Infrared-Emitting QDs for Thermal Therapy with Real-Time Subcutaneous Temperature Feedback

Nowadays, one of the most exciting applications of nanotechnology in biomedicine is the development of localized, noninvasive therapies for diverse diseases, such as cancer. Among them, nanoparticle-based photothermal therapy (PTT), which destroys malignant cells by delivering heat upon optical excitation of nanoprobes injected into a living specimen, is emerging with great potential. Two main milestones that must be reached for PTT to become a viable clinical treatment are deep penetration of the triggering optical excitation and real-time accurate temperature monitoring of the ongoing therapy, which constitutes a critical factor to minimize collateral damage. In this work, a yet unexplored capability of near-infrared emitting semiconductor nanocrystals (quantum dots, QDs) is demonstrated. Temperature self-monitored ­QD-based PTT is presented for the first time using PbS/CdS/ZnS QDs emitting in the second biological window. These QDs are capable of acting, simultaneously, as photothermal agents (heaters) and high-resolution fluorescent thermal sensors, making it possible to achieve full control over the intratumoral temperature increment during PTT. The differences observed between intratumoral and surface temperatures in this comprehensive investigation, through different irradiation conditions, highlight the need for real-time control of the intratumoral temperature that allows for a dynamic adjustment of the treatment conditions in order to maximize the efficacy of the therapyThis project has been supported by the Spanish Ministerio de Economía y Competitividad under project and MAT2013-47395-C4-1-R. B. del Rosal thanks Universidad Autónoma de Madrid for an FPI grant. F. Ren acknowledges scholarship support from the Fonds de recherche du Québec – Nature et technologies (FRQNT) under the Programme de Bourses d’Excellence (Merit Scholarship Program for Foreign Students

Heat in optical tweezers

Laser-induced thermal effects in optically trapped microspheres and single cells have been investigated by Luminescence Thermometry. Thermal spectroscopy has revealed a non-localized temperature distribution around the trap that extends over tens of microns, in agreement with previous theoretical models. Solvent absorption has been identified as the key parameter to determine laser-induced heating, which can be reduced by establishing a continuous fluid flow of the sample. Our experimental results of thermal loading at a variety of wavelengths reveal that an optimum trapping wavelength exists for biological applications close to 820 nm. This has been corroborated by a simultaneous analysis of the spectral dependence of cellular heating and damage in human lymphocytes during optical trapping. Minimum intracellular heating, well below the cytotoxic level (43 °C), has been demonstrated to occur for optical trapping with 820 nm laser radiation, thus avoiding cell damage

Interferon-Gamma Release Assays Differentiate Between Mycobacterium avium Complex and Tuberculous Lymphadenitis in Children

OBJECTIVES: To assess the performance of interferon-gamma release assays (IGRAs) in the differential diagnosis between Mycobacterium avium complex (MAC) and tuberculosis (TB) in children affected with subacute/chronic submandibular/cervical lymphadenitis. STUDY DESIGN: Multicenter observational study comparing children with microbiologically-confirmed MAC lymphadenitis from the European NontuberculouS MycoBacterial Lymphadenitis in childrEn (ENSeMBLE) study with children with TB lymphadenitis from the Spanish Network for the Study of Pediatric TB (pTBred) database. RESULTS: Overall, 78 patients with MAC and 34 with TB lymphadenitis were included. Among MAC cases, 44/74 (59.5%) had positive tuberculin skin test (TST) results at the 5 mm cutoff, compared with 32/33 (97%) TB cases (p<0.001); at the 10 mm cutoff TST results were positive in 23/74 (31.1%) vs. 26/31 (83.9%), respectively (P < .001). IGRA results were positive in only 1/32 (3.1%) MAC cases who had undergone IGRA testing, compared with 21/23 (91.3%) TB cases (p<0.001). Agreement between TST and IGRA results was poor in MAC (23.3%;κ=0.017), but good in TB cases (95.6%;κ=0.646). IGRAs had a specificity of 96.9% (95%CI:84.3-99.8%), positive predictive value (PPV) of 95.4% (95%CI:78.2-99.8%), and negative predictive value (NPV) of 93.9% (95%CI:80.4-98.9%) for TB lymphadenitis. CONCLUSIONS: In contrast to TST, IGRAs have high specificity, NPV and PPV for TB lymphadenitis in children with subacute/chronic lymphadenopathy, and consequently can help to discriminate between TB and MAC disease. Therefore, IGRAs are useful tools in the diagnostic work-up of children with lymphadenopathy, particularly when culture- and PCR-results are negative

The severity of pandemic H1N1 influenza in the United States, from April to July 2009: A Bayesian analysis

Background: Accurate measures of the severity of pandemic (H1N1) 2009 influenza (pH1N1) are needed to assess the likely impact of an anticipated resurgence in the autumn in the Northern Hemisphere. Severity has been difficult to measure because jurisdictions with large numbers of deaths and other severe outcomes have had too many cases to assess the total number with confidence. Also, detection of severe cases may be more likely, resulting in overestimation of the severity of an average case. We sought to estimate the probabilities that symptomatic infection would lead to hospitalization, ICU admission, and death by combining data from multiple sources. Methods and Findings: We used complementary data from two US cities: Milwaukee attempted to identify cases of medically attended infection whether or not they required hospitalization, while New York City focused on the identification of hospitalizations, intensive care admission or mechanical ventilation (hereafter, ICU), and deaths. New York data were used to estimate numerators for ICU and death, and two sources of data - medically attended cases in Milwaukee or self-reported influenza-like illness (ILI) in New York - were used to estimate ratios of symptomatic cases to hospitalizations. Combining these data with estimates of the fraction detected for each level of severity, we estimated the proportion of symptomatic patients who died (symptomatic case-fatality ratio, sCFR), required ICU (sCIR), and required hospitalization (sCHR), overall and by age category. Evidence, prior information, and associated uncertainty were analyzed in a Bayesian evidence synthesis framework. Using medically attended cases and estimates of the proportion of symptomatic cases medically attended, we estimated an sCFR of 0.048% (95% credible interval [CI] 0.026%-0.096%), sCIR of 0.239% (0.134%-0.458%), and sCHR of 1.44% (0.83%-2.64%). Using self-reported ILI, we obtained estimates approximately 7-96lower. sCFR and sCIR appear to be highest in persons aged 18 y and older, and lowest in children aged 5-17 y. sCHR appears to be lowest in persons aged 5-17; our data were too sparse to allow us to determine the group in which it was the highest. Conclusions: These estimates suggest that an autumn-winter pandemic wave of pH1N1 with comparable severity per case could lead to a number of deaths in the range from considerably below that associated with seasonal influenza to slightly higher, but with the greatest impact in children aged 0-4 and adults 18-64. These estimates of impact depend on assumptions about total incidence of infection and would be larger if incidence of symptomatic infection were higher or shifted toward adults, if viral virulence increased, or if suboptimal treatment resulted from stress on the health care system; numbers would decrease if the total proportion of the population symptomatically infected were lower than assumed.published_or_final_versio

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Advances and challenges for fluorescence nanothermometry.

Fluorescent nanothermometers can probe changes in local temperature in living cells and in vivo and reveal fundamental insights into biological properties. This field has attracted global efforts in developing both temperature-responsive materials and detection procedures to achieve sub-degree temperature resolution in biosystems. Recent generations of nanothermometers show superior performance to earlier ones and also offer multifunctionality, enabling state-of-the-art functional imaging with improved spatial, temporal and temperature resolutions for monitoring the metabolism of intracellular organelles and internal organs. Although progress in this field has been rapid, it has not been without controversy, as recent studies have shown possible biased sensing during fluorescence-based detection. Here, we introduce the design principles and advances in fluorescence nanothermometry, highlight application achievements, discuss scenarios that may lead to biased sensing, analyze the challenges ahead in terms of both fundamental issues and practical implementations, and point to new directions for improving this interdisciplinary field

From Molecular Complexes to Complex Metallic Nanostructures-H-2 Solid-State NMR Studies of Ruthenium-Containing Hydrogenation Catalysts

In the last years, the combination of H-2 solid-state NMR techniques with quantum-chemical calculations has evolved into a powerful spectroscopic tool for the characterization of the state of hydrogen on the surfaces of heterogeneous catalysts. In the present minireview, a brief summary of this development is given, in which investigations of the structure and dynamics of hydrogen in molecular complexes, clusters and nanoparticle systems are presented, aimed to understand the reaction mechanisms on the surface of hydrogenation catalysts. The surface state of deuterium/hydrogen is analyzed employing a combination of variable-temperature H-2 static and magic-angle spinning (MAS) solid-state NMR techniques, in which the dominant quadrupolar interactions of deuterium give information on the binding situation and local symmetry of deuterium/hydrogen on molecular species. Using a correlation database from molecular complexes and clusters, the possibility to distinguish between terminal RuD, bridged Ru2D, three-fold Ru3D, and interstitial Ru6D is demonstrated. Combining these results with quantum-chemical density functional theory (DFT) calculations allows the interpretation of H-2 solid-state data of complex real world nanostructures, which yielded new insights into reaction pathways at the molecular level

Como evitar que la fatiga pandémica nos haga bajar la guardia

El tercer estado de alarma provocado por el coronavirus ha terminado. La pandemia, todavía no. Las campañas de vacunación avanzan a paso firme y todo indica que se cumplirá el objetivo de inmunizar al 70 % de la población a lo largo de verano. Sin embargo, la incidencia de la covid-19 en muchas Comunidades Autónomas sigue siendo elevadísima y menos del 30 % de los españoles ha recibido al menos su primera dosis. Hay motivos para el optimismo, pero también para la cautela. La fatiga pandémica nos azota y es un factor que puede hacernos tropezar a escasos metros de la línea de meta. Preguntamos a sociólogos, psicólogos y expertos en comunicación cómo evitar este escenario

H-2 NMR calculations on polynuclear transition metal complexes: on the influence of local symmetry and other factors

It is now well-known that H-2 solid-state NMR techniques can bring a better understanding of the interaction of deuterium with metal atoms in organometallic mononuclear complexes, clusters or nanoparticles. In that context, we have recently obtained experimental quadrupolar coupling constants and asymmetry parameters characteristic of deuterium atoms involved in various bonding situations in ruthenium clusters, namely D4Ru4(CO)(12), D2Ru6(CO)(18) and other related compounds Gutmann et al., J. Am. Chem. Soc., 2010, 132, 11759, which are model compounds for edge-bridging (mu-H) and face-capping (mu(3)-H) coordination types on ruthenium surfaces. The present work is in line with density functional theory (DFT) calculations of the electric field gradient (EFG) tensors in deuterated organometallic ruthenium complexes. The comparison of quadrupolar coupling constants shows an excellent agreement between calculated and observed values. This confirms that DFT is a method of choice for the analysis of deuterium NMR spectra. Such calculations are achieved on a large number of ruthenium clusters in order to obtain quadrupolar coupling constants characteristic of a given coordination type: terminal-D, eta(2)-D-2, mu-D, mu(3)-D as well as mu(4)-D and mu(6)-D (i.e. interstitial deuterides). Given the dependence of such NMR parameters mainly on local symmetry, these results are expected to remain valid for large assemblies of ruthenium atoms, such as organometallic ruthenium nanoparticles