TeraHz tuning of whispering gallery modes in a PDMS, stand-alone, stretchable microsphere

We report on tuning the optical whispering gallery modes in a poly dimethyl siloxane-based (PDMS) microsphere resonator by more than a THz. The PDMS microsphere system consists of a solid spherical resonator directly formed with double stems on either side. The stems act like tie-rods for simple mechanical stretching of the microresonator over tens of microns, resulting in tuning of the whispering gallery modes by one free spectral range. Further investigations demonstrate that the whispering gallery mode shift has a higher sensitivity (0.13 nm/{\mu}N) to an applied force when the resonator is in its maximally stretched state compared to its relaxed state.Comment: 3 pages, 4 figures, submitted to Optics Letter

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions

Eine doppelblinde, randomisierte, placebokontrollierte Überkreuzstudie um die Wirkung einer 15 mg Einzeldosis Eplivanserin auf die Atemfunktion und Schlafstruktur bei Patienten mit leichter bis mittelschwerer chronisch obstruktiver Lungenerkrankung (COPD) zu untersuchen

This study was designed to evaluate the effects of 15 mg eplivanserin compared with placebo on respiratory function and sleep parameters in patients with COPD of mild to moderate intensity. It showed that a single dose of 15 mg eplivanserin compared with placebo had no significant effects on respiratory function as measured by spirometry or body plethysmography or on different sleep stages as measured by Polysomnography (PSG) and finger-pulse oximetry. Moreover, no significant effects were found in capillary blood gas analysis. Polysomnography showed a reduction in the number of awakenings after sleep onset, a reduction of the apnea-hypopnea index and of wake duration after persistent sleep onset, and an increase in total sleep time. PSG measurements showed no changes in latency to persistent sleep. The Bond and Lader VAS score and LSEQ, performed after treatment, did not show any significant changes compared with placebo. The performed descriptive statistics did not show any significant differences based on gender or between mild and moderate COPD patients. No significant changes were observed in any of the safety parameters (ECG, laboratory results, vital signs or reported adverse events). The data collected confirmed that a single dose of eplivanserin 15 mg was well tolerated in mild to moderate COPD patients without any worsening in their respiratory condition.In Rahmen einer doppelblinden, randomisierten, placebokontrollierten Überkreuzstudie wurde die Wirkung einer 15 mg Einzeldosis von Eplivanserin auf die Atemfunktion und Schlafstruktur bei Patienten mit leichter bis mittelschwerer chronisch obstruktiver Lungenerkrankung (COPD) untersucht. Eplivanserin gehört zu einer neuen Arzneimittelklasse, den 5HT2A Rezeptor Antagonisten, die zur Behandlung von Schlaflosigkeit eingesetzt werden könnten. Insgesamt 28 Patienten in Alter von 20 bis 75 Jahren, die seit mindestens drei Jahren an COPD litten, wurden in die Studie eingeschlossen. Die Patienten wurden in jeder Periode eingeladen, zur Eingewöhnung eine Nacht in Schlaflabor zu verbringen. Alle Teilnehmer erhielten sowohl 15 mg Eplivanserin als auch Placebo in zwei Behandlungsperioden, 14 Patienten in der Reihenfolge Eplivanserin – Placebo und 14 Patienten Placebo – Eplivanserin. Zur Beurteilung der Atemfunktion wurde die Sauerstoffsättigung (SaO2) über Nacht während der Polysomnographie-Aufzeichnung gemessen. Während des Tages wurden Spirometrien, Bodyplethysmographien sowie Kapillarblutgasanalysen zu Beurteilung der Lungenfunktion durchgeführt. Die Ergebnisse der Studie zeigen, dass eine Einzeldosis von 15 mg Eplivanserin die Atemfunktion in Patienten mit leichter bis mittelschwerer COPD im Vergleich zu Placebo nicht negativ beeinflusst. Es konnten keine wesentlichen Unterschiede zwischen 15 mg Eplivanserin in Vergleich zu Placebo, weder in den SaO2 Messungen während der Nacht noch bei der Spirometrie bzw. Bodyplethysmographie während des Tages, beobachtet werden. Die Polysomnographie zeigte eine Reduktion des Apnea- hypopnea-Indexes und die Dauer der Wachphasen nach dem Anfang des durchgehendem Schlafes (wake duration after persistence sleep onset), eine Erhöhung der Gesamtschlafzeit, eine Reduktion der Anzahl von Aufwachsphasen nach dem Einschlafen und keine Änderung in der Latenzzeit bis zu durchgehenden Schlaf. Die Untersuchungen mit der visuellen Analogskala (VAS) sowie des Schlaf-Fragebogens (LSEQ) zur Beurteilung der Schlafqualität zeigten minimale bzw. keine Veränderungen im Vergleich zur zum Ausgangswert vor der Dosierung. Insgesamt konnte gezeigt werden, dass ein Einzel Dosierung von 15 mg Eplivanserin in Patienten mit leichter bis mittelschwerer COPD gut verträglich ist und insbesondere ihre Lungenfunktion nicht negativ beeinflusst

Determinazione della sensibilità agli antimicrobici di enterococchi isolati da alimenti di origine animale

RIASSUNTO Gli enterococchi costituiscono una parte importante delle microflore intestinali di uomo ed animali e sono ampiamente distribuiti nell’ambiente esterno. Sono pertanto isolabili da molti alimenti, specialmente di origine animale. Essi hanno inoltre un ruolo di rilievo come agenti di infezioni nosocomiali, anche in virtù della loro capacità di acquisire resistenze nei confronti di diversi antimicrobici usati in terapia. Scopo del presente lavoro è la determinazione del pattern di sensibilità nei confronti di 16 antimicrobici di 68 ceppi di enterococchi isolati da prodotti di origine animale, sia lattiero-caseari che carnei, commercializzati in Toscana. I ceppi, identificati fenotipicamente, sono risultati appartenere alle specie Enterococcus faecium, E. faecalis ed E. durans. Tutti sono risultati resistenti a ceftazidime e sulfisoxazolo ed hanno evidenziato alte percentuali di resistenza di tipo “low-level” agli aminoglicosidi, come prevedibile. Una percentuale di resistenza superiore al 40% è stata riscontrata per rifampicina, eritromicina, nitrofurantoina, ciprofloxacina e superiore al 20% per penicillina e tetraciclina. La resistenza verso la quinopristina/dalfopristina è risultata, per E. faecium, dell’8,7% nei ceppi di origine lattiero-casearia e del 13,3% in quelli di derivazione carnea. Resistenza di tipo “high-level” verso la gentamicina è stata riscontrata in percentuale dell’11,7% e quasi esclusivamente a carico di E. faecalis. Gli isolati sono risultati altamente sensibili ai glicopeptidi, all’imipenem e, relativamente ad E. faecium e E. faecalis, all’amoxicillina. Nonostante il rilievo di percentuali piuttosto elevate di ceppi multiresistenti, gli enterococchi in esame si sono rivelati generalmente sensibili ai più importanti antimicrobici di uso terapeutico nell’uomo. SUMMARY Enterococci constitute an important part of the intestinal flora of both animals and men. They are widely distributed in the environment and in many foods, especially of animal origin. They also represent a cause of nosocomial infections of increasing significance also considering that they are known to be able to acquire resistance to many antimicrobials used in medical practice. Aim of this work was to determine the susceptibility to 16 antimicrobial agents by the disk diffusion method for 68 enterococcal strains isolated from both dairy and meat products, purchased at retail level in Tuscany. The strains, phenotypically identified, belonged to Enterococcus faecium, E. faecalis and E. durans species. All isolates were resistant to ceftazidime and sulfisoxazole and showed high percentages of “low-level” resistance to aminoglycosides, as expected. A percentage of resistance of more than 40% was registered for rifampicin, erythromycin, nitrofurantoin, ciprofloxacin and of more than 20% for penicillin and tetracycline. With regard to E. faecium, resistance to quinupristin/dalfopristin ranged from 8,7% in dairy strains to 13,3% in those from meat products. “High-level” resistance to gentamicin was found in percentage of 11,7% and almost exclusively in E. faecalis strains. Finally, the isolates resulted highly susceptible to glycopeptides, imipenem and, with regard to E. faecium and E. faecalis, to amoxicillin. Though an high percentage of multiresistant strains was registered, the studied strains revealed to be generally susceptible to the most important antimicrobials of therapeutic use in humans

Omitting axillary staging in selected patients: Rationale of Choosing Wisely in breast cancer treatment.

Axillary surgery for breast cancer has continually evolved, with sentinel lymph node biopsy for clinically node-negative women with invasive breast cancer having long replaced axillary lymph node dissection. The information obtained from axillary staging has been important in providing prognostic information and guiding adjuvant treatment recommendations. However, recent studies suggest that sentinel lymph node biopsy should be omitted in select low-risk patients whose axillary surgery provides minimal prognostic value. This was highlighted by the Society of Surgical Oncology Choosing Wisely Guidelines, advocating against routine axillary staging in older women with early-stage hormone receptor-positive breast cancer. Since the guideline release, ongoing research has continued to identify the subset of low-risk patients who would benefit from the omission of axillary staging and improve adherence to Choosing Wisely to prevent overtreatment in older people

Molecular and biochemical biomarkers in environmental monitoring: a study with a benthic fish living in the Venice Lagoon

Introduction. The Venice Lagoon (VEL) is a coastal ecosystem known to be heavily contaminated (Locatello, 2009). In the present study, the effects of persistent organic pollutants on the aryl hydrocarbon receptor (AhR) and cytochrome P450 1A (CYP1A) expression and catalytic activity (ethoxyresorufin O-deethylase, EROD) were measured in situ by using Zosterisessor ophiocephalus, a benthic species living in the VEL and showing a resident behaviour. Materials and Methods. Fishes were sampled during spring and autumn seasons from three VEL areas (Porto Marghera, Val di Brenta and Porto Canale) with a high, intermediate or low level of contamination, respectively. A total of 189 pools, each one consisting of the liver of three animals, were prepared. Total RNA was extracted and liver microsomes obtained by using common procedures. Species-specific AhR, CYP1A and \u3b2-actin (reference gene) coding sequences were identified and sequenced. Aryl hydrocarbon receptor and CYP1A mRNA levels as well as CYP1A apoprotein and EROD were measured by using a quantitative Real Time RT-PCR approach, immunoblotting and a HPLC method, respectively. Confirmatory residue analyses (non-dioxin-like and dioxin-like polychlorinated biphenyls) were executed on the lipid component of pooled muscle by gas-chromatography. Results. When compared to Porto Canale, significant increases of CYP1A expression and EROD were noticed in samples from Porto Marghera and Val di Brenta. Data from residues analysis mirrored this trend to induction. Furthermore, season-differences were observed for CYP1A expression (higher in the spring, which represents the reproductive season) and EROD activity (higher in the autumn season). Contrasting results were obtained for AhR gene expression. Conclusions. This integrated biomarker approach confirmed Porto Marghera as the most polluted area of VEL (Zonta, 2007). Collectively, CYP1A expression was proved as a suitable biomarker of effect in Zoosterisessor ophiocephalus; therefore, this species may, in turn, be considered as a good sentinel species for VEL environmental monitoring in situ. Less clear-cut results were obtained for EROD. Present AhR data need further molecular investigations, also in light of its role in other physiological mechanisms, including reproduction (Cal\uf2, 2010). References. Locatello L., Matozzo V., Marin M. G., 2009. Biomarker responses in the crab Carcinus aestuarii to assess environmental pollution in the Lagoon of Venice (Italy). Ecotoxicology, 18:869-877. Zonta R., Botter M., Cassin D., Pini R., Scattolin M., Zaggia L. 2007. Sediment chemical contamination of a shallow water close to the industrial zone of Porto Marghera (Venice Lagoon, Italy). Marine Pollution Bulletin, 55:529-542. Cal\uf2 M., Alberghina D., Bitto A., Lauriano E.R., Lo Cascio P. 2010. Estrogenic followed by anti-estrogenic effects of PCBs exposure in juvenil fish (Sparus aurata). Food and Chemical Toxicology 48:2458-2463. Acknowledgements. Project supported by grants from Regione del Veneto (Dgr. 3094 03/10/2006) to M.D. and F.M. and Universit\ue0 degli Studi di Padova (60A08\u20104049/11) to M.G

Evaluation of autophagy in lymphocyte populations during atherosclerotic plaque progression with flow cytometry

Atherosclerosis is a chronic inflammatory disorder of the large arteries and represents the primary cause of heart disease and stroke. The exact cause of atherosclerosis is not known. A variety of studies show that autophagy deficiency may be pro-atherogenic and the role of autophagy in smooth muscle cells, macrophages and endothelial cells has been investigated. However, to date no studies addressed the effect of autophagy on lymphocyte subsets playing a role in plaque formation and development. The present project aims to better clarify the role played by autophagy in lymphocytes homeostasis in human atherosclerotic plaques. We characterized lymphocyte populations in different types of lesion by using flow cytometry. In particular, we detected OX40 as marker for conventional T cells promoting division and survival of effector and memory populations and pS6, a marker for an active mTOR pathway and autophagy detection. The understanding of the role of autophagy as a further mechanism underlying lymphocytes stability may open new therapeutic avenues for atherosclerosis