Delayed Collagen Production without Myofibroblast Formation Contributes to Reduced Scarring in Adult Skin Microwounds.

In adult mammals, wound healing predominantly follows a fibrotic pathway, culminating in scar formation. However, cutaneous microwounds generated through fractional photothermolysis, a modality that produces a constellation of microthermal zones, exhibit a markedly different healing trajectory. Our study delineates the cellular attributes of these microthermal zones, underscoring a temporally limited, subclinical inflammatory milieu concomitant with rapid re-epithelialization within 24 hours. This wound closure is facilitated by the activation of genes associated with keratinocyte migration and differentiation. In contrast to macrothermal wounds, which predominantly heal through a robust myofibroblast-mediated collagen deposition, microthermal zones are characterized by absence of wound contraction and feature delayed collagen remodeling, initiating 5-6 weeks after injury. This distinct wound healing is characterized by a rapid re-epithelialization process and a muted inflammatory response, which collectively serve to mitigate excessive myofibroblast activation. Furthermore, we identify an initial reparative phase characterized by a heterogeneous extracellular matrix protein composition, which precedes the delayed collagen remodeling. These findings extend our understanding of cutaneous wound healing and may have significant implications for the optimization of therapeutic strategies aimed at mitigating scar formation.

Cabozantinib promotes erythroid differentiation in K562 erythroleukemia cells through global changes in gene expression and JNK activation.

Cabozantinib is a potent tyrosine kinase inhibitor with multiple targets including MET, VEGFR2, RET, KIT, and FLT3. Cabozantinib is widely used for the treatment of medullary thyroid cancer and renal cell carcinoma. We recently suggested cabozantinib as a potential therapeutic alternative for acute myeloid leukemia (AML) patients with FLT3-internal tandem duplication (FLT3-ITD). Here, we report that cabozantinib can promote differentiation in erythroid leukemia cells. We found that K562 erythroid leukemia cells treated with 1 µM cabozantinib for 72 h underwent erythroid lineage differentiation. Transcriptomic analysis revealed that various pathways associated with heme biosynthesis, hemoglobin production, and GATA1 targets were upregulated, whereas cell survival pathways were downregulated. Further examination revealed that cabozantinib-induced erythroid differentiation is at least in part regulated by JNK activation and phosphorylation. Levels of phosphorylated BCR-ABL, AKT, STAT5, ERK, and p38 also decreased following cabozantinib treatment. Therefore, we indicate that cabozantinib has dual functions. First, it induces K562 cell differentiation toward the erythroid lineage by upregulating heme biosynthesis, globin synthesis, and erythroid-associated reactions. Second, cabozantinib inhibits K562 cell proliferation by inhibiting the phosphorylation of BCR-ABL and the downstream MAPK, PI3K-AKT, and JAK-STAT signaling pathways.

Correction: A COVID-19 Pandemic Artificial Intelligence-Based System With Deep Learning Forecasting and Automatic Statistical Data Acquisition: Development and Implementation Study.

[This corrects the article DOI: 10.2196/27806.].

A COVID-19 Pandemic Artificial Intelligence-Based System With Deep Learning Forecasting and Automatic Statistical Data Acquisition: Development and Implementation Study.

BACKGROUND: More than 79.2 million confirmed COVID-19 cases and 1.7 million deaths were caused by SARS-CoV-2; the disease was named COVID-19 by the World Health Organization. Control of the COVID-19 epidemic has become a crucial issue around the globe, but there are limited studies that investigate the global trend of the COVID-19 pandemic together with each country's policy measures. OBJECTIVE: We aimed to develop an online artificial intelligence (AI) system to analyze the dynamic trend of the COVID-19 pandemic, facilitate forecasting and predictive modeling, and produce a heat map visualization of policy measures in 171 countries. METHODS: The COVID-19 Pandemic AI System (CPAIS) integrated two data sets: the data set from the Oxford COVID-19 Government Response Tracker from the Blavatnik School of Government, which is maintained by the University of Oxford, and the data set from the COVID-19 Data Repository, which was established by the Johns Hopkins University Center for Systems Science and Engineering. This study utilized four statistical and deep learning techniques for forecasting: autoregressive integrated moving average (ARIMA), feedforward neural network (FNN), multilayer perceptron (MLP) neural network, and long short-term memory (LSTM). With regard to 1-year records (ie, whole time series data), records from the last 14 days served as the validation set to evaluate the performance of the forecast, whereas earlier records served as the training set. RESULTS: A total of 171 countries that featured in both databases were included in the online system. The CPAIS was developed to explore variations, trends, and forecasts related to the COVID-19 pandemic across several counties. For instance, the number of confirmed monthly cases in the United States reached a local peak in July 2020 and another peak of 6,368,591 in December 2020. A dynamic heat map with policy measures depicts changes in COVID-19 measures for each country. A total of 19 measures were embedded within the three sections presented on the website, and only 4 of the 19 measures were continuous measures related to financial support or investment. Deep learning models were used to enable COVID-19 forecasting; the performances of ARIMA, FNN, and the MLP neural network were not stable because their forecast accuracy was only better than LSTM for a few countries. LSTM demonstrated the best forecast accuracy for Canada, as the root mean square error (RMSE), mean absolute error (MAE), and mean absolute percentage error (MAPE) were 2272.551, 1501.248, and 0.2723075, respectively. ARIMA (RMSE=317.53169; MAPE=0.4641688) and FNN (RMSE=181.29894; MAPE=0.2708482) demonstrated better performance for South Korea. CONCLUSIONS: The CPAIS collects and summarizes information about the COVID-19 pandemic and offers data visualization and deep learning-based prediction. It might be a useful reference for predicting a serious outbreak or epidemic. Moreover, the system undergoes daily updates and includes the latest information on vaccination, which may change the dynamics of the pandemic.

Lower proximal cup and outer root sheath cells regenerate hair bulbs during anagen hair follicle repair after chemotherapeutic injury.

The cell dynamics and cell origin for anagen hair follicle (HF) repair following chemotherapeutic injury are unclear. We first mapped the HF response to cyclophosphamide (CYP) at natural anagen VI in mice. We found that 30-60 mg/kg of CYP leads to dose-dependent HF dystrophy that was spontaneously repaired with anagen resumption, while 120 mg/kg of CYP prematurely induced catagen/telogen entry. To explore how anagen HF repair is achieved in the dystrophic anagen pathway, we analysed the cell dynamics at 30 mg/kg of CYP. Hair bulbs first shrunk due to matrix cell apoptosis associated with DNA double-strand breaks. DNA damage was repaired, and ordered hair bulb structures were restored within 96 hours. Bulge stem cells did not undergo apoptosis nor proliferation. K5+ basal lower proximal cup cells and outer root sheath cells quickly replenished the cells in the germinative zone and regenerated the concentric layered structures of the lower HF segment. Therefore, anagen HFs are able to summon extra-bulge progenitor cells in close proximity to the damaged matrix for quick repair after CYP injury.

Endoscopy-Assisted Total Mastectomy with and without Immediate Reconstruction: An Extended Follow-Up, Multicenter Study.

BACKGROUND: Endoscopy-assisted total mastectomy has been used for surgical intervention of breast cancer patients; however, large cohort studies with long-term follow-up data are lacking. METHODS: Breast cancer patients who underwent endoscopy-assisted total mastectomy from May of 2009 to March of 2018 were collected prospectively from multiple centers. Clinical outcome, impact of different phases, oncologic results, and patient-reported aesthetic outcomes of endoscopy-assisted total mastectomy were reported. RESULTS: A total of 436 endoscopy-assisted total mastectomy procedures were performed; 355 (81.4 percent) were nipple-sparing mastectomy, and 81 (18.6 percent) were skin-sparing mastectomy. Three hundred fourteen (75.4 percent) of the procedures were associated with immediate breast reconstruction; 255 were prosthesis based and 59 were associated with autologous flaps. The positive surgical margin rate for endoscopy-assisted total mastectomy was 2.1 percent. In morbidity evaluation, there were 19 cases (5.4 percent) with partial nipple necrosis, two cases (0.6 percent) with total nipple necrosis, and three cases (0.7 percent) with implant loss. Compared with the early phase, surgeons operating on patients in the middle or late phase had significantly decreased operation time and blood loss. With regard to patient-reported cosmetic outcomes, approximately 94.4 percent were satisfied with the aesthetic results. Patients who underwent breast reconstruction with preservation of the nipple had higher satisfaction rates. Over a median follow-up of 54.1 ± 22.4 months, there were 14 cases of locoregional recurrence (3.2 percent), three distant metastases (0.7 percent), and one mortality (0.2 percent). CONCLUSION: This multicenter study showed that endoscopy-assisted total mastectomy is a reliable surgical intervention for early breast cancer, with high patient satisfaction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

A Novel Treatment Modality for Malignant Peripheral Nerve Sheath Tumor Using a Dual-Effect Liposome to Combine Photodynamic Therapy and Chemotherapy.

Neurofibromatosis type 1 (NF1) is an inherited neurological disorder. Approximately 5-13% of NF1 patients may develop a malignant peripheral nerve sheath tumor (MPNST), which is a neurofibrosarcoma transformed from the plexiform neurofibroma or schwannoma. Given the large size and easy metastasis of MPNST, it remains difficult to be cured by either surgical or conventional chemotherapy. In this study, we investigated the possibility of combining photodynamic therapy (PDT) and chemotherapy to treat MPNST by using a dual-effect liposome (named as PL-cDDP-Ce6), in which a chemotherapeutic agent, cisplatin (cDDP), and photosensitizer, chlorine e6 (Ce6) were encapsulated in the same carrier. The cytotoxic effect of PL-cDDP-Ce6 against MPNST cells was significantly higher than cells treated with liposomal cDDP or Ce6 alone or in combination after light irradiation. Treatment with the dual-effect liposomes in mice bearing xenograft MPNST tumor reveals a significant increase in survival rate compared to those treated with liposomal cDDP and Ce6 in combination. Moreover, there is no weight loss or derangements of serum biochemistry. In conclusion, this study demonstrates the clinical potential and advantage of using this liposomal drug for the treatment of MPNST.

Blockchain-Enabled iWellChain Framework Integration With the National Medical Referral System: Development and Usability Study.

BACKGROUND: Medical referral is the transfer of a patient's care from one physician to another upon request. This process involves multiple steps that require provider-to-provider and provider-to-patient communication. In Taiwan, the National Health Insurance Administration (NHIA) has implemented a national medical referral (NMR) system, which encourages physicians to refer their patients to different health care facilities to reduce unnecessary hospital visits and the financial stress on the national health insurance. However, the NHIA's NMR system is a government-based electronic medical referral service, and its referral data access and exchange are limited to authorized clinical professionals using their national health smart cards over the NHIA virtual private network. Therefore, this system lacks scalability and flexibility and cannot establish trusting relationships among patients, family doctors, and specialists. OBJECTIVE: To eliminate the existing restrictions of the NHIA's NMR system, this study developed a scalable, flexible, and blockchain-enabled framework that leverages the NHIA's NMR referral data to build an alliance-based medical referral service connecting health care facilities. METHODS: We developed a blockchain-enabled framework that can integrate patient referral data from the NHIA's NMR system with electronic medical record (EMR) and electronic health record (EHR) data of hospitals and community-based clinics to establish an alliance-based medical referral service serving patients, clinics, and hospitals and improve the trust in relationships and transaction security. We also developed a blockchain-enabled personal health record decentralized app (DApp) based on our blockchain-enabled framework for patients to acquire their EMR and EHR data; DApp access logs were collected to assess patients' behavior and investigate the acceptance of our personal authorization-controlled framework. RESULTS: The constructed iWellChain Framework was installed in an affiliated teaching hospital and four collaborative clinics. The framework renders all medical referral processes automatic and paperless and facilitates efficient NHIA reimbursements. In addition, the blockchain-enabled iWellChain DApp was distributed for patients to access and control their EMR and EHR data. Analysis of 3 months (September to December 2018) of access logs revealed that patients were highly interested in acquiring health data, especially those of laboratory test reports. CONCLUSIONS: This study is a pioneer of blockchain applications for medical referral services, and the constructed framework and DApp have been applied practically in clinical settings. The iWellChain Framework has the scalability to deploy a blockchain environment effectively for health care facilities; the iWellChain DApp has potential for use with more patient-centered applications to collaborate with the industry and facilitate its adoption.

Cytarabine-Resistant FLT3-ITD Leukemia Cells are Associated with TP53 Mutation and Multiple Pathway Alterations-Possible Therapeutic Efficacy of Cabozantinib.

Internal tandem duplication of FLT3 juxtamembrane domain (FLT3-ITD)-positive acute myeloid leukemia (AML) leads to poor clinical outcomes after chemotherapy. We aimed to establish a cytarabine-resistant line from FLT3-ITD-positive MV4-11 (MV4-11-P) cells and examine the development of resistance. The FLT3-ITD mutation was retained in MV4-11-R; however, the protein was underglycosylated and less phosphorylated in these cells. Moreover, the phosphorylation of ERK1/2, Akt, MEK1/2 and p53 increased in MV4-11-R. The levels of Mcl-1 and p53 proteins were also elevated in MV4-11-R. A p53 D281G mutant emerged in MV4-11-R, in addition to the pre-existing R248W mutation. MV4-11-P and MV4-11-R showed similar sensitivity to cabozantinib, sorafenib, and MK2206, whereas MV4-11-R showed resistance to CI-1040 and idarubicin. MV4-11-R resistance may be associated with inhibition of Akt phosphorylation, but not ERK phosphorylation, after exposure to these drugs. The multi-kinase inhibitor cabozantinib inhibited FLT3-ITD signaling in MV4-11-R cells and MV4-11-R-derived tumors in mice. Cabozantinib effectively inhibited tumor growth and prolonged survival time in mice bearing MV4-11-R-derived tumors. Together, our findings suggest that Mcl-1 and Akt phosphorylation are potential therapeutic targets for p53 mutants and that cabozantinib is an effective treatment in cytarabine-resistant FLT3-ITD-positive AML.

Chitosan Inhibits the Rehabilitation of Damaged Microbes Induced by Photodynamic Inactivation.

Previously, we showed that chitosan could augment the biocidal efficacy mediated by photodynamic treatment against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. In this study, we showed that the antimicrobial action of chitosan in augmenting photodynamic inactivation (PDI) is related to the increase in cell surface destruction. The microbial cell surfaces exhibit severe irregular shapes after PDI in the presence of chitosan as demonstrated by transmitted electron microscopy. Furthermore, increases in the concentration or incubation time of chitosan significantly reduced the amounts of photosensitizer toluidine blue O required, indicating that chitosan could be an augmenting agent used in conjunction with PDI against S. aureus, P. aeruginosa, and C. albicans. A prolonged lag phase was found in microbial cells that survived to PDI, in which chitosan acted to completely eradicate the cells. Once the exponential log stage and cell rebuild began, their cellular functions from PDI-induced damage returned and the increased cytotoxic effect of chitosan disappeared. Together, our results suggest that chitosan can prevent the rehabilitation of PDI-surviving microbial cells, leading to increased biocidal efficacy.

CD40-mediated HIF-1α expression underlying microangiopathy in diabetic nerve pathology.

To understand the pathology and molecular signatures of microangiopathy in diabetic neuropathy, we systemically and quantitatively examined the morphometry of microvascular and nerve pathologies of sural nerves. In the endoneurium of diabetic nerves, prominent microangiopathy was observed, as evidenced by reduced capillary luminal area, increased capillary basement membrane thickness and increased proportion of fibrin(+) blood vessels. Furthermore, capillary basement membrane thickness and the proportion of fibrin(+) blood vessels were correlated with small myelinated fiber density in diabetic nerves. In diabetic nerves, there was also significant macrophage and T cell infiltration, and cluster of differentiation 40 (CD40) expression was increased. The molecular alterations observed were upregulation of hypoxia-inducible factor-1α (HIF-1α), mitogen-activated protein kinase-activated protein kinase 2 (MK2; MAPKAPK2) and phosphatase and tensin homolog (PTEN). In addition, HIF-1α was correlated with small myelinated fiber density and capillary luminal area, while both MK2 and PTEN were correlated with capillary basement membrane thickness. The molecular cascades were further demonstrated and replicated in a cell model of microangiopathy on human umbilical vein endothelial cells (HUVECs) exposed to high-glucose medium by silencing of CD40, PTEN and HIF-1α in HUVECs using shRNA. These data clarified the hierarchy of the molecular cascades, i.e. upregulation of CD40 leading to HIF-1α expression in endothelium and nerve fibers. In conclusion, this study revealed the association of microangiopathy, thrombosis and inflammatory infiltrates with nerve degeneration in diabetic nerves, demonstrating that CD40 is a key molecule for the upregulation of HIF-1α and PTEN underlying the severity of microangiopathy.

cAMP receptor protein regulates mouse colonization, motility, fimbria-mediated adhesion, and stress tolerance in uropathogenic Proteus mirabilis.

Cyclic AMP receptor protein (Crp) is a major transcriptional regulator in bacteria. This study demonstrated that Crp affects numerous virulence-related phenotypes, including colonization of mice, motility, fimbria-mediated adhesion, and glucose stress tolerance in uropathogenic Proteus mirabilis. Diabetic mice were more susceptible to kidney colonization by wild-type strain than nondiabetic mice, in which the crp mutant exhibited increased kidney colonization. Loss of crp or addition of 10% glucose increased the P. mirabilis adhesion to kidney cells. Direct negative regulation of pmpA (which encodes the major subunit of P-like fimbriae) expression by Crp was demonstrated using a reporter assay and DNase I footprinting. Moreover, the pmpA/crp double mutant exhibited reduced kidney adhesion comparable to that of the pmpA mutant, and mouse kidney colonization by the pmpA mutant was significantly attenuated. Hence, the upregulation of P-like fimbriae in the crp mutant substantially enhanced kidney colonization. Moreover, increased survival in macrophages, increased stress tolerance, RpoS upregulation, and flagellum deficiency leading to immune evasion may promote kidney colonization by the crp mutant. This is the first study to elucidate the role of Crp in the virulence of uropathogenic P. mirabilis, underlying mechanisms, and related therapeutic potential.

Risk factors for complications following immediate tissue expander based breast reconstruction in Taiwanese population.

BACKGROUND/PURPOSE: Breast cancer patients in Asia show considerable disparities from Caucasian patients, such as younger age of onset and lower rates of smoking, obesity, and diabetes. Findings of prior studies regarding risk factors associated with complications in tissue expander may not hold for Asian populations, since most of these studies involved Caucasian patients. In this study, we surveyed risk factors in the Taiwanese population, providing additional evidence about the important differences and discuss the implications for clinical practice. METHODS: Patients who underwent immediate, two-stage, tissue expander breast reconstruction from December 2008 to August 2014 in the National Taiwan University Hospital, Taipei, Taiwan were included. Follow-up observations of all patients were conducted until December 2014. Complications occurring during the tissue expander stage were evaluated. Multivariate regression modeling was used to identify risk factors for complications. RESULTS: A total of 246 consecutive, immediate, smooth round tissue expander placements were performed for breast reconstruction. The most common complication was skin necrosis (4.9%), followed by wound dehiscence (4.1%). In the multivariate model, body mass index (BMI) ≥ 24 kg/m2 was the only risk factor that reached statistical significance (odds ratio: 2.41, 95% confidence interval: 1.17-4.96). CONCLUSION: We provided evidence that racial disparities have an impact on the risk factors for complications associated with tissue expander breast reconstruction. BMI≥24 kg/m2 was the only risk factor significantly associated with complications. Clinically, BMI≥24 kg/m2, rather than the standard definition of obesity (BMI > 30 kg/m2), may be a more suitable cutoff point for risk in patients of Asian ethnicity.

Postoperative Showering for Clean and Clean-contaminated Wounds: A Prospective, Randomized Controlled Trial.

OBJECTIVE: To evaluate wound infection rates, pain scores, satisfaction with wound care, and wound care costs starting 48 hours after surgery. BACKGROUND: Showering after surgery is a controversial issue for wound care providers and patients. We investigated the benefits and detriments of showering for postoperative wound care. METHODS: Patients undergoing thyroid, lung, inguinal hernia, and face and extremity surgeries with clean or clean-contaminated wounds were included. The patients were randomized to allow showering (shower group) or to keep the wound dry (nonshower group) for postoperative wound care starting 48 hours after surgery. The primary endpoint was the rate of surgical wound infection. The secondary endpoints included the wound pain score, satisfaction with wound care, and cost of wound care. RESULTS: Between May 2013 and March 2014, there were 222 patients randomized to the shower group and 222 to the nonshower group. Two patients in each group were lost to follow-up. There were 4 superficial surgical site infections in the shower group and 6 in the nonshower group (4/220, 1.8% vs 6/220, 2.7%, P = 0.751). Postoperative pain scores were comparable between the 2 groups. Patients in the shower group were more satisfied with their method of wound care, and their wound care costs were lower when compared with the nonshower group. CONCLUSIONS: Clean and clean-contaminated wounds can be safely showered 48 hours after surgery. Postoperative showering does not increase the risk of surgical site complications. It may increase patients' satisfaction and lower the cost of wound care.

Clinical Application of Different Surgical Navigation Systems in Complex Craniomaxillofacial Surgery: The Use of Multisurface 3-Dimensional Images and a 2-Plane Reference System.

BACKGROUND: Intraoperative navigation is a tool that provides surgeons with real-time guidance based on patients' preoperative imaging studies. The application of intraoperative navigation to neurosurgery and otolaryngology has been well documented; however, only isolated reports have analyzed its potential in the field of craniomaxillofacial surgery. METHODS: From November 2010 to July 2014, 15 patients were operated on for complex craniomaxillofacial surgery with assistance by 3 different navigation systems, which used either infrared or electromagnetic technologies. We imported fine-cut (0.625-mm) computed tomographic scan images of the patients to the navigation systems whose software processed them into multisurface 3-dimentional models used as guiding material for the surgical navigation. We also developed a simple "2-plane reference system" to ensure that the final results were symmetric to the normal half of the face. Appearance outcome was evaluated by questionnaire. RESULTS: Of these 15 cases, 3 cases were performed with infrared-based navigation, and the remaining 12 cases were accomplished by electromagnetic technology. Most of these cases resulted in satisfactory outcomes after tumor resection, posttraumatic reconstruction, and postablative reconstruction. CONCLUSION: Navigation systems offer highly valuable intraoperative assistance in complex craniomaxillofacial surgery. Not only can these systems pinpoint deep-seated lesions as neurosurgeons or otolaryngologists do, but they can also use a simple 2-plane reference system for accurate bone alignment. Moreover, advancements in multisurface 3-D models provide us more reliable intuitive image guidance. The application of electromagnetic technology, with its smaller reference obviation of the line-of-sight problem, makes the manipulation of craniomaxillofacial surgery more comfortable.

Treatment and long-term follow-up of oral cancer postoperative sialorrhea with dermal sling operation.

INTRODUCTION: Reconstruction of a full-thickness defect that includes oral commissure presents a considerable challenge to maxillofacial and plastic surgeons. The goals of reconstruction are both functional and cosmetic. Sialorrhea, or drooling, is a major problem after flap reconstruction and influences the quality of life of the patient. In this article, we report on our experience performing a dermal sling operation to treat postoperative sialorrhea in patients with oral cancer. MATERIALS AND METHODS: Preoperative and postoperative levels of sialorrhea were evaluated based on the Drooling Severity and Frequency Scale. Dermal sling operations were performed on 27 patients from January 2000 to December 2013. In these patients, 12 cases were reviewed and followed up over 1 year. RESULTS: Of the 12 patients, 11 were men and one was a woman, with the mean age of 58 years (range, 40-79 years). There were no operative complications. The mean preoperative score was 4.75 (range, 3-7), and the mean postoperative score was 3.83 (range, 2-5). This change was significant (P=0.005), with valuation with the Wilcoxon signed rank test. The mean time of follow-up was 3.5 years (range, 1.1-7.7 years). CONCLUSIONS: The dermal sling operation is an acceptable treatment for postoperative sialorrhea in patients with commissure-involved oral cancer.

New aspects of RpoE in uropathogenic Proteus mirabilis.

Proteus mirabilis is a common human pathogen causing recurrent or persistent urinary tract infections (UTIs). The underlying mechanisms for P. mirabilis to establish UTIs are not fully elucidated. In this study, we showed that loss of the sigma factor E (RpoE), mediating extracytoplasmic stress responses, decreased fimbria expression, survival in macrophages, cell invasion, and colonization in mice but increased the interleukin-8 (IL-8) expression of urothelial cells and swarming motility. This is the first study to demonstrate that RpoE modulated expression of MR/P fimbriae by regulating mrpI, a gene encoding a recombinase controlling the orientation of MR/P fimbria promoter. By real-time reverse transcription-PCR, we found that the IL-8 mRNA amount of urothelial cells was induced significantly by lipopolysaccharides extracted from rpoE mutant but not from the wild type. These RpoE-associated virulence factors should be coordinately expressed to enhance the fitness of P. mirabilis in the host, including the avoidance of immune attacks. Accordingly, rpoE mutant-infected mice displayed more immune cell infiltration in bladders and kidneys during early stages of infection, and the rpoE mutant had a dramatically impaired ability of colonization. Moreover, it is noteworthy that urea (the major component in urine) and polymyxin B (a cationic antimicrobial peptide) can induce expression of rpoE by the reporter assay, suggesting that RpoE might be activated in the urinary tract. Altogether, our results indicate that RpoE is important in sensing environmental cues of the urinary tract and subsequently triggering the expression of virulence factors, which are associated with the fitness of P. mirabilis, to build up a UTI.

CD200 in growing rat lungs: developmental expression and control by dexamethasone.

CD200 belongs to cell adhesion molecules of the immunoglobulin superfamily. It lacks intracellular signaling motifs and exerts immunosuppressive effect in various tissues. We have reported previously that CD200 is predominantly associated with the capillary network in the alveolar septum of adult rats. The alveolar endothelial cells express CD200, which is confined to their luminal cell membrane facing the blood-air barrier. Our present results show that lung CD200 protein increases gradually with advancing age, being maximally expressed in the early postnatal (P) period. CD200 protein expression, however, declines at P5 but increases again after P7, reaching the adult level at P21. In developing lungs in fetal and neonatal stages, double-immunofluorescence staining has confirmed intense CD200 immunoreactivity delineating the vascular profiles in the double layers of the alveolar capillaries; this staining becomes diffuse and patchy with time. Unlike in adult lungs, immunoelectron microscopy has revealed that CD200 expression in fetal and early postnatal lungs is localized over the entire luminal cell membrane and in the cytoplasm of the endothelia. CD200 expression is progressively redistributed to a specific luminal domain of alveolar endothelia during pulmonary microvascular maturation. In neonatal rats treated with dexamethasone, the amount of lung CD200 significantly increases and is also elevated with time. Upregulation of endothelial CD200 has further been confirmed in isolated pulmonary microvascular endothelial cells treated with dexamethasone. Thus, lung CD200 is developmentally regulated, possibly under hormonal influence.

Reconstruction for osteoradionecrosis of the mandible: superiority of free iliac bone flap to fibula flap in postoperative infection and healing.

BACKGROUND: Osteoradionecrosis (ORN) of the mandible is not an uncommon complication after radiotherapy for head and neck cancers. Although definitive treatment has been confirmed as radical excision of the necrotic bone with simultaneous vascularized osteocutaneous flap reconstruction, it remains a unique challenge. In this study, we compare our results of reconstruction with free iliac and fibula flaps in flap survival, bony union, and postoperative complications. PATIENTS AND METHODS: From 1986 to 2011, there were 153 mandibular ORN cases in our center that were treated with radical resection of the necrotic bone and reconstruction with either vascularized iliac (n=108) or fibula flaps (n=45). Data collected for analysis included patient demographics, flap survival rate, postoperative infection rate, nonunion/malunion rate, mean hospital stay, and antibiotics use. RESULTS: All patients healed eventually without recurrence of ORN. However, we observed difference in the complication rate between the iliac flap group and fibula flap group. In the group with iliac flap reconstruction, patients required less days of hospital stay for intravenous antibiotics treatment postoperatively. The average days required for intravenous antibiotics in the iliac flap group were 10.46 (2.28) versus 16.09 (3.88) days in the fibula group (P<0.01). In the group with fibula flap reconstruction, 9 (20.0%) patients had subsequent neck infection due to healing problem, compared to 8 (7.4%) patients in the iliac flap group (P=0.04). In the iliac flap group, the nonunion and malunion rates were 4.6% and 2.8% respectively; whereas in the fibula group, the rates were 15.5% and 6.6%, respectively (P=0.04 and 0.36, respectively). CONCLUSIONS: For ORN patients, vascularized iliac bone flap provides more reliable results compared to fibula flap. The merits of vascularized iliac flap include the following: (1) its natural curve mimics the shape of mandible and does not need osteotomy; (2) it offers more volume of bone that matches better to the native mandible to allow later osteointegration as well as faster bony union, due to the nature of being a membranous bone; and (3) it carries more abundant soft tissue to obliterate possible dead space. The only disadvantages are short pedicle and requiring special management of skin paddle, which can be overcome by training in microsurgery.

Blastocystis hominis infection in a post-cardiotomy patient on extracorporeal membrane oxygenation support: A case report and literature review.

INTRODUCTION: Opportunistic pathogens can cause severe damage leading to irreversible complications in immune-compromised patients. Here we describe a patient who sustained Blastocystis hominis infection resulting in severe sepsis while on extracorporeal membrane oxygenation (ECMO) support, and the course of treatment taken to treat him. PRESENTATION OF CASE: Our case, a 34-year-old Filipino man, was hospitalized for valvular disease and received valve replacements. ECMO and an intra-aortic balloon pump (IABP) were implemented when the patient developed progressive heart failure after cardiac surgery. Unfortunately, the patient suffered from sepsis with persistent fever and diarrhea, and subsequent examinations indicated the patient was infected by B. hominis. After adequate administration of the antibiotic metronidazole, the patient's symptoms subsided and he was discharged. DISCUSSION: Blastocystis hominis is a unicellular protozoa commonly found in the intestinal tract, and the prevalence of B. hominis is 1.5-10% in developed countries and 30-50% in developing countries. The patient needed the support of ECMO and IABP, was immunocompromised to a certain extent; B. hominis can be a harmful opportunistic pathogen for them and lead to severe irreversible complications such as death. CONCLUSION: This is the first published article showing that the opportunistic pathogen, B. hominis, can cause severe infection in patients on ECMO support, a result that should be kept in mind when patients come from a place with a high prevalence of B. hominis. The prophylactic medication should be administered routinely when patients live in the region and extracorporeal life-support is used.