Plio-Pleistocene changes in water mass exchange and erosional inputs in the Fram Strait

We determined the isotopic composition of neodymium (Nd) and lead (Pb) of past seawater to reconstruct water mass exchange and erosional input between the Arctic Ocean and the Norwegian-Greenland Seas over the past 5 Ma. For this purpose, sediments of ODP site 911 (leg 151) located at 900 m water depth on the Yermak Plateau in the Fram Strait were used. The paleo-seawater variability of Nd and Pb isotopes was extracted from the sea water-derived metal oxide coatings on the sediment particles following the leaching method of Gutjahr et al. (2007). All radiogenic isotope data were acquired by Multi-Collector (MC) ICP-MS. The site 911 stratigraphy of Knies et al. (2009) was applied. Surface sediment Sr and Nd isotope data, as well as downcore Sr isotope data obtained on the same leaches are close to seawater and confirm the seawater origin of the Nd and Pb isotope signatures. The deep water Nd isotope time series extracted from site 911 was in general more radiogenic ("Nd = -7.5 to -10) than present day deep water ("Nd = -9.8 to -11.8) in the area of the Fram Strait (Andersson et al., 2008) and does not show a systematic trend with time. In contrast, the radiogenic isotope composition of Pb evolved from 206Pb/204Pb ratios around 18.7 to more radiogenic values around 19.2 between 2 Ma and today. The data indicate that mixing of water masses from the Arctic Ocean and the Norwegian-Greenland Seas has controlled the Nd isotope signatures of deep waters on the Yermak Plateau over the past 5 Ma. Prior to 1.7 Ma the Nd isotope signatures on the Yermak Plateau were less radiogenic than waters from the same depth in the central Arctic Ocean (Haley et al., 2008) pointing to a greater influence from the Norwegian-Greenland Seas. After 1.7 Ma the central Arctic and Yermak Plateau data have varied around similar values indicating water mass mixing overall similar to today. In contrast, the Pb isotope composition of deep waters in the Fram Strait appears to have been dominated by weathering inputs from glacially weathering old continental landmasses, such as Greenland or parts of Svalbard since 2 Ma. A similar control over the Pb isotope evolution of seawater since the onset of Northern Hemisphere Glaciation was recorded by ferromanganese crusts that grew from North Atlantic DeepWater in the western North Atlantic. References: Gutjahr, M., Frank, M., Stirling, C.H., Klemm, V., van de Flierdt, T. and Halliday, A.N. (2007): Reliable extraction of a deepwater trace metal isotope signal from Fe-Mn oxyhydroxide coatings of marine sediments.- Chemical Geology 242, 351-370 Haley B. A., M. Frank, R.F. Spielhagen and A. Eisenhauer (2008): Influence of brine formation on Arctic Ocean circulation over the past 15 million years. Nature Geoscience 1, 68–72 Andersson, P.S., Porcelli, D., Frank, M., Björk, G., Dahlqvist, R. and Gustafsson, Ö. (2008): Neodymium isotopes in seawater from the Barents Sea and Fram Strait Arctic- Atlantic gateways.- Geochim. Cosmochim. Acta 72, 2854-2867 Knies, J., J. Matthiessen, C. Vogt, J.S. Laberg, B.O. Hjelstuen, M.Smelror, E. Larsen, K. Andreassen, T. Eidvin and T.O. Vorren (2009): The Plio-Pleistocene glaciation of the Barents Sea–Svalbard region: a new model based on revised chronostratigraphy - Quaternary Science Reviews 28, 9-10, 812-82

Management of fibromyalgia syndrome – an interdisciplinary evidence-based guideline

The prevalence of fibromyalgia syndrome (FMS) of 1–2% in the general population associated with high disease-related costs and the conflicting data on treatment effectiveness had led to the development of evidence-based guidelines designed to provide patients and physicians guidance in selecting among the alternatives. Until now no evidence-based interdisciplinary (including patients) guideline for the management of FMS was available in Europe

Evaluation of 3-(3-chloro-phenyl)-5-(4-pyridyl)-4,5-dihydroisoxazole as a Novel Anti-Inflammatory Drug Candidate

BACKGROUND: 3-(3-chloro-phenyl)-5-(4-pyridyl)-4,5-dihydroisoxazole (DIC) is a five-membered heterocyclic compound containing a N-O bond. The anti-inflammatory effects of this compound were studied both in vitro and in vivo. PRINCIPAL FINDINGS: DIC effectively decreased TNF-α and IL-6 release from LPS-stimulated macrophages in a dose dependent manner. DIC diminished the levels of COX-2 with subsequent inhibition of PGE(2) production. DIC also compromised HMGB1 translocation from the nucleus to the cytoplasm. Moreover, DIC prevented the nuclear translocation of NF-κB and inhibited the MAPK pathway. In vivo, DIC inhibited migration of neutrophils to the peritoneal cavity of mice. CONCLUSIONS: This study presents the potential utilization of a synthetic compound, as a lead for the development of novel anti-inflammatory drugs

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Efficacy of fluoride varnish for preventing white spot lesions and gingivitis during orthodontic treatment with fixed appliances—a prospective randomized controlled trial

The development of white spot lesions around orthodontic brackets and gingivitis is a common problem during orthodontic treatment with fixed appliances. This prospective randomized double-blind controlled clinical trial investigated the preventive efficacy of a one-time application of two commonly used fluoride varnishes in patients with low to moderate caries risk. Ninety adolescent orthodontic patients with a low to moderate caries risk were prospectively randomized to three groups of 30 patients each: (1) standardized dental hygiene with fluoride toothpaste and one-time application of placebo varnish (control) or (2) of elmexA (R) fluid or (3) of Fluor Protector S on all dental surfaces at the start of fixed therapy. The extent of enamel demineralization and gingivitis was determined with the ICDAS and the gingivitis index (GI) at baseline and after 4, 12, and 20 weeks. Each treatment group showed a significant increase of the ICDAS index, but not of the GI over the course of time with no significant intergroup differences detectable. A one-time application of fluoride varnish at the start of orthodontic treatment did not provide any additional preventive advantage over sufficient dental hygiene with fluoride toothpaste with regard to formation of white spots and gingivitis in patients with a low to moderate caries risk. In dental practice, patients often receive an application of fluoride varnish at the start of orthodontic treatment with fixed appliances. However, the efficacy of this procedure is still unclear

Plio-Pleistocene evolution of water mass exchange and erosional input in the Fram Strait

We determined the isotopic composition of neodymium (Nd), lead (Pb) and beryllium (Be) of past seawater to reconstruct water mass exchange and erosional input between the Arctic Ocean and the Norwegian-Greenland Seas (NGS) over the past approximately 5 Myr. For this purpose, sediments of ODP site 911 (leg 151) from 900 m water depth on Yermak Plateau in the Fram Strait were leached to extract the isotopic composition of past bottom water from early diagenetic metal oxide coatings on the sediment particles [1]. Nd isotope signatures extracted from site 911 agree well with the present day deep water &Nd signature of -11.8 ± 0.4 [2]. Overall the Nd isotope composition was more radiogenic in the core section older than 2.7 Ma (&Nd = -9 to -10) and then progressively decreased to less radiogenic values (&Nd = -11 to -12) similar to the present isotopic composition. 206Pb/204Pb ratios evolved from 18.7 to more radiogenic values around 19.2 between 2 Ma and today. The &Nd data indicate that mixing of water masses from the Arctic Ocean and the NGS has controlled the Nd isotope signatures of deep waters on the Yermak Plateau since the onset of the Northern Hemisphere Glaciation (NHG). In contrast, the 206Pb/204Pb of deep waters in the Fram Strait appears to have been dominated by glacial weathering inputs from old continental landmasses, such as Greenland or parts of Svalbard since 2 Ma. The changes in the &Nd and 206Pb/204Pb were similar to those found for the central Arctic Ocean and the North Atlantic (derived from Fe-Mn crusts). A record of cosmogenic 10Be normalized to 9Be in the same leaches shows a strikingly similar short term variability to those of &Nd and 206Pb/204Pb suggesting that all three isotope systems have been influenced by the same process controlled by the extent of continental ice sheets and the associated weathering inputs. [1] Gutjahr et al. (2007) Chemical Geology 242, 351–370. [2] Andersson et al. (2008) GCA 72, 2854–2867

The choice of cytostatic in hyperthermic isolated limb perfusion. Chemosensitivity testing on five human melanoma cell lines

Sensitivity of 5 human melanoma cell lines towards melphalan (L-PAM), dacarbazine (DIC), methotrexate (MTX), vinblastine (VBL), dactinomycin (DACT), doxorubicin (ADM), mitoxantrone (DHAQ), cisplatin (cDDP), and carboplatin (CDBCA) was tested by a standardized kinetic microassay. With respect to achievable plasma concns. in hyperthermic isolated limb perfusion VBL, DHAQ, ADM, DACT, and cDDP seem promising for further pharmacokinetically controlled in vivo-studies

The rectovaginal septum: visible on magnetic resonance images of women with Mayer-Rokitansky-Kuster-Hauser syndrome (Mullerian agenesis)

INTRODUCTION AND HYPOTHESIS: Ongoing debate exists about whether the rectovaginal septum (Denonvilliers' fascia) is myth or reality. This study evaluates magnetic resonance images (MRI) of women with Müllerian agenesis for the presence of fascial layers between the rectum and the bladder to test the hypothesis that this layer exists in the absence of the vagina. METHODS: This is a secondary analysis of a study describing MRI aspects in women with vaginal agenesis before and after laparoscopic Vecchietti procedure. Study participants (n =16) had a multiplanar pelvic MR scan. Images were evaluated independently by two investigators (MH, JOLD) for the appearance of layers separate from the bladder and rectum in the area of interest, with characteristic anatomical features of the septum. RESULTS: Participants' mean age was 19.4±2.6 years ± standard deviation (SD). In 12 of 16 patients (75 %) a distinct layer between rectum and bladder was identified in either the axial (4/16; 25 %) or sagittal (12/16; 75 %) scan or both. Characteristic anatomical features included lateral attachment to the levator ani muscle, cranial fusion to the cul-de-sac peritoneum, and caudal insertion into the perineal body. CONCLUSIONS: Three quarters of women with Müllerian agenesis have a visible layer between bladder and rectum. As none of the participants had a vagina, these results support the existence of a rectovaginal septum, separate from a vaginal adventitia

Risk factors for severe outcomes following 2009 influenza A (H1N1) infection: a global pooled analysis

Background Since the start of the 2009 influenza A pandemic (H1N1pdm), the World Health Organization and its member states have gathered information to characterize the clinical severity of H1N1pdm infection and to assist policy makers to determine risk groups for targeted control measures. Methods and Findings Data were collected on approximately 70,000 laboratory-confirmed hospitalized H1N1pdm patients, 9,700 patients admitted to intensive care units (ICUs), and 2,500 deaths reported between 1 April 2009 and 1 January 2010 from 19 countries or administrative regions—Argentina, Australia, Canada, Chile, China, France, Germany, Hong Kong SAR, Japan, Madagascar, Mexico, the Netherlands, New Zealand, Singapore, South Africa, Spain, Thailand, the United States, and the United Kingdom—to characterize and compare the distribution of risk factors among H1N1pdm patients at three levels of severity: hospitalizations, ICU admissions, and deaths. The median age of patients increased with severity of disease. The highest per capita risk of hospitalization was among patients <5 y and 5–14 y (relative risk [RR] = 3.3 and 3.2, respectively, compared to the general population), whereas the highest risk of death per capita was in the age groups 50–64 y and ≥65 y (RR = 1.5 and 1.6, respectively, compared to the general population). Similarly, the ratio of H1N1pdm deaths to hospitalizations increased with age and was the highest in the ≥65-y-old age group, indicating that while infection rates have been observed to be very low in the oldest age group, risk of death in those over the age of 64 y who became infected was higher than in younger groups. The proportion of H1N1pdm patients with one or more reported chronic conditions increased with severity (median = 31.1%, 52.3%, and 61.8% of hospitalized, ICU-admitted, and fatal H1N1pdm cases, respectively). With the exception of the risk factors asthma, pregnancy, and obesity, the proportion of patients with each risk factor increased with severity level. For all levels of severity, pregnant women in their third trimester consistently accounted for the majority of the total of pregnant women. Our findings suggest that morbid obesity might be a risk factor for ICU admission and fatal outcome (RR = 36.3). Conclusions Our results demonstrate that risk factors for severe H1N1pdm infection are similar to those for seasonal influenza, with some notable differences, such as younger age groups and obesity, and reinforce the need to identify and protect groups at highest risk of severe outcomes