The long-distance exchange of amazonite and increasing social complexity in the Sudanese Neolithic

The presence of exotic materials in funerary contexts in the Sudanese Nile Valley suggests increasing social complexity during the fifth and sixth millennia BC. Amazonite, both in artefact and raw material form, is frequently recovered from Neolithic Sudanese sites, yet its provenance remains unknown. Geochemical analyses of North and East African raw amazonite outcrops and artefacts found at the Neolithic cemetery of R12 in the Sudanese Nile Valley reveals southern Ethiopia as the source of the R12 amazonite. This research, along with data on different exotic materials from contemporaneous Sudanese cemeteries, suggests a previously unknown, long-distance North African exchange network and confirms the emergence of local craft specialisation as part of larger-scale developing social complexity

Leukotriene B4 production in human mononuclear phagocytes is modulated by interleukin-4-induced 15-lipoxygenase

The aim of this study was to evaluate the consequences of interleukin (IL)-4-induced 15-lipoxygenase (15-LO) expression on leukotriene B4 (LTB4) synthesis in human monocytes. Human monocytes incubated for 24, 48, and 72 h with IL-4 (10 ng/ml) were stimulated with Ca2+-ionophore A23187 (calcimycin; 5 \u3bcM) or opsonized zymosan. 15(S)-hydroxyeicosatetraenoic acid [15(S)-HETE], LTB4, and arachidonic acid (AA) release were measured by high-performance liquid chromotography/radioimmunoassay, liquid chromotography/tandem mass spectrometry (LC/MS/MS), or gas chromatography/mass spectrometry. 15-LO activity was evaluated in AA-treated monocytes. 15-LO, 5-lipoxygenase (5-LO) and 5-LO activating protein (FLAP) expression were analyzed by reverse transcription-polymerase chain reaction. Neutrophil chemotactic activity was evaluated using a microtaxis chamber assay. A23187-induced synthesis of 15(S)-HETE was significantly increased after treatment with IL-4 (10 ng/ml) for 48 and 72 h (p < 0.001). Concomitant decrease of LTB4 release was observed after 72 h of incubation with IL-4 (p < 0.001). LC/MS/MS analysis confirmed the production of 15(S)-HETE and the significant inhibition of LTB4 synthesis in IL-4-treated monocyte after challenge with opsonized zymosan. IL-4 treatment induced 15-LO enzymatic activity as well as 15-LO mRNA, but did not affect either 5-LO or FLAP mRNA expression in monocytes. Supernatant from IL-4-treated monocytes showed significantly lower neutrophil chemotactic activity than controls. 15(S)-HETE significantly inhibited LTB4 production induced by A23187-stimulated human monocytes without affecting AA release. IL-4-induced expression of 15-LO in monocytes caused a significant reduction of LTB4 production. Whereas this effect did not reflect changes in 5-LO and FLAP mRNA expression, synthetic 15(S)-HETE was able to significantly inhibit the synthesis of LTB4, without affecting AA release

Palaeoecological data indicates land-use changes across Europe linked to spatial heterogeneity in mortality during the Black Death pandemic

The Black Death (1347–1352 CE) is the most renowned pandemic in human history, believed by many to have killed half of Europe’s population. However, despite advances in ancient DNA research that conclusively identified the pandemic’s causative agent (bacterium Yersinia pestis), our knowledge of the Black Death remains limited, based primarily on qualitative remarks in medieval written sources available for some areas of Western Europe. Here, we remedy this situation by applying a pioneering new approach, ‘big data palaeoecology’, which, starting from palynological data, evaluates the scale of the Black Death’s mortality on a regional scale across Europe. We collected pollen data on landscape change from 261 radiocarbon-dated coring sites (lakes and wetlands) located across 19 modern-day European countries. We used two independent methods of analysis to evaluate whether the changes we see in the landscape at the time of the Black Death agree with the hypothesis that a large portion of the population, upwards of half, died within a few years in the 21 historical regions we studied. While we can confirm that the Black Death had a devastating impact in some regions, we found that it had negligible or no impact in others. These inter-regional differences in the Black Death’s mortality across Europe demonstrate the significance of cultural, ecological, economic, societal and climatic factors that mediated the dissemination and impact of the disease. The complex interplay of these factors, along with the historical ecology of plague, should be a focus of future research on historical pandemics.The authors acknowledge the following funding sources: Max Planck Independent Research Group, Palaeo-Science and History Group (A.I., A.M. and C.V.); Estonian Research Council #PRG323, PUT1173 (A.Pos., T.R., N.S. and S.V.); European Research Council #FP7 263735 (A.Bro. and A.Plu.), #MSC 655659 (A.E.); Georgetown Environmental Initiative (T.N.); Latvian Council of Science #LZP-2020/2-0060 (N.S. and N.J.); LLNL-JRNL-820941 (I.T.); NSF award #GSS-1228126 (S.M.); Polish-Swiss Research Programme #013/2010 CLIMPEAT (M.Lam.), #086/2010 CLIMPOL (A.W.); Polish Ministry of Science and Higher Education #N N306 275635 (M.K.); Polish National Science Centre #2019/03/X/ST10/00849 (M.Lam.), #2015/17/B/ST10/01656 (M.Lam.), #2015/17/B/ST10/03430 (M.Sło.), #2018/31/B/ST10/02498 (M.Sło.), #N N304 319636 (A.W.); SCIEX #12.286 (K.Mar.); Spanish Ministry of Economy and Competitiveness #REDISCO-HAR2017-88035-P (J.A.L.S.); Spanish Ministry of Education, Culture and Sports #FPU16/00676 (R.L.L.); Swedish Research Council #421-2010-1570 (P.L.), #2018-01272 (F.C.L. and A.S.); Volkswagen Foundation Freigeist Fellowship Dantean Anomaly (M.B.), Spanish Ministry of Science and Innovation #RTI2018-101714-B-I00 (F.A.S. and D.A.S.), OP RDE, MEYS project #CZ.02.1.01/0.0/0.0/16_019/0000728 (P.P.)Peer reviewe

Beclomethasone/formoterol versus budesonide/formoterol combination therapy in asthma.

The present study was designed to compare the fixed combination of beclomethasone and formoterol in a hydrofluoroalkane Modulite (Chiesi Farmaceutici, Parma, Italy) pressurised metered-dose inhaler (pMDI), with a combination of budesonide and formoterol administered via a Turbuhaler (AstraZeneca, Lund, Sweden) dry powder inhaler (DPI). This was a phase III, multinational, multicentre, double-blind, double-dummy, randomised, two-arm parallel groups, controlled study design. After a 2-week run-in period, 219 patients with moderate-to-severe asthma were randomised to a 12-week treatment with beclomethasone 200 microg plus formoterol 12 microg b.i.d. delivered via a pMDI or budesonide 400 microg plus formoterol 12 microg b.i.d. delivered via a DPI. The analysis of noninferiority on primary outcome, morning peak expiratory flow in the last 2 weeks of treatment, showed no difference between groups. A statistically significant improvement from baseline in lung function, symptoms and rescue medication use was observed in both groups at all time-points. No differences were observed between treatments in either rate of asthma exacerbations or frequency of adverse events. The new fixed combination of beclomethasone and formoterol in hydrofluoroalkane Modulite pressurised metered-dose inhaler is equivalent to the marketed combination of budesonide and formoterol in terms of efficacy and tolerability profile

Beclomethasone/formoterol vs fluticasone/salmeterol inhaled combination in moderate to severe asthma.

BACKGROUND: Recommended treatment for moderate to severe asthma is the combination of an inhaled corticosteroid and a long-acting beta(2)-agonist. The present study was designed to compare a new fixed combination of extrafine beclomethasone and formoterol, with the fixed combination fluticasone and salmeterol. METHODS: This was a phase III, multinational, multicentre, double-blind, randomized, two-arm parallel groups, controlled study. After a 2-week run-in period, 228 patients with moderate to severe asthma were randomized to a 12-week treatment with either beclomethasone 100 microg plus formoterol 6 microg or fluticasone 125 microg plus salmeterol 25 microg, both delivered two inhalations b.i.d. via a pressurized metered dose inhaler. RESULTS: The analysis of noninferiority on the primary outcome, morning peak expiratory flow in the last 2 weeks of treatment, showed no difference between groups (difference -3.32 l/min; 95% CI -17.92 to 11.28). A significant improvement from baseline in lung function, symptom score and rescue medication use was observed in both groups at all time points. Beclomethasone plus formoterol combination showed a significantly faster onset of bronchodilation when compared with fluticasone plus salmeterol with the difference maintained for up to 1 h postdosing. No differences were observed between treatments in the rate of asthma exacerbations, frequency of adverse events and overnight urinary cortisol/creatinine ratio. CONCLUSIONS: The new combination of extrafine beclomethasone plus formoterol is not inferior to the marketed combination of fluticasone and salmeterol in terms of efficacy and tolerability, with the advantage of a faster onset of bronchodilation. ( ClinicalTrials.gov number, NCT00394368)

Beclomethasone/formoterol vs fluticasone/salmeterol inhaled combination in moderate to severe asthma

BACKGROUND: Recommended treatment for moderate to severe asthma is the combination of an inhaled corticosteroid and a long-acting beta(2)-agonist. The present study was designed to compare a new fixed combination of extrafine beclomethasone and formoterol, with the fixed combination fluticasone and salmeterol. METHODS: This was a phase III, multinational, multicentre, double-blind, randomized, two-arm parallel groups, controlled study. After a 2-week run-in period, 228 patients with moderate to severe asthma were randomized to a 12-week treatment with either beclomethasone 100 microg plus formoterol 6 microg or fluticasone 125 microg plus salmeterol 25 microg, both delivered two inhalations b.i.d. via a pressurized metered dose inhaler. RESULTS: The analysis of noninferiority on the primary outcome, morning peak expiratory flow in the last 2 weeks of treatment, showed no difference between groups (difference -3.32 l/min; 95% CI -17.92 to 11.28). A significant improvement from baseline in lung function, symptom score and rescue medication use was observed in both groups at all time points. Beclomethasone plus formoterol combination showed a significantly faster onset of bronchodilation when compared with fluticasone plus salmeterol with the difference maintained for up to 1 h postdosing. No differences were observed between treatments in the rate of asthma exacerbations, frequency of adverse events and overnight urinary cortisol/creatinine ratio. CONCLUSIONS: The new combination of extrafine beclomethasone plus formoterol is not inferior to the marketed combination of fluticasone and salmeterol in terms of efficacy and tolerability, with the advantage of a faster onset of bronchodilation. ( ClinicalTrials.gov number, NCT00394368)

Airway inflammation in patients affected by obstructive sleep apnea syndrome

AbstractObstructive sleep apnea syndrome (OSAS) has been shown to be associated to upper airway inflammation. The object of the present study was to establish the presence of bronchial inflammation in OSAS subjects.In 16 subjects affected by OSAS, and in 14 healthy volunteers, airway inflammation was detected by the cellular analysis of the induced sputum.OSAS patients, as compared to control subjects, showed a higher percentage of neutrophils (66.7±18.9 vs. 25.8±15.6) (P<0.001) and a lower percentage of macrophages (29.4±18.4 vs. 70.8±15.3) (P<0.001). The percentage of eosinophils and lymphocytes were not significantly different in the two groups.OSAS subjects show bronchial inflammation characterized by a significant increase in neutrophils