The prognostic importance of chronic end-stage diseases in geriatric patients admitted to 163 Italian ICUs

BACKGROUND: The number of elderly patients undergoing major surgical interventions and then needing admission to intensive care unit (ICU) grows steadily. We investigated this issue in a cohort of 232,278 patients admitted in five years (2011-2015) to 163 Italian general ICUs. METHODS: Surgical patients older than 75 registered in the GiViTI MargheritaPROSAFE project were analyzed. The impact on hospital mortality of important chronic conditions (severe COPD, NYHA class IV, dementia, end-stage renal disease, cirrhosis with portal hypertension) was investigated with two prognostic models developed yearly on patients staying in the ICU less or more than 24 hours. RESULTS: 44,551 elderly patients (19.2%) underwent emergency (47.3%) or elective surgery (52.7%). At least one severe comorbidity was present in 14.6% of them, yielding a higher hospital mortality (32.4%, vs. 21.1% without severe comorbidity). In the models for patients staying in the ICU 24 hours or more, cirrhosis, NYHA class IV, and severe COPD were constant independent predictors of death (adjusted odds ratios [ORs] range 1.67-1.97, 1.54-1.91, and 1.34-1.50, respectively), while dementia was statistically significant in four out of five models (adjusted ORs 1.23-1.28). End-stage renal disease, instead, never resulted to be an independent prognostic factor. For patients staying in the ICU less than 24 hours, chronic comorbidities were only occasionally independent predictors of death. CONCLUSIONS: Our study confirms that elderly surgical patients represent a relevant part of all ICUs admissions. About one of seven bear at least one severe chronic comorbidity, that, excluding end-stage renal disease, are all strong independent predictors of hospital death

The Link of the Prion Protein with Ca2+ Metabolism and ROS Production, and the Possible Implication in A\u3b2 Toxicity

The cellular prion protein (PrPC) is an ubiquitous cell surface protein mostly expressed in neurons, where it localizes to both pre- and post-synaptic membranes. PrPC aberrant conformers are the major components of mammalian prions, the infectious agents responsible for incurable neurodegenerative disorders. PrPC was also proposed to bind aggregated misfolded proteins/peptides, and to mediate their neurotoxic signal. In spite of long-lasting research, a general consensus on the precise pathophysiologic mechanisms of PrPC has not yet been reached. Here we review our recent data, obtained by comparing primary neurons from PrP-expressing and PrP-knockout mice, indicating a central role of PrPC in synaptic transmission and Ca2+ homeostasis. Indeed, by controlling gene expression and signaling cascades, PrPC is able to optimize glutamate secretion and regulate Ca2+ entry via store-operated channels and ionotropic glutamate receptors, thereby protecting neurons from threatening Ca2+ overloads and excitotoxicity. We will also illustrate and discuss past and unpublished results demonstrating that A\u3b2 oligomers perturb Ca2+ homeostasis and cause abnormal mitochondrial accumulation of reactive oxygen species by possibly affecting the PrP-dependent downregulation of Fyn kinase activity

Brassavola tuberculata Hook.: in vitro growth and ex vitro establishment as a function of the micropropagation system and sucrose

Abstract This study examines the in vitro growth and ex vitro establishment of Brassavola tuberculata in relation to the micropropagation system and sucrose concentration employed in the in vitro culture. A completely randomized experimental design was utilized, employing a 2 x 5 factorial arrangement. The experimental period began with seedlings cultivated in vitro for 180 days, which were subsequently transferred to Murashige and Skoog culture media containing sucrose concentrations of 0, 15, 30, 45, or 60 g L-1. The cultures were subjected to two micropropagation systems: conventional and gas exchange. After 90 days of in vitro cultivation, the plants were evaluated, transplanted into a substrate, and placed in a screened nursery for ex vitro cultivation. After 300 days of ex vitro cultivation, the survival and initial characteristics of the plants were assessed. The micropropagation system allowing gas exchange and sucrose concentrations up to 30 g L-1 enhanced the shoot and root growth of in vitro propagated plants. No noticeable anatomical differences were observed after 90 days of in vitro culture among the different sucrose concentrations and micropropagation systems used. In the ex vitro establishment, irrespective of sucrose concentration, the micropropagation system facilitating gas exchange positively influenced all evaluated characteristics

A mathematical model of mitochondrial swelling

<p>Abstract</p> <p>Background</p> <p>The <it>permeabilization </it>of mitochondrial membranes is a decisive event in apoptosis or necrosis culminating in cell death. One fundamental mechanism by which such permeabilization events occur is the calcium-induced mitochondrial permeability transition. Upon Ca²⁺-uptake into mitochondria an increase in inner membrane permeability occurs by a yet unclear mechanism. This leads to a net water influx in the mitochondrial matrix, mitochondrial swelling, and finally the rupture of the outer membrane. Although already described more than thirty years ago, many unsolved questions surround this important biological phenomenon. Importantly, theoretical modeling of the mitochondrial permeability transition has only started recently and the existing mathematical models fail to characterize the swelling process throughout the whole time range.</p> <p>Results</p> <p>We propose here a new mathematical approach to the mitochondrial permeability transition introducing a specific delay equation and resulting in an optimized representation of mitochondrial swelling. Our new model is in accordance with the experimentally determined course of volume increase throughout the whole swelling process, including its initial lag phase as well as its termination. From this new model biological consequences can be deduced, such as the confirmation of a positive feedback of mitochondrial swelling which linearly depends on the Ca²⁺-concentration, or a negative exponential dependence of the average swelling time on the Ca²⁺-concentration. Finally, our model can show an initial shrinking phase of mitochondria, which is often observed experimentally before the actual swelling starts.</p> <p>Conclusions</p> <p>We present a model of the mitochondrial swelling kinetics. This model may be adapted and extended to diverse other inducing/inhibiting conditions or to mitochondria from other biological sources and thus may benefit a better understanding of the mitochondrial permeability transition.</p

The Use of Anti-VDAC2 Antibody for the Combined Assessment of Human Sperm Acrosome Integrity and Ionophore A23187-Induced Acrosome Reaction

Voltage-dependent anion channel (VDAC) is mainly located in the mitochondrial outer membrane and participates in many biological processes. In mammals, three VDAC subtypes (VDAC1, 2 and 3) have been identified. Although VDAC has been extensively studied in various tissues and cells, there is little knowledge about the distribution and function of VDAC in male mammalian reproductive system. Several studies have demonstrated that VDAC exists in mammalian spermatozoa and is implicated in spermatogenesis, sperm maturation, motility and fertilization. However, there is no knowledge about the respective localization and function of three VDAC subtypes in human spermatozoa. In this study, we focused on the presence of VDAC2 in human spermatozoa and its possible role in the acrosomal integrity and acrosome reaction using specific anti-VDAC2 monoclonal antibody for the first time. The results exhibited that native VDAC2 existed in the membrane components of human spermatozoa. The co-incubation of spermatozoa with anti-VDAC2 antibody did not affect the acrosomal integrity and acrosome reaction, but inhibited ionophore A23187-induced intracellular Ca2+ increase. Our study suggested that VDAC2 was located in the acrosomal membrane or plasma membrane of human spermatozoa, and played putative roles in sperm functions through mediating Ca2+ transmembrane transport

Investigation of the influence of vacuum venting on mould surface temperature in micro injection moulding

YesThe application of vacuum venting for the removal of air from mould cavity has been introduced in injection moulding with the intent to enhance micro/nano features replication and definition. The technique is adopted to remove air pockets trapped in the micro-features, which are out of reach for conventional venting technologies and can create considerable resistance to the melt filling flow. Nonetheless, several studies have revealed a negative effect on replication that could possibly arise from the application of vacuum venting. Although the incomplete filling of micro-scale features has often been attributed to poor venting, the limited research examining the application of vacuum venting has produced mixed results. In this work, the effect of air evacuation was experimentally investigated, monitoring mould and polymer temperature evolution during the micro injection moulding process by means of a high speed infrared camera and a sapphire window, which forms part of the mould wall. The results show that air evacuation removes a mould surface heating effect caused by rapid compression of the air ahead of the flow front and subsequent conduction of that heat into the mould surface. Hence, with the increase of the surface-to-volume ratio in micro-cavities, air evacuation has a detrimental effect on the cavity filling with polymers that are sensitive to changes of the mould temperature

Otimização multiobjetivo das dimensões dos ambientes de uma residência unifamiliar baseada em simulação energética e estrutural

Resumo O desenvolvimento da tecnologia computacional nas últimas décadas levou a otimização associada à parametrização a possibilitar o desenvolvimento de projetos de melhor desempenho, com ou sem integração com a simulação. O intuito deste trabalho foi aplicar a otimização baseada em simulação na forma de uma edificação residencial unifamiliar com o objetivo de encontrar a composição que apresentasse o melhor desempenho térmico com o menor custo dos materiais construtivos, considerando-se restrições estruturais. Foram utilizados os programas Rhinoceros e Energy Plus, além de plug-ins para modelagem paramétrica, o intercâmbio de informações entre os programas e a condução da otimização. Foram realizadas duas simulações, a primeira considerando os custos dos componentes construtivos e os graus-hora de aquecimento e resfriamento combinados e a segunda considerando os custos e graus-hora de aquecimento, que produziu resultados mais relevantes. Dois casos de cada solução de Pareto foram selecionados para análise, dentre 19,8 mil e 27,4 mil casos obtidos com uso de algoritmos evolucionários. Apesar das limitações de algumas das ferramentas, foi verificado um grande potencial de aplicação deste método no desenvolvimento de projetos arquitetônicos

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR &lt; 60 mL/min/1.73 m2) or eGFR reduction &gt; 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR &lt; 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR &gt; 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Comparison of crystallization characteristics and mechanical properties of polypropylene processed by ultrasound and conventional micro injection molding

YesUltrasound injection molding has emerged as an alternative production route for the manufacturing of micro-scale polymeric components, where it offers significant benefits over the conventional micro-injection molding process. In this work, the effects of ultrasound melting on the mechanical and morphological properties of micro-polypropylene parts were characterized. The ultrasound injection molding process was experimentally compared to the conventional micro-injection molding process using a novel mold, which allows mounting on both machines and visualization of the melt flow for both molding processes. Direct measurements of the flow front speed and temperature distributions were performed using both conventional and thermal high-speed imaging techniques. The manufacturing of micro-tensile specimens allowed the comparison of the mechanical properties of the parts obtained with the different processes. The results indicated that the ultrasound injection molding process could be an efficient alternative to the conventional process