Advanced technique for measuring relative length changes under control of temperature and helium-gas pressure.

We report the realization of an advanced technique for measuring relative length changes ΔL/L of mm-sized samples under the control of temperature (T) and helium-gas pressure (P). The system, which is an extension of the apparatus described in the work of Manna et al. [Rev. Sci. Instrum. 83, 085111 (2012)], consists of two 4He-bath cryostats, each of which houses a pressure cell and a capacitive dilatometer. The interconnection of the pressure cells, the temperature of which can be controlled individually, opens up various modes of operation to perform measurements of ΔL/L under the variation of temperature and pressure. Special features of this apparatus include the possibility (1) to increase the pressure to values far in excess of the external pressure reservoir, (2) to substantially improve the pressure stability during temperature sweeps, (3) to enable continuous pressure sweeps with both decreasing and increasing pressure, and (4) to simultaneously measure the dielectric constant of the pressure-transmitting medium, viz., helium, εr He(T,P), along the same T-P trajectory as that used for taking the ΔL(T, P)/L data. The performance of the setup is demonstrated by measurements of relative length changes (ΔL/L)T at T = 180 K of single crystalline NaCl upon continuously varying the pressure in the range 6 ≤ P ≤ 40 MPa.

Covalent Self-Labeling of Tagged Proteins with Chemical Fluorescent Dyes in BY-2 Cells and Arabidopsis Seedlings.

Synthetic chemical fluorescent dyes promise to be useful for many applications in biology. Covalent, targeted labeling, such as with a SNAP-tag, uses synthetic dyes to label specific proteins in vivo for studying processes such as endocytosis or for imaging via super-resolution microscopy. Despite its potential, such chemical tagging has not been used effectively in plants. A major drawback has been the limited knowledge regarding cell wall and membrane permeability of the available synthetic dyes. Of 31 synthetic dyes tested here, 23 were taken up into BY-2 cells, while eight were not. This creates sets of dyes that can serve to measure endocytosis. Three of the dyes that were able to enter the cells, SNAP-tag ligands of diethylaminocoumarin, tetramethylrhodamine, and silicon-rhodamine 647, were used to SNAP-tag α-tubulin. Successful tagging was verified by live cell imaging and visualization of microtubule arrays in interphase and during mitosis in Arabidopsis (Arabidopsis thaliana) seedlings. Fluorescence activation-coupled protein labeling with DRBG-488 was used to observe PIN-FORMED2 (PIN2) endocytosis and delivery to the vacuole as well as preferential delivery of newly synthesized PIN2 to the actively forming cell plate during mitosis. Together, the data demonstrate that specific self-labeling of proteins can be used effectively in plants to study a wide variety of cellular and biological processes.

Preservation of the mesureter to reduce urinary complications: analysis of data from the observational Leipzig School MMR study.

OBJECTIVE: To evaluate the feasibility and effect of mesureteral preservation on urinary complications in the context of total mesometrial resection (TMMR), a surgical treatment for cervical cancer. DESIGN: Retrospective cohort study with historic control. SETTING: Single tertiary academic centre. POPULATION: Women older than 18 with primary cervical cancer staged FIGO IB1-IIB enrolled in the prospective Leipzig School MMR study and underwent total mesometrial resection (TMMR) without adjuvant radiation. METHOD: We retrospectively analysed 100 consecutive TMMR procedures which were performed for cancer of the uterine cervix and in which the mesureter was preserved (intervention group, 01/2014-06/2017). We compared this group with the previous 100 consecutive TMMRs, which were performed before the introduction of mesureteral preservation (control group, 09/2010-01/2014). MAIN OUTCOME MEASURES: The occurrence of urological and specifically ureteral complications. RESULTS: Mesureteral preservation was feasible and was associated with a significant decrease in ureteral complications (11% without mesureteral preservation versus 3% with mesureteral preservation, P = 0.049). Furthermore, we found a significant decrease in the number of postoperative percutaneous nephrostomies and re-operations (7% versus none, P = 0.014). There was also a trend towards a decrease in other urinary complications such as postoperative bladder atony and uretero-vaginal fistulas. CONCLUSION: The mesureter constitutes a convenient dissection plane enabling the preservation of lateral ureteral blood supply during TMMR. In our study, maintenance of mesureteral integrity was associated with a significant reduction in ureteral complications. Mesureteral preservation might also be useful in other types of pelvic surgeries that carry a high risk of ureteral damage. TWEETABLE ABSTRACT: Surgical preservation of the mesureter in cervical cancer patients was associated with a reduction in urinary complications.

Simultaneous changes in seed size, oil content and protein content driven by selection of SWEET homologues during soybean domestication.

Soybean accounts for more than half of the global production of oilseed and more than a quarter of the protein used globally for human food and animal feed. Soybean domestication involved parallel increases in seed size and oil content, and a concomitant decrease in protein content. However, science has not yet discovered whether these effects were due to selective pressure on a single gene or multiple genes. Here, re-sequencing data from >800 genotypes revealed a strong selection during soybean domestication on GmSWEET10a. The selection of GmSWEET10a conferred simultaneous increases in soybean-seed size and oil content as well as a reduction in the protein content. The result was validated using both near-isogenic lines carrying substitution of haplotype chromosomal segments and transgenic soybeans. Moreover, GmSWEET10b was found to be functionally redundant with its homologue GmSWEET10a and to be undergoing selection in current breeding, leading the the elite allele GmSWEET10b, a potential target for present-day soybean breeding. Both GmSWEET10a and GmSWEET10b were shown to transport sucrose and hexose, contributing to sugar allocation from seed coat to embryo, which consequently determines oil and protein contents and seed size in soybean. We conclude that past selection of optimal GmSWEET10a alleles drove the initial domestication of multiple soybean-seed traits and that targeted selection of the elite allele GmSWEET10b may further improve the yield and seed quality of modern soybean cultivars.

Graft Preparation with Intraoperative Vancomycin Decreases Infection After ACL Reconstruction: A Review of 1,640 Cases.

BACKGROUND: Reported infection rates following anterior cruciate ligament (ACL) reconstruction are low, but infections are associated with high morbidity including reoperations and inferior clinical outcomes. The purpose of the current study was to investigate the rate of infection after ACL reconstruction with and without graft preparation with a vancomycin irrigant. METHODS: All ACL reconstructions performed between May 2009 and August 2018 at a single academic institution were reviewed and categorized based on vancomycin use. Patients with <90-day follow-up, intraoperative graft preparation with an antibiotic other than vancomycin, or previous ipsilateral knee infection were excluded. Infection was defined as a return to the operating room for irrigation and debridement within 90 days after ACL reconstruction. Descriptive and inferential statistical analysis using t tests and Poisson regression were performed, with significance defined as p < 0.05. RESULTS: In total, 1,640 patients (952 males; 58.0%) with a mean age (and standard deviation) of 27.7 ± 11.4 years underwent ACL reconstruction (1,379 primary procedures; 84.1%) and were included for analysis. Intraoperative vancomycin was used in 798 cases (48.7%), whereas 842 ACL reconstructions (51.3%) were performed without intraoperative vancomycin. In total, 11 reconstructions (0.7%) were followed by infection, which occurred in 10 (1.2%) of the patients in whom the graft was not soaked in vancomycin and in 1 (0.1%) of the patients in whom the graft was soaked in vancomycin (p = 0.032). Age (p = 0.571), sex (p = 0.707), smoking (p = 0.407), surgeon (p = 0.124), and insurance type (p = 0.616) were not associated with postoperative infection risk. Autograft use was associated with decreased infections (p = 0.045). There was an 89.4% relative risk reduction with the use of intraoperative vancomycin. An increased body mass index (BMI) (p = 0.029), increased operative time (p = 0.001), and the absence of ACL graft preparation with vancomycin (p = 0.032) independently predicted postoperative infection. CONCLUSIONS: The use of vancomycin-soaked grafts was associated with a 10-fold reduction in infection after ACL reconstruction (0.1% versus 1.2%; p = 0.032). Other risk factors for infection after ACL reconstruction included increased BMI and increased operative time. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Critical Care of Patients After Pulmonary Thromboendarterectomy.

Pulmonary thromboendarterectomy (PTE) remains the only curative surgery for patients with chronic thromboembolic pulmonary hypertension (CTEPH). Postoperative intensive care unit care challenges providers with unique disease physiology, operative sequelae, and the potential for detrimental complications. Central concerns in patients with CTEPH immediately after PTE relate to neurologic, pulmonary, hemodynamic, and hematologic aspects. Institutional experience in critical care for the CTEPH population, a multidisciplinary team approach, patient risk assessment, and integration of current concepts in critical care determine outcomes after PTE surgery. In this review, the authors will focus on specific aspects unique to this population, with integration of current available evidence and future directions. The goal of this review is to provide the cardiac anesthesiologist and intensivist with a comprehensive understanding of postoperative physiology, potential complications, and contemporary intensive care unit management immediately after pulmonary endarterectomy.

Regional Left Ventricular Myocardial Dysfunction After Cardiac Surgery Characterized by 3-Dimensional Strain.

BACKGROUND: Three-dimensional (3D) strain is an echocardiographic modality that can characterize left ventricular (LV) function with greater accuracy than ejection fraction. While decreases in global strain have been used to predict outcomes after cardiac surgery, changes in regional 3D longitudinal, circumferential, radial, and area strain have not been well described. The primary aim of this study was to define differential patterns in regional LV dysfunction after cardiac surgery using 3D speckle tracking strain imaging. Our secondary aim was to investigate whether changes in regional strain can predict postoperative outcomes, including length of intensive care unit stay and 1-year event-free survival. METHODS: In this prospective clinical study, demographic, operative, echocardiographic, and clinical outcome data were collected on 182 patients undergoing aortic valve replacement, mitral valve repair or replacement, coronary artery bypass graft, and combined cardiac surgery. Three-dimensional transthoracic echocardiograms were performed preoperatively and on the second to fourth postoperative day. Blinded analysis was performed for LV regional longitudinal, circumferential, radial, and area strain in the 17-segment model. RESULTS: Regional 3D longitudinal, circumferential, radial, and area strains were associated with differential patterns of myocardial dysfunction, depending on the surgical procedure performed and strain measure. Patients undergoing mitral valve repair or replacement had reduced function in the majority of myocardial segments, followed by coronary artery bypass graft, while patients undergoing aortic valve replacement had reduced function localized only to apical segments. After all types of cardiac surgery, segmental function in apical segments was reduced to a greater extent as compared to basal segments. Greater decrements in regional function were seen in circumferential and area strain, while smaller decrements were observed in longitudinal strain in all surgical patients. Both preoperative regional strain and change in regional strain preoperatively to postoperatively were correlated with reduced 1-year event-free survival, while postoperative strain was not predictive of outcomes. Only preoperative strain values were predictive of intensive care unit length of stay. CONCLUSIONS: Changes in regional myocardial function, measured by 3D strain, varied by surgical procedure and strain type. Differences in regional LV function, from presurgery to postsurgery, were associated with worsened 1-year event-free survival. These findings suggest that postoperative changes in myocardial function are heterogeneous in nature, depending on the surgical procedure, and that these changes may have long-term impacts on outcome. Therefore, 3D regional strain may be used to identify patients at risk for worsened postoperative outcomes, allowing early interventions to mitigate risk.

Extravascular lung water monitoring for thoracic and lung transplant surgeries.

PURPOSE OF REVIEW: Excessive accumulation of extravascular lung water (EVLW) resulting in pulmonary edema is the most feared complication following thoracic surgery and lung transplant. ICUs have long relied on chest radiography to monitor pulmonary status postoperatively but the increasing recognition of the limitations of bedside plain films has fueled development of newer technologies, which offer earlier detection, quantitative assessments, and can aide in preoperative screening of surgical candidates. In this review, we focus on the emergence of transpulmonary thermodilution (TPTD) and lung ultrasound with a focus on the clinical integration of these modalities into current intraoperative and critical care practices. RECENT FINDINGS: Recent studies demonstrate transpulmonary thermodilution and lung ultrasound provide greater sensitivity and earlier detection of lung water accumulation and are useful to guide clinical management. Assessments from these techniques have predictive value of postoperative outcome. Further, EVLW assessment shows promise as a preoperative screening tool in lung transplant patients. SUMMARY: Monitoring EVLW in the perioperative period offers clinicians a powerful tool to guide fluid therapy and manage pulmonary edema. Both TPTD and lung ultrasound have unique attributes in the care of thoracic surgery and lung transplant patients.

[Update from France Macula Federation: Treatment of Wet AMD]. / Actualisations de la Fédération France Macula : prise en charge thérapeutique de la DMLA exsudative.

PURPOSE: To update the recommendations of the France Macula Federation for treatment of wet age-related macular degeneration (AMD). METHODS: Analysis of literature and expert opinion. RESULTS: The FFM recommends initiating anti-VEGF therapy as soon as possible after diagnosis of exudative AMD. There has been no major change in the last several years concerning the procedure of intravitreal injection itself. However, the litigious points are discussed: simultaneous bilateral injection; antibiotic therapy; medico-legal aspects. All anti-VEGF strategies possess advantages and limitations. The strategy should be left to the ophthalmologists' preference. However, the chosen strategy should be explained to patients and strictly followed. CONCLUSION: The treatment of wet-AMD is more precisely codified than before. However, various strategies still coexist.

A Phase II Study of Pembrolizumab in EGFR-Mutant, PD-L1+, Tyrosine Kinase Inhibitor Naïve Patients With Advanced NSCLC.

BACKGROUND: Despite the significant antitumor activity of pembrolizumab in NSCLC, clinical benefit has been less frequently observed in patients whose tumors harbor EGFR mutations compared to EGFR wild-type patients. Our single-center experience on the KEYNOTE-001 trial suggested that pembrolizumab-treated EGFR-mutant patients, who were tyrosine kinase inhibitor (TKI) naïve, had superior clinical outcomes to those previously treated with a TKI. As TKI naïve EGFR-mutants have generally been excluded from pembrolizumab studies, data to guide treatment decisions in this patient population is lacking, particularly in patients with programmed death ligand 1 (PD-L1) expression ≥50%. METHODS: We conducted a phase II trial (NCT02879994) of pembrolizumab in TKI naive patients with EGFR mutation-positive, advanced NSCLC and PD-L1-positive (≥1%, 22C3 antibody) tumors. Pembrolizumab was administered 200 mg every 3 weeks. The primary endpoint was objective response rate. Secondary endpoints included safety of pembrolizumab, additional pembrolizumab efficacy endpoints, and efficacy and safety of an EGFR TKI after pembrolizumab. RESULTS: Enrollment was ceased due to lack of efficacy after 11 of 25 planned patients were treated. Eighty-two percent of trial patients were treatment naïve, 64% had sensitizing EGFR mutations, and 73% had PD-L1 expression ≥50%. Only 1 patient had an objective response (9%), but repeat analysis of this patient's tumor definitively showed the original report of an EGFR mutation to be erroneous. Observed treatment-related adverse events were similar to prior experience with pembrolizumab, but two deaths within 6 months of enrollment, including one attributed to pneumonitis, were of concern. CONCLUSIONS: Pembrolizumab's lack of efficacy in TKI naïve, PD-L1+, EGFR-mutant patients with advanced NSCLC, including those with PD-L1 expression ≥50%, suggests that it is not an appropriate therapeutic choice in this setting.

Management of the Critically Ill Adult With Congenital Heart Disease.

Survival of adults with congenital heart disease (CHD) has improved significantly over the last 2 decades, leading to an increase in hospital and intensive care unit (ICU) admissions of these patients. Whereas most of the ICU admissions in the past were related to perioperative management, the incidence of medical emergencies from long-term sequelae of palliative or corrective surgical treatment of these patients is rising. Intensivists now are confronted with patients who not only have complex anatomy after congenital cardiac surgery, but also complex pathophysiology due to decades of living with abnormal cardiac anatomy and diseases of advanced age. Comorbidities affect all organ systems, including cognitive function, pulmonary and cardiovascular systems, liver, and kidneys. Critical care management requires an in-depth understanding of underlying anatomy and pathophysiology in order to apply contemporary concepts of adult ICU care to this population and optimize patient outcomes. In this review, the main CHD lesions and their common surgical management approaches are described, and the sequelae of CHD physiology are discussed. In addition, the effects of chronic comorbidities on the management of critically ill adults are explored, and the adjustments of current ICU management modalities and pharmacology to optimize care are discussed.

[Definition, diagnostics and therapy of chronic widespread pain and the (so-called) fibromyalgia syndrome in children and adolescents : Updated guidelines 2017]. / Definition, Diagnostik und Therapie von chronischen Schmerzen in mehreren Körperregionen und des (sog.) Fibromyalgiesyndroms bei Kindern und Jugendlichen : Aktualisierte Leitlinie 2017.

BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF number 145/004, was scheduled for April 2017. METHODS: The guidelines were developed by 13 scientific societies and 2 patient self-help organizations coordinated by the German Pain Society. Working groups (n = 8) with a total of 42 members were formed balanced with respect to gender, medical expertise, position in the medical or scientific hierarchy and potential conflicts of interest. A search of the literature for case series (cross-sectional- and longitudinal studies) for the topics diagnosis, etiology and pathophysiology and for randomised controlled trials (RCT) for treatment modalities from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine version 2009. The strength of recommendations was achieved by multiple step formalized procedures to reach a consensus. Efficacy, risks, patient preferences and applicability of available therapies were weighed up against each other. The guidelines were reviewed and approved by the board of directors of the societies engaged in the development of the guidelines. RESULTS AND CONCLUSION: No consensus was achieved in the guideline group on whether the diagnostic label "juvenile fibromyalgia" should be used in the management of children and adolescents with chronic widespread pain. There was consensus in the guideline group that antidepressants and anticonvulsants should not be used to treat pain in the so-called juvenile fibromyalgia syndrome.

[Complementary and alternative procedures for fibromyalgia syndrome : Updated guidelines 2017 and overview of systematic review articles]. / Komplementäre und alternative Verfahren beim Fibromyalgiesyndrom : Aktualisierte Leitlinie 2017 und Übersicht von systematischen Übersichtsarbeiten.

BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF number 145/004, was scheduled for April 2017. METHODS: The guidelines were developed by 13 scientific societies and 2 patient self-help organizations coordinated by the German Pain Society. Working groups (n =8) with a total of 42 members were formed balanced with respect to gender, medical expertise, position in the medical or scientific hierarchy and potential conflicts of interest. A search of the literature for systematic reviews of randomized controlled trials of complementary and alternative therapies from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine version 2009. The strength of recommendations was formed by multiple step formalized procedures to reach a consensus. Efficacy, risks, patient preferences and applicability of available therapies were weighed up against each other. The guidelines were reviewed and approved by the board of directors of the societies engaged in the development of the guidelines. RESULTS AND CONCLUSION: Meditative movement therapies (e.g. qi gong, tai chi and yoga) are strongly recommended. Acupuncture and weight reduction in cases of obesity can be considered.

[Multimodal therapy of fibromyalgia syndrome : Updated guidelines 2017 and overview of systematic review articles]. / Multimodale Therapie des Fibromyalgiesyndroms : Aktualisierte Leitlinie 2017 und Übersicht von systematischen Übersichtsarbeiten.

BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF number 145/004, was scheduled for April 2017. METHODS: The guidelines were developed by 13 scientific societies and 2 patient self-help organizations coordinated by the German Pain Society. Working groups (n = 8) with a total of 42 members were formed balanced with respect to gender, medical expertise, position in the medical or scientific hierarchy and potential conflicts of interest. A search of the literature for systematic reviews on randomized controlled trials of multimodal therapy from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine version 2009. The strength of recommendations was achieved by multiple step formalized procedures to reach a consensus. Efficacy, risks, patient preferences and applicability of available therapies were weighed up against each other. The guidelines were reviewed and approved by the board of directors of the societies engaged in the development of the guidelines. RESULTS AND CONCLUSION: The use of multimodal therapy (combination of aerobic exercise with at least one psychological therapy) with a duration of at least 24 h is strongly recommended for patients with severe forms of fibromyalgia.

Molecular Characterization of LjSWEET3, a Sugar Transporter in Nodules of Lotus japonicus.

Symbiotic nitrogen fixation in legumes contributes greatly to the global nitrogen cycle on the earth. In nodules, resident rhizobia supply nitrogen nutrient fixed from atmospheric N2 to the host plant; in turn, the plant provides photosynthetic metabolites to bacteroids as a carbon source. In this process, various transporters are involved at different membrane systems; however, little is known at the molecular level about the flow of carbon from the host cells to the symbiotic bacteria. We have been studying transporters functioning in nodules of Lotus japonicus, and found that out of 13 SWEET genes in the L. japonicus genome LjSWEET3, a member of the SWEET transporter family, is highly expressed in nodules. The SWEET family was first identified in Arabidopsis, where members of the family are involved in phloem loading, nectar secretion, pollen nutrition and seed filling. The expression of LjSWEET3 strongly increased during nodule development and reached the highest level in mature nodules. Histochemical analysis using L. japonicus plants transformed with LjSWEET3 promoter:GUS (ß-glucuronidase) showed strong expression in the vascular systems of nodules. Analysis of an LjSWEET3-green fluorescent protein (GFP) fusion expressed in Nicotiana banthamiana and Coptis japonica indicates that LjSWEET3 localizes to the plasma membrane. Together these data are consistent with a role for LjSWEET3 in sugar translocation towards nodules and also suggest the possible existence of multiple routes of carbon supply into nodules.

Phylogenetic evidence for a fusion of archaeal and bacterial SemiSWEETs to form eukaryotic SWEETs and identification of SWEET hexose transporters in the amphibian chytrid pathogen Batrachochytrium dendrobatidis.

SWEETs represent a new class of sugar transporters first described in plants, animals, and humans and later in prokaryotes. Plant SWEETs play key roles in phloem loading, seed filling, and nectar secretion, whereas the role of archaeal, bacterial, and animal transporters remains elusive. Structural analyses show that eukaryotic SWEETs are composed of 2 triple-helix bundles (THBs) fused via an inversion linker helix, whereas prokaryotic SemiSWEETs contain only a single THB and require homodimerization to form transport pores. This study indicates that SWEETs retained sugar transport activity in all kingdoms of life, and that SemiSWEETs are likely their ancestral units. Fusion of oligomeric subunits into single polypeptides during evolution of eukaryotes is commonly found for transporters. Phylogenetic analyses indicate that THBs of eukaryotic SWEETs may not have evolved by tandem duplication of an open reading frame, but rather originated by fusion between an archaeal and a bacterial SemiSWEET, which potentially explains the asymmetry of eukaryotic SWEETs. Moreover, despite the ancient ancestry, SWEETs had not been identified in fungi or oomycetes. Here, we report the identification of SWEETs in oomycetes as well as SWEETs and a potential SemiSWEET in primitive fungi. BdSWEET1 and BdSWEET2 from Batrachochytrium dendrobatidis, a nonhyphal zoosporic fungus that causes global decline in amphibians, showed glucose and fructose transport activities.-Hu, Y.-B., Sosso, D., Qu, X.-Q., Chen, L.-Q., Ma, L., Chermak, D., Zhang, D.-C., Frommer, W. B. Phylogenetic evidence for a fusion of archaeal and bacterial SemiSWEETs to form eukaryotic SWEETs and identification of SWEET hexose transporters in the amphibian chytrid pathogen Batrachochytrium dendrobatidis.

LINE-1 induces hTERT and ensures telomere maintenance in tumour cell lines.

A hallmark of cancer cells is an activated telomere maintenance mechanism, which allows prolonged survival of the malignant cells. In more than 80% of tumours, telomeres are elongated by the enzyme telomerase, which adds de novo telomere repeats to the ends of chromosomes. Cancer cells are also characterized by expression of active LINE-1 elements (L1s, long interspersed nuclear elements-1). L1 elements are abundant retrotransposons in the eukaryotic genome that are primarily known for facilitating aberrant recombination. Using L1-knockdown (KD), we show for the first time that L1 is critical for telomere maintenance in telomerase-positive tumour cells. The reduced length of telomeres in the L1-KD-treated cells correlated with an increased rate of telomere dysfunction foci, a reduced expression of shelterin proteins and an increased rate of anaphase bridges. The decreased telomere length was associated with a decreased telomerase activity and decreased telomerase mRNA level; the latter was increased upon L1 overexpression. L1-KD also led to a decrease in mRNA and protein expression of cMyc and KLF-4, two main transcription factors of telomerase and altered mRNA levels of other stem-cell-associated proteins such as CD44 and hMyb, as well as a corresponding reduced growth of spheroids. The KD of KLF-4 or cMyc decreased the level of L1-ORF1 mRNA, suggesting a specific reciprocal regulation with L1. Thus, our findings contribute to the understanding of L1 as a pathogenicity factor in cancer cells. As L1 is only expressed in pathophysiological conditions, L1 now appears to be target in the rational treatment of telomerase-positive cancer.

KOOS pain as a marker for significant knee pain two and six years after primary ACL reconstruction: a Multicenter Orthopaedic Outcomes Network (MOON) prospective longitudinal cohort study.

OBJECTIVE: The prevalence of radiographic osteoarthritis (OA) after anterior cruciate ligament reconstruction (ACLR) approaches 50%, yet the prevalence of significant knee pain is unknown. We applied three different models of Knee injury and Osteoarthritis Outcome Score (KOOS) thresholds for significant knee pain to an ACLR cohort to identify prevalence and risk factors. DESIGN: Multicenter Orthopaedic Outcomes Network (MOON) prospective cohort patients with a unilateral primary ACLR and normal contralateral knee were assessed at 2 and 6 years. Independent variables included patient demographics, validated Patient Reported Outcomes (PRO; Marx activity score, KOOS), and surgical characteristics. Models included: (1) KOOS criteria for a painful knee = quality of life subscale <87.5 and ≥2 of: KOOSpain <86.1, KOOSsymptoms <85.7, KOOSADL <86.8, or KOOSsports/rec <85.0; (2) KOOSpain subscale score ≤72 (≥2 standard deviations below population mean); (3) 10-point KOOSpain drop from 2 to 6 years. Proportional odds models (alpha ≤ 0.05) were used. RESULTS: 1761 patients of median age 23 years, median body mass index (BMI) 24.8 kg/m(2) and 56% male met inclusion, with 87% (1530/1761) and 86% (1506/1761) follow-up at 2 and 6 years, respectively. At 6 years, n = 592 (39%), n = 131 (9%) and n = 169 (12%) met criteria for models #1 through #3, respectively. The most consistent and strongest independent risk factor at both time-points was subsequent ipsilateral knee surgery. Low 2-year Marx activity score increased the odds of a painful knee at 6 years. CONCLUSIONS: Significant knee pain is prevalent after ACLR; with those who undergo subsequent ipsilateral surgery at greatest risk. The relationship between pain and structural OA warrants further study.

[Efficacy of epidural steroid injections for chronic lumbar pain syndromes without neurological deficits. A randomized, double blind study as part of a multimodal treatment concept]. / Wirksamkeit periduraler Steroidinjektionen in der Therapie von nichtradikulären chronischen Rückenschmerzen. Eine randomisierte, doppelverblindete Vergleichsstudie im Rahmen eines multimodalen Behandlungskonzeptes.

BACKGROUND: Chronic lumbar pain syndromes without neurological deficits are generated by a multitude of causes. Functional, morphological and psychosocial factors are discussed. In many cases a diseased intervertebral disc is found on radiological examination but the clinical relevance of these findings is not clear. For this study it was postulated that a diseased disc results in a local inflammatory reaction therefore causing pain and impairing treatability of patients. An epidural injection of steroids can reduce inflammation and therefore improve treatability and ultimately treatment outcome. METHODS: A double blind randomized prospective trial was carried out. Patients treated in hospital for a chronic lumbar pain syndrome without neurological deficits within a multimodal treatment program were screened for indications for an epidural steroid injection (e.g. diseased lumbar disc and intention to treat). Patients eligible for the study were randomized into two groups. The treatment group received an epidural injection of 80 mg triamcinolone and 8 ml bupivacaine 0.25 %. The control group received only an epidural injection of 8 ml bupivacaine 0.25 %. RESULTS: In both groups pain intensity and treatability showed a statistically significant improvement after the epidural injection. The differences between the control and treatment groups were small and not clinically relevant. A small subgroup might profit from the steroid injection. In addition the treatability was dependent on psychometric values and the long-term outcome from a reduction of muscular skeletal dysfunctions. DISCUSSION: After the epidural injection the decrease in pain and increase in treatability was statistically significant. The mechanism of the improvement is not clear and should be examined further. The epidural injection of a steroid in this subgroup of patients did not lead to a clinical improvement in the outcome.