Lymphotoxin regulates commensal responses to enable diet-induced obesity.

Microbiota are essential for weight gain in mouse models of diet-induced obesity (DIO), but the pathways that cause the microbiota to induce weight gain are unknown. We report that mice deficient in lymphotoxin, a key molecule in gut immunity, were resistant to DIO. Ltbr(-/-) mice had different microbial community composition compared to their heterozygous littermates, including an overgrowth of segmented filamentous bacteria (SFB). Furthermore, cecal transplantation conferred leanness to germ-free recipients. Housing Ltbr(-/-) mice with their obese siblings rescued weight gain in Ltbr(-/-) mice, demonstrating the communicability of the obese phenotype. Ltbr(-/-) mice lacked interleukin 23 (IL-23) and IL-22, which can regulate SFB. Mice deficient in these pathways also resisted DIO, demonstrating that intact mucosal immunity guides diet-induced changes to the microbiota to enable obesity.

Comparative effectiveness of low-level laser therapy for adult androgenic alopecia: a system review and meta-analysis of randomized controlled trials.

The purpose of this review is to explore the effectiveness of low-level laser therapy (LLLT) in the treatment of adult androgenic alopecia (AGA). A systematic search of studies on LLLT for AGA was conducted mainly in Pubmed, Embase, and Cochrane Systematic Reviews. The standardized mean difference (SMD) in the changes of hair density treated by LLLT versus sham devices was analyzed. The meta-analysis included 8 studies comprising a total of 11 double-blinded randomized controlled trials. The quantitative analysis showed a significant increase in hair density for those treated by LLLT versus sham group (SMD 1.316, 95% confidence interval, CI 0.993 to 1.639). The subgroup analysis demonstrated that LLLT increases hair growth in both genders, in both comb- and helmet-type devices, and in short- and long-term treatment course. The subgroup analysis also showed a more significant increase of hair growth for the LLLT versus sham in the low-frequency treatment group (SMD 1.555, 95% CI 1.132 to 1.978) than in the high-frequency group (SMD 0.949, 95% CI 0.644 to 1.253). The review was limited by the heterogeneity of included trials. LLLT significantly increased hair density in AGA. The meta-analysis suggests that low treatment frequency by LLLT have a better hair growth effect than high treatment frequency. LLLT represents a potentially effective treatment for AGA in both male and female. The types of LLLT devices and LLLT treatment course duration did not affect the effectiveness in hair growth.

Murine gut microbiota and transcriptome are diet dependent.

OBJECTIVE: Here, we determine how formula feeding impacts the gut microbiota and host transcriptome. BACKGROUND: Formula-fed (FF) infants are at risk for diseases that involve complex interactions between microbes and host immune elements such as necrotizing enterocolitis. The aims of this study were to simultaneously examine the microbiota and host transcriptional profiles of FF and maternal-fed (MF) mice to evaluate how diet impacts gut colonization and host genes. METHODS: After 72 hours of FF or MF, colonic tissue was collected. 16S ribosomal RNA was sequenced with Roche GS-FLX (Genome Sequencer-FLX) pyrosequencing. Operational taxonomical unit clustering, diversity analysis, and principal coordinate analysis (PCA) were performed. Complementary DNA libraries were sequenced by Solexa. Reads were annotated by BLAST (Basic Local Alignment Search Tool) search against mouse RNA database [National Center for Biotechnology Information (NCBI) build-37] and functionally classified using the KOG (Eukaryotic Orthologous Groups) database (NCBI). RESULTS: Firmicutes (P < 0.001) was the dominant phylum in MF pups, whereas Proteobacteria (P < 0.001) and Bacteroidetes (P < 0.05) were dominant in FF mice. On the genus level, FF mice had increased Serratia (P < 0.001) and Lactococcus (P < 0.05) whereas MF mice had increased Lactobacillus (P < 0.001). PCA confirmed clustering by diet. Solexa sequencing demonstrated different (P < 0.05) messenger RNA transcript levels in 148 genes. Heme oxygenase 1 (P < 0.01), an oxidative stress marker, was increased 25-fold in FF mice. In addition, decreased vinculin (P < 0.05), a cytoskeletal protein associated with adherens junctions in FF pups suggested impaired gut structural integrity. Diet also impacted immune regulation, cell cycle control/gene expression, cell motility, and vascular function genes. CONCLUSIONS: FF shifted gut microbiota and structural integrity, oxidative stress, and immune function genes, presumably increasing vulnerability to disease in FF mice. Interrogation of microbial and host gene expression in FF neonates may offer new insight on how diet affects disease pathogenesis.

Primary hyperparathyroidism in adolescents: the same but different.

PURPOSE: Primary hyperparathyroidism has been studied more extensively in adults than in adolescents. The objective of this study is to define the similarities and differences that exist between these groups. METHODS: A retrospective review of 1,000 primary hyperparathyroidism patients undergoing parathyroidectomy at a single tertiary-care university teaching hospital between 1990 and 2004. All patients 20 years of age or younger comprised our study cohort, and were compared to two historical adult groups. RESULTS: Of 1,000 parathyroidectomies, 21 (2.1 %) were 20 years of age or younger (adolescent). The adolescents presented with higher serum calcium levels (p < 0.01) more severe symptoms (p = 0.02), more renal stones (p = 0.048), and a higher incidence of hypercalcemic crisis (p = 0.02), when compared with adults. We found that 67 % suffered from a triad of tiredness, weakness, and depression versus 39 % of adults (p = 0.02). Sestamibi scans were less helpful in the adolescents than in adults. Similar to the adults, 86 % of adolescent patients had single gland disease, and 95 % were cured at the first operation. CONCLUSION: Adolescents with primary hyperparathyroidism typically have more severe disease than adults. Contrary to popular belief, most adolescents have single gland disease and not hyperplasia associated with a genetic disorder.

Pseudomonas aeruginosa virulence expression is directly activated by morphine and is capable of causing lethal gut-derived sepsis in mice during chronic morphine administration.

OBJECTIVE: This study was designed to examine the effect of morphine administration on the intestinal mucus barrier and determine its direct effect on the virulence and lethality of Pseudomonas aeruginosa, one of the most frequent pathogens to colonize the gut of critically ill patients. BACKGROUND DATA: Surgical injury is associated with significant exposure of host tissues to morphine from both endogenous release and its use as a potent analgesic agent. Morphine use in surgical patients exposed to extreme physiologic stress is well established to result in increased infection risk. Although morphine is a known immunosuppressant, whether it directly induces virulence expression and lethality in microbes that colonize the human gut remains unknown. METHODS: Mice were implanted with a slow release morphine or placebo pellet with and without intestinal inoculation of P. aeruginosa created by direct cecal injection. Mucus production and epithelial integrity was assessed in cecal tissue via Alcian blue staining and histologic analysis. In vivo and in vitro P. aeruginosa virulence expression was examined using reporter strains tagged to the epithelial barrier disrupting protein PA-I lectin. P. aeruginosa chemotaxis toward morphine was also assayed in vitro. Finally, the direct effect of morphine to induce PA-I lectin expression was determined in the absence and presence of methylnaltrexone, a µ opioid receptor antagonist. RESULTS: Mice intestinally inoculated with P. aeruginosa and implanted with a morphine pellet demonstrated significant suppression of intestinal mucus, disrupted intestinal epithelium, and enhanced mortality; whereas exposure of mice to either systemic morphine or intestinal P. aeruginosa alone enhanced intestinal mucus without mortality, suggesting a shift in P. aeruginosa during morphine exposure to a mucus suppressing, barrier disrupting, and lethal phenotype. Direct exposure of P. aeruginosa to morphine in vitro confirmed that morphine can transform P. aeruginosa to a more virulent phenotype that is attenuated in part by methylnaltrexone. CONCLUSIONS: Morphine administration shifts intestinal P. aeruginosa to express a virulent phenotype and may play a role in its ability to causes lethal gut-derived sepsis in a susceptible host.

Human CD1D gene expression is regulated by LEF-1 through distal promoter regulatory elements.

CD1d-expressing cells present lipid Ag to CD1d-restricted NKT cells, which play an important role in immune regulation and tumor rejection. Lymphoid enhancer-binding factor-1 (LEF-1) is one of the regulators of the Wnt signaling pathway, which is a powerful regulator in cellular growth, differentiation, and transformation. There is little evidence connecting Wnt signaling to CD1d expression. In this study, we have identified LEF-1 as a regulator of the expression of the gene encoding the human CD1d molecule (CD1D). We found that LEF-1 binds specifically to the CD1D promoter. Overexpression of LEF-1 in K562 or Jurkat cells suppresses CD1D promoter activity and downregulates endogenous CD1D transcripts, whereas knockdown of LEF-1 using LEF-1-specific small interfering RNA increases CD1D transcripts in K562 and Jurkat cells but there are different levels of surface CD1d on these two cell types. Chromatin immunoprecipitation showed that the endogenous LEF-1 is situated at the CD1D promoter and interacts with histone deacetylase-1 to facilitate the transcriptional repressor activity. Knockdown of LEF-1 using small interfering RNA potentiates an acetylation state of histone H3/H4, supporting the notion that LEF-1 acts as a transcriptional repressor for the CD1D gene. Our finding links LEF-1 to CD1D and suggests a role of Wnt signaling in the regulation of the human CD1D gene.

Red death in Caenorhabditis elegans caused by Pseudomonas aeruginosa PAO1.

During host injury, Pseudomonas aeruginosa can be cued to express a lethal phenotype within the intestinal tract reservoir-a hostile, nutrient scarce environment depleted of inorganic phosphate. Here we determined if phosphate depletion activates a lethal phenotype in P. aeruginosa during intestinal colonization. To test this, we allowed Caenorhabditis elegans to feed on lawns of P. aeruginosa PAO1 grown on high and low phosphate media. Phosphate depletion caused PAO1 to kill 60% of nematodes whereas no worms died on high phosphate media. Unexpectedly, intense redness was observed in digestive tubes of worms before death. Using a combination of transcriptome analyses, mutants, and reporter constructs, we identified 3 global virulence systems that were involved in the "red death" response of P. aeruginosa during phosphate depletion; they included phosphate signaling (PhoB), the MvfR-PQS pathway of quorum sensing, and the pyoverdin iron acquisition system. Activation of all 3 systems was required to form a red colored PQS+Fe(3+) complex which conferred a lethal phenotype in this model. When pyoverdin production was inhibited in P. aeruginosa by providing excess iron, red death was attenuated in C. elegans and mortality was decreased in mice intestinally inoculated with P. aeruginosa. Introduction of the red colored PQS+Fe(3+) complex into the digestive tube of C. elegans or mouse intestine caused mortality associated with epithelial disruption and apoptosis. In summary, red death in C. elegans reveals a triangulated response between PhoB, MvfR-PQS, and pyoverdin in response to phosphate depletion that activates a lethal phenotype in P. aeruginosa.

The human microbiome and surgical disease.

OBJECTIVE: The purpose of this review article is to summarize what is currently known about microbes associated with the human body and to provide examples of how this knowledge impacts the care of surgical patients. BACKGROUND: Pioneering research over the past decade has demonstrated that human beings live in close, constant contact with dynamic communities of microbial organisms. This new reality has wide-ranging implications for the care of surgical patients. METHODS AND RESULTS: Recent advances in the culture-independent study of the human microbiome are reviewed. To illustrate the translational relevance of these studies to surgical disease, we discuss in detail what is known about the role of microbes in the pathogenesis of obesity, gastrointestinal malignancies, Crohn disease, and perioperative complications including surgical site infections and sepsis. The topics of mechanical bowel preparation and perioperative antibiotics are also discussed. CONCLUSIONS: Heightened understanding of the microbiome in coming years will likely offer opportunities to refine the prevention and treatment of a wide variety of surgical conditions.

Prevention of siderophore- mediated gut-derived sepsis due to P. aeruginosa can be achieved without iron provision by maintaining local phosphate abundance: role of pH.

BACKGROUND: During extreme physiological stress, the intestinal tract can be transformed into a harsh environment characterized by regio- spatial alterations in oxygen, pH, and phosphate concentration. When the human intestine is exposed to extreme medical interventions, the normal flora becomes replaced by pathogenic species whose virulence can be triggered by various physico-chemical cues leading to lethal sepsis. We previously demonstrated that phosphate depletion develops in the mouse intestine following surgical injury and triggers intestinal P. aeruginosa to express a lethal phenotype that can be prevented by oral phosphate ([Pi]) supplementation. RESULTS: In this study we examined the role of pH in the protective effect of [Pi] supplementation as it has been shown to be increased in the distal gut following surgical injury. Surgically injured mice drinking 25 mM [Pi] at pH 7.5 and intestinally inoculated with P. aeruginosa had increased mortality compared to mice drinking 25 mM [Pi] at pH 6.0 (p < 0.05). This finding was confirmed in C. elegans. Transcriptional analysis of P. aeruginosa demonstrated enhanced expression of various genes involved in media alkalization at pH 6.0 and a global increase in the expression of all iron-related genes at pH 7.5. Maintaining the pH at 6.0 via phosphate supplementation led to significant attenuation of iron-related genes as demonstrated by microarray and confirmed by QRT-PCR analyses. CONCLUSION: Taken together, these data demonstrate that increase in pH in distal intestine of physiologically stressed host colonized by P. aeruginosa can lead to the expression of siderophore-related virulence in bacteria that can be prevented without providing iron by maintaining local phosphate abundance at pH 6.0. This finding is particularly important as provision of exogenous iron has been shown to have untoward effects when administered to critically ill and septic patients. Given that phosphate, pH, and iron are near universal cues that dictate the virulence status of a broad range of microorganisms relevant to serious gut origin infection and sepsis in critically ill patients, the maintenance of phosphate and pH at appropriate physiologic levels to prevent virulence activation in a site specific manner can be considered as a novel anti-infective therapy in at risk patients.

Targeting pediatric pedestrian injury prevention efforts: teasing the information through spatial analysis.

BACKGROUND: Pediatric pedestrian injuries remain a major cause of childhood death, hospitalization, and disability. To target injury prevention efforts, it is imperative to identify those children at risk. Racial disparities have been noted in the rates of pediatric pedestrian injury and death. Children from low-income families living in dense, urban residential neighborhoods have a higher risk of sustaining pedestrian injury. Geographic information systems (GIS) analysis of associated community factors such as child population density and median income may offer insights into prevention. METHODS: Using trauma registry E-codes for pedestrian motor vehicle crashes, children younger than 16 years were identified, who received acute care and were hospitalized at the University of Chicago Medical Center, a Level I pediatric trauma center, after being struck by a motor vehicle from 2002 to 2009. By retrospective chart review and review of the Emergency Medical Services run sheets, demographic data and details of the crash site were collected. Crash sites were aggregated on a block by block basis. A "hot spot" analysis was performed to localize clusters of injury events. Using Gi* statistical method, spatial clusters were identified at different confidence intervals using a fixed distance band of 400 m (≈ » mile). Maps were generated using GIS with 2000 census data to evaluate race, employment, income, density of public and private schools, and density of children living in the neighborhoods surrounding our medical center where crash sites were identified. Spatial correlation is used to identify statistically significant locations. RESULTS: There were 3,521 children admitted to the University of Chicago Medical Center for traumatic injuries from 2002 to 2009; 27.7% (974) of these children sustained injuries in pedestrian motor vehicle injuries. From 2002 to 2009, there were a total of 106 traumatic deaths, of which 29 (27.4%) were due to pedestrian motor vehicle crashes. Pediatric pedestrian motor vehicle crash sites occurred predominantly within low-income, predominantly African-American neighborhoods. A lower prevalence of crash sites was observed in the predominantly higher income, non-African-American neighborhoods. CONCLUSIONS: Spatial analysis using GIS identified associations between pediatric pedestrian motor vehicle crash sites and the neighborhoods served by our pediatric trauma center. Pediatric pedestrian motor vehicle crash sites occurred predominantly within low-income, African-American neighborhoods. The disparity in prevalence of crash sites is somewhat attributable to the lower density of children living in the predominantly higher income, non-African-American neighborhoods, including the community immediately around our hospital. Traffic volume patterns, as a denominator of these injury events, remain to be studied.

Pseudomonas aeruginosa potentiates the lethal effect of intestinal ischemia-reperfusion injury: the role of in vivo virulence activation.

BACKGROUND: Experimental models of intestinal ischemia-reperfusion (IIR) injury are invariably performed in mice harboring their normal commensal flora, even though multiple IIR events occur in humans during prolonged intensive care confinement when they are colonized by a highly pathogenic hospital flora. The aims of this study were to determine whether the presence of the human pathogen Pseudomonas aeruginosa in the distal intestine potentiates the lethality of mice exposed to IIR and to determine what role any in vivo virulence activation plays in the observed mortality. METHODS: Seven- to 9-week-old C57/BL6 mice were exposed to 15 minutes of superior mesenteric artery occlusion (SMAO) followed by direct intestinal inoculation of 1.0 × 10(6) colony-forming unit of P. aeruginosa PAO1 into the ileum and observed for mortality. Reiterative studies were performed in separate groups of mice to evaluate both the migration/dissemination pattern and in vivo virulence activation of intestinally inoculated strains using live photon camera imaging of both a constitutive bioluminescent P. aeruginosa PAO1 derivative XEN41 and an inducible reporter derivative of PAO1, the PAO1/lecA:luxCDABE that conditionally expresses the quorum sensing-dependent epithelial disrupting virulence protein PA 1 Lectin (PA-IL). RESULTS: Mice exposed to 15 minutes of SMAO and reperfusion with intestinal inoculation of P. aeruginosa had a significantly increased mortality rate (p < 0.001) of 100% compared with <10% for sham-operated mice intestinally inoculated with P. aeruginosa without SMAO and IIR alone (<50%). Migration/dissemination patterns of P. aeruginosa in mice subjected to IIR demonstrated proximal migration of distally injected strains and translocation to mesenteric lymph nodes, liver, spleen, lung, and kidney. A key role for in vivo virulence expression of the barrier disrupting adhesin PA-IL during IIR was established since its expression was enhanced during IR and mutant strains lacking PA-IL displayed attenuated mortality. CONCLUSIONS: The presence of intestinal P. aeruginosa potentiates the lethal effect of IIR in mice in part due to in vivo virulence activation of its epithelial barrier disrupting protein PA-IL.

Activation of Deoxyribonuclease I by Nicotinamide as a New Strategy to Attenuate Tetracycline-Resistant Biofilms of Cutibacterium acnes.

Biofilms of Cutibacterium (C.) acnes (formerly Propionibacterium acnes) are responsible for the persistence and antibiotic resistance of acne vulgaris. In addition to the standard treatments for acne vulgaris, a common adjunctive treatment is the topical administration of nicotinamide (NAM). However, the effects of NAM on biofilms of C. acnes have never been explored. This study comprehensively investigates the effects of NAM against biofilms of C. acnes using in vitro and in vivo approaches. The results showed that NAM potentiated the efficacy of suboptimal dosing of tetracycline against C. acnes. Moreover, NAM alone decreased the formation and increased the degradation of biofilms in C. acnes. The antibiofilm effect of NAM against C. acnes was further enhanced in combination with deoxyribonuclease (DNase) I, an enzyme with known antibiofilm properties. The computational molecular docking, surface plasmon resonance analysis, and enzymatic kinetic assay demonstrated that NAM binds to DNase I and accelerated its reaction. In conclusion, NAM activates DNase I to attenuate biofilms of C. acnes. This offers valuable insights into the strategies against biofilms that are worth elaborating on in other biofilm-related chronic cutaneous infections in the future.

Ultra-microangiography in evaluating the disease activity of rheumatoid arthritis and enhancing the efficacy of ultrasonography: A preliminary study.

OBJECTIVE: Ultra-microangiography (UMA) is a novel Doppler technique that has high sensitivity for low-velocity blood flows. In this study, a distinctive imaging feature, penetrating blood vessels on the surface of eroded bones within the inflamed joints, was observed on UMA. We aimed to investigate the feasibility of UMA in assessing disease activity and identify the clinical value of the UMA feature for evaluating rheumatoid arthritis (RA). METHODS AND MATERIALS: Power-Doppler ultrasound (PDUS) and UMA were performed on small joints of RA patients. The semiquantitative scores of PDUS and UMA of the joints were assessed and compared. The UMA imaging feature of penetrating vessels on the surface of eroded bones was evaluated, and the patients were divided into three groups based on imaging features. (Group 1: no inflammatory signs; Group 2: inflammatory US features but no UMA features; and Group 3: detected UMA features). The correlations between the groups and clinical parameters were assessed. RESULTS: A total of 52 patients with RA were recruited, with 364 joints (MCP, PIP, MTP and wrist) scanned. Synovial blood vessel signals were detected for 68 by PDUS and for 93 by UMA (display rate of blood vessel signals: 18.68 % VS 25.55 %). UMA presented better display capability of blood vessels within the inflamed regions than that of PDUS in overall. Significant differences were detected in clinical scores (P < 0.0001 for DAS28 [ESR], DAS28 [CRP], SDAI, CDAI, CRP P = 0.0303, SJC P = 0.0059, and TJC P = 0.0423) between Group 2 and 3. Significant correlations between the groups and clinical parameters were also observed (DAS28 [ESR] ρ=0.750; DAS28 [CRP] ρ=0.762; SDAI ρ=0.778; CDAI ρ=0.773; CRP ρ= 0.524; SJC ρ=0.742; TJC ρ=0.693, P < 0.0001), indicating that the UMA feature was related to high disease activity. CONCLUSIONS: UMA can help enhance the detection rate of micro-vascularization. The UMA feature of the penetrating vessels on the surface of eroded bones is likely to be associated with severe disease activity.

The α9 Nicotinic Acetylcholine Receptor Mediates Nicotine-Induced PD-L1 Expression and Regulates Melanoma Cell Proliferation and Migration.

Cigarette smoking is associated with an increased risk of melanoma metastasis. Smokers show higher PD-L1 expression and better responses to PD-1/PD-L1 inhibitors than nonsmokers. Here, we investigate whether nicotine, a primary constituent of tobacco, induces PD-L1 expression and promotes melanoma cell proliferation and migration, which is mediated by the α9 nicotinic acetylcholine receptor (α9-nAChR). α9-nAChR overexpression in melanoma using melanoma cell lines, human melanoma tissues, and assessment of publicly available databases. α9-nAChR expression was significantly correlated with PD-L1 expression, clinical stage, lymph node status, and overall survival (OS). Overexpressing or knocking down α9-nAChR in melanoma cells up- or downregulated PD-L1 expression, respectively, and affected melanoma cell proliferation and migration. Nicotine-induced α9-nAChR activity promoted melanoma cell proliferation through stimulation of the α9-nAChR-mediated AKT and ERK signaling pathways. In addition, nicotine-induced α9-nAchR activity promoted melanoma cell migration via activation of epithelial-mesenchymal transition (EMT). Moreover, PD-L1 expression was upregulated in melanoma cells after nicotine treatment via the transcription factor STAT3 binding to the PD-L1 promoter. These results highlight that nicotine-induced α9-nAChR activity promotes melanoma cell proliferation, migration, and PD-L1 upregulation. This study may reveal important insights into the mechanisms underlying nicotine-induced melanoma growth and metastasis through α9-nAChR-mediated carcinogenic signals and PD-L1 expression.

Utility of Gram staining for diagnosis of Malassezia folliculitis.

Malassezia folliculitis (MalF) mimics acne vulgaris and bacterial folliculitis in clinical presentations. The role of Gram staining in rapid diagnosis of MalF has not been well studied. In our study, 32 patients were included to investigate the utility of Gram staining for MalF diagnosis. The final diagnoses of MalF were determined according to clinical presentation, pathological result and treatment response to antifungal agents. Our results show that the sensitivity and specificity of Gram staining are 84.6% and 100%, respectively. In conclusion, Gram staining is a rapid, non-invasive, sensitive and specific method for MalF diagnosis.

Handlebar injuries in children: should we raise the bar of suspicion?

Injury prevention strategies for child bicyclists have focused on helmet use to prevent head trauma. Handlebars are another source of injury. A retrospective review from 2005 identified 385 admissions to a Level 1 pediatric trauma center of which 23 (5.9%) were pedal cyclists. Four cases (<1.0%) of handlebar injuries were identified. Three children (two bicyclists, one riding a scooter) sustained handlebar impact to the neck. All children with neck injuries had subcutaneous emphysema. Two of the children had pneumomediastinum, which after work-up was managed nonoperatively. One child had a tracheal injury requiring operative intervention. Another child was struck in the upper abdomen resulting in a traumatic abdominal wall hernia requiring emergent exploration and hernia repair. Discordance exists between the apparently minor circumstances of handlebar trauma and the severity of injury sustained by bicyclists. Recognizing the mechanism of handlebar-related injuries and maintaining a high index of suspicion for visceral injuries aids in the diagnosis. The incidence of these injuries is underestimated due to insufficient documentation of the circumstances of injury events and a lack of applicable E-codes specific for handlebar injury.

Disseminated cutaneous Mycobacterium kansasii infection presenting with Rosai-Dorfman disease-like histological features in a patient carrying anti-interferon-γ autoantibodies.

Typical cutaneous non-tuberculous mycobacteria (NTM) infections show a histopathology pattern of granulomas with admixed Langhans giant cells, and abscesses may be observed in acute lesions. Herein, we describe a patient carrying a high titer of autoantibodies to interferon (IFN)-γ with disseminated Mycobacterium kansasii infection presenting with emperipolesis and Rosai-Dorfman disease (RDD)-like histopathological features characterized by remarkable, large, pale-staining "RD cells", which were CD68 and S100 positive and CD1a negative. The patient was misdiagnosed with RDD initially, but exhibited a poor response to all interventions. A re-biopsy revealed Langhans-type multinucleated giant cells; multiple definite acid-fast bacilli were also found. M. kansasii was isolated from cultured tissues. Anti-NTM treatment was initiated. After treatment, all lesions resolved almost completely within the following month. High-titer anti-IFN-γ autoantibodies were detected during follow up, leading to the diagnosis of adult-onset immunodeficiency syndrome. In conclusion, patients carrying high-titer autoantibodies to IFN-γ who also have a disseminated cutaneous M. kansasii infection may present with RDD-like histopathological features, which may be a pitfall in the diagnosis of disseminated cutaneous NTM infections.

Discovery of a novel family of SARS-CoV protease inhibitors by virtual screening and 3D-QSAR studies.

The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) 3C-like protease (3CL(pro) or M(pro)) is an attractive target for the development of anti-SARS drugs because of its crucial role in the viral life cycle. In this study, a compound database was screened by the structure-based virtual screening approach to identify initial hits as inhibitors of SARS-CoV 3CL(pro). Out of the 59,363 compounds docked, 93 were selected for the inhibition assay, and 21 showed inhibition against SARS-CoV 3CL(pro) (IC(50)

Improved infant swallowing after gastroesophageal reflux disease treatment: a function of improved laryngeal sensation?

OBJECTIVE: The objective of this study was to describe improvements in pediatric swallowing after gastroesophageal reflux treatment. STUDY DESIGN: The authors conducted a retrospective database and chart review at two tertiary care children's hospitals. PARTICIPANTS: Patients (21 males, 7 females) ranged in age from 1 to 32 months. All patients had clinical evidence of gastroesophageal reflux disease (GERD) as well as evidence of dysphagia with aspiration (laryngeal vestibule and/or trachea) or hypopharyngeal pooling on flexible endoscopic evaluation of swallowing and sensation testing (FEESST) or videofluoroscopic swallow study (VSS). INTERVENTION: Each child underwent either medical or surgical intervention for control of their GERD. OUTCOME MEASURES: Outcome measures were change in laryngopharyngeal sensation and swallowing function with repeat swallow evaluation after GERD treatment. RESULTS: A significant improvement in both swallow function and sensory testing was demonstrated after GERD treatment. CONCLUSIONS: GERD may result in decreased laryngopharyngeal sensitivity, which may contribute to pediatric swallowing dysfunction. Control of GERD may improve swallow function. These findings have important clinical implications that need further study.

Pediatric pelvic fractures: a marker for injury severity.

Pelvic fractures comprise a small number of annual Level I pediatric trauma center admissions. This is a review of the University of Chicago Level I Pediatric Trauma Center experience with pediatric pelvic fractures. This is a retrospective review of the University of Chicago Level I Pediatric Trauma Center experience with pediatric pelvic fractures during the 12-year period from 1992 to 2004. From 1992 to 2004, there were 2850 pediatric trauma admissions. Thirteen patients were identified with pelvic fractures; seven were boys and six were girls. The average age was 8 years old. The mechanism of injury in all cases was motor vehicle related; 11 patients (87%) sustained pedestrian-motor vehicle crashes. According to the Torode and Zeig classification system, type III fractures occurred in eight patients (62%) and type IV fractures occurred in six patients (31%). Associated injuries occurred in eight patients (62%). Seven of these patients (88%) had associated injuries involving two or more organ systems. Of the associated injuries, additional orthopedic injuries were the most common, occurring in 62 per cent of our patients. Neurological injuries occurred in 54 per cent of patients, vascular injuries in 39 per cent, pulmonary injuries in 31 per cent, and genitourinary injuries in 15 per cent. Five patients (38%) were treated operatively; only two patients underwent operative management directly related to their pelvic fracture. The remaining three patients underwent operative management of associated injuries. The mortality rate was 0 per cent. Although pelvic fractures are an uncommon injury in pediatric trauma patients, the morbidity associated with these injuries can be profound. The majority of pelvic fractures in children are treated nonoperatively, however, more than one-half of these patients have concomitant injuries requiring operative management. When evaluating and treating pediatric pelvic fractures, a systematic multidisciplinary approach must be taken to evaluate and prioritize the pelvic fracture and the associated injuries.