Tree species traits but not diversity mitigate stem breakage in a subtropical forest following a rare and extreme ice storm

Peer reviewedPublisher PD

Insight into human alveolar macrophage and M. tuberculosis interactions via metabolic reconstructions

A human alveolar macrophage genome-scale metabolic reconstruction was reconstructed from tailoring a global human metabolic network, Recon 1, by using computational algorithms and manual curation.A genome-scale host–pathogen network of the human alveolar macrophage and Mycobacterium tuberculosis is presented. This involved integrating two genome-scale network reconstructions.The reaction activity and gene essentiality predictions of the host–pathogen model represent a more accurate depiction of infection.Integration of high-throughput data into a host-pathogen model followed by systems analysis was performed in order to elucidate major metabolic differences under different types of M. tuberculosis infection

Age-adjusted Charlson comorbidity index in recurrent glioblastoma: a new prognostic factor?

BACKGROUND: For recurrent glioblastoma (GB) patients, several therapy options have been established over the last years such as more aggressive surgery, re-irradiation or chemotherapy. Age and the Karnofsky Performance Status Scale (KPSS) are used to make decisions for these patients as these are established as prognostic factors in the initial diagnosis of GB. This study’s aim was to evaluate preoperative patient comorbidities by using the age-adjusted Charlson Comorbidity Index (ACCI) as a prognostic factor for recurrent GB patients. METHODS: In this retrospective analysis we could include 123 patients with surgery for primary recurrence of GB from January 2007 until December 2016 (43 females, 80 males, mean age 57 years (range 21–80 years)). Preoperative age, sex, ACCI, KPSS and adjuvant treatment regimes were recorded for each patient. Extent of resection (EOR) was recorded as a complete/incomplete resection of the contrast-enhancing tumor part. RESULTS: Median overall survival (OS) was 9.0 months (95% CI 7.1–10.9 months) after first re-resection. Preoperative KPSS > 80% (P < 0.001) and EOR (P = 0.013) were associated with significantly improved survival in univariate analysis. Including these factors in multivariate analysis, preoperative KPSS < 80 (HR 2.002 [95% CI: 1.246–3.216], P = 0.004) and EOR are the only significant prognostic factor (HR 1.611 [95% CI: 1.036–2.505], P = 0.034). ACCI was not shown as a prognostic factor in univariate and multivariate analyses. CONCLUSION: For patients with surgery for recurrent glioblastoma, the ACCI does not add further information about patient’s prognosis besides the well-established KPSS and extent of resection

Safe Brain Tumor Resection Does not Depend on Surgery Alone - Role of Hemodynamics

Aim of this study was to determine if perioperative hemodynamics have an impact on perioperative infarct volume and patients' prognosis. 201 cases with surgery for a newly diagnosed or recurrent glioblastoma were retrospectively analyzed. Clinical data and perioperative hemodynamic parameters, blood tests and time of surgery were recorded. Postoperative infarct volume was quantitatively assessed by semiautomatic segmentation. Mean diastolic blood pressure (dBP) during surgery (rho -0.239, 95% CI -0.11 - -0.367, p = 0.017), liquid balance (rho 0.236, 95% CI 0.1-0.373, p = 0.017) and mean arterial pressure (MAP) during surgery (rho -0.206, 95% CI -0.07 - -0.34, p = 0.041) showed significant correlation to infarct volume. A rank regression model including also age and recurrent surgery as possible confounders revealed mean intraoperative dBP, liquid balance and length of surgery as independent factors for infarct volume. Univariate survival analysis showed mean intraoperative dBP and MAP as significant prognostic factors, length of surgery also remained as significant prognostic factor in a multivariate model. Perioperative close anesthesiologic monitoring of blood pressure and liquid balance is of high significance during brain tumor surgery and should be performed to prevent or minimize perioperative infarctions and to prolong survival

Prognostic value of tumour volume in patients with a poor Karnofsky performance status scale – a bicentric retrospective study

Backround: Median overall survival (OS) after diagnosis of glioblastoma (GBM) remains 15 months amongst patients receiving aggressive surgical resection, chemotherapy and irradiation. Treatment of patients with a poor preoperative Karnofsky Performance Status Scale (KPSS) is still controversial. Therefore, we retrospectively assessed the outcome after surgical treatment in patients with a KPSS of ≤60%. Methods: We retrospectively included patients with a de-novo glioblastoma WHO °IV and preoperative KPSS ≤60%, who underwent surgery at two neurosurgical centres between September 2006 and March 2016. We recorded pre- and postoperative tumour volume, pre- and postoperative KPSS, OS, age and MGMT promoter status. Results: One hundred twenty-three patients (58 females/65 males, mean age 67.4 ± 13.4 years) met the inclusion criteria. Seventy-five of the 123 patients (61%) underwent surgical resection. 48/123 patients (39%) received a biopsy. The median preoperative and postoperative tumour volume of all patients was 33.0 ± 31.3 cm3 (IR 15.0–56.5cm3) and 3.1 ± 23.8 cm3 (IR 0.2–15.0 cm3), respectively. The median KPSS was 60% (range 20–60%) preoperatively and 50% (range 0–80%) postoperatively. Patients who received a biopsy showed a median OS for patients who received a biopsy only was 3.0 months (95% CI 2.0–4.0 months), compared to patients who had a resection and had a median OS of 8 months (95% CI 3.1–12.9 months). Age (p &lt; 0.001, HR: 1.045 [95% CI 1.022–1.068]), postoperative tumour volume (p = 0.02, HR: 1.016 [95% CI 1.002–1.029]) and MGMT promotor status (p = 0.016, HR: 0.473 [95% CI 0.257–0.871]) were statistically significant in multivariate analysis. In subgroup analyses only age was shown as a significant prognostic factor in multivariate analyses for patients receiving surgery (p &lt; 0.001, HR: 1.046 [95% CI 1.022–1.072]). In the biopsy group no significant prognostic factors were shown in multivariate analysis. Conclusion: GBM patients with a preoperative KPSS of ≤60% might profit from surgical reduction of tumour burden

Human neutrophil clearance of bacterial pathogens triggers anti-microbial gamma delta T cell responses in early infection

Human blood Vc9/Vd2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vc9/Vd2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vc9/Vd2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-c and tumor necrosis factor (TNF)-a. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vc9/Vd2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-a dependent proliferation of Vc9/Vd2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting cd T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vc9/Vd2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The cd T celldriven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of cd T cells and TNF-a and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive cd T cells in early infection and suggest novel diagnostic and therapeutic approaches.Martin S. Davey, Chan-Yu Lin, Gareth W. Roberts, Sinéad Heuston, Amanda C. Brown, James A. Chess, Mark A. Toleman, Cormac G.M. Gahan, Colin Hill, Tanya Parish, John D. Williams, Simon J. Davies, David W. Johnson, Nicholas Topley, Bernhard Moser and Matthias Eber

Characterization of the binding sites of the anticancer ruthenium(III) complexes KP1019 and KP1339 on human serum albumin via competition studies

Indazolium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (KP1019) and its Na+ analogue (KP1339) are two of the most prominent non-platinum antitumor metal complexes currently undergoing clinical trials. After intravenous administration, they are known to bind to human serum albumin (HSA) in a noncovalent manner. To elucidate their HSA binding sites, displacement reactions with the established site markers warfarin and dansylglycine as well as bilirubin were monitored by spectrofluorimetry, ultrafiltration-UV-vis spectrophotometry, and/or capillary zone electrophoresis. Conditional stability constants for the binding of KP1019 and KP1339 to sites I and II of HSA were determined, indicating that both Ru(III) compounds bind to both sites with moderately strong affinity (log K (1)' = 5.3-5.8). No preference for either binding site was found, and similar results were obtained for both metal complexes, demonstrating low influence of the counter ion on the binding event

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Millicurrent stimulation of human articular chondrocytes cultivated in a collagen type-I gel and of human osteochondral explants

<p>Abstract</p> <p>Background</p> <p>Here we investigate the effect of millicurrent treatment on human chondrocytes cultivated in a collagen gel matrix and on human osteochondral explants.</p> <p>Methods</p> <p>Human chondrocytes from osteoarthritic knee joints were enzymatically released and transferred into a collagen type-I gel. Osteochondral explants and cell-seeded gel samples were cultivated in-vitro for three weeks. Samples of the verum groups were stimulated every two days by millicurrent treatment (3 mA, sinusoidal signal of 312 Hz amplitude modulated by two super-imposed signals of 0.28 Hz), while control samples remained unaffected. After recovery, collagen type-I, type-II, aggrecan, interleukin-1β, IL-6, TNFα and MMP13 were examined by immunohistochemistry and by real time PCR.</p> <p>Results</p> <p>With regard to the immunostainings 3 D gel samples and osteochondral explants did not show any differences between treatment and control group. The expression of all investigated genes of the 3 D gel samples was elevated following millicurrent treatment. While osteochondral explant gene expression of col-I, col-II and Il-1β was nearly unaffected, aggrecan gene expression was elevated. Following millicurrent treatment, IL-6, TNFα, and MMP13 gene expression decreased. In general, the standard deviations of the gene expression data were high, resulting in rarely significant results.</p> <p>Conclusions</p> <p>We conclude that millicurrent stimulation of human osteoarthritic chondrocytes cultivated in a 3 D collagen gel and of osteochondral explants directly influences cell metabolism.</p