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Abstract Patients with chronic kidney disease (CKD) are at a high risk of cardiovascular (CV) complications. In these patients, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to reduce CV events. Mineralocorticoid receptor antagonists (MRAs) exert similar benefits in diabetic CKD, though their effects in non-diabetic CKD remain unclear. This study aimed to evaluated whether the combination of Dapagliflozin (DAPA) and Eplerenone (EPLE) would have positive effects on cardiorenal functions in a non-diabetic CKD model. CKD was induced in rats via 5/6 nephrectomy, followed by treatment with DAPA (5 mg/kg/day PO), EPLE (100 mg/kg/day PO) or the combination for 3 months following CKD induction. Cardiorenal functions were assessed after the treatment period. All treated groups showed reduced kidney fibrosis though plasma creatinine and urea levels remained unchanged. Compared to untreated CKD, EPLE or DAPA/EPLE reduced left ventricle (LV) end-diastolic pressure and LV end-diastolic pressure volume relationship, whereas DAPA alone did not achieve significant reductions. Compared to untreated CKD, EPLE and DAPA/EPLE improved cardiac perfusion but DAPA alone did not. Cardiac fibrosis in CKD was blunted by either DAPA or EPLE alone, with the combination showing an additive effect. In conclusion, co-treatment with DAPA and EPLE enhances diastolic function, cardiac perfusion and reduces myocardial fibrosis in non-diabetic CKD rats.

Introduction Psychopathological exploration (PPE) involves an assessment of the mental state of patients, where psychological signs and symptoms are analyzed, which collectively form a syndrome. To conduct this assessment, the clinician must utilize their expertise to identify the presence and authenticity of a series of symptoms that, once recognized, allow for a diagnosis (1). The presence of this subjective component could explain why, despite the continuous growth of artificial intelligence (AI), its application in clinical psychiatry practice remains limited. However, the combination of the clinician's work with AI could enhance diagnostic accuracy and our understanding of diseases (2). Objectives The objective of this study is to investigate whether AI can make accurate diagnoses through an initial psychopathological evaluation. Methods A random sample was selected from our medical records of all patients admitted to our acute mental health inpatient unit through the hospital's emergency services in the year 2022. An anonymized database was created, including sociodemographic information, the results of the psychopathological assessment in the emergency department, and the diagnosis at the time of discharge. The psychopathological assessment conducted in the emergency department was provided to the AI chatbot ChatGPT, with a request to establish a diagnosis according to the DSM-5. Diagnoses such as brief psychotic disorder, schizophreniform disorder, and schizophrenia were considered, given their acute symptom similarities, as well as major depressive disorder (unipolar) and bipolar disorder. The level of agreement between both diagnoses was evaluated using the kappa coefficient. Results The sample consisted of 15 patients, of whom 60% were male, with a mean age of 45 years (standard deviation = 15.6). 73.3% of the patients had prior mental health follow-up, and 66.7% had been previously hospitalized. Diagnoses included psychotic disorder in 33.3% of cases, bipolar disorder with manic episode in 26.7%, depressive disorder in 13.3%, delusional disorder in 13.3%, schizoaffective disorder in 6.7%, and borderline personality disorder in 6.7%. A kappa value of 0.561 was obtained, indicating a moderate degree of agreement between the diagnoses. Conclusions Despite the inherent subjectivity in psychopathological assessment, this study suggests that AI, in the form of natural language processing chatbots like ChatGPT, can be a useful tool to assist mental health professionals in the diagnostic process. While AI shows promising potential, it should not entirely replace the experience and clinical judgment of mental health professionals. Instead, the importance of potential collaboration between AI and clinicians for achieving more precise and comprehensive diagnoses is highlighted. Disclosure of Interest None Declared

Introduction It is estimated that the prevalence of severe Intellectual Disability (ID) is 6 per 1,000 people. ID is sometimes the cause of Behavioral Disorders (BD) with aggressive and impulsive behaviors that make family and social life difficult. However, despite its high prevalence, the number of studies on it is very scarce. When BD appears, it should be evaluated if there is a physical or psychiatric cause that causes it and assess non-pharmacological treatments. If they are insufficient, treatments such as risperidone are used to manage BD. When these are ineffective, the use of drugs with greater difficulties in their effects and clinical management, such as clozapine, is required. Objectives The objective is to describe the use of clozapine in patients with severe ID associated with BD. Methods Retrospective descriptive study. Patients older than 18 years with severe ID and BD, treated with clozapine for at least two years were included. Those with medical or psychiatric comorbidity were excluded. Results The sample consisted of 12 patients, 16.67% women (n=2) and 83.33% men (n=10), aged 47.57±9.27 years. Prior to the introduction of clozapine, a mean of 2.67±1.21 antipsychotics had been tested. The mean dose of clozapine was 264.24±70.50 mg/day. The patients had received treatment for 51.57±25.67 months, following the usual controls. None had hematological adverse effects or other serious adverse effects. Conclusions Clozapine can be an effective and safe therapeutic alternative in the treatment of BD in intellectual disabled patients which do not respond to other treatments. The clinical benefits of clozapine treatment seem to outweigh the potential risks associated with the treatment. However, more studies are needed to evaluate the effects of clozapine in patients with intellectual disabilities. Disclosure of Interest None Declared

Introduction Lithium associated with hypercalcemia may mimic a psychiatric condition and be confused for a relapse of bipolar disorder. The etiology seems to be due to a reduced sensitivity of the parathyroid cells to calcium, altering the parathyroid hormone (PTH) response. Lithium as an essential monovalent cation has some structural similarity to calcium (Ca) and can interact with protein receptors. This leads to changes in the inhibitory configuration of PTH and increased serum calcium concentrations, rising the threshold necessary to suppress hormone secretion. Lithium-induced hyperparathyroidism (HIL) is the main cause of hypercalcemia in these patients. Objectives Based on a clinical case of lithium-associated hypercalcemia in a patient with bipolar disorder, review the existing literature and state the needs for periodic monitoring protocols. Methods Case report and bibliographical review. Results A 38-year-old woman, diagnosed with bipolar affective disorder at the age of 18, has been treated with lithium during which she developed secondary tubulointerstitial nephropathy as an adverse effect. Recently, she requested medical evaluation for constitutional syndrome associated with deterioration of general condition with loss of strength and difficulty in walking. Analytically, mild hypercalcemia was detected, and the study was extended to include Ca and PTH. Chronic lithium therapy often develops mild hypercalcemia (approximately 10 to 20 percent of patients taking lithium), most likely due to increased secretion of PTH. Lithium can also unmask previously unrecognized mild hyperparathyroidism in patients with adenomas within a few years of starting therapy or induce parathyroid hyperplasia with a chronic use. The hypercalcemia usually, but not always, subsides when the lithium is stopped. Normalization of serum calcium is more likely to occur one to four weeks post-lithium withdrawal in patients with a relatively short duration of lithium use. It is less likely in patients receiving lithium for more than 10 years. Regarding the case to be presented, a review of the literature is carried out and the need to propose periodic calcium monitoring protocols is exposed. Conclusions Recommendations include determination of serum calcium every 6 months, urinary calcium and creatinine every 12 months, and bone mineral density monitoring every 1 to 3 years. Regular analytical monitoring including total calcium, PTH and vitamin D, would identify patients with a tendency to hypercalcemia so that appropriate measures could be taken. So as chronic treatment with lithium can develop mild hypercalcemia, I consider it necessary to develop periodic monitoring protocols for this adverse effect. Disclosure of Interest None Declared

Introduction Postictal suppression (PSI) is considered a key feature for ECT’s outcomes because higher values have been correlated with clinical efficacy. However, little is known about the demographic factors influencing this parameter. Objectives To analyze the influence of sex, age, diagnosis and treatment phase on ECT efficacy measured with PSI value. Methods 3251 ECT sessions were performed on 182 patients during two years at a university hospital. PSI was retrospectively analyzed comparing it according to sex (male, female), age, main diagnosis (major depressive disorder [MDD], bipolar disorder [BD], schizoaffective disorder [SZA], schizophrenia [SCZ]) and treatment phase (acute [a-ECT], continuation [c-ECT], maintenance [m-ECT]). Results PSI values were 69.76 % (SD 17.05) in women and 70.72 % (SD 16.81) in men without differences between sexes (F=0.979; p=0.607). PSI was correlated with age (r=-0.058; p=0.031). MDD PSI was 70.01 % (SD 16.88), for BD it was 69.48 % (SD 17.00), for SZA it was 68.62 % (SD 17.39), and for SCZ it was 70.73 % (SD 17.18), without differences between diagnosis (F=1.085; p=0.141). According to treatment phase, PSI in the a-ECT was 72.26 % (SD 16.43), in the c-ECT it was 67.83 % (SD 17.53), and in the m-ECT it was 68.47 % (SD 17.02), without differences between phases (F=0.901; p=0.915). Conclusions Although there exist statistically significant association between age and PSI it is a negligible correlation with no clinical relevance. Thus, we conclude that neither sex nor age, nor diagnosis, nor treatment phase seem to influence PSI to a relevant degree. Disclosure No significant relationships.

Abstract Clinical phenotypes of COVID-19, associated with mortality risk, have been identified in the general population. The present study assesses their applicability in solid organ transplant recipients (SOTR) hospital-admitted by COVID-19. In a cohort of 488 SOTR, nonvaccinated (n = 394) and vaccinated (n = 94) against SARS-CoV-2, we evaluated 16 demographic, clinical, analytical, and radiological variables to identify the clinical phenotypes A, B, and C. The median age was 61.0 (51–69) years, 330 (67.6%) and 158 (32.4%) were men and women, respectively, 415 (85%) had pneumonia, and 161 (33%) had SpO2

The objective of the extraction process in the ethanol production from sugarcane is to separate the sucrose-containing juice from the remainder of the cane, mainly fibre. The two currents, products of this process, are the juice and the bagasse. The juice is used to produce ethanol and the bagasse is the fuel for the boilers. Two types of devices are employed to perform this operation: mills and diffusers. Each one of them consumes different types of energy: mills consume mechanical energy, diffusers consume basically thermal energy. As both devices utilize an important quantity of energy, their effect in the energy balance of the factory needs to be taken into account. Aiming to discuss and characterize these effects, simulations of the complete ethanol production process, including the cogeneration system, were carried out using the Aspen Plus software, considering both devices. Process integration was also performed targeting to reduce the energy consumption. These results are presented and compared. Considering the integrated ethanol production process, with extraction -condensing steam turbines in cogeneration system, working with mills, it can produce an electricity surplus of 83.4 kWh/t of sugarcane, however, for the same conditions, working with the diffusion extraction process a production of 91.3 kWh/t of cane can be obtained, including also a small increase of 2 % in the ethanol production.

The sugarcane industry represents one of the most important economic activities in Brazil producing sugar and ethanol for the internal and external markets. Most of the sugarcane plants in Brazil have been projected to produce both sugar and ethanol, prioritizing one over the other according to market prices. There are also plants dedicated only to ethanol production. Nevertheless, this change in the production pattern affects parameters in their production such as water consumption, steam demands, bagasse surplus and electricity production. Thus, the aim of this study is to evaluate the production parameters for different configurations of sugarcane plant: (a) all sugarcane juice is destined to produce ethanol without sugar production and (b) distribution of 50 %/50 % of total recoverable sugars in sugar and ethanol production. Simulations in ASPEN PLUS® software were performed in order to evaluate the mass and energy balances and thermal integration using the Pinch Method was applied in order to minimize the utilities consumption.

Vapour recompression is a means of upgrading energy by the compressing of a lower pressure vapour up to a higher pressure, thus making the energy more available to do useful work. There are two types of vapour recompression: thermo-compression and mechanical recompression. Thermo-compression uses high pressure steam through a nozzle to compress a lower pressure vapour to an intermediate pressure. On the other hand, in mechanical recompression “mechanical” means that the compression task is done through the expenditure of mechanical energy for instance a steam turbine driven a compressor. Other means of driving could be also include an electric motor or an internal combustion engine. In both of cases the main advantage of vapour recompression is that it is not necessary to supply the latent heat of vaporization to the vapour being compressed. The aim of this study is to evaluate the possibilities of the incorporation of mechanical vapour recompression in the ethanol production process from the energy point of view. Thus mechanical vapour recompression is integrated to the juice evaporation system which is composed by a multiple effect evaporator. Simulations in Aspen Plus were accomplished to perform the mass and energy balances. Results showed that the introduction of vapour recompression promoted a reduction in steam consumption of approximately 10 % in evaporation system and 4 % in overall process. In order to further reduce the steam consumption of the plant, Pinch Analysis was applied to integrate the vapour recompression process coupled to evaporation system to all available streams in ethanol production process.

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[This corrects the article DOI: 10.1371/journal.pone.0269875.].

It is currently recommended that antiretroviral prophylaxis to prevent mother-to-child transmission (MTCT) of HIV be initiated at 14 weeks of gestation. However, the relevance of early-gestation HIV viral load level for intrauterine MTCT is unknown. The objective of this study was to determine the relationship between prenatal maternal viral load and intrauterine MTCT. Records of HIV-infected pregnant women in two centers in Brazil, from 1999 to 2004 were analyzed. Three pregnancy periods were considered: earlier than 14 weeks, 14 to 27 6/7 weeks, and 28 weeks of gestation or more. Peripartum HIV exposure was also computed. Maximum viral load in each period was the measure of HIV exposure. Four hundred fifty-seven HIV-infected pregnant women were evaluated, but 53 were excluded. The MTCT rate was 0.49% (2/404-95% confidence interval (CI95) = 0.14-1.79%). Newborns were not breast-fed. Median viral load for the earlier-than-14-week period was 9,900 copies/mL (P25-75 1,000-50,775 copies/mL), 8,350 copies/mL (P25-75 707-42,000 copies/mL) for the 14 to 27 6/7-week period, and 435 copies/mL (P25-75 90-7,775 copies/mL) after the 28-week period. The peripartum median viral load was 400 copies/mL (P25-75 80-500 copies/mL). MTCT in mothers with VL > 1,000 copies/mL during the first 14 weeks (0.67%, 2/298) was not different from those with VL =1,000 copies/mL (0.0%, 0/96, P=1). Analogously, in the 14 to 27 6/7-week period, MTCT was similar in groups with VL higher (0.68%, 2/292) or lower (0%, 0/106) than 1,000 copies/mL (P=1). Regarding VL >1,000 copies/mL at 28-weeks-or-later and at peripartum periods, MTCT rates were 1.15% (2/173, P = 0.18) and 2.8% (2/71, P = 0.03), respectively. Intrauterine transmission does not seem to be influenced by HIV viremia during the first 28 weeks of pregnancy.

Se describe un bosque mesófilo de montalia dominado por Engelhardtia mexianna del norte del Estado de Oaxaca (México). Esta comunidad prospera entre 1400 y 1800 m de altitud, sobre laderas de fuerte pendiente, expuestas a un régimen de muy frecuentes neblinas, con precipitación media anual de 5000 a 6000 mm y sin que en ningún mes llueva en promedio menos de 200 mm. Es un bosque denso y perennifolio, de 30 a 40 m de alto, rico en epifitas, con predominancia absoluta de Engelhardtia en el estrato arbóreo superior. Una gramínea bambúsea (Yushania sp.) el helecho arbustivo Alsophla salvinii así como varias Melastomaceae (Miconia) y Palmae (Chamaedorea) destacan cuantitativamente a niveles inferiores. Con respecto a las relaciones geográficas de la flora, predominan elementos neotropicales, les siguen en import ancia los pantropicales y escasean los holárticos. Al realizar el anális palinológico de los sedimentos del Mioceno Inferior del NW del Estado de Chiapas (México), se encontraron tres muestras con franca predominancia de polen de Engelhardtia. Se presentan los espectros de estas muestras y al compararlos con gráficas y listas de la lluvia de polen actual del bosque de Engelhardtia del N de Oaxaca, se encuentra un buengrado de similitud. Las diferencias mas notables entre ambas lluvias de polen consisten en: 1a porcentajes ligeramente mayores de polen de Engelhardtia en el bosque actual, 2a porcentajes superiores de esporas de pteridofitas (sobre todo de Polypodiaceae) en los hosques miocénicos, 3a falta en los espectros actuales del polen de Tricolpopollenites y Picea, de los cuales el primero parece haberse extinguido por completo y el segundo dejó de existir en el centro y sur de México desde el Pleistoceno Superior. El género Engelhardtia tuvo una amplia distribución en el hemisferio boreal duralite el Terciario, pero en el presente parece hallarse restringid o a pequenas áreas en: a) el sureste de México y Centroamérica, y b) el sureste de Asia.

Introduction Ceftaroline, tedizolid, dalbavancin, ceftazidime-avibactam and ceftolozane-tazobactam are novel antibiotics used to treat infections caused by multidrug-resistant pathogens (MDR). Their use should be supervised and monitored as part of an antimicrobial stewardship programme (ASP). Appropriate use of the new antibiotics will be improved by including consensual indications for their use in local antibiotic guidelines, together with educational interventions providing advice to prescribers to ensure that the recommendations are clearly understood.Methods and analysis This study will be implemented in two phases. First, a preliminary historical cohort (2017–2019) of patients from 13 Andalusian hospitals treated with novel antibiotics will be analysed. Second, a quasiexperimental intervention study will be developed with an interrupted time-series analysis (2020–2021). The intervention will consist of an educational interview between prescribers and ASP leaders at each hospital to reinforce the proper use of novel antibiotics. The educational intervention will be based on a consensus guideline designed and disseminated by leaders after the retrospective cohort data have been analysed. The outcomes will be acceptance of the intervention and appropriateness of prescription. Incidence of infection and colonisation with MDR organisms as well as incidence of Clostridioides difficile infection will also be analysed. Changes in prescription quality between periods and the safety profile of the antibiotics in terms of mortality rate and readmissions will also be measured.Ethics and dissemination Ethical approval will be obtained from the Andalusian Coordinating Institutional Review Board. The study is being conducted in compliance with the protocol and regulatory requirements consistent with International Council of Harmonisation E6 Good Clinical Practice and the ethical principles of the latest version of the Declaration of Helsinki. The results will be published in peer-reviewed journals and disseminated at national and international conferences.Trial registration number NCT03941951; Pre-results.

Introduction Patients with negative blood cultures (BCx) represent 85%–90% of all patients with BCx taken during hospital admission. This population usually includes a heterogeneous group of patients admitted with infectious diseases or febrile syndromes that require a blood culture. There is very little evidence of the clinical characteristics and antibiotic treatment given to these patients.Methods and analysis In a preliminary exploratory prospective cohort study of patients with BCx taken, the clinical/therapeutic characteristics and outcomes/antimicrobial stewardship opportunities of a population of patients with negative BCx will be analysed. In the second phase, using a cluster randomised crossover design, the implementation of an antimicrobial stewardship intervention targeting patients with negative BCx will be evaluated in terms of quality of antimicrobial use (duration and de-escalation), length of hospital stay and mortality.Ethics and dissemination This study has been and registered with clinicaltrials.gov. The findings of our study may support the implementation in clinical practice of an antimicrobial stewardship intervention to optimise the use of antibiotics in patients with negative BCx. The results of this study will be published in peer-reviewed journals and disseminated at national and international conferences.Trial registration number NCT03535324.

Abstract Background Kawasaki disease (KD) is an acute self-limited systemic vasculitis of unknown etiology. Intravenous immunoglobulin (IVIG) is an effective treatment and decreases the risk of cardiac complications to less than 5%. In spite of its effectiveness, some children do not respond to this therapy and still develop coronary aneurysms (CAA). The optimal treatment for IVIG non-responsive patients remains controversial although corticoids have been suggested to be an effective treatment in some patients. For those patients still resistant to IVIG and corticoids, interleukin-1 receptor antagonists (IL-1RA) such anakinra could be an alternative. Case presentation We present a 3 year-old Caucasian patient with KD without cardiac complications but with important resistance to treatment. After becoming resistant to IVIG and corticoids, anakinra proved to be an effective treatment. Conclusions To our knowledge, this is the first report of the utility of IL-1RA in refractory KD without coronary impairment. The patient fulfilled the classical criteria for KD and, after becoming resistant to first and second line treatments, anakinra proved to be an effective treatment. Further studies are required to determine if this is an effective treatment option for other cases of resistant Kawasaki disease.