Facial Implants in Male Rejuvenation.

Many different methods achieve male facial augmentation. Arranged from shorter- to longer-term results, these methods include filler, fat/tissue grafting, fat/tissue transposition, and alloplastic implants. This study solely reviews allografts, which provide the most predictable hard-tissue augmentation. An array of alloplasts will be discussed in this study including chin, cheek, mandibular angle, frontal, and temporal implants. The most common and severe complications will also be explored with preventative and treatment algorithms.

Human serous cavity macrophages and dendritic cells possess counterparts in the mouse with a distinct distribution between species.

In mouse peritoneal and other serous cavities, the transcription factor GATA6 drives the identity of the major cavity resident population of macrophages, with a smaller subset of cavity-resident macrophages dependent on the transcription factor IRF4. Here we showed that GATA6+ macrophages in the human peritoneum were rare, regardless of age. Instead, more human peritoneal macrophages aligned with mouse CD206+ LYVE1+ cavity macrophages that represent a differentiation stage just preceding expression of GATA6. A low abundance of CD206+ macrophages was retained in C57BL/6J mice fed a high-fat diet and in wild-captured mice, suggesting that differences between serous cavity-resident macrophages in humans and mice were not environmental. IRF4-dependent mouse serous cavity macrophages aligned closely with human CD1c+CD14+CD64+ peritoneal cells, which, in turn, resembled human peritoneal CD1c+CD14-CD64- cDC2. Thus, major populations of serous cavity-resident mononuclear phagocytes in humans and mice shared common features, but the proportions of different macrophage differentiation stages greatly differ between the two species, and dendritic cell (DC2)-like cells were especially prominent in humans.

Experiences of healthcare providers with a novel emergency response intubation team during COVID-19.

OBJECTIVES: In the early stages of the COVID-19 pandemic, there were significant concerns about the infectious risks of intubation to healthcare providers. In response, a dedicated emergency response intubation team (ERIT) consisting of anesthesiologists and allied health providers was instituted for our emergency department (ED). Given the high-risk nature of intubations and the new interprofessional team dynamics, we sought to assess health-care provider experiences and potential areas of improvement. METHODS: Surveys were distributed to healthcare providers at the University Health Network, a quaternary healthcare centre in Toronto, Canada, which includes two urban EDs seeing over 128,000 patients per year. Participants included ED physicians and nurses, anesthesiologists, anesthesia assistants, and operating room nurses. The survey included free-text questions. Responses underwent thematic analysis using grounded theory and were independently coded by two authors to generate descriptive themes. Discrepancies were resolved with a third author. Descriptive themes were distilled through an inductive, iterative process until fewer main themes emerged. RESULTS: A total of 178 surveys were collected (68.2% response rate). Of these, 123 (69%) participated in one or more ERIT activations. Positive aspects included increased numbers of staff to assist, increased intubation expertise, improved safety, and good team dynamics within the ERIT team. Challenges included a loss of scope (primarily ED physicians and nurses) and unfamiliar workflows, perceived delays to ERIT team arrival or patient intubation, role confusion, handover concerns, and communication challenges between ED and ERIT teams. Perceived opportunities for improvement included interprofessional training, developing clear guidelines on activation, inter-team role clarification, and guidelines on handover processes post-intubation. CONCLUSIONS: Healthcare providers perceived that a novel interprofessional collaboration for intubations of COVID-19 patients presented both benefits and challenges. Opportunities for improvement centred around interprofessional training, shared decision making between teams, and structured handoff processes.

RéSUMé: OBJECTIFS: Aux premiers stades de la pandémie de COVID-19, les risques infectieux de l'intubation pour les prestataires de soins de santé ont suscité de vives inquiétudes. En réponse, une équipe d'intervention d'urgence en intubation (emergency response intubation team ERIT), composée d'anesthésistes et de prestataires de services paramédicaux, a été mise en place dans notre service d'urgence. Compte tenu de la nature à haut risque des intubations et de la nouvelle dynamique d'équipe interprofessionnelle, nous avons cherché à évaluer les expériences des prestataires de soins et les domaines d'amélioration potentiels. MéTHODES: Les questionnaires ont été distribués aux prestataires de soins de santé du University Health Network, un centre de soins de santé quaternaire de Toronto, au Canada, qui comprend deux urgences urbaines accueillant plus de 128 000 patients par an. Les participants comprenaient des médecins et des infirmiers des urgences, des anesthésistes, des assistants en anesthésie et des infirmiers de salle d'opération. Les réponses ont fait l'objet d'une analyse thématique fondée sur la théorie de la base et ont été codées indépendamment par deux auteurs afin de générer des thèmes descriptifs. Les divergences ont été résolues avec un troisième auteur. Les thèmes descriptifs ont été distillés par un processus inductif et itératif jusqu'à ce qu'un nombre réduit de thèmes principaux émerge. RéSULTATS: Au total, 178 sondages ont été recueillis (taux de réponse de 68,2 %). Parmi ceux-ci, 123 (69 %) ont participé à une ou plusieurs activations d'ERIT. Les aspects positifs comprenaient un nombre accru de personnel pour aider, une expertise accrue en matière d'intubation, une sécurité améliorée et une bonne dynamique d'équipe au sein de l'équipe ERIT. Parmi les difficultés rencontrées, citons la perte du champ d'action (principalement les médecins et les infirmières des services d'urgence) et les flux de travail non familiers, les retards perçus dans l'arrivée de l'équipe d'ERIT ou l'intubation du patient, la confusion des rôles, les problèmes de transfert et les difficultés de communication entre les équipes des services d'urgence et d'ERIT. Les possibilités d'amélioration perçues comprennent la formation interprofessionnelle, l'élaboration de directives claires sur l'activation, la clarification des rôles entre les équipes et les directives sur les processus de transfert après l'intubation. CONCLUSIONS: Les prestataires de soins de santé ont perçu qu'une nouvelle collaboration interprofessionnelle pour les intubations des patients COVID-19 présentait à la fois des avantages et des défis.

Orbital cellulitis secondary to sinusitis in upstate New York: current incidence, seasonality, severity, management and outcomes.

PURPOSE: While sinusitis carries a seasonal variation, the temporal features of sinusitis-related orbital cellulitis (SRC) are unclear. This study analyzes the incidence, seasonality, management, and outcomes of SRC in northeastern New York. METHODS: A retrospective review of 79 patients was performed from January 2008 - December 2018. Cases of orbital cellulitis without comitant sinusitis were excluded. Demographic, radiographic, clinical features, month at presentation, interventions (surgical and nonsurgical), microbiology, and hospitalization duration were recorded. Fisher-exact test, Mann-Whitney test, and Kruskal Wallis test statistical analyses were performed in consultation with our institution's statistician via a dedicated software package (vassarstats.net). RESULTS: 79 patients were admitted for SRC. 25 patients were treated with antibiotics only, 31 underwent orbitotomy exclusively and 23 received combined orbitotomy and functional endoscopic sinus surgery (FESS). Of the 31 patients who underwent orbitotomy only, 8 (26%) returned to the operating room. In contrast, of those who underwent concomitant orbitotomy and FESS, only one patient (4.3%) required re-operation (fisher exact test, p = .021). The median length of stay for the antibiotic-only group (4 days), orbitotomy-only group (6 days), and combined surgery group (5 days) were statistically different (Kruskal Wallis, p = .004, Figure 3). Interestingly, there was no significant relationship of incidence or severity of SRC related to seasonality (fisher-exact test, p = .76). CONCLUSION: Our findings suggest that cases requiring surgical management for SRC should undergo coinitial orbitotomy with FESS to reduce re-operation rates. Additionally, SRC incidence and severity did not correlate with season.

Grafts in Endonasal Rhinoplasty.

Rhinoplasty is arguably one of the most challenging but rewarding procedures for the facial plastic surgeon. To adequately improve facial aesthetic parameters and preserve nasal function, the appropriate utilization of grafts is of utmost importance. While there is no best method, I found that in my hands, the endonasal approach allowed me to achieve greater control over my results by limiting dissection, utilizing less cartilage, and minimizing variables. In this manuscript, I outline the surgical pearls I have developed throughout my career that have helped me execute these grafts efficiently and effectively.

Targeted FGFR/VEGFR/PDGFR inhibition with dovitinib enhances the effects of nab-paclitaxel in preclinical gastric cancer models.

Standard chemotherapy regimens for gastric adenocarcinoma (GAC) have limited efficacy and considerable toxicity profiles. Nab-paclitaxel has shown promising antitumor benefits in previous GAC preclinical studies. Dovitinib inhibits members of the receptor tyrosine kinase family including FGFR, VEGFR and PDGFR, and has exhibited antitumor effects in many solid tumors including GAC. Based on the antimitotic, antistromal and EPR effects of nab-paclitaxel, we investigated augmentation of nab-paclitaxel response by dovitinib in multiple GAC preclinical models. In MKN-45 subcutaneous xenografts, inhibition in tumor growth by nab-paclitaxel and dovitinib was 75% and 76%, respectively. Dovitinib plus nab-paclitaxel had an additive effect on tumor growth inhibition and resulted in tumor regression (85% of its original value). Dovitinib monotherapy resulted in minimal improvement in animal survival (25 days) compared to control (23 days), while nab-paclitaxel monotherapy or dovitinib plus nab-paclitaxel combination therapy led to a clinically significant lifespan extension of 83% (42 days) and 187% (66 days), respectively. IHC analysis of subcutaneous tumors exhibited reduced tumor cell proliferation and tumor vasculature by dovitinib. In vitro studies demonstrated that dovitinib and nab-paclitaxel individually reduced tumor cell proliferation, with an additive effect from combination therapy. Immunoblot analyses of MKN-45 and KATO-III cells revealed that dovitinib decreased phospho-FGFR, phospho-AKT, phospho-ERK, phospho-p70S6K, phospho-4EBP1, Bcl-2 and increased cleaved PARP-1, cleaved-caspase-3, p27, Bax, Bim, with an additive effect from combination therapy. These results demonstrate that the FGFR/VEGFR/PDGFR inhibitor, dovitinib, has the potential to augment the antitumor effects of nab-paclitaxel, with implications for use in the advancement of clinical GAC therapy.

A shift from glycolytic and fatty acid derivatives toward one-carbon metabolites in the developing lung during transitions of the early postnatal period.

During postnatal lung development, metabolic changes that coincide with stages of alveolar formation are poorly understood. Responding to developmental and environmental factors, metabolic changes can be rapidly and adaptively altered. The objective of the present study was to determine biological and technical determinants of metabolic changes during postnatal lung development. Over 118 metabolic features were identified by liquid chromatography with tandem mass spectrometry (LC-MS/MS, Sciex QTRAP 5500 Triple Quadrupole). Biological determinants of metabolic changes were the transition from the postnatal saccular to alveolar stages and exposure to 85% hyperoxia, an environmental insult. Technical determinants of metabolic identification were brevity and temperature of harvesting, both of which improved metabolic preservation within samples. Multivariate statistical analyses revealed the transition between stages of lung development as the period of major metabolic alteration. Of three distinctive groups that clustered by age, the saccular stage was identified by its enrichment of both glycolytic and fatty acid derivatives. The critical transition between stages of development were denoted by changes in amino acid derivatives. Of the amino acid derivatives that significantly changed, a majority were linked to metabolites of the one-carbon metabolic pathway. The enrichment of one-carbon metabolites was independent of age and environmental insult. Temperature was also found to significantly influence the metabolic levels within the postmortem sampled lung, which underscored the importance of methodology. Collectively, these data support not only distinctive stages of metabolic change but also highlight amino acid metabolism, in particular one-carbon metabolites as metabolic signatures of the early postnatal lung.

A Comprehensive Approach to Midface Rejuvenation: Our Philosophy, Algorithm, and Surgical Technique.

With a greater understanding of the aging process and relevant anatomy, the facial plastic surgeon has an expansive armamentarium of options for midface rejuvenation. Upon reflection, our practice has evolved over the years and only recently found a select number of interventions that have consistently produced excellent results. In this article, we discuss the steps needed to establish an effective patient relationship, present an algorithm on how to approach midface rejuvenation, describe our surgical technique, and review the attributes and liabilities of each procedure.

Return to Baseline Functional Status in Older Women Undergoing Surgery for Pelvic Organ Prolapse.

OBJECTIVE: The aim of the study was to determine the rate of return to baseline functional status 3 months after surgery for pelvic organ prolapse (POP) in women 65 years or older. METHODS: This is a multicenter prospective cohort study of women older than 65 years undergoing POP surgery. Functional status was determined by the Activities Assessment Scale at the preoperative visit and 3 months after surgery. We compared a variety of clinical variables and preoperative functional status scores for women who worsened, improved, or returned to baseline functional status after surgery using univariable and multivariable analysis. RESULTS: A total of 192 women were enrolled in the study. Of 176 women who completed both sets of questionnaires, 59% improved, 35% returned, and 6% worsened from their baseline functional status. Variables significantly associated with postoperative functional status score were depression (P < 0.002) and preoperative functional status score (P < 0.001). The group that improved from baseline had the lowest (worst) preoperative functional status score (78.7 ± 16.4), whereas the group that worsened after surgery had the highest (best) preoperative functional status score (98.6 ± 2.2). After adjusting for age and depression, higher preoperative functional status score was predictive of failure to return to baseline functional status. CONCLUSIONS: Most older women undergoing surgery for POP, including those with low preoperative functional status, return to or improve from their baseline functional status within 3 months of surgery. Women with higher functional status before surgery are less likely to report improvement in physical functioning after surgery.

Video Virtual Clinical Encounters Versus Office Visits for Postoperative Care After Pelvic Organ Prolapse Surgery: A Randomized Clinical Trial.

OBJECTIVES: To determine if patient satisfaction of virtual clinical encounters is noninferior to traditional in-office clinical encounters for postoperative follow-up after reconstructive surgery for pelvic organ prolapse. METHODS: This was a randomized controlled noninferiority trial of women undergoing surgery for pelvic organ prolapse. Women were recruited and randomized during their preoperative counseling visit to virtual clinical encounters via video conference technology or in-office clinical encounters for their 30-day postoperative follow-up visits. The primary outcome was patient satisfaction measured by the validated Patient Satisfaction Questionnaire-18 (score range, 18-90, with higher scores indicating greater satisfaction) administered by telephone following the 30-day visit. Additional information regarding demographics, postoperative health care utilization, and complications was collected via chart review and compared between groups. RESULTS: A total of 52 women were randomly assigned to virtual clinical encounters via videoconference technology or traditional in-office clinical encounters (26 per group). The mean patient satisfaction score was 80.7 ± 2.6 in the virtual group and 81.2 ± 2.8 in the office group (difference, -0.46 points; 95% confidence interval, -1.95 to 1.03), which was consistent with noninferiority. Postoperative complication rates were 31% in the virtual group and 46% in the office group (P = 0.3). There were no significant between-group differences in secondary measures of unscheduled telephone calls (88% versus 77%, P = 0.5) and office visits (35% versus 38%, P = 0.8), emergency room visits (15% versus 19%, P = 1.0), and hospital readmissions (4% versus 12%, P = 0.6) within 90 days of surgery. CONCLUSIONS: For patients with pelvic organ prolapse undergoing reconstructive surgery, postoperative virtual clinical encounters via video conference technology are noninferior to traditional in-office clinical encounters with high levels of short-term patient satisfaction and no differences in postoperative health care utilization and complications rates.

Mechanistic regulation of SPHK1 expression and translocation by EMAP II in pulmonary smooth muscle cells.

Phosphorylation of sphingosine by sphingosine kinase 1 (SPHK1) produces the bioactive sphingolipid sphingosine-1-phosphate (S1P), a microvascular and immuno-modulator associated with vascular remodeling in pulmonary arterial hypertension (PAH). The low intracellular concentration of S1P is under tight spatial-temporal control. Molecular mechanisms that mediate S1P burden and S1P regulation of vascular remodeling are poorly understood. Similarities between two early response pro-inflammatory cytokine gene transcript activation profiles, S1P and Endothelial Monocyte Activating Polypeptide II (EMAP II), suggested a strategic link between their signaling pathways. We determined that EMAP II triggers a bimodal phosphorylation, transcriptional regulation and membrane translocation of SPHK1 through a common upstream process in both macrophages and pulmonary artery smooth muscle cells (PASMCs). EMAP II initiates a dual function of ERK1/2: phosphorylation of SPHK1 and regulation of the transcription factor EGR1 that induces expression of SPHK1. Activated ERK1/2 induces a bimodal phosphorylation of SPHK1 which reciprocally increases S1P levels. This identified common upstream signaling mechanism between a protein and a bioactive lipid initiates cell specific downstream signaling representing a multifactorial mechanism that contributes to inflammation and PASMC proliferation which are cardinal histopathological phenotypes of PAH.

Influence of aminoacyl-tRNA synthetase complex-interacting multifunctional protein 1 on epithelial differentiation and organization during lung development.

Proper development of the respiratory bronchiole and alveolar epithelium proceeds through coordinated cross talk between the interface of epithelium and neighboring mesenchyme. Signals that facilitate and coordinate the cross talk as the bronchial forming canalicular stage transitions to construction of air-exchanging capillary-alveoli niche in the alveolar stage are poorly understood. Expressed within this decisive region, levels of aminoacyl-tRNA synthetase complex-interacting multifunctional protein 1 (AIMP1) inversely correlate with the maturation of the lung. The present study addresses the role of AIMP1 in lung development through the generation and characterization of Aimp1-/- mutant mice. Mating of Aimp1+/- produced offspring in expected Mendelian ratios throughout embryonic development. However, newborn Aimp1-/- pups exhibited neonatal lethality with mild cyanosis. Imaging both structure and ultrastructure of Aimp1-/- lungs showed disorganized bronchial epithelium, decreased type I but not type II cell differentiation, increased distal vessels, and disruption of E-cadherin deposition in cell-cell junctions. Supporting the in vivo findings of disrupted epithelial cell-cell junctions, in vitro biochemical experiments show that a portion of AIMP1 binds to phosphoinositides, the lipid anchor of proteins that have a fundamental role in both cellular membrane and actin cytoskeleton organization; a dramatic disruption in F-actin cytoskeleton was observed in Aimp1-/- mouse embryonic fibroblasts. Such observed structural defects may lead to disrupted cell-cell boundaries. Together, these results suggest a requirement of AIMP1 in epithelial cell differentiation in proper lung development.

Cell-Cell Communication Breakdown and Endothelial Dysfunction.

Guided by organ-specific signals in both development and disease response, the heterogeneous endothelial cell population is a dynamic member of the vasculature. Functioning as the gatekeeper to fluid, inflammatory cells, oxygen, and nutrients, endothelial cell communication with its local environment is critical. Impairment of endothelial cell-cell communication not only disrupts this signaling process, but also contributes to pathologic disease progression. Expanding our understanding of those processes that mediate endothelial cell-cell communication is an important step in the approach to treatment of disease processes.

Head and Neck Dystonia Following Chimeric-Antigen Receptor T-Cell Immunotherapy: A Case Report.

Chimeric antigen receptor T-cell therapy (CAR-T) is a novel immunotherapy used for the treatment of refractory B-cell leukemias and lymphoma. As clinical trials continue to expand, multiple treatment toxicities have been documented. Treatment-associated toxicities are typically systemic, however, focal manifestations have been described. We present a unique case of a 55-year-old female who developed oropharyngeal and laryngeal dystonia following CAR-T therapy. This case points to a possible association between CAR-T therapy and focal head and neck dystonia. Laryngoscope, 2020.

Separability and geometry of object manifolds in deep neural networks.

Stimuli are represented in the brain by the collective population responses of sensory neurons, and an object presented under varying conditions gives rise to a collection of neural population responses called an 'object manifold'. Changes in the object representation along a hierarchical sensory system are associated with changes in the geometry of those manifolds, and recent theoretical progress connects this geometry with 'classification capacity', a quantitative measure of the ability to support object classification. Deep neural networks trained on object classification tasks are a natural testbed for the applicability of this relation. We show how classification capacity improves along the hierarchies of deep neural networks with different architectures. We demonstrate that changes in the geometry of the associated object manifolds underlie this improved capacity, and shed light on the functional roles different levels in the hierarchy play to achieve it, through orchestrated reduction of manifolds' radius, dimensionality and inter-manifold correlations.

A distinct transcriptional profile in response to endothelial monocyte activating polypeptide II is partially mediated by JAK-STAT3 in murine macrophages.

Macrophages are important responders to environmental changes such as secreted factors. Among the secreted factors in injured tissues, the highly conserved endothelial monocyte activating polypeptide II (EMAP II) has been characterized to limit vessel formation, to be locally expressed near sites of injury labeling it a "find-me" signal, and to recruit macrophages and neutrophils. The molecular mechanisms mediated by EMAP II within macrophages once they are recruited are unknown. In this study, using a model of partially activated, recruited thioglycollate-elicited peritoneal macrophages, a transient, transcription profile of key functional genes in macrophages exposed to EMAP II was characterized. We found that EMAP II-mediated changes were elicited mainly through signal transducer and activator of transcription 3 (STAT3) as evidenced by increased Y705 phosphorylation and changes in activity and upstream of it, Janus associated kinase (JAK)1/2 upstream. Both inhibition of JAK1/2 and knockdown of Stat3 abrogated a subset of genes that are upregulated by EMAP II. Our results identify a rapid EMAP II-mediated STAT3 activation that coincides with altered pro- and anti-inflammatory gene expression in macrophages.

The Quality of Health Information Available on the Internet for Patients With Fecal Incontinence.

OBJECTIVE: The aim of this study was to assess the quality of information available through the Internet for a variety of search terms for fecal incontinence (FI). METHODS: Using the Google search engine, searches were performed for 4 terms: "bowel control problem," "accidental bowel leakage," "fecal incontinence," and "leaking stool." The DISCERN quality analysis tool and JAMA benchmark criteria were implemented by 2 independent reviewers to evaluate the first 20 search results for each term. To determine if 1 term provided higher-quality information, mean DISCERN and JAMA criteria scores as well as Web site category were compared using analysis of variance and Pearson χ tests. RESULTS: Mean DISCERN scores for all terms fell in the middle range of possible scores. DISCERN questions addressing risks of treatment options, effects of treatment on quality of life, and gaps in knowledge/differences in expert opinion had the lowest scores across all search terms (range of scores, 1.1-1.7/5). JAMA criteria on authorship and attribution were most frequently missing on average in 48 of 80 and 42 of 80 Web sites, respectively. There were significant differences in mean DISCERN scores among the terms, with "fecal incontinence" yielding the highest mean score. The term "accidental bowel leakage" yielded the highest number of marketing Web sites, whereas "leaking stool" had the highest proportion of social Web sites. CONCLUSIONS: The quality of available information about FI on the Internet is variable, and key components are often missing. The term "fecal incontinence" yielded the highest quality information of all search terms.

Willingness of Women With Pelvic Floor Disorders to Use Mobile Technology to Communicate With Their Health Care Providers.

OBJECTIVES: The aim of this study was to assess willingness of women with pelvic floor disorders to adopt nontraditional mobile communication methods with health care providers. METHODS: This is a cross-sectional study of women with pelvic floor disorders. Women completed a survey regarding what technology they owned, how they utilized it, and their willingness to use technology to communicate with providers. RESULTS: Overall mobile technology ownership was high; however, older women were significantly less likely to own a smartphone (75%) compared with younger (100%) and middle-aged women (98%; P < 0.01). On univariable analysis, factors significantly associated with willingness to use mobile technology were age (P < 0.01) and education status (P < 0.01). A relationship between travel distance to the clinic and willingness to adopt various mobile technologies was not noted. On multivariable analysis, after controlling for education and travel distance to clinic, older women remained significantly less likely to express willingness to use various technologies: video-conference technology (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.95-0.99), text messaging (OR, 0.94; 95% CI, 0.91-0.97), Internet-based patient portal (OR, 0.96; 95% CI, 0.94-0.98), and e-mail (OR, 0.94; 95% CI, 0.91-0.98). However, almost 50% of older women and greater than 65% of middle-aged women expressed willingness to adopt technologies for health care communication. CONCLUSIONS: Age-related differences exist in the ownership, utilization, and willingness to communicate with medical providers through mobile technology. However, the majority of women across all age-groups, irrespective of travel distance, are willing to adopt alternative mobile technologies to communicate with their health care providers.