Immunity-linked genes are stimulated by a membrane stress pathway linked to Golgi function and the ARF-1 GTPase.

Infection response and other immunity-linked genes (ILGs) were first named in Caenorhabditis elegans-based expression after pathogen challenge, but many are also up-regulated when lipid metabolism is perturbed. Why pathogen attack and metabolic changes both increase ILGs is unclear. We find that ILGs are activated when phosphatidylcholine (PC) levels change in membranes of secretory organelles in C. elegans. RNAi targeting of the ADP-ribosylation factor arf-1, which disrupts the Golgi and secretory function, also activates ILGs. Low PC limits ARF-1 function, suggesting a mechanism for ILG activation via lipid metabolism, as part of a membrane stress response acting outside the ER. RNAi of selected ILGs uncovered defects in the secretion of two GFP reporters and the accumulation of a pathogen-responsive complement C1r/C1s, Uegf, Bmp1 (CUB) domain fusion protein. Our data argue that up-regulation of some ILGs is a coordinated response to changes in trafficking and may act to counteract stress on secretory function.

S-adenosylmethionine synthases specify distinct H3K4me3 populations and gene expression patterns during heat stress.

Methylation is a widely occurring modification that requires the methyl donor S-adenosylmethionine (SAM) and acts in regulation of gene expression and other processes. SAM is synthesized from methionine, which is imported or generated through the 1-carbon cycle (1 CC). Alterations in 1 CC function have clear effects on lifespan and stress responses, but the wide distribution of this modification has made identification of specific mechanistic links difficult. Exploiting a dynamic stress-induced transcription model, we find that two SAM synthases in Caenorhabditis elegans, SAMS-1 and SAMS-4, contribute differently to modification of H3K4me3, gene expression and survival. We find that sams-4 enhances H3K4me3 in heat shocked animals lacking sams-1, however, sams-1 cannot compensate for sams-4, which is required to survive heat stress. This suggests that the regulatory functions of SAM depend on its enzymatic source and that provisioning of SAM may be an important regulatory step linking 1 CC function to phenotypes in aging and stress.

The combination of target motion and dynamic changes in context greatly enhance visual size illusions.

Perceived size is a function of viewing distance, retinal images size, and various contextual cues such as linear perspective and the size and location of neighboring objects. Recently, we demonstrated that illusion magnitudes of classic visual size illusions may be greatly enhanced or reduced by adding dynamic elements. Specifically, a dynamic version of the Ebbinghaus illusion (classically considered a "size contrast" illusion) led to a greatly enhanced illusory effect, whereas a dynamic version of the Corridor illusion (a "size constancy" illusion) led to a greatly diminished illusory effect. Although these differences may arise from the different processes underlying these illusions (size contrast vs. size constancy), the dynamic variants we tested in our previous work also differed in the nature of the dynamic elements; specifically, whereas the Dynamic Ebbinghaus included a moving target and inducers that changed size and position, the Dynamic Corridor only included a moving target on a static background. Here, we explore further dynamic versions of the Ebbinghaus illusion and the Corridor and Ponzo illusions by separately manipulating three types of dynamic elements: target motion, context translation, and dynamic changes in context. Across five experiments examining 21 dynamic illusory configurations, adding target motion or a dynamically changing context separately resulted in little-to-no illusory effect. In contrast, the combination of target motion and a dynamically changing context led to a robust size illusion, consistent with an interactive effect. However, illusory effects that exceeded the matched classic, static illusory configuration were only observed for the dynamic versions of the Ebbinghaus illusion and the Revealed Ponzo illusions, in which the contextual elements changed size. We conclude that the combination of target motion and a dynamically changing context are necessary to produce dynamic size illusions, but that enhancement above and beyond static illusions may be largely specific to size contrast effects. Our results have important implications for the integration of motion signals, a ubiquitous environmental stimulus, in the perception of object size.

The Arthroscopic "Bellows" Sign Identifies Hidden Rotator Cuff Tears.

The intraoperative recognition of rotator cuff tears continues to be a challenge in some cases, despite clinical suspicion, a physical examination suggesting a rotator cuff tear, and detection on preoperative imaging studies. Intraoperative identification can be elusive in partial tears including intratendinous tears and obscured full-thickness tears. The purpose of this Technical Note, and the associated technique video, is to discuss a visual sign for the detection of various rotator cuff tear pathologies. Derived from the dynamic fluid expansion and contraction of the affected tissues, this indicator is termed the arthroscopic "bellows" sign.

Geographic Distribution of Foot and Ankle Orthopedic Surgeons Throughout the United States.

BACKGROUND: At present, the geographic distribution of orthopedic foot and ankle (OFA) surgeons in the United States is poorly defined. The purpose of this investigation is to determine the geographic distribution of OFA surgeons in the United States. We hypothesize that there will be differences in OFA surgeon density throughout the United States and that economic factors may play a role in access to subspecialty OFA care. METHODS: A current membership list was obtained from the American Orthopaedic Foot & Ankle Society (AOFAS). Active members were categorized relative to states and US congressional districts, using publicly available census data. The relationship between income and surgeon density was determined using a Pearson correlation. RESULTS: We identified a list of 1103 active AOFAS members. There was an average of 0.38 and 0.40 OFA surgeons per 100 000 people in each state and congressional district, respectively. We found a weak negative relationship demonstrating that regions with higher levels of poverty had fewer OFA surgeons, with a Pearson correlation coefficient of -0.14 (95% CI: -0.24, -0.04), P = .008. CONCLUSION: There is wide geographic variation of OFA surgeon density throughout the United States. Regions with higher levels of poverty were weakly associated with decreased population density of OFA surgeons compared to regions with lower poverty levels. Understanding these trends may aid in developing both recruitment and referral strategies for complex foot and ankle care in underserved regions. LEVEL OF EVIDENCE: Level V.

Revision Posterior Cruciate Ligament Surgery.

Successful posterior cruciate ligament (PCL) reconstruction surgery results from identification and treatment of associated pathology such as posterolateral instability, posteromedial instability, and lower extremity malalignment. The use of strong graft material, properly placed tunnels to as closely as possible approximate the PCL insertion sites, and minimization of graft bending also enhance the probability of PCL reconstruction success. In addition, mechanical graft tensioning, primary and back-up PCL graft fixation, and the appropriate postoperative rehabilitation program are also necessary ingredients for PCL reconstruction success. Both single-bundle and double-bundle PCL reconstruction surgical techniques are successful when evaluated with stress radiography, KT 1000 arthrometer measurements, and knee ligament rating scales. PCL reconstruction failure may result when any or all of these surgical principles are violated. The purpose of this manuscript was to discuss revision PCL surgery. This presentation will include causes of unsuccessful PCL reconstruction, surgical indications and goals, patient evaluation, surgical decision making, graft selection, surgical technique, associated surgical procedures, postoperative rehabilitation, and revision PCL reconstruction results.

The Mini C-arm Adds Quality and Efficiency to the Pediatric Orthopedic Outpatient Clinic.

The mini C-arm has become increasingly popular in the practice of orthopedics. To the authors' knowledge, its use in the pediatric orthopedic outpatient clinic has not been reported. The purpose of this study was to evaluate the practice efficiency and radiation exposure to the patient when the mini C-arm was used in the pediatric orthopedic outpatient clinic. One hundred consecutive midshaft and distal forearm fractures were evaluated by one orthopedic surgeon in follow-up using a mini C-arm. For each case, the radiation physicist calculated the amount of skin exposure in milligray (mGy). The average skin exposure to the patient from the mini C-arm was 0.58 mGy, compared with 0.2 mGy for anteroposterior view and lateral view radiographs. Use of the mini C-arm, in place of plain radiographs obtained in the radiology department, decreased time waiting during clinic visits by 23 minutes. This study reports 2 important findings. First, surprisingly, the mini C-arm used a slightly higher radiation dose than standard imaging with plain radiographs. Second, use of the mini C-arm saved time and improved the efficiency of the clinic visit. Overall, the mini C-arm improves quality and efficiency in the pediatric orthopedic outpatient clinic. [Orthopedics. 2016; 39(6):e1097-e1099.].

In-Toeing Is Often a Primary Care Orthopedic Condition.

OBJECTIVE: To evaluate in-toeing consults to a pediatric orthopedic clinic to determine the proportion that could be managed by a primary care physician. STUDY DESIGN: A prospective registry was created for 143 consecutive children referred to a pediatric orthopedic clinic for "in-toeing." Each patient underwent a careful history and physical examination, which included a rotational profile. We recorded the final diagnosis, treatment offered, follow-up visit results, and the source of the referral. RESULTS: After pediatric orthopedic evaluation, 85% of patients had a confirmed diagnosis of in-toeing, and 15% had a different final diagnosis. Seventy-four percent of patients had 1 consultation visit, 18% had 2, and 8% had >2 visits. None of the referred patients was a candidate for treatment by casting or surgery. CONCLUSION: In most cases, in-toeing is a normal variation of development that can be managed by counseling and observation by the primary care physician alone. Rare cases of severe in-toeing >2 standard deviations from the mean should likely still prompt referral to a pediatric orthopedic surgeon for potential intervention.

Combined anterior cruciate ligament and posterolateral reconstruction of the knee using allograft tissue in chronic knee injuries.

Combined anterior cruciate ligament (ACL) and posterolateral injury of the knee can result in significant functional instability for the affected individual. Both components of the instability must be treated to maximize the probability of success for the surgical procedure. Higher failure rates of the ACL reconstruction have been reported when the posterolateral instability has been left untreated. The purpose of this article is to describe our surgical technique, and present the results of 34 chronic combined ACL posterolateral reconstructions in 34 knees using allograft tissue, and evaluating these patient outcomes with KT 1000 knee ligament arthrometer, Lysholm, Tegner, and Hospital for Special Surgery knee ligament rating scales. In addition, observations regarding patient demographics with combined ACL posterolateral instability, postoperative range of motion loss, postinjury degenerative joint disease, infection rate, return to function, and the use of radiated and nonirradiated allograft tissues will be presented.

Mechanisms for the reaction of thiophene and methylthiophene with singlet and triplet molecular oxygen.

Mechanisms for the reaction of thiophene and 2-methylthiophene with molecular oxygen on both the triplet and singlet potential energy surfaces (PESs) have been investigated using ab initio methods. Geometries of various stationary points involved in the complex reaction routes are optimized at the MP2/6-311++G(d, p) level. The barriers and energies of reaction for all product channels were refined using single-point calculations at the G4MP2 level of theory. For thiophene, CCSD(T) single point energies were also determined for comparison with the G4MP2 energies. Thiophene and 2-methylthiophene were shown to react with O(2) via two types of mechanisms, namely, direct hydrogen abstraction and addition/elimination. The barriers for reaction with triplet oxygen are all significantly large (i.e., >30 kcal mol(-1)), indicating that the direct oxidation of thiophene by ground state oxygen might be important only in high temperature processes. Reaction of thiophene with singlet oxygen via a 2 + 4 cycloaddition leading to endoperoxides is the most favorable channel. Moreover, it was found that alkylation of the thiophene ring (i.e., methyl-substituted thiophene) is capable of lowering the barrier height for the addition pathway. The implication of the current theoretical results may shed new light on the initiation mechanisms for combustion of asphaltenes.

Association of pharyngitis with oral antibiotic use for the treatment of acne: a cross-sectional and prospective cohort study.

OBJECTIVE: To prospectively evaluate the association between antibiotics used to treat acne and pharyngitis. DESIGN: Cross-sectional and 9-month prospective cohort. SETTING: Urban university setting. PARTICIPANTS: University students. INTERVENTION: Participants were asked to fill out a survey form, were swabbed for culture, and had a visual examination for acne. MAIN OUTCOME MEASURE: Report of pharyngitis. RESULTS: In the cross-sectional study, 10 of the 15 students receiving oral antibiotics for acne reported an episode of pharyngitis in the previous 30 days, whereas 47 of the 130 students not receiving oral antibiotics, but who had acne, reported an episode of pharyngitis in the prior month. The unadjusted odds ratio (OR) (95% CI) associating current oral antibiotic use in acne patients with a self-reported episode of pharyngitis was 3.53 (95% CI, 1.14-10.95). In the cohort study, there were 358 female and 218 male participants; 36 (6.2%) received oral antibiotics for acne during the study, and 96 (16.6%) received topical antibiotics for acne. Using mixed model logistic regression, the OR was 4.34 (95% CI, 1.51-12.47) associating oral antibiotic use with pharyngitis. Less than 1% of participants were colonized by group A streptococcus, which was not associated with pharyngitis. CONCLUSIONS: Our studies show that that the odds of reporting pharyngitis is more than 3 times baseline in patients receiving oral antibiotics for acne vs those who are not receiving oral antibiotics. The true clinical importance of these findings needs to be evaluated further by prospective studies, but this finding is not associated with group A streptococcus.

Antibiotics, acne, and Staphylococcus aureus colonization.

OBJECTIVES: To determine the frequency of Staphylococcus aureus colonization among patients with acne and to compare the susceptibility patterns between the patients who are using antibiotics and those who are not using antibiotics. DESIGN: Survey (cross-sectional) study of patients treated for acne. SETTING: Dermatology outpatient office practice PARTICIPANTS: The study included 83 patients who were undergoing treatment and evaluation for acne. MAIN OUTCOME: Measure Colonization of the nose or throat with S aureus. RESULTS: A total of 36 of the 83 participants (43%) were colonized with S aureus. Two of the 36 patients (6%) had methicillin-resistant S aureus ; 20 (56%) had S aureus solely in their throat; 9 (25%) had S aureus solely in their nose; and 7 (19%) had S aureus in both their nose and their throat. When patients with acne who were antibiotic users were compared with nonusers, the prevalence odds ratio for the colonization of S aureus was 0.16 (95% confidence interval [CI], 0.08-1.37) after 1 to 2 months of exposure and increased to 0.52 (95% CI, 0.12-2.17) after 2 months of exposure (P = .31). Many of the S aureus isolates were resistant to treatment with clindamycin and erythromycin (40% and 44%, respectively), particularly the nasal isolates. Very few showed resistance rates (< 10%) to treatment with tetracycline antibiotics. CONCLUSION: Unlike current dogma about the long-term use of antimicrobial agents, the prolonged use of tetracycline antibiotics commonly used to treat acne lowered the prevalence of colonization by S aureus and did not increase resistance to the tetracycline antibiotics.

Potential association between the oral tetracycline class of antimicrobials used to treat acne and inflammatory bowel disease.

OBJECTIVES: Previous studies have shown an association between isotretinoin and inflammatory bowel disease (IBD). The majority of patients prescribed isotretinoin for their acne are previously on an extended course of antibiotics. Therefore, it is important to consider antibiotic use as a confounding variable for the development of IBD. METHODS: We performed a retrospective cohort study using The Health Improvement Network database of the United Kingdom. We identified 94,487 individuals with acne who were followed up by a general practitioner for 406,294 person-years. RESULTS: >A prescription for minocycline was received by 24,085 individuals, for tetracycline/oxytetracycline by 38,603 individuals, and doxycycline by 15,032 individuals. IBD was noted in 41 individuals exposed to minocycline, 79 individuals exposed to tetracycline/oxytetracycline, 32 individuals exposed to doxycycline, and 55 (0.11%) individuals not exposed to any of these antibiotics. The hazard ratio (HR) for developing IBD for any exposure to a tetracycline antibiotic was 1.39 (1.02, 1.90). HRs for individual antibiotics were 1.19 (0.79, 1.79) for minocycline, 1.43 (1.02, 2.02) for tetracycline/oxytetracycline, and 1.63 (1.05, 2.52) for doxycycline. For ulcerative colitis, the associations (HR) were 1.10 (0.76, 1.82) for minocycline, 1.27 (0.78, 2.07) for tetracycline/oxytetracycline, and 1.06 (0.53, 2.13) for doxycycline. For Crohn's disease (CD), the associations (HR) were 1.28 (0.72, 2.30) for minocycline, 1.61 (0.995, 2.63) for tetracycline/oxytetracycline, and 2.25 (1.27 4.00) for doxycycline. CONCLUSIONS: Tetracycline class antibiotics, and particularly doxycycline use may be associated with the development of IBD, particularly CD. Potential confounding by previous doxycycline exposure should be considered when assessing whether treatment with other acne medications increases the risk of IBD.