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Background: Reducing the rate of adverse drug events in the ambulatory setting may require large investments in quality improvement efforts and technologic innovations. Little evidence is available on the potential resulting savings.Objective: The objective of this study was to estimate the costs associated with adverse drug events among older adults in the ambulatory setting.Research Design: This study consisted of a 1-year retrospective cohort study among Medicare enrollees of a large multispecialty group practice. The study included 1210 older adults with an adverse drug event. A matched comparison group was randomly selected from enrollees with recent healthcare encounters and medication dispenses.Outcome Measure: Difference between estimated costs for medical care utilization during the 6 weeks before and 6 weeks beginning on the day of an adverse drug event.Results: For all adverse drug events, the increase in postevent costs over the preevent period was $1310 (95% confidence interval [CI], $625-$1995) greater for those experiencing an adverse drug event than the comparison group after controlling for age, sex, comorbidity, number of scheduled medications, and having been hospitalized during the preevent period. For preventable adverse drug events, the adjusted increase was $1983 (95% CI, $193-$3773) greater for cases. Based on rates of adverse drug events and these cost estimates, 1000 older adults would have annual costs related to adverse drug events in the ambulatory setting of $65,631 with $27,365 of this associated with preventable events.Conclusions: Adverse drug events in the ambulatory setting substantially increase the healthcare costs of elderly persons. [ABSTRACT FROM AUTHOR]

Inflammation is associated with the formation of reactive oxygen species (ROS) and the formation of lipid-derived compounds, such as isolevuglandins (IsoLGs), malondialdehyde, 4-hydroxy-nonenal, and 4-oxo-nonenal. The most reactive of these are the IsoLGs, which form covalent adducts with lysine residues and other cellular primary amines leading to changes in protein function, immunogenicity, and epigenetic alterations and have been shown to contribute to a number of inflammatory diseases. 2-Hydroxybenzylamine (2-HOBA) is a natural compound found in buckwheat seeds and reacts with all IsoLG adducts preventing adduct formation with proteins and DNA. Therefore, 2-HOBA is well positioned as an agent for the prevention of inflammatory-prone diseases. In this study, we examined the potential beneficial effects of 2-HOBA on oxidative stress and inflammatory biomarkers in two cohorts of healthy younger and older adults. We utilized the Olink ® targeted inflammation panel before and after an oral 15-day treatment regimen with 2-HOBA. We found significant relative changes in the plasma concentration of 15 immune proteins that may reflect the in vivo immune targets of 2-HOBA. Treatment of 2-HOBA resulted in significant increased levels of CCL19, IL-12β, IL-20Rα, and TNFβ, whereas levels of TWEAK significantly decreased. Ingenuity Pathway Analysis identified canonical pathways regulated by the differentially secreted cytokines, chemokines, and growth factors upon 2-HOBA treatment and further points to biofunctions related to the recruitment, attraction, and movement of different immune cell types. In conclusion, 2-HOBA significantly altered the protein biomarkers CCL19, IL-12β, IL-20Rα, TNFβ, and TWEAK, and these may be responsible for the protective effects of 2-HOBA against reactive electrophiles, such as IsoLGs, commonly expressed in conditions of excessive oxidative stress. 2-HOBA has a role as a IsoLG scavenger to proactively improve immune health in a variety of conditions., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The leucine metabolite, 3-hydroxy-3-methylbutyrate (HMB), primarily utilized as the calcium salt (CaHMB) has become one of the most widely used supplements and food ingredients to promote muscle health. While both CaHMB and HMB free acid have published sub-chronic toxicity studies, and CaHMB has published studies on genotoxicity, data are lacking on the acute dosing of HMB which is important for regulatory and transportation classification as well as in cases of accidental overconsumption. Therefore, an acute oral toxicity study was conducted with CaHMB following OECD 420 guidelines. One rat was used in the dosage sighting study and four rats were used in the main study. In both studies, rats were given a single oral dose of 2000 mg/kg body weight by gavage and monitored for 14 days following the dosage for changes in body weight, clinical signs as noted in OECD 420, and at the end of the study a necropsy was conducted to determine any gross tissue abnormalities. The dosage of CaHMB administered resulted in no deaths, no significant adverse clinical signs, and no findings of lesions or abnormal tissues. Under the Global Harmonized System of classification, CaHMB was found to be in the least toxic Category 5 or non-toxic., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Chronic oral ATP supplementation benefits cardiovascular health, muscular performance, body composition, and recovery while attenuating muscle breakdown and fatigue. A single 400 mg dose of oral ATP supplementation improved lower body resistance training performance and energy expenditure in recreational resistance trained males, however, the minimal effective dose is currently unknown. Materials and Methods: Twenty recreationally trained men (age 28.6 ± 1.0 years, body mass 81.2 ± 2.0 kg, height 175.2 ± 1.4 cm, 1RM 141.5 ± 5.0 kg) consumed a single dose of either 400 mg, 200 mg, or 100 mg ATP (PEAK ATP ® , TSI USA LLC, Missoula, MT, USA) or a placebo in a randomized, placebo-controlled crossover design, separated by a one week wash out between treatments. After warm-up, participants performed 4 sets of half-squats using free-weights until movement failure separated by 2 mins of rest between sets. Results: In comparison to placebo, 400 mg ATP significantly increased the number of set 1 repetitions (+13%, p = 0.04), and numerically increased total repetitions (+7%, p = 0.19) and total weight lifted (+6%, p = 0.22). 200 mg ATP numerically increased set 1 repetitions (+4% p = 0.47), while 100 mg ATP showed no improvements over placebo. 100 mg ATP (-4%, p < 0.05) and 400 mg ATP (-4%, p = 0.11) decreased the perceived rate of exertion compared to placebo. Conclusions: In this study, the effective minimal dose of acute oral ATP supplementation during resistance exercise to increase performance was determined to be 400 mg, while as little as 100 mg showed improvements in perceived exertion., Competing Interests: RJ and MP were employed by company Increnovo LLC. JR was employed by company MTI BioTech, Inc. This study received funding from TSI USA LLC, Missoula, MT, USA. JF is employed by TSI. RJ and MP are paid consultants to TSI. JR was involved in the study design and statistical analysis of data. JF and MP were involved in the study design. RJ was involved in study design and writing of the manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 dos Santos Nunes de Moura, Jäger, Purpura, Rathmacher, Fuller and Rossi.)

Objective: To determine the effects of the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) on strength, muscle mass, and contractile material in muscle wasting induced by onabotulinumtoxin type-A (BoNT-A) injection into the quadriceps femoris muscles of New Zealand white rabbits., Methods: A total of 21, female rabbits were divided into 3 groups (n=7, each). Group 1 (Control) received intramuscular injection of saline. Groups 2 and 3 received intramuscular injection of BoNT-A (3.5 units/kg), with group 3 receiving supplementation with HMB (120 mg/kg-BW/day). Muscle morphology, mass, and strength were assessed 8 weeks later in both injected and non-injected contralateral limbs., Results: Injected muscle strength of group 2 (BoNT-A) and group 3 (BoNT-A+HMB) was reduced by 63% and 60%, respectively, compared with Controls (p<0.0001). Strength in contralateral muscles of group 2 was reduced by 23% vs Controls (p<0.002), while in group 3, strength was similar to Controls. Muscle mass in the injected muscles of the BoNT-A and BoNT-A+HMB groups was significantly reduced, by 46% and 48%, respectively., Conclusion: While HMB did not prevent loss of muscle strength and mass in the BoNT-A-injected musculature, it prevented significant loss of contractile material in the injected musculature and strength loss in the contralateral non-injected musculature.

Description Learning theories are necessary to help inform teaching strategies and promote successful educational outcomes. Having an in-depth knowledge about learning theories and their applicability to teaching and educating healthcare professionals will help support and promote excellence in medical education. Demonstrating an understanding of effective learning theories in the classroom will benefit both educators and trainees, while supporting a collaborative mentor-mentee relationship., Competing Interests: Conflicts of Interest Jacklyn C. Fuller declares that she has no conflicts of interest., (© 2021 HCA Physician Services, Inc. d/b/a Emerald Medical Education.)

Purpose of Review: To explore recent advances in therapeutic interventions for nonflaccid facial paralysis (NFFP), including new evidence for surgical and nonsurgical treatments. Timing of treatment is also discussed, along with possible future treatments., Recent Findings: NFFP remains a difficult disease to treat. Chemodenervation with botulinum toxin remains a first-line treatment to suppress aberrant and antagonistic movements during voluntary use of muscles. More permanent treatments such as selective neurectomy, myectomy, and nerve and muscle transfers have been shown to offer promising results for the nonflaccidly paralyzed face., Summary: NFFP is commonly seen in patients who have incomplete recovery from facial paralysis, and carries high psychosocial morbidity. A large array of treatments have been described in the literature, both procedural and nonprocedural. Both treatment type and timing are important in optimal patient recovery., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective  This study aimed to describe the impact of adverse clinical and pathologic features in sinonasal squamous cell carcinoma (SCC). Design  This study is designed with retrospective chart review. Setting  The present study is conducted at a tertiary care institution. Participants  All patients treated surgically for sinonasal SCC at our tertiary care institution between January 2006 and December 2013. Main Outcome Measures  Overall survival (OS) and disease free survival (DFS) are the final measurement of this study. Results  Forty-eight patients were identified. Mean age at surgery was 65.8 years, and mean follow-up time was 40.7 months. Eighteen patients (38%) had T1-T3 disease, while 30 patients (63%) had T4 disease. Seven patients (8.3%) had nodal disease at presentation. At 2, 5, and 10 years, OS was 71, 54, and 48%, respectively, while DFS was 64, 51, and 45%, respectively. Twelve patients (25%) experienced local recurrences with mean time to recurrence of 15.3 months. Twenty-five patients (52%) had positive margins, 24 (50%) had high-grade tumors, 18 (38%) had perineural invasion (PNI), and 15 (31%) had lymphovascular invasion (LVI). In the univariate analysis, T4 disease (risk ratio [RR] = 2.7) and high grade (RR = 2.4) had a significant association with DFS. In the multivariate analysis, high grade (RR = 4.0 and 4.5) and LVI (RR = 4.1 and 4.7) had a significant association with OS and DFS. Conclusion  Our single-institution experience of 48 patients suggests that high grade and LVI are independently associated with survival outcomes in sinonasal SCC, while PNI and microscopically positive margins do not have a significant impact., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Dorsal hump reduction is a key component of rhinoplasty. Spreader grafts are the most frequently used technique; however, dorsal irregularities may result. The modified Skoog method involves removal of the osseocartilaginous dorsal hump, its modification, further reduction of the nasal dorsum, replacement of the modified dorsal segment, and suspension of the upper lateral cartilages. The dorsal segment acts as an onlay spreader graft, preserves the middle vault, closes the open roof deformity, and creates a smooth dorsal contour from radix to anterior septal angle. The modified Skoog method produces optimal functional and aesthetic outcomes in appropriately selected patients., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Saddle nose deformity is a well-described condition that most commonly results from trauma or prior surgery. For larger saddle nose deformity defects, bone grafts are a reconstructive option that provide adequate structure for repair. One new technique for repair of these deformities is a vomerian bone onlay graft. We aim to provide a review of literature on autogenous repair of saddle nose deformities, as well as introduce a new technique in which the vomer bone is used as an onlay bone graft., Methods: Literature review and case series. Five cases in which vomer onlay grafts were used for repair of saddle nose deformity were reviewed between January 2013 and December 2015. Aesthetic outcomes and postoperative complications were evaluated at subsequent follow-up visits in clinic., Results: In all cases where vomer bone was harvested, the vomer onlay graft provided adequate structure to traverse the saddle nose deformity. No postoperative complications were observed in an 18 month follow-up period., Conclusion: Vomerian bone onlay grafts are a reconstructive option for saddle nose deformity and nasal dorsum defects. While septal cartilage is commonly used, and ethmoidal bone has been previously described as an option for composite graft reconstruction, vomer bone onlay grafting has not been well described in the literature. This method may be of use when previous nasal surgery has been performed and standard septal cartilage is not possible to harvest. The aesthetic outcomes following nasal dorsum reconstruction using onlay grafts are favorable, but long-term outcomes of these grafts require further study., Level of Evidence: IV., Competing Interests: The authors declare no conflicts of interest., (© 2020 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

The primary aim of this study was to determine whether supplementation with calcium β-hydroxy-β-methylbutyrate (HMB) and vitamin D3 (D) would enhance muscle function and strength in older adults. Older adults over 60 years of age with insufficient circulating 25-hydroxy-vitamin D (25OH-D) levels were enrolled in a double-blinded controlled 12-month study. Study participants were randomly assigned to treatments consisting of: (a) Control + no exercise, (b) HMB+D + no exercise, (c) Control + exercise, and (d) HMB+D + exercise. The study evaluated 117 participants via multiple measurements over the 12 months that included body composition, strength, functionality, and questionnaires. HMB+D had a significant benefit on lean body mass within the nonexercise group at 6 months (0.44 ± 0.27 kg, HMB+D vs -0.33 ± 0.28 kg, control, p < .05). In nonexercisers, improvement in knee extension peak torque (60°/s) was significantly greater in HMB+D-supplemented participants than in the nonsupplemented group (p = .04) at 3 months, 10.9 ± 5.7 Nm and -5.2 ± 5.9 Nm, respectively. A composite functional index, integrating changes in handgrip, Get Up, and Get Up and Go measurements, was developed. HMB+D + no exercise resulted in significant increases in the functional index compared with those observed in the control + no exercise group at 3 (p = .03), 6 (p = .04), and 12 months (p = .04). Supplementation with HMB+D did not further improve the functional index within the exercising group. This study demonstrated the potential of HMB and vitamin D3 supplementation to enhance muscle strength and physical functionality in older adults, even in individuals not engaged in an exercise training program., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Adenosine-5'-triphosphate (ATP) is the primary source of energy for cells and oral supplementation with ATP offers numerous different health benefits, including the regulation of blood flow and muscle contraction. In this study, ATP, disodium salt, was administered by gavage to rats for 90 consecutive days at doses of 0 (control), 500, 1000, and 2000 mg kg BW -1 ·d -1 (n = 10 per sex/group). Subchronic administration of ATP was well tolerated at all dose levels. Body weights and feed consumption body weight gains were similar between ATP-treated and control rats. Minor differences were seen in hematology and blood chemistry; however, these changes were not dose related and therefore not of biological or toxicological significance. Only one difference was observed in absolute organ weights, females of the high dose had increased kidney and increased relative kidney and liver weights; however, these differences were not seen in males nor appeared to be dose related. No biological or toxicological significant differences were observed in thyroid function or urine analysis. The incidence of histopathological lesions was low and similar between treated and control groups. Based upon these findings, the no-observed-adverse-effect level (NOAEL) was determined to be ≥ 2000 mg kg BW -1 ·d -1 , which was the highest dose tested., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: 2-Hydroxybenzylamine (2-HOBA) is a selective dicarbonyl electrophile scavenger being developed as a nutritional supplement to help protect against the development of conditions associated with dicarbonyl electrophile formation, such as the cognitive decline observed with Mild Cognitive Impairment or Alzheimer's disease., Methods: This study evaluated the safety, tolerability, and pharmacokinetics of repeated oral doses of 2-HOBA acetate (500 or 750 mg) administered to healthy volunteers every eight hours for two weeks. The effects of 2-HOBA on cyclooxygenase function and cerebrospinal fluid penetrance of 2-HOBA were also investigated., Results: Repeated oral administration of 2-HOBA was found to be safe and well-tolerated up to 750 mg TID for 15 days. 2-HOBA was absorbed within 2 h of administration, had a half-life of 2.10-3.27 h, and an accumulation ratio of 1.38-1.52. 2-HOBA did not interfere with cyclooxygenase function and was found to be present in cerebrospinal fluid 90 min after dosing., Conclusions: Repeated oral administration of 2-HOBA was found to be safe and well-tolerated. These results support continued development of 2-HOBA as a nutritional supplement., Trial Registration: Studies are registered at ClinicalTrials.gov (NCT03555682 Registered 13 June 2018, NCT03554096 Registered 12 June 18).

Objective: To identify characteristics of patients presenting preoperatively for functional septorhinoplasty associated with increased Nasal Obstruction Symptom Evaluation (NOSE) scores., Study Design: Retrospective analysis of a prospective cohort at a tertiary medical center. Only baseline assessments were analyzed in this cross-sectional study., Methods: 1,338 patients completed baseline nasal evaluation, resulting in 1,034 NOSE scores. Demographics, medical history, surgical history, and physical exam findings were recorded., Results: The average preoperative NOSE score was 59.8 out of 100 (standard deviation: 24.9). Fifty-four percent (578 per 1,074) of respondents were female, although sex did not affect baseline NOSE score (P = 0.7). Forty-five percent (404 per 896) reported prior nasal surgery. History of rhinoplasty was not associated with a difference in baseline NOSE score (P = 0.1924); however, history of septoplasty (P = 0.0390) was associated with an increased baseline NOSE score. Snoring was also both associated with higher baseline NOSE score (P = 0.0003). All 12 septal/nasal valve measurements were associated with higher preoperative NOSE score, whereas the internal nasal valve narrowing variables retained significance in multivariate analysis (left: P = .0490; right: P = .0077)., Conclusion: Patients presenting for nasal airway obstruction were evaluated. Sex was not associated with difference in NOSE score. History of septoplasty was associated with higher baseline NOSE score, as were snoring and internal nasal valve narrowing at rest., Level of Evidence: 2C Laryngoscope, 130:25-31, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Necrotizing sialometaplasia (NSM) is a benign, reactive metaplastic condition of the minor salivary gland tissue typically seen in the setting of injury, chemical or traumatic, and is nonneoplastic and self-limited. The diagnosis may be challenging as it may clinically mimic malignancy. We present the case of a 74-year-old male with a 1 pack per day smoking history for 60 years who presented with a reported 20-pound weight loss, dysphagia, and dysphonia progressing over the course of 6 months and found to have a 3.5-cm hypopharyngeal mass on computed tomography imaging and fiberoptic laryngoscopy. Initial frozen section of the mass was concerning for squamous cell carcinoma in situ, but permanent specimens returned as nondiagnostic. Repeat biopsy established a diagnosis of NSM. Two-month follow-up showed complete resolution of the mass. Clinicians should be aware that NSM may present in unusual locations when considering differential diagnoses for laryngeal masses and evaluating for malignancy.

Importance: Using health utility values (HUVs) as an outcome measure for surgical procedures, including rhinoplasty, allows for a standardized measurement of the qualitative and financial benefit of that procedure on overall health., Objective: To use Euroqol 5-Dimension (EQ-5D)-derived HUVs to evaluate nasal obstruction outcomes following surgery between primary rhinoplasty (PSRP) and rhinoplasty with previous nasal surgery (RNS) in a prospective cohort study., Design, Setting, and Participants: A single-institution prospective cohort study between 2013 and 2017 was carried out including 185 patients who underwent RNS before functional rhinoplasty and 278 patients who underwent PSRP for nasal obstruction. The analysis was carried out between December 2018 and February 2019., Main Outcomes and Measures: Patients in the RNS cohort and PSRP cohort who completed the EQ-5D questionnaire immediately prior to surgery and postoperatively at 2, 4, 6, and 12 months were included in the study. The EQ-5D scores were converted to HUV scores and compared to evaluate for improvement in health status following surgery., Results: Of the 185 patients in the RNS cohort, 97 (52%) were women and the mean (SD) age was 42.6 (13.4) years. Of the 278 in the PSRP cohort, 156 (55%) were women and the mean (SD) age was 36.0 (15.8) years. Both cohorts experienced significant improvement in HUV postoperatively. The mean (SD) HUV values were decreased in the RNS cohort versus the PSRP cohort both preoperatively (0.85 [0.16] versus 0.89 [0.14]) and postoperatively at 1 year (0.92 [0.14] versus 0.94 [0.11]); however, the difference in HUV was not statistically significant after 6 months postoperatively. Patients in the RNS cohort were typically older (76 [41%] older than 40 years vs 84 [31%], P = .02) and more likely to have sleep apnea (31 [19%] vs 24 [10%], P = .01) than in the PSRP cohort. On multivariable analysis, the use of spreader grafts and alar rim grafts in the PSRP cohort was significantly associated with improved HUV at 12 months. (r = -0.06; 95% CI, -0.11 to -0.01, P = .03)., Conclusions and Relevance: Patients with a history of prior nasal surgery may represent a unique cohort when assessing health utility outcomes. Euroqol 5-dimension questionnaire-derived HUVs are a valid predictor of outcomes in all patients who undergo septorhinoplasty. Although outcomes were significantly improved for both cohorts, previous surgical history should be considered when performing cost utility analysis on the benefits of functional rhinoplasty., Level of Evidence: 3.

Importance: By measuring health utility values (HUVs) for patients with nasal obstruction after septorhinoplasty, the association of nasal congestion with overall health can be measured and the functional outcomes of septorhinoplasty can be determined., Objective: To use the EuroQol 5-Dimension (EQ-5D) questionnaire to evaluate nasal obstruction outcomes after septorhinoplasty and to determine HUVs., Design, Setting, and Participants: This prospective cohort study included patients who underwent septorhinoplasty for nasal obstruction at a single institution by a single surgeon from January 1, 2013, through December 31, 2017. Participants completed the EQ-5D questionnaire immediately before surgery and postoperatively at 2, 4, 6, and 12 months. The EQ-5D scores were converted to HUVs using population-based data for individuals with chronic diseases. Data were analyzed from May 1 through December 31, 2018., Exposure: Functional septorhinoplasty., Main Outcomes and Measures: Preoperative and postoperative EQ-5D scores were compared to evaluate improvement in overall health after septorhinoplasty., Results: A total of 463 patients (53.8% women; mean [SD] age, 36.8 [15.7] years) who underwent septorhinoplasty and completed EQ-5D surveys at baseline and postoperatively were included in the study population. Overall mean (SD) preoperative HUV was 0.872 (0.01), compared with 1.00 for those with a perfect state of health. On univariate analysis, female sex (mean [SD] HUV, 0.853 [0.01]; P = .004), previous nasal surgery (mean [SD] HUV, 0.85 [0.16]; P = .02), previous septoplasty (mean [SD] HUV, 0.88 [0.15]; P = .02), and previous sinus surgery (mean [SD] HUV, 0.79 [0.20]; P = .009) were associated with significantly lower baseline HUVs. On multivariate regression including these variables, only previous septoplasty was significantly associated with a positive change in mean (SD) HUV (0.88 [0.15] vs 0.85 [0.16]; P = .02). Mean (SD) HUV was significantly improved at 2 months postoperatively to 0.91 (0.14; P = .001) and remained significantly improved from baseline at 12 months, at 0.93 (0.13; P < .001)., Conclusions and Relevance: Nasal obstruction is associated with significant detriment to overall health, in line with other chronic conditions affecting the US population. Functional septorhinoplasty appears to substantially improve overall health, as measured by HUV, in an immediate and sustained fashion., Level of Evidence: 3.

Importance: Spreader grafts have been shown to improve nasal airway obstruction in patients with nasal valve dysfunction; however, their use has been limited by concerns over their aesthetic penalty of widening the nasal dorsum., Objective: To evaluate the association of functional septorhinoplasty (FSRP) using spreader graft placement with patient satisfaction with nasal appearance postoperatively., Design, Setting, and Participants: This prospective cohort study was conducted in a university-based tertiary care medical center. All participants were patients undergoing FSRP for the treatment of nasal obstruction who had spreader grafts placed between June 2016 and May 2018., Exposures: The Nasal Obstruction Symptom Evaluation (NOSE) scale and the FACE-Q Satisfaction With Nose, FACE-Q Satisfaction With Nostrils, and FACE-Q Social Functioning scales were administered to patients preoperatively and at 2, 4, 6, and 12 months postoperatively. Patient demographics, nasal history, and outcomes were analyzed., Main Outcomes and Measures: Comparison of preoperative and postoperative NOSE and FACE-Q scores., Results: A total of 154 patients (72 male [46.8%]) with mean (SD) age of 36.8 (15.4) years underwent FSRP with spreader graft placement. Mean (SD) last follow-up was 5.8 (4.1) months postoperatively (range, 2-12 months). Fifty-seven patients had 6 months follow-up, and 42 patients had at least 12 months of follow-up. At time of last follow-up, mean (SD) NOSE and FACE-Q Satisfaction With Nose, Satisfaction With Nostrils, and Social Functioning scores significantly improved from 62.7 (20.7) to 22.8 (21.0) (P < .001), 54.7 (22.2) to 76.2 (25.1) (P < .001), 59.4 (27.9) to 83.6 (24.8) (P < .001), and 73.6 (21.8) to 81.7 (21.9) (P < .001), respectively. When separated into those with only spreader grafts (n = 89) and those with spreader grafts plus other graft types (n = 65), there was no significant difference between score improvements in the 2 groups. There were no significant differences in final nasal appearance scores between patients undergoing functional vs dual functional and cosmetic FSRP., Conclusions and Relevance: Despite concerns that placement of spreader grafts for the treatment of nasal obstruction due to nasal valve dysfunction during FSRP may have a negative impact on nasal aesthetics, this study shows that both nasal obstruction and patient satisfaction with their nasal appearance were significantly improved following surgery., Level of Evidence: 3.

Background: Patients' lack of awareness of available services is a significant barrier to delivering surgical care in resource-limited settings. Short message service (SMS) text messaging is a potential means to disseminate this information in resource-limited settings, where rates of mobile phone usage are high., Methods: A blast SMS text informing local populations of upcoming cleft lip-palate (CLP) surgical services was distributed to 25% of the subscriber base 1 week prior to arrival of a (CLP) surgical team in Zimbabwe. A retrospective cohort analysis comparing characteristics of patients presenting to the CLP clinic in the year prior to (2016) and 2 years following (2017-2018) the implementation of the blast SMS text messaging system is performed to assess its impact., Results: Patients presenting to a single Zimbabwean CLP surgical program in the years with SMS messaging notifications were significantly more likely (52 [64%] vs. 5 [17%], P  < .001) to have been informed of surgical services through their mobile phones. The average distance traveled per patient was not significantly different prior to implementation of mass text messaging (180.4 km [SD114.8] vs. 167.4 km [SD105.9], P = .580). The average patient age was significantly higher following the implementation of mass text messaging (7.4 [SD8.7] vs. 3.0 [SD2.8] years, P = .010)., Conclusions: SMS messaging is an effective method of informing patients of CLP surgical services in resource-limited settings. After implementation of SMS text notifications, surgical patients were of increased age, but showed no difference in distance traveled., Level of Evidence: IV.

Objectives: (1) To describe electronic communication between global surgeons and trainees in a low-middle income country (LMIC) and to gauge appeal of the WhatsApp platform (2) To introduce a novel intensive ear reconstruction teaching module for surgical capacity building using simulation in a LMIC., Design: Prospective cohort study., Setting: University-based medical center in Haiti., Participants: Eleven otolaryngology trainees and faculty in Haiti., Results: Three months prior to on-site arrival, a WhatsApp Messenger group was created for information-sharing and distribution of teaching materials. A surgical curriculum was created to incorporate didactics, cartilage framework simulation, and live surgery. During the intensive on-site week, WhatsApp was used to distribute materials and to recap learning points from each case, with pre- and postoperative surgical photographs circulated. Postmodule written, oral, and practical testing was conducted on the final day, and a postmodule survey was administered a month later. Post-tests scores were significantly improved from pretests scores. Initial scores on the written, oral, and practical tests averaged 24.6%. Postmodule scores averaged 86.9% (p < 0.001). Participants rated the use of WhatsApp to be highly important to their learning and requested further use of mobile health technology., Conclusions: WhatsApp Messenger technology complemented a reconstructive surgery education module in a LMIC. WhatsApp provides opportunities for premodule patient screening, real-time discussion, and postmodule review. Its usage was well-received by Haitian otolaryngology trainees and faculty. Our results suggest that the combination of didactic teaching, simulated surgery, and live surgery resulted in successful transfer of both skills and knowledge., (Published by Elsevier Inc.)

Objective: To evaluate the utility of peak nasal inspiratory flow (PNIF) as a measure of nasal airflow and functional septorhinoplasty (FSRP) outcomes., Methods: Patients with nasal obstruction were administered Nasal Obstruction Symptom Evaluation (NOSE) questionnaire and PNIF testing between January 2015 and 2018. Surgical patients repeated these tests at 2, 4, 6, 12, and 24 months postoperatively. Patient demographics and operative techniques were recorded., Results: A total of 610 patients were evaluated for nasal obstruction with mean (standard deviation [SD]) NOSE score of 61.5 (23.2) and PNIF of 74.1 (35.4) liters per minute (L/min); correlation -0.16 (P < 0.001). Predictors of lower PNIF were female gender (β = -13.3, 95% confidence interval [CI] 7.7 to 18.2, P < .001) and higher NOSE scores (β = -0.43, 95% CI 0.19 to 0.68, P < 0.001). A total of 281 patients underwent FSRP with statistically and clinically significant improvements in both mean NOSE and PNIF scores that were stable out to 2 years. NOSE scores changed -41.0 (25.5) points, and PNIF improved 20.7 (35.5) L/min at last follow-up. Grafting material did not affect outcomes, whereas spreader grafts improved PNIF values (β = 25.46, 95% CI 5.5 to 45.4, P = 0.013). Clinically significant changes between NOSE and PNIF were concordant, although the correlation was weak (r = -0.26, P = 0.02)., Conclusion: Peak nasal inspiratory flow is a rapid, cheap, and easily performed test that detects nasal obstruction and clinically significant improvements in airflow following FSRP. Although PNIF does not correlate well enough with the patient experience of nasal obstruction to be used as a diagnostic tool, it does provide unique and complementary information useful for evaluating, understanding, and improving the effects of surgical techniques., Level of Evidence: 2C Laryngoscope, 129:594-601, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

In functional septorhinoplasty (FSRP), alternative grafting material is used if septal cartilage is insufficient for reconstructive needs. Autologous costal cartilage (ACC) and irradiated homologous costal cartilage (IHCC) are compared via the Nasal Obstruction Symptom Evaluation (NOSE) scale. One-hundred forty-one patients who underwent FSRP with ACC or IHCC between January 2013 and March 2018 were administered the NOSE scale pre- and postoperatively at 2, 4, 6, and 12 months. There was no significant difference in mean NOSE scores between the ACC and IHCC cohorts at the preoperative visit (68.5 [standard deviation, SD 24.1] and 71.7 [20.1], respectively; p  < 0.6) or first postoperative visit (30.4 [26.6] and 33.9 [30.4], respectively; p  < 0.6) or subsequent visits. NOSE scores demonstrated a clinically and statistically significant improvement at all follow-up time points for both the ACC and IHCC groups. Patients who underwent grafting with IHCC were significantly older than those with ACC; average age of 55.6 [SD: 17.3] versus 40.1 [SD:12.1]; ( p  < 0.001). Two IHCC (0.05%) patients had postoperative infections; both resolved with antibiotics, but one required revision surgery. Both ACC and IHCC provide reliable grafting material when septal cartilage is insufficient. In FSRP for nasal airway obstruction, ACC and IHCC both provide a clinically and statistically significant reduction in NOSE scores postoperatively that remain stable between follow-up time points. The authors find no difference in NOSE scores between the ACC and IHCC groups; however, IHCC did have a higher rate of postoperative infection. Both materials should be discussed with patients and are an important part of the informed consent process., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: 2-Hydroxybenzylamine (2-HOBA) is a selective scavenger of dicarbonyl electrophiles that protects proteins and lipids from being modified by these electrophiles. It is currently being developed for use as a nutritional supplement to help maintain good health and protect against the development of conditions associated with dicarbonyl electrophile formation, such as the cognitive decline associated with Mild Cognitive Impairment and Alzheimer's disease., Methods: In this first-in-human study, the safety, tolerability, and pharmacokinetics of six ascending single oral doses of 2-HOBA acetate were tested in eighteen healthy human volunteers., Results: Reported adverse events were mild and considered unlikely to be related to 2-HOBA. There were no clinically significant changes in vital signs, ECG recordings, or clinical laboratory parameters. 2-HOBA was fairly rapidly absorbed, with a t max of 1-2 h, and eliminated, with a t 1/2 of approximately 2 h. Both t max and t 1/2 were independent of dose level, while C max and AUC increased proportionally with dose level., Conclusions: 2-HOBA acetate was safe and well-tolerated at doses up to 825 mg in healthy human volunteers, positioning it as a good candidate for continued development as a nutritional supplement., Trial Registration: This study is registered at ClinicalTrials.gov (NCT03176940).

Objective: To introduce 3 novel intensive facial plastic and reconstructive surgery teaching modules for surgical capacity building using simulation in a low-middle income country., Design: Prospective cohort study., Setting: University-based medical center in Quito, Ecuador., Participants: First- and second-year otolaryngology residents in Quito, Ecuador., Results: Residents participated in an intensive 3-day teaching program focused on microtia, nasoseptal abnormalities, and facial paralysis that included didactic lectures, simulation workshops, and live surgery. Residents underwent rigorous pre- and postmodule testing including written, oral, and practical examinations in each subject area. All participants completed anonymous feedback surveys with ratings on a Likert scale from 0 (very poor) to 10 (excellent). Nineteen residents completed both pre- and postmodule testing. The training module was successfully implemented and testing performance across all 3 subject areas significantly improved. Resident feedback was exceedingly positive, with average scores for each component ranging from 8.9 to 9.8, with highest scores given to the simulation workshops. The postmodule survey indicated that all residents found the course helpful and they desired additional courses covering more subject areas., Conclusions: Implementation of an intensive surgical training module combining didactics, surgical simulation, and live surgery resulted in the successful transfer of both skills and knowledge. While the long-term benefit of this program is yet to be determined, this model of training may prove to be a useful tool to help address surgical capacity building in the developing world., (Copyright © 2018 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

2-hydroxybenzylamine (2-HOBA), a naturally occurring compound found in buckwheat, has potential for use as a nutrition supplement due to its ability to protect against the damaging effects of oxidative stress. In a series of rodent toxicity studies, 2-HOBA acetate was well-tolerated and did not produce any toxic effects over 28 or 90 days of repeated oral administration. However, it remained necessary to test the potential toxicity of 2-HOBA acetate in a non-rodent species. In this investigation, 2-HOBA acetate was orally administered to male and female New Zealand White Rabbits for 90 days at doses of 100, 500, and 1000 mg·kg BW -1 ·day -1 (n = 5 per sex/group). As previously observed in rodents, 2-HOBA acetate administration was well tolerated. No toxic effects of 2-HOBA acetate were detected in body weight, feed consumption, hematology, blood chemistry, urine chemistry, organ weights, gross pathology or histopathology. Based on these findings, the no-observed-adverse-effect-level of 2-HOBA acetate in rabbits was determined to be 1000 mg·kg BW -1 ·day -1 , which was the highest dose tested. These results provide further support for the safety of 2-HOBA acetate administration., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

β-Hydroxy-β-methylbutyrate (HMB) is a leucine metabolite available in calcium salt (CaHMB) and free acid forms as a sports nutrition ergogenic aid. HMB has also been used to support muscle health in the elderly and other populations needing to maintain muscle mass. Several human studies have reported safety data for CaHMB, and rodent sub-chronic toxicity studies have been conducted; however, there are no published genotoxicity studies for HMB. Therefore, three studies (a bacterial reverse mutation test, an in vitro mammalian chromosomal aberration test, and an in vivo mammalian cell micronucleus test) were performed. In the Ames test, no changes in revertant colonies or background were noted with CaHMB concentrations up to 5000 μg per plate, either with or without metabolic activation in five bacterial strains. In the chromosomal aberration test, the number of aberrations associated with up to 2.5 mM CaHMB (long-term) or 10.0 mM (short-term) were similar to those observed for negative controls (<5%), and no polyploidy was observed. Lastly, in the mammalian micronucleus test, no changes in immature erythrocyte or micronuclei frequencies were observed in animals treated with up to 2000 mg·kg -1 body weight CaHMB. In conclusion, CaHMB was determined to have no genotoxic effects., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

2-Hydroxybenzylamine (2-HOBA), a naturally occurring compound found in buckwheat, can protect cells and tissues from oxidative stress. In this study, 2-HOBA acetate was orally administered to male and female rats for 90 consecutive days at doses of 100, 500, and 1000 mg·kg BW -1 ·d -1 (n = 20 per sex/group). Subchronic administration of 2-HOBA was well tolerated at all dose levels. 2-HOBA-treated male rats were slightly heavier in the last weeks of the study, but this difference was very small (<5%), did not show a dose-response relationship, and was not observed in female rats. Similarly, some statistically significant changes in serum biochemistry and hematology parameters were noted, but these were not considered to be of biological or toxicological significance. Sporadic differences in organ weights were observed between groups, but all were small (<10%) and unlikely to indicate toxicity. The incidence of histopathological lesions was similar between treated and control groups across all organs. Based upon these findings, the no-observed-adverse-effect level was determined to be ≥ 1000 mg·kg BW -1 ·d -1 , which was the highest dose tested. These results further support no toxicity associated with oral consumption of 2-HOBA acetate in rats and the continued development of 2-HOBA as a dietary supplement or functional food., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

2-hydroxybenzylamine (2-HOBA), a compound found in buckwheat, is a potent scavenger of reactive γ-ketoaldehydes, which are increased in diseases associated with inflammation and oxidative stress. While the potential of 2-HOBA is promising, studies were needed to characterize the safety of the compound before clinical trials. In a series of experiments, the risks of 2-HOBA-mediated mutagenicity and cardio-toxicity were assessed in vitro. The effects of 2-HOBA on the mRNA expression of select cytochrome P450 (CYP) enzymes were also assessed in cryopreserved human hepatocytes. Further, the distribution and metabolism of 2-HOBA in blood were determined. Our results indicate that 2-HOBA is not cytotoxic or mutagenic in vitro and does not induce the expression of CYP1A2, CYP2B6, or CYP3A4 in human hepatocytes. The results of the hERG testing showed a low risk of cardiac QT wave prolongation. Plasma protein binding and red blood cell distribution characteristics indicate low protein binding and no preferential distribution into erythrocytes. The major metabolites identified were salicylic acid and the glycoside conjugate of 2-HOBA. Together, these findings support development of 2-HOBA as a nutritional supplement and provide important information for the design of further preclinical safety studies in animals as well as for human clinical trials with 2-HOBA., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

2-hydroxybenzylamine (2-HOBA), a compound naturally found in buckwheat, has been shown to protect cells and tissues from the damaging effects of oxidative stress. The purpose of this report was to evaluate 2-HOBA in preclinical oral rodent toxicity studies. This report includes the results from three oral toxicity studies in rodents: a preliminary 28-day feeding study in mice, a 14-day acute oral toxicity study in rats, and a 28-day repeated dose oral toxicity study in rats. The preliminary mouse feeding study showed no adverse effects of 2-HOBA at concentrations up to 0.456% by weight in feed, but decreased food intake and weight loss were observed at 1.56% 2-HOBA in the diet, likely due to poor palatability. In the acute dosing study, 2000 mg/kg BW 2-HOBA resulted in mortality in one of the six tested female rats, indicating a median lethal dose of 2500 mg/kg BW. In the 28-day repeated oral dose study, small differences were observed between 2-HOBA treated and control group rats, but none of these differences were determined to be of toxicological significance. Together, these studies support the lack of toxicity of oral administration of 2-HOBA acetate at doses up to 1000 mg/kg BW d -1 in rodents., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Nasal airway obstruction (NAO) is a common complaint in the otolaryngologist's office and can have a negative influence on quality of life (QOL). Existing diagnostic methods have improved, but little consensus exists on optimal tools. Furthermore, although surgical techniques for nasal obstruction continue to be developed, effective outcome measurement is lacking. An update of recent advances in diagnostic and therapeutic management of NAO is warranted., Objective: To review advances in diagnosis and treatment of NAO from the last 5 years., Evidence Review: PubMed, Embase, CINAHL, the Cochrane Library, LILACS, Web of Science, and Guideline.gov were searched with the terms nasal obstruction and nasal blockage and their permutations from July 26, 2012, through October 23, 2017. Studies were included if they evaluated NAO using a subjective and an objective technique, and in the case of intervention-based studies, the Nasal Obstruction Symptom Evaluation (NOSE) scale and an objective technique. Exclusion criteria consisted of animal studies; patients younger than 14 years; nasal foreign bodies; nasal masses including polyps; choanal atresia; sinus disease; obstructive sleep apnea or sleep-disordered breathing; allergic rhinitis; and studies not specific to nasal obstruction., Findings: The initial search resulted in 942 articles. After independent screening by 2 investigators, 46 unique articles remained, including 2 randomized clinical trials, 3 systematic reviews, 3 meta-analyses, and 39 nonrandomized cohort studies (including a combined systematic review and meta-analysis). An aggregate of approximately 32 000 patients were reviewed (including meta-analyses). Of the subjective measures available for NAO, the NOSE scale is outstanding with regard to disease-specific validation and correlation with symptoms. No currently available objective measure can be considered a criterion standard. Structural measures of flow, pressure, and volume appear to be necessary but insufficient to assess NAO. Therefore, novel variables and techniques must continue to be explored in search of an ideal instrument to aid in assessment of surgical outcomes., Conclusions and Relevance: Nasal airway obstruction is a clinical diagnosis with considerable effects on QOL. An adequate diagnosis begins with a focused history and physical examination and requires a patient QOL measure such as the NOSE scale. Objective measures should be adjunctive and require further validation for widespread adoption. These results are limited by minimal high-quality evidence among studies and the risk of bias in observational studies., Level of Evidence: NA.

Objectives: To describe pediatric and adolescent patients undergoing functional septorhinoplasty and to analyze both subjective and objective outcomes., Methods: Retrospective review of prospective cohort study of patients ≤18 years old undergoing functional septorhinoplasty between 2013 and 2016 at a tertiary care center. Patient demographics, nasal exam, procedure, and pre- and postoperative nasal obstruction symptom evaluation (NOSE) score, EuroQOL 5-dimension (EQ5D), and peak nasal inspiratory flow (PNIF) scores were analyzed., Results: 39 patients, 48.7% male, mean age 15.9 years (range 7-18), with nasal obstruction underwent functional septorhinoplasty with mean follow up of 8.5 months. Patients reported a history of allergies (46.5%), nasal fracture (59.0%), and previous nasal surgery (25.6%). Most common exam findings included internal nasal valve narrowing (92.3%), superior/dorsal septal deviation (74.4%), external nasal valve narrowing (43.6%), caudal septal deviation (35.9%), and a narrow middle vault (33.3%). Septal cartilage grafts were placed in 79.5% of patients and PDS plate was used in 28.2%. Most common procedures included spreader grafts (84.6%), columellar strut graft (30.8%), and swinging door (23.1%). Of patients with both baseline and postoperative scores, at last follow up NOSE scores (SD) decreased from 59.0 (23.7) to 21.2 (8.8) (n = 26, p < 0.001), EQ5D VAS scores increased from 76.2 (17.7) to 85.8 (13.5), (n = 19, p = 0.056), and PNIF scores increased from 66.2 (25.3) to 90.8 (46) L/min, (n = 13, p < 0.01); all mean differences met the minimal clinically important difference for each score. 2 patients underwent revision surgery and there was one complication of a nasal abscess., Conclusions: Functional septorhinoplasty is safe and effective in select pediatric and adolescent patients with significant nasal obstruction and results in significant improvements in both subjective and objective outcomes measures., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives/hypothesis: To evaluate the safety, efficacy, and result stability of polydioxanone (PDS) plate use for L-strut stabilization., Study Design: Retrospective analysis of a prospective cohort., Methods: Patients who underwent functional septorhinoplasty with the use of PDS plates between January 2013 and January 2017 were administered the Nasal Obstruction Symptom Evaluation (NOSE) scale pre- and postoperatively at 2, 4, 6, and 12 months. Patient demographics, reason for PDS use, graft type, complications, and outcomes were analyzed., Results: Eighty-eight patients aged 34.3 years (standard deviation [SD] = 15.7 years; range, 7.5-71.5 years) were included. All patients were found to have a fracture and/or severe deviation of the L-strut for which the PDS plate was used for rigid support. Mean preoperative NOSE score 65.2 (SD = 22.1) significantly decreased to 19.6 (SD = 21.6) at 7.2 months (SD = 5.5 months) postoperatively. There were no significant differences in NOSE scores between follow-up time points. There was one complication, a septal abscess, and one revision., Conclusions: A PDS plate is a safe and effective material to be utilized in functional septorhinoplasty for patients with a fracture or iatrogenic injury to the septal L-strut or poor quality septal cartilage that requires stability without additional width. Outcomes are stable at 6 and 12 months, after the plate has dissolved. The use of a PDS plate may decrease the need for rib grafting in patients with a history of previous septoplasty and persistent nasal obstruction with a dorsal or caudal C-shaped septal deformity or fracture of the L-strut., Level of Evidence: 2c. Laryngoscope, 127:2725-2730, 2017., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose of Review: The field of global surgery is undergoing rapid transformation, owing to several recent prominent reports positioning it as a cost-effective means of relieving global disease burden. The purpose of this article is to review the recent advances in the field of global surgery., Recent Findings: Efforts to grow the global surgical workforce and procedural capacity have focused on innovative methods to increase surgeon training, enhance international collaboration, leverage technology, optimize existing health systems, and safely implement task-sharing. Computer modeling offers a novel means of informing policy to optimize timely access to care, equitably promote health and financial protection, and efficiently grow infrastructure. Tools and checklists have recently been developed to enhance data collection and ensure methodologically rigorous publications to inform planning, benchmark surgical systems, promote accurate modeling, track key health indicators, and promote safety. Creation of institutional partnerships and trainee exchanges can enrich training, stimulate commitment to humanitarian work, and promote the equal exchange of ideas and expertise., Summary: The recent body of work creates a strong foundation upon which work toward the goal of universal access to safe, affordable surgical care can be built; however, further collection and analysis of country-specific data is necessary for accurate modeling and outcomes research into the efficacy of policies such as task-sharing is greatly needed.

In recent years, several pet food recalls have been attributed to Salmonella contamination. In addition to the negative impacts on animal health, Salmonella-contaminated pet foods have been linked to infection in humans. With that in mind, the U.S. Food and Drug Administration has set forth a zero-tolerance policy for Salmonella in pet foods. Typically, pet foods are extruded or processed at high temperatures that are sufficient to reduce pathogenic bacteria. However, the possibility for postextrusion contamination still exists. One potential method to reduce the risk of postextrusion contamination of pet foods with Salmonella is through the addition of a chemical additive coating. The objective of this research was to evaluate the ability of β-hydroxy-β-methylbutyrate (HMB), in either free acid (HMBFA) or calcium salt (CaHMB) form, to reduce postextrusion contamination of dry extruded dog kibble with Salmonella. Three trials were conducted with HMBFA and CaHMB coated onto the kibbles at levels of 0, 0.1, 0.3, 0.5, 0.9, and 1.5% (w/w). The coated kibbles were then inoculated with Salmonella enterica subsp. enterica Enteritidis (ATCC 13076), with enumeration done on days 0, 1, 2, 7, and 14 postinoculation. Subsamples on each day were serially diluted, spread plated to xylose lysine deoxycholate agar, and incubated at 37°C for 24 h. Salmonella colonies were then counted and log CFU per gram was calculated. The 1.5% HMBFA reduced counts by 4.9 ± 0.2 log units on day 1, whereas the positive control only decreased 2.2 ± 0.1 log units (P < 0.0001). The 1.5% CaHMB level decreased counts by 7.1 ± 0.04 log units by day 7 compared with the control decrease of 2.1 ± 0.1 log units (P < 0.0001). All HMBFA and CaHMB treatments resulted in the elimination of detectable Salmonella counts by day 14 (P < 0.0001 versus controls). In conclusion, HMB coating was effective at reducing Salmonella artificially inoculated to dog kibbles in a model of postextrusion contamination.

Importance: Nasal airway obstruction is a common presenting complaint among patients in otolaryngology practices, and its treatment necessitates critical outcomes evaluation and cost-utility analysis., Objective: To evaluate the utility and applicability of the EuroQol 5-Dimension (EQ5D) global health-related quality-of-life (HRQoL) questionnaire for the assessment of clinical outcomes in functional septorhinoplasty., Design, Setting, and Participants: Prospective cohort study at a university-based tertiary medical center of patients undergoing functional septorhinoplasty for treatment of nasal obstruction., Interventions: Patient demographic characteristics, operative intervention, and preoperative and postoperative Nasal Obstruction Symptom Evaluation (NOSE) and EQ5D scores were collected and analyzed between November 2013 and June 2016., Main Outcomes and Measures: Comparison of preoperative and postoperative EQ5D and NOSE scores at 2 and 6 or more months following surgery (long-term follow-up)., Results: A total of 135 patients (56.3% male; mean [SD] age, 36.8 [14.8] years) completed EQ5D and NOSE surveys preoperatively and postoperatively, with mean (SD) follow-up of 5.82 (4.1) months. Of these, 117 completed the 2-month survey and 64 completed their last survey at 6 or more months. Baseline NOSE and EQ5D visual analog scale (VAS) scores were moderately correlated (r = -0.37, P < .001) as were changes in NOSE and EQ5D VAS scores at long-term follow-up (r = -0.33, P = .007). Mean baseline NOSE score of 64.3 (95% CI, 60.5-68.2) decreased to 24.8 (95% CI, 18.8-30.9) at long-term follow-up (P < .001). The frequency of patients reporting problems in the EQ5D domains of pain/discomfort and usual activity decreased by more than half in the long-term follow-up group (30 [47%] vs 14 [22%] and 11 [17%] vs 4 [6%]; P = .002 and .02, respectively). The minimal clinically important difference of the EQ5D VAS score was calculated at 9.5. The EQ5D VAS scores had statistically and clinically significant improvement at long-term follow-up in patients with NOSE score improvements of 30 to 60 points (EQ5D VAS increased from mean [SD] of 72.3 [20] to 85.9 [10]; P < .001) and 65 to 100 points (EQ5D VAS increased from mean [SD] of 66.2 [25] to 82.0 [13]; P = .01)., Conclusions and Relevance: The EQ5D, a global HRQoL instrument, was able to detect clinically significant improvement following functional septorhinoplasty for nasal obstruction. Nasal valve correction improved not only disease-specific quality of life but also global HRQoL. The ability to calculate health utility values from the EQ5D and its low response burden make it an attractive tool for septorhinoplasty outcomes research., Level of Evidence: 4.

Objectives  Review outcomes of lateral temporal bone resections for ear and temporal bone malignancy. Design, Setting, and Participants  Retrospective review of all lateral temporal bone resections performed from 2008 to 2015 at a single tertiary care center. Main Outcome Measures  Patient demographics, perioperative variables, overall survival, disease-free survival (DFS), and comparison of Kaplan-Meier curves. Results  Overall, 56 patients were identified with a mean follow-up period of 2.3 ± 1.8 years. The predominant histopathologic diagnosis was squamous cell carcinoma (SCC, 54%), followed by salivary gland tumors (18%), and basal cell carcinoma (9%). Tumor stages were T1-T2 in 23%, T3-T4 in 73%, and two unknown primary lesions. Mean overall survival was 4.6 ± 0.4 years. Comparison of tumors with and without lymph node involvement or perineural invasion approached statistical significance for overall survival ( p  = 0.07 and 0.06, respectively). DFS was 2.5 ± 0.3 years. Stratification by lymph node status had a statistically significant difference in DFS ( p  = 0.03). Subgroup analysis of SCC patients did not reveal significant differences. Conclusions  Based on our cohort, most patients with temporal bone malignancies present with advanced disease, making it difficult to achieve negative margins. Overall, lymph node status was the strongest predictor of survival in this group.

We present the results for CAPRI Round 30, the first joint CASP-CAPRI experiment, which brought together experts from the protein structure prediction and protein-protein docking communities. The Round comprised 25 targets from amongst those submitted for the CASP11 prediction experiment of 2014. The targets included mostly homodimers, a few homotetramers, and two heterodimers, and comprised protein chains that could readily be modeled using templates from the Protein Data Bank. On average 24 CAPRI groups and 7 CASP groups submitted docking predictions for each target, and 12 CAPRI groups per target participated in the CAPRI scoring experiment. In total more than 9500 models were assessed against the 3D structures of the corresponding target complexes. Results show that the prediction of homodimer assemblies by homology modeling techniques and docking calculations is quite successful for targets featuring large enough subunit interfaces to represent stable associations. Targets with ambiguous or inaccurate oligomeric state assignments, often featuring crystal contact-sized interfaces, represented a confounding factor. For those, a much poorer prediction performance was achieved, while nonetheless often providing helpful clues on the correct oligomeric state of the protein. The prediction performance was very poor for genuine tetrameric targets, where the inaccuracy of the homology-built subunit models and the smaller pair-wise interfaces severely limited the ability to derive the correct assembly mode. Our analysis also shows that docking procedures tend to perform better than standard homology modeling techniques and that highly accurate models of the protein components are not always required to identify their association modes with acceptable accuracy. Proteins 2016; 84(Suppl 1):323-348. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Chronic aspiration poses a major health risk to the pediatric population. We describe four cases in which work up for chronic aspiration with a brain MRI revealed a Chiari I malformation, a poorly described etiology of pediatric aspiration. All patients had at least one non-specific neurologic symptom but had swallow studies more characteristic of an anatomic than a neurologic etiology. Patients were referred to neurosurgery and underwent posterior fossa decompression with symptom improvement. A high index of suspicion for Chiari malformation should be maintained when the standard work up for aspiration is non-diagnostic, particularly when non-specific neurologic symptoms are present., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Lowery, RP, Joy, JM, Rathmacher, JA, Baier, SM, Fuller, JC Jr, Shelley, MC II, Jäger, R, Purpura, M, Wilson, SMC, and Wilson, JM. Interaction of beta-hydroxy-beta-methylbutyrate free acid and adenosine triphosphate on muscle mass, strength, and power in resistance trained individuals. J Strength Cond Res 30(7): 1843-1854, 2016-Adenosine-5'-triphosphate (ATP) supplementation helps maintain performance under high fatiguing contractions and with greater fatigue recovery demands also increase. Current evidence suggests that the free acid form of β-hydroxy-β-methylbutyrate (HMB-FA) acts by speeding regenerative capacity of skeletal muscle after high-intensity or prolonged exercise. Therefore, we investigated the effects of 12 weeks of HMB-FA (3 g) and ATP (400 mg) administration on lean body mass (LBM), strength, and power in trained individuals. A 3-phase double-blind, placebo-, and diet-controlled study was conducted. Phases consisted of an 8-week periodized resistance training program (phase 1), followed by a 2-week overreaching cycle (phase 2), and a 2-week taper (phase 3). Lean body mass was increased by a combination of HMB-FA/ATP by 12.7% (p < 0.001). In a similar fashion, strength gains after training were increased in HMB-FA/ATP-supplemented subjects by 23.5% (p < 0.001). Vertical jump and Wingate power were increased in the HMB-FA/ATP-supplemented group compared with the placebo-supplemented group, and the 12-week increases were 21.5 and 23.7%, respectively. During the overreaching cycle, strength and power declined in the placebo group (4.3-5.7%), whereas supplementation with HMB-FA/ATP resulted in continued strength gains (1.3%). In conclusion, HMB-FA and ATP in combination with resistance exercise training enhanced LBM, power, and strength. In addition, HMB-FA plus ATP blunted the typical response to overreaching, resulting in a further increase in strength during that period. It seems that the combination of HMB-FA/ATP could benefit those who continuously train at high levels such as elite athletes or military personnel.

The dynamics of protein binding pockets are crucial for their interaction specificity. Structural flexibility allows proteins to adapt to their individual molecular binding partners and facilitates the binding process. This implies the necessity to consider protein internal motion in determining and predicting binding properties and in designing new binders. Although accounting for protein dynamics presents a challenge for computational approaches, it expands the structural and physicochemical space for compound design and thus offers the prospect of improved binding specificity and selectivity. A cavity on the surface or in the interior of a protein that possesses suitable properties for binding a ligand is usually referred to as a binding pocket. The set of amino acid residues around a binding pocket determines its physicochemical characteristics and, together with its shape and location in a protein, defines its functionality. Residues outside the binding site can also have a long-range effect on the properties of the binding pocket. Cavities with similar functionalities are often conserved across protein families. For example, enzyme active sites are usually concave surfaces that present amino acid residues in a suitable configuration for binding low molecular weight compounds. Macromolecular binding pockets, on the other hand, are located on the protein surface and are often shallower. The mobility of proteins allows the opening, closing, and adaptation of binding pockets to regulate binding processes and specific protein functionalities. For example, channels and tunnels can exist permanently or transiently to transport compounds to and from a binding site. The influence of protein flexibility on binding pockets can vary from small changes to an already existent pocket to the formation of a completely new pocket. Here, we review recent developments in computational methods to detect and define binding pockets and to study pocket dynamics. We introduce five different classes of protein pocket dynamics: (1) appearance/disappearance of a subpocket in an existing pocket; (2) appearance/disappearance of an adjacent pocket on the protein surface in the direct vicinity of an already existing pocket; (3) pocket breathing, which may be caused by side-chain fluctuations or backbone or interdomain vibrational motion; (4) opening/closing of a channel or tunnel, connecting a pocket inside the protein with solvent, including lid motion; and (5) the appearance/disappearance of an allosteric pocket at a site on a protein distinct from an already existing pocket with binding of a ligand to the allosteric binding site affecting the original pocket. We suggest that the class of pocket dynamics, as well as the type and extent of protein motion affecting the binding pocket, should be factors considered in choosing the most appropriate computational approach to study a given binding pocket. Furthermore, we examine the relationship between pocket dynamics classes and induced fit, conformational selection, and gating models of ligand binding on binding kinetics and thermodynamics. We discuss the implications of protein binding pocket dynamics for drug design and conclude with potential future directions for computational analysis of protein binding pocket dynamics.

The high-mobility group box 1 (HMGB1) protein has a central role in immunological antitumour defense. Here we show that natural killer cell-derived HMGB1 directly eliminates cancer cells by triggering metabolic cell death. HMGB1 allosterically inhibits the tetrameric pyruvate kinase isoform M2, thus blocking glucose-driven aerobic respiration. This results in a rapid metabolic shift forcing cells to rely solely on glycolysis for the maintenance of energy production. Cancer cells can acquire resistance to HMGB1 by increasing glycolysis using the dimeric form of PKM2, and employing glutaminolysis. Consistently, we observe an increase in the expression of a key enzyme of glutaminolysis, malic enzyme 1, in advanced colon cancer. Moreover, pharmaceutical inhibition of glutaminolysis sensitizes tumour cells to HMGB1 providing a basis for a therapeutic strategy for treating cancer.

β-Hydroxy-β-methylbutyrate (HMB), a leucine metabolite, has long been supplemented as a Ca salt (Ca-HMB) to increase strength and performance gains with exercise and to reduce recovery time. Recently, the free acid form of HMB (HMB-FA) has become commercially available in capsule form (gelcap). The current study was conducted to compare the bioavailability of HMB using the two commercially available capsule forms of HMB-FA and Ca-HMB. We also compared the pharmacokinetics of each form when administered mixed in water. Ten human subjects (five male and five female) were studied in a randomised crossover design. There was no significant sex by treatment interaction for any of the pharmacokinetic parameters measured. HMB-FA administered in capsules was more efficient than Ca-HMB capsule at HMB delivery with a 37 % increase in plasma clearance rate (74·8 (sem 4·0) v. 54·5 (sem 3·2) ml/min, P<0·0001) and a 76 % increase in peak plasma HMB concentration (270·2 (sem 17·8) v. 153·9 (sem 17·9) μmol/l, P<0·006), which was reached in one-third the time (P<0·009). When HMB-FA and Ca-HMB were administered in water, the differences still favoured HMB-FA, albeit to a lesser degree. Plasma HMB with HMB-FA administered in water was greater during the early phase of absorption (up to 45 min postadministration, P<0·05); this resulted in increased AUC during the first 60 min after administration, when compared with Ca-HMB mixed in water (P<0·03). In conclusion, HMB-FA in capsule form improves clearance rate and availability of HMB compared with Ca-HMB in capsule form.

Macromolecular interactions play a crucial role in biological systems. Simulation of diffusional association (SDA) is a software for carrying out Brownian dynamics simulations that can be used to study the interactions between two or more biological macromolecules. webSDA allows users to run Brownian dynamics simulations with SDA to study bimolecular association and encounter complex formation, to compute association rate constants, and to investigate macromolecular crowding using atomically detailed macromolecular structures. webSDA facilitates and automates the use of the SDA software, and offers user-friendly visualization of results. webSDA currently has three modules: 'SDA docking' to generate structures of the diffusional encounter complexes of two macromolecules, 'SDA association' to calculate bimolecular diffusional association rate constants, and 'SDA multiple molecules' to simulate the diffusive motion of hundreds of macromolecules. webSDA is freely available to all users and there is no login requirement. webSDA is available at http://mcm.h-its.org/webSDA/., (© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The leucine metabolite β-hydroxy-β-methylbutyrate (HMB) has been studied by many researchers over the last two decades. In particular, the utility of HMB supplementation in animals has been shown in numerous studies, which have demonstrated enhanced body weight gain and carcass yield in slaughter animals; positive immunostimulatory effect; decreased mortality; attenuation of sarcopenia in elderly animals; and potential use in pathological conditions such as glucocorticoid-induced muscle loss. The aim of this study was to summarize the body of research on HMB supplementation in animals and to examine possible mechanisms of HMB action. Furthermore, while the safety of HMB supplementation in animals is well documented, studies demonstrating efficacy are less clear. The possible reasons for differences in these findings will also be examined., (Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.)