Ecological and economic effects of COVID-19 in marine fisheries from the Northwestern Mediterranean Sea.

The SARS-CoV-2 coronavirus pandemic starting at the end of 2019 impacted many human activities. We analysed the abrupt reduction in fishing pressure of the mixed small-scale and industrial fisheries in the Catalan Sea, Spanish Mediterranean, and resulting ecological and economic impacts during the first half of 2020. We used detailed fisheries data on fishing effort, landings, revenues, landings per unit of effort (LPUE) and revenues per unit of effort from January to June 2020, and complemented it with the outcomes of a marine ecosystem model. We analysed data from 2017 to 2019 and compared these to 2020 to characterise changes in the fishing activity from before (January-February) to during (March-May) the lockdown. Fishing effort during the lockdown dropped by 34%, landings were down by 49% and revenues declined by 39% in comparison with the same period in 2017-2019. LPUEs did not show significant changes during the lockdown, with the exception of shrimp species, especially the deep-water rose shrimp, which significantly increased in LPUE during March-May. These increases may reflect positive effects of reduced fishing on fast-growing species. Positive effects mostly disappeared in June 2020 with the relaxation of the lockdown. In agreement, the ecological simulations projected slight short-term increases of biomass for fast-growing, small-sized organisms during 2020, which quickly vanished when fishing resumed, and which had no detectable ecosystem effects. Three additional alternative ecological simulations illustrated that to substantially recover commercial species and ensure ecosystem sustainability in the study area, a sustained and notable reduction of fishing activity would be needed.

Abnormal pulmonary function tests predict the development of radiation-induced pneumonitis in advanced non-small cell lung Cancer.

BACKGROUND: Radiation pneumonitis (RP) is a frequent complication of concurrent chemoradiotherapy (CCRT) and is associated with severe symptoms that decrease quality of life and might result in pulmonary fibrosis or death. The aim of this study is to identify whether pulmonary function test (PFT) abnormalities may predict RP in non-small cell lung cancer (NSCLC) patients. METHODS: A prospective multi-institutional study was conducted with locally advanced and oligometastatic NSCLC patients. All participants were evaluated at baseline, end of CCRT, week 6, 12, 24, and 48 post-CCRT. They completed forced spirometry with a bronchodilator, body plethysmography, impulse oscillometry, carbon monoxide diffusing capacity (DLCO), molar mass of CO2, six-minute walk test and exhaled fraction of nitric oxide (FeNO). Radiation pneumonitis was assessed with RTOG and CTCAE. The protocol was registered in www.clinicaltrials.gov (NCT01580579), registered April 19, 2012. RESULTS: Fifty-two patients were enrolled; 37 completed one-year follow-up. RP ≥ Grade 2 was present in 11/37 (29%) for RTOG and 15/37 (40%) for CTCAE. Factors associated with RP were age over 60 years and hypofractionated dose. PFT abnormalities at baseline that correlated with the development of RP included lower forced expiratory volume in one second after bronchodilator (p = 0.02), DLCO (p = 0.02) and FeNO (p = 0.04). All PFT results decreased after CCRT and did not return to basal values at follow-up. CONCLUSIONS: FEV1, DLCO and FeNO prior to CCRT predict the development of RP in NSCLC. This study suggests that all patients under CCRT should be assessed by PFT to identify high-risk patients for close follow-up and early treatment.

Occurrence of anthropozoonotic parasitic infections and faecal microbes in free-ranging sperm whales (Physeter macrocephalus) from the Mediterranean Sea.

Sperm whales (Physeter macrocephalus) are the largest toothed whales and only living member of family Physeteridae. Present survey represents first report on cultivable faecal microbes and gastrointestinal helminths and protozoans infecting free-ranging sperm whales inhabiting Mediterranean Sea waters surrounding Balearic Archipelago, Spain. Twenty-five individual sperm whale scat samples, including one calf, were collected without disturbance of animals during the summer of 2016. Parasitological diagnostic methods, such as sodium acetate acetic formalin (SAF) method, carbol fuchsin-stained faecal smears, Giardia/Cryptosporidium coproantigen ELISAs and an Anisakis-specific PCR were applied for further identification. Five bacterial genera, i.e. Acinetobacter, Clostridium, Enterococcus, Staphylococcus and Streptococcus, and one fungus namely Cladosporium were identified. Parasitological infections included seven different parasite species with some of them bearing anthropozoonotic potential. Thus, four of these parasites were zoonotic, i.e. Anisakis, Balantidium, Diphyllobothriidae gen. sp. and Giardia. Additionally, Zalophotrema curilensis eggs, spirurid-like eggs and Cystoisospora-like oocysts were identified. Molecular characterization identified Anisakis physeteris as the species infecting these whales. This survey provides first records on occurrence of two zoonotic enteropathogenic protozoan parasites (Giardia and Balantidium) and of facultative pathogenic bacteria (Clostridium and Enterococcus) in sperm whales. Presented data should be considered as a baseline study for future monitoring surveys on anthropozoonotic pathogens affecting free-living sperm whale populations and enhance investigations on possible impact on public health as well as on isolated Mediterranean sperm whale subpopulation.

Pathways from assaultive violence to post-traumatic stress, depression, and generalized anxiety symptoms through stressful life events: longitudinal mediation models.

BACKGROUND: Assaultive violence events are associated with increased risk for adverse psychiatric outcomes, including post-traumatic stress (PTS), depression, and generalized anxiety. Prior research has indicated that economic, legal, and social stressors that could follow assaultive events may explain the increased risk for adverse psychiatric outcomes, yet longitudinal studies have not adequately examined this pathway. In the current study, we aimed to address this limitation. METHODS: Participants (N = 1360) were part of a longitudinal population-based study of adults living in Detroit. At three waves, participants indicated their exposure to assaultive violence and economic, legal, and social stressors, and completed inventories of PTS, depression, and generalized anxiety. Longitudinal mediation models were used to test the hypothesized pathway from assaultive violence to each psychiatric outcome. RESULTS: The hypothesized models evidenced good fit with the data and, in each, the paths from Wave 1 (W1) assaultive violence to W2 stressors, and from W2 stressors to W3 symptoms were significant (range of Standardized Estimates: 0.09-0.15, all p < 0.01). Additionally, the indirect paths from W1 assaultive violence to W3 symptoms were significant (range of Standardized Estimates: 0.01-0.02, all p < 0.05). CONCLUSIONS: The findings illustrate that the economic, legal, and social stressors that could follow assaultive violence increase risk for a range of psychiatric symptoms. Although future research is needed, the results suggest that investment in interventions that prevent and mitigate assaultive violence survivors' exposure to such stressors may be an effective way to prevent mental illness in the aftermath of violent assaults.

Which adolescents develop persistent substance dependence in adulthood? Using population-representative longitudinal data to inform universal risk assessment.

BACKGROUND: To our knowledge, there are no universal screening tools for substance dependence that (1) were developed using a population-based sample, (2) estimate total risk briefly and inexpensively by incorporating a relatively small number of well-established risk factors, and (3) aggregate risk factors using a simple algorithm. We created a universal screening tool that incorporates these features to identify adolescents at risk for persistent substance dependence in adulthood. METHOD: Participants were members of a representative cohort of 1037 individuals born in Dunedin, New Zealand in 1972-1973 and followed prospectively to age 38 years, with 95% retention. We assessed a small set of childhood and adolescent risk factors: family history of substance dependence, childhood psychopathology (conduct disorder, depression), early exposure to substances, frequent substance use in adolescence, sex, and childhood socioeconomic status. We defined the outcome (persistent substance dependence in adulthood) as dependence on one or more of alcohol, tobacco, cannabis, or hard drugs at ⩾3 assessment ages: 21, 26, 32, and 38 years. RESULTS: A cumulative risk index, a simple sum of nine childhood and adolescent risk factors, predicted persistent substance dependence in adulthood with considerable accuracy (AUC = 0.80). CONCLUSIONS: A cumulative risk score can accurately predict which adolescents in the general population will develop persistent substance dependence in adulthood.

Mesenchymal stromal cells overexpressing vascular endothelial growth factor in ovine myocardial infarction.

Mesenchymal stromal cells (MSCs) are cardioprotective in acute myocardial infarction (AMI). Besides, we have shown that intramyocardial injection of plasmid-VEGF(165) (pVEGF) in ovine AMI reduces infarct size and improves left ventricular (LV) function. We thus hypothesized that MSCs overexpressing VEGF(165) (MSCs-pVEGF) would afford greater cardioprotection than non-modified MSCs or pVEGF alone. Sheep underwent an anteroapical AMI and, 1 week later, received intramyocardial MSCs-pVEGF in the infarct border. One month post treatment, infarct size (magnetic resonance) decreased by 31% vs pre-treatment. Of note, myocardial salvage occurred predominantly at the subendocardium, the myocardial region displaying the largest contribution to systolic performance. Consistently, LV ejection fraction recovered to almost its baseline value because of marked decrease in end-systolic volume. None of these effects were observed in sheep receiving non-transfected MSCs or pVEGF. Although myocardial retention of MSCs decreased steeply over time, the treatment induced significant capillary and arteriolar proliferation, which reduced subendocardial fibrosis. We conclude that in ovine AMI, allogeneic VEGF-overexpressing MSCs induce subendocardial myocardium salvage through microvascular proliferation, reducing infarct size and improving LV function more than non-transfected MSCs or the naked plasmid. Importantly, the use of a plasmid rather than a virus allows for repeated treatments, likely needed in ischemic heart disease.

The course of posttraumatic stress symptoms and functional impairment following a disaster: what is the lasting influence of acute versus ongoing traumatic events and stressors?

PURPOSE: Ongoing traumatic events and stressors, rather than acute sources of trauma, may shape long-term post-disaster mental health. The purpose of this study was to compare the influence of acute hurricane-related exposures and ongoing post-hurricane exposures on the short- and long-term course of posttraumatic stress symptoms (PTSS) and functional impairment (FI). METHODS: A random sample of adults (n = 658) in Galveston and Chambers Counties, Texas, was selected 2-6 months after Hurricane Ike and interviewed 3 times over 18 months. Hurricane-related exposures included traumatic events such as death of a family member due to the hurricane and stressors such as loss/damage to personal property due to the hurricane. Post-hurricane exposures included traumatic events such as sexual assault and stressors such as divorce or serious financial problems. RESULTS: Experiencing an acute hurricane-related traumatic event or stressor was associated with initial post-hurricane PTSS [RR = 1.92 (95% CI = 1.13-3.26) and RR = 1.62 (1.36-1.94), respectively] and FI [RR = 1.76; (1.05-2.97) and RR = 1.74 (1.46-2.08)], respectively, and acute hurricane-related stressors were associated with a higher rate of increase in FI over time [RR = 1.09; (1.01-1.19)]. In contrast, ongoing post-hurricane daily stressors were not associated within initial PTSS and FI, but were associated with PTSS and FI at the second and third interviews. CONCLUSIONS: While immediate postdisaster interventions may influence short-term mental health, investment in the prevention of ongoing stressors may be instrumental to manage long-term mental health status.

Protein and Energy Requirements for Maintenance and Growth in Juvenile Meagre Argyrosomus regius (Asso, 1801) (Sciaenidae).

The meagre is a carnivorous species and might be a suitable candidate species for the diversification of aquaculture in the Mediterranean region. This is based on its high growth and flesh quality. Nevertheless, there is little information available about its growth rates and nutrient requirements. The objective of this study was to determine the protein and energy requirements of juvenile meagre (Argyrosomus regius). Two trials for different weights of 53 and 188 g were conducted with rations from starvation to apparent satiation with the scope of studying its nutritional needs. In the first trial, the initial mean body weight of the fish was 53 g, and they were fed at feeding rates, measured as a percentage of the body weight, of 0, 0.75, 1.5, 2.5, 3.5, and 4.5%, with two replicates per treatment. In a second trial, another group with approximately 188 g of initial body weight was fed at feeding rates of 0, 0.5, 1.5, and 2.5%, with two replicates per treatment. The optimum thermal growth coefficient was obtained with a feed intake of 2.2% day-1 in trial A and 1.73% day-1 in trial B. The digestible protein (DP) intake for maintenance was determined as 0.57 g kg-0.7 day-1, the DP intake for maximum growth was 6.0 g kg-0.7 day-1, and the point for maximum efficiency in protein retention was 1.8 g kg-0.7 day-1. The requirement for digestible energy (DE) intake for maintenance was recorded at 25.4 kJ kg-0.82 day-1, the DE intake to maximize growth was 365 kJ kg-0.82 day-1, and the point for maximum efficiency in energy retention occurs with a digestible energy intake of 93 kJ kg-0.82 day-1. The requirements and retention efficiency of protein and energy in Argyrosomus regius tend to be within the range other fish species. The maintenance needs are in agreement with species with low voluntary activity and growth requirements in agreement with fast-growth species.

Sensitization to tomato peel and pulp extracts in the Mediterranean Coast of Spain: prevalence and co-sensitization with aeroallergens.

BACKGROUND: Tomatoes (Lycopersicon esculentum) are consumed world-wide. The prevalence of sensitization to tomatoes remains unknown. OBJECTIVE: To determine the prevalence of skin test reactivity to tomato and to describe the characteristics of tomato-sensitized subjects. METHODS: Individuals attending for the first time during the period of the study to six Allergy centres, located along the Mediterranean coast of Spain, reporting respiratory and/or cutaneous symptoms, were included. All patients were skin prick tested with a battery of inhalant allergens and with peel and pulp of Canary tomato extracts. RESULTS: The study included 1734 individuals (757 males, 977 females; 31.9+/-17.8 years old). The prevalence of sensitization to tomato was 6.52% (113 patients; 65 males, 48 females; 29.5+/-13 years old). The peel extract was positive in 110 patients and the pulp extract in 47 patients; three patients were positive exclusively to pulp. Only 1.8% of individuals reported symptoms with tomato; 44% of them had skin test negative to both extracts. Among tomato-sensitized subjects, 16% reported symptoms with tomato, 97% were sensitized to inhalant aeroallergens, including 84% to pollens (mainly Artemisia vulgaris and Platanus hybrida), with differences between Northern and Southern centres. CONCLUSIONS: The prevalence found of skin test sensitivity to tomato is high. Peel extracts detected most of the sensitized subjects. Most of the sensitized subjects were asymptomatic and some patients reported symptoms without skin test sensitivity. Positive subjects were very frequently sensitized to pollens, suggesting allergen cross-reactivity. Regional differences may exist, possibly related to the pattern of sensitization to cross-reacting pollens.

Oestrogen-dependent hereditary angio-oedema with normal C1 inhibitor: description of six new cases and review of pathogenic mechanisms and treatment.

BACKGROUND: Hereditary angio-oedema (HAE) is a rare condition in which there is a deficiency in the quantity or activity of C1 inhibitor (C1INH). Recently, an additional type of HAE with no alterations in the levels or the function of C1INH has been reported. It is defined as HAE with normal C1INH, and named type III HAE or oestrogen-dependent HAE. The aim of this study is to describe the clinical and laboratory findings of six new cases of type III HAE and to review the literature about this disease. METHODS: A short description of six women with recurrent angio-oedema is provided. The characteristics of the patients are compared with the previously reported case series in a literature-based review. RESULTS: The mean age of the patients at onset was 22 years (range 16-30). All of them had angio-oedema attacks during oestrogen-based contraceptive treatment and four reported episodes during pregnancy. Four patients reported a positive past family history. Two of them had experienced episodes of laryngeal oedema. None of the patients responded to corticoids or antihistamines during the attacks. Levels and functional activity of C1INH were within the normal range in all cases. CONCLUSIONS: Clinical and laboratory findings mirror the observations of previous reports of oestrogen-dependent angio-oedema with normal C1INH. This is the first published series of type III HAE in Spain.

Predictive and prognostic clinical and pathological factors of nivolumab efficacy in non-small-cell lung cancer patients.

BACKGROUND: Immunotherapy increases overall response rate (ORR) and overall survival (OS) in patients with non-small-cell lung cancer (NSCLC). Prognostic and predictive factors are a high need. PATIENTS AND METHODS: Retrospective review of NSCLC patients treated with nivolumab was performed. Analyzed variables included age, sex, stage, performance status (PS), location of metastases, presence of tumour-related symptoms and comorbidities, number of metastasis locations, previous chemotherapy, anti-angiogenic and radiotherapy treatments, and analytical data from the standard blood count and biochemistry. RESULTS: A total of 175 patients were included. Median age was 61.5 years, 73.1% were men, 77.7% were ECOG-PS 0-1, and 86.7% were included with stage IV disease. Histology was non-squamous in 77.1%. Sixty-five received nivolumab in second line (37.1%). Thirty-eight patients had brain metastasis (22%), and 39 (22.3%) liver metastasis and 126 (72%) had more than one metastatic location. The ORR was 15.7% with median Progression free survival (PFS) 2.8 months and median OS 5.81 months. Stage III vs IV and time since the beginning of the previous line of treatment ≥ 6 vs < 6 months were associated with better response. PS 2, time since the previous line of treatment < 6 vs ≥ 6 months, and more than one metastatic location were independently associated with shorter OS in multivariable analysis (7.8 vs 2.7 months, 11.2 vs 4.6 months, and 9.4 vs 5.1 month). Finally, time since the previous treatment < 6 vs ≥ 6 months and more than one metastatic location were independently associated with shorter PFS in multivariable analysis (4.3 vs 2.3 months and 4.7 vs 2.3 months). CONCLUSION: Poor PS, short period of time since the previous treatment, and more than one metastatic location were associated with poorer prognostic.

Correction to: Predictive and prognostic clinical and pathological factors of nivolumab efficacy in non-small-cell lung cancer patients.

Clinical and Translational Oncology.

Development and validation of a new Spanish instrument to measure health-related quality of life in patients with allergic rhinitis: the ESPRINT questionnaire.

OBJECTIVES: To develop and validate an instrument to measure health-related quality of life (HRQOL) specific to patients with allergic rhinitis (AR) and primarily for use in Spanish and Spanish-speaking populations. METHODS: An initial item pool was generated from literature review, focus groups with AR patients, and consultations with clinical experts. Item reduction was performed using clinimetric and psychometric approaches after administration of the item pool to 400 AR patients. The resulting instrument's internal consistency, test-retest (2-4 weeks) reliability, known groups and convergent validity, and sensitivity to change were tested in a longitudinal, observational, multicenter study in 210 AR patients who also completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). RESULTS: The new questionnaire took a mean (SD) of 7.1 (5.4) minutes to answer. Floor and ceiling effects were less than 15% on all dimensions. Cronbach's alpha values and intraclass correlation coefficient values for six of the sevendimensions and the overall score exceeded 0.70. Statistically significant differences (P < 0.01) were observed on all ESPRINT-28 dimensions and the overall score between patients with mild (mean overall score 1.97, SD 0.99), moderate (mean overall score 2.78, SD 0.88), and severe AR (mean overall score 3.89, SD 0.87). Patients with persistent AR had worse scores (P < 0.05) on all dimensions than patients with intermittent AR. Correlations between the ESPRINT-28 and the RQLQ were generally as expected. Effect sizes for score changes between the two study visits ranged from 0.96 to 1.76 for individual dimensions and the overall score. CONCLUSIONS: This new, Spanish-developed instrument to measure HRQOL in AR patients has shown good reliability, validity, and sensitivity to change. It has also proved easy to use and administer.

The Bronze Age burials from Cova Dels Blaus (Vall d'Uixó, Castelló, Spain): an approach to palaeodietary reconstruction through dental pathology, occlusal wear and buccal microwear patterns.

This paper reports a palaeodietary investigation of the human remains found in the collective Bronze Age burial cave from Vall d'Uixó (Castelló, Spain). Dental pathology, tooth wear as well as buccal dental microwear were analysed. Percentages of dental pathologies were compared with Chalcolithic and Bronze Age sites from the same territory. Dental caries, ante-mortem tooth loss, periodontal disease and abscess frequencies indicate a diet rich in carbohydrate foods. However, dental calculus percentages and macroscopic wear patterns suggest a diet not exclusively relying on agricultural resources. In addition, buccal dental microwear density and length by orientation recorded on micrographs using a scanning electron microscope showed inter-group differences with regard to carnivorous hunter-gatherers and farming populations related to the amount of abrasives in the diet that could correspond to a different dependence on agricultural resources or food preparation technology.

Co-administration of pentoxifylline and thiopental causes death by acute pulmonary oedema in rats.

BACKGROUND AND PURPOSE: Pentoxifylline exhibits rheological properties that improve microvascular flow and it is widely used in vascular perfusion disorders. It also exhibits marked anti-inflammatory properties by inhibiting tumour necrosis factor alpha production. Thiopental is one of the most widely used drugs for rapid induction of anaesthesia. During experimental studies on the treatment of acute pancreatitis, we observed that when pentoxifylline was administered after anaesthesia with thiopental, most of the rats exhibited dyspnea, signs of pulmonary oedema and died. The aim of the work described here was to investigate the cause of the unexpected toxic effect of the combined treatment with thiopental and pentoxifylline. EXPERIMENTAL APPROACH: Pulmonary vascular permeability and arterial blood gases were measured, and a histological analysis was performed. The possible role of haemodynamic changes in the formation of pulmonary oedema was also assessed. KEY RESULTS: Co-administration of pentoxifylline and thiopental increased pulmonary vascular permeability and markedly decreased arterial pO2, with one third of rats suffering from hypoxemia. This combined treatment caused death by acute pulmonary oedema in 27% of normal rats and aggravated the respiratory insufficiency associated with acute pancreatitis in which the mortality rate increased to 60%. This pulmonary oedema was not mediated by cardiac failure or by pulmonary hypertension. CONCLUSIONS AND IMPLICATIONS: Co-administration of pharmacological doses of pentoxifylline and thiopental caused pulmonary oedema and death in rats. Consequently, pentoxifylline should not be administered when anaesthesia is induced with thiopental to avoid any possible risk of acute pulmonary oedema and death in humans.

Towards patient stratification and treatment in the autoimmune disease lupus erythematosus using a systems pharmacology approach.

Drug development in Systemic Lupus Erythematosus (SLE) has been hindered by poor translation from successful preclinical experiments to clinical efficacy. This lack of success has been attributed to the high heterogeneity of SLE patients and to the lack of understanding of disease physiopathology. Modelling approaches could be useful for supporting the identification of targets, biomarkers and patient subpopulations with differential response to drugs. However, the use of traditional quantitative models based on differential equations is not justifiable in a sparse data situation. Boolean networks models are less demanding on the required data to be implemented and can provide insights into the dynamics of biological networks. This methodology allows the integration of all the available knowledge into a single framework to evaluate the behavior of the system under different conditions and test hypotheses about unknown aspects of the disease. In this proof-of-concept study, we explored the potential of a systems pharmacology model based on Boolean networks to support drug development in SLE. We focused the analysis on the antigen presentation by the antigen presenting cells (APC) to the T-cells to evaluate the scope of this methodology in a medium size network before full implementation of the whole SLE pathway. The heterogeneity of SLE patients was replicated using this methodology simulating subjects with distinct pathway alterations. A perturbation analysis of the network coupled with clustering analysis showed potential to identify drug targets, optimal combinatorial regimens and subpopulations of responders and non-responders to drug treatment. We propose this approach as a first step towards the development of more quantitative platforms to address the current challenges in drug development for complex diseases.