Study of risk factors for injuries due to cardiopulmonary resuscitation with special focus on the role of the heart: A machine learning analysis of a prospective registry with multiple sources of information (ReCaPTa Study).

Background: The study of thoracic injuries and biomechanics during CPR requires detailed studies that are very scarce. The role of the heart in CPR biomechanics has not been determined. This study aimed to determine the risk factors importance for serious ribcage damage due to CPR. Methods: Data were collected from a prospective registry of out-of-hospital cardiac arrest between April 2014 and April 2017. This study included consecutive out-of-hospital CPR attempts undergoing an autopsy study focused on CPR injuries. Cardiac mass ratio was defined as the ratio of real to expected heart mass. Pearson's correlation coefficient was used to select clinically relevant variables and subsequently classification tree models were built. The Gini index was used to determine the importance of the associated serious ribcage damage factors. The LUCAS® chest compressions device forces and the cardiac mass were analyzed by linear regression. Results: Two hundred CPR attempts were included (133 manual CPR and 67 mechanical CPR). The mean age of the sample was 60.4 ± 13.5, and 56 (28%) were women. In all, 65.0% of the patients presented serious ribcage damage. From the classification tree build with the clinically relevant variables, age (0.44), cardiac mass ratio (0.26), CPR time (0.22), and mechanical CPR (0.07), in that order, were the most influential factors on serious ribcage damage. The chest compression forces were greater in subjects with higher cardiac mass. Conclusions: The heart plays a key role in CPR biomechanics being cardiac mass ratio the second most important risk factor for CPR injuries.

The FAAH inhibitor URB597 reduces cocaine intake during conditioned punishment and mitigates cocaine seeking during withdrawal.

The endocannabinoid system is prominently implicated in the control of cocaine reinforcement due to its relevant role in synaptic plasticity and neurotransmitter modulation in the mesocorticolimbic system. The inhibition of fatty acid amide hydrolase (FAAH), and the resulting increase in anandamide and other N-acylethanolamines, represents a promising strategy for reducing drug seeking. In the present study, we aimed to assess the effects of the FAAH inhibitor URB597 (1 mg/kg) on crucial features of cocaine addictive-like behaviour in mice. Therefore, we tested the effects of URB597 on acquisition of cocaine (0.6 mg/kg/inf) self-administration, compulsive-like cocaine intake and cue-induced drug-seeking behaviour during withdrawal. URB597 reduced cocaine intake under conditioned punishment while having no impact on acquisition. This result was associated to increased cannabinoid receptor 1 gene expression in the ventral striatum and medium spiny neurons activation in the nucleus accumbens shell. Moreover, URB597 mitigated cue-induced drug-seeking behaviour during prolonged abstinence and prevented the withdrawal-induced increase in FAAH gene expression in the ventral striatum. In this case, URB597 decreased activation of medium spiny neurons in the nucleus accumbens core. Our findings evidence the prominent role of endocannabinoids in the development of cocaine addictive-like behaviours and support the potential of FAAH inhibition as a therapeutical target for the treatment of cocaine addiction.

The role of PPAR-γ in memory deficits induced by prenatal and lactation alcohol exposure in mice.

Patients diagnosed with fetal alcohol spectrum disorder (FASD) show persistent cognitive disabilities, including memory deficits. However, the neurobiological substrates underlying these deficits remain unclear. Here, we show that prenatal and lactation alcohol exposure (PLAE) in mice induces FASD-like memory impairments. This is accompanied by a reduction of N-acylethanolamines (NAEs) and peroxisome proliferator-activated receptor gamma (PPAR-γ) in the hippocampus specifically in a childhood-like period (at post-natal day (PD) 25). To determine their role in memory deficits, two pharmacological approaches were performed during this specific period of early life. Thus, memory performance was tested after the repeated administration (from PD25 to PD34) of: i) URB597, to increase NAEs, with GW9662, a PPAR-γ antagonist; ii) pioglitazone, a PPAR-γ agonist. We observed that URB597 suppresses PLAE-induced memory deficits through a PPAR-γ dependent mechanism, since its effects are prevented by GW9662. Direct PPAR-γ activation, using pioglitazone, also ameliorates memory impairments. Lastly, to further investigate the region and cellular specificity, we demonstrate that an early overexpression of PPAR-γ, by means of a viral vector, in hippocampal astrocytes mitigates memory deficits induced by PLAE. Together, our data reveal that disruptions of PPAR-γ signaling during neurodevelopment contribute to PLAE-induced memory dysfunction. In turn, PPAR-γ activation during a childhood-like period is a promising therapeutic approach for memory deficits in the context of early alcohol exposure. Thus, these findings contribute to the gaining insight into the mechanisms that might underlie memory impairments in FASD patients.

Effects of fast-acting antidepressant drugs on a postpartum depression mice model.

Postpartum depression (PPD) is a severe psychiatric disorder with devastating consequences on child development and mother's health. Dysregulation of glutamatergic and GABAergic signalling has been described in the corticolimbic system of PPD patients, who also show a downregulation of allopregnanolone levels in serum. Consequently, a synthetic allopregnanolone-based treatment is the current eligible drug to treat PPD patients. Alternatively, ketamine appears to be a promising medication for preventing PPD, nevertheless the differences in efficacy between both treatments remains unknown due to the lack of comparative studies. On this basis, the present study aims to compare the effectiveness of allopregnanolone and ketamine on a PPD-like mouse model. Our results show that postpartum females undergoing a maternal separation with early weaning (MSEW) protocol show increased despair-like behaviour, anhedonia and disrupted maternal care. Such symptoms are accompanied by lower allopregnanolone serum levels, reduction of vesicular transporters of GABA (VGAT) and glutamate (VGLUT1) in the infralimbic cortex (IL), as well as decreased hippocampal cellular proliferation. Furthermore, both drugs prevent despair-like behaviour while only ketamine reverts anhedonia. Both treatments increase hippocampal neurogenesis, while only allopregnanolone raises VGAT and VGLUT1 markers in IL. These findings suggest that ketamine might be even more effective than allopregnanolone, which points out the necessity of including ketamine in clinical studies for PPD patients. Altogether, we propose a new mice model that recapitulates the core symptomatology and molecular alterations shown in PPD patients, which allows us to further investigate both the neurobiology of PPD and the therapeutic potential of antidepressant drugs.

Bmal1-knockout mice exhibit reduced cocaine-seeking behaviour and cognitive impairments.

Brain and Muscle Arnt-like Protein 1 (BMAL1) is an essential component of the molecular clock underlying circadian rhythmicity. Its function has been recently associated with mood and reward processing alterations. We investigated the behavioural and neurobiological impact of Bmal1 gene deletion in mice, and how this could affect rewarding effects of cocaine. Additionally, key clock genes and components of the dopamine system were assessed in several brain areas. Our results evidence behavioural alterations in Bmal1-KO mice, including changes in locomotor activity with impaired habituation to environments, short-term memory and social recognition impairments. In addition, Bmal1-KO mice experienced reduced cocaine-induced sensitisation and rewarding effects of cocaine as well as reduced cocaine-seeking behaviour. Furthermore, Bmal1 deletion influenced the expression of other clock-related genes in the mPFC and striatum, as well as alterations in the expression of dopaminergic elements. Overall, the present article offers a novel and extensive characterisation of Bmal1-KO animals. We suggest that reduced cocaine's rewarding effects in these mutant mice might be related to Bmal1 role as an expression regulator of MAO and TH, two essential enzymes involved in dopamine metabolism.

Reviewing the Role of the Endocannabinoid System in the Pathophysiology of Depression.

Major depressive disorder is a high-impact, debilitating disease and it is currently considered the most prevalent mental illness. It is associated with disability, as well as increased morbidity and mortality. Despite its significant repercussions in our society, its exact pathophysiology remains unclear and therefore, available antidepressant treatment options are limited and, in some cases, ineffective. In the past years, research has focused on the development of a multifactorial theory of depression. Simultaneously, evidence supporting the role of the endocannabinoid system in the neurobiology of neuropsychiatric diseases has emerged. Studies have shown that the endocannabinoid system strongly impacts neurotransmission, and the neuroendocrine and neuroimmune systems, which are known to be dysfunctional in depressive patients. Accordingly, common antidepressants were shown to have a direct impact on the expression of cannabinoid receptors throughout the brain. Therefore, the relationship between the endocannabinoid system and major depressive disorder is worth consideration. Nevertheless, most studies focus on smaller pieces of what is undoubtedly a larger mosaic of interdependent processes. Therefore, the present review summarizes the existing literature regarding the role of the endocannabinoid system in depression aiming to integrate this information into a holistic picture for a better understanding of the relationship between the two.

Decreasing temporal trends of polychlorinated dibenzo-p-dioxins and dibenzofurans in adipose tissue from residents near a hazardous waste incinerator.

Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) are very toxic chemicals which are emitted in waste incineration and whose exposure has important adverse effects for the human health. In 2019, adipose tissue samples were collected from 15 individuals with a median age of 61 years, who had been living near a hazardous waste incinerator in Constantí (Spain). The content of PCDD/Fs in each sample was analyzed. The results were compared with data from previous studies, conducted before (1998) and after (2002, 2007 and 2013) the facility started to operate, and based on populations of similar age. In 2019, the mean concentration of PCDD/Fs in adipose tissue was 6.63 pg WHO-TEQ/g fat, ranging from 0.95 to 12.95 pg WHO-TEQ/g fat. A significant reduction was observed with respect to the baseline study (1998), when a mean PCDD/Fs concentration of 40.1 pg WHO-TEQ/g fat was found. Moreover, the current level was much lower than those observed in the 3 previous studies (9.89, 14.6 and 11.5 pg WHO-TEQ/g fat in 2002, 2007 and 2013, respectively). The body burdens of PCDD/Fs were strongly correlated with age. The significant reduction of PCDD/Fs levels in adipose tissue fully agreed with the decreasing trend of the dietary intake of PCDD/Fs by the population of the zone (from 210.1 pg I-TEQ/day in 2018 to 8.54 pg WHO-TEQ/day in 2018). Furthermore, a similar decrease has been also observed in other biological, such as breast milk and plasma. The current data in adipose tissue, as well as those in other biological monitors, indicate that the population living near the HWI is not particularly exposed to high levels of PCDD/Fs. However, biomonitoring studies cannot differentiate the impact of the HWI emissions from food consumption patterns. This question can be only solved by conducting complementary investigations and contrasting the results of monitoring and epidemiological studies.

Biomonitoring of Trace Elements in Subjects Living Near a Hazardous Waste Incinerator: Concentrations in Autopsy Tissues.

The only hazardous waste incinerator (HWI) in Spain started to operate in 1999. Twenty years later, the levels of 11 trace elements (As, Be, Cd, Cr, Hg, Mn, Ni, Pb, Sn, Tl and V) were analyzed in five different autopsy tissues (kidney, liver, brain, bone and lung) from 20 individuals who had been living near the facility. In 2019, As, Be, Tl and V were not detected in any of the analyzed tissues, while Hg could be only quantified in very few samples. The highest levels of Cd and Pb were found in kidney and bone, respectively, while those of Mn were observed in liver and kidney. In turn, the mean concentrations of Cr and Sn were very similar in all tissues. A consistent temporal trend (1998-2019) was only found for Cr and Pb. On the one hand, the mean Cr concentrations in kidney and bone have increased progressively since 1998. In contrast, the mean levels of Pb decreased significantly over time, probably due to ban of Pb as gasoline additive. The data global analysis indicates that the emissions of trace elements by the HWI have not increased the exposure and/or accumulation of these elements in individuals living near the facility.

Muerte súbita por hernia diafragmática congénita no diagnosticada / Sudden death due to undiagnosed congenital diaphragmatic hernia

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Necrosis miocárdica masiva por síndrome de Churg-Strauss / Massive myocardial necrosis due to Churg-Strauss syndrome

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The ReCaPTa study - a prospective out of hospital cardiac arrest registry including multiple sources of surveillance for the study of sudden cardiac death in the Mediterranean area.

BACKGROUND: Cardiovascular diseases are one of the leading causes of death in the industrialized world. Sudden cardiac death is very often the first manifestation of the disease and it occurs in the prehospital setting. The determination of the sudden cardiac death phenotype is challenging. It requires prospective studies in the community including multiple sources of case ascertainment that help to identify the cause and circumstances of death. The aim of the Clinical and Pathological Registry of Tarragona (ReCaPTa) is to study incidence and etiology of Sudden Cardiac Death in the Tarragona region (Catalonia, Spain). METHODS: ReCaPTa is a population-based registry of OHCA using multiple sources of surveillance. The population base is 511,662. This registry is compiled chronologically in a relational database and it prospectively contains data on all the OHCA attended by the EMS from April 2014 to April 2017. ReCaPTa collects data after each emergency medical assistance using an online application including variables of the onset of symptoms. A quality control is performed and it permits monitoring the percentage of cases included by the emergency crew. Simultaneously, data from the medico-legal autopsies is taken from the Pathology Center of the area. All the examination findings following a specific protocol for the sudden death study are entered into the ReCaPTa database by one trained person. Survivors admitted to hospital are followed up and their clinical variables are collected in each hospital. The primary care researchers analyze the digital clinical records in order to obtain medical background. All the available data will be reviewed after an adjudication process with the aim of identifying all cases of sudden cardiac death. DISCUSSION: There is a lack of population-based registries including multiple source of surveillance in the Mediterranean area. The ReCaPTa study could provide valuable information to prevent sudden cardiac death and develop new strategies to improve its survival.

Lesiones por reanimación cardiopulmonar en autopsias forenses: protocolo del Registro Clínico-Patológico de Tarragona (ReCaPTa) / Cardiopulmonary resuscitation-related injuries in forensic autopsies: worksheet of the Clinical and Pathological Registry of Tarragona (ReCaPTa)

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