Transcriptomic analysis reveals the key regulators and molecular mechanisms underlying myometrial activation during equine placentitis†.

The key event in placentitis-induced preterm labor is myometrial activation with the subsequent initiation of labor. However, the molecular mechanisms underlying myometrial activation are not fully understood in the mares. Therefore, the equine myometrial transcriptome was characterized during placentitis (290.0 ± 1.52 days of GA, n = 5) and the prepartum period (330 days of GA, n = 3) in comparison to normal pregnant mares (289.8 ± 2.18 days of GA, n = 4). Transcriptome analysis identified 596 and 290 DEGs in the myometrium during placentitis and the prepartum period, respectively, with 138 DEGs in common. The placentitis DEGs included eight genes (MMP1, MMP8, S100A9, S100A8, PI3, APOBEC3Z1B, RETN, and CXCL2) that are exclusively expressed in the inflamed myometrium. Pathway analysis elucidated that inflammatory signaling, Toll-like receptor signaling, and apoptosis pathways dominate myometrial activation during placentitis. The prepartum myometrium was associated with overexpression of inflammatory signaling, oxidative stress, and 5-hydroxytryptamine degradation. Gene ontology enrichment analysis identified several chemoattractant factors in the myometrium during placentitis and prepartum period, including CCL2, CXCL1, CXCL3, and CXCL6 in common. Upstream regulator analysis revealed 19 potential upstream regulators in placentitis dataset including transcription regulators (E2F1, FOXM1, HIF1A, JUNB, NFKB1A, and STAT1), transmembrane receptors (FAS, ICAM1, SELP, TLR2, and TYROBP), growth factors (HGF and TGFB3), enzymes (PTGS2 and PRKCP), and others (S100A8, S100A9, CD44, and C5AR1). Additionally, three upstream regulators (STAT3, EGR1, and F2R) were identified in the prepartum dataset. These findings revealed the key regulators and pathways underlying myometrial activation during placentitis, which aid in understanding the disease and facilitate the development of efficacious therapies.

Steroid synthesis and metabolism in the equine placenta during placentitis.

Equine placentitis is associated with alterations in maternal peripheral steroid concentrations, which could negatively affect pregnancy outcome. This study aimed to elucidate the molecular mechanisms related to steroidogenesis and steroid-receptor signaling in the equine placenta during acute placentitis. Chorioallantois (CA) and endometrial (EN) samples were collected from mares with experimentally induced placentitis (n = 4) and un-inoculated gestationally age-matched mares (control group; n = 4). The mRNA expression of genes coding for steroidogenic enzymes (3ßHSD, CYP11A1, CYP17A1, CYP19A1, SRD5A1, and AKR1C23) was evaluated using qRT-PCR. The concentration of these enzyme-dependent steroids (P5, P4, 5αDHP, 3αDHP, 20αDHP, 3ß-20αDHP, 17OH-P, DHEA, A4, and estrone) was assessed using liquid chromatography-tandem mass spectrometry in both maternal circulation and placental tissue. Both SRD5A1 and AKR1C23, which encode for the key progesterone metabolizing enzymes, were downregulated (P < 0.05) in CA from the placentitis group compared to controls, and this downregulation was associated with a decline in tissue concentrations of 5αDHP (P < 0.05), 3αDHP (P < 0.05), and 3ß-20αDHP (P = 0.052). In the EN, AKR1C23 was also downregulated in the placentitis group compared to controls, and this downregulation was associated with a decline in EN concentrations of 3αDHP (P < 0.01) and 20αDHP (P < 0.05). Moreover, CA expression of CYP19A1 tended to be lower in the placentitis group, and this reduction was associated with lower (P = 0.057) concentrations of estrone in CA. Moreover, ESR1 (steroid receptors) gene expression was downregulated (P = 0.057) in CA from placentitis mares. In conclusion, acute equine placentitis is associated with a local withdrawal of progestins in the placenta and tended to be accompanied with estrogen withdrawals in CA.

Effect of homeostatic T-cell proliferation in the vaccine responsiveness against influenza in elderly people.

BACKGROUND: Seasonal influenza virus infection is a significant cause of morbimortality in the elderly. However, there is poor vaccine efficacy in this population due to immunosenescence. We aimed to explore several homeostatic parameters in the elderly that could impact influenza vaccine responsiveness. METHODS: Subjects (> 60 years old) who were vaccinated against influenza virus were included, and the vaccine response was measured by a haemagglutination inhibition (HAI) test. At baseline, peripheral CD4 and CD8 T-cells were phenotypically characterized. Thymic function and the levels of different inflammation-related biomarkers, including Lipopolysaccharide Binding Protein (LBP) and anti-cytomegalovirus (CMV) IgG antibodies, were also measured. RESULTS: Influenza vaccine non-responders showed a tendency of higher frequency of regulatory T-cells (Tregs) before vaccination than responders (1.49 [1.08-1.85] vs. 1.12 [0.94-1.63], respectively, p = 0.061), as well as higher expression of the proliferation marker Ki67 in Tregs and different CD4 and CD8 T-cell maturational subsets. The levels of inflammation-related biomarkers correlated with the frequencies of different proliferating T-cell subsets and with thymic function (e.g., thymic function with D-dimers, r = - 0.442, p = 0.001). CONCLUSIONS: Age-related homeostatic dysregulation involving the proliferation of CD4 and CD8 T-cell subsets, including Tregs, was related to a limited responsiveness to influenza vaccination and a higher inflammatory status in a cohort of elderly people.

Expression Profile of the Chromosome 14 MicroRNA Cluster (C14MC) Ortholog in Equine Maternal Circulation throughout Pregnancy and Its Potential Implications.

Equine chromosome 24 microRNA cluster (C24MC), the ortholog of human C14MC, is a pregnancy-related miRNA cluster. This cluster is believed to be implicated in embryonic, fetal, and placental development. The current study aimed to characterize the expression profile of this cluster in maternal circulation throughout equine gestation. The expression profile of miRNAs belonging to this cluster was analyzed in the serum of non-pregnant (diestrus), pregnant (25 d, 45 d, 4 mo, 6 mo, 10 mo), and postpartum mares. Among the miRNAs examined, 11 miRNAs were differentially expressed across the analyzed time-points. Four of these miRNAs (eca-miR-1247-3p, eca-miR-134-5p, eca-miR-382-5p, and eca-miR-433-3p) were found to be enriched in the serum of pregnant mares at Day 25 relative to non-pregnant mares. To further assess the accuracy of these miRNAs in differentiating pregnant (25 d) from non-pregnant mares, receiver operating characteristic (ROC) analysis was performed for each of these miRNAs, revealing that eca-miR-1247-3p and eca-miR-134-5p had the highest accuracy (AUCROC = 0.92 and 0.91, respectively; p < 0.05). Moreover, eca-miR-1247-3p, eca-miR-134-5p, eca-miR-409-3p, and eca-miR-379-5p were enriched in the serum of Day 45 pregnant mares. Among those miRNAs, eca-miR-1247-3p and eca-miR-409-3p retained the highest accuracy as shown by ROC analysis. GO analysis revealed that these miRNAs are mainly implicated in nervous system development as well as organ development. Using in situ hybridization, we localized eca-miR-409-3p in the developing embryo (25 d) and extra-embryonic membranes (25 and 45 d). In conclusion, the present study is the first to elucidate the circulating maternal profile of C24MC-associated miRNAs throughout pregnancy and to suggest that serum eca-miR-1247-3p, eca-miR-134-5p, and eca-miR-409-3p could be used as pregnancy-specific markers during early gestation (25 and 45 d). Overall, the high abundance of these embryo-derived miRNAs in the maternal circulation suggests an embryo-maternal communication during the equine early pregnancy.

Valorization of date palm (Phoenix dactylifera L.) pruning biomass by co-composting with urban and agri-food sludge.

In the Mediterranean countries, there is an increasing production of date palm wastes (Phoenix dactylifera L.), not only due to the raising production of date palm fruits, but also derived from the maintenance of urban and peri-urban green areas, especially in those affected by red palm weevil (Rhynchophorus ferrugineus). The management of this increasing volume of green wastes usually concludes with a controlled disposal that implies an important loss of resources, in terms of organic matter, nutrients and energy. In addition, the rise of wastewater generation and the incentive of the wastewater treatment processes have derived in an increase of the amount of the sludge produced, which makes difficult its management. This work studies the feasibility of co-composting palm wastes with sludge from the urban and agri-food sectors as alternative treatment to manage these organic waste streams and to obtain added-value compost. For this, four mixtures (P1, P2, P3 and P4) were prepared using as main component palm leave waste (PL) mixed with different types of sludge. In the piles P1, P2 and P3, sewage sludge (SS) was used as co-composting agent, while agri-food sludge (AS) was used in P4. Throughout composting, the thermal profile of the composting piles was assessed, as were physical, chemical, physico-chemical and maturity parameters. In addition, the changes in water-soluble organic matter were assessed using chemical analytical methods and the excitation-emission matrix (EEM) fluorescence spectroscopy. The results obtained showed the viability of the co-composting process to obtain end-products with adequate maturity degree and physical characteristics for their potential use as substrates, except for the salt contents that can limit their use in some agricultural sectors.

Urotensinergic system genes in experimental subarachnoid hemorrhage.

OBJECTIVE: Cerebral vasospasm, one of the main complications of subarachnoid hemorrhage (SAH), is characterized by arterial constriction and mainly occurs from day 4 until the second week after the event. Urotensin-II (U-II) has been described as the most potent vasoconstrictor peptide in mammals. An analysis is made of the serum U-II concentrations and mRNA expression levels of U-II, urotensin related peptide (URP) and urotensin receptor (UT) genes in an experimental murine model of SAH. DESIGN: An experimental study was carried out. SETTING: Experimental operating room of the Biomedicine Institute of Seville (IBiS), Virgen del Rocío University Hospital (Seville, Spain). PARTICIPANTS: 96 Wistar rats: 74 SAH and 22 sham intervention animals. INTERVENTIONS: Day 1: blood sampling, followed by the percutaneous injection of 100µl saline (sham) or blood (SAH) into the subarachnoid space. Day 5: blood sampling, followed by sacrifice of the animals. MAIN VARIABLES OF INTEREST: Weight, early mortality, serum U-II levels, mRNA values for U-II, URP and UT. RESULTS: Serum U-II levels increased in the SAH group from day 1 (0.62pg/mL [IQR 0.36-1.08]) to day 5 (0.74pg/mL [IQR 0.39-1.43]) (p<0.05), though not in the sham group (0.56pg/mL [IQR 0.06-0.83] day 1; 0.37pg/mL [IQR 0.23-0.62] day 5; p=0.959). Between-group differences were found on day 5 (p<0.05). The ROC analysis showed that the day 5 serum U-II levels (AUC=0.691), URP mRNA (AUC=0.706) and UT mRNA (AUC=0.713) could discriminate between sham and SAH rats. The normal serum U-II concentration range in rats was 0.56pg/mL (IQR 0.06-0.83). CONCLUSION: The urotensinergic system is upregulated on day 5 in an experimental model of SAH.

TNF-α levels in HIV-infected patients after long-term suppressive cART persist as high as in elderly, HIV-uninfected subjects.

BACKGROUND: Chronic and systemic inflammatory alterations occur in HIV-infected patients and elderly uninfected subjects and in both scenarios these alterations are associated with the development of chronic morbidities and mortality. However, whether the levels of inflammatory alterations in untreated HIV-infected patients and elderly individuals are similar is unknown. Moreover, whether long-term antiretroviral therapy normalizes inflammatory alterations compared with HIV-uninfected persons of different age is not known. METHODS: We analysed soluble inflammatory levels [high-sensitivity C-reactive protein, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8 and IL-17] in a cohort of viraemic HIV-infected patients compared with (i) age-matched, (ii) elderly and (iii) non-survivor elderly, uninfected healthy controls. We longitudinally analysed the effect of long-term 48 and 96 week suppressive combined antiretroviral therapy (cART) on the soluble inflammatory levels compared with those found in control subjects. RESULTS: Baseline IL-6 and IL-8 levels were at similar or lower concentrations in untreated patients compared with healthy elderly individuals. However, TNF-α and IFN-γ levels broadly exceeded those found in survivors and non-survivor elderly individuals. Long-term suppressive cART normalized most of the inflammatory markers, with the exception of TNF-α levels, which persisted as high as those in elderly non-survivor controls. CONCLUSIONS: Chronic inflammatory alterations associated with HIV infection are maintained at a different level from those of ageing. The persistent alteration of TNF-α levels in HIV-infected patients might cause tissue damage and have implications for developing non-AIDS-defining illnesses, even when HIV replication is long-term controlled by cART.

Chronic inflammation decreases arcuate kisspeptin expression in male sheep.

Lipopolysaccharide (LPS) from Gram-negative bacteria induces an immune response and impairs reproduction through suppression of gonadotropin releasing hormone (GnRH), subsequently luteinizing hormone (LH) secretion. While there is evidence that acute inflammation inhibits kisspeptin, little is known about the impact of chronic inflammation on this key reproductive neuropeptide in livestock species. Thus, we sought to examine a central mechanism whereby LPS suppresses LH secretion in sheep. Twenty wethers were randomly assigned to one of five treatment groups: control (CON; n=4), single acute IV LPS dose (SAD; n=4), daily acute IV LPS dose (DAD; n=4), daily increasing IV LPS dose (DID; n=4), and chronic subcutaneous LPS dose (CSD; n=4). On Days 1 and 7, blood samples were collected every 12 minutes for 360 minutes using jugular venipuncture. Following blood collection on Day 7, all animals were euthanized, brain tissue was perfused with 4% paraformaldehyde, and hypothalamic blocks were removed and processed for immunohistochemistry. On Day 1, LH pulse frequency was significantly lower (p=0.02) in SAD (0.25 ± 0.1 pulses/hour), DAD (0.25 ± 0.1 pulses/hour), DID (0.35 ± 0.1 pulses/hour), and CSD (0.40 ± 0.1 pulses/hour) compared to CON (0.70 ±0.1 pulses/hour). On Day 7, only DID animals (0.35 ± 0.1 pulses/hour) had significantly lower (p=0.049) LH pulse frequency compared to controls (0.85 ± 0.1 pulse/hour). Furthermore, only DID animals (33.3 ± 10.9 cells/section/animal) had significantly fewer (p=0.001) kisspeptin-immunopositive cells compared to controls (82.6 ± 13.6 cells/section/animal). Taken together, we suggest that daily increasing doses of LPS is a powerful inhibitor of kisspeptin neurons in young male sheep and a physiologically relevant model to examine the impact of chronic inflammation on the reproductive axis in livestock.

Incidence and prevalence of multiple sclerosis in China and other Asian countries.

The prevalence of multiple sclerosis (MS) in Asian countries is thought to be lower than in Western countries, with Asian populations presenting 80% less risk of MS than white populations. Incidence and prevalence rates in Asian countries are therefore not well defined and their association with rates in neighboring countries, as well as with ethnic, environmental, and socioeconomic factors, are not well understood. We performed a comprehensive literature review of epidemiological data from China and neighbouring countries to study the frequency of the disease, focusing on prevalence, and the progression over time and the influence of sex-related, environmental, dietary, and sociocultural factors. Prevalence rates in China range between 0.88 cases/100,000 population in 1986 and 5.2 cases/100,000 population in 2013, with a non-significant upwards trend (p = .08). The increase observed in Japan, where figures ranged between 8.1 and 18.6 cases/100,000 population was highly significant (p < .001). Prevalence rates in countries with predominantly white populations are considerably higher and have increased over time, reaching 115 cases/100,000 population in 2015 (r2 = 0.79, p < .0001). In conclusion, the prevalence of MS in China appears to have risen in recent years, although Asian populations (including Chinese and Japanese populations, among others) appear to present less risk than other populations. Within Asia, geographical latitude appears not to be a determining factor for developing MS.

RADIOPROTECTION SURVEILLANCE OF THE TJ-II OPERATION BY TLD.

The TJ-II stellarator presently in operation at the National Laboratory of Fusion is subject to radiological surveillance in compliance with the Spanish Nuclear Regulation. During its pulsed operation hard X-rays are emitted by the runaway electrons, and soft X-rays are generated by bremsstrahlung of thermalized electrons. Inside the experimental hall, the plasma heating systems and some active diagnostics are additional sources of radiation. Outside the experimental hall, some auxiliary systems, such as high-voltage power supplies, must be checked for radiological influence. In order to verify the adequate radiological classification of the different working areas, 15 dosemeters are distributed in radiologically controlled areas close to the machine, as well as in areas of public use in the TJ-II building. The integrated dose equivalent is analyzed to help establish the range of radiological influence of the stellarator. The results of the period 2015-20 are presented and analyzed.

Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) and the Spanish Society of Pediatric Intensive Care (SECIP) consensus recommendations for ECMO transport.

The evolution of extracorporeal membrane oxygenation treatment and the transport of patients receiving this treatment has changed dramatically in the last decade unevenly in different regions. The creation of specialized referral centers has been shown to improve outcomes. For all these reasons, it has been necessary to create networks of specialized teams and the number of secondary transports of patients with this treatment is increasing. In order to improve the quality of treatment and offer a guide to the services involved in these transports, the critical transport working groups of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) and the Spanish Society of Pediatric Intensive Care (SECIP) have carried out a joint effort to prepare these recommendations, focused on the following aspects: indications, reference center systems, means of transport, characteristics and equipment, human teams, training and clinical safety.

The social and occupational consequences of the COVID-19 pandemic among patients with multiple sclerosis in three distinct populations: A web-based cross-sectional survey.

Background: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the disease COVID-19, has caused a pandemic that has rapidly affected the whole world and caused a significant threat to public health. The aim of this study was to investigate and analyze the social and occupational effects of the COVID-19 pandemic on patients with multiple sclerosis (MS) in three different countries: China, Spain, and Cuba. Methods: A cross-sectional survey was designed to assess the social and occupational effects of the COVID-19 pandemic in MS patients in these three countries, using a 25-item anonymous online questionnaire, structured into three sections. Quantitative data are expressed as mean (standard deviation), and quantitative data as absolute frequency and percentage. Results: A total of 361 participants responded to the questionnaire: 194 from China, 104 from Spain, and 63 from Cuba. We found no cases of COVID-19 among Chinese patients with MS, and few cases in Spain and Cuba. Respondents reported different levels of impact on relationships with friends, family, and colleagues, and patients in all three countries described increased use of digital or social media platforms. Spanish patients reported a significantly less negative impact than those in Cuba and China. Mental and cognitive effects were similar in all three countries, although China seemed to have a better situation. We also found that the time spent exercising decreased at specific points during the pandemic, but with few changes in dietary habits. Patients reported little or no change in their means of transport in all three countries. Most patients in all three countries reported little or no physical deterioration, especially in Chinese patients (82.47%), compared to the Spanish (70.20%) and Cuban respondents (73.02%). In general, patients from all three countries demonstrated confidence in overcoming the COVID-19 pandemic, although to a lesser extent among Spanish respondents. Conclusions: During the pandemic, family support was more effective in China than in Cuba and Spain. Neither COVID-19 infections nor the number of MS relapses increased significantly during lockdown in any of the three countries. Regarding their economic situation, Spanish MS patients reported a significantly less severe negative impact than those in Cuba and China. Patients from all three countries used digital or social media platforms more frequently, probably to maintain personal relationships. Chinese and Cuban respondents were more confident of the control of the pandemic than the Spanish, who were more pessimistic.

Introducción: El nuevo coronavirus de tipo 2, causante del síndrome respiratorio agudo severo o COVID-19, se ha expandido rápidamente a nivel mundial, convirtiéndose en una grave amenaza para la salud pública en forma de pandemia. El objetivo de este estudio es analizar los efectos sociolaborales de la pandemia de COVID-19 en pacientes con esclerosis múltiple (EM) en 3 países diferentes (China, España y Cuba). Métodos: Diseñamos un estudio transversal para valorar los efectos sociolaborales de la pandemia de COVID-19 en pacientes con EM procedentes de China, España y Cuba mediante un cuestionario digital de 25 preguntas divididas en 3 apartados. Los datos cuantitativos se expresan como medias y desviaciones estándar, mientras que los datos cualitativos se expresan mediante valores y porcentajes. Resultados: Un total de 361 pacientes respondieron al cuestionario (194 de China, 104 de España y 63 de Cuba). No encontramos ningún paciente chino con EM que hubiera padecido COVID-19, y los casos diagnosticados en España y Cuba fueron muy infrecuentes. A raíz de la pandemia, se observaron cambios en las relaciones con amigos, familiares y compañeros; además, los pacientes con EM usaron plataformas digitales y redes sociales con más frecuencia en los 3 países. El impacto negativo fue significativamente menor en España que en Cuba o China. Los efectos mentales y cognitivos de la pandemia fueron similares en los 3 países, aunque parece que la situación previa era mejor en China. Igualmente, observamos que el tiempo dedicado al ejercicio se redujo en momentos específicos durante la pandemia. Por el contrario, no se detectaron grandes cambios en los hábitos alimentarios. Los pacientes de los 3 países consideraron que no se produjeron cambios en su medio de transporte, o que estos fueron escasos. La mayoría de los pacientes ha experimentado poco o ningún deterioro físico, particularmente los pacientes chinos (82,47%) en comparación con los españoles (70,20%) y cubanos (73,02%). En líneas generales, todos los pacientes se mostraron esperanzados en superar la pandemia, aunque los pacientes españoles en menor grado. Conclusiones: Durante la pandemia, el apoyo familiar fue más importante en China que en Cuba o España. En ninguno de los 3 países se observó un aumento significativo en el número de casos de COVID-19 ni de brotes o recaídas durante el periodo de confinamiento. En términos económicos, los pacientes con EM españoles sufrieron un impacto negativo significativamente menor que los cubanos y chinos. Todos los pacientes usaron plataformas digitales o redes sociales con más frecuencia, probablemente con el fin de mantener relaciones personales. Los pacientes chinos y cubanos mostraron mayor confianza en el control de la pandemia que los españoles, que resultaron ser más pesimistas.

CYFRA 21-1 as a tool for distant metastasis detection in lung cancer.

BACKGROUND: A study to analyse tumor markers (CEA, CA125, CA15.3, CA19.9, CYFRA 21-1, and NSE) for metastasis detection in lung cancer patients. METHODS: Serum tumor markers from 73 lung cancer patients were measured before they were diagnosed. After lung cancer diagnosis, tumor markers were analyzed for the detection of distant metastases. RESULTS: In NSCLC patients CYFRA 21-1 and NSE showed differences between stage IV and any of the other stages, p < 0.05. The accuracy for metastasis detection was AUC = 81.5 % for CYFRA 21-1 and AUC = 78.6 % for < 0.05) were independent predictors for metastasis presence. No tumor marker showed significant differences according to stages in SCLC patients. CONCLUSIONS: CYFRA 21-1 could be used as a screening tool for metastasis detection in lung cancer patients without symptoms of metastasis as well as CYFRA 21-1 and NSE in NSCLC patients.

[Role of vaginal infection in fetal and neonatal mortality]. / Ruolo delle infezioni vaginali nella mortalità fetale e neonetale.

Preterm delivery is the chief problem in obstetrics today and the main determinant of infant mortality and morbidity. Despite the dramatic decrease in infant mortality rate during the past several years, the percentage of preterm (<37 weeks gestation) and low birth weight (LBW) (<2500) rates remain elevated. Approximately 10% of all births are preterm, with a rate of 1-2% of infant born before the end of the 32 weeks of gestation and with a weight <1500 g. Despite the importance of the problem, the majority of preterm live births remain unexplained, and programmatic attempts at reversing the high level of preterm births have not been successful. Numerous studies have linked bacterial vaginosis, chorioamniotitis and endometritis with preterm birth and LBW, especially among African women. The number of preterm live births among African women is twice the one among Caucasians. Bacterial vaginosis is an independent risk factor for preterm and LBW births and the mechanism by which bacterial vaginosis causes the preterm birth of an infant with LBW is unknown. The aim of this article was to underline the importance of the treatment and early identification of vaginal infection, in particular if due to bacterial vaginosis, as it can have a substantial affect on the incidence of preterm delivery with LBW.

Lung nodule management: a new classification proposal.

Management of solitary pulmonary nodule (SPN) and micronodule (SPMN) is still debated. The use of 18F-FDG PET/CT or CT multislice screening for early lung cancer detection, have increased the frequency of displaying indeterminate single lung nodule with diameter between 0.1 cm and 2 cm. The first choice is to wait and do radiological follow-up, since the evaluation of temporal changes in a small mass may contribute to differentiate a malign from benign pathology. In case of unchanged images not capable of orientating the diagnostician or no possible preoperative diagnosis by bronchoscopy and percutaneous needle biopsy, surgical treatment is necessary allowing the histological characterization of lesion and a good prognosis of disease. Video-assisted thoracoscopic surgery and muscle-sparing minithoracotomy have become routine, each of these furnishing precise indications. The purpose of the study was to establish the main investigative method for indeterminate lung nodules, considering the continuous evolution of endoscopic and radiological techniques.

[Pembrolizumab-associated autoimmune encephalitis in an elderly patient with advanced non-small cell lung cancer. A clinical case].

Therapeutic objectives for the geriatric patient are improvement of quality of life and functional capacity rather than a mere increase in survival. In neoplastic disease, the decision to initiate administration of curative therapies, especially immunotherapy, should be taken only after any potential risks have been taken into account. Geriatric patients are more susceptible to developing more serious adverse reactions than the younger population. We report the case of an octogenarian patient with non-small cell lung cancer who developed neurologic toxicity following pembroli-zumab therapy. We carry out a differential diagnosis of encephalitis and provide a literature review of pembrolizumab-associated auto-immune encephalitis cases in order to improve our knowledge of this unusual toxicity. An interdisciplinary approach and comprehensive geriatric assessment are essential components to prevent functional decline in the elderly.

Olive mill wastewater-evaporation ponds long term stored: Integrated assessment of in situ bioremediation strategies based on composting and vermicomposting.

During the last two decades, the method most widely used to manage olive mill wastewater (OMW) derived from olive oil production has been its disposal in evaporation ponds. Long-term storage of OMW leads to the accumulation of toxic sediments (OMWS) rich in recalcitrant compounds with phytotoxic and antimicrobial properties, which limit their use for agronomic purpose. The aim of this study was to compare the effect of two in situ bioremediation strategies (composting and a combination of composting followed by vermicomposting) to remove the potential toxicity of the sediments derived from long-term stored OMW. The results obtained showed that the composting method assisted with the earthworms enhanced the depletion of phenolic compounds and OMWS ecotoxicity more than composting, especially during the maturation stage. Moreover, vermicomposting was more effective in the reduction of the OMWS salinity. However, a pre-composting process to the OMWS is necessary prior to vermicomposting to provide the suitable conditions for earthworms survival and activity. Furthermore, the final compost showed a phytostimulating effect. Therefore, these in situ bioremediation strategies can be considered potential tools for decontamination and recovery of long-term stored OMWS in evaporation ponds, which currently poses an unsolved environmental problem.

Changes in circulating concentrations of testosterone and estrone sulfate after human chorionic gonadotropin administration and subsequent to castration of 2-year-old stallions.

Reproductive steroids testosterone (T) and estrone sulfate (E1S) are used as diagnostic markers for cryptorchidism in horses. The human chorionic gonadotropin (hCG) stimulation test is used as a diagnostic aid because administration of this hormone results in greater incremental differences in circulating steroid concentrations. Thoughts regarding optimal sampling times following hCG administration, however, are inconsistent. Additionally, determination of half-life of these steroids is important in postsurgical samples to confirm complete removal of testicular tissue. Objectives of this study, therefore, were to determine optimal sampling periods for peak T and E1S after hCG administration and half-life of these steroids after castration. Eight pony stallions were randomly assigned to control or treatment groups (5000 IU hCG). Blood samples were collected following hCG administration. Subsequently, stallions were castrated and blood samples were collected post-castration. The T concentrations were greatest at 72 h after hCG and were greater (P < 0.02) in samples from hCG-treated than control animals: 9,903.4 ± 384 and 784.0 ± 192 pg/mL, respectively (Mean ± SEM). The T concentrations were also greater at 1, 12, 24, 48 and 96 h. The E1S concentrations did not change after administration of hCG. The T response to hCG administration was biphasic with a maximal response between 48-96 h after administration. Half-lives of T and E1S were 1.1 and 0.7 h, respectively, and concentration of T and E1S was similar to that of geldings at 24 h post-castration, which, therefore, should be considered an optimal time to ensure complete castration has occurred.

Serum amyloid A, Serum Amyloid A1 and Haptoglobin in pregnant mares and their fetuses after experimental induction of placentitis.

Serum amyloid A (SAA) and Haptoglobin (Hp) are acute phase proteins, produced during inflammation, such as placentitis. In horses, SAA and SAA1 are protein coding genes. Objectives were to analyze SAA and Hp concentrations and relative abundance of SAA, SAA1 and Hp mRNA transcript in maternal and fetal tissues after experimental induction of placentitis or mares of a control group. Serum Amyloid A family proteins were in marked abundance in the stroma of the endometrium and chorioallantois associated with inflammatory cells. Maternal plasma SAA concentrations were greater (P = 0.01) in mares with experimentally induced placentitis compared to those of the control group. Maternal Hp from the groups were not different, but fetal Hp concentrations of mares with experimentally induced placentitis were greater (P = 0.02). Maternal plasma SAA and Hp concentrations were greater than fetal plasma concentrations in mares with experimentally induced placentitis (P < 0.05). Relative abundance of SAA mRNA transcript was greater in the maternal, fetal liver and chorioallantois of mares with experimentally induced placentitis (P < 0.05) compared to those in the control group. Interestingly, relative abundance of SAA1 mRNA transcript was greater in the chorioallantois of mares with experimentally induced placentitis (P < 0.05). The SAA and Hp concentrations, therefore, were greater in mares with induced placentitis. Furthermore, relative abundance of SAA1 mRNA transcript is specifically greater in the chorioallantois of mares with placentitis, which warrants further studies to elucidate the immunological response of SAA1 in the chorioallantois of mares with placentitis.

A novel interplay between membrane and nuclear melatonin receptors in human lymphocytes: significance in IL-2 production.

Human lymphocyte melatonin, through membrane and nuclear receptors binding, acts as an activator in IL-2 production. Antagonism of membrane melatonin receptors using luzindole exacerbates the drop of the IL-2 production induced by PGE(2) in peripheral blood mononuclear and Jurkat cells. This paper studies the melatonin membrane and nuclear receptors interplay in PGE(2)-diminished IL-2 production. The decrease in IL-2 production after PGE(2) and/or luzindole administration correlated with downregulation in the nuclear receptor RORalpha. We also highlighted a role of cAMP in the pathway, because forskolin mimicked the effects of luzindole and/or PGE(2) in the RORalpha expression. Finally, a significant RORalpha downregulation was observed in T cells permanently transfected with inducible MT(1) antisense. In conclusion, we show a novel connection between melatonin membrane receptor signalling and RORalpha expression, opening a new way to understand melatonin regulation in lymphocyte physiology.