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Supplementary Table 1 from Expression Profiling of t(12;22) Positive Clear Cell Sarcoma of Soft Tissue Cell Lines Reveals Characteristic Up-Regulation of Potential New Marker Genes Including ERBB3

Supplementary Table 2 from Expression Profiling of t(12;22) Positive Clear Cell Sarcoma of Soft Tissue Cell Lines Reveals Characteristic Up-Regulation of Potential New Marker Genes Including ERBB3

Clear cell sarcoma of soft tissue (CCSST), also known as malignant melanoma of soft parts, represents a rare lesion of the musculoskeletal system usually affecting adolescents and young adults. CCSST is typified by a chromosomal t(12;22)(q13;q12) translocation resulting in a fusion between the Ewing sarcoma gene (EWSR1) and activating transcription factor 1 (ATF1), of which the activity in nontransformed cells is regulated by cyclic AMP. Our aim was to identify critical differentially expressed genes in CCSST tumor cells in comparison with other solid tumors affecting children and young adults to better understand signaling pathways regulating specific features of the development and progression of this tumor entity. We applied Affymetrix Human Genome U95Av2 oligonucleotide microarrays representing ∼12,000 genes to generate the expression profiles of the CCSST cell lines GG-62, DTC-1, KAO, MST2, MST3, and Su-CC-S1 in comparison with 8 neuroblastoma, 7 Ewing tumor, and 6 osteosarcoma cell lines. Subsequent hierarchical clustering of microarray data clearly separated all four of the tumor types from each other and identified differentially expressed transcripts, which are characteristically up-regulated in CCSST. Statistical analysis revealed a group of 331 probe sets, representing ∼300 significant (P < 0.001) differentially regulated genes, which clearly discriminated between the CCSST and other tumor samples. Besides genes that were already known to be highly expressed in CCSST, like S100A11 (S100 protein) or MITF (microphthalmia-associated transcription factor), this group shows an obvious portion of genes that are involved in cyclic AMP response or regulation, in pigmentation processes, or in neuronal structure and signaling. Comparison with other expression profile analyses on neuroectodermal childhood tumors confirms the high robustness of this strategy to characterize tumor entities based on their gene expression. We found the avian erythroblastic leukemia viral oncogene homologue 3 (ERBB3) to be one of the most dramatically up-regulated genes in CCSST. Quantitative real-time PCR and Northern blot analysis verified the mRNA abundance and confirmed the absence of the inhibitory transcript variant of this gene. The protein product of the member of the epidermal growth factor receptor family ERBB3 could be shown to be highly present in all of the CCSST cell lines investigated, as well as in 18 of 20 primary tumor biopsies. In conclusion, our data demonstrate new aspects of the phenotype and the biological behavior of CCSST and reveal ERBB3 to be a useful diagnostic marker.

Background: Ultrasound can provide evaluation of the anatomy of the carpal tunnel in a convenient, noninvasive office setting. This study is intended to determine the accuracy and diagnostic performance of ultrasound, used by surgeons, for the evaluation of completeness of carpal tunnel release (CTR). Methods: Ten cadaver arms underwent randomized sectioning of 0%, 25%, 50%, 75%, or 100% of the transverse carpal ligament. Following a brief training session, a blinded observer used ultrasound to evaluate the percentage of the transverse carpal ligament release. The release amount was then confirmed with an open exposure of the transverse carpal ligament. Results: Cronbach α and Pearson correlation coefficients were 0.92 and 0.87, demonstrating excellent reliability and validity of the technique. Diagnostic performance including sensitivity, specificity, positive predictive value, and negative predictive value was 100%, 75%, 86%, and 100%, respectively, for the diagnosis of incomplete release of the transverse carpal ligament by a novice sonographer orthopedic surgeon. Conclusions: The ultrasound is a highly accurate tool for the diagnosis of incomplete transverse carpal ligament release and requires a minimal amount of training to use for this purpose. It provides a rapid means of diagnosing incomplete release of the transverse carpal ligament following CTR.

In May 2019, the Council of the European Union (EU) adopted a new Central Asia Strategy. Drivers behind the strategic renewal were transformations in Central Asia, the new geopolitical context, lessons from the implementation of the previous strategy, and the new EU Global Strategy of 2016. With regard to these developments, a number of expectations towards the new strategy derived. Based on an outline of recent developments, the article identifies current challenges and expectations and assesses whether the new strategy lives up to them. It concludes that the 2019 strategy is rather a framework for action than a strategic document. However, its major assets are “flexibility” with regard to future trends and “inclusiveness” in terms of stakeholders’ ownership for the EU’s Central Asia policy. To sustain this ownership, the Central Asia policy needs sufficient funding under the next multiannual financial framework. During programming, the EU has to define clear priorities for bilateral and regional measures. To generate synergies, the EU institutions and member states have to agree on an internal division of labor. Finally, the EU has to put “principled pragmatism” into practice by finding a balance between the promotion of values and interests.

RCUK funded OA Mycobacterium tuberculosis (MTb) is the causative agent of pulmonary tuberculosis (TB). MTb colonizes the human lung, often entering a non-replicating state before progressing to life-threatening active infections. Transcriptional reprogramming is essential for TB pathogenesis. In vitro, Cmr (a member of the CRP/FNR super-family of transcription regulators) bound at a single DNA site to act as a dual regulator of cmr transcription and an activator of the divergent rv1676 gene. Transcriptional profiling and DNA-binding assays suggested that Cmr directly represses dosR expression. The DosR regulon is thought to be involved in establishing latent tuberculosis infections in response to hypoxia and nitric oxide. Accordingly, DNA-binding by Cmr was severely impaired by nitrosation. A cmr mutant was better able to survive a nitrosative stress challenge but was attenuated in a mouse aerosol infection model. The complemented mutant exhibited a ∼2-fold increase in cmr expression, which led to increased sensitivity to nitrosative stress. This, and the inability to restore wild-type behaviour in the infection model, suggests that precise regulation of the cmr locus, which is associated with Region of Difference 150 in hypervirulent Beijing strains of Mtb, is important for TB pathogenesis.

Background: The purpose of this study was to look for differences in mechanism, radiographic findings, and treatment between mallet fractures of the thumb and mallet fractures of the index through small fingers. Methods: This retrospective study included 24 mallet fractures of the thumb and 392 mallet fractures of other digits. We compared demographics, injury factors (side, dominant hand, time between injury and first visit, and injury mechanism), subluxation, fragment size, treatment, and time from injury to final evaluation between the 2 groups. Results: Mallet fractures of the thumb presented for treatment sooner after injury (2.9 vs 13 days on average), had less fragment displacement (27% vs 33%), and less articular involvement (39% vs 46% on average). None of the mallet fractures of the thumb had radiographic evidence of subluxation, whereas 25% of mallet fractures of other fingers had initial or later subluxation. Conclusions: Mallet fractures of the thumb are not likely to subluxate.

Surgical site infections are one of the more common major complications of elbow fracture surgery and can contribute to other adverse outcomes, prolonged hospital stays, and increased healthcare costs. We asked: (1) What are the factors associated with a surgical site infection after elbow fracture surgery? (2) When taking the subset of closed elbow fractures only, what are the factors associated with a surgical site infection? (3) What are the common organisms isolated from an elbow infection after open treatment? One thousand three hundred twenty adult patients underwent surgery for an elbow fracture between January 2002 and July 2014 and were included in our study. Forty-eight of 1320 patients (4%) had a surgical site infection develop. Thirty-four of 1113 patients with a closed fracture (3%) had a surgical site infection develop. For all elbow fractures, use of plate and screw fixation (adjusted odds ratio [OR]= 2.2; 95% CI, 1.0–4.5; p = 0.041) and use of external fixation before surgery (adjusted OR = 4.7; 95% CI, 1.1–21; p = 0.035) were associated with higher infection rates. When subset analysis was performed for closed fractures, only smoking (adjusted OR = 2.2; 95% CI, 1.1–4.5; p = 0.023) was associated with higher infection rates. Staphylococcus aureus was the most common bacteria cultured (59%). The only modifiable risk factor for a surgical site infection after open reduction and internal fixation was cigarette smoking. Plate fixation and temporary external fixation are likely surrogates for more complex injuries, therefore no recommendations should be inferred from this association. Surgeons should counsel patients who smoke. Level IV, prognostic study.

Allogeneic blood transfusions have an immunomodulating effect, and the previous studies in other fields of medicine demonstrated an increased risk of infections after administration of allogeneic blood transfusions.Our primary null hypothesis is that exposure to allogeneic blood transfusion in patients undergoing lumbar spine surgery is not associated with postoperative infections after controlling for patient and treatment characteristics. Second, we assessed if there was a dose-response relationship per unit of blood transfused.This is a retrospective cohort study from a tertiary care spine referral center.A total of 3,721 patients underwent laminectomy and/or arthrodesis of the lumbar spine.Postoperative infections, pneumonia, endocarditis, meningitis, urinary tract infection, central venous line infection, surgical site infection, and sepsis, within 90 days after lumbar spine surgery were included.Multivariable logistic regression analyses were used to assess the relationship of perioperative allogeneic blood transfusion with specific and overall postoperative infections accounting for age, duration of surgery, duration of hospital stay, comorbidity status, preoperative hemoglobin, sex, type of operation, multilevel treatment, operative approach, and year of surgery.The adjusted odds ratio for exposure to allogeneic blood transfusion from multivariable logistic regression analysis was 2.6 for any postoperative infection (95% confidence interval [CI]: 1.7-3.9, p.001); 2.2 for urinary tract infections (95% CI: 1.3-3.9, p=.004); 2.3 for pneumonia (95% CI: 0.96-5.3, p=.062); and 2.6 for surgical site infection requiring incision and drainage (95% CI: 1.3-5.3, p=.007). Secondary analyses demonstrated no dose-response relationship between the number of blood units transfused and any of the postoperative infections. Because of the low number of endocarditis (1 case, 0.031%), meningitis (1 case, 0.031%), central venous line infection (1 case, 0.031%), and sepsis (14 cases, 0.43%), we abstained from multivariable analysis.Conscious of the limitations of this retrospective study, our data suggest an increased risk of surgical site infection, urinary tract infection, and overall postoperative infections, but not pneumonia, after exposure to allogeneic blood transfusion in patients undergoing lumbar spine surgery. These findings should be taken into account when considering blood transfusion and developing transfusion policies for patients undergoing lumbar spine procedures.

Background Orthopaedic surgical site infections (SSIs) can delay recovery, add impairments, and decrease quality of life, particularly in patients undergoing spine surgery, in whom SSIs may also be more common. Efforts to prevent and treat SSIs of the spine rely on the identification and registration of these adverse events in large databases. The effective use of these databases to answer clinical questions depends on how the conditions in question, such as infection, are defined in the databases queried, but the degree to which different definitions of infection might cause different risk factors to be identified by those databases has not been evaluated.

Analysis of the genome sequence ofPseudomonas aeruginosaPA14 revealed the presence of an operon encoding an ABC-type transporter (NppA1A2BCD) showing homology to the Yej transporter ofEscherichia coli. The Yej transporter is involved in the uptake of the peptide-nucleotide antibiotic microcin C, a translation inhibitor that targets the enzyme aspartyl-tRNA synthetase. Furthermore, it was recently shown that the Opp transporter fromP. aeruginosaPAO1, which is identical to Npp, is required for uptake of the uridyl peptide antibiotic pacidamycin, which targets the enzyme translocase I (MraY), which is involved in peptidoglycan synthesis. We used several approaches to further explore the substrate specificity of the Npp transporter. Assays of growth in defined minimal medium containing peptides of various lengths and amino acid compositions as sole nitrogen sources, as well as Biolog Phenotype MicroArrays, showed that the Npp transporter is not required for di-, tri-, and oligopeptide uptake. Overexpression of thenppoperon increased susceptibility not just to pacidamycin but also to nickel chloride and the peptidyl nucleoside antibiotic blasticidin S. Furthermore, heterologous expression of thenppoperon in ayej-deficient mutant ofE. coliresulted in increased susceptibility to albomycin, a naturally occurring sideromycin with a peptidyl nucleoside antibiotic. Additionally, heterologous expression showed that microcin C is recognized by theP. aeruginosaNpp system. Overall, these results suggest that the NppA1A2BCD transporter is involved in the uptake of peptidyl nucleoside antibiotics byP. aeruginosaPA14.IMPORTANCEOne of the world's most serious health problems is the rise of antibiotic-resistant bacteria. There is a desperate need to find novel antibiotic therapeutics that either act on new biological targets or are able to bypass known resistance mechanisms. Bacterial ABC transporters play an important role in nutrient uptake from the environment. These uptake systems could also be exploited by a Trojan horse strategy to facilitate the transport of antibiotics into bacterial cells. Several natural antibiotics mimic substrates of peptide uptake routes. In this study, we analyzed an ABC transporter involved in the uptake of nucleoside peptidyl antibiotics. Our data might help to design drug conjugates that may hijack this uptake system to gain access to cells.

The outer membrane of Gram-negative bacteria presents an efficient barrier to the permeation of antimicrobial molecules. One strategy pursued to circumvent this obstacle is to hijack transport systems for essential nutrients, such as iron. BAL30072 and MC-1 are two monobactams conjugated to a dihydroxypyridone siderophore that are active against Pseudomonas aeruginosa and Acinetobacter baumannii . Here, we investigated the mechanism of action of these molecules in A. baumannii . We identified two novel TonB-dependent receptors, termed Ab -PiuA and Ab -PirA, that are required for the antimicrobial activity of both agents. Deletion of either piuA or pirA in A. baumannii resulted in 4- to 8-fold-decreased susceptibility, while their overexpression in the heterologous host P. aeruginosa increased susceptibility to the two siderophore-drug conjugates by 4- to 32-fold. The crystal structures of PiuA and PirA from A. baumannii and their orthologues from P. aeruginosa were determined. The structures revealed similar architectures; however, structural differences between PirA and PiuA point to potential differences between their cognate siderophore ligands. Spontaneous mutants, selected upon exposure to BAL30072, harbored frameshift mutations in either the ExbD3 or the TonB3 protein of A. baumannii , forming the cytoplasmic-membrane complex providing the energy for the siderophore translocation process. The results of this study provide insight for the rational design of novel siderophore-drug conjugates against problematic Gram-negative pathogens.

The β-lactam antibiotic temocillin (6-α-methoxy-ticarcillin) shows stability to most extended spectrum β-lactamases, but is considered inactive against Pseudomonas aeruginosa. Mutations in the MexAB-OprM efflux system, naturally occurring in cystic fibrosis (CF) isolates, have been previously shown to reverse this intrinsic resistance. In the present study, we measured temocillin activity in a large collection (n = 333) of P. aeruginosa CF isolates. 29% of the isolates had MICs ≤ 16 mg/L (proposed clinical breakpoint for temocillin). Mutations were observed in mexA or mexB in isolates for which temocillin MIC was ≤512 mg/L (nucleotide insertions or deletions, premature termination, tandem repeat, nonstop, and missense mutations). A correlation was observed between temocillin MICs and efflux rate of N-phenyl-1-naphthylamine (MexAB-OprM fluorescent substrate) and extracellular exopolysaccharide abundance (contributing to a mucoid phenotype). OpdK or OpdF anion-specific porins expression decreased temocillin MIC by ∼1 two-fold dilution only. Contrarily to the common assumption that temocillin is inactive on P. aeruginosa, we show here clinically-exploitable MICs on a non-negligible proportion of CF isolates, explained by a wide diversity of mutations in mexA and/or mexB. In a broader context, this work contributes to increase our understanding of MexAB-OprM functionality and help delineating how antibiotics interact with MexA and MexB., SCOPUS: ar.j, info:eu-repo/semantics/published

© 2017 Elamin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. For clinicians, Pseudomonas aeruginosa is a nightmare pathogen that is one of the top three causes of opportunistic human infections. Therapy of P. aeruginosa infections is complicated due to its natural high intrinsic resistance to antibiotics. Active efflux and decreased uptake of drugs due to cell wall/membrane permeability appear to be important issues in the acquired antibiotic tolerance mechanisms. Bacterial cell wall biosynthesis enzymes have been shown to be essential for pathogenicity of Gram-negative bacteria. However, the role of these targets in virulence has not been identified in P. aeruginosa. Here, we report knockout (k.o) mutants of six cell wall biosynthesis targets (murA, PA4450; murD, PA4414; murF, PA4416; ppiB, PA1793; rmlA, PA5163; waaA, PA4988) in P. aeruginosa PAO1, and characterized these in order to find out whether these genes and their products contribute to pathogenicity and virulence of P. aeruginosa. Except waaA k.o, deletion of cell wall biosynthesis targets significantly reduced growth rate in minimal medium compared to the parent strain. The k.o mutants showed exciting changes in cell morphology and colonial architectures. Remarkably, ΔmurF cells became grossly enlarged. Moreover, the mutants were also attenuated in vivo in a mouse infection model except ΔmurF and ΔwaaA and proved to be more sensitive to macrophage-mediated killing than the wild-type strain. Interestingly, the deletion of the murA gene resulted in loss of virulence activity in mice, and the virulence was restored in a plant model by unknown mechanism. This study demonstrates that cell wall targets contribute significantly to intracellular survival, in vivo growth, and pathogenesis of P. aeruginosa. In conclusion, these findings establish a link between cell wall targets and virulence of P. aeruginosa and thus may lead to development of novel drugs for the treatment of P. aeruginosa infection.

Radiographs and medical record of all adult patients with a mallet fracture in three hospitals between 2004 and 2014 were reviewed. International Classification of Diseases, Ninth Revision (ICD-9) codes and text search in radiographic reports were used to identify all acute patients with potential mallet fractures in our institutional database. Manually checking, 392 true mallet fractures were identified among them, 78 had subluxation at the time of diagnosis and 19 had subluxation at a later time point during treatment. Fragment size, fragment displacement, and interval between injury and treatment were associated with initial and late subluxation. Subluxation was not observed when the fracture size was less than 39% of the total articular surface. For each 1% increase in total articular surface involvement in fractures with more than 39% involvement, the risk of subluxation increased by 4% and for each 1% of displacement, the risk of subluxation increased by 4%.Level of Evidence: IV

Background: Variation in pain intensity and magnitude of disability among patients with musculoskeletal illness is largely accounted for by variations in symptoms of depression, catastrophic thinking, and heightened illness concern. It is possible that patients with greater stress, distress, and less effective coping strategies might be more likely to seek the use of Complementary Health Approaches (CHA). This study addressed the primary null hypothesis that there are no demographic, illness-related, or psychological factors associated with CHA use among patients with upper extremity illness. Methods: A cohort of 170 patients completed a web-based Complementary and Alternative Medicine (CAM) questionnaire the Patient Reported Outcomes Measurement Information System (PROMIS) Depression and Pain Interference questionnaires. We evaluated differences between patients who sought CAM treatment regarding the PROMIS Pain Interference and PROMIS Depression scores. Ninety-four patients (56%) use or plan to use CAM treatment. A CAM provider was consulted by 61 patients (37%): most commonly a massage therapist (30/61), chiropractor (26/61), or acupuncturist (14/61). Results: In bivariate analysis patients who sought CAM reported greater average PROMIS Pain Interference than those who did not. In multivariable logistic regression, CAM use was associated with a higher Pain Interference Score and the specific surgeon. Conclusion: In conclusion, CHA use is prevalent amongst orthopaedic patients and associated with less effective coping strategies. Orthopaedic surgeons might consider asking patients about CHA use and determining whether those patients are interested in cognitive behavioral therapy.

Little is known about factors related to patient satisfaction with treatment for trigger digits. This study tested the null hypothesis that there are no factors associated with treatment satisfaction 2 months after completion of treatment (absence of triggering) or 4 months after the last visit for patients with a trigger thumb or finger. Secondary null hypotheses were: 1) There are no factors associated with a change in patients' preferred treatment before and after consultation with a hand surgeon; and 2) Initial treatment provided is not different from final received treatment. In an observational study, 63 English-speaking adult patients were enrolled after being diagnosed with one or more new idiopathic trigger digits by one of two hand surgeons, but before the hand surgeon discussed treatment options. Patients were asked to fill out questionnaires at enrollment. Final evaluation was by phone. Satisfaction with treatment was not related to the initial treatment or other patient or disease factors. Twenty-three patients (37 %) had a different preference for treatment after talking with a hand surgeon. Involvement of the long and ring fingers were the only factors associated with staying with pre-visit treatment preferences. There was a significant difference in proportions of the various treatments provided at enrollment and final treatment recorded at the final phone evaluation, 14 patients (22 %) had a subsequent alternative form of treatment. Patients' preferences for trigger finger treatment often change after consulting with a hand surgeon and during treatment, but these choices do not affect treatment satisfaction.

Gene silencing of Lyc e 1 leads to reduced allergenicity of tomato fruits but impaired growth of transgenic tomato plants. The aim of the study was to restore growth of Lyc e 1-deficient tomato plants while retaining reduced allergenicity by simultaneous complementation of profilin deficiency by expression of nonallergenic yeast profilin. Transgenic plants were generated and tested by RT-PCR and immunoblotting; allergenicity of yeast profilin and transgenic fruits was investigated by IgE binding, basophil activation, and skin-prick tests. Lyc e 1 content of transgenic tomato fruits was

Several plant pathogenic bacteria belonging to the species Pseudomonas syringae produce the phytotoxin coronatine to enhance their virulence. Pseudomonas syringae pv. glycinea PG4180 synthesizes coronatine at the virulence-promoting temperature of 18 degrees C, but not at 28 degrees C, its optimal growth temperature. In contrast, temperature has virtually no effect on coronatine synthesis in P. syringae pv. tomato strain DC3000. A modified two-component system controlling coronatine synthesis and consisting of the histidine protein kinase (HPK), CorS, the response regulator, CorR, and a third essential component, CorP, had been identified previously in both strains. CorS had been identified previously as a potential thermo-sensor. Comparison of the amino acid sequences of the HPKs from the two organisms revealed distinct differences. Site-directed mutagenesis of CorS from PG4180 was used to identify amino acyl residues potentially important for temperature signal perception. Point mutations and combinations of these were introduced into corS of PG4180 to generate corS variants with increased similarities to the respective allele from strain DC3000. These mutations resulted in either loss of activity, increase of thermoresponsiveness, or had no effect on CorS activity. Although none of the introduced mutations resulted in a clear conversion of CorS activity from thermo-responsive to temperature-independent, amino acyl residues important for temperature-dependent CorS activity and coronatine biosynthesis were identified.

Decreased drug accumulation is a common cause of antibiotic resistance in microorganisms. However, there are few reliable general techniques capable of quantifying drug uptake through bacterial membranes. We present a semiquantitative optofluidic assay for studying the uptake of autofluorescent drug molecules in single liposomes. We studied the effect of the Escherichia coli outer membrane channel OmpF on the accumulation of the fluoroquinolone antibiotic, norfloxacin, in proteoliposomes. Measurements were performed at pH 5 and pH 7, corresponding to two different charge states of norfloxacin that bacteria are likely to encounter in the human gastrointestinal tract. At both pH values, the porins significantly enhance drug permeation across the proteoliposome membranes. At pH 5, where norfloxacin permeability across pure phospholipid membranes is low, the porins increase drug permeability by 50-fold on average. We estimate a flux of about 10 norfloxacin molecules per second per OmpF trimer in the presence of a 1 mM concentration gradient of norfloxacin. We also performed single channel electrophysiology measurements and found that the application of transmembrane voltages causes an electric field driven uptake in addition to concentration driven diffusion. We use our results to propose a physical mechanism for the pH mediated change in bacterial susceptibility to fluoroquinolone antibiotics.

Prospective cohort study.Some third-party payers require hand therapists to rate patient's functional disability based on patient self-rating using patient-reported outcome measures (PROMs), objective measurements of impairment, and observation of functional tasks-hand therapist-rated function (HTRF).To test the correlation between HTRF and PROMs (upper limb functional index [ULFI] and Patient-Reported Outcomes Measurement Information System upper extremity [PROMIS UE]) and its association with psychological factors.In 2014, 100 new patients with upper extremity illness presenting to hand therapists were asked to participate in an observational cross-sectional study. Demographic-, condition-related, and psychological factors were obtained in addition to PROMs and HTRF.HTRF correlated moderately with PROMIS UE (r = -0.49, P.001) and ULFI (r = -0.56, P.001). Correlation between PROMIS UE and ULFI was strong (r = 0.78, P.001). Psychological factors explained most of the variations in both HTRF and PROMs.Hand therapists' ratings of patient function correlate less strongly with PROMs than PROMs correlate with one other. The discrepancy between HTRF and PROMs may offer an opportunity to address stress, distress, or ineffective coping strategies that can interfere with recovery-an opportunity for therapists and patients to collaborate and develop goals and for future research to develop effective and feasible strategies for hand therapists.Level II, diagnostic study.

Surgical resection is the only curative treatment for pancreatic neuroendocrine tumors (PNETs), but pancreatic operations carry a significant morbidity. We investigated whether the resection of small, asymptomatic nonfunctioning PNETs is beneficial. Clinicopathologic factors were retrospectively reviewed for all PNET cases from 1998 to 2014.Kaplan-Meier survival and multivariable regression analyses were performed. A total of 249 patients had nonfunctioning PNETs with adequate follow-up, of whom 193 were resected and 56 were observed. Median age was 56 years, and 48 % of the patients were female.Overall, the resected patients had a significantly longer survival (OS) (p = 0.001). However, for the patients with PNETs ≤2.5 cm in size and without metastasis at presentation, tumor size significantly modified the effect of resection on overall survival (p 0.05). The protective effect of resection increased as tumor size increased. An operation became a significant predictor of overall survival for tumors1.5 cm (p = 0.050 or less for larger tumors) but was not significant for tumors1.5 cm (p = 0.317 or more for smaller tumors), controlling for age-adjusted Charlson comorbidity index.Resection of nonfunctioning PNETs over 1.5 cm is independently and significantly associated with a longer survival. However, the benefit of resection for tumors under 1.5 cm is unclear.

Surgery for fixation of olecranon fractures is associated with reoperation, mostly for implant removal. A study of a large cohort of patients treated by many different surgeons allows us to determine if specific techniques or implants are associated with a higher rate of reoperation. After open reduction and internal fixation of isolated olecranon fractures, what factors are associated with (1) reoperation and (2) implant removal? Three hundred ninety-two adult patients who had operative treatment of a displaced olecranon fracture not associated with other fractures, dislocation, or subluxation at two area hospitals between January 2002 and May 2014 were analyzed to determine factors associated with reoperation. One hundred thirty-eight (35%) patients had plate and screw fixation and 254 (65%) tension band wiring. Nearly 100% of patients with displaced olecranon fractures are currently treated operatively at our hospitals. All patients were followed for at least four months. Two hundred three of the 392 (52%) patients were followed for one year or more. Ninety-nine patients (25%) had a second operation, 92 (93%) at least in part for implant removal (12 for wire migration [3% of all fractures, 12% of reoperations]). We considered patient-related, fracture-related, and implant-related endpoints as possible factors associated with reoperation. With a total sample size of 99 reoperations, an α of 0.05, and an effect size of 0.3, we had 87% power. Reoperation was less common in men (36 [36%], women: 63 [64%]; adjusted odds ratio, 0.32; 95% confidence interval, 0.18–0.56; p < 0.001) and older patients (adjusted odds ratio, 0.75; 95% confidence interval, 0.65–0.87; p < 0.001). Similarly, request for implant removal was less in men (33 [36%], women: 59 [64%], adjusted odds ratio, 0.31; 95% confidence interval, 0.18–0.56; p < 0.001) and older patients (adjusted odds ratio, 0.75; 95% confidence interval, 0.65–0.87; p < 0.001). Patients who have operative fixation of a fracture of the olecranon can be counseled that most patients keep their implants, that only 3% experience implant migration, and that technical factors such as the type or configuration of an implant seem less important than personal factors in determining who requests a second surgery for implant removal. Level III, prognostic study.

Purpose To identify factors associated with reoperation for early loosening or breakage of implants or nonunion after operative treatment of AO type C distal humerus fractures. Methods We retrospectively analyzed 129 adult patients who had operative treatment of an isolated AO type C distal humerus fracture at 1 of 5 hospitals to determine factors associated with reoperation for early loosening or breakage of implants or nonunion. Results Within 6 months of original fixation, 16 of 129 fractures (12%) required reoperation for loosening or breakage of implants (n = 8) or nonunion (n = 8). In bivariate analyses, the Charlson comorbidity index, smoking, a coded diagnosis of obesity, diabetes mellitus, and radiographic osteoarthritis were significantly associated with reoperation for early loosening or breakage of implants or nonunion. Conclusions With the numbers available, patient factors rather than technical factors were associated with reoperation for loosening or breakage of implants and nonunion. Because of the relative infrequency of fixation problems and nonunion, a much larger study is needed to address technical deficiencies. Type of study/level of evidence Therapeutic IV.

Foreword Leila Harris 1. Introduction: Towards a feminist political ecology of women, global change and vulnerable waterscapes Anne-Marie Hanson and Stephanie Buechler Part 1: Feminist Political Ecology and Large-scale Water Resource Management 2. Interrogating Large-scale Development and Inequality in Lesotho: Bridging Feminist Political Ecology, Intersectionality and Environmental Justice Frameworks Yvonne Braun 3. The Silent (and Gendered) Violence: Understanding Water Access in Mining Areas Kuntala Lahiri-Dutt 4. Urban Water Visibility in Los Angeles: Legibility and Access for all Kathleen Kambic 5. Advances and Setbacks in Women's Participation in Water Management in Brazil Andrea Moraes Part 2: Women and Innovative Adaptations to Global Environmental Change 6. Climate-water Challenges and Gendered Adaptation Strategies in Rayon, a Riparian Community in Sonora, Mexico Stephanie Buechler 7. International Partnerships of Women for Sustainable Watershed Governance in Times of Climate Change Patricia E. (Ellie) Perkins and Patricia Figuieredo Walker 8. Women's Contributions to Climate Change Adaptation in Egypt's Mubarak Resettlement Scheme through Cactus Cultivation and Adjusted Irrigation Dina Najjar Part 3: Stories, Narratives and Knowledge Production of Socio-Environmental Change 9. Shoes in the Seaweed and Bottles on the Beach: Global Garbage and Women's Oral Histories of Socio-Environmental Change in Coastal Yucatan Anne-Marie Hanson 10. Heen Kas' el'ti Zoo: Among the Ragged Lakes - Storytelling and Collaborative Water Research with Carcross/Tagish First Nation (Yukon Territory, Canada) Eleanor Hayman with Mark Wedge and Colleen James 11. Pamiri Women and the Melting Glaciers of Tajikistan: A Visual Knowledge Exchange for Improved Environmental Governance Citt Williams and Ivan Golovnev 12. Conclusion: Advancing Multi-Disciplinary Scholarship on Gender, Water and Environmental Change through Feminist Political Ecology Stephanie Buechler, Anne-Marie Hanson, Diana Liverman and Miriam Gay-Antaki

Introduction. Chondrosarcomas are malignant bone tumors that are characterized by the production of chondroid tissue. Since radiation therapy and chemotherapy have limited effect on chondrosarcoma, treatment of most patients depends on surgical resection. We conducted this study to identify independent predictive factors and survival characteristics for conventional central chondrosarcoma and dedifferentiated central chondrosarcoma.Methods. A systematic literature review was performed in September 2014 using the Pubmed, Embase, and Cochrane databases. Subsequent to a beforehand-composed selection procedure we included 13 studies, comprising a total of 1114 patients.Results. The prognosis of central chondrosarcoma is generally good for the histologically low-grade tumors. Prognosis for the high-grade chondrosarcoma and the dedifferentiated chondrosarcoma is poor with lower survival rates. Poor prognostic factors in conventional chondrosarcoma for overall survival are high-grade tumors and axial/pelvic tumor location. In dedifferentiated chondrosarcoma the percentage of dedifferentiated component has significant influence on disease-free survival.Conclusion. Despite the fact that there are multiple prognostic factors identified, as shown in this study, there is a need for prospective and comparative studies. The resulting knowledge about prognostic factors and survival can give direction in the development of better therapies. This could eventually lead to an evidence-based foundation for treating chondrosarcoma patients.

Telomerase activity (TA) has been shown to correlate with poor clinical outcome in various tumour entities, indicating that tumours expressing this enzyme may be more aggressive and that TA may be a useful prognostic marker. For breast cancer, however, TA is a controversial prognostic marker; whereas some studies suggest an association between TA and disease outcome, others do not find this association. This study used tissue microarrays (breast carcinoma prognosis arrays) containing 611 samples (each 0.6 mm in diameter) from the tumour centre of paraffin-embedded breast carcinomas to analyse the catalytic subunit of telomerase, human telomerase reverse-transcriptase (hTERT), and the internal RNA component (hTR), which are the core components of the telomerase holoenzyme complex. hTERT protein expression was obtained by immunohistochemistry (human anti-telomerase antibody Ab-2, Calbiochem), and hTR RNA was measured by radioactive in situ hybridization. hTERT and hTR expression were determined semi-quantitatively and graded (scores 1-4). Clinical data, such as histological subtype, pT stage, tumour diameter, pN stage, BRE grade, tumour-specific survival (in months), patient's age and others, were available for statistical analysis. A statistically significant correlation was found between tumour-specific survival (overall survival) and hTERT expression (p < 0.0001) or hTR expression (p = 0.00110). Tumours with higher scores (scores 3, 4) for hTR and/or hTERT were associated with a worse prognosis. In multivariate analysis, hTERT expression was an independent prognostic factor. Previous studies, focusing on analysis of TA in smaller numbers of fresh-frozen breast carcinomas by the TRAP assay, gave controversial results with respect to TA as a prognostic marker. Using tissue microarrays from 611 breast carcinomas, this study has demonstrated that increased expression levels of the telomerase core components, hTERT and hTR, are associated with lower overall survival. These findings suggest that TA should be included in future validation studies as a prognostic marker in breast cancer.

The MyHealthAvatar (MHA) is an EC FP7 project aimed to focus on research and demonstration actions, through which the achievability of an innovative representation of the health status of citizens is explored. The aim of MHA survey was to enhance our understanding of patient and public views about the MHA platform. First, we investigated the background (sociodemographic characteristics) of our respondents, their understating of the basic terms like EHR and PHR. Second, we addressed complex questions about the expected and proposed for implementation MHA platform's functionalities and of special interest were the questions about the security and privacy concerns the end users might have. In general terms the survey allowed us to examine individuals' specific hopes and concerns about MHA platform and now we have a deeper understanding of patient and public views about further MHA platform's functionalities.

Previous studies have shown that perioperative blood transfusion increases cancer recurrence and decreases patient survival after resection of primary malignancies. The question arises whether this association also exists in patients with already disseminated disease undergoing surgery for metastatic long-bone fractures.We sought to determine whether perioperative allogeneic blood transfusion is associated with decreased survival after operative treatment of long-bone metastatic fractures after accounting for clinical, laboratory, and treatment factors. Secondarily, we aimed to identify potential factors that are associated with decreased survival.We included 789 patients in our retrospective study who underwent surgery at two institutions for a pathologic or impending metastatic long-bone fracture. We used multivariable Cox proportional hazards regression model analysis to assess the relationship of perioperative allogeneic blood transfusion with survival, and accounted for patient age, sex, comorbidities, BMI, tumor type, fracture type and location, presence of other bone and visceral metastases, previous radiotherapy and systemic therapy, preoperative embolization, preoperative hemoglobin level, treatment type, anesthesia time, blood loss, duration of hospital admission, year of surgery, and hospital.Considering transfusion as an "exposure," and comparing patients who received transfusions with those who did not, we found that blood transfusion was not associated with decreased survival after accounting for all explanatory variables (hazard ratio [HR] 1.06; 95% CI, 0.87-1.30; p = 0.57). Evaluating transfusion in terms of dose-response, we found that patients who received more transfusions had lower survival compared with those who had fewer transfusions after accounting for all explanatory variables (HR per unit of blood transfused, 1.07; 95% CI, 1.02-1.12; p = 0.005). We found that age (HR, 1.02; 95% CI, 1.01-1.02; p 0.001), comorbidity status (HR, 1.06; 95% CI, 1.01-1.10; p = 0.014), duration of hospital stay (HR, 1.02; 95% CI 1.00-1.03; p = 0.021), tumor type (HR, 1.71; 95% CI, 1.44-2.03; p 0.001), and visceral metastases (HR, 1.59; 95% CI, 1.34-1.88; p 0.001) were independently associated with survival.We found that exposure to perioperative allogeneic blood transfusion does not decrease survival, with the numbers available. However, our sample size might have been insufficient to reveal a small but potentially relevant effect. Our results do suggest a dose-response relationship; patients who received more transfusions had lower survival compared with those with fewer transfusions. Risk of death increased by 7% per unit of blood transfused.Level III, prognostic study.

In this study, we show that the dppBCDF operon of Pseudomonas aeruginosa PA14 encodes an ABC transporter responsible for the utilization of di/tripeptides. The substrate specificity of ABC transporters is determined by its associated substrate-binding proteins (SBPs). Whereas in E. coli only one protein, DppA, determines the specificity of the transporter, five orthologous SBPs, DppA1-A5 are present in P. aeruginosa. Multiple SBPs might broaden the substrate specificity by increasing the transporter capacity. We utilized the Biolog phenotype MicroArray technology to investigate utilization of di/tripeptides in mutants lacking either the transport machinery or all of the five SBPs. This high-throughput method enabled us to screen hundreds of dipeptides with various side-chains, and subsequently, to determine the substrate profile of the dipeptide permease. The substrate spectrum of the SBPs was elucidated by complementation of a penta mutant, deficient of all five SBPs, with plasmids carrying individual SBPs. It became apparent that some dipeptides were utilized with different affinity for each SBP. We found that DppA2 shows the highest flexibility on substrate recognition and that DppA2 and DppA4 have a higher tendency to utilize tripeptides. DppA5 was not able to complement the penta mutant under our screening conditions. Phaseolotoxin, a toxic tripeptide inhibiting the enzyme ornithine carbamoyltransferase, is also transported into P. aeruginosa via the DppBCDF permease. The SBP DppA1, and with much greater extend DppA3, are responsible for delivering the toxin to the permease. Our results provide a first overview of the substrate pattern of the ABC dipeptide transport machinery in P. aeruginosa.