No abstract

During healing of the skin, the cytoskeleton of keratinocytes and their matrix adhesions, including focal adhesions (FAs), undergo reorganization. These changes are coordinated by small GTPases and their regulators, including the guanine nucleotide exchange factor β-PIX (also known as ARHGEF7). In fibroblasts, β-PIX activates small GTPases, thereby enhancing migration. In keratinocytes in vitro, β-PIX localizes to FAs. To study β-PIX functions, we generated β-PIX knockdown keratinocytes. During wound closure of β-PIX knockdown cell monolayers, disassembly of FAs is impaired, and their number and size are increased. In addition, in the β-PIX knockdown cells, phosphorylated myosin light chain (MLC; also known as MYL2) is present not only in the leading edge of cells at the wound front, but also in the cells following the front, while p21-activated kinase 2 (PAK2), a regulator of MLC kinase (MYLK), is mislocalized. Inhibition or depletion of MYLK restores FA distribution in β-PIX knockdown cells. Traction forces generated by β-PIX knockdown cells are increased relative to those in control cells, a result consistent with an unexpected enhancement in the migration of single β-PIX knockdown cells and monolayers of such cells. We propose that targeting β-PIX might be a means of promoting epithelialization of wounds in vivo.

Branching morphogenesis of epithelia involves division of cells into leader (tip) and follower (stalk) cells. Published work on cell lines in culture has suggested that symmetry‐breaking takes place via a secreted autocrine inhibitor of motility, the inhibitor accumulating more in concave regions of the culture boundary, slowing advance of cells there, and less in convex areas, allowing advance and a further exaggeration of the concave/convex difference. Here we test this hypothesis using a two‐dimensional culture system that includes strong flow conditions to remove accumulating diffusible secretions. We find that, while motility does indeed follow boundary curvature in this system, flow makes no difference: this challenges the hypothesis of control by a diffusible secreted autocrine inhibitor.

BackgroundObstructive Sleep Apnea (OSA) is prevalent throughout the world. However, there are currently limited data concerning the prevalence of OSA in populations that originate from developing countries; the prevalence of OSA is expected to rise in these countries. OSA is poorly characterized amongst Ethiopians, and our study is the first to describe clinical characteristics of OSA among Ethiopians.MethodsWe conducted a retrospective study of primarily Ethiopian patients at an internal medicine clinic in Rockville, Maryland. All patients (n=24) were evaluated for daytime sleepiness using the Epworth Sleepiness Scale (ESS) and received physical examinations and polysomnograms (PSG) by either portable monitoring (Itamar WatchPAT 200 device) or in-lab. Statistical analyses were performed in R.ResultsLinear regression model of Body-Mass Index (BMI) and Apnea-Hypopnea Index (AHI) indicated that for every 1-unit increase in BMI, there was a 0.8657-unit increase in AHI (p<0.05). Pearson's correlation coefficient indicateda positive linear relationship between BMI and AHI (0.47) (p<0.05). Adjusted linear regression model for AHI and oxygen saturation indicated that for every 1-unit increase of AHI, there was a 0.8452-unit decrease in nocturnal oxygen saturation (p<0.05). Pearson's correlation coefficient did not demonstrate significance between AHI and oxygen desaturation (p=0.062). Patients received either continuous positive airway pressure (CPAP) (n=15) or oral appliance therapy (n=3).ConclusionAll patients who complied with therapy reported improved sleep quality, snoring resolution, and improved daytime alertness. Practitioners in developing countries should suspect OSA in the right clinical setting and offer diagnostic and therapeutic services when available.

A 69-year-old Caucasian woman presented with chronic lymphocytic leukaemia (CLL; stage 1-Rai System), significant oropharyngeal lymphoid enlargement, snoring and fatigue. Overnight polysomnography revealed moderately severe obstructive sleep apnoea (OSA), which was managed successfully with oral appliance therapy with resolution of snoring and daytime fatigue. Structural abnormalities of the upper airways are known to cause OSA. Airway narrowing can result from bony structural abnormalities, nasopharyngeal growth, soft tissue redundancy, macroglossia, malignant and benign growth of the upper aero-digestive tract, and adenotonsilar enlargement. Clinicians should be encouraged to consider a diagnosis of OSA in patients with CLL when they present with symptoms of worsening fatigue.

BACKGROUND፡ Gilbert syndrome is a well-recognized condition causing unconjugated hyperbilirubinemia with otherwise normal transaminases and liver function tests. CASE: A 21 year old male patient presented with recurrent episodes of jaundice over four years. The episodes were preceded by stressful conditions and intercurrent illnesses. All laboratory prameters were normal except an unconjugated hyperbilirubinemia. A diagnosis of Gilbert syndrome was made after careful clinical evaluation.CONCLUSION: Recognizing Gilbert syndrome has important clinical implicaitions by avoiding uncessary and expensive workup of patients with jaundice. Mangement entails avoiding stressful conditions and prolonged fasting.

Background: Split thickness skin grafting is a widely used surgical technique for wound coverage. Despite the popularity of this procedure, outcomes data has been poorly reported. Methods: Under IRB approval we reviewed the records of all patients receiving split thickness skin grafting for lower extremity wounds from 2014 to 2016. We have defined success as wound healing of ≥99.5%. Results: 180 diabetic patients were included in this study. 103 (95%) had hypertension, 75 (69%) had hyperlipidemia, 29 (27%) had congestive heart failure, and 22 (20%) had venous stasis. Complete epithelialization was obtained for 29 (22%) patients at 30d, 48 (36%) patients at 60d, 63 (48%) patients at 90d, and 77 (58%) patients at 365d of follow-up. At last available follow-up 79 (60%) wounds obtained complete healing (≥99.5% coverage). Venous stasis led to inadequate healing at 30d (p&lt;0.0371), 90d (p&lt;0.0006), and 365d (p&lt;0.0005) and trended toward significance at 60d (p&lt;0.0809). Congestive heart failure led to inadequate healing at 60d (p&lt;0.0334), and 90d (p&lt;0.0015). The presence of bacteria on wound bed cultures did not show a significant effect on wound healing. The most common bacteria were coagulase negative Staphylococcus, MRSA, and Enterococcus faecalis. Only enterococcus faecalis showed significance at 30d if present following the initial debridement. Conclusion: The data suggests that split thickness skin grafting can be a successful coverage technique for diabetic patients with chronic lower extremity wounds. The bacterial milieu of chronic wounds in diabetics is diverse but with excisional debridement these bacteria have little impact on wound healing after split-thickness skin grafting. However, comorbidities (i.e., congestive heart failure and venous stasis) can significantly impact the healing of skin grafts and should be taken into consideration when contemplating split thickness skin grafting in a diabetic patient. Disclosure E. Walters: None. G. Stimac: None. N. Rajpal: None. I. Naz: None. T. Elmarsafi: None. J. Steinberg: Consultant; Self; Acelity, Integra LifeSciences. K. Evans: None. C. Attinger: Consultant; Self; Acelity, Integra LifeSciences. P. Kim: Consultant; Self; Acelity, Integra LifeSciences.

Summary: Careful consideration of radiotherapy can determine the success of reconstructive therapy. There is a broad spectrum of radiotherapy modalities, both benign and malignant. Delivery mechanisms differ in the physical design, setup, radiation source, administrable dosage, and mode of delivery. This range of options allows radiation oncologists to tailor individualized treatment; however, radiotherapy concepts can be challenging for nonspecialists. The purpose of this article is to review general radiation oncology concepts, including essential equipment and radiobiology, and provide plastic surgeons with a basic conceptual understanding to facilitate effective multidisciplinary collaboration with radiation oncologists.