations for adjuvant therapy. Of the 8 recurrences, 2 died, 2 are alive with disease, and 4 were successfully salvaged. Five patients died of unrelated causes. Lymphovascular invasion (LVI, P =.016) had a significant impact on recurrence, while other pathologic features of the primary tumor such as size, location, human papillomavirus (HPV) status, and margin status did not. Margins were classified as "positive" in 4 patients, "close" in 54, and "negative" in 16. There were 3 local recurrences (4.1%), each of whom had declined adjuvant therapy. Lymph node features such as N-stage (P =.0004), number of positive nodes (P =.0005), and presence of extra-nodal extension (ENE, P =.0042) had a statistically significant impact on relapse. Smoking history and surgical approach showed no significant impact on recurrence. Conclusion: Patients who undergo surgery for HPV-positive OPSCC with negative margins, no PNI, no LVI, and ≤1 positive lymph node without ENE have low risk for recurrence. These patients can likely be safely treated with surgery alone. Patients with these risk factors who decline adjuvant therapy are at risk for recurrence, and should be monitored. [ABSTRACT FROM AUTHOR]

Background: Transoral robotic surgery (TORS) was approved by the Food and Drug Administration in 2009 for the treatment of oropharyngeal cancers (oropharyngeal squamous cell carcinoma [OPSCC]). This study investigated the adoption and safety of TORS. Methods: All patients who underwent TORS for OPSCC in the National Cancer Data Base from 2010 to 2016 were selected. Trends in the positive margin rate (PMR), 30‐day unplanned readmission, and early postoperative mortality were evaluated. Outcomes after TORS, nonrobotic surgery (NRS), and nonsurgical treatment were compared with matched‐pair survival analyses. Results: From 2010 to 2016, among 73,661 patients with OPSCC, 50,643 were treated nonsurgically, 18,024 were treated with NRS, and 4994 were treated with TORS. TORS utilization increased every year from 2010 (n = 363; 4.2%) to 2016 (n = 994; 8.3%). The TORS PMR for base of tongue malignancies decreased significantly over the study period (21.6% in 2010‐2011 vs 15.8% in 2015‐2016; P =.03). The TORS PMR at high‐volume centers (≥10 cases per year; 11.2%) was almost half that of low‐volume centers (<10 cases per year; 19.3%; P <.001). The rates of 30‐day unplanned readmission (4.1%) and 30‐day postoperative mortality (1.0%) after TORS were low and did not vary over time. High‐volume TORS centers had significantly lower rates of 30‐day postoperative mortality than low‐volume centers (0.5% vs 1.5%; P =.006). In matched‐pair analyses controlling for clinicopathologic cofactors, 30‐, 60‐, and 90‐day posttreatment mortality did not vary among patients with OPSCC treated with TORS, NRS, or nonsurgical treatment. Conclusions: TORS has become widely adopted and remains safe across the country with a very low risk of severe complications comparable to the risk with NRS. Although safety is excellent nationally, high‐volume TORS centers have superior outcomes with lower rates of positive margins and early postoperative mortality. Transoral robotic surgery (TORS) has become widely adopted and remains safe across the country with a very low risk of severe complications comparable to the risk with nonrobotic surgery. Although safety is excellent nationally, high‐volume TORS centers have superior outcomes with lower rates of positive margins and early postoperative mortality. [ABSTRACT FROM AUTHOR]

P2Y receptors, including eight subtypes, are G protein-coupled receptors that can be activated by extracellular nucleotides. Nearly all P2Y receptors are expressed in bone cells, suggesting their involvements in bone physiology and pathology. However, their exact roles in bone homeostasis are not entirely clear. Therefore, this mini review summarizes new research developments regarding individual P2Y receptors and their roles in bone biology, particularly detailing those which execute both anabolic and catabolic functions. This dual function has highlighted the conundrum of pharmacologically targeting these P2Y receptors in bone-wasting diseases. Further research in finding more precise targeting strategy, such as promoting anabolic effects via combining with physical exercise, should be prioritized. [ABSTRACT FROM AUTHOR]

Purpose of Review: Fibroblast growth factor 23 (FGF23) is a bone- and bone marrow-derived hormone that is critical to maintain phosphate homeostasis. The principal actions of FGF23 are to reduce serum phosphate levels by decreasing kidney phosphate reabsorption and 1,25-dihydroxyvitamin D synthesis. FGF23 deficiency causes hyperphosphatemia and ectopic calcifications, while FGF23 excess causes hypophosphatemia and skeletal defects. Excess FGF23 also correlates with kidney disease, where it is associated with increased morbidity and mortality. Accordingly, FGF23 levels are tightly regulated, but the mechanisms remain incompletely understood. Recent Findings: In addition to bone mineral factors, additional factors including iron, erythropoietin, inflammation, energy, and metabolism regulate FGF23. All these factors affect Fgf23 expression, while some also regulate FGF23 protein cleavage. Conversely, FGF23 may have a functional role in regulating these biologic processes. Summary: Understanding the bi-directional relationship between FGF23 and non-bone mineral factors is providing new insights into FGF23 regulation and function. [ABSTRACT FROM AUTHOR]