Design and validation of a GMP stem cell manufacturing protocol for MPSII hematopoietic stem cell gene therapy.

Hematopoietic stem cell gene therapy (HSCGT) is a promising therapeutic strategy for the treatment of neurodegenerative, metabolic disorders. The approach involves the ex vivo introduction of a missing gene into patients' own stem cells via lentiviral-mediated transduction (TD). Once transplanted back into a fully conditioned patient, these genetically modified HSCs can repopulate the blood system and produce the functional protein, previously absent or non-functional in the patient, which can then cross-correct other affected cells in somatic organs and the central nervous system. We previously developed an HSCGT approach for the treatment of Mucopolysaccharidosis type II (MPSII) (Hunter syndrome), a debilitating pediatric lysosomal disorder caused by mutations in the iduronate-2-sulphatase (IDS) gene, leading to the accumulation of heparan and dermatan sulfate, which causes severe neurodegeneration, skeletal abnormalities, and cardiorespiratory disease. In HSCGT proof-of-concept studies using lentiviral IDS fused to a brain-targeting peptide ApoEII (IDS.ApoEII), we were able to normalize brain pathology and behavior of MPSII mice. Here we present an optimized and validated good manufacturing practice hematopoietic stem cell TD protocol for MPSII in preparation for first-in-man studies. Inclusion of TEs LentiBOOST and protamine sulfate significantly improved TD efficiency by at least 3-fold without causing adverse toxicity, thereby reducing vector quantity required.

Loss of ADAM29 does not affect viability and fertility in mice but improves wound healing.

ADAM29 (a disintegrin and metalloprotease domain 29) is a member of the membrane-anchored ADAM family of proteins, which is highly expressed in testis and may mediate different physiological and pathological processes. Although the functions of many ADAM family members have been well characterized, the biological relevance of ADAM29 has remained largely unknown. Here, we report the generation of an Adam29-deficient mouse model to delve deeper into the in vivo functions of this ADAM family member. We show that ADAM29 depletion does not affect mice viability, development, or fertility, but somehow impinges on metabolism and energy expenditure. We also report herein that ADAM29 deficiency leads to an accelerated wound healing process, without affecting cell reprogramming in mouse-derived fibroblasts. Collectively, our findings provide new insights into ADAM29 biological functions, highlighting the importance of non-catalytic ADAM proteases.

Impaired photoacclimation in a kleptoplastidic dinoflagellate reveals physiological limits of early stages of endosymbiosis.

Dinophysis dinoflagellates are predators of Mesodinium ciliates, from which they retain only the plastids of cryptophyte origin. The absence of nuclear photosynthetic cryptophyte genes in Dinophysis raises intriguing physiological and evolutionary questions regarding the functional dynamics of these temporary kleptoplastids within a foreign cellular environment. In an experimental setup including two light conditions, the comparative analysis with Mesodinium rubrum and the cryptophyte Teleaulax amphioxeia revealed that Dinophysis acuminata possessed a smaller and less dynamic functional photosynthetic antenna for green light, a function performed by phycoerythrin. We showed that the lack of the cryptophyte nucleus prevented the synthesis of the phycoerythrin α subunit, thereby hindering the formation of a complete phycoerythrin in Dinophysis. In particular, biochemical analyses showed that Dinophysis acuminata synthesized a poorly stable, incomplete phycoerythrin composed of chromophorylated ß subunits, with impaired performance. We show that, consequently, a continuous supply of new plastids is crucial for growth and effective photoacclimation in this organism. Transcriptome analyses revealed that all examined strains of Dinophysis spp. have acquired the cryptophyte pebA and pebB genes through horizontal gene transfer, suggesting a potential ability to synthesize the phycobilin pigments bound to the cryptophyte phycoerythrin. By emphasizing that a potential long-term acquisition of the cryptophyte plastid relies on establishing genetic independence for essential functions such as light harvesting, this study highlights the intricate molecular challenges inherent in the enslavement of organelles and the processes involved in the diversification of photosynthetic organisms through endosymbiosis.

A Comparison of the Clinical Characteristics of Short-, Mid-, and Long-Term Mortality in Patients Attended by the Emergency Medical Services: An Observational Study.

AIM: The development of predictive models for patients treated by emergency medical services (EMS) is on the rise in the emergency field. However, how these models evolve over time has not been studied. The objective of the present work is to compare the characteristics of patients who present mortality in the short, medium and long term, and to derive and validate a predictive model for each mortality time. METHODS: A prospective multicenter study was conducted, which included adult patients with unselected acute illness who were treated by EMS. The primary outcome was noncumulative mortality from all causes by time windows including 30-day mortality, 31- to 180-day mortality, and 181- to 365-day mortality. Prehospital predictors included demographic variables, standard vital signs, prehospital laboratory tests, and comorbidities. RESULTS: A total of 4830 patients were enrolled. The noncumulative mortalities at 30, 180, and 365 days were 10.8%, 6.6%, and 3.5%, respectively. The best predictive value was shown for 30-day mortality (AUC = 0.930; 95% CI: 0.919-0.940), followed by 180-day (AUC = 0.852; 95% CI: 0.832-0.871) and 365-day (AUC = 0.806; 95% CI: 0.778-0.833) mortality. DISCUSSION: Rapid characterization of patients at risk of short-, medium-, or long-term mortality could help EMS to improve the treatment of patients suffering from acute illnesses.

Global 30-Day Morbidity and Mortality of Primary Bariatric Surgery Combined with Another Procedure: The BLEND Study.

BACKGROUND: No robust data are available on the safety of primary bariatric and metabolic surgery (BMS) alone compared to primary BMS combined with other procedures. OBJECTIVES: The objective of this study is to collect a 30-day mortality and morbidity of primary BMS combined with cholecystectomy, ventral hernia repair, or hiatal hernia repair. SETTING: This is as an international, multicenter, prospective, and observational audit of patients undergoing primary BMS combined with one or more additional procedures. METHODS: The audit took place from January 1 to June 30, 2022. A descriptive analysis was conducted. A propensity score matching analysis compared the BLEND study patients with those from the GENEVA cohort to obtain objective evaluation between combined procedures and primary BMS alone. RESULTS: A total of 75 centers submitted data on 1036 patients. Sleeve gastrectomy was the most commonly primary BMS (N = 653, 63%), and hiatal hernia repair was the most commonly concomitant procedure (N = 447, 43.1%). RYGB accounted for the highest percentage (20.6%) of a 30-day morbidity, followed by SG (10.5%). More than one combined procedures had the highest morbidities among all combinations (17.1%). Out of overall 134 complications, 129 (96.2%) were Clavien-Dindo I-III, and 4 were CD V. Patients who underwent a primary bariatric surgery combined with another procedure had a pronounced increase in a 30-day complication rate compared with patients who underwent only BMS (12.7% vs. 7.1%). CONCLUSION: Combining BMS with another procedure increases the risk of complications, but most are minor and require no further treatment. Combined procedures with primary BMS is a viable option to consider in selected patients following multi-disciplinary discussion.

Assessment of visuospatial functions in post-Covid 19 patients: Beyond the traditional paradigm.

Several studies indicate that some cognitive changes occur after COVID-19. Visuospatial alterations have been reported in 24-40 %. These alterations may be useful as early biomarkers of neurodegenerative disease. Thus, we can emphasize the importance of visuospatial processes in cognition through quantitative and qualitative analysis of performance on the Clock Test (CDT) and the Rey-Osterrieth Complex Figure (FCRO). Our objective was to describe the performance of post COVID 19 patients in visuospatial tests, with different degrees of respiratory impairment and to perform a qualitative analysis of the performance to check its relationship with alterations in attention and executive functions. This will allow highlighting the executive component of the performance of the CDT and ROCF and differentiate patients with possible cognitive impairment. 77 patients with SARS-CoV-2 infection were evaluated (3 months post-infection) with a complete neuropsychological battery and MRI. Overall, there is a significant difference between FCRO and CDT, with FCRO having only 9 % change and CDT having 51.9 % change. Regarding the correlations observed between groups (VM Inv, VM non I and non hospitalized) the highest correlations were observed between Boston with FCRO copy (r=0.497; p=0.001) and with FCRO memory (r=0.429; p=0.001). Comparing the performance between groups by severity, significant differences were observed only in the TMT A (13.706 p=0.001) and B (9.583 p=0.008) tests and in the phonological fluency letter A (13.445 p=0.001), we observed that the group of non-hospitalized patients had a better performance. Neuropsychological deficits often have a direct impact on daily life by affecting the ability to learn and adapt. Thus, a useful strategy for the neuropsychological characterization of post-COVID-19 patients is the qualitative analysis of visuospatial abilities in conjunction with executive functions that cannot be analyzed in isolation.

Effect of Exercise Prior to Sedentary Behavior on Vascular Health Parameters: A Systematic Review and Meta-Analysis of Crossover Trials.

BACKGROUND: Sedentary behavior has been shown to negatively affect parameters of endothelial function and central hemodynamics, both of which are closely associated with vascular health. Exercise prior to sedentary behavior has demonstrated potential as a preventive strategy to mitigate these detrimental effects. To evaluate the impact of exercise prior to sedentary behavior on vascular health parameters in the adult population, a systematic review and meta-analysis were conducted, synthesizing the available body of knowledge. METHODS: A literature search was carried out in 6 databases. For each outcome, standard error and mean difference or standardized mean difference were calculated, as appropriate. An analysis was performed using a random effects model with a 95% confidence interval, using the inverse variance statistical method. Risk of bias assessment was performed using ROB2 and considerations for crossover trials. The quality of evidence was assessed using the GRADE system. RESULTS: Exercise performed prior to prolonged sedentary behavior resulted in increased flow-mediated vasodilation at the first and third hours of sedentary time, compared with the control condition of sedentary behavior without prior exercise [MD: 1.51% (95% CI: 0.57 to 2.45) and MD: 1.36% (95% CI: 0.56 to 2.16), respectively]. Moreover, prior exercise led to increased shear rate at the first and third hours of sedentary time [MD: 7.70 s^-1 (95% CI: 0.79 to 14.61) and MD: 5.21 s^-1 (95% CI: 1.77 to 8.43), respectively]. Furthermore, it increased blood flow at the third hour [SMD: 0.40 (95%CI: 0.07 to 0.72)], compared with the control condition of prolonged sedentary behavior without prior exercise. Regarding hemodynamic parameters, exercise prior to prolonged sedentary behavior decreased mean arterial pressure during the first and third hours of sedentary behavior [MD: -1.94 mmHg (95% CI: -2.77 to -1.11) and MD: -1.90 mmHg (95% CI: -3.27 to -0.53), respectively], and an increase in heart rate during the first hour [MD: 4.38 beats per minute (95%CI: 2.78 to 5.98)] compared with the control condition of prolonged sedentary behavior without prior exercise. CONCLUSIONS: The findings of this research suggest that prior exercise may prevent the impairment of vascular health parameters caused by sedentary behavior. However, the quality of the evidence was estimated as moderate. Therefore, further experimental studies and high-quality clinical trials are needed in this field to strengthen the results and conclusions drawn. PROSPERO REGISTRATION NUMBER: CRD42023393686.

Enhancing motor functional recovery in spinal cord injury through pharmacological inhibition of Dickkopf-1 with BHQ880 antibody.

BACKGROUND: Mounting experimental evidence has underscored the remarkable role played by the Wnt family of proteins in the spinal cord functioning and therapeutic potential in spinal cord injury (SCI). We aim to provide a therapeutic prospect associated with the modulation of canonical Wnt signaling, examining the spatio-temporal expression pattern of Dickkopf-1 (Dkk1) and its neutralization after SCI. We employ an intraparenchymal injection of the clinically validated Dkk1-blocking antibody, BHQ880, to elucidate its effects in SCI. METHODS: A rat model of contusion SCI was used. Histological analyses were performed, wherein Dkk1 protein was sought, and ELISA analyses were employed for Dkk1 detection in cerebrospinal fluid and serum. To ascertain the BHQ880 therapeutic effect, rats were subjected to SCI and then injected with the antibody in the lesion epicenter 24 hours post-injury (hpi). Subsequent evaluation of motor functional recovery extended up to 56 days post-injury (dpi). qRT-PCR and histological analyses were conducted. RESULTS: We demonstrate the presence of Dkk1 in the healthy rat spinal cord, with pronounced alterations observed following injury, primarily concentrated in the epicenter regions. Notably, a significative upregulation of Dkk1 was detected at 24 hpi, peaking at 3 dpi and remaining elevated until 42 dpi. Moreover, we revealed that early administration of BHQ880 considerably improved motor functional recovery, promoted preservation of myelinated tissue, and reduced astroglial and microglia/macrophage reactivity. Furthermore, there was a decrease in the acute expression of different inflammatory genes. CONCLUSIONS: Collectively, our findings highlight the therapeutic potential of BHQ880 treatment in the context of SCI.

Adapting response to a measles outbreak in a context of high vaccination and breakthrough cases: an example from Vaud, Switzerland, January to March 2024.

A measles outbreak with 51 cases occurred in the canton of Vaud, Switzerland, between January and March 2024. The outbreak was triggered by an imported case, and 37 (72.5%) subsequent cases were previously vaccinated individuals. Epidemiological investigations showed that vaccinated measles cases were symptomatic and infectious. In a highly vaccinated population, it is important to raise awareness among healthcare professionals to suspect and test for measles virus when an outbreak is declared, irrespective of the vaccination status of the patients.

Asia-Pacific consensus on long-term and sequential therapy for osteoporosis.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition. The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and antiresorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to antiresorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for individuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions: This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Modulation of neuronal dynamics by sustained and activity-dependent continuous-wave near-infrared laser stimulation.

Significance: Near-infrared laser illumination is a non-invasive alternative/complement to classical stimulation methods in neuroscience but the mechanisms underlying its action on neuronal dynamics remain unclear. Most studies deal with high-frequency pulsed protocols and stationary characterizations disregarding the dynamic modulatory effect of sustained and activity-dependent stimulation. The understanding of such modulation and its widespread dissemination can help to develop specific interventions for research applications and treatments for neural disorders. Aim: We quantified the effect of continuous-wave near-infrared (CW-NIR) laser illumination on single neuron dynamics using sustained stimulation and an open-source activity-dependent protocol to identify the biophysical mechanisms underlying this modulation and its time course. Approach: We characterized the effect by simultaneously performing long intracellular recordings of membrane potential while delivering sustained and closed-loop CW-NIR laser stimulation. We used waveform metrics and conductance-based models to assess the role of specific biophysical candidates on the modulation. Results: We show that CW-NIR sustained illumination asymmetrically accelerates action potential dynamics and the spiking rate on single neurons, while closed-loop stimulation unveils its action at different phases of the neuron dynamics. Our model study points out the action of CW-NIR on specific ionic-channels and the key role of temperature on channel properties to explain the modulatory effect. Conclusions: Both sustained and activity-dependent CW-NIR stimulation effectively modulate neuronal dynamics by a combination of biophysical mechanisms. Our open-source protocols can help to disseminate this non-invasive optical stimulation in novel research and clinical applications.

Beyond VEGF: Angiopoietin-Tie Signaling Pathway in Diabetic Retinopathy.

Complications from diabetic retinopathy such as diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) constitute leading causes of preventable vision loss in working-age patients. Since vascular endothelial growth factor (VEGF) plays a major role in the pathogenesis of these complications, VEGF inhibitors have been the cornerstone of their treatment. Anti-VEGF monotherapy is an effective but burdensome treatment for DME. However, due to the intensive and burdensome treatment, most patients in routine clinical practice are undertreated, and therefore, their outcomes are compromised. Even in adequately treated patients, persistent DME is reported anywhere from 30% to 60% depending on the drug used. PDR is currently treated by anti-VEGF, panretinal photocoagulation (PRP) or a combination of both. Similarly, a number of eyes, despite these treatments, continue to progress to tractional retinal detachment and vitreous hemorrhage. Clearly there are other molecular pathways other than VEGF involved in the pathogenesis of DME and PDR. One of these pathways is the angiopoietin-Tie signaling pathway. Angiopoietin 1 (Ang1) plays a major role in maintaining vascular quiescence and stability. It acts as a molecular brake against vascular destabilization and inflammation that is usually promoted by angiopoietin 2 (Ang2). Several pathological conditions including chronic hyperglycemia lead to Ang2 upregulation. Recent regulatory approval of the bi-specific antibody, faricimab, may improve long term outcomes in DME. It targets both the Ang/Tie and VEGF pathways. The YOSEMITE and RHINE were multicenter, double-masked, randomized non-inferiority phase 3 clinical trials that compared faricimab to aflibercept in eyes with center-involved DME. At 12 months of follow-up, faricimab demonstrated non-inferior vision gains, improved anatomic outcomes and a potential for extended dosing when compared to aflibercept. The 2-year results of the YOSEMITE and RHINE trials demonstrated that the anatomic and functional results obtained at the 1 year follow-up were maintained. Short term outcomes of previously treated and treatment-naive eyes with DME that were treated with faricimab during routine clinical practice suggest a beneficial effect of faricimab over other agents. Targeting of Ang2 has been reported by several other means including VE-PTP inhibitors, integrin binding peptide and surrobodies.

Feasibility and Short-Term Outcomes in Liver-First Approach: A Spanish Snapshot Study (the RENACI Project).

(1) Background: The liver-first approach may be indicated for colorectal cancer patients with synchronous liver metastases to whom preoperative chemotherapy opens a potential window in which liver resection may be undertaken. This study aims to present the data of feasibility and short-term outcomes in the liver-first approach. (2) Methods: A prospective observational study was performed in Spanish hospitals that had a medium/high-volume of HPB surgeries from 1 June 2019 to 31 August 2020. (3) Results: In total, 40 hospitals participated, including a total of 2288 hepatectomies, 1350 for colorectal liver metastases, 150 of them (11.1%) using the liver-first approach, 63 (42.0%) in hospitals performing <50 hepatectomies/year. The proportion of patients as ASA III was significantly higher in centers performing ≥50 hepatectomies/year (difference: 18.9%; p = 0.0213). In 81.1% of the cases, the primary tumor was in the rectum or sigmoid colon. In total, 40% of the patients underwent major hepatectomies. The surgical approach was open surgery in 87 (58.0%) patients. Resection margins were R0 in 78.5% of the patients. In total, 40 (26.7%) patients had complications after the liver resection and 36 (27.3%) had complications after the primary resection. One-hundred and thirty-two (89.3%) patients completed the therapeutic regime. (4) Conclusions: There were no differences in the surgical outcomes between the centers performing <50 and ≥50 hepatectomies/year. Further analysis evaluating factors associated with clinical outcomes and determining the best candidates for this approach will be subsequently conducted.

Spanish vs USA cohort comparison of prehospital trauma scores to predict short-term mortality.

BACKGROUND: This study aimed to evaluate three prehospital early warning scores (EWSs): RTS, MGAP and MREMS, to predict short-term mortality in acute life-threatening trauma and injury/illness by comparing United States (US) and Spanish cohorts. METHODS: A total of 8,854 patients, 8,598/256 survivors/nonsurvivors, comprised the unified cohort. Datasets were randomly divided into training and test sets. Training sets were used to analyse the discriminative power of the scores in terms of the area under the curve (AUC), and the score performance was assessed in the test set in terms of sensitivity (SE), specificity (SP), accuracy (ACC) and balanced accuracy (BAC). RESULTS: The three scores showed great discriminative power with AUCs>0.90, and no significant differences between cohorts were found. In the test set, RTS/MREMS/MGAP showed SE/SP/ACC/BAC values of 86.0/89.9/89.6/87.1%, 91.0/86.9/87.5/88.5%, and 87.7/82.9/83.4/85.2%, respectively. CONCLUSIONS: All EWSs showed excellent ability to predict the risk of short-term mortality, independent of the country.

Long-term risk of death in patients with infection attended by prehospital emergency services. / Modelo de riesgo de mortalidad a largo plazo en pacientes con infección atendidos por servicios de emergencias prehospitalarios.

OBJECTIVES: To develop and validate a risk model for 1-year mortality based on variables available from early prehospital emergency attendance of patients with infection. MATERIAL AND METHODS: Prospective, observational, noninterventional multicenter study in adults with suspected infection transferred to 4 Spanish hospitals by advanced life-support ambulances from June 1, 2020, through June 30, 2022. We collected demographic, physiological, clinical, and analytical data. Cox regression analysis was used to develop and validate a risk model for 1-year mortality. RESULTS: Four hundred ten patients were enrolled (development cohort, 287; validation cohort, 123). Cumulative mortality was 49% overall. Sepsis (infection plus a Sepsis-related Organ Failure Assessment score of 2 or higher) was diagnosed in 29.2% of survivors vs 56.7% of nonsurvivors. The risk model achieved an area under the receiver operating characteristic curve of 0.89 for 1-year mortality. The following predictors were included in the model: age; institutionalization; age-adjusted Charlson comorbidity index; PaCO2; potassium, lactate, urea nitrogen, and creatinine levels; fraction of inspired oxygen; and diagnosed sepsis. CONCLUSION: The model showed excellent ability to predict 1-year mortality based on epidemiological, analytical, and clinical variables, identifying patients at high risk of death soon after their first contact with the health care system.

OBJETIVO: Diseñar y validar un modelo de riesgo con variables determinadas a nivel prehospitalario para predecir el riesgo de mortalidad a largo plazo (1 año) en pacientes con infección. METODO: Estudio multicéntrico, observacional prospectivo, sin intervención, en pacientes adultos con sospecha infección atendidos por unidades de soporte vital avanzado y trasladados a 4 hospitales españoles entre el 1 de junio de 2020 y el 30 de junio de 2022. Se recogieron variables demográficas, fisiológicas, clínicas y analíticas. Se construyó y validó un modelo de riesgo para la mortalidad a un año usando una regresión de Cox. RESULTADOS: Se incluyeron 410 pacientes, con una tasa de mortalidad acumulada al año del 49%. La tasa de diagnóstico de sepsis (infección e incremento sobre el SOFA basal $ 2 puntos) fue del 29,2% en supervivientes frente a un 56,7% en no supervivientes. El modelo predictivo obtuvo un área bajo la curva de la característica operativa del receptor para la mortalidad a un año fue de 0,89, e incluyó: edad, institucionalización, índice de comorbilidad de Charlson ajustado por edad, presión parcial de dióxido de carbono, potasio, lactato, nitrógeno ureico en sangre, creatinina, saturación en relación con fracción inspirada de oxígeno y diagnóstico de sepsis. CONCLUSIONES: El modelo desarrollado con variables epidemiológicas, analíticas y clínicas mostró una excelente capacidad predictiva, y permitió identificar desde el primer contacto del paciente con el sistema sanitario, a modo de evento centinela, casos de alto riesgo.

Human olfactory neural progenitor cells reveal differences in IL-6, IL-8, thrombospondin-1, and MCP-1 in major depression disorder and borderline personality disorder.

Background: Discovering biological markers is essential for understanding and treating mental disorders. Despite the limitations of current non-invasive methods, neural progenitor cells from the olfactory epithelium (hNPCs-OE) have been emphasized as potential biomarker sources. This study measured soluble factors in these cells in Major Depressive Disorder (MDD), Borderline Personality Disorder (BPD), and healthy controls (HC). Methods: We assessed thirty-five participants divided into MDD (n=14), BPD (n=14), and HC (n=7). MDD was assessed using the Hamilton Depression Rating Scale. BPD was evaluated using the DSM-5 criteria and the Structured Clinical Interview for Personality Disorders. We isolated hNPCs-OE, collected intracellular proteins and conditioned medium, and quantified markers and soluble factors, including Interleukin-6, interleukin-8, and others. Analysis was conducted using one-way ANOVA or Kruskal-Wallis test and linear regression. Results: We found that hNPCs-OE of MDD and BPD decreased Sox2 and laminin receptor-67 kDa levels. MASH-1 decreased in BPD, while tubulin beta-III decreased in MDD compared to controls and BPD. Also, we found significant differences in IL-6, IL-8, MCP-1, and thrombospondin-1 levels between controls and MDD, or BPD, but not between MDD and BPD. Conclusions: Altered protein markers are evident in the nhNPCs-OE in MDD and BPD patients. These cells also secrete higher concentrations of inflammatory cytokines than HC cells. The results suggest the potential utility of hNPCs-OE as an in vitro model for researching biological protein markers in psychiatric disorders. However, more extensive validation studies are needed to confirm their effectiveness and specificity in neuropsychiatric disorders.

Study of Salmonella spp. from Cage Papers Belonging to Pet Birds in an Argentinean Canary Breeder Championship.

Birds, including canaries and other birds, have become increasingly popular as pets. Bird fairs, where breeders gather and show their production in a championship setting, present a setting for possible Salmonella spp. contamination and transmission. Therefore, this study estimated the rate of Salmonella spp. isolation from cage papers, located in the bottom of cages of exotic pet birds, including canaries. Collected Salmonella isolates were used to determine the antimicrobial resistance profile to 52 antibiotics and 17 commercial disinfectants, based on pure or a mixture of acids, alcohols, aldehydes, alkalis, halogens, peroxygen, and quaternary ammonium compounds. The samples consisted of 774 cage papers taken in the 2015 Argentinean canary breeder championship, pooling three cage papers into one sterile sampling bag. Only one pool of the cage papers was positive for Salmonella spp. (0.4%), which belonged to the sample from three frill canary cages. Two strains of Salmonella serotype Glostrup were isolated, which were only resistant to sulfonamides and erythromycin and sensitive to alkali-based product PL301 AS. Although the rate of Salmonella spp. isolation from cage papers in an Argentinean canary breeder championship is low, it should not be discounted because Salmonella ser. Glostrup can be a source of human Salmonella outbreaks and they show high resistance to disinfecting products.

Analysis of Protection and Immune Response against Teladorsagia circumcincta in Goats Immunised with Thiol-Binding Proteins from Adult Worms.

In view of the increasing occurrence of anthelmintic-resistant strains of gastrointestinal nematodes in ruminants, various alternative control strategies have been investigated, such as those based on the induction of protective immune responses by immunisation with parasite antigens. In this study, the protective activity of somatic antigens from adult worms of Teladorsagia circumcincta purified by affinity chromatography on thiol-sepharose was analysed in goats. After challenge, the enriched products induced a slight reduction in the cumulative faecal egg counts (21%) and in the number of worms (23.3%), with a greater effect on female worms, which also showed a reduction in parameters related to their fertility. These parasitological findings were associated with a Th2 immune response, with a prominent local humoral response and an eosinophilic infiltrate in the gastric mucosa (negatively associated with the fertility of female worms and the number of worms, respectively), as well as an infiltration of MCHII+, CD4+, IgG+ and IgA+ cells. However, several analyses showed an increase in CD8+ cells in the mucosa, as well as IL-2 expression in the gastric lymph nodes, which may have been associated with inhibition of protective responses or with the development of mixed Th1/Th2 responses, a finding that should be analysed in future studies.

Screening of Microalgae for Bioactivity with Antiviral, Antibacterial, Anti-Inflammatory and Anti-Cancer Assays.

Marine microalgae are a rich reservoir of natural compounds, including bioactives. Nonetheless, these organisms remain fairly unexplored despite their potential biotechnological applications. Culture collections with diverse taxonomic groups and lifestyles are a good source to unlock this potential and discover new molecules for multiple applications such as the treatment of human pathologies or the production of aquaculture species. In the present work extracts from thirty-three strains (including twenty dinoflagellates, four diatoms and nine strains from seven other algal classes), cultivated under identical conditions, were examined for their antiviral, antibacterial, anti-inflammatory and anti-cancer activities. Among these, antiviral and anti-inflammatory activities were detected in a few strains while the antibacterial tests showed positive results in most assays. In turn, most trials did not show any anti-cancer activity. Significant differences were observed between species within the same class, in particular dinoflagellates, which were better represented in this study. These preliminary findings pave the way for an in-depth characterization of the extracts with highest signals in each test, the identification of the compounds responsible for the biological activities found and a further screening of the CCVIEO culture collection.

Response of the toxic dinoflagellate Alexandrium minutum to exudates of the eelgrass Zostera marina.

Biotic interactions are a key factor in the development of harmful algal blooms. Recently, a lower abundance of planktonic dinoflagellates has been reported in areas dominated by seagrass beds, suggesting a negative interaction between both groups of organisms. The interaction between planktonic dinoflagellates and marine phanerogams, as well as the way in which bacteria can affect this interaction, was studied in two experiments using a non-axenic culture of the toxic dinoflagellate Alexandrium minutum exposed to increasing additions of eelgrass (Zostera marina) exudates from old and young leaves and to the presence or absence of antibiotics. In these experiments, A. minutum abundance, growth rate and photosynthetic efficiency (Fv/Fm), as well as bacterial abundance, were measured every 48 h. Toxin concentration per cell was determined at the end of both experiments. Our results demonstrated that Z. marina exudates reduced A. minutum growth rate and, in one of the experiments, also the photosynthetic efficiency. These results are not an indirect effect mediated by the bacteria in the culture, although their growth modify the magnitude of the negative impact on the dinoflagellate growth rate. No clear pattern was observed in the variation of toxin production with the treatments.