Comprehensive genomic profiles of small cell lung cancer

We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

The Effects of rGO Content and Drying Method on the Textural, Mechanical, and Thermal Properties of rGO/Polymer Composites

Composite hydrogels samples consisting of poly(methyl methacrylate/butyl acrylate/2-hydroxyethylmethacrylate) (poly-OH) and up to 60% reduced graphene oxide (rGO) containing rGO were synthesized. The method of coupled thermally induced self-assembly of graphene oxide (GO) platelets within a polymer matrix and in situ chemical reduction of GO was applied. The synthesized hydrogels were dried using the ambient pressure drying (APD) and freeze-drying (FD) methods. The effects of the weight fraction of rGO in the composites and the drying method on the textural, morphological, thermal, and rheological properties were examined for the dried samples. The obtained results indicate that APD leads to the formation of non-porous xerogels (X) of high bulk density (D), while FD results in the formation of highly porous aerogels (A) with low D. An increase in the weight fraction of rGO in the composite xerogels leads to an increase in D, specific surface area (SA), pore volume (Vp), average pore diameter (dp), and porosity (P). With an increase in the weight fraction of rGO in A-composites, the D values increase while the values of SP, Vp, dp, and P decrease. Thermo-degradation (TD) of both X and A composites takes place through three distinct steps: dehydration, decomposition of residual oxygen functional group, and polymer chain degradation. The thermal stabilities (TS) of the X-composites and X-rGO are higher than those of the A-composites and A-rGO. The values of the storage modulus (E’) and the loss modulus (E”) of the A-composites increase with the increase in their weight fraction of rGO

Kinetics of the Release of Nicotinamide Absorbed on Partially Neutralized Poly(acrylic-co-methacrylic acid) Xerogel under the Conditions of Simultaneous Microwave Heating and Cooling

The kinetics of release of nicotinamide (NIAM) that was absorbed on partially neutralized poly(acrylic-co-methacrylic) (PAM) xerogel/hydrogel, under the conditions of simultaneous microwave heating and cooling (SMHC) were examined. The kinetics curves of NIAM release into an aqueous solution at temperatures of 308–323 K were recorded. By applying the model-fitting method (MFM), it was found that the kinetics of NIAM release can be modeled by a kinetic model of a first-order chemical reaction. The values of the release rate constants (kM) at different temperatures were calculated, and their values were found to be within the range 8.4 10−3 s −1−15.7 10−3 s−1. It has been established that the Arrhenius equation was valid even in the conditions of SMHC. The values of the kinetic parameters (activation energy (Ea) and pre-exponential factor (A) of the NIAM release process adsorbed on PAM xerogel/hydrogel were calculated as follows: Ea = 25.6 kJ/mol and ln (A/s−1) = 5.21. It has been proven that the higher value of the rate constant at SMHC in relation to CH is not a consequence of the overheating of the reaction system or the appearance of “hot-points”. The values of change of the enthalpy of activation (ΔH*) and the change of entropy of activation (ΔS*) were calculated as follows: ΔH* = +23.82 kJ/mol and ΔS* = −201.4 J/mol K. The calculated higher values of the kinetic parameters and thermodynamic parameters of activation are explained by the formation of a specific activated complex under SMHC, whose structure and degree of order are different than in the one formed under CH

Influence of the Primary Structural Parameters of a Precipitated SiO on the Specific Parameters of the Adsorption Isotherms of Cholesterol Dissolved in Toluene

The influence of the primary structural parameters of the precipitated SiO 2 [globular diameter (d g ), coordination number (CN) and coalescence coefficient (CC)] on the specific parameters associated with the shapes of the adsorption isotherms [range of linearity (P), adsorption sensitivity (IS) and equilibrium adsorption capacity (a max )], the constants of the Freundlich isotherm (k and z) and the energy density distribution function parameters of the adsorption centres (β, m) was investigated. It was found that increasing the coordination number and coalescence coefficient values led to a decrease in the a max and z values, as well as in the fraction of dominant adsorption centres, while the β value and the specific amount of cholesterol adsorbed on the remained centres (a 2 ) increased. The changes in the range of linearity (P) of the adsorption isotherms were in agreement with the parameter values of the density distribution function, while the changes in adsorption sensitivity and the Freundlich constant k correlated with the changes in the specific amount of cholesterol adsorbed at the dominant adsorption centres. The optimal values for cholesterol adsorption and of the primary structural parameters of the adsorbents based on the precipitated SiO 2 were defined

Potential Influence of Selenium, Copper, Zinc and Cadmium on L-Thyroxine Substitution in Patients with Hashimoto Thyroiditis and Hypothyroidism

Background: Besides genetic factors, it is known that some trace elements, as Selenium, Copper, and Zinc are essential for thyroid gland fuction and thyroid hormone metabolism. Moreover, there were some metals effect that suggested patterns associated with overt thyroid disease. Aim of study: Hashimoto thyroiditis (HT), chronic autoimune inflamation of thyroid gland with cosequtive hipothyroidism, is common disease in Serbia, and we thought it is worthwile to explore potential effects of essential and toxic metals and metalloides on thyroid function and ability to restore euthyroid status of them. Results: This cross-sectional, case-control, study investigated the status of essential elements (Selenium,Copper,and Zinc) and toxic metals and metalloides (Al, Cr, Mn, Co, As, Cd, Sb, Ba, Be, Pb and Ni) from the blood of 22 female, patients with Hashimoto thyroiditis and overt hypothyroidism, and compared it with those of 55 female healthy persons. We tried to establish the presence of any correlation between previous mentioned elements and thyroid function in hypothyroid patients and healthy participants. Conclusions: The results of our study suggested that the blood concentration of essential trace elements, especially the ratio of Copper, and Selenium may influence directly thyroid function in patients with HT and overt hypothyroidism. Thus, our findings may have implication to life-long substitution therapy in terms of l-thyroxine dose reduction. Furthermore, for the first time, our study shown potential toxic effect of Cadmium on thyroid function in HT patients, which may implicate the dose of l-thyroxine substitution

Igm seroconversion to campylobacter jejuni in the first two years of life of children with Gastrointestinal Symptoms

Campylobacter is the most common bacteria isolated when sampling food and it is considered to be the most common cause of acute diarrhoea in people of all ages. In most countries, there are only data related to sporadic cases of Campylobacter infection, which is manifested by acute diarrhoea. The aim of this paper is to establish the existence of exposure to Campylobacter jejuni by serological analysis in healthy children under 2 years of age, who have previously had gastrointestinal symptoms. The examined group consisted of 77 healthy children under two years of age, who had had a history record of the existence of gastrointestinal symptoms prior to testing. Campylobacter concentration of IgM in serum was determined by ELISA method. Out of 77 children under the age of two, the existence of serum IgM antibodies to Campylobacter jejuni was confirmed in 32 children (42%), while the borderline result was found in 11 children (14%). Seroconversion occurs during the first year of life, and all children in the second year of life were IgM seropositive for Campylobacter jejuni. In the histories of seropositive children the most common symptoms had the form of heavy cramps in 48%. Considering the high incidence and variability of symptoms, the acquisition of Campylobacter jejuni is a major public health problem and there is a need to establish precise epidemiological data primarily in order to develop acquisition control of Campylobacter jejuni