The Na+, K+-ATPase ß1 subunit regulates epithelial tight junctions via MRCKα.

An intact lung epithelial barrier is essential for lung homeostasis. The Na+, K+-ATPase (NKA), primarily serving as an ion transporter, also regulates epithelial barrier function via modulation of tight junctions. However, the underlying mechanism is not well understood. Here, we show that overexpression of the NKA ß1 subunit upregulates the expression of tight junction proteins, leading to increased alveolar epithelial barrier function by an ion transport-independent mechanism. Using IP and mass spectrometry, we identified a number of unknown protein interactions of the ß1 subunit, including a top candidate, myotonic dystrophy kinase-related cdc42-binding kinase α (MRCKα), which is a protein kinase known to regulate peripheral actin formation. Using a doxycycline-inducible gene expression system, we demonstrated that MRCKα and its downstream activation of myosin light chain is required for the regulation of alveolar barrier function by the NKA ß1 subunit. Importantly, MRCKα is expressed in both human airways and alveoli and has reduced expression in patients with acute respiratory distress syndrome (ARDS), a lung illness that can be caused by multiple direct and indirect insults, including the infection of influenza virus and SARS-CoV-2. Our results have elucidated a potentially novel mechanism by which NKA regulates epithelial tight junctions and have identified potential drug targets for treating ARDS and other pulmonary diseases that are caused by barrier dysfunction.

Comparison of Phasix, polypropylene, and primary closure of the abdominal donor site after bilateral free flap breast reconstruction: Long-term evaluation of abdominal hernia and bulge formation.

BACKGROUND: Abdominal free flap harvest for breast reconstruction may result in significant morbidity in terms of hernias and bulges. Reinforcement of the donor site with mesh has been recommended to minimize the risk of hernias and bulges, but no studies exist evaluating the optimal type of mesh. Polypropylene has traditionally been used but the development of Phasix restorable mesh may be a reasonable alternative. Here, we compared the use of Phasix to polypropylene and primary closure and hypothesize that the former has lower rates of abdominal morbidity in the long term. PATIENTS AND METHODS: A retrospective review of all patients undergoing bilateral free flap breast reconstruction from the abdomen was performed while patients with pedicle flaps or alternative donor sites were excluded. Patient demographics, medical/surgical history, cancer treatments, and flap type were analyzed. All patients were monitored for a minimum of 2 years for early donor site complications as well as hernia/bulges. RESULTS: Sixty-six consecutive patients were included (40 patients with Phasix, 20 patients with polypropylene, and 6 patients with primary closure). Use of Phasix mesh resulted in higher initial operative costs ($2,750 vs. $72 vs. $0). Two patients with polypropylene mesh and one patient undergoing primary closure developed an abdominal bulge in an average follow-up of 25.2 months (11.5% vs. 0%, p = .04). CONCLUSIONS: Mesh placement for abdominal wall reinforcement after bilateral free flap breast reconstruction minimizes the risk of hernias and bulges. Although Phasix results in increased initial costs, abdominal morbidity is significantly decreased after follow-up beyond 2 years.

Shoulder Subluxation Pain as a Secondary Indication for Trapezius to Deltoid Transfer.

Brachial plexus injuries can be debilitating. We have observed that manual reduction of the patients' shoulder subluxation improves their pain and have used this as a second reason to perform the trapezius to deltoid muscle transfer beyond motion. The authors report a series of nine patients who all had significant improvement of pain in the shoulder girdle and a decrease in pain medication use after a trapezius to deltoid muscle transfer. All patients were satisfied with the outcomes and stated that they would undergo the procedure again if offered the option. The rate of major complications was low. The aim is not to describe a new technique, but to elevate a secondary indication to a primary for the trapezius to deltoid transfer beyond improving shoulder function: pain relief from chronic shoulder subluxation.

Comparison of Histological Characteristics of Acellular Dermal Matrix Capsules to Surrounding Breast Capsules in Acellular Dermal Matrix-Assisted Breast Reconstruction.

INTRODUCTION: Despite the widespread adaptation of acellular dermal matrix (ADM) to breast reconstruction, we are just now exploring how these materials integrate and perform in vivo. The goal of this study was to compare the histological characteristics between expander capsules to an area without the ADM. METHODS: Women undergoing implant-based breast reconstruction at the University of Virginia Health System using a decellularized regenerative dermal matrix were enrolled in this prospective, evaluator-blinded, institutional review board-approved study. Twenty-four non-ADM and 24 ADM breast capsule biopsy specimens were collected from 15 women and analyzed for the histological parameters of inflammation, vascular proliferation, capsule fibrosis, foreign body giant cell inflammatory reaction, and myofibroblasts using a previously described semiquantitative scoring system. The pathologist evaluating the specimens was blinded to the tissue source and biopsy location. RESULTS: There was significantly less inflammation and fewer myofibroblasts in the ADM capsule biopsy samples compared with the no-ADM capsule biopsy samples (inflammation: ADM, 0.83; no-ADM, 1.83; P = 0.001; myofibroblasts: ADM, 0.79; no-ADM, 1.46; P = 0.024). Significantly less vascular proliferation in the ADM samples was seen compared with the no-ADM samples (ADM, 0.75; no-ADM, 1.42; P = 0.036). No statistical difference in the presence of an inflammatory capsule was observed in the no-ADM biopsy samples compared with the ADM capsule biopsy samples (P = 0.060). CONCLUSIONS: When used for staged breast reconstruction, this unique, sterile ADM seems to induce less inflammation. Moreover, the significantly decreased presence of myofibroblasts in this material supports the observed clinical findings of decreased capsular contracture in ADM-assisted breast reconstruction.

The Average Size and Position of the Umbilicus in Young Men and Women.

INTRODUCTION: Abdominoplasty was the third most common cosmetic surgical procedure in 2012. The umbilicus is transposed within the abdominal skin flap during this procedure. Few studies address the size and location of the umbilicus with precise measurements as well as those that do report on a heterogeneous population. The goal of our study was to determine the average size and position of the ideal umbilicus by limiting the study to young men and women of normal body habitus. METHODS: Subjects were recruited in a University of Virginia Institutional Review Board-approved study. Demographics of the subjects were recorded. Each subject's umbilicus was assessed for height, width, and position relative to existing landmarks. RESULTS: Eighty subjects met the inclusion criteria: 43 women and 37 men. Most of the subjects were white (72.5%). The mean ± SD BMI was 22.4 ± 2.5 kg/m. The mean ± SD height and width of the umbilicus was 2.1 ± 0.6 cm and 2.3 ± 0.7 cm, respectively. The umbilicus was located at a mean ± SD of -0.7 ± 1.3 cm in relation to the iliac crest (crest at zero). There were differences seen in the position between men and women. There were no statistical differences in measurements between the races. CONCLUSION: Our study serves as a guide for umbilical positioning with mean measurements for men and women, and categorized by sex and race.

Primary cutaneous cryptococcosis treated with debridement and fluconazole monotherapy in an immunosuppressed patient: a case report and review of the literature.

Cryptococcus neoformans is an opportunistic yeast present in the environment. Practitioners are familiar with the presentation and management of the most common manifestation of cryptococcal infection, meningoencephalitis, in patients with AIDS or other conditions of immunocompromise. There is less awareness, however, of uncommon presentations where experience rather than evidence guides therapy. We report a case of primary cutaneous cryptococcosis (PCC) in a patient who had been immunosuppressed by chronic high-dose corticosteroid for the treatment of severe asthma. This case highlights the importance of early recognition of aggressive cellulitis that fails standard empiric antibiotic treatment in an immunocompromised patient. It also demonstrates successful treatment of PCC with a multispecialty approach including local debridement and fluconazole monotherapy.

Acquired digital fibrokeratoma: a case report.

Acquired digital fibrokeratomas are benign, rare tumors that develop most commonly on the fingers. They can have an appearance of a rudimentary supernumerary digit or be misdiagnosed as a more common condition, such as verruca vulgaris. There are no case reports described in the plastic surgery literature. We are reporting a case that presented to our institution recently.

Effect of cleft palate repair on the susceptibility to contraction-induced injury of single permeabilized muscle fibers from congenitally-clefted goat palates.

OBJECTIVE: Despite cleft palate repair, velopharyngeal competence is not achieved in approximately 15% of patients, often necessitating secondary surgical correction. Velopharyngeal competence postrepair may require the conversion of levator veli palatini muscle fibers from injury-susceptible type 2 fibers to injury-resistant type 1 fibers. As an initial step to determining the validity of this theory, we tested the hypothesis that, in most cases, repair induces the transformation to type 1 fibers, thus diminishing susceptibility to injury. INTERVENTIONS: Single permeabilized levator veli palatini muscle fibers were obtained from normal palates and nonrepaired congenitally-clefted palates of young (2 months old) and adult (14 to 15 months old) goats and from repaired palates of adult goats (8 months old). Repair was done at 2 months of age using a modified von Langenbeck technique. MAIN OUTCOME MEASURES: Fiber type was determined by contractile properties and susceptibility to injury was assessed by force deficit, the decrease in maximum force following a lengthening contraction protocol expressed as a percentage of initial force. RESULTS: For normal palates and cleft palates of young goats, the majority of the fibers were type 2 with force deficits of approximately 40%. Following repair, 80% of the fibers were type 1 with force deficits of 20% +/- 2%; these deficits were 45% of those for nonrepaired cleft palates of adult goats (p < .0001). CONCLUSION: The decrease in the percentage of type 2 fibers and susceptibility to injury may be important for the development of a functional levator veli palatini muscle postrepair.

The effect of cleft palate repair on contractile properties of single permeabilized muscle fibers from congenitally cleft goat palates.

Inherent differences in the levator veli palatini (LVP) muscle of cleft palates before palatoplasty may play a role in persistent postrepair velopharyngeal insufficiency (VPI). Contractile properties of LVP muscle fibers were analyzed from young (2-month) normal (YNP), young congenitally cleft (YCP) and again on the same YCP subjects 6 months after palatoplasty, mature repaired palate (MRP). The cross-sectional area and rate of force development (ktr) were measured. Specific force (sF(0)) and normalized power (nP(max)) were calculated. Using k(tr) to determine fiber type composition, YNP was 44% type 1 and 56% type 2, while YCP was 100% type 2. Two MRP subjects shifted to 100% type 1; 1 demonstrated increased resistance to fatigue. No differences in sF(0) were observed. nP(max) increased with presence of type 2 fibers. The persistent state of type 2 fibers following palatoplasty leads to increased fatigue in the LVP of MRP subjects and may cause VPI symptoms.

Contractile properties of single permeabilized muscle fibers from congenital cleft palates and normal palates of Spanish goats.

BACKGROUND: Analysis of the composition of muscle fibers constituent to a cleft palate could provide significant insight into the cause of velopharyngeal inadequacy. The authors hypothesized that levator veli palatini muscle dysfunction inherent to cleft palates could affect the timing and outcome of cleft palate repair. METHODS: Single, permeabilized muscle fibers from levator veli palatini muscles of three normal (n = 19 fibers) and three chemically induced congenital cleft palates (n = 21 fibers) of 14-month-old goats were isolated, and contractile properties were evaluated. The maximum isometric force and rate constants of tension redevelopment (ktr) were measured, and the specific force and normalized power were calculated for each fiber. RESULTS: The ktr measures indicate that cleft fibers are predominantly fast-fatigable; normal fibers are slow fatigue-resistant: after a 10-minute isometric contraction, fibers from cleft palates had a loss of force 16 percent greater than that from normal palates (p = 0.0001). The cross-sectional areas of the fibers from cleft palates (2750 +/- 209 microm2) were greater (p = 0.05) than those from normal palates (2226 +/- 143 microm2). Specific forces did not differ between the two groups. Maximum normalized power of fibers from cleft palates (11.05 +/- 1.82 W/l) was greater (p = 0.0001) than fibers from normal palates (1.60 +/- 0.12 W/l). CONCLUSIONS: There are clear physiologic differences in single muscle fibers from cleft palates and normal palates: cleft palate fibers are physiologically fast, have greater fatigability, and have greater power production. Detection of functional and/or fiber type differences in muscles of cleft palates may provide preoperative identification of a patient's susceptibility to velopharyngeal inadequacy and permit early surgical intervention to correct this clinical condition.

Contraction-induced injury to single permeabilized muscle fibers from normal and congenitally-clefted goat palates.

OBJECTIVE: Levator veli palatini muscles from normal palates of adult humans and goats are predominantly slow oxidative (type 1) fibers. However, 85% of levator veli palatini fibers from cleft palates of adult goats are physiologically fast (type 2). This fiber composition difference between cleft and normal palates may have implications in palatal function. For limb muscles, type 2 muscle fibers are more susceptible to lengthening contraction-induced injury than are type 1 fibers. We tested the hypothesis that, compared with single permeabilized levator veli palatini muscle fibers from normal palates of adult goats, those from cleft palates are more susceptible to lengthening contraction-induced injury. INTERVENTIONS: Congenital cleft palates were the result of chemically-induced decreased movement of the fetal head and tongue causing obstruction of palatal closure. Each muscle fiber was maximally activated and lengthened. OUTCOME MEASURES: Fiber type was determined by contractile properties and gel electrophoresis. Susceptibility to injury was assessed by measuring the decrease in maximum force following the lengthening contraction, expressed as a percentage of the initial force. RESULTS: Compared with fibers from normal palates that were all type 1 and had force deficits of 23 +/- 1%, fibers from cleft palates were all type 2 and sustained twofold greater deficits, 40 +/- 1% (p = .001). CONCLUSION: Levator veli palatini muscles from cleft palates of goats contain predominantly type 2 fibers that are highly susceptible to lengthening contraction-induced injury. This finding may have implications regarding palatal function and the incidence of velopharyngeal incompetence.

Endoscopic versus open tissue-expander placement: is less invasive better?

BACKGROUND: Skin tissue expansion provides an excellent option for reconstruction of large cutaneous defects. Unfortunately, the complication rate with tissue-expander reconstruction is very high. One potential alternative to reduce these complications and improve recovery time is to place the tissue expanders endoscopically. The authors hypothesize that endoscopic placement of tissue expanders will reduce the complication rate, operative time, and time to full expansion. METHODS: Sixty-nine patients have undergone 81 surgical procedures for placement of 202 tissue expanders over the past 8 years at the University of Michigan Health System. The charts for all patients were reviewed retrospectively and the data analyzed to evaluate outcomes following open and endoscopic tissue-expander placement. RESULTS: Fifty-one patients underwent open placement of 127 tissue expanders for reconstruction, whereas 18 patients underwent endoscopic placement of 75 expanders. The average operative time for placement of each expander was significantly reduced in the endoscopic group (34.0 minutes) compared with the open group (49.2 minutes) (p < 0.0001). The major complication rate per tissue expander was also reduced in the endoscopically placed expander group (2.7 percent) compared with the open group (22.0 percent) (p = 0.0000056). Time to full expansion and length of hospital stay were also significantly reduced in the endoscopic group (p < 0.05 and p < 0.005, respectively). CONCLUSIONS: Endoscopic tissue-expander placement significantly reduced operative time for placement of each expander, major complication rate, time to full expansion, and length of hospital stay for this reconstructive technique. The authors conclude that endoscopic placement of tissue expanders is a safe and effective method for tissue-expander reconstructions of large, difficult wounds.

Nevus sebaceus of Jadassohn revisited with reconstruction options.

BACKGROUND: Nevus sebaceus of Jadassohn (NS) has the classic presentation on the head and neck of a yellow-orange-colored, waxy, pebble-like, papule or plaque. Its reported malignant potential varies between 0.8% and 50%. The common location of NS on the temporal hairline leaves a cosmetic defect. METHODS: We retrospectively reviewed a consecutive series of patients with NS located in the temporal scalp region. Thirteen patients were included. Twelve patients were reconstructed with a temporal flap. One patient had a primary linear scalp closure after excision. Clinical, histopathologic, surgical, and photographic records were used to review the clinical, anatomic, and pathologic presentation of the lesions. Reconstructions were rated on a scale of 1-5 by two independent examiners. The cosmetic results were also assessed by the patients. RESULTS: Patients ranged in age from 3 to 40 years. All of the lesions were located in the temporal area of the scalp. All cases were pathologically determined as NS. Two cases contained basal cell carcinoma (15%). Two cases were re-excisions of confirmed NS. One case was excised and closed with difficulty using a linear primary closure. Rotation flaps based on the superior temporal artery were used for the reconstruction of the defects in 12 patients. Nine of the flaps were anterior rotation flaps and three were posterior. The average score for the cosmetic results of the patients was 3.75, with the lowest score being 2, and the highest 5. The score for the linear closure was 2. CONCLUSION: A rotation flap based on the superficial temporal artery is an excellent reconstructive solution for NS located in the temporal scalp region.

A virtual team group process.

Virtual teams are a phenomenon of the Information Era and their existence in health care is anticipated to increase with technology enhancements such as telehealth and groupware. The mobilization and support of high performing virtual teams are important for leading knowledge-based health professionals in the 21st century. Using an adapted McGrath group development model, the four staged maturation process of a virtual team consisting of four masters students is explored in this paper. The team's development is analyzed addressing the interaction of technology with social and task dynamics. Throughout the project, leadership competencies of value to the group that emerged were demonstrated and incorporated into the development of a leadership competency assessment instrument. The demonstration of these competencies illustrated how they were valued and internalized by the group. In learning about the work of this virtual team, the reader will gain understanding of how leadership impacts virtual team performance.

Inhibition of cyclooxygenase 2 blocks human cytomegalovirus replication.

Cyclooxygenase 2 (COX-2) mRNA, protein, and activity are transiently induced after infection of human fibroblasts with human cytomegalovirus. Prostaglandin E(2), the product of COX-2 activity, is transiently increased by a factor of >50 in cultures of virus-infected fibroblasts. Both specific (BMS-279652, 279654, and 279655) and nonspecific (indomethacin) COX-2 inhibitors can abrogate the virus-mediated induction of prostaglandin E(2) accumulation. Levels of COX-2 inhibitors that completely block the induction of COX-2 activity, but do not compromise cell viability, reduce the yield of human cytomegalovirus in human fibroblasts by a factor of >100. Importantly, the yield of infectious virus can be substantially restored by the addition of prostaglandin E(2) together with the inhibitory drug. This finding argues that elevated levels of prostaglandin E(2) are required for efficient replication of human cytomegalovirus in fibroblasts. COX-2 inhibitors block the accumulation of immediate-early 2 mRNA and protein, but have little effect on the levels of immediate-early 1 mRNA and protein. Viral DNA replication and the accumulation of some, but not all, early and late mRNAs are substantially blocked by COX-2 inhibitors. Elevated levels of prostaglandin E(2) apparently facilitate the production of immediate-early 2 protein. The failure to produce normal levels of this critical viral regulatory protein in the presence of COX-2 inhibitors might block normal progression beyond the immediate-early phase of human cytomegalovirus infection.