Implications of Malignancy, Radiation, and Timing of Major Nasal Reconstruction.

Owing to the complex, multilayered anatomy of the nose in the central face, major nasal reconstruction can pose a significant challenge for reconstructive surgeons. It is the responsibility of reconstructive surgeons to have an understanding of the most common cutaneous malignancies and excisional techniques that may lead to complex nasal defects. The purpose of this article is to discuss these malignancies, excisional techniques, and impacts of radiation on tissue that has implications for reconstructive surgeons.

British Association of Dermatologists national clinical audit on the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults.

BACKGROUND: UK guidelines for managing adults with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), published by the British Association of Dermatologists (BAD) in 2016, outline a set of audit standards. OBJECTIVES: To audit current management of SJS/TEN in adults against standards in the BAD guidelines. METHODS: BAD members were invited to submit data on five consecutive adults with SJS/TEN per department over an 8-week period in 2022. RESULTS: Thirty-nine dermatology centres in the UK (29%) participated, and data for 147 adults with SJS/TEN were collected. Within 24 h of the diagnosis being made or suspected, the following were documented, per 147 submitted cases: Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) for 76 (52%), list of medications for 113 (77%) and timelines for commencement/alterations of medications for 104 (71%). The initial assessment was documented of the eyes by an ophthalmologist in 71 (48%), of the mouth in 130 (88%), of the genital skin in 103 (70%) and of the urinary tract in 93 (63%). During the first 10 days after a suspected or confirmed diagnosis of SJS/TEN, daily assessments of the mouth were documented in 26 of 147 cases (18%), of the eyes in 12 (8%), and of the urinary tract and genital skin in 14 (10%). At discharge, a drug was declared to be the cause of SJS/TEN for 130 of 147 cases (88%), while 9 (6%) were thought to be secondary to infection. Eleven of 147 (8%) had no response to this question. Documentation regarding advice was present on avoidance of the culprit drug in 76 of 130 declared SJS/TEN cases (58%), and on requesting a MedicAlert® bracelet/amulet in 9 of the 147 cases (6%). CONCLUSIONS: This audit suggests that a clinical review checklist might be needed to enable colleagues to maintain standards outlined in the guidelines, including documentation of SCORTEN, daily assessments of mucosal areas, and advice to avoid culprit drug(s) and to request a MedicAlert® bracelet/amulet.

Short- and long-range cis interactions between integrated HPV genomes and cellular chromatin dysregulate host gene expression in early cervical carcinogenesis.

Development of cervical cancer is directly associated with integration of human papillomavirus (HPV) genomes into host chromosomes and subsequent modulation of HPV oncogene expression, which correlates with multi-layered epigenetic changes at the integrated HPV genomes. However, the process of integration itself and dysregulation of host gene expression at sites of integration in our model of HPV16 integrant clone natural selection has remained enigmatic. We now show, using a state-of-the-art 'HPV integrated site capture' (HISC) technique, that integration likely occurs through microhomology-mediated repair (MHMR) mechanisms via either a direct process, resulting in host sequence deletion (in our case, partially homozygously) or via a 'looping' mechanism by which flanking host regions become amplified. Furthermore, using our 'HPV16-specific Region Capture Hi-C' technique, we have determined that chromatin interactions between the integrated virus genome and host chromosomes, both at short- (<500 kbp) and long-range (>500 kbp), appear to drive local host gene dysregulation through the disruption of host:host interactions within (but not exceeding) host structures known as topologically associating domains (TADs). This mechanism of HPV-induced host gene expression modulation indicates that integration of virus genomes near to or within a 'cancer-causing gene' is not essential to influence their expression and that these modifications to genome interactions could have a major role in selection of HPV integrants at the early stage of cervical neoplastic progression.

Identification of host transcriptional networks showing concentration-dependent regulation by HPV16 E6 and E7 proteins in basal cervical squamous epithelial cells.

Development of cervical squamous cell carcinoma requires increased expression of the major high-risk human-papillomavirus (HPV) oncogenes E6 and E7 in basal cervical epithelial cells. We used a systems biology approach to identify host transcriptional networks in such cells and study the concentration-dependent changes produced by HPV16-E6 and -E7 oncoproteins. We investigated sample sets derived from the W12 model of cervical neoplastic progression, for which high quality phenotype/genotype data were available. We defined a gene co-expression matrix containing a small number of highly-connected hub nodes that controlled large numbers of downstream genes (regulons), indicating the scale-free nature of host gene co-expression in W12. We identified a small number of 'master regulators' for which downstream effector genes were significantly associated with protein levels of HPV16 E6 (n = 7) or HPV16 E7 (n = 5). We validated our data by depleting E6/E7 in relevant cells and by functional analysis of selected genes in vitro. We conclude that the network of transcriptional interactions in HPV16-infected basal-type cervical epithelium is regulated in a concentration-dependent manner by E6/E7, via a limited number of central master-regulators. These effects are likely to be significant in cervical carcinogenesis, where there is competitive selection of cells with elevated expression of virus oncoproteins.

A Deletion in the Canine POMC Gene Is Associated with Weight and Appetite in Obesity-Prone Labrador Retriever Dogs.

Sequencing of candidate genes for obesity in Labrador retriever dogs identified a 14 bp deletion in pro-opiomelanocortin (POMC) with an allele frequency of 12%. The deletion disrupts the ß-MSH and ß-endorphin coding sequences and is associated with body weight (per allele effect of 0.33 SD), adiposity, and greater food motivation. Among other dog breeds, the deletion was only found in the closely related flat-coat retriever (FCR), where it is similarly associated with body weight and food motivation. The mutation is significantly more common in Labrador retrievers selected to become assistance dogs than pets. In conclusion, the deletion in POMC is a significant modifier of weight and appetite in Labrador retrievers and FCRs and may influence other behavioral traits.

Preparation of molecularly imprinted polymeric fibers using a single bifunctional monomer for the solid-phase microextraction of parabens from environmental solid samples.

In this study, molecularly imprinted polymer fibers for solid-phase microextraction have been prepared with a single bifunctional monomer, N,O-bismethacryloyl ethanolamine using the so-called "one monomer molecularly imprinted polymers" method, replacing the conventional combination of functional monomer and cross-linker to form high fidelity binding sites. For comparison, imprinted fibers were prepared following the conventional approach based on ethylene glycol dimethacrylate as cross-linker and methacrylic acid as monomer. The recognition performance of the new fibers was evaluated in the solid-phase microextraction of parabens, and from this study it was concluded that they provided superior performance over conventionally formulated fibers. Ultimately, real-world environmental testing on spiked solid samples was successful by the molecularly imprinted solid-phase microextraction of samples, and the relative recoveries obtained at enrichment levels of 10 ng/g of parabens were within 78-109% for soil and 83-109% for sediments with a relative standard deviation <15% (n = 3).

Development, factor structure and application of the Dog Obesity Risk and Appetite (DORA) questionnaire.

Background. Dogs are compelling models in which to study obesity since the condition shares many characteristics between humans and dogs. Differences in eating behaviour are recognised to contribute to obesity susceptibility in other species but this has not been systematically studied in dogs. Aim. To develop and validate an owner-reported measure of canine eating behaviour and owner or dog related factors which can alter the development of obesity. Further, to then test variation in food-motivation in dogs and its association with obesity and owner management. Methods. Owner interviews, a literature review and existing human appetite scales were used to identify relevant topics and generate items for the questionnaire. Following a pilot phase, a 75 item online questionnaire was distributed via social media. Responses from 302 dog/owner dyads were analysed and factor structure and descriptive statistics calculated. Results were compared with descriptions of dog behaviour and management from a subset of respondents during semi-structured interviews. The optimum questions were disseminated as a 34 item final questionnaire completed by 213 owners, with a subset of respondents repeating the questionnaire 3 weeks later to assess test-retest reliability. Results. Analysis of responses to the final questionnaire relating to 213 dog/owner dyads showed a coherent factor structure and good test-retest reliability. There were three dog factors (food responsiveness and satiety, lack of selectivity, Interest in food), four owner factors (owner motivation to control dog weight, owner intervention to control dog weight, restriction of human food, exercise taken) and two dog health factors (signs of gastrointestinal disease, current poor health). Eating behaviour differed between individuals and between breed groups. High scores on dog factors (high food-motivation) and low scores on owner factors (less rigorous control of diet/exercise) were associated with obesity. Owners of more highly food-motivated dogs exerted more control over their dogs' food intake than those of less food-motivated dogs. Conclusions. The DORA questionnaire is a reliable and informative owner-reported measure of canine eating behaviour and health and management factors which can be associated with obesity development. The tool will be applicable to study of the canine obesity model and to clinical veterinarians. Results revealed eating behaviour to be similarly associated with obesity as exercise and owners giving titbits.

Evaluation of the phenol red thread tear test in falconiformes.

Falconiformes are active searchers and hunters that require visual precision to catch their prey and survive in the wild. Despite this, ocular disease is likely to be underdiagnosed in these species, at least in part because of limited proven diagnostic methods and lack of published scientific data. Tear film deficiency is recognized as an important ocular surface disease in dogs but has not been well evaluated in birds. To evaluate the phenol red thread (PRT) tear test as an alternative method to the Schirmer tear test (STT) for determining tear production in Falconiformes, we assessed the PRT tear test twice for each eye in 21 birds from the genus Falco. The mean PRT test values for the right (OD) and left (OS) eyes were OD=30.2±4.6 mm/15 s and OS=29.1±3.7 mm/15 s, with an overall PRT test value for both eyes (OU) of 30.6±4.2 mm/15 s. Good reproducibility was seen with the PRT test as shown by the strong positive correlation between the first and second tests in the birds. The PRT test method provides repeatable results that are easy to obtain, easy to read, and achieved under the same conditions as the STT.

Volume rejuvenation of the facial upper third.

The next three articles in this issue take a unique approach to discussing volumetric restoration. Robert Glasgold has provided an assessment for each facial region and five different renowned authors (TK, SPS, RF, SML, and EFW) have been asked to speak on a particular volumetric product, of which they are considered an expert, as it applies to the different regions of the face. The articles are broken into the following: (1) upper third which corresponds to the upper eyelid, brow, temple, and forehead; (2) middle third which will cover lower eyelid, cheek, and perioral area; and (3) lower third which discusses the marionette, prejowl, and jawline. Our hope is that by placing differing opinions of experienced authors, organized by facial region together, the reader will have the opportunity to more readily compare the options. The contributing authors and their product area are as follows: Theda Kontis, MD-hyaluronic acid; Steve Smith, MD-calcium hydroxyl appetite; Rebecca Fitzgerald, MD-poly-L lactic acid; Sam Lam, MD-polymethyl methacrylate; and Edwin Williams, MD-Autologous Fat Transfer. If the author included general comments on the product, they are included in the article on the upper face only and are not repeated. Please note that other individuals may also have significantly assisted in the production of these articles, but those listed above are the senior authors.

Volume management of the middle third-lower orbit/midface.

This is the second of the three articles discussing volumetric rejuvenation of the face. The previous article, Volume Rejuvenation of the Facial Upper Third, focused on the upper one-third of the face while this article focuses on the middle one-third, primarily the lower eyelid, cheek, and perioral area. Again, the authors (RG, TK, SPS, RF, SL, and EFW) from the upper face article have provided a summary of rejuvenation utilizing a product of which they are considered an expert. Robert Glasgold has provided volumetric analysis of the region as an introduction.

Volume rejuvenation of the lower third, perioral, and jawline.

This is the third and final article discussing volumetric rejuvenation of the face. The previous two articles, Rejuvenation of the Upper Third and Management of the Middle Third, focused on the upper two-thirds of the face while this article focuses on the lower face, including the marionette area, jawline, and neck. Again, the authors of the previous two articles have provided a summary of rejuvenation utilizing a product of which they are considered an expert. Robert Glasgold has provided volumetric analysis of the region as an introduction.

The relationship between body composition and preseason performance tests of collegiate male lacrosse players.

Numerous studies have examined the effects that body composition has on performance in football, soccer, and ice hockey; yet, there are no similar studies examining this relationship in men's lacrosse. The purpose of the study was to examine the physiological profiles and the relationship between body composition and performance in aerobic and anaerobic tests. Fifty-four (19.63 ± 1.21 years; 178.53 ± 6.17 cm; 81.66 ± 14.96 kg) Division III intercollegiate athletes participated. Performance tests, including a 1 repetition maximum power clean (PC), body weight (lbs), bench press repetitions, parallel bar triceps dips to fatigue (DR), two 300-yard shuttles, and a 1-mile run (MT), were completed after the completion of fall preseason practices. Body composition was estimated using air-displacement plethysmography. Correlation coefficients determined relationships between percent body fat (%BF), fat-free mass (FFM), and testing variables. Increased %BF was negatively correlated to DR (r = -0.36, p = 0.01) whereas positively correlated to each 300-yard shuttle time (T1 and T2), total 300-yard shuttle time (TT), and MT (r = 0.64, p = 0.00; r = 0.68, p = 0.00; r = 0.69, p = 0.00; and r = 0.44, p = 0.00, respectively). Increased FFM was positively correlated with PC (r = 0.58, p = 0.00) yet not correlated (p ≥ 0.05) with other variables. Results indicated that increased %BF might be a detriment to the repetitive anaerobic performance and aerobic capacity vital to on-field lacrosse performance. Body composition also demonstrated a significant relationship to moving internal vs. external resistances.

Autologous fat and fillers in periocular rejuvenation.

Facial volume loss is an important component of facial aging, especially in the periocular region. The authors evaluate the normal and aging anatomy of the periocular region and then discuss volume restoration of this region using hyaluronic acid, calcium hydroxylapatite, and autologous fat transfer. Preoperative assessment, operative technique, postoperative care, and complications are addressed.

A novel technique for prevention of self-mutilation in three Harris' hawks (Parabuteo unicinctus).

Feather destructive behavior is an ever-increasing problem in captive birds of prey and any associated self-mutilation can be challenging to manage. This clinical report describes a noninvasive, nonpainful, temporary beak modification technique used to prevent self-mutilation in 3 Harris' hawks (Parabuteo unicinctus), when other methods and husbandry modifications had failed. The technique was successful in all 3 birds, and no adverse effects were observed. Further investigations are required to further evaluate if this beak modification technique causes any psychologic or physical stress to the avian patient.

The scientific basis for lipotransfer: is it the ideal filler?

A loss of volume results from a reduction in the subcutaneous fat, muscle atrophy, and changes in skeletal framework. Such loss of tissue volume compounded with tissue laxity leads to the aged appearance of the periorbital, perioral, cheek, and mandibular areas. Many facial plastic surgeons have sought to replace this volume with various injectable agents, both synthetic and autologous, in search for the ideal soft tissue filler. This article reviews the literature on lipotransfer and specifically the scientific basis underlying the approach.

Management of cutaneous juvenile hemangiomas.

Past descriptions of vascular lesions often confused vascular malformations and hemangiomas using interchangeable definitions which led to inappropriate treatment and inconsistency in the medical literature. The work of Mulliken and Glowacki systematically delineated the difference between hemangiomas and the multiple varieties of vascular malformations. Hemangiomas are in fact as the suffix "oma" suggests true tumors exhibiting cellular proliferation on histology. Additionally, treatment has been clouded by numerous reports in the literature of near universal complete spontaneous resolution and conversely arguments that every lesion demands treatment. More recently, thoughtful studies of the natural course of hemangiomas have been completed, algorithms for intervention versus observation proposed, and effective safe treatment plans devised. The following article will be presented in two sections. The first section will review the diagnosis and natural history of hemangiomas as appreciated in modern literature and compare this to a review of historical articles. This information will then be used to describe a rational and thoughtful algorithm for observation or intervention and recommend appropriate treatment options. Special emphasis will be given to surgical technique and several cases of late involuting hemangiomas of the face will be presented.

Perioral rejuvenation: complementary techniques and procedures.

The intertwined nature of the aging process necessitates the use of complementary techniques to address each different aspect. Aging affects the perioral region in very specific ways that involve the upper lip, oral commissures, vermilion and philtral columns, lower lip, nasolabial folds, marionette lines, and perioral rhytids.

Impact of [18F]-2-fluorodeoxyglucose-positron emission tomography/computed tomography on previously untreated head and neck cancer patients.

OBJECTIVES: The role of fused modality [F]-2-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) in diagnosing and accurately staging patients with primary, metastatic, and recurrent head and neck (HN) cancer is evolving, and the clinical implications need to be further defined. A few retrospective studies have been performed, but adequate sample sizes are lacking because the number of HN cancer patients is relatively small. This study evaluates the positive predictive value (PPV), sensitivity, specificity, and accuracy of PET/CT in previously untreated HN cancer patients at a single tertiary care institution. The purpose of this study is to evaluate the role of this new technology in the management of previously untreated HN cancer patients. STUDY DESIGN: Retrospective cohort outcomes study at a tertiary National Cancer Institute Comprehensive Cancer Center. MATERIALS AND METHODS: Institutional review board exemption #4 (45 CFR 46.101 [4]) criteria were applied for and accepted by the office of responsible research practices at the Ohio State University College of Medicine. The authors identified 268 consecutive PET/CT examinations between March 2005 and January 2006 for HN cancer ordered by the two senior authors at the James Cancer Hospital and Solove Research Institute of the Ohio State University Medical Center. PET/CT examinations were interpreted by one of three neuroradiologists. PPV, sensitivity, specificity, accuracy, diagnostic upstaging, and treatment management changes were determined from subset analysis of 123 previously untreated patients with HN cancer. Synchronous lesions were detected in 10 patients with use of this modality. PET/CT was also used to help manage 22 patients with unknown primary HN cancer. The statistics were verified by comparing PET/CT results with surgical specimen histopathology. RESULTS: : PET/CT was true-positive in 82.9% (102/123), with a per patient PPV of 87.2% and a per lesion PPV of 89.4%. PET/CT was false-positive in 12.2% (15/123) of patients and had a false-positive rate of 8.3% when calculated per lesion. In 67 patients who underwent neck dissection, PET/CT had a PPV of 92.7%. The accuracy was 89.7% in 20 patients who had bilateral neck dissections. The unknown primary site was found in 72.7% (16/22) of patients with unknown primary HN cancer. Synchronous lesions were found in 8.1% of patients by PET/CT, with a PPV of 66.6%. Distant metastases were detected in 15.4% (19/123) of patients. Treatment was altered in 30.9% (38/123) of patients as a result of this imaging modality. CONCLUSIONS: The benefit of the PET/CT imaging modality resides in its fusion of anatomic detail of the HN region with the sensitivity of detecting tumors with increased metabolic activity at distant sites. Treatment was altered in 30.9% of our previously untreated HN cancer patients because of this imaging technique, with altered treatment including upstaging, diagnosing distant and unresectable disease, and working-up second primary malignancies. The false-positive findings did not result in additional morbidity to these patients. Although PET/CT is sensitive in detecting occult cervical nodal metastases, it does not yet have the ability to replace neck dissection as the diagnostic standard of care. This study supports the use of PET/CT in patients with newly diagnosed HN cancer because of its high PPV and superiority of detecting distant metastases and synchronous lesions.