Compassionate use of esketamine intranasal in patients with severe major depressive disorder resistant to the treatment.

BACKGROUND: Treatment-resistant depression (TRD) is defined as the failure of at least two antidepressants in adequate doses and timing during a major depressive episode. Esketamine intranasal (ESK-IN) has been approved by the Food and Drug Administration and the European Medicines Agency for the treatment of TRD in combination with other antidepressants. AIMS: To assess the effectiveness and tolerability of a sample of TRD patients who received treatment with ESK-IN as part of the compassionate use program. METHODS: A retrospective, observational study was carried out on patients with a diagnosis of TRD enrolled in the early access program of ESK-IN in nine centers. Effectiveness was assessed with the Montgomery-Asberg depression rating scale (MADRS) at four time points: baseline, 28, 90, and 180 days of treatment. RESULTS: The sample included 71 patients (70% women) with a mean baseline MADRS score of 38.27 ± 5.9 and total or partial work disability rates of 85%. ESK-IN treatment was associated with a statistically and clinically significant reduction in the severity of depressive symptoms at all time points assessed. The presence of side effects was common but the majority were mild in severity and resolved after the observation period. Those patients who received psychotherapy in combination with ESK-IN showed a significantly lower MADRS score at 90 and 180 days than those patients who did not undergo psychotherapy. CONCLUSION: ESK-IN has proven to be effective and safe in a clinical sample of patients with severe TRD. To optimize clinical outcomes, the pharmacological treatment for TRD should always be integrated into a comprehensive therapeutic plan that encompasses strategies such as psychotherapy, social support, and family interventions.

Long-term COVID-19 pandemic impact on suicide Thoughts and Behaviors (STB): An interrupted time series analysis in Spain 2-year after pandemic outbreak.

This study assessed the impact of the COVID-19 pandemic on suicidal thoughts and behaviors (STB) by age and gender in Cantabria, Spain, from January 2019 to March 2022, using interrupted time series analysis. Post-lockdown, STB declined in males (-42 %, p = 0.01) and females (-25 %, p = 0.58), with a gradual increase in both genders. The reduction was most pronounced in older adults (-39 %, p = 0.56), followed by middle-aged (-26 %, p = 0.36) and younger groups (-8.3 %, p = 0.25). Subsequent upward trends in STB were more pronounced in younger (p = 0.15) and older age groups (p = 0.25), likely due to prolonged isolation and economic hardship.

Effectiveness of early and intensive intervention on suicide prevention: CARS programme.

The aim of this study was to evaluate the outcomes of the Programme for Management of Suicidal Behaviour and Suicide Prevention (CARS). Individuals treated in the emergency department of University Hospital Marqués de Valdecilla for suicidal thoughts or attempts (N = 401) between 1-March-2016 and 31-December-2018 were considered. No randomization by patients or groups was performed. Student's t-test, chi-square and repeated measure analysis of variance were used. Kaplan-Meier survival function and Cox proportional hazard regression models were employed to estimate the risks of relapse. Outcome of those who voluntary enrol CARS were compared with treatment as usual (TAU) at 6- and 12-months follow-up. The results indicate a significant reduction and delayed occurrence of suicidal behaviour over a 12-month follow-up period with the CARS programme compared to TAU, along with a decreased frequency of hospital admissions. CARS programme demonstrates a substantial impact, significantly reducing the risk of recurrent suicidal behaviour by 35.5 % and the risk of repeated suicidal attempts by 47.2 % at the 12-month follow-up. The programme exhibits a dual protective effect, diminishing suicidal behaviour and fostering improved long-term outcomes. In conclusion, CARS effectively reduced suicidal behaviour recurrence, achieving significant decreases in suicidal thoughts, plans and attempts.

Meningoencephalitis due to Mycobacterium lentiflavum in an immunocompromised patient: Case report.

The first case of meningoencephalitis due to Mycobacterium lentiflavum in an immunocompromised patient is reported. Clinical and radiological characteristics are described, as well as the treatment and prognosis of the patient.

Approach to a fungal treatment of a biologically treated landfill leachate.

White-rot fungi (WRF) have the ability to synthetize extracellular enzymes that could degrade recalcitrant pollutants. The aim of this work was to evaluate the use of P. chrysosporium to treat a biologically and physically pre-treated landfill leachate which high load of refractory compounds (COD>1000 mg/L, BOD5<50 mg/L) in order to reduce COD and colour. Batch tests were carried out at 26 °C and 135 rpm for 15 days. The soluble chemical oxygen demand (sCOD), soluble biological oxygen demand (sBOD5) and colour, as well as the lignin peroxidase (LiP) and manganese peroxidase (MnP) enzymatic activities were analysed. Besides, the effects of different operating conditions, i.e., pH control, permeate dilution and supplementation, on treatment efficacy were investigated. The control of pH was shown to be key for fungal treatment. In addition, it was found that the addition of carbon and nitrogen sources improved the enzymatic synthesis and the removals of sCOD and colour. Data here obtained open the possibility of using fungi for reducing the amount of recalcitrant pollutants still present in treated landfill leachates or similar effluents.

Evaluating and Handling the Pain of People With Intellectual Disability.

Anecdotal reports have suggested people with intellectual disabilities experience more pain than the general population due to additional co-morbidities and secondary conditions. This multicenter comparative cross-sectional study aimed to evaluate the prevalence, factors, and treatment modalities in people with intellectual disabilities (PID) as observed by their caregivers and reported through distributed questionnaires. The study sample included 130 PID users of centers in Ciudad Real (Spain). Variables related to sociodemographic characteristics, health problems, problem behaviors, and pain were collected. Among participants, 78 (60%) of PID were males, and their mean age was 43.8 years (SD = 13.57). Pain was identified in 29 PID (22.3%; 95% confidence interval [CI] 14.99-29.81), and drugs for pain were administered to 33 PID (26.4%; 95%CI 19-34). The prevalence of pain in the sampled PID, its severity, and the analgesic administration rate were lower than those in the general population. This situation may be aggravated for PID with communication problems.

Suicidal behaviour: emergency department attendance for suicidal recurrence and other psychiatric or medical reasons in the 6 months following the index episode.

The prevention of a complex phenomenon, such as suicide, requires an interdisciplinary approach that provides a comprehensive response to the care needs of people with suicidal behavior (SB). The aim of this study is to investigate the clinical and healthcare features of people presenting thoughts and/or attempts of suicide to define risk factors for recurrence.

Conducta Suicida: frecuentación en elservicio de urgencias por recurrenciasuicida y otros motivos psiquiátricos omédicos en los 6 meses posteriores alepisodio índice / Suicidal Behaviour: frequentation in the emergency emergency department for suicidal recurrence suicidal recurrence and other psychiatric or medical medical reasons in the 6 months after the index episode

Introducción: El suicidio es un fenómeno complejo cuyaprevención requiere un abordaje interdisciplinar que proporcione respuesta integral a las necesidades asistenciales de laspersonas con conductas suicidas (CS). El objetivo de este estudio es investigar las características clínicas y asistencialesde las personas que presentan ideas y/o tentativas de suicidiopara definir factores de riesgo de recurrencia.Método. Se ha llevado a cabo un estudio de cohorte conseguimiento de 6 meses. La cohorte está constituida por laspersonas atendidas en el servicio de urgencias del HospitalUniversitario Marqués de Valdecilla (Santander) por ideas y/otentativas de suicidio, durante un periodo de reclutamientode 4 meses: 1-marzo a 30-junio 2015. Se recogen variablessociodemográficas y clínicas en el episodio índice y las visitasal servicio de urgencias durante los siguientes 6 meses.Resultados. 143 pacientes valorados por CS, informacióndisponible para seguimiento en 110 (edad media 43,31 años;rango 16-84; 65% mujeres). Hubo 21% de recurrencia de CS:10% tentativas, 6% ideación, 5% ambas; 1 (0,7%) suicidio;con mayor frecuencia entre 30-65 años y con enfermedadmental. Durante el seguimiento el 60% consultó repetidamente no solo por CS sino también por otros motivos psiquiátricos o médicos, independientemente del seguimientoen salud mental.Conclusiones. La recurrencia de CS es frecuente a pesar deestar en seguimiento en el servicio de salud mental. Además,las personas con CS consultan frecuente y reiteradamente enurgencias por otros motivos psiquiátricos y médicos, lo quesugiere que el abordaje convencional de la comorbilidad conla CS resulta insuficiente. (AU)

Introduction: The prevention of a complex phenomenon, such as suicide, requires an interdisciplinary approachthat provides a comprehensive response to the care needs ofpeople with suicidal behavior (SB). The aim of this study isto investigate the clinical and healthcare features of peoplepresenting thoughts and/or attempts of suicide to define riskfactors for recurrence.Methods. A cohort study was carried out with a 6-monthfollow-up. The cohort consisted of persons admitted to theemergency department of the Hospital Universitario Marqués de Valdecilla (Santander) presenting thoughts and/orattempts of suicide, throughout a 4-month recruitment period: 1-March to 30-June 2015. Sociodemographic and clinical variables were collected in the index episode and visits tothe emergency department during the following 6 months.Results. 143 patients were assessed by SB, and it waspossible to collect information on recurrence in 110 (averageage of 43.31; range 16-84; 65% women). Twenty-one percent presented recurrence of SB: 10% attempted, 6% thoughts, and 5% both; 1 (0.7%) committed suicide; most frequently with age 30-65 years and with a history of mentalillness. During follow-up, 60% consulted repeatedly in theemergency department not only for SB but also for otherpsychiatric or medical reasons, independently of follow-upin the mental health service.Conclusions. Recurrence of SB is common despite beingfollowed up in the mental health service. In addition, peoplewith SB frequently and repeatedly consult the emergencydepartment for other psychiatric and medical reasons, suggesting that the conventional approach to comorbidity withSB is insufficient. Further studies are needed to define riskprofiles and design specific interdisciplinary strategies for SBmanagement and suicide prevention, avoiding fragmentation. This will contribute more efficiently to early identification, appropriate management and prevention of suiciderecurrences and deaths. (AU)

Selective Interleukin-6 Trans-Signaling Blockade Is More Effective Than Panantagonism in Reperfused Myocardial Infarction.

Interleukin (IL)-6 is an emerging therapeutic target in myocardial infarction (MI). IL-6 has 2 distinct signaling pathways: trans-signaling, which mediates inflammation, and classic signaling, which also has anti-inflammatory effects. The novel recombinant fusion protein sgp130Fc achieves exclusive trans-signaling blockade, whereas anti-IL-6 antibodies (Abs) result in panantagonism. In a rat model of reperfused MI, sgp130Fc, but not anti-IL-6-Ab, attenuated neutrophil and macrophage infiltration into the myocardium, reduced infarct size, and preserved cardiac function 28 days after MI. These data demonstrate the efficacy of exclusive IL-6 trans-signaling blockade and support further investigation of sgp130Fc as a potential novel therapy in MI.

Physico-chemical pre-treatments of anaerobic digestion liquor for aerobic treatment.

Centrifugation of anaerobically digested sewage sludge gives rise to a solid phase, which could be employed as a fertilizer, and a liquid fraction (ADL), which should be treated before being spilled out. This is not an easy task because this liquor is characterized for presenting high COD (~16000 mg O2/L), high ammonium content (~4000 mg/L) and low biodegradability (BOD5/COD ~0.2). With the objective to pre-treat this aqueous waste before its treatment by means of more traditional aerobic processes, different physico-chemical methods (ultrasound, ozonation, hydrolysis and wet air oxidation) were assessed in this work. Ultrasound and thermal hydrolysis gave solubilizations around 47% and 68% respectively. The best results in terms of total COD removal were obtained when wet air oxidation (8 h, 160 C-200 °C and 6.0 MPa) and ozonation (8 h, 25 °C, 12 g/h O3) techniques were employed achieving COD degradations of 71% and 38%, respectively. The pre-treatment of ADL with the four assayed techniques improved considerably the biodegradability (BOD5/COD) of the effluent, with values around 0.3-0.4, depending on the treatment. The experimental data were successfully fitted by kinetic models and the kinetic constants for the solubilization and degradation steps were obtained. Application of the proposed models can be of interest for the optimization and selection of the most suitable techniques and operational conditions, in each particular case.

Recurrence of suicidal thoughts and behaviors during one year of follow-up: An exploratory study.

Suicidal thoughts and behaviors (STB) include suicidal ideation (SI), suicide attempt (SA) and completed suicide. We aimed to identify recurrence predictors of any type of STB, and separately for SA and SI, and to analyze the time until event. A 108-subject cohort presenting at Emergencies with STB was followed during one year. Recurrence risk factors were investigated by multiple Cox survival regressions. Within one year, 31.5%, 23.1% and 9.3% patients recurred with any STB, SA, and SI respectively. Most recurrences (~70%) occurred within the first 6 months. Seeking emergency psychiatric assistance for problems other than STB during follow-up was a common predictor for recurrence of any STB, and SA and SI specifically. Previous SA history and contact with psychiatry outpatient units during follow-up predicted both STB in general and SA in particular. A specific predictor for SA was hospitalization at index, while SI recurrence was associated to SI at index. These results highlight the importance of early intervention and multidisciplinary follow-up considering concurrent psychosocial or adaptive problems. A careful exploration at Emergencies is needed to target potential predictors.

Impact of anaerobic digestion and centrifugation/decanting processes in bacterial communities fractions.

Sewage sludge can be treated by anaerobic processes that frequently are followed by physical separation processes. In this work, a high-throughput sequencing technology, based on variation in the bacterial 16S rRNA gene, has been used to characterise the bacterial populations present in samples taken from different points of an industrial anaerobic digestion process fed with sewage sludge. Relative abundances of phyla and classes throughout the biological process and the subsequent separation steps were determined. Results revealed that the Bacteroidetes, Firmicutes and Proteobacteria phyla were the most representative. However, significant changes in relative abundance were detected along treatments, showing the influence of operational parameters on the distribution of microorganisms throughout the process. After anaerobic digestion, phylum Firmicutes doubled its relative abundance, which seems to indicate that the anaerobic conditions and the nutrients favoured its growth, in contrast to other phyla that almost disappeared. After centrifugation, Proteobacteria went preferentially to the solid phase, in contrast to Firmicutes which was the dominant phylum in the liquid phase. After decanting the liquid phase during 45 h, an important growth of Proteobacteria, Spirochaetes and Tenericutes was detected. At class level, only significantly changes were observed for Proteobacteria classes being α-proteobacteria dominant in the digestate, while γ-proteobacteria was the majority since this point to the final steps. To know the changes on the kind and abundance of microbial populations throughout the anaerobic and separation processes is very important to understand how the facilities design and operation conditions can influence over the efficiencies of next biological treatments.

Valoración del diámetro interno del dializador en hemodiafiltración on-line / Evaluation of the dialyser inner diameter in online haemodiafiltration

Introducción: Se ha asociado la hemodiafiltración on-line (HDF-OL) a un aumento de la supervivencia. Hasta el momento no está bien establecida la influencia del diámetro interno de las fibras capilares del dializador sobre la capacidad convectiva. El objetivo del estudio fue valorar el efecto del aumento del diámetro interno del dializador sobre el volumen convectivo y la capacidad depurativa. Material y métodos: Se incluyeron 16 pacientes en HDF-OL posdilucional con reposición automática. Cada paciente recibió 4 sesiones, en las que se varió el diámetro interno, 185μm (FX60 Cordiax y FX80 Cordiax) versus 210μm (FX600 Cordiax y FX800 Cordiax). En cada sesión se determinaron diferentes solutos al inicio y al final de la diálisis. Resultados: El incremento de diámetro interno entre FX60 vs. FX600 y FX80 vs. FX800 no reflejó diferencias en el volumen convectivo: 32,3±3,1 vs. 31,8±3,6 y 33,7±4,3 vs. 33,5±3,8L/sesión, respectivamente. Los porcentajes de reducción tampoco mostraron diferencias: urea 83,7±4,5 vs. 84,1±3,4 para FX60 y FX600 y 82,7±4,1 vs. 83,6±3,8 para FX80 vs. FX800; creatinina similar 78,2±5,6 vs. 77,8±4,6 y 77,1±5,4 vs. 78,1±4,9; β2-microglobulina 82,2±4,3 vs. 82,9±4,2 y 82,9±4,7 vs. 84,0±3,8; mioglobina 71,0±10, vs. 70,2±9 y 72,8±11 vs. 75,0±10; prolactina 70,4±9 vs. 68,1±9 y 72,2±10 vs. 73,4±8,2; y α1-microglobulina 22,9±10 vs. 21,6±10 y 26,5±12 vs. 28,8±11, respectivamente. Conclusión: El incremento del diámetro interno de las fibras capilares no ha significado una mayor eficacia en el volumen convectivo ni en la capacidad depurativa (AU)

Introduction: Online haemodiafiltration (OL-HDF) has been associated with increased survival. To date, the influence of the inner diameter of the hollow fibres of the dialyser on convective volume has not been well established. The objective of the study was to evaluate the effect of increasing the inner diameter of the dialyser on the convective volume and removal capacity. Material and methods: We included 16 patients in posdilutional OL-HDF with autosubstitution. Each patient was analysed in 4 sessions in which the inner diameter varied; 185μm (FX60 Cordiax and FX80 Cordiax) versus 210μm (FX600 Cordiax and FX800 Cordiax). Different solutes were measured at the beginning and end of each dialysis session. Results: No differences in the convective volume were found with an increased inner diameter: 32.3±3.1 vs. 31.8±3.6 l/session (FX60 vs. FX600) and 33.7±4.3 vs. 33.5±3.8 l/session (FX80 vs. FX800). The reduction percentages also did not differ: urea 83.7±4.5 vs. 84.1±3.4 for FX60 and FX600, and 82.7±4.1 vs. 83.6±3.8 for FX80 vs. FX800; creatinine similar 78.2±5.6 vs. 77.8±4.6 y 77.1±5.4 vs. 78.1±4.9; β2-microglobulin 82.2±4.3 vs. 82.9±4.2, and 82.9±4.7 vs. 84.0±3.8; myoglobin 71.0±10 vs. 70.2±9 and 72.8±11 vs. 75.0±10; prolactin 70.4±9 vs. 68.1±9, and 72.2±10 vs. 73.4±8.2; and α1-microglobulin 22.9±10 vs. 21.6±10, and 26.5±12 vs. 28.8±11, respectively. Conclusion: The increase in the inner diameter of the hollow fibres did not result in improved convective volume and removal capacity (AU)

Evaluation of the dialyser inner diameter in online haemodiafiltration. / Valoración del diámetro interno del dializador en hemodiafiltración on-line.

INTRODUCTION: Online haemodiafiltration (OL-HDF) has been associated with increased survival. To date, the influence of the inner diameter of the hollow fibres of the dialyser on convective volume has not been well established. The objective of the study was to evaluate the effect of increasing the inner diameter of the dialyser on the convective volume and removal capacity. MATERIAL AND METHODS: We included 16 patients in posdilutional OL-HDF with autosubstitution. Each patient was analysed in 4 sessions in which the inner diameter varied; 185µm (FX60 Cordiax and FX80 Cordiax) versus 210µm (FX600 Cordiax and FX800 Cordiax). Different solutes were measured at the beginning and end of each dialysis session. RESULTS: No differences in the convective volume were found with an increased inner diameter: 32.3±3.1 vs. 31.8±3.6 l/session (FX60 vs. FX600) and 33.7±4.3 vs. 33.5±3.8 l/session (FX80 vs. FX800). The reduction percentages also did not differ: urea 83.7±4.5 vs. 84.1±3.4 for FX60 and FX600, and 82.7±4.1 vs. 83.6±3.8 for FX80 vs. FX800; creatinine similar 78.2±5.6 vs. 77.8±4.6 y 77.1±5.4 vs. 78.1±4.9; ß2-microglobulin 82.2±4.3 vs. 82.9±4.2, and 82.9±4.7 vs. 84.0±3.8; myoglobin 71.0±10 vs. 70.2±9 and 72.8±11 vs. 75.0±10; prolactin 70.4±9 vs. 68.1±9, and 72.2±10 vs. 73.4±8.2; and α1-microglobulin 22.9±10 vs. 21.6±10, and 26.5±12 vs. 28.8±11, respectively. CONCLUSION: The increase in the inner diameter of the hollow fibres did not result in improved convective volume and removal capacity.

Treatment of supermarket vegetable wastes to be used as alternative substrates in bioprocesses.

Fruits and vegetables have the highest wastage rates at retail and consumer levels. These wastes have promising potential for being used as substrates in bioprocesses. However, an effective hydrolysis of carbohydrates that form these residues has to be developed before the biotransformation. In this work, vegetable wastes from supermarket (tomatoes, green peppers and potatoes) have been separately treated by acid, thermal and enzymatic hydrolysis processes in order to maximise the concentration of fermentable sugars in the final broth. For all substrates, thermal and enzymatic processes have shown to be the most effective. A new combined hydrolysis procedure including these both treatments was also assayed and the enzymatic step was successfully modelled. With this combined hydrolysis, the percentage of reducing sugars extracted was increased, in comparison with the amount extracted from non-hydrolysed samples, approximately by 30% in the case of tomato and green peeper wastes. For potato wastes this percentage increased from values lower than 1% to 77%. In addition, very low values of fermentation inhibitors were found in the final broth.

New Wistar Kyoto and spontaneously hypertensive rat transgenic models with ubiquitous expression of green fluorescent protein.

The Wistar Kyoto (WKY) rat and the spontaneously hypertensive (SHR) rat inbred strains are well-established models for human crescentic glomerulonephritis (CRGN) and metabolic syndrome, respectively. Novel transgenic (Tg) strains add research opportunities and increase scientific value to well-established rat models. We have created two novel Tg strains using Sleeping Beauty transposon germline transgenesis, ubiquitously expressing green fluorescent protein (GFP) under the rat elongation factor 1 alpha (EF1a) promoter on the WKY and SHR genetic backgrounds. The Sleeping Beauty system functioned with high transgenesis efficiency; 75% of new rats born after embryo microinjections were transgene positive. By ligation-mediated PCR, we located the genome integration sites, confirming no exonic disruption and defining a single or low copy number of the transgenes in the new WKY-GFP and SHR-GFP Tg lines. We report GFP-bright expression in embryos, tissues and organs in both lines and show preliminaryin vitroandin vivoimaging data that demonstrate the utility of the new GFP-expressing lines for adoptive transfer, transplantation and fate mapping studies of CRGN, metabolic syndrome and other traits for which these strains have been extensively studied over the past four decades.

Enzymatic vegetable organic extracts as soil biochemical biostimulants and atrazine extenders.

The purpose of this study was to gather information on the potential effects of organic biostimulants on soil activity and atrazine biodegradation. Carob germ enzymatic extract (CGEE) and wheat condensed distiller solubles enzymatic extract (WCDS-EE) have been obtained using an enzymatic process; their main organic components are soluble carbohydrates and proteins in the form of peptides and free amino acids. Their application to soil results in high biostimulation, rapidly increased dehydrogenase, phosphatase and glucosidase activities, and an observed atrazine extender capacity due to inhibition of its mineralization. The extender capacity of both extracts is proportional to the protein/carbohydrate ratio content. As a result, these enzymatic extracts are highly microbially available, leading to two independent phenomena, fertility and an atrazine persistence that is linked to increased soil activity.

Induction of an IL7-R(+)c-Kit(hi) myelolymphoid progenitor critically dependent on IFN-gamma signaling during acute malaria.

Although the relationship between hematopoietic stem cells and progenitor populations has been investigated extensively under steady-state conditions, the dynamic response of the hematopoietic compartment during acute infection is largely unknown. Here we show that after infection of mice with Plasmodium chabaudi, a c-Kit(hi) progenitor subset positive for interleukin 7 receptor-alpha (IL-7Ralpha) emerged that had both lymphoid and myeloid potential in vitro. After being transferred into uninfected alymphoid or malaria-infected hosts, IL-7Ralpha(+)c-Kit(hi) progenitors generated mainly myeloid cells that contributed to the clearance of infected erythrocytes in infected hosts. The generation of these infection-induced progenitors was critically dependent on interferon-gamma (IFN-gamma) signaling in hematopoietic progenitors. Thus, IFN-gamma is a key modulator of hematopoiesis and innate and adaptive immunity during acute malaria infection.