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T cells engineered to express chimeric-antigen receptors (CAR-T cells) can effectively control relapsed and refractory haematological malignancies in the clinic. However, the successes of CAR-T cell therapy have not been recapitulated in solid tumours due to a range of barriers such as immunosuppression, poor infiltration, and tumour heterogeneity. Numerous strategies are being developed to overcome these barriers, which include improving culture conditions and manufacturing protocols, implementing novel CAR designs, and novel approaches to engineering the T cell phenotype. In this review, we describe the various emerging strategies to improve CAR T cell therapy for solid tumours. We specifically focus on new strategies to modulate cell function and fate that have precipitated from the growing knowledge of transcriptional circuits driving T cell differentiation, with the ultimate goal of driving more productive anti-tumour T cell immunity. Evidence shows that enrichment of particular phenotypic subsets of T cells in the initial cell product correlates to improved therapeutic responses and clinical outcomes. Furthermore, T cell exhaustion and poor persistence are major factors limiting therapeutic efficacy. The latest preclinical work shows that targeting specific master regulators and transcription factors can overcome these key barriers, resulting in superior T cell therapeutic products. This can be achieved by targeting key transcriptional circuits promoting memory-like phenotypes or sustaining key effector functions within the hostile tumour microenvironment. Additional discussion points include emerging considerations for the field such as (i) targeting permutations of transcription factors, (ii) transient expression systems, (iii) tissue specificity, and (iv) expanding this strategy beyond CAR-T cell therapy and cancer.

Abstract Background Vascular adverse events after collagenase injection for Dupuytren disease are absent in large trials and systematic reviews. The aim of this study is to present a case series of delayed vascular complications after collagenase treatment. Methods A prospective evaluation of 1181 consecutively treated patients at one orthopedic department identified three patients reporting symptoms of possible vascular complication. Baseline demographics and description of symptoms were collected, with a physical examination documenting extension deficit and neurovascular status. All patients completed the Cold Intolerance Symptom Severity (CISS) scale (range 4-100, lower is better) and underwent Doppler sonography examination of the digital arteries. Results All patients were treated in the small finger and two had an isolated proximal interphalangeal joint contracture. All patients had a delayed presentation of a few months, with episodes of white discoloration of the treated finger relieved within 30 min and associated with variable pain, paresthesia, stiffness and weakness. Two of the patients reported cold exposure as an episode trigger and had a pathological CISS score (40 and 36, respectively). Doppler sonography identified a nonpatent ulnar digital artery in one patient. Conclusions Delayed vascular complication after collagenase treatment is rare, but surgeons and patients should be aware of the risk, especially when treating the small finger.

Oral biofilms, comprising hundreds of bacteria and other microorganisms on oral mucosal and dental surfaces, play a central role in oral health and disease dynamics. Streptococcus oralis, a key constituent of these biofilms, contributes significantly to the formation of which, serving as an early colonizer and microcolony scaffold. The interaction between S. oralis and the orally predominant mucin, MUC5B, is pivotal in biofilm development, yet the mechanism underlying MUC5B degradation remains poorly understood. This study introduces MdpS (Mucin Degrading Protease from Streptococcus oralis), a protease that extensively hydrolyses MUC5B and offers an insight into its evolutionary conservation, physicochemical properties, and substrate- and amino acid specificity. MdpS exhibits high sequence conservation within the species and also explicitly among early biofilm colonizing streptococci. It is a calcium or magnesium dependent serine protease with strict physicochemical preferences, including narrow pH and temperature tolerance, and high sensitivity to increasing concentrations of sodium chloride and reducing agents. Furthermore, MdpS primarily hydrolyzes proteins with O-glycans, but also shows activity toward immunoglobulins IgA1/2 and IgM, suggesting potential immunomodulatory effects. Significantly, MdpS extensively degrades MUC5B in the N- and C-terminal domains, emphasizing its role in mucin degradation, with implications for carbon and nitrogen sequestration for S. oralis or oral biofilm cross-feeding. Moreover, depending on substrate glycosylation, the amino acids serine, threonine or cysteine triggers the enzymatic action. Understanding the interplay between S. oralis and MUC5B, facilitated by MdpS, has significant implications for the management of a healthy eubiotic oral microenvironment, offering potential targets for interventions aimed at modulating oral biofilm composition and succession. Additionally, since MdpS does not rely on O-glycan removal prior to extensive peptide backbone hydrolysis, the MdpS data challenges the current model of MUC5B degradation. These findings emphasize the necessity for further research in this field.

Abstract Background The use of complementary and alternative medicine (CAM) by patients is widespread. However, there is a lack of knowledge regarding the extent and details of patient CAM use in Sweden, especially in rural Sweden. The aim of this study was to estimate the extent and characteristics of CAM use among cancer patients in Region Gävleborg. Methods A total of 631 questionnaires were distributed to which 376 responses were registered, yielding a response rate of 59.6%. Questionnaires were distributed to oncology patients at their first visit for curative treatment at the Department of Oncology, Gävle Hospital. Palliative patients were recruited at their first visit and during enrollment in palliative outpatient care in their own homes. The characteristics of the respondents were presented with standard descriptive statistics. A multivariable logistic model was fitted to calculate odds ratios (ORs) and identify potential predictors (Age, Gender, Education, Diagnosis) of CAM use post-cancer diagnosis. Results 54% of all participants reported lifetime CAM use, 34% reported CAM use post-diagnosis. The most common CAM methods used after diagnosis are vitamins, health food preparations, herbal teas, prayer and dietary methods. The most common source of information reported is family and friends. Almost 70% of those who used CAM after their diagnosis stated that they did not discuss their use with healthcare professionals. Most patients reported that they would like some CAM modalities to be offered within conventional care regardless of their own CAM use. Conclusions The use of CAM is common among patients with cancer in the region of Gävleborg, and previous studies show a similar use in Sweden in general. Based on the widespread use of CAM and patient interest in discussing CAM use with healthcare professionals, greater attention and focus should be placed on creating a basis for this dialogue. If we, as healthcare professionals, are to emphasise our commitment to providing patient-centred care, we must acknowledge that patients use CAM and are seeking a dialogue about CAM use in their care.

IntroductionThe glycosylation of immunoglobulin (Ig) G regulates IgG interaction capability with Fc gamma receptors found in all immune cells. In pathogenic conditions, estrogen can impact IgG levels and glycosylation. Following menopause, when estrogen levels decline affecting the immune system and potentially leading to a heightened susceptibility of immune activation.PurposeIn this study, we aim to determine if estrogen levels can regulate IgG glycosylation in postmenopausal healthy situations.MethodsMice were ovariectomized to simulate an estrogen-deficient postmenopausal status and then treated with 17-beta-estradiol (E2) at different doses and different administration strategies.ResultsUsing a highly sensitive liquid chromatography-tandem mass spectrometry (MS/MS) glycoproteomic method, we demonstrated that E2 treatment increased the degree of glycosylation on IgG-Fc with both galactosylation and sialylation in the position required for interaction with Fc gamma receptors. We also observed that only long-term estrogen deficiency reduces IgG levels and that estrogen status had no impact on total IgG sialylation on both Fab and Fc domains or general glycoprotein sialylation evaluated by ELISA. Furthermore, E2 status did not affect the total sialic acid content of total cells in lymphoid organs and neither B cells nor plasma cells.ConclusionThe study concluded that E2 treatment does not affect total serum glycoprotein sialylation but alters IgG glycosylation, including IgG sialylation, implying that estrogen functions as an intrinsic modulator of IgG sialylation and could thereby be one pathway by which estrogen modulates immunity.

Abstract Background Acute hypoxemic respiratory failure (AHRF) is a leading concern in critically ill patients. Experimental and clinical data suggest that early sedation with volatile anesthestics may improve arterial oxygenation and reduce the plasma and alveolar levels of markers of alveolar epithelial injury and of proinflammatory cytokines. Methods An a priori hypothesis substudy of a multicenter randomized controlled trial (The Sedaconda trial, EUDRA CT Number 2016-004551-67). In the Sedaconda trial, 301 patients on invasive mechanical ventilation were randomized to 48 h of sedation with isoflurane or propofol in a 1:1 ratio. For the present substudy, patients with a ratio of arterial pressure of oxygen (PaO2) to inspired fraction of oxygen (FiO2), PaO2/FiO2, of ≤ 300 mmHg at baseline were included (n = 162). The primary endpoint was the change in PaO2/FiO2 between baseline and the end of study sedation. A subgroup analysis in patients with PaO2/FiO2 ≤ 200 mmHg was performed (n = 82). Results Between baseline and the end of study sedation (48 h), oxygenation improved to a similar extent in the isoflurane vs. the propofol group (isoflurane: 199 ± 58 to 219 ± 76 mmHg (n = 70), propofol: 202 ± 62 to 236 ± 77 mmHg (n = 89); p = 0.185). On day seven after randomization, PaO2/FiO2 was 210 ± 79 mmHg in the isoflurane group (n = 41) and 185 ± 87 mmHg in the propofol group (n = 44; p = 0.411). In the subgroup of patients with PaO2/FiO2 ≤ 200 mmHg, PaO2/FiO2 increase between baseline and end of study sedation was 152 ± 33 to 186 ± 54 mmHg for isoflurane (n = 37), and 150 ± 38 to 214 ± 85 mmHg for propofol (n = 45; p = 0.029). On day seven, PaO2/FiO2 was 198 ± 69 mmHg in patients randomized to isoflurane (n = 20) and 174 ± 106 mmHg in patients randomized to propofol (n = 20; p = 0.933). Both for the whole study population and for the subgroup with PaO2/FiO2 ≤ 200 mmHg, no significant between-group differences were observed for PaCO2, pH and tidal volume as well as 30-day mortality and ventilator-free days alive. Conclusions In patients with AHRF, inhaled sedation with isoflurane for a duration of up to 48 h did not lead to improved oxygenation in comparison to intravenous sedation with propofol. Trial registration The main study was registered in the European Medicines Agency’s EU Clinical Trial register (EudraCT), 2016-004551-67, before including the first patient. The present substudy was registered at German Clinical Trials Register (DRKS, ID: DRKS00018959) on January 7th, 2020, before opening the main study data base and obtaining access to study results.

Abstract The spondylodysplastic type of Ehlers–Danlos syndrome (spEDS) is caused by genetic defects in the B4GALT7 or B3GALT6 genes both deranging the biosynthesis of the glycosaminoglycan linkage region of chondroitin/dermatan sulfate and heparan sulfate proteoglycans. In this study, we have analyzed the linkage regions of urinary chondroitin sulfate proteoglycans of three siblings, diagnosed with spEDS and carrying biallelic pathogenic variants of the B3GALT6 gene. Proteoglycans were digested with trypsin, glycopeptides enriched on anion‐exchange columns, depolymerized with chondroitinase ABC, and analyzed by nLC‐MS/MS. In urine of the unaffected mother, the dominating glycopeptide of bikunin/protein AMBP appeared as only one dominating (99.9%) peak with the canonical tetrasaccharide linkage region modification. In contrast, the samples of the three affected siblings contained two different glycopeptide peaks, corresponding to the canonical tetrasaccharide and to the non‐canonical trisaccharide linkage region modifications in individual ratios of 61/38, 73/27, and 59/41. We propose that the relative distribution of glycosaminoglycan linkage regions of urinary bikunin glycopeptides may serve as a phenotypic biomarker in a diagnostic test but also as a biomarker to follow the effect of future therapies in affected individuals.

We conducted a long-term inventory of the herpetofauna of Wildsumaco Wildlife Sanctuary in the eastern part of the Napo Province in Ecuador. This private preserve is about 500 ha in size and is located on the southern slopes of Volcán Sumaco. The preserve contains primary forest, secondary forest, and pasture habitats. Based mostly on nocturnal transect sampling we documented 39 species of amphibians including one species of salamander, two species of caecilians, and 36 species of frogs. Rain frogs (Pristimantis Jiminez de la Espada, 1871) were diverse with 14 species documented. A diverse species assemblage of 45 reptile species was also documented on the preserve. Six amphibian species found were listed by the IUCN Red List. At least three species exhibited substantial geographic range extensions and seven species showed elevational range extensions. We discovered several undescribed species including one salamander, three frogs, one lizard, and one snake.

Abstract Background An important aspect of end-of-life care is the place of death. A majority of cancer patients prefer home death to hospital death. At the same time, the actual location of death is often against patient’s last-known wish. The aim of this study was to analyze whether socioeconomic factors influence if Swedish palliative cancer patients die at home or at a hospital. There is no previous study on location of death encompassing several years in Swedish cancer patients. Methods Data was collected from the Swedish Register of Palliative Care for patients diagnosed with brain tumor, lung, colorectal, prostate or breast cancer recorded between 2011 and 2014. The data was linked to the Swedish Cancer Register, the Cause of Death Register and the Longitudinal Integration Database for health-insurance and labor-market studies. A total of 8990 patients were included. Results We found that marital status was the factor that seemed to affect the place of death. Lack of a partner, compared to being married, was associated with a higher likelihood of dying at a hospital. Conclusion Our findings are in line with similar earlier studies encompassing only 1 year and based on patients in other countries. Whether inequalities at least partly explain the differences remains to be investigated. Patients dying of cancer in Sweden, who do not have a life partner, may not have the option of dying at home due to lack of informal support. Perhaps the need of extensive community support services to enable home death have to improve, and further studies are warranted to answer this question.

La cordillera del Kutukú está ubicada al sureste de Ecuador y se encuentra parcialmente aislada de la cordillera de los Andes. Realizamos cinco expediciones a este macizo, donde obtuvimos de manera directa información referente a la riqueza de aves. Además, con el fin de generar un listado más completo, realizamos una recopilación de registros publicados y revisamos colecciones de museos ecuatorianos. En total registramos 501 especies de aves, en un rango entre 500 – 2300 m de altitud. Encontramos trece especies con nuevas ampliaciones de distribución altitudinal y/o latitudinal. Veintiséis especies de aves (5.2%) están en alguna categoría de amenaza a su conservación, a nivel mundial y nacional. Las escasas vías de acceso, sumadas a las políticas de ingreso al territorio, por parte de la etnia Shuar, han favorecido la preservación de los bosques, especialmente aquellos por encima de los 1800 m. Es así que, el conocimiento biológico de esta área queda aún por descubrir. Esta zona remota protege una importante diversidad, así como poblaciones de aves amenazadas, recursos hídricos, además del territorio y cultura de las comunidades que la habitan. Desafortunadamente la totalidad de la cordillera se encuentra concesionada para exploraciones de proyectos mineros. Por tanto, se requiere la atención de las autoridades regionales y nacionales para aunar esfuerzos que aseguren su conservación y exploración biológica.

ObjectivesTo investigate the cost-effectiveness of abatacept (ABA) as first-line (1L) therapy in Japanese rheumatoid arthritis (RA) patients using data from the Institute of Rheumatology, Rheumatoid Arthritis database.MethodsA decision-analytic model was used to estimate the cost per American College of Rheumatology response of at least 50% improvement (ACR50) responder and per patient in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) remission from a Japanese healthcare payers' perspective over a 2-year time horizon. Clinical characteristics of patients on ABA-1L were matched with those of patients on ABA second or later line (2L+) or tumour necrosis factor inhibitor (TNFi)-1L directly or using propensity scores. Resource utilisation and medical costs were calculated from the Japan Medical Data Center claims database. Parameter uncertainty was addressed by sensitivity and subgroup analyses (age, treatment duration, Japanese version of Health Assessment Questionnaire [J-HAQ] score).ResultsIncremental costs per member per month (ΔPMPM) for ABA-1L versus TNFi-1L and ABA-2L+ were -1,571 Japanese Yen (JPY) and 81 JPY, respectively. For ABA-1L versus TNFi-1L, ΔPMPM by ACR50 response was -11,715 JPY and by CDAI and SDAI remission 11,602 JPY and 47,003 JPY, respectively. Corresponding costs for ABA-1L were lower for all outcome parameters versus those for ABA-2L+. Scenario analyses showed that ABA-1L was cost-effective over TNFi-1L in patients ConclusionsABA-1L demonstrated a favourable cost-effectiveness profile in RA patients, accruing savings for the Japanese healthcare payers.

Chondroitin sulfate proteoglycans (CSPGs) are found at cell surfaces and in connective tissues, where they interact with a multitude of proteins involved in various pathophysiological processes. From a methodological perspective, the identification of CSPGs is challenging, as the identification requires the combined sequencing of specific core proteins, together with the characterization of the CS polysaccharide modification(s). According to the current notion of CSPGs, they are often considered in relation to a functional role in which a given proteoglycan regulates a specific function in cellular physiology. Recent advances in glycoproteomic methods have, however, enabled the identification of numerous novel chondroitin sulfate core proteins, and their glycosaminoglycan attachment sites, in humans and in various animal models. In addition, these methods have revealed unexpected structural complexity even in the linkage regions. These findings indicate that the number and structural complexity of CSPGs are much greater than previously perceived. In light of these findings, the prospect of finding additional CSPGs, using improved methods for structural and functional characterizations, and studying novel sample matrices in humans and in animal models is discussed. Further, as many of the novel CSPGs are found in low abundance and with not yet assigned functions, these findings may challenge the traditional notion of defining proteoglycans. Therefore, the concept of proteoglycans is considered, discussing whether “a proteoglycan” should be defined mainly on the basis of an assigned function or on the structural evidence of its existence.

Abstract Background Our aim was to compare CT images from native, nephrographic and excretory phases using image quality criteria as well as the detection of positive pathological findings in CT Urography, to explore if the radiation burden to the younger group of patients or patients with negative outcomes can be reduced. Methods This is a retrospective study of 40 patients who underwent a CT Urography examination on a 192-slice dual source scanner. Image quality was assessed for four specific renal image criteria from the European guidelines, together with pathological assessment in three categories: renal, other abdominal, and incidental findings without clinical significance. Each phase was assessed individually by three radiologists with varying experience using a graded scale. Certainty scores were derived based on the graded assessments. Statistical analysis was performed using visual grading regression (VGR). The limit for significance was set at p = 0.05. Results For visual reproduction of the renal parenchyma and renal arteries, the image quality was judged better for the nephrogram phase (p

Background: Isolated limb perfusion (ILP) is a treatment option for unresectable in-transit melanoma metastases of the extremities. Approximately two-thirds of the patients have a complete response, and known predictive factors mainly regard tumor burden. In an attempt to identify subgroups with higher response rates, we retrospectively analyzed the predictive value of the BRAF V600E/K mutation for response at our institution. Methods: Between January 2012 and December 2017, 98 consecutive patients underwent first-time ILP with melphalan for melanoma in-transit metastases and were included in the study. Data was retrieved from our prospectively kept database. Tumor burden was assessed preoperatively as number of lesions and largest tumor diameter. BRAF status was determined according to clinical routine. Response rates were classified according to WHO criteria. Results: Of the 98 patients included in the analysis, 32 patients had a BRAF V600E/K mutation (33%) and 66 patients were BRAF wild type (wt). There was no difference in age, sex or tumor burden between the groups. Comparing response between BRAF V600E/K mutation and BRAF wt, the overall response rate was 69% vs. 77% (p=.36) and the complete response rate was 47% vs. 52% (p=.67). There was no difference in survival, with a median survival of 47 months. Conclusion: In this consecutive series of patients, BRAF V600E/K mutation was not found to be a significant factor for response or survival following ILP.

The Sda histo-blood group antigen (GalNAcβ1-4(NeuAcα2-3)Galβ-R) is implicated in various infections and constitutes a potential biomarker for colon cancer. Sd(a−) individuals (2–4% of Europeans) may produce anti-Sda, which can lead to incompatible blood transfusions, especially if donors with the high-expressing Sd(a++)/Cad phenotype are involved. We previously reported the association of B4GALNT2 mutations with Sd(a−), which established the SID blood-group system. The present study provides causal proof underpinning this correlation. Sd(a−) HEK293 cells were transfected with different B4GALNT2 constructs and evaluated by immunostaining and glycoproteomics. The predominant SIDnull candidate allele with rs7224888:T>C (p.Cys406Arg) abolished Sda synthesis, while this antigen was detectable as N- or O-glycans on glycoproteins following transfection of wildtype B4GALNT2. Surprisingly, two rare missense variants, rs148441237:A>G and rs61743617:C>T, found in a Sd(a−) compound heterozygote, gave results similar to wildtype. To elucidate on whether Sd(a++)/Cad also depends on B4GALNT2 alterations, this gene was sequenced in five individuals. No Cad-specific changes were identified, but a detailed erythroid Cad glycoprotein profile was obtained, especially for glycophorin-A (GLPA) O-glycosylation, equilibrative nucleoside transporter 1 (S29A1) O-glycosylation, and band 3 anion transport protein (B3AT) N-glycosylation. In conclusion, the p.Cys406Arg β4GalNAc-T2 variant causes Sda-deficiency in humans, while the enigmatic Cad phenotype remains unresolved, albeit further characterized.

Vitamin B1 (thiamin) deficiency is an issue periodically affecting a wide range of taxa worldwide. In aquatic pelagic systems, thiamin is mainly produced by bacteria and phytoplankton and is transferred to fish and birds via zooplankton, but there is no general consensus on when or why this transfer is disrupted. We focus on the occurrence in salmon (Salmo salar) of a thiamin deficiency syndrome (M74), the incidence of which is highly correlated among populations derived from different spawning rivers. Here, we show that M74 in salmon is associated with certain large-scale abiotic changes in the main common feeding area of salmon in the southern Baltic Sea. Years with high M74 incidence were characterized by stagnant periods with relatively low salinity and phosphate and silicate concentrations but high total nitrogen. Consequently, there were major changes in phytoplankton and zooplankton, with, e.g., increased abundances of Cryptophyceae, Dinophyceae, Diatomophyceae and Euglenophyceae and Acartia spp. during high M74 incidence years. The prey fish communities also had increased stocks of both herring and sprat in these years. Overall, this suggests important changes in the entire food web structure and nutritional pathways in the common feeding period during high M74 incidence years. Previous research has emphasized the importance of the abundance of planktivorous fish for the occurrence of M74. By using this 27-year time series, we expand this analysis to the entire ecosystem and discuss potential mechanisms inducing thiamin deficiency in salmon.

We assessed the impact of new antineoplastic agents on the overall survival (OS) of advanced non-small cell lung cancer (aNSCLC) patients followed up until 2012. Multivariate regression models were run for OS (outcome) and four proxies for innovation (exposure): Index (InnovInd, for SEER-Research data 1973-2012) and three levels of aggregation of Mean Medication Vintage, i.e. Overall (MMVOverall), using data aggregated at the State Level (MMVState), and using patient-level data (MMVPatient) using data from the US captured in SEER-Medicare 1991-2012. We derived Hazard ratios (HR) from Royston-Parmar models and odds ratios (OR) from a logistic regression on 1-year OS. Including 164,704 patients (median age 72 years, 56.8% stage IV, 61.8% with no comorbidities, 37.8% with adenocarcinoma, 22.9% with squamous-cell, 6.1% were censored). One-year OS improved from 0.22 in 1973 to 0.39 in 2012, in correlation with InnovInd (r = 0.97). Ten new NSCLC drugs were approved and 28 more used off-label. Regression-models results indicate that therapeutic innovation only marginally reduced the risk of dying (HROverall = 0.98 [0.98-0.98], HRMMV-Patient = 0.98 [0.97-0.98], and HRMMV-State = 0.98 [0.98-0.98], and slightly improved 1-year survival (ORMMV-Overall = 1.05 95%CI [1.04-1.05]). These results were validated with data from the Swedish National Health Data registers. Until 2013, aNSCLC patients were treated undifferentiated and the introduction of innovative therapies had statistically significant, albeit modest, effects on survival. Most treatments used off-guidelines highlight the high unmet need; however new advancements in treatment may further improve survival.

Abstract Background Chronic low back pain is a common health problem for adult workers and causes an enormous economic burden. With the improvement of minimally invasive surgical techniques (MIS) in spinal fusion and the development of fusion devices, more lumbar operations are today being performed through a less invasive technique. When compared with open surgeries (OS), MIS has demonstrated better clinical outcomes including operation time, blood loss, complication rates and length of hospital stay. The aim of this review was to identify and summarize evidence on the time to return to work and the duration of post-operation narcotic use for patients who had lumbar spinal fusion operations using MIS and OS techniques. Methods A systematic literature review was performed including studies identified from PubMed, EMBASE, the Cochrane Collaboration, and the Centre for Review and Dissemination (CRD) (January 2004–April 2014) for publications reporting on time to return to work and post-operation narcotic use after MIS or OS lumbar spinal fusion surgeries. Results Out of a total of 36 included studies, 28 reported on the time to return to work and 17 on the narcotic use after MIS or OS. Four studies described the time to return to work directly comparing MIS and OS. Three studies, from the US, directly compared the duration of narcotic use between MIS- transforaminal lumbar interbody fusion (TLIF) and OS-TLIF. In addition to the time to return to work, 23 studies reported on the rate of return to work and the employment rate before and after surgery, and two Swedish studies presented sick leave data. Conclusions There is a gap of good quality data describing the time to return to work and narcotic use after lumbar spinal fusion operations using MIS or OS techniques. However, the current systematic literature review indicates that patients who have lumbar spinal fusion operations, with the MIS procedure, generally return to work after surgery more quickly and require less post-operation narcotics for pain control compared to patients who have OS.

A recombinant subunit vaccine (Shingrix®) was recently licensed for use against herpes zoster. This vaccine is based on glycoprotein E (gE) of varicella zoster virus (VZV), the most abundantly expressed protein of VZV, harboring sites for N- and O-linked glycosylation. The subunit vaccine elicits stronger virus-specific CD4+ T cell response as well as antibody B cell response to gE, compared to the currently used live attenuated vaccine (Zostavax®). This situation is at variance with the current notion since a live vaccine, causing an active virus infection, should be far more efficient than a subunit vaccine based on only one single viral glycoprotein. We previously found gE to be heavily glycosylated, not least by numerous clustered O-linked glycans, when it was produced in human fibroblasts. However, in contrast to Zostavax®, which is produced in fibroblasts, the recombinant gE of Shingrix® is expressed in Chinese hamster ovary (CHO) cells. Hence, the glycan occupancy and glycan structures of gE may differ considerably between the two vaccine types. Here, we aimed at (i) defining the glycan structures and positions of recombinant gE and (ii) identifying possible features of the recombinant gE O-glycosylation pattern contributing to the vaccine efficacy of Shingrix®. Firstly, recombinant gE produced in CHO cells (“Shingrix situation„) is more scarcely decorated by O-linked glycans than gE from human fibroblasts (“Zostavax situation„), with respect to glycan site occupancy. Secondly, screening of immunodominant B cell epitopes of gE, using a synthetic peptide library against serum samples from VZV-seropositive individuals, revealed that the O-linked glycan signature promoted binding of IgG antibodies via a decreased number of interfering O-linked glycans, but also via specific O-linked glycans enhancing antibody binding. These findings may, in part, explain the higher protective efficacy of Shingrix®, and can also be of relevance for development of subunit vaccines to other enveloped viruses.

We summarize bird species records submitted to the Committee for Ecuadorian Records in Ornithology (CERO) from July 2013 to March 2014. CERO compiles Ecuador’s official country checklist and updates it annually. We present four new country records (Amazonetta brasiliensis, Porzana albicollis, Haematopus ater, Chroicocephalus Philadelphia), one new country record that antedates earlier records (Vireo flavifrons), first voucher documentation for four species (Larus californicus, Pangara guttata, Conirostrum bicolor, Cardellina pusilla), and 26 significant range extensions or records of rare and poorly known species (Oceanodroma leucorhoa, Oceanodroma hornbyi, Sula leucogaster, Phalacrocorax bougainvillii, Butorides virescens, Ardea herodias, Egretta rufescens, Egretta caerulea, Eudocimus albus, Eudocimus ruber, Anas clypeata, Anas cyanoptera, Aythya afflnis, Gallinago delicata, Limosa fedoa, Larus delawarensis, Hydroprogne caspia, Glaucidium griseiceps, Chloroceryle aenea, Platyrinchus saturatus, Myiarchus crinitus, Tyrannus niveigularis, Knipolegus poecilurus, Doliomis remseni, Setophaga castanea, Lonchura malacca). Three records are from the Galapagos Islands (Oceanodroma leucorhoa, Butorides virescens, Egretta caerulea), while all others were obtained in mainland Ecuador. Six species are eliminated from the Ecuadorian list (Geotrygon violácea, Topaza pella, Attila bolivianos, Pachyramphus rufus, Pachyramphus validus, Lonchura atricapilla). Two additional records were postponed for further expert revision (Thalassarche cauta) or for additional evidence (Neomorphus pucheranit) and three submitted records were rejected (Patagioenas oenops, Hydropsalis maculicaudus, Colaptes rupicola). This information updates our knowledge of the distribution and status of poorly known species in Ecuador, as well as the national bird checklist that currently reaches 1673 species (1608 confirmed with voucher documentation, 65 hypothetical).

The Cks1 component of the SCF(Skp2) complex is necessary for p27(Kip1) ubiquitylation and degradation. Cks1 expression is elevated in various B cell malignancies including Burkitt lymphoma and multiple myeloma. We have previously shown that loss of Cks1 results in elevated p27(Kip1) levels and delayed tumor development in a mouse model of Myc-induced B cell lymphoma. Surprisingly, loss of Skp2 in the same mouse model also resulted in elevated p27(Kip1) levels but exhibited no impact on tumor onset. This raises the possibility that Cks1 could have other oncogenic activities than suppressing p27(Kip1). To challenge this notion we have targeted overexpression of Cks1 to B cells using a conditional retroviral bone marrow transduction-transplantation system. Despite potent ectopic overexpression, Cks1 was unable to promote B cell hyperproliferation or B cell malignancies, indicating that Cks1 is not oncogenic when overexpressed in B cells. Since Skp2 overexpression can drive T-cell tumorigenesis or other cancers we also widened the quest for oncogenic activity of Cks1 by ubiquitously expressing Cks1 in hematopoetic progenitors. At variance with c-Myc overexpression, which caused acute myeloid leukemia, Cks1 overexpression did not induce myeloproliferation or leukemia. Therefore, despite being associated with a poor prognosis in various malignancies, sole Cks1 expression is insufficient to induce lymphoma or a myeloproliferative disease in vivo.

Non-linear properties of iterative reconstruction (IR) algorithms can alter image texture. We evaluated the effect of a model-based IR algorithm (advanced modelled iterative reconstruction; ADMIRE) and dose on computed tomography thorax image quality. Dual-source scanner data were acquired at 20, 45 and 65 reference mAs in 20 patients. Images reconstructed with filtered back projection (FBP) and ADMIRE Strengths 3–5 were assessed independently by six radiologists and analysed using an ordinal logistic regression model. For all image criteria studied, the effects of tube load 20 mAs and all ADMIRE strengths were significant (p  < 0.001) when compared to reference categories 65 mAs and FBP. Increase in tube load from 45 to 65 mAs showed image quality improvement in three of six criteria. Replacing FBP with ADMIRE significantly improves perceived image quality for all criteria studied, potentially permitting a dose reduction of almost 70% without loss in image quality. [ABSTRACT FROM AUTHOR]