Field dependent transition to the non-linear regime in magnetic hyperthermia experiments: Comparison between maghemite, copper, zinc, nickel and cobalt ferrite nanoparticles of similar sizes

Further advances in magnetic hyperthermia might be limited by biological constraints, such as using sufficiently low frequencies and low field amplitudes to inhibit harmful eddy currents inside the patient's body. These incite the need to optimize the heating efficiency of the nanoparticles, referred to as the specific absorption rate (SAR). Among the several properties currently under research, one of particular importance is the transition from the linear to the non-linear regime that takes place as the field amplitude is increased, an aspect where the magnetic anisotropy is expected to play a fundamental role. In this paper we investigate the heating properties of cobalt ferrite and maghemite nanoparticles under the influence of a 500 kHz sinusoidal magnetic field with varying amplitude, up to 134 Oe. The particles were characterized by TEM, XRD, FMR and VSM, from which most relevant morphological, structural and magnetic properties were inferred. Both materials have similar size distributions and saturation magnetization, but strikingly different magnetic anisotropies. From magnetic hyperthermia experiments we found that, while at low fields maghemite is the best nanomaterial for hyperthermia applications, above a critical field, close to the transition from the linear to the non-linear regime, cobalt ferrite becomes more efficient. The results were also analyzed with respect to the energy conversion efficiency and compared with dynamic hysteresis simulations. Additional analysis with nickel, zinc and copper-ferrite nanoparticles of similar sizes confirmed the importance of the magnetic anisotropy and the damping factor. Further, the analysis of the characterization parameters suggested core-shell nanostructures, probably due to a surface passivation process during the nanoparticle synthesis. Finally, we discussed the effect of particle-particle interactions and its consequences, in particular regarding discrepancies between estimated parameters and expected theoretical predictions. Copyright 2012 Author(s). This article is distributed under a Creative Commons Attribution 3.0 Unported License. [http://dx.doi. org/10.1063/1.4739533]

Detection of the Epstein-Barr virus in blood and bone marrow mononuclear cells of patients with aggressive B-cell non-Hodgkin's lymphoma is not associated with prognosis

The Epstein-Barr virus (EBV) is associated with a large spectrum of lymphoproliferative diseases. Traditional methods of EBV detection include the immunohistochemical identification of viral proteins and DNA probes to the viral genome in tumoral tissue. The present study explored the detection of the EBV genome, using the BALF5 gene, in the bone marrow or blood mononuclear cells of patients with diffuse large B-cell lymphomas (DLBCL) and related its presence to the clinical variables and risk factors. The results show that EBV detection in 21.5% of patients is not associated with age, gender, staging, B symptoms, international prognostic index scores or any analytical parameters, including lactate dehydrogenase (LDH) or beta-2 microglobulin (B2M). The majority of patients were treated with R-CHOP-like (rituximab. cyclophosphamide, doxorubicin, vincristine and prednisolone or an equivalent combination) and some with CHOP-like chemotherapy. Response rates [complete response (CR) + partial response (PR)] were not significantly different between EBV-negative and -positive cases, with 93.2 and 88.9%, respectively. The survival rate was also similar in the two groups, with 5-year overall survival (OS) rates of 64.3 and 76.7%, respectively. However, when analyzing the treatment groups separately there was a trend in EBV-positive patients for a worse prognosis in patients treated with CHOP-like regimens that was not identified in patients treated with R-CHOP-like regimens. We conclude that EBV detection in the bone marrow and blood mononuclear cells of DLBC patients has the same frequency of EBV detection on tumoral lymphoma tissue but is not associated with the risk factors, response rate and survival in patients treated mainly with immunochemotherapy plus rituximab. These results also suggest that the addition of rituximab to chemotherapy improves the prognosis associated with EBV detection in DLBCL.

Induction of chronic non-inflammatory widespread pain increases cardiac sympathetic modulation in rats

Fibromyalgia (FM) is characterized by chronic non-inflammatory widespread pain (CWP) and changes in sympathetic function. In attempt to elucidate the pathophysiological mechanisms of FM we used a well-established CWP animal model. We aimed to evaluate changes in cardiac autonomic balance and baroreflex function in response to CWP induction in rats. CWP was induced by two injections of acidic saline (pH 4.0, n = 8) five days apart into the left gastrocnemius muscle. Control animals were injected twice with normal saline (pH 7.2, n = 6). One day after the second injection of acidic saline or normal saline, the animals had pulse interval (PI) and systolic arterial pressure (SAP) variability, and spontaneous baroreflex sensitivity (BRS) evaluated. After induction of CWP, there was an increase of power in the low frequency (LF) band of PI spectrum (12.75 +/- 1.04 nu), a decrease in the high frequency (HF) band (87.25 +/- 1.04 nu) and an increase of LF/HF ratio (0.16 +/- 0.01), when compared to control animals (7.83 +/- 1.13 nu LF; 92.16 +/- 1.13 nu HF; 0.08 +/- 0.01 LF/HF). In addition, there was an increase of power in the LF band of SAP spectrum (7.93 +/- 1.39 mmHg(2)) when compared to control animals (2.97 +/- 0.61 mmHg(2)). BRS was lower in acidic saline injected rats (0.59 +/- 0.06 ms/mmHg) when compared to control animals (0.71 +/- 0.03 ms/mmHg). Our results showed that induction of CWP in rats shifts cardiac sympathovagal balance towards sympathetic predominance and decreases BRS. These data corroborate findings in humans with FM. (C) 2011 Elsevier B.V. All rights reserved.

Effects of light intensity and temperature on Cylindrospermopsis raciborskii (Cyanobacteria) with straight and coiled trichomes: growth rate and morphology

Cylindrospermopsis raciborskii (Woloszynska) Seenayya et Subba Raju (Ordem Nostocales) is one of the most troublesome bloom-forming species in Brazil. Understanding the population dynamics of the different morphotypes of C. raciborskii (straight and coiled) could assist in the prediction of favourable conditions for the proliferation of this potentially toxin-producing species. The aim of the present study was to assess the effects of two different light intensities and temperatures on the growth rate and morphology of the trichomes of the straight and coiled morphotypes. For such, two non-toxin producing strains of C. raciborskii were used - one with a coiled trichome (ITEP31) and another with a straight trichome (ITEP28). The strains were cultured in BG-11 medium in a climatic chamber under controlled conditions. Two light intensities (30 and 90 mu mol.m(-2).s(-1)) were combined at temperatures of 21 and 31 degrees C and the growth rate and morphological changes were analysed. The morphotypes responded differently to the different temperatures and light intensities. Both strains exhibited faster growth velocities when submitted to higher light intensity and temperature. The lower temperature and higher luminosity hampered the development of both strains. Variations in cellular morphology and an absence of akinetes in both strains were related to the lower temperature (21 C). The coiled morphotype demonstrated considerable phenotype plasticity, changing the morphology of trichome throughout its growth curve. Although molecular analysis does not sustain the separation of the morphotypes as distinct species, their different eco-physiological responses should be considered further knowledge of extreme importance for the population control of these potentially toxic organisms.

The implementation of the Medical Regulation Office and Mobile Emergency Attendance System and its impact on the gravity profile of non-traumatic afflictions treated in a University Hospital: a research study

Abstract Background The public health system of Brazil is structured by a network of increasing complexity, but the low resolution of emergency care at pre-hospital units and the lack of organization of patient flow overloaded the hospitals, mainly the ones of higher complexity. The knowledge of this phenomenon induced Ribeirão Preto to implement the Medical Regulation Office and the Mobile Emergency Attendance System. The objective of this study was to analyze the impact of these services on the gravity profile of non-traumatic afflictions in a University Hospital. Methods The study conducted a retrospective analysis of the medical records of 906 patients older than 13 years of age who entered the Emergency Care Unit of the Hospital of the University of São Paulo School of Medicine at Ribeirão Preto. All presented acute non-traumatic afflictions and were admitted to the Internal Medicine, Surgery or Neurology Departments during two study periods: May 1996 (prior to) and May 2001 (after the implementation of the Medical Regulation Office and Mobile Emergency Attendance System). Demographics and mortality risk levels calculated by Acute Physiology and Chronic Health Evaluation II (APACHE II) were determined. Results From 1996 to 2001, the mean age increased from 49 ± 0.9 to 52 ± 0.9 (P = 0.021), as did the percentage of co-morbidities, from 66.6 to 77.0 (P = 0.0001), the number of in-hospital complications from 260 to 284 (P = 0.0001), the mean calculated APACHE II mortality risk increased from 12.0 ± 0.5 to 14.8 ± 0.6 (P = 0.0008) and mortality rate from 6.1 to 12.2 (P = 0.002). The differences were more significant for patients admitted to the Internal Medicine Department. Conclusion The implementation of the Medical Regulation and Mobile Emergency Attendance System contributed to directing patients with higher gravity scores to the Emergency Care Unit, demonstrating the potential of these services for hierarchical structuring of pre-hospital networks and referrals.

Severe lower respiratory tract infection in infants and toddlers from a non-affluent population: viral etiology and co-detection as risk factors

Abstract Background Lower respiratory tract infection (LRTI) is a major cause of pediatric morbidity and mortality, especially among non-affluent communities. In this study we determine the impact of respiratory viruses and how viral co-detections/infections can affect clinical LRTI severity in children in a hospital setting. Methods Patients younger than 3 years of age admitted to a tertiary hospital in Brazil during the months of high prevalence of respiratory viruses had samples collected from nasopharyngeal aspiration. These samples were tested for 13 different respiratory viruses through real-time PCR (rt-PCR). Patients were followed during hospitalization, and clinical data and population characteristics were collected during that period and at discharge to evaluate severity markers, especially length of hospital stay and oxygen use. Univariate regression analyses identified potential risk factors and multivariate logistic regressions were used to determine the impact of specific viral detections as well as viral co-detections in relation to clinical outcomes. Results We analyzed 260 episodes of LRTI with a viral detection rate of 85% (n = 222). Co-detection was observed in 65% of all virus-positive episodes. The most prevalent virus was Respiratory Syncytial Virus (RSV) (54%), followed by Human Metapneumovirus (hMPV) (32%) and Human Rhinovirus (HRV) (21%). In the multivariate models, infants with co-detection of HRV + RSV stayed 4.5 extra days (p = 0.004), when compared to infants without the co-detection. The same trends were observed for the outcome of days of supplemental oxygen use. Conclusions Although RSV remains as the main cause of LRTI in infants our study indicates an increase in the length of hospital stay and oxygen use in infants with HRV detected by RT-PCR compared to those without HRV. Moreover, one can speculate that when HRV is detected simultaneously with RSV there is an additive effect that may be reflected in more severe clinical outcome. Also, our study identified a significant number of children infected by recently identified viruses, such as hMPV and Human Bocavirus (HBov), and this is a novel finding for poor communities from developing countries.

Independent of ErbB1 gene copy number, EGF stimulates migration but is not associated with cell proliferation in non-small cell lung cancer

Abstract Background Lung cancer often exhibits molecular changes, such as the overexpression of the ErbB1 gene. ErbB1 encodes epidermal growth factor receptor (EGFR), a tyrosine kinase receptor, involved mainly in cell proliferation and survival. EGFR overexpression has been associated with more aggressive disease, poor prognosis, low survival rate and low response to therapy. ErbB1 amplification and mutation are associated with tumor development and are implicated in ineffective treatment. The aim of the present study was to investigate whether the ErbB1 copy number affects EGFR expression, cell proliferation or cell migration by comparing two different cell lines. Methods The copies of ErbB1 gene was evaluated by FISH. Immunofluorescence and Western blotting were performed to determine location and expression of proteins mentioned in the present study. Proliferation was studied by flow cytometry and cell migration by wound healing assay and time lapse. Results We investigated the activation and function of EGFR in the A549 and HK2 lung cancer cell lines, which contain 3 and 6 copies of ErbB1, respectively. The expression of EGFR was lower in the HK2 cell line. EGFR was activated after stimulation with EGF in both cell lines, but this activation did not promote differences in cellular proliferation when compared to control cells. Inhibiting EGFR with AG1478 did not modify cellular proliferation, confirming previous data. However, we observed morphological alterations, changes in microfilament organization and increased cell migration upon EGF stimulation. However, these effects did not seem to be consequence of an epithelial-mesenchymal transition. Conclusion EGFR expression did not appear to be associated to the ErbB1 gene copy number, and neither of these aspects appeared to affect cell proliferation. However, EGFR activation by EGF resulted in cell migration stimulation in both cell lines.

Sensitivity, specificity and predictive values of linear and nonlinear indices of heart rate variability in stable angina patients

Abstract Background Decreased heart rate variability (HRV) is related to higher morbidity and mortality. In this study we evaluated the linear and nonlinear indices of the HRV in stable angina patients submitted to coronary angiography. Methods We studied 77 unselected patients for elective coronary angiography, which were divided into two groups: coronary artery disease (CAD) and non-CAD groups. For analysis of HRV indices, HRV was recorded beat by beat with the volunteers in the supine position for 40 minutes. We analyzed the linear indices in the time (SDNN [standard deviation of normal to normal], NN50 [total number of adjacent RR intervals with a difference of duration greater than 50ms] and RMSSD [root-mean square of differences]) and frequency domains ultra-low frequency (ULF) ≤ 0,003 Hz, very low frequency (VLF) 0,003 – 0,04 Hz, low frequency (LF) (0.04–0.15 Hz), and high frequency (HF) (0.15–0.40 Hz) as well as the ratio between LF and HF components (LF/HF). In relation to the nonlinear indices we evaluated SD1, SD2, SD1/SD2, approximate entropy (−ApEn), α1, α2, Lyapunov Exponent, Hurst Exponent, autocorrelation and dimension correlation. The definition of the cutoff point of the variables for predictive tests was obtained by the Receiver Operating Characteristic curve (ROC). The area under the ROC curve was calculated by the extended trapezoidal rule, assuming as relevant areas under the curve ≥ 0.650. Results Coronary arterial disease patients presented reduced values of SDNN, RMSSD, NN50, HF, SD1, SD2 and -ApEn. HF ≤ 66 ms2, RMSSD ≤ 23.9 ms, ApEn ≤−0.296 and NN50 ≤ 16 presented the best discriminatory power for the presence of significant coronary obstruction. Conclusion We suggest the use of Heart Rate Variability Analysis in linear and nonlinear domains, for prognostic purposes in patients with stable angina pectoris, in view of their overall impairment.

Stochastic lattice model describing a vector-borne disease

We employ the approach of stochastic dynamics to describe the dissemination of vector-borne diseases such as dengue, and we focus our attention on the characterization of the threshold of the epidemic. The coexistence space comprises two representative spatial structures for both human and mosquito populations. The human population has its evolution described by a process that is similar to the Susceptible-Infected-Recovered (SIR) dynamics. The population of mosquitoes follows a dynamic of the type of the Susceptible Infected-Susceptible (SIS) model. The coexistence space is a bipartite lattice constituted by two structures representing the human and mosquito populations. We develop a truncation scheme to solve the evolution equations for the densities and the two-site correlations from which we get the threshold of the disease and the reproductive ratio. We present a precise deØnition of the reproductive ratio which reveals the importance of the correlations developed in the early stage of the disease. According to our deØnition, the reproductive rate is directed related to the conditional probability of the occurrence of a susceptible human (mosquito) given the presence in the neighborhood of an infected mosquito (human). The threshold of the epidemic as well as the phase transition between the epidemic and the non-epidemic states are also obtained by performing Monte Carlo simulations. References: [1] David R. de Souza, T^ania Tom∂e, , Suani R. T. Pinho, Florisneide R. Barreto and M∂ario J. de Oliveira, Phys. Rev. E 87, 012709 (2013). [2] D. R. de Souza, T. Tom∂e and R. M. ZiÆ, J. Stat. Mech. P03006 (2011).

A system for classification of time-series data from industrial non-destructive device

This work proposes a system for classification of industrial steel pieces by means of magnetic nondestructive device. The proposed classification system presents two main stages, online system stage and off-line system stage. In online stage, the system classifies inputs and saves misclassification information in order to perform posterior analyses. In the off-line optimization stage, the topology of a Probabilistic Neural Network is optimized by a Feature Selection algorithm combined with the Probabilistic Neural Network to increase the classification rate. The proposed Feature Selection algorithm searches for the signal spectrogram by combining three basic elements: a Sequential Forward Selection algorithm, a Feature Cluster Grow algorithm with classification rate gradient analysis and a Sequential Backward Selection. Also, a trash-data recycling algorithm is proposed to obtain the optimal feedback samples selected from the misclassified ones.

Coupling between upper ocean layer variability and size-fractionated phytoplankton in a non-nutrient-limited environment

[EN] We describe the coupling between upper ocean layer variability and size-fractionated phytoplankton distribution in the non-nutrient-limited Bransfield Strait region (BS) of Antarctica. For this purpose we use hydrographic and size-fractionated chlorophyll a data from a transect that crossed 2 fronts and an eddy, together with data from 3 stations located in a deeply mixed region, the Antarctic Sound (AS). In the BS transect, small phytoplankton (<20 μm equivalent spherical diameter [ESD]) accounted for 80% of total chl a and their distribution appeared to be linked to cross-frontal variability. On the deepening upper mixed layer (UML) sides of both fronts we observed a deep subducting column-like structure of small phytoplankton biomass. On the shoaling UML sides of both fronts, where there were signs of restratification, we observed a local shallow maximum of small phytoplankton biomass. We propose that this observed phytoplankton distribution may be a response to the development of frontal vertical circulation cells. In the deep, turbulent environment of the AS, larger phytoplankton (>20 μm ESD) accounted for 80% of total chl a. The proportion of large phytoplankton increases as the depth of the upper mixed layer (ZUML), and the corresponding rate of vertical mixing, increases. We hypothesize that this change in phytoplankton composition with varying ZUML is related to the competition for light, and results from modification of the light regime caused by vertical mixing.

Significance of non‐sinking particulate organic carbon and dark CO2 fixation to heterotrophic carbon demand in the mesopelagic northeast Atlantic

[EN] It is generally assumed that sinking particulate organic carbon (POC) constitutes the main source of organic carbon supply to the deep ocean's food webs. However, a major discrepancy between the rates of sinking POC supply (collected with sediment traps) and the prokaryotic organic carbon demand (the total amount of carbon required to sustain the heterotrophic metabolism of the prokaryotes; i.e., production plus respiration, PCD) of deep-water communities has been consistently reported for the dark realm of the global ocean. While the amount of sinking POC flux declines exponentially with depth, the concentration of suspended, buoyant non-sinking POC (nsPOC; obtained with oceanographic bottles) exhibits only small variations with depth in the (sub)tropical Northeast Atlantic. Based on available data for the North Atlantic we show here that the sinking POC flux would contribute only 4–12% of the PCD in the mesopelagic realm (depending on the primary production rate in surface waters). The amount of nsPOC potentially available to heterotrophic prokaryotes in the mesopelagic realm can be partly replenished by dark dissolved inorganic carbon fixation contributing between 12% to 72% to the PCD daily. Taken together, there is evidence that the mesopelagic microheterotrophic biota is more dependent on the nsPOC pool than on the sinking POC supply. Hence, the enigmatic major mismatch between the organic carbon demand of the deep-water heterotrophic microbiota and the POC supply rates might be substantially smaller by including the potentially available nsPOC and its autochthonous production in oceanic carbon cycling models.

Genomic and non genomic effects of elevated concentration of anabolic steroids in human neuronal cells

Nandrolone and other anabolic androgenic steroids (AAS) at elevated concentration can alter the expression and function of neurotransmitter systems and contribute to neuronal cell death. This effect can explain the behavioural changes, drug dependence and neuro degeneration observed in steroid abuser. Nandrolone treatment (10-8M–10-5M) caused a time- and concentration-dependent downregulation of mu opioid receptor (MOPr) transcripts in SH-SY5Y human neuroblastoma cells. This effect was prevented by the androgen receptor (AR) antagonist hydroxyflutamide. Receptor binding assays confirmed a decrease in MOPr of approximately 40% in nandrolonetreated cells. Treatment with actinomycin D (10-5M), a transcription inhibitor, revealed that nandrolone may regulate MOPr mRNA stability. In SH-SY5Y cells transfected with a human MOPr luciferase promoter/reporter construct, nandrolone did not alter the rate of gene transcription. These results suggest that nandrolone may regulate MOPr expression through post-transcriptional mechanisms requiring the AR. Cito-toxicity assays demonstrated a time- and concentration dependent decrease of cells viability in SH-SY5Y cells exposed to steroids (10-6M–10-4M). This toxic effects is independent of activation of AR and sigma-2 receptor. An increased of caspase-3 activity was observed in cells treated with Nandrolone 10-6M for 48h. Collectively, these data support the existence of two cellular mechanisms that might explain the neurological syndromes observed in steroids abuser.

Purging e alte dosi di chemioterapia con reinfusione di cellule staminali autologhe in linfomi non Hodgkin follicolari resistenti/refrattari

In the era of monoclonal antibodies the role of autologous stem cell transplantation (ASCT) in the management of follicular lymphoma (FL) is still debated. To evaluate the safety and efficacy of myeloablative therapy with rescue of purged or unpurged harvests in FL pts. At our institution form 1997 to 2007 28 pts with refractory/resistant FL were eligible for ASCT. Before high dose therapy they received 2-3 cycles of CHOP-like regimen (ACOD), followed by Cyclophosphamide 4g/mq to mobilize the stem cells (SC). After SC collection the pts underwent 3 cycles of subcutaneous Cladribine at a daily dose of 0,14-0,10 mg/Kg for Day 1-5 every 3-4 weeks. The conditioning regimen was based on Mitoxantrone 60mg/mq + Melphalan 180 mg/mq, followed by SC re-infusion 24-hours later and G-CSF starting 24 hours after re-infusion. In 19 pts the SC underwent purging: in 10 harvests the CD34+ were selected by immunomagnetic beads, while in the other 9 pts, only Rituximab was used as “purging in vivo” agent. The remaining 9 pts received unpurged SC. Before ASCT 11 pts were in complete response (CR), 9 in partial response (PR) and 2 in stable disease. Two pts were not eligible for ASCT because of progressive disease (PD). The remaining 25 pts were eligible for ASCT. The engraftment was at a median of 11 days for leucocytes and 14 days for platelets (>20.000/mmc), with a delay of one day in the pts, who received purged SC. Grade 3-4 mucositis was described in 8 pts. During aplasia a 48% infection rate was reported, without differences between pts with purged or unpurged SC. One patient in CR presented myelodysplastic syndrome at 18 months from ASCT. After ASCT 22 pts were in CR, 2 in PR and one patient were not valuable, because died before response assessment. Nine pts in CR showed PD at a median time of 14 months from ASCT. With a median follow up of 5 years (range 2 months -10 years), 22 pts are alive and 11 (44%) in CR. Ten pts died, 5 for progressive disease and 5 for treatment-related causes; in particular 7 of them received in-vitro purged SC. Conclusions: Our chemotherapy regimen, which included the purine analogue Cladribine in the induction phase, seems safe and feasible. The high rate of CR reported and the sustained freedom from progression up to now, makes such modality of treatment a valid option principally in relapsing FL patients. In our experience, the addition of a monoclonal antibody as part of treatment confirms its role “in vivo purging” without observing an increased incidence of infection.

Nell'incertezza scientifica e morale. Il dilemma delle cure intensive ai neonati estremamente prematuri

Definizione del problema: Nonostante il progresso della biotecnologia medica abbia consentito la sopravvivenza del feto, fuori dall’utero materno, ad età gestazionali sempre più basse, la prognosi a breve e a lungo termine di ogni nuovo nato resta spesso incerta e la medicina non è sempre in grado di rimediare completamente e definitivamente ai danni alla salute che spesso contribuisce a causare. Sottoporre tempestivamente i neonati estremamente prematuri alle cure intensive non ne garantisce la sopravvivenza; allo stesso modo, astenervisi non ne garantisce la morte o almeno la morte immediata; in entrambi i casi i danni alla salute (difetti della vista e dell’udito, cecità, sordità, paralisi degli arti, deficit motori, ritardo mentale, disturbi dell’apprendimento e del comportamento) possono essere gravi e permanenti ma non sono prevedibili con certezza per ogni singolo neonato. Il futuro ignoto di ogni nuovo nato, insieme allo sgretolamento di terreni morali condivisi, costringono ad affrontare laceranti dilemmi morali sull’inizio e sul rifiuto, sulla continuazione e sulla sospensione delle cure. Oggetto: Questo lavoro si propone di svolgere un’analisi critica di alcune strategie teoriche e pratiche con le quali, nell’ambito delle cure intensive ai neonati prematuri, la comunità scientifica, i bioeticisti e il diritto tentano di aggirare o di risolvere l’incertezza scientifica e morale. Tali strategie sono accomunate dalla ricerca di criteri morali oggettivi, o almeno intersoggettivi, che consentano ai decisori sostituti di pervenire ad un accordo e di salvaguardare il vero bene del paziente. I criteri esaminati vanno dai dati scientifici riguardanti la prognosi dei prematuri, a “fatti” di natura più strettamente morale come la sofferenza del paziente, il rispetto della libertà di coscienza del medico, l’interesse del neonato a sopravvivere e a vivere bene. Obiettivo: Scopo di questa analisi consiste nel verificare se effettivamente tali strategie riescano a risolvere l’incertezza morale o se invece lascino aperto il dilemma morale delle cure intensive neonatali. In quest’ultimo caso si cercherà di trovare una risposta alla domanda “chi deve decidere per il neonato?” Metodologia e strumenti: Vengono esaminati i più importanti documenti scientifici internazionali riguardanti le raccomandazioni mediche di cura e i pareri della comunità scientifica; gli studi scientifici riguardanti lo stato dell’arte delle conoscenze e degli strumenti terapeutici disponibili ad oggi; i pareri di importanti bioeticisti e gli approcci decisionali più frequentemente proposti ed adoperati; alcuni documenti giuridici internazionali riguardanti la regolamentazione della sperimentazione clinica; alcune pronunce giudiziarie significative riguardanti casi di intervento o astensione dall’intervento medico senza o contro il consenso dei genitori; alcune indagini sulle opinioni dei medici e sulla prassi medica internazionale; le teorie etiche più rilevanti riguardanti i criteri di scelta del legittimo decisore sostituto del neonato e la definizione dei suoi “migliori interessi” da un punto di vista filosofico-morale. Struttura: Nel primo capitolo si ricostruiscono le tappe più importanti della storia delle cure intensive neonatali, con particolare attenzione agli sviluppi dell’assistenza respiratoria negli ultimi decenni. In tal modo vengono messi in luce sia i cambiamenti morali e sociali prodotti dalla meccanizzazione e dalla medicalizzazione dell’assistenza neonatale, sia la continuità della medicina neonatale con il tradizionale paternalismo medico, con i suoi limiti teorici e pratici e con lo sconfinare della pratica terapeutica nella sperimentazione incontrollata. Nel secondo capitolo si sottopongono ad esame critico le prime tre strategie di soluzione dell’incertezza scientifica e morale. La prima consiste nel decidere la “sorte” di un singolo paziente in base ai dati statistici riguardanti la prognosi di tutti i nati in condizioni cliniche analoghe (“approccio statistico”); la seconda, in base alla risposta del singolo paziente alle terapie (“approccio prognostico individualizzato”); la terza, in base all’evoluzione delle condizioni cliniche individuali osservate durante un periodo di trattamento “aggressivo” abbastanza lungo da consentire la raccolta dei dati clinici utili a formulare una prognosi sicura(“approccio del trattamento fino alla certezza”). Viene dedicata una più ampia trattazione alla prima strategia perché l’uso degli studi scientifici per predire la prognosi di ogni nuovo nato accomuna i tre approcci e costituisce la strategia più diffusa ed emblematica di aggiramento dell’incertezza. Essa consiste nella costruzione di un’ “etica basata sull’evidenza”, in analogia alla “medicina basata sull’evidenza”, in quanto ambisce a fondare i doveri morali dei medici e dei genitori solo su fatti verificabili (le prove scientifiche di efficacia delle cure)apparentemente indiscutibili, avalutativi o autocertificativi della moralità delle scelte. Poiché la forza retorica di questa strategia poggia proprio su una (parziale) negazione dell’incertezza dei dati scientifici e sulla presunzione di irrilevanza della pluralità e della complessità dei valori morali nelle decisioni mediche, per metterne in luce i limiti si è scelto di dedicare la maggior parte del secondo capitolo alla discussione dei limiti di validità scientifica degli studi prognostici di cui i medici si avvalgono per predire la prognosi di ogni nuovo nato. Allo stesso scopo, in questo capitolo vengono messe in luce la falsa neutralità morale dei giudizi scientifici di “efficacia”, “prognosi buona”, “prognosi infausta” e di “tollerabilità del rischio” o dei “costi”. Nel terzo capitolo viene affrontata la questione della natura sperimentale delle cure intensive per i neonati prematuri al fine di suggerire un’ulteriore ragione dell’incertezza morale, dell’insostenibilità di obblighi medici di trattamento e della svalutazione dell’istituto del consenso libero e informato dei genitori del neonato. Viene poi documentata l’esistenza di due atteggiamenti opposti manifestati dalla comunità scientifica, dai bioeticisti e dal diritto: da una parte il silenzio sulla natura sperimentale delle terapie e dall’altra l’autocertificazione morale della sperimentazione incontrollata. In seguito si cerca di mostrare come entrambi, sebbene opposti, siano orientati ad occultare l’incertezza e la complessità delle cure ai neonati prematuri, per riaffermare, in tal modo, la precedenza dell’autorità decisionale del medico rispetto a quella dei genitori. Il quarto capitolo, cerca di rispondere alla domanda “chi deve decidere in condizioni di incertezza?”. Viene delineata, perciò, un’altra strategia di risoluzione dell’incertezza: la definizione del miglior interesse (best interest) del neonato, come oggetto, limite e scopo ultimo delle decisioni mediche, qualsiasi esse siano. Viene verificata l’ipotesi che il legittimo decisore ultimo sia colui che conosce meglio di ogni altro i migliori interessi del neonato. Perciò, in questo capitolo vengono esposte e criticate alcune teorie filosofiche sul concetto di “miglior interesse” applicato allo speciale status del neonato. Poiché quest’analisi, rivelando l’inconoscibilità del best interest del neonato, non consente di stabilire con sicurezza chi sia intitolato a prendere la decisione ultima, nell’ultimo capitolo vengono esaminate altre ragioni per le quali i genitori dovrebbero avere l’ultima parola nelle decisioni di fine o di proseguimento della vita. Dopo averle scartate, viene proposta una ragione alternativa che, sebbene non risolutiva, si ritiene abbia il merito di riconoscere e di non mortificare l’irriducibilità dell’incertezza e l’estrema complessità delle scelte morali, senza rischiare, però, la paralisi decisionale, il nichilismo morale e la risoluzione non pacifica dei conflitti.