Impact of primary aldosteronism on kidney function: results from the SPAIN-ALDO registry.

AIM: To evaluate the impact of aldosterone excess on renal function in individuals with primary aldosteronism and to compare its evolution after surgery or mineralocorticoid receptor antagonist (MRA) treatment. METHODS: A multicentre, retrospective cohort study of primary aldosteronism patients in follow-up in 36 Spanish tertiary hospitals, who underwent specific treatment for primary aldosteronism (MRA or adrenalectomy). RESULTS: A total of 789 patients with primary aldosteronism were included, with a median age of 57.5 years and 41.8% being women. At primary aldosteronism diagnosis, the prevalence of chronic kidney disease (CKD) was 10.7% ( n  = 84), with 75% of cases classified as state 3a ( n  = 63). Primary aldosteronism patients with CKD had a longer duration of hypertension, a higher prevalence of type 2 diabetes, dyslipidaemia, cardiovascular events, hypokalaemia, and albuminuria. Unilateral adrenalectomy was performed in 41.8% of cases ( n  = 330), and 459 patients were treated with MRA. After a median follow-up of 30.7 months (range 13.3-68.4), there was a significant decline in the estimated glomerular filtration rate (eGFR) in operated patients and those receiving MRA. During follow-up, 24.4% of patients with CKD at the time of primary aldosteronism diagnosis had normalized renal function, and 39% of those with albuminuria had albuminuria remission. There were no differences in renal function or albuminuria regression between the two therapy groups. However, development of albuminuria was less common in operated than in medically treated patients (0 vs. 6.0%, P  = 0.009). CONCLUSION: CKD affects around 10% of the patients with primary aldosteronism, with a higher risk in individuals with long-term hypertension, type 2 diabetes, dyslipidaemia, cardiovascular events, hypokalaemia, and albuminuria. At short-term, both MRA and surgical treatment lead to a reduction of renal function, but adrenalectomy led to higher renal protection.

Van Wyk-Grumbach Syndrome and Gonadectomy.

Van Wyk-Grumbach syndrome (VWGS) refers to the development of peripheral precocious puberty, long-standing hypothyroidism, and gonadal masses; when not diagnosed, an unnecessary gonadectomy may be performed. Herein, we present a case of a 10-year-old girl with Down's syndrome, short stature, and vitiligo who presented to our hospital with vaginal bleeding and a palpable pelvic mass. Upon ultrasound and topographical examination, bilateral ovarian masses with negative tumor markers were detected. After bilateral gonadectomy, endocrine studies revealed profound hypothyroidism and peripheral puberty that led to the VWGS syndrome diagnosis (TSH 367.3 mUI/mL, isolated menstruation, indetectable LH, and elevated estradiol). Levothyroxine treatment improved obesity and short stature, and sexual hormone replacement began at 13 years of age. The literature on Van Wyk-Grumbach syndrome shows that it presents most often in women, and classic hypothyroidism symptoms always precede the diagnosis. Approximately 11% of patients have Down's syndrome, sometimes tumor markers are elevated, and some develop severe symptoms (myopathy, short stature, mental delay, ascites, pericardial effusion, Cullen's sign, pituitary hyperplasia, and severe anemia) that respond to levothyroxine treatment. Conclusions: Children with peripheral precocious puberty and gonadal masses must be studied for hypothyroidism before any radical decision is made.

2D Amino-Functionalized Black Phosphorus: A New Approach to Improve Hydrogen Gas Detection Performance.

In recent years, hydrogen has gained attention as a potential solution to replace fossil fuels, thus reducing greenhouse gas emissions. The development of ever improving hydrogen sensors is a topic that is constantly under study due to concerns about the inherent risk of leaks of this gas and potential explosions. In this work, a new, long-term, stable phosphorene-based sensor was developed for hydrogen detection. A simple functionalization of phosphorene using urea was employed to synthesize an air-stable material, subsequently used to prepare films for gas sensing applications, via the drop casting method. The material was deeply characterized by different techniques (scanning electron microscopy, X-ray diffraction, X-ray photoelectron, and Raman spectroscopy), and the stability of the material in a noninert atmosphere was evaluated. The phosphorene-based sensor exhibited high sensitivity (up to 700 ppm) and selectivity toward hydrogen at room temperature, as well as long-term stability over five months under ambient conditions. To gain further insight into the gas sensing mechanism over the surface, we employed a dedicated apparatus, namely operando diffuse reflectance infrared Fourier transform, by exposing the chemoresistive sensor to hydrogen gas under dry air conditions.

Prospective observational cohort study of the change of the marginal bone crest in relation to the prosthetic abutment height and the peri-implant vertical mucosal thickness at implants positioned subcrestally.

AIM: To evaluate the influence on peri-implant crestal bone loss exerted by the vertical mucosal thickness and the abutment height over 12 months after placement of the restoration on subcrestal implants with change of platform, using a restoration abutment platform smaller than the implant platform. MATERIALS AND METHODS: A total of 99 implants were rehabilitated in the maxillary and mandibular posterior regions. A total of 22 implants were rehabilitated in the maxilla and 77 implants in the mandible, using digitally designed customized abutments with Atlantis weborder software, from the commercial house Dentsply Sirona (Dentsply Sirona S.A., Barcelona, Spain), version 4.6.5, adapting the height to the vertical thickness of the mucosa. Clinical and radiographic monitoring begins during the surgical procedure of placement of the implant and ends 12 months afterwards. Crestal bone loss was evaluated through the Carestream® CS8100 3D radiographic equipment. RESULTS: In all cases, the greatest loss of marginal bone occurred between the day of surgery (Tx) and placement of the rehabilitation (To). The average bone loss between both times was greater when the abutment height and vertical mucosal thickness did not exceed 3 mm. Subsequently, bone loss slowed and stabilized at 12 months. CONCLUSIONS: The minimum abutment height and the vertical mucosal thickness are factors to take into account when minimizing peri-implant marginal bone loss, the abutment height having the greatest importance according to the clinical data obtained.

Outcomes and safety of endovascular treatment from 6 to 24 hours in patients with a pre-stroke moderate disability (mRS 3): a multicenter retrospective study.

BACKGROUND: Approximately 30% of patients presenting with acute ischemic stroke (AIS) due to large vessel occlusion have pre-stroke modified Rankin Scale (mRS) scores ≥2. We aimed to investigate the safety and outcomes of endovascular treatment (EVT) in patients with AIS with moderate pre-stroke disability (mRS score 3) in an extended time frame (ie, 6-24 hours from the last time known well). METHODS: Data were collected from five centers in Europe and the USA from January 2018 to January 2023 and included 180 patients who underwent EVT in an extended time frame. Patients were divided into two groups of 90 each (Group 1: pre-mRS 0-2; Group 2: pre-mRS 3; 71% women, mean age 80.3±11.9 years). Primary outcomes were: (1) 3-month good clinical outcome (Group 1: mRS 0-2, Group 2: mRS 0-3) and ΔmRS; (2) any hemorrhagic transformation (HT); and (3) symptomatic HT. Secondary outcomes were successful and complete recanalization after EVT and 3-month mortality. RESULTS: No between-group differences were found in the 3-month good clinical outcome (26.6% vs 25.5%, P=0.974), any HT (26.6% vs 22%, P=0.733), and symptomatic HT (8.9 vs 4.4%, P=0.232). Unexpectedly, ΔmRS was significantly smaller in Group 2 compared with Group 1 (1.64±1.61 vs 2.97±1.69, P<0.001). No between-group differences were found in secondary outcomes. CONCLUSION: Patients with pre-stroke mRS 3 are likely to have similar outcomes after EVT in the extended time frame to those with pre-stroke mRS 0-2, with no difference in safety.

Mechanical Transfer of Black Phosphorus on a Silk Fibroin Substrate: A Viable Method for Photoresponsive and Printable Biomaterials.

Despite the technological importance of semiconductor black phosphorus (BP) in materials science, maintaining the stability of BP crystals in organic media and protecting them from environmental oxidation remains challenging. In this study, we present the synthesis of bulk BP and the exploitation of the viscoelastic properties of a regenerated silk fibroin (SF) film as a biocompatible substrate to transfer BP flakes, thereby preventing oxidation. A model based on the flow of polymers revealed that the applied flow-induced stresses exceed the yield stress of the BP aggregate. Raman spectroscopy was used to investigate the exfoliation efficiency as well as the environmental stability of BP transferred on the SF substrate. Notably, BP flakes transferred to the SF substrate demonstrated improved stability when SF was dissolved in a phosphate-buffered saline medium, and in vitro cancer cell viability experiments demonstrate the tumor ablation efficiency under visible to near-infrared (Vis-nIR) radiation. Moreover, the SF and BP-enriched SF (SF/BP) solution was shown to be processable via extrusion-based three-dimensional (3D) printing. Therefore, this work paves the way for a general method for the transferring of BP on natural biodegradable polymers and processing them via 3D printing toward novel functionalities and complex shapes for biomedical purposes.

Identification of Dhx15 as a Major Regulator of Liver Development, Regeneration, and Tumor Growth in Zebrafish and Mice.

RNA helicase DHX15 plays a significant role in vasculature development and lung metastasis in vertebrates. In addition, several studies have demonstrated the overexpression of DHX15 in the context of hepatocellular carcinoma. Therefore, we hypothesized that this helicase may play a significant role in liver regeneration, physiology, and pathology. Dhx15 gene deficiency was generated by CRISPR/Cas9 in zebrafish and by TALEN-RNA in mice. AUM Antisense-Oligonucleotides were used to silence Dhx15 in wild-type mice. The hepatocellular carcinoma tumor induction model was generated by subcutaneous injection of Hepa 1-6 cells. Homozygous Dhx15 gene deficiency was lethal in zebrafish and mouse embryos. Dhx15 gene deficiency impaired liver organogenesis in zebrafish embryos and liver regeneration after partial hepatectomy in mice. Also, heterozygous mice presented decreased number and size of liver metastasis after Hepa 1-6 cells injection compared to wild-type mice. Dhx15 gene silencing with AUM Antisense-Oligonucleotides in wild-type mice resulted in 80% reduced expression in the liver and a significant reduction in other major organs. In addition, Dhx15 gene silencing significantly hindered primary tumor growth in the hepatocellular carcinoma experimental model. Regarding the potential use of DHX15 as a diagnostic marker for liver disease, patients with hepatocellular carcinoma showed increased levels of DHX15 in blood samples compared with subjects without hepatic affectation. In conclusion, Dhx15 is a key regulator of liver physiology and organogenesis, is increased in the blood of cirrhotic and hepatocellular carcinoma patients, and plays a key role in controlling hepatocellular carcinoma tumor growth and expansion in experimental models.

Determinación de tiempos quirúrgicos estándar de los procedimientos más comunes de cirugía general y su probabilidad de extensión para eficientizar la programación de cirugías / Estimation of the standard surgical times of the most common general surgery procedures and the probability of extending them to make surgery scheduling more efficient

RESUMEN Objetivo: Determinar los tiempos quirúrgicos estándar de los cuatro procedimientos más comunes en cirugía general (hernioplastia inguinal unilateral, hernioplastia inguinal bilateral, hernioplastia umbilical y colecistectomía) de un hospital de segundo nivel y calcular la probabilidad de extensión de cada uno de los procedimientos. La eficiencia es un fenómeno ampliamente estudiado en el ámbito económico, pues hace referencia a la necesidad de menor cantidad de factores para la producción de un determinado nivel de bienes y servicios, por ello, es de vital importancia incluirlo en el ámbito quirúrgico. Materiales y métodos: Estudio observacional, descriptivo y retrospectivo. Se utilizaron los registros de quirófano de un hospital de segundo nivel del año 2017 al 2019 del servicio de Cirugía General. A partir de esta información, se estandarizó el tiempo necesario para cada procedimiento mediante la media de cada uno (hernioplastia umbilical, hernioplastia inguinal unilateral o bilateral y colecistectomía). Se calculó la probabilidad de extensión de las cirugías tomando en consideración los datos obtenidos y el intervalo de confianza. Resultados: Para el procedimiento de hernioplastia inguinal unilateral se obtuvo una media de 76 min (IC 95,00 %: 72-80 min, DE 23); en hernioplastia inguinal bilateral, una media de 104,38 min (IC 95,00 %: 91-116 min, DE 41,7); en hernioplastia umbilical, una media de 59,31 min (IC 95,00 %: 54-63 min, DE 29,9), y en colecistectomía, una media de 85,735 min (IC 95,00 %: 83-88 min). La probabilidad de que se programen tres cirugías y todas estén a tiempo (límite superior del IC) es de 92,69 %, la probabilidad de que se programen tres cirugías y todas se prolonguen es de 0,0016 % (límite inferior del IC). Conclusiones: Es posible realizar la planeación de las cirugías programadas mediante el uso de tiempos quirúrgicos estandarizados. Se requiere contar con estadística actualizada de los procedimientos quirúrgicos (promedios del tiempo de realización de cada procedimiento), ya que es posible detectar y supervisar de manera más precisa la dinámica de quirófano mediante la detección de las áreas de oportunidad, de esta manera, se eficientizará el tiempo de quirófano para beneficio de los sistemas de salud y los pacientes.

ABSTRACT Objective: To determine the standard surgical times of the four most common general surgery procedures (unilateral inguinal hernioplasty, bilateral inguinal hernioplasty, umbilical hernioplasty and cholecystectomy) in a second-level hospital and to estimate the probability of extending the time of each of the procedures. Efficiency is a widely studied subject in economics. It involves the need for fewer elements in the production of a certain level of goods and services. Therefore, it is extremely important to consider it in the field of surgery. Materials and methods: An observational, descriptive and retrospective study. It used the operating room records from 2017 to 2019 of the General Surgery service in a second-level hospital. Based on this information, the time required for each procedure was standardized using the mean for each one (umbilical hernioplasty, unilateral or bilateral inguinal hernioplasty and cholecystectomy). The probability of extending surgical times was estimated based on the obtained data and confidence interval. Results: The mean for unilateral inguinal hernioplasty was 76 min (95.00 % CI: 72-80 min, SD 23), for bilateral inguinal hernioplasty 104.38 min (95.00 % CI: 91-116 min, SD 41.7), for umbilical hernioplasty 59.31 min (95.00 % CI: 54-63 min, SD 29.99) and for cholecystectomy 85.735 min (95.00 % CI: 83-88 min). The probability of scheduling three surgical interventions and completing all of them on time (upper limit of the CI) is 92.69 %, and the probability of scheduling three surgical interventions and extending the time of all of them is 0.0016 % (lower limit of the CI). Conclusions: Planning scheduled operations using standardized surgical times is feasible. Updated statistics on surgical procedures (average time for each procedure) are required since it is possible to more accurately detect and supervise operating room dynamics by identifying opportunity areas. This will make operating room time more efficient for the benefit of health care systems and patients.

Invention of MK-7845, a SARS-CoV-2 3CL Protease Inhibitor Employing a Novel Difluorinated Glutamine Mimic.

As SARS-CoV-2 continues to circulate, antiviral treatments are needed to complement vaccines. The virus's main protease, 3CLPro, is an attractive drug target in part because it recognizes a unique cleavage site, which features a glutamine residue at the P1 position and is not utilized by human proteases. Herein, we report the invention of MK-7845, a novel reversible covalent 3CLPro inhibitor. While most covalent inhibitors of SARS-CoV-2 3CLPro reported to date contain an amide as a Gln mimic at P1, MK-7845 bears a difluorobutyl substituent at this position. SAR analysis and X-ray crystallographic studies indicate that this group interacts with His163, the same residue that forms a hydrogen bond with the amide substituents typically found at P1. In addition to promising in vivo efficacy and an acceptable projected human dose with unboosted pharmacokinetics, MK-7845 exhibits favorable properties for both solubility and absorption that may be attributable to the unusual difluorobutyl substituent.

A theragenerative bio-nanocomposite consisting of black phosphorus quantum dots for bone cancer therapy and regeneration.

Recently, the term theragenerative has been proposed for biomaterials capable of inducing therapeutic approaches followed by repairing/regenerating the tissue/organ. This study is focused on the design of a new theragenerative nanocomposite composed of an amphiphilic non-ionic surfactant (Pluronic F127), bioactive glass (BG), and black phosphorus (BP). The nanocomposite was prepared through a two-step synthetic strategy, including a microwave treatment that turned BP nanosheets (BPNS) into quantum dots (BPQDs) with 5 ± 2 nm dimensions in situ. The effects of surfactant and microwave treatment were assessed in vitro: the surfactant distributes the ions homogenously throughout the composite and the microwave treatment chemically stabilizes the composite. The presence of BP enhanced bioactivity and promoted calcium phosphate formation in simulated body fluid. The inherent anticancer activity of BP-containing nanocomposites was tested against osteosarcoma cells in vitro, finding that 150 µg mL-1 was the lowest concentration which prevented the proliferation of SAOS-2 cells, while the counterpart without BP did not affect the cell growth rate. Moreover, the apoptosis pathways were evaluated and a mechanism of action was proposed. NIR irradiation was applied to induce further proliferation suppression on SAOS-2 cells through hyperthermia. The inhibitory effects of bare BP nanomaterials and nanocomposites on the migration and invasion of bone cancer, breast cancer, and prostate cancer cells were assessed in vitro to determine the anticancer potential of nanomaterials against primary and secondary bone cancers. The regenerative behavior of the nanocomposites was tested with healthy osteoblasts and human mesenchymal stem cells; the BPQDs-incorporated nanocomposite significantly promoted the proliferation of osteoblast cells and induced the osteogenic differentiation of stem cells. This study introduces a new multifunctional theragenerative platform with promising potential for simultaneous bone cancer therapy and regeneration.

Renin as a Biomarker to Guide Medical Treatment in Primary Aldosteronism Patients. Findings from the SPAIN-ALDO Registry.

INTRODUCTION: Primary aldosteronism (PA) is associated with several cardiometabolic comorbidities. Specific treatment by mineralocorticoid receptor antagonists (MRA) or adrenalectomy has been reported to reduce the cardiometabolic risk. However, the cardiovascular benefit could depend on plasma renin levels in patients on MRA. AIM: To compare the development of cardiovascular, renal and metabolic complications between medically treated patients with PA and those who underwent adrenalectomy, taking the renin status during MRA treatment into account. METHODS: A multicenter retrospective study (SPAIN-ALDO Register) of patients with PA treated at 35 Spanish tertiary hospitals. Patients on MRA were divided into two groups based on renin suppression (n = 90) or non-suppression (n = 70). Both groups were also compared to unilateral PA patients (n = 275) who achieved biochemical cure with adrenalectomy. RESULTS: Adrenalectomized patients were younger, had higher plasma aldosterone concentration, and lower potassium levels than MRA group. Patients on MRA had similar baseline characteristics when stratified into treatment groups with suppressed and unsuppressed renin. 97 (55.1%) of 176 patients without comorbidities at diagnosis, developed at least one comorbidity during follow-up (median 12 months vs. 12.5 months' follow-up after starting MRA and surgery, respectively). Surgery group had a lower risk of developing new cardiovascular events (HR 0.40 [95% CI 0.18-0.90]) than MRA group. Surgical treatment improved glycemic and blood pressure control, increased serum potassium levels, and required fewer antihypertensive drugs than medical treatment. However, there were no differences in the cardiometabolic profile or the incidence of new comorbidities between the groups with suppressed and unsuppressed renin levels (HR 0.95 [95% CI 0.52-1.73]). CONCLUSION: Cardiovascular, renal, and metabolic events were comparable in MRA patients with unsuppressed and suppressed renin. Effective surgical treatment of PA was associated with a decreased incidence of new cardiovascular events when compared to MRA therapy.

Liver FoxO1 overexpression is positively associated with the degree of liver injury in cirrhotic patients.

Objectives: Chronic liver disease and related complications, cirrhosis and hepatocellular carcinoma, are associated with high mortality. Curative treatments, partial hepatectomy or liver transplantation, have limited applicability in patients with cirrhosis due to the poor liver regenerative capacity. Thus, we need to find new diagnostic and therapeutic alternatives, to block the disease progression and to improve the survival of patients. In this context, preclinical studies have demonstrated the key role of the protein kinase B (Akt) in liver dysfunction, but the status of Akt and its targets in patients with chronic hepatopathy remains unknown. Aims: To determine the activation status of the Akt pathway and their association with liver functionality in cirrhotic patients. Methods: This retrospective study includes liver tissue samples from 36 hepatectomized patients with (n=27) and without (n=9) cirrhosis. Multiplex analysis of proteins involved in the Akt/mTOR pathway was performed using a Luminex panel and Western blot. Conventional liver function tests were determined in serum before resection surgery. Results: Akt and forkhead box protein O1 (FoxO1) are overexpressed in the liver of cirrhotic patients: (2.1 vs. 1.0 densitometric relative units (DRU); p<0.01, and 9.5 vs. 4.4 DRU; p<0.01, respectively). FoxO1 showed the best correlation with markers of liver injury (aspartate aminotransferase (ASAT): r=0.51, p<0.05; alanine aminotransferase (ALAT): r=0.49, p<0.05), and was the only enzyme in the Akt pathway identified as an independent predictor of ASAT and ALAT levels. Conclusions: The intrahepatic expression of FoxO1 could have clinical utility as a potential prognostic marker for patients with advanced liver disease.

Inflammatory macrophages reprogram to immunosuppression by reducing mitochondrial translation.

Acute inflammation can either resolve through immunosuppression or persist, leading to chronic inflammation. These transitions are driven by distinct molecular and metabolic reprogramming of immune cells. The anti-diabetic drug Metformin inhibits acute and chronic inflammation through mechanisms still not fully understood. Here, we report that the anti-inflammatory and reactive-oxygen-species-inhibiting effects of Metformin depend on the expression of the plasticity factor ZEB1 in macrophages. Using mice lacking Zeb1 in their myeloid cells and human patient samples, we show that ZEB1 plays a dual role, being essential in both initiating and resolving inflammation by inducing macrophages to transition into an immunosuppressed state. ZEB1 mediates these diverging effects in inflammation and immunosuppression by modulating mitochondrial content through activation of autophagy and inhibition of mitochondrial protein translation. During the transition from inflammation to immunosuppression, Metformin mimics the metabolic reprogramming of myeloid cells induced by ZEB1. Mechanistically, in immunosuppression, ZEB1 inhibits amino acid uptake, leading to downregulation of mTORC1 signalling and a decrease in mitochondrial translation in macrophages. These results identify ZEB1 as a driver of myeloid cell metabolic plasticity, suggesting that targeting its expression and function could serve as a strategy to modulate dysregulated inflammation and immunosuppression.

Is adrenal venous sampling always necessary to differentiate between unilateral and bilateral primary aldosteronism? Lesson from the SPAIN-ALDO register.

PURPOSE: To evaluate whether the clinical, biochemical and radiological features of patients with primary aldosteronism (PA) can predict both main subtypes of PA. METHODS: A retrospective multicenter study of PA patients followed in 27 Spanish tertiary hospitals (SPAIN-ALDO Register). Only patients with confirmed unilateral or bilateral PA based on adrenal venous sampling (AVS) and/or postsurgical biochemical cure after adrenalectomy were included. Supervised regression techniques were used for model development. RESULTS: 328 patients [270 unilateral PA (UPA), 58 bilateral PA (BPA)] were included. The area under the curve (AUC) for aldosterone/potassium ratio and aldosterone responses following saline infusion test were 0.602 [95%CI 0.520 to 0.684] and 0.574 [95% CI 0.446-0.701], respectively, to differentiate UPA from BPA. The AUC was 0.825 [95% 0.764-0.886] when the prediction model with seven parameters - comorbidities (dyslipidemia, cerebrovascular disease, sleep apnea syndrome [SAS]), systolic blood pressure (SBP), plasma aldosterone levels (PAC), hypokalemia and unilateral adrenal nodule >1 cm and normal contralateral adrenal gland on CT/MRI - was used. In patients without comorbidities, hypokalemia, SBP > 160 mmHg, PAC > 40 ng/dL, and unilateral adrenal lesions were associated with a likelihood of having a UPA of 98.5%. The chance of BPA was higher in individuals with comorbidities, SBP < 140 mmHg, normokalemia, low PAC levels, and no adrenal tumors on the CT/MRI (91.5%). CONCLUSION: A combination of high PAC, SBP > 160 mmHg, low serum potassium, a unilateral adrenal nodule>1 cm and no comorbidities could predict a UPA with a 98.5% accuracy.

Novel prognostic biomarkers in decompensated cirrhosis: a systematic review and meta-analysis.

BACKGROUND: Patients with decompensated cirrhosis experience high mortality rates. Current prognostic scores, including the model for end-stage liver disease (MELD), may underperform in settings other than in those they were initially developed. Novel biomarkers have been proposed to improve prognostication accuracy and even to predict development of complications. METHODS: We performed a systematic review and meta-analysis on novel urine and blood biomarkers and their ability to predict 90-day mortality in patients with decompensated cirrhosis. Secondary outcomes included 28-day and 1-year mortality, and development of acute-on-chronic liver failure, acute kidney injury and other complications. To overcome differences in units, temporal changes in assays and reporting heterogeneity, we used the ratio of means (RoM) as measure of association for assessing strength in predicting outcomes. An RoM>1 implies that the mean biomarker level is higher in those that develop the outcome than in those that do not. RESULTS: Of 6629 unique references, 103 were included, reporting on 29 different biomarkers, with a total of 31 362 biomarker patients. Most studies were prospective cohorts of hospitalised patients (median Child-Pugh-Turcotte score of 9 and MELD score of 18). The pooled 90-day mortality rate was 0.27 (95% CI 0.24 to 0.29). The RoM for predicting 90-day mortality was highest for interleukin 6 (IL-6) (2.56, 95% CI 2.39 to 2.74), followed by urinary neutrophil gelatinase-associated lipocalin (uNGAL) (2.42, 95% CI 2.20 to 2.66) and copeptin (2.33, 95% CI 2.17 to 2.50). These RoMs were all higher than for MELD (1.44, 95% CI 1.42 to 1.46). CONCLUSION: Novel biomarkers, including IL-6, uNGAL and copeptin, can probably improve prognostication of patients with decompensated cirrhosis compared with MELD alone.

Psychometric properties and factor structure of the brief Wisconsin Inventory of Smoking Dependence Motives among Spanish smokers from the general population.

INTRODUCTION: The brief version of the Wisconsin Inventory of Smoking Dependence Motives (B-WISDM) is a well-established instrument to measure the multidimensional nature of nicotine dependence. However, no previous research has assessed its psychometric properties in the Spanish context. The aim of the present study was to analyze the factor structure and measurement invariance across gender of this instrument among Spanish smokers from the general population. METHODS: This cross-sectional study assessed 480 smokers through an online questionnaire including information on tobacco use and several nicotine dependence measures. Confirmatory Factor Analysis was used to assess the factorial structure of the Spanish B-WISDM, its internal consistency, measurement invariance across gender and convergent validity with the Fagerström Test for Nicotine Dependence (FTND) and the Glover-Nilsson Smoking Behavioral Questionnaire (GN-SBQ) scores. RESULTS: Results indicate that the eleven correlated factors solution had a better fit when compared to the other tested models (two correlated factors and two second-order factors with eleven first-order correlated factors solution), remaining such structure invariant across gender. Internal consistency of the scale was high (α = 0.950; dimension α values ranged between 0.657 and 0.921). Overall scores and dimensions of the scale significantly and positively correlated with other nicotine dependence measures (except for Social/Environmental Goads and FTND). CONCLUSIONS: This is the first version of the B-WISDM validated to assess nicotine dependence with a multidimensional perspective within the Spanish culture. Results show adequate psychometric properties regarding its factor structure and measurement invariance across gender, supporting its utility to evaluate the motives driving tobacco use among Spanish smokers from the general population.

Microalgae-Based Biotechnology as Alternative Biofertilizers for Soil Enhancement and Carbon Footprint Reduction: Advantages and Implications.

Due to the constant growth of the human population and anthropological activity, it has become necessary to use sustainable and affordable technologies that satisfy the current and future demand for agricultural products. Since the nutrients available to plants in the soil are limited and the need to increase the yields of the crops is desirable, the use of chemical (inorganic or NPK) fertilizers has been widespread over the last decades, causing a nutrient shortage due to their misuse and exploitation, and because of the uncontrolled use of these products, there has been a latent environmental and health problem globally. For this reason, green biotechnology based on the use of microalgae biomass is proposed as a sustainable alternative for development and use as soil improvers for crop cultivation and phytoremediation. This review explores the long-term risks of using chemical fertilizers for both human health (cancer and hypoxia) and the environment (eutrophication and erosion), as well as the potential of microalgae biomass to substitute current fertilizer using different treatments on the biomass and their application methods for the implementation on the soil; additionally, the biomass can be a source of carbon mitigation and wastewater treatment in agro-industrial processes.

Role of Damage-Associated Molecular Patterns (DAMPS) in the Postoperative Period after Colorectal Surgery.

Anastomotic leakage (AL) is a defect of the intestinal wall at the anastomotic site and is one of the most severe complications in colorectal surgery. Previous studies have shown that the immune system response plays a significant role in the development of AL. In recent years, DAMPs (damage-associated molecular patterns) have been identified as cellular compounds with the ability to activate the immune system. The NLRP3 inflammasome plays an important role in the inflammatory responses which are mediated by DAMPs such as ATP, HSP proteins or uric acid crystals, when found in extracellular environments. Recent publications suggest that systemic concentration of DAMPs in patients with colorectal surgery may determine the inflammatory process and have a role in the occurrence of AL and other post-surgery complications. This review provides valuable knowledge about the current evidence supporting this hypothesis and highlights the possible role of these compounds in postoperative processes, which could open a new path to explore new strategies to prevent possible post-surgical complications.

Unraveling the Role of Nickel Nanoparticles Functionalization in the Electronic Properties and Structural Features of 2D Black Phosphorene Exposed to Ambient Conditions.

Layered black phosphorus (BP) is endowed with peculiar chemico-physical properties that make it a highly promising candidate in the field of electronics. Nevertheless, as other 2D materials with atomic scale thickness, it suffers from easy degradation under ambient conditions. Herein, it is shown that the functionalization of BP with preformed and in situ grown Ni NPs, affects the electronic properties of the material. In particular, Ni functionalization performed in situ leads to a narrowing of the average BP band gap from 1.15 to 0.95 eV and to a marked shift in the conduction band maximum from -0.33 V to -0.07 V, which, in turn, improve the ambient stability. Structural studies carried out by XAS can well distinguish the two nanohybrids and reveal that once Ni NPs are grown on BP nanosheets, a Ni-P coordinative bond is formed, featuring a short Ni-P distance of 2.27 Å, which is not observed when preformed Ni NPs are immobilized on BP. Comparing the XANES and EXAFS spectra of fresh and aged samples of both nanohybrids, suggests that the interaction between Ni and P atoms results in a stabilization effect exerted via a dual electronic and redox mechanism, that infers a much superior ambient stability to BP, even if the surface functionalization is far to achieve a full coverage.

Estradiol and Estrone Have Different Biological Functions to Induce NF-κB-Driven Inflammation, EMT and Stemness in ER+ Cancer Cells.

In general, the risk of being diagnosed with cancer increases with age; however, the development of estrogen-receptor-positive (ER+) cancer types in women are more closely related to menopausal status than age. In fact, the general risk factors for cancer development, such as obesity-induced inflammation, show differences in their association with ER+ cancer risk in pre- and postmenopausal women. Here, we tested the role of the principal estrogens in the bloodstream before and after menopause, estradiol (E2) and estrone (E1), respectively, on inflammation, epithelial-to-mesenchymal transition (EMT) and cancer stem cell enrichment in the human ER+ cervical cancer cell line HeLa. Our results demonstrate that E1, contrary to E2, is pro-inflammatory, increases embryonic stem-transcription factors (ES-TFs) expression and induces EMT in ER+ HeLa cells. Moreover, we observed that high intratumoural expression levels of 17ß-Hydroxysteroid dehydrogenase (HSD17B) isoforms involved in E1 synthesis is a poor prognosis factor, while overexpression of E2-synthetizing HSD17B isoforms is associated with a better outcome, for patients diagnosed with ER+ ovarian and uterine corpus carcinomas. This work demonstrates that E1 and E2 have different biological functions in ER+ gynaecologic cancers. These results open a new line of research in the study of ER+ cancer subtypes, highlighting the potential key oncogenic role of E1 and HSD17B E1-synthesizing enzymes in the development and progression of these diseases.