Increase of Diversity of Mumps Virus Genotype G SH Variants Circulating Among a Highly Immunized Population: Spain, 2007-2019.

MuV caused three epidemic waves in Spain since genotype G emerged in 2005, despite high vaccination coverage. SH gene sequencing according to WHO protocols allowed the identification of seven relevant variants and 88 haplotypes. While the originally imported MuVi/Sheffield.GBR/1.05/-variant prevailed during the first two waves, it was subsequently replaced by other variants originated by either local evolution or importation, according to the additional analysis of hypervariable NCRs. The time of emergence of the MRCA of each MuV variant clade was concordant with the data of the earliest sequence. The analysis of Shannon entropy showed an accumulation of variability on six particular positions as the cause of the increase on the number of circulating SH variants. Consequently, SH gene sequencing needs to be complemented with other more variable markers for mumps surveillance immediately after the emergence of a new genotype, but the subsequent emergence of new SH variants turns it unnecessary.

Acute respiratory distress syndrome due to COVID-19. Clinical and prognostic features from a medical Critical Care Unit in Valencia, Spain.

Objective: Information from critically ill coronavirus disease 2019 (COVID-19) patients is limited and in many cases coming from health systems approaches different from the national public systems existing in most countries in Europe. Besides, patient follow-up remains incomplete in many publications. Our aim is to characterize acute respiratory distress syndrome (ARDS) patients admitted to a medical critical care unit (MCCU) in a referral hospital in Spain. Design: Retrospective case series of consecutive ARDS COVID-19 patients admitted and treated in our MCCU. Setting: 36-bed MCCU in referral tertiary hospital. Patients and participants: SARS-CoV-2 infection confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay of nasal/pharyngeal swabs. Interventions: None. Main variables of interest: Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. Results: Forty-four ARDS COVID-19 patients were included in the study. Median age was 61.50 (53.25 - 67) years and most of the patients were male (72.7%). Hypertension and dyslipidemia were the most frequent co-morbidities (52.3 and 36.4% respectively). Steroids (1mg/Kg/day) and tocilizumab were administered in almost all patients (95.5%). 77.3% of the patients needed invasive mechanical ventilation for a median of 16 days [11-28]. Prone position ventilation was performed in 33 patients (97%) for a median of 3 sessions [2-5] per patient. Nosocomial infection was diagnosed in 13 patients (29.5%). Tracheostomy was performed in ten patients (29.4%). At study closing all patients had been discharged from the CCU and only two (4.5%) remained in hospital ward. MCCU length of stay was 18 days [10-27]. Mortality at study closing was 20.5% (n 9); 26.5% among ventilated patients. Conclusions: The seven-week period in which our MCCU was exclusively dedicated to COVID-19 patients has been challenging. Despite the severity of the patients and the high need for invasive mechanical ventilation, mortality was 20.5%.

Objetivo: La información de pacientes críticos con enfermedad por coronavirus 2019 (COVID-19) es limitada y, en muchos casos, proviene de sistemas de salud diferentes a la organización pública de la mayoría de los países de Europa. Además, el seguimiento del paciente sigue siendo incompleto en muchas publicaciones. Nuestro objetivo es caracterizar a los pacientes con síndrome de distres respiratorio agudo (SDRA) ingresados en una unidad de cuidados críticos médicos (MCCU) en un hospital de referencia en España. Diseño: Serie retrospectiva de casos de pacientes consecutivos con SDRA por COVID-19 ingresados y tratados en nuestra MCCU. Lugar: UCC de 36 camas en un hospital terciario de referencia. Pacientes y participantes: Infección por SARS-CoV-2 confirmada por ensayo en tiempo real de la transcriptasa inversa-reacción en cadena de la polimerasa (RT-PCR) de hisopos nasales/faríngeos. Intervenciones: Ninguna. Principales variables de interés: Se recopilaron datos demográficos y clínicos, incluidos datos sobre manejo clínico, insuficiencia respiratoria y mortalidad del paciente. Resultados: Cuarenta y cuatro pacientes con SDRA por COVID-19 fueron incluidos en el estudio. La mediana de edad fue de 61.50 (53.25 - 67) años y la mayoría de los pacientes eran hombres (72.7%). La hipertensión y la dislipidemia fueron las comorbilidades más frecuentes (52,3 y 36,4%, respectivamente). Se administraron esteroides (1mg/kg/día) y tocilizumab en casi todos los pacientes (95,5%). El 77,3% de los pacientes necesitaron ventilación mecánica invasiva durante una mediana de 16 días [11-28]. La ventilación en posición prono se realizó en 33 pacientes (97%) con una mediana de 3 sesiones [2-5] por paciente. Se diagnosticó una infección nosocomial en 13 pacientes (29,5%). La traqueotomía se realizó en diez pacientes (29,4%). Al cierre del estudio, todos los pacientes habían sido dados de alta de la MCCU y solo dos permanecían hospitalizados. La estancia en MCCU fue de 18 días [10-27]. La mortalidad al cierre del estudio fue del 20,5% (n 9); 26.5% para pacientes ventilados. Conclusiones: El período de siete semanas en el que nuestra MCCU se dedicó exclusivamente a pacientes con COVID-19 ha sido un gran desafío. A pesar de la gravedad de los pacientes y la elevada necesidad de ventilación mecánica invasiva, la mortalidad fue del 20,5%.

Silver-embedded screens in the intensive care unit. A new tool to control multi-drug resistant bacterial cross-transmission.

The purpose of this study was to assess the effectiveness of silver-embedded surfaces (BactiBlock®) to prevent surface colonization by multi-resistant bacteria (MRB) and to reduce the incidence of MRB colonization and infection in patients admitted to an intensive care unit (ICU). A 6-month prospective observational study in a 24-bed mixed ICU divided into two identical subunits (12 beds each) was designed. Seven solid mobile screens were placed in one of the subunits while in the other cloth screens remained. Solid screens were constructed with high-density polyethylene embedded in Bactiblock®. To evaluate the effectiveness of screens coated with Bactiblock®, number of MRB isolates on screens were compared for 6 months. Likewise, numbers of new patients and ICU-stays with MRB colonization in the two subunits were compared. One hundred forty screen samples were collected in 10-point prevalent days. MRB were detected on 28 (20.0%) samples. Over the 70 samples taken on cloth folding screens, MRB were detected in 25 (35.7%), while only 3 (4.3%) of the 70 samples taken on Bactiblock® screens were positive for MRB (p < 0.001). The unit with Bactiblock® screens presented fewer number of ICU stays with MRB colonization (27.8% vs 47.1%; p < 0.001). No significant differences were found in the global incidence of MRB nosocomial infection. The presence of Bactiblock® embedded in solid folding screens avoided MRB surface colonization and reduced MRB transmission to patients admitted to critical care units, proving to be an useful tool in the control of MRB.

The microtubular cytoskeleton of olfactory neurons derived from patients with schizophrenia or with bipolar disorder: Implications for biomarker characterization, neuronal physiology and pharmacological screening.

Schizophrenia (SZ) and Bipolar Disorder (BD) are highly inheritable chronic mental disorders with a worldwide prevalence of around 1%. Despite that many efforts had been made to characterize biomarkers in order to allow for biological testing for their diagnoses, these disorders are currently detected and classified only by clinical appraisal based on the Diagnostic and Statistical Manual of Mental Disorders. Olfactory neuroepithelium-derived neuronal precursors have been recently proposed as a model for biomarker characterization. Because of their peripheral localization, they are amenable to collection and suitable for being cultured and propagated in vitro. Olfactory neuroepithelial cells can be obtained by a non-invasive brush-exfoliation technique from neuropsychiatric patients and healthy subjects. Neuronal precursors isolated from these samples undergo in vitro the cytoskeletal reorganization inherent to the neurodevelopment process which has been described as one important feature in the etiology of both diseases. In this paper, we will review the current knowledge on microtubular organization in olfactory neurons of patients with SZ and with BD that may constitute specific cytoskeletal endophenotypes and their relation with alterations in L-type voltage-activated Ca(2+) currents. Finally, the potential usefulness of neuronal precursors for pharmacological screening will be discussed.

Stroke-related mortality in a tertiary care hospital in Andalusia: Analysis and reflections. / Mortalidad asociada al ictus en un hospital andaluz de tercer nivel. Análisis y reflexiones.

OBJECTIVES: Stroke is a very common cause of death, especially in southern Spain. The present study analyses in-hospital mortality associated with stroke in an Andalusian tertiary care hospital. METHODS: We gathered the files of all patients who had died at Hospital Universitario Virgen de las Nieves in Granada in 2013 and whose death certificates indicated stroke as the cause of death. We also gathered stroke patients discharge data and compared them to that of patients with acute coronary syndrome (ACS). RESULTS: A total of 825 patients had a diagnosis of stroke (96 deaths, 11.6%); of these, 562 had ischaemic stroke (44 deaths, 7.8%) and 263 haemorrhagic stroke (52 deaths, 19.7%). Patients with haemorrhagic stroke therefore showed greater mortality rate (OR=2.9). Patients in this group died after a shorter time in hospital (median, 4 vs 7 days; mean, 6 days). However, patients with ischaemic stroke were older and presented with more comorbidities. On the other hand, 617 patients had a diagnosis of ACS (36 deaths, 5.8%). The mortality odds ratio (MOR) was 2.1 (stroke/SCA). Around 23% of the patients who died from stroke were taking anticoagulants. 60% of the deceased patients with ischaemic stroke and 20% of those with haemorrhagic stroke had atrial fibrillation (AF); 35% of the patients with ischaemic stroke and AF were taking anticoagulants. CONCLUSIONS: Stroke is associated with higher admission and in-hospital mortality rates than SCA. Likewise, patients with haemorrhagic stroke showed higher mortality rates than those with ischaemic stroke. Patients with fatal stroke usually had a history of long-term treatment with anticoagulants; 2 thirds of the patients with fatal ischaemic stroke and atrial fibrillation were not receiving anticoagulants. According to our results, optimising prevention in patients with AF may have a positive impact on stroke-related in-hospital mortality.

Overexpression of hypoxia-inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides--cutaneous T-cell lymphoma: clinical implications.

Mycosis fungoides (MF) is the most common variant of primary cutaneous T-cell lymphoma, and decreased forkhead box P3 (FoxP3) expression has been reported in MF late stages. Hypoxia-inducible factor 1 alpha (HIF-1α) may regulate FoxP3 expression; however, it is unknown whether HIF-1α is expressed in the CD4(+) T cells of MF patients and how it could affect the expression of FoxP3. Therefore, we evaluated the expression of HIF-1α and FoxP3 in CD4(+) T cells obtained from the skin lesions of MF patients. We found increased cell proliferation and an increase in CD4(+) T cells with an aberrant phenotype among early stage MF patients. HIF-1α was overexpressed in these CD4(+) T cells. In addition, we found a decrease in the percentage of FoxP3(+) cells both in the skin of MF patients, when compared with control skin samples, and with disease progression. In addition, a negative correlation was established between HIF-1α and FoxP3 expression. Skin HIF-1α expression in MF patients correlated with the extent of the affected area and increased with the disease progression. Finally, we showed that ex vivo inhibition of HIF-1α degradation increases the percentage of FoxP3(+) T cells in skin lesions. Our results suggest that overexpression of HIF-1α affects the levels of FoxP3 in MF patients, which could have relevant implications in terms of disease outcome.

Viral infections of the central nervous system in Spain: a prospective study.

The aim of the study was to determine the incidence of viruses causing aseptic meningitis, meningoencephalitis, and encephalitis in Spain. This was a prospective study, in collaboration with 17 Spanish hospitals, including 581 cases (CSF from all and sera from 280): meningitis (340), meningoencephalitis (91), encephalitis (76), febrile syndrome (7), other neurological disorders (32), and 35 cases without clinical information. CSF were assayed by PCR for enterovirus (EV), herpesvirus (herpes simplex [HSV], varicella-zoster [VZV], cytomegalovirus [CMV], Epstein-Barr [EBV], and human herpes virus-6 [HHV-6]), mumps (MV), Toscana virus (TOSV), adenovirus (HAdV), lymphocytic choriomeningitis virus (LCMV), West Nile virus (WNV), and rabies. Serology was undertaken when methodology was available. Amongst meningitis cases, 57.1% were characterized; EV was the most frequent (76.8%), followed by VZV (10.3%) and HSV (3.1%; HSV-1: 1.6%; HSV-2: 1.0%, HSV non-typed: 0.5%). Cases due to CMV, EBV, HHV-6, MV, TOSV, HAdV, and LCMV were also detected. For meningoencephalitis, 40.7% of cases were diagnosed, HSV-1 (43.2%) and VZV (27.0%) being the most frequent agents, while cases associated with HSV-2, EV, CMV, MV, and LCMV were also detected. For encephalitis, 27.6% of cases were caused by HSV-1 (71.4%), VZV (19.1%), or EV (9.5%). Other positive neurological syndromes included cerebellitis (EV and HAdV), seizures (HSV), demyelinating disease (HSV-1 and HHV-6), myelopathy (VZV), and polyradiculoneuritis (HSV). No rabies or WNV cases were identified. EVs are the most frequent cause of meningitis, as is HSV for meningoencephalitis and encephalitis. A significant number of cases (42.9% meningitis, 59.3% meningoencephalitis, 72.4% encephalitis) still have no etiological diagnosis.

Identifying Dementia Risk in Older Veterans Using A Mailing Survey.

Evidence suggests that dementia can be prevented. Patients with frailty may be particularly at risk for cognitive impairment (CI). The aim of this study was to determine dementia risk in older Veterans and whether the risk varies according to frailty status. We also evaluated the feasibility of mailed dementia risk screening. Participants were mailed a questionnaire and the Self-Administered Gerocognitive Examination (SAGE). High dementia risk was defined as having mild cognitive impairment (MCI) on SAGE or a CAIDE score ≥6. Out of 5,432 mailed surveys, we obtained a response rate of 19.75%. Most responders completed the questionnaire items. We identified a total of 689 (75.9%) subjects to be at high risk for dementia. Individuals with frailty were at a greater risk for dementia when compared to robust individuals OR:1.921 (95%CI:1.259-2.930), p=.002. The mailed screening represents a convenient, alternative and scalable approach to screen for dementia risk.

Decreased Brain Ventricular Volume in Psychiatric Inpatients with Serotonin Reuptake Inhibitor Treatment.

Background: Brain ventricles have been reported to be enlarged in several neuropsychiatric disorders and in aging. Whether human cerebral ventricular volume can decrease over time with psychiatric treatment is not well-studied. The aim of this study was to examine whether inpatients taking serotonin reuptake inhibitors (SRI) exhibited reductions in cerebral ventricular volume. Methods: Psychiatric inpatients, diagnosed mainly with depression, substance use, anxiety, and personality disorders, underwent two imaging sessions (Time 1 and Time 2, approximately 4 weeks apart). FreeSurfer was used to quantify volumetric features of the brain, and ANOVA was used to analyze ventricular volume differences between Time 1 and Time 2. Inpatients' brain ventricle volumes were normalized by dividing by estimated total intracranial volume (eTIV). Clinical features such as depression and anxiety levels were collected at Time 1, Time 1.5 (approximately 2 weeks apart), and Time 2. Results: Inpatients consistently taking SRIs (SRI + , n = 44) showed statistically significant reductions of brain ventricular volumes particularly for their left and right lateral ventricular volumes. Reductions in their third ventricular volume were close to significance (p = .068). The inpatients that did not take SRIs (SRI-, n = 25) showed no statistically significant changes in brain ventricular volumes. The SRI + group also exhibited similar brain structural features to the healthy control group based on the 90% confidence interval comparsions on brain ventricular volume parameters, whereas the SRI- group still exhibited relatively enlarged brain ventricular volumes after treatment. Conclusions: SRI treatment was associated with decreased brain ventricle volume over treatment.

High incidence of COVID-19 at nursing homes in Madrid, Spain, despite preventive measures.

OBJECTIVE: To assess the impact of COVID-19 at nine nursing homes in Madrid, Spain, during the first wave of COVID-19 infection and lockdown period when preventive measures were taken to avoid transmission among residents. METHODS: Nine hundred forty-two residents and 846 staff members from nine nursing homes participated in the study (April 18 to June 20, 2020). All participants were tested for SARS-CoV-2 in the nasopharynx by PCR and for IgG antibodies detection. Microbiological status at sampling was defined as active infection (positive PCR ± presence of antibodies), past infection (negative PCR + presence of antibodies), or naïve participants (negative PCR + absence of antibodies). RESULTS: Laboratory results helped classify the residents as having active infection (n=224; 23.8%), past infection (n=462; 49.1%), or being naïve (n=256; 27.1%); staff members were actively infected (n=127; 15.1%), had had a past infection (n=290; 34.2%), or were naïve (n=429; 50.7%). Overall, the percentage of participants with COVID-19 was significantly higher in residents than in staff members (72.8% vs 49.2%; P=0.001). The clinical situation of residents vs staff at sampling was as follows: acute manifestations compatible with COVID-19 (7.3% vs 3.9%; P<0.01) and no manifestations of infection (92.7% vs 96.0%; P<0.01). A large proportion of both asymptomatic and symptomatic residents (69.4% vs 86.6%; P=0.015) had positive PCR results (mostly alongside positive IgG determinations). CONCLUSIONS: COVID-19 affects 75% of the residents in nursing homes in Madrid. The high impact in these settings, despite the strict restrictions adopted during the lockdown, demonstrates the ability of SARS-CoV-2 to cause outbreaks.

Change of the melanocortin system caused by bilateral subthalamic nucleus stimulation in Parkinson's disease.

OBJECTIVES - Determine whether bilateral subthalamic nucleus stimulation (STN-DBS) in Parkinson's disease (PD) is associated with an increase in neuropeptide Y (NPY) and/or resistance to inhibition by leptin in relation to post-surgery weight gain. MATERIALS AND METHODS - This prospective study included 20 patients who underwent bilateral STN-DBS and 17 who refused surgery. Data were obtained at baseline, 3 and 6 months on neurological and nutritional status, including determination of body mass index (BMI) and serum NPY and leptin levels. RESULTS - NPY and leptin levels changed over time, with a distinct pattern. The BMI increase at 6 months was greater in the surgical group (5.5 ± 6.3% vs 0.5 ± 3.5%; P = 0.035). Medical group exhibited a reduction in leptin level (-2.0 ± 4.3 ng/ml) and a consequent increase in NPY level (72.4 ± 58.7 pmol/ml). However, STN-DBS patients showed an increase in leptin (3.1 ± 5.0 ng/ml; P = 0.001 vs medical group) and also in NPY (12.1 ± 53.6 pmol/ml; P = 0.022 vs medical group) levels, which suggests resistance to inhibition by leptin. Rise in NPY level correlated with higher stimulation voltages. CONCLUSIONS - Bilateral STN-DBS causes disruption of the melanocortin system, probably related to diffusion of the electric current to the hypothalamus. This mechanism may in part explain the weight gain of patients with PD after surgery.

Acute respiratory distress syndrome due to COVID-19. Clinical and prognostic features from a medical Critical Care Unit in Valencia, Spain.

OBJECTIVE: Information from critically ill coronavirus disease 2019 (COVID-19) patients is limited and in many cases coming from health systems approaches different from the national public systems existing in most countries in Europe. Besides, patient follow-up remains incomplete in many publications. Our aim is to characterize acute respiratory distress syndrome (ARDS) patients admitted to a medical critical care unit (MCCU) in a referral hospital in Spain. DESIGN: Retrospective case series of consecutive ARDS COVID-19 patients admitted and treated in our MCCU. SETTING: 36-bed MCCU in referral tertiary hospital. PATIENTS AND PARTICIPANTS: SARS-CoV-2 infection confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay of nasal/pharyngeal swabs. INTERVENTIONS: None MAIN VARIABLES OF INTEREST: Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. RESULTS: Forty-four ARDS COVID-19 patients were included in the study. Median age was 61.50 (53.25 - 67) years and most of the patients were male (72.7%). Hypertension and dyslipidemia were the most frequent co-morbidities (52.3 and 36.4% respectively). Steroids (1mg/Kg/day) and tocilizumab were administered in almost all patients (95.5%). 77.3% of the patients needed invasive mechanical ventilation for a median of 16 days [11-28]. Prone position ventilation was performed in 33 patients (97%) for a median of 3 sessions [2-5] per patient. Nosocomial infection was diagnosed in 13 patients (29.5%). Tracheostomy was performed in ten patients (29.4%). At study closing all patients had been discharged from the CCU and only two (4.5%) remained in hospital ward. MCCU length of stay was 18 days [10-27]. Mortality at study closing was 20.5% (n 9); 26.5% among ventilated patients. CONCLUSIONS: The seven-week period in which our MCCU was exclusively dedicated to COVID-19 patients has been challenging. Despite the severity of the patients and the high need for invasive mechanical ventilation, mortality was 20.5%.

Circulation of mumps virus genotypes in Spain from 1996 to 2007.

Although the WHO recommends the use of genotyping as a tool for epidemiological surveillance for mumps, limited data on mumps virus (MV) genotype circulation that may be used to trace the patterns of virus spread are available. We describe the first complete series of data from Spain. The small hydrophobic region was sequenced from 237 MV-positive samples from several regions of Spain collected between 1996 and 2007. Six different genotypes were identified: A, C, D (D1), G (G1, G2), H (H1, H2), and J. Genotype H1 was predominant during the epidemic that occurred from 1999 to 2003 but was replaced by genotype G1 as the dominant genotype in the epidemic that occurred from 2005 to 2007. The same genotype G1 strain caused concomitant outbreaks in different parts of the world (the United States, Canada, and the United Kingdom). The remaining genotypes (genotypes A, C, D, and J) appeared in sporadic cases or small limited outbreaks. This pattern of circulation seems to reflect continuous viral circulation at the national level, despite the high rates of vaccine coverage.

Efficacy and safety of pallidal stimulation in primary dystonia: results of the Spanish multicentric study.

BACKGROUND: Dystonia is a complex clinical syndrome originated by a wide range of aetiologies. The diagnosis of dystonia is made after the evaluation of aetiological, phenomenological and genetic factors. Medications, except in patients with dopa-responsive dystonia, are of limited efficacy. Botulinum toxin injections are not applicable to patients with generalised dystonia, since many muscular groups contribute to disability. Clinical studies in children and adults with primary generalised dystonia (PGD) have reported beneficial effects of bilateral GPi deep brain stimulation (DBS) in both motor symptoms and disability produced by dystonia as well as a favourable impact of DBS in the health-related quality of life (HRQoL). Some clinical aspects of GPi stimulation in primary dystonia still remain controversial such as the influence of disease duration or age at onset in determining the postoperative clinical outcome. RESULTS: The authors report the results of a multicentric study designed to assess the tolerability and clinical effects of bilateral pallidal DBS on motor impairment, functional disability, quality of life, pain and mood in patients with medically refractory primary generalised or segmental dystonia.

Magnetic field induced inversion in the effect of particle size on powder cohesiveness.

Experimental measurements are reported on the tensile yield stress of magnetofluidized beds of fine magnetic powders operated in the cross-flow configuration. In the absence of externally applied magnetic field the yield stress of the powder depends on particle size as expected, i.e., it increases as bead size is decreased. This trend is however inverted when an external magnetic field is applied. It is suggested that the average orientation of interparticle contacts relative to the direction of the field as affected by particle size plays a relevant role on the magnetic yield stress of these systems.

[Calamities in movement disorders]. / Catástrofes en trastornos del movimiento.

The field of movement disorders largely covers subacute or chronic diseases that are usually treated in outpatient clinics. However, the much less frequent acute disorders require urgent recognition and treatment. The present article reviews the entities that frequently require neurointensive management and whose development can prove "calamitous". These include neuroleptic malignant syndrome and related conditions, status dystonicus, and hemiballism.

[Ethical recommendations for a difficult decision-making in intensive care units due to the exceptional situation of crisis by the COVID-19 pandemia: A rapid review & consensus of experts]. / Recomendaciones éticas para la toma de decisiones difíciles en las unidades de cuidados intensivos ante la situación excepcional de crisis por la pandemia por COVID-19: revisión rápida y consenso de expertos.

In view of the exceptional public health situation caused by the COVID-19 pandemic, a consensus work has been promoted from the ethics group of the Spanish Society of Intensive, Critical Medicine and Coronary Units (SEMICYUC), with the objective of finding some answers from ethics to the crossroads between the increase of people with intensive care needs and the effective availability of means.In a very short period, the medical practice framework has been changed to a 'catastrophe medicine' scenario, with the consequent change in the decision-making parameters. In this context, the allocation of resources or the prioritization of treatment become crucial elements, and it is important to have an ethical reference framework to be able to make the necessary clinical decisions. For this, a process of narrative review of the evidence has been carried out, followed by a unsystematic consensus of experts, which has resulted in both the publication of a position paper and recommendations from SEMICYUC itself, and the consensus between 18 scientific societies and 5 institutes/chairs of bioethics and palliative care of a framework document of reference for general ethical recommendations in this context of crisis.

Synthesis, chemical and biochemical characterization of Lu2O3-iPSMA nanoparticles activated by neutron irradiation.

Among the nanomaterials, rare sesquioxides (lanthanide oxides such as Lu2O3) are of interest due to their adequate thermal conductivity, excellent chemical stability, and high light output. The prostate-specific membrane antigen (PSMA) is an integral multifunctional protein overexpressed in various types of cancer cells. The radiolabeled PSMA inhibitor peptides (iPSMA) have demonstrated their usefulness as specific probes in the treatment and detection of a wide variety of neoplasms, mainly due to their high in vivo recognition by the PSMA protein. The objective of this research was to synthesize Lu2O3-iPSMA nanoparticles (NPs) and characterize their physicochemical properties before and after neutron activation, as well as to assess their biodistribution profile and in vitro potential to target cells overexpressing PSMA. The Lu2O3 NPs were synthesized by the precipitation-calcination method and conjugated to the iPSMA peptide using DOTA (1,4,7,10-tetraazocyclodecane-N,N',N″,N‴-tetraacetic acid) as a linking agent. Results of the physicochemical characterization by FT-IR and UV-Vis spectroscopies, SEM, TEM, DLS, HRTEM, SAED, DSC-TGA, and X-ray diffraction indicated the formation of Lu2O3-iPSMA NPs (diameter of 29.98 ± 9.07 nm), which were not affected in their physicochemical properties after neutron activation. 177Lu2O3-iPSMA NPs showed high affinity (Kd = 5.7 ± 1.9 nM) for the PSMA protein, evaluated by the saturation assay on HepG2 hepatocellular carcinoma cells (PSMA-positive). The biodistribution profile of the nanosystem in healthy mice showed the main uptake in the liver. After irradiation, radioactive Lu2O3-iPSMA NPs exhibited radioluminescent properties, making the in vivo acquisition of their biodistribution, via optical imaging, possible. The results obtained from this research validate the execution of additional preclinical studies with the objective of evaluating the potential of the 177Lu2O3-iPSMA NPs for the targeted radiotherapy and in vivo imaging of tumors overexpressing the PSMA protein.

Synthesis and Biochemical Evaluation of Samarium-153 Oxide Nanoparticles Functionalized with iPSMA-Bombesin Heterodimeric Peptide.

Developments in the design of lanthanide oxide nanoparticles (NPs) have unleashed a wide variety of biomedical applications. Several types of hepatic cancer cells overexpress two proteins: the gastrin-releasing peptide receptor (GRPr), which specifically recognizes the bombesin (BN) peptide, and the prostate-specific membrane antigen (PSMA), which specifically binds to several peptides that inhibit its activity (iPSMA). This research synthesized and physicochemically characterized Sm2O3 nanoparticles functionalized with the iPSMA-BN heterodimeric peptide and studied the effects on their structural, biochemical and preclinical properties after activation by neutron irradiation for possible use in molecular dual-targeted radiotherapy of hepatocellular carcinoma. The Sm2O3 NPs were synthesized by the precipitation-calcination method and functionalized with iPSMA-BN peptide using the DOTA macrocycle as a linking agent. Analysis of physicochemical characterization via TEM, EDS, XRD, UV-Vis, FT-IR, DSL, and zeta potential results showed the formation of Sm2O3-iPSMA-BN NPs (94.23 ± 5.98 nm), and their physicochemical properties were not affected after neutron activation. The nanosystem showed a high affinity with respect to PSMA and GRPr in HepG2 cells ( Kd = 6.6 ± 1.6 nM) and GRPr in PC3 cells ( Kd = 10.6 ± 1.9 nM). 153Sm2O3-iPSMA-BN NPs exhibited radioluminescent properties, making possible in vivo optical imaging of their biodistribution in mice. The results obtained from this research support further preclinical studies designed to evaluate the dosimetry and therapeutic efficacy of 153Sm2O3-iPSMA-BN nanoparticles for in vivo imaging and molecular dual-targeted radiotherapy of liver tumors overexpressing PSMA and/or GRPr proteins.