Duodenal Pseudolipomatosis. Literature review and case report of a very unusual finding.

Pseudolipomatosis (PL) is a rare, benign, iatrogenic condition first described in colorectal mucosa. This condition is thought to arise from gas penetration into the mucosa due to mechanical or chemical injury during endoscopy. Despite these associations and its characteristic appearence, the definitive pathogenesis remains unclear and it continues to be underrecognized by some pathologists and endoscopists, which is crucial to avoid any further unnecessary treatments. Immunohistochemistry techniques play a role in differentiating PL from similar conditions such as cystic intestinal pneumatosis, intestinal lipomatosis, or lymphangiectasia. A 70-year-old man with a family history of colon adenocarcinoma was diagnosed with duodenal pseudolipomatosis after a routine endoscopic assessment. To the best of our knowledge, there have been only two reports of PL diagnosed in the duodenum. A review of over 500 duodenal biopsies at our centre revealed that no other instances were identified, emphasizing the unusual occurrence of this particular location.

Decídetexto: Mobile Cessation Support for Latino Adults Who Smoke: A Randomized Clinical Trial.

BACKGROUND: Latino adults experience multiple barriers to health care access and treatment that result in tobacco-related disparities. Mobile interventions have the potential to deliver smoking cessation treatment among Latino adults, the highest users of mobile technologies. RESEARCH QUESTION: Is Decídetexto, a culturally accommodated mobile health intervention, more effective for smoking cessation compared with standard care among Latinx adults who smoke? STUDY DESIGN AND METHODS: A two-arm parallel group randomized clinical trial (RCT) was conducted in Kansas, New Jersey, and New York between October 2018 and September 2021. Eligible Latino adults who smoke (n = 457) were randomly assigned to Decídetexto or a standard care group. The primary outcome was biochemically verified 7-day smoking abstinence at week 24. Secondary outcomes included self-reported 7-day smoking abstinence at weeks 12 and 24 and uptake and adherence of nicotine replacement therapy (NRT). RESULTS: Participants' mean age was 48.7 (SD, 11.1) years, 45.2% were female, and 50.3% smoked ≥10 cigarettes per day. Two hundred twenty-nine participants were assigned to Decídetexto and 228 to standard care. Treating those lost to follow-up as participants who continued smoking, 14.4% of participants in the Decídetexto group were biochemically verified abstinent at week 24 compared with 9.2% in the standard care group (OR, 1.66; 95% CI, 0.93-2.97; P = .09). Treating those lost to follow-up as participants who continued smoking, 34.1% of the participants in the Decídetexto group self-reported smoking abstinence at week 24 compared with 20.6% of participants in the standard care group (OR, 1.99; 95% CI, 1.31-3.03; P < .001). Analyzing only participants who completed the assessment at week 24, 90.6% (174/192) of participants in the Decídetexto group self-reported using NRT for at least 1 day compared with 70.2% (139/198) of participants in standard care (OR, 4.10; 95% CI, 2.31-7.28; P < .01). INTERPRETATION: Among Latino adults who smoke, the Decídetexto intervention was not associated with a statistically significant increase in biochemically verified abstinence at week 24. However, the Decídetexto intervention was associated with a statistically significant increase in self-reported 7-day smoking abstinence at weeks 12 and 24 and uptake of NRT. This RCT provides encouragement for the use of Decídetexto for smoking cessation among Latino adults. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03586596.

Measuring the individualization potential of treatment individualization rules: Application to rules built with a new parametric interaction model for parallel-group clinical trials.

For personalized medicine, we propose a general method of evaluating the potential performance of an individualized treatment rule in future clinical applications with new patients. We focus on rules that choose the most beneficial treatment for the patient out of two active (nonplacebo) treatments, which the clinician will prescribe regularly to the patient after the decision. We develop a measure of the individualization potential (IP) of a rule. The IP compares the expected effectiveness of the rule in a future clinical individualization setting versus the effectiveness of not trying individualization. We illustrate our evaluation method by explaining how to measure the IP of a useful type of individualized rules calculated through a new parametric interaction model of data from parallel-group clinical trials with continuous responses. Our interaction model implies a structural equation model we use to estimate the rule and its IP. We examine the IP both theoretically and with simulations when the estimated individualized rule is put into practice in new patients. Our individualization approach was superior to outcome-weighted machine learning according to simulations. We also show connections with crossover and N-of-1 trials. As a real data application, we estimate a rule for the individualization of treatments for diabetic macular edema and evaluate its IP.

Single nucleotide polymorphism rs4961 in the adducin 1 gene is not associated with gastric cancer or preneoplastic cancer lesions.

Gastric cancer (GC) is the fourth most deadly cancer globally. The adducin 1 (ADD1) protein is involved in oncogenic signal transduction pathways in several types of cancer, and the rs4961 variant (c.1378 G>T, p.Gly460Trp) of the ADD1 gene is associated with salt-sensitive hypertension, renal cell cancer and breast cancer susceptibility; however, it has not been investigated in GC. The aim of the present study was to evaluate the association between the rs4961 variant and the development of GC and preneoplastic gastric lesions (PGLs) in a population from western Mexico. A total of 225 individuals who underwent an endoscopy were evaluated, of which 71 patients had histopathologically diagnosed GC and 53 patients had PGLs, with 101 patients used as controls. The rs4961 variant was genotyped by using PCR and DNA sequencing. The frequency of the mutated homozygous genotype (TT) of the rs4961 variant was <10% in the three evaluated groups, and the frequency of the minor allele (T) was <21% in the GC, PGL and control groups. Genotypic and allelic frequencies were similarly distributed in all of the studied groups (P>0.05). In summary, in the study population, the rs4961 variant was not associated with GC risk; however, its role in other populations and in other types of cancer is worthy of future research.

Impact of Implementing an Antimicrobial Stewardship Program for Optimizing Antibiotic Treatment in Gram-negative Bacilli Bacteremia.

BACKGROUND: Antibiotic Stewardship Programs (ASP) have improved empirical and directed antibiotic treatment in Gram-negative bloodstream infections. A decrease in mortality, readmission, and length of hospitalization has been reported. MATERIALS AND METHODS: A pre-post-quasi-experimental study was conducted between November and April 2015-2016 (pre-intervention period), 2016-2017, 2017-2018, and 2018-2019 (post-intervention periods), to analyse the impact of ASP on empirical, directed, and entire treatment optimization, as well as mortality, readmission, and length of hospitalization, in hospitalized patients with Gram-negative bacilli (GNB) bloodstream infections. RESULTS: One hundred seventy-four patients were included (41 in the pre-intervention group, 38 in the first-year post-intervention group, 50 in the second-year post-intervention group, and 45 in the third-year post-intervention group). There was a significant improvement in directed treatment optimization (43.9% in the pre-intervention group, 68.4% in the first-year post-intervention group, 74% in the second-year post-intervention group, and 88.9% in the third-year post-intervention group, P <0.001), as well as in entire treatment optimization (19.5%, 34.2%, 40.0%, and 46.7%, respectively, P=0.013), with increased optimal directed (adjusted odds ratio [aOR], 3.71; 95% confidence interval [CI], 1.60-8.58) and entire treatment (aOR, 3.31; 95% CI, 1.27-8.58). Although a tendency toward improvement was observed in empirical treatment after ASP implementation, it did not reach statistical significance (41.5% vs. 57.9%, P=0.065). No changes in mortality, readmission, or length of hospitalization were detected. CONCLUSION: ASP implementation improved both directed and entire treatment optimization in patients with GNB bloodstream infections over time. Nevertheless, no improvement was found in clinical outcomes such as mortality, readmission, or length of hospitalization.

Sex differences in the association between social frailty and diet quality among older adults in Spain.

OBJECTIVE: The aim was to examine the association between social frailty and diet quality in adults over 65 years of age, and whether results differed by sex. DESIGN: Population-based cross-sectional study using data from the Spanish National Health Survey. PARTICIPANTS: 5,071 community-dwelling people ≥65 years from Spain. MEASUREMENTS: Social frailty was deemed to exist when the person both lived alone and had low social support, measured with the Duke-UNC scale. Diet was assessed with the Spanish Healthy Eating Index (S-HEI), ranging from 0 to 100 points (highest diet quality). Means and 95% confidence intervals of the S-HEI score for each social frailty group were calculated using linear regressions, with socially robust people as reference. Analyses were adjusted for main confounders, including sociodemographic, lifestyle and morbidity variables. RESULTS: There were no differences in the S-HEI adjusted mean of socially frail (74.3 points, 95%CI: 73.4-75.2) compared to socially robust older adults (75.4 points; 95%CI: 75.1-75.7). In sex-stratified analyses, the S-HEI adjusted mean of socially frail men (71.9 points; 95%CI: 70.6-73.2) was lower than robust men (74.8 points; 95%CI: 74.4-75.3). Specifically, social frailty was associated with lower consumption of vegetables, fruits, dairy and lower diet variety in men. Differences were not observed according to social frailty among older women. CONCLUSIONS: Social frailty was associated with poor diet quality in community-dwelling older men, but not in women in Spain. Gender differences in self-care could partly explain this association. Sex-specific interventions are required to minimize the impact of social frailty on diet quality.

Frequency of rs1051338 and rs116928232 Variants in Individuals from Northwest Mexico.

BACKGROUND: LIPA, situated on chromosome 10q23.2-q23.3, encodes the enzyme lysosomal acid lipase (LAL) (EC 3.1.1.13). Genetic alterations in LIPA lead to lysosomal acid lipase deficiency (LALD), an inborn error causing lipid metabolism anomalies and impairing cholesterol and triacylglyceride degradation. Over 40 LIPA variants have been documented, yet this study focuses on just two. The rs1051338 variant (NM_000235:c.46A>C) affects the signal peptide in Exon 2, whereas rs116928232, located in Exon 8, alters the splice site (NM_000235:c.894G>A), impacting lysosomal acid lipase activity. Considering the diverse clinical manifestations of LALD and the rising hepatic steatosis prevalence in Mexican population, mainly due to diet, these variants were investigated within this demographic to uncover potential contributing factors. This study aimed to reveal the frequency of rs1051338 and rs116928232 among healthy mestizo individuals in Northwest Mexico, marking a significant genetic exploration in this demographic. METHODS: Three hundred ten healthy mestizo individuals underwent PCR-RFLP analysis for both variants, and Sanger sequencing was performed for variant rs116928232. Bioinformatic analysis was also performed to predict protein changes. RESULTS: Allele frequencies for rs1051338 (FA = 0.39, p value = 0.15) and rs116928232 (FA = 0.0016, p value = 0.49) aligned with reported data, while bioinformatic analysis allowed us to identify the protein alteration observed in both variants; finally, the variants showed no linkage between them (normalized D' = 1.03, p value = 0.56). CONCLUSIONS: Allelic frequencies closely matched reported data, and protein structure analysis confirmed variant impacts on LAL enzyme function. Notably, this study marks the first analysis of rs1051338 and rs116928232 in a healthy Mexican mestizo population.

Coping-strategies as a mediator between emotional disorders and problematic alcohol use.

BACKGROUND: Epidemiological studies reveal a high prevalence of alcohol use and comorbidity rates with emotional disorders. This study aims to explore the possible mediational effect of stress-coping strategies on the relationship between symptoms of emotional disorders and problematic alcohol use. METHODS: The sample included 1014 participants (33.82% male, 66.17% female) aged 18 to 75 years (M = 33.0, SD = 15.15). Three mediation analyzes were carried out, for depressive, anxious and somatization symptomatology measured with the LSB-50 in which they acted as an independent variable, the coping strategies of the CSQ as a mediating variable and the problematic alcohol use, measured with AUDIT, as a dependent variable. Additionally, sex, age, educational level, and socioeconomic status were entered as covariates. RESULTS: In all the models, problematic alcohol use was mediated by Problem-Solving Focus and Open Emotional Expression. However, while in depressive symptoms was a fully mediation, in anxious and somatization symptomatology was partially mediated. CONCLUSIONS: The similarities found may be due to shared variance between emotional disorders. Interventions focused on Problem-Solving Focus could improve the emotional symptoms and the problematic alcohol use.

Paraneoplastic glomerulonephritis and kidney infiltration by mantle cell lymphoma: A diagnostic challenge.

Mantle cell lymphoma (MCL) is a rare and aggressive type of lymphoma that can affect the kidneys. The disease can lead to kidney impairment, and glomerulonephritis (GN) is a rare but serious complication of MCL. We report a case of MCL with kidney interstitial infiltration and membranoproliferative glomerulonephritis with focal and segmental glomerulosclerosis. A 75-year-old man presented recurrent acute kidney failure and worsening of nephrotic syndrome. Kidney biopsy revealed membranoproliferative glomerulonephritis presented immunoglobulin and complement deposition, focal and segmental glomerulosclerosis of not otherwise specified type, and infiltration by mantle cell lymphoma. Bone marrow biopsy and PET/CT scan confirmed the diagnosis of mantle cell lymphoma. The patient was treated with R-CHOP21 chemotherapy with cyclophosphamide dose adjustment for nephroprotection. He achieved complete remission with normalization of hematological parameters, improvement of kidney function, and reduction of proteinuria and albuminuria. This case shows the importance of considering alternative diagnoses in patients with recurrent chronic kidney disease and worsening nephrotic syndrome. Early diagnosis and treatment of mantle cell lymphoma can lead to favorable outcomes.

Assessment of Adolescents in Child-to-Parent Violence: Invariance, Prevalence, and Reasons.

Child-to-parent violence is a form of family violence where the children are the aggressors. OBJECTIVE: This study first aimed to analyze the psychometric validity of the Child-to-Parent Violence Questionnaire (CPV-Q) among Ecuadorian adolescents. Second, the measurement invariance across the children's sex was examined. Finally, the prevalence of child-to-parent violence (CPV) was also determined. METHODS: A total of 2084 adolescents aged 12 to 18 years participated in this study. The participants were residents of two provinces in southern Ecuador. A higher percentage of participants were women. They lived mostly with their father and mother. The married marital status of the parents was the most frequently reported. Most of the fathers and mothers of the participants completed primary education. The sampling design was probabilistic, with proportional allocation by age and quotas according to the number of inhabitants per province. The sample size was determined by using a finite population formula. All the participants were randomly selected. The CPV-Q was used to assess child-to-parent violence. The items were adapted linguistically and tailored to the Ecuadorian context. RESULTS: The questionnaire demonstrated excellent model fit and adequate reliability. Full measurement invariance was held for all scales except for the reasons subscale pertaining to fathers. Statistically significant differences were observed with respect to the sex of the aggressor, with control/domain behaviors toward both parents and psychological violence toward the mother being more frequent among daughters than sons. Similarly, reactive reasons were more frequent among daughters than sons. CONCLUSION: This study provides significant psychometric evidence on the CPV-Q in Ecuadorian adolescents along with data on the prevalence of violence against parents.

Establishment of a multisite umbrella cohort study protocol to describe the epidemiology and aetiologies of acute undifferentiated febrile illness in Latin America.

INTRODUCTION: Acute undifferentiated febrile illnesses (AUFIs) impose a large burden in the tropics. Understanding of AUFI's epidemiology is limited. Insufficient diagnostic capacity hinders the detection of outbreaks. The lack of interconnection in healthcare systems hinders timely response. We describe a protocol to study the epidemiology and aetiologies of AUFI and pathogen discovery in strategic areas of Latin America (LA). METHODS AND ANALYSIS: Global Infectious Diseases Network investigators comprising institutions in Colombia, Dominican Republic, México, Perú and the USA, developed a common cohort study protocol. The primary objective is to determine the aetiologies of AUFI at healthcare facilities in high-risk areas. Data collection and laboratory testing for viral, bacterial and parasitic agents are performed in rural and urban healthcare facilities and partner laboratories. Centralised laboratory and data management cores deploy diagnostic tests and data management tools. Subjects >6 years with fever for <8 days without localised infection are included in the cohort. They are evaluated during the acute and convalescent phases of illness. Study personnel collect clinical and epidemiological information. Blood, urine, nasal or pharyngeal swabs and saliva are collected in the acute phase and blood in convalescent phase. Specimens are banked at -80°C. Malaria, dengue and COVID-19 are tested onsite in the acute phase. The acute-phase serum is PCR tested for dengue, chikungunya, Venezuelan equine encephalitis, Mayaro, Oropouche, Zika, and yellow fever viruses. Paired convalescent and acute serum antibody titters are tested for arbovirus, Leptospira spp, and Rickettsia spp. Serum is used for viral cultures and next-generation sequencing for pathogen discovery. Analysis includes variable distributions, risk factors and regression models. Laboratory results are shared with health authorities and network members. ETHICS AND DISSEMINATION: The protocol was approved by local ethics committees and health authorities. The results will be published in peer-reviewed journals. All study results are shared with local and regional health authorities.

Emotional Regulation as a Transdiagnostic Process of Emotional Disorders in Therapy: A Systematic Review and Meta-Analysis.

CONTEXT: Several studies have shown that emotional regulation (ER) is a transdiagnostic construct of emotional disorders. Therefore, if therapy improves ER, it would improve psychological distress. OBJECTIVE: This review assesses and compares the changes in ER due to psychological treatment in different therapies. METHODS: A systematic review and meta-analysis of RCTs published in the databases PubMed, PsycINFO and Web of Science was performed. It was registered in PROSPERO under the number CRD42023387317. Two independent experts in the field reviewed the articles. RESULTS: A total of 18 articles met the criteria for inclusion in the review. Analysis of these studies suggests that in unified protocol (UP), cognitive behaviour therapy, dialectical behaviour therapy (DBT) and mindfulness, there is evidence to support that a moderate effect occurs during treatment. Furthermore, in mindfulness and DBT, the effect was moderate in the follow-up period, while in UP, it was high. LIMITATIONS: Given the heterogeneity of the applied interventions and the methodological limitations found in the reviewed trials, the results should be interpreted with caution. CONCLUSIONS: UP, cognitive behaviour therapy, DBT and mindfulness can improve ER after therapy, while UP, DBT and mindfulness in the follow-up period. Other therapies, such as SKY or Flotation REST, require more research.

INTRODUCCIÓN: Varios estudios han demostrado que la regulación emocional es un constructo transdiagnóstico de los trastornos emocionales. Por lo tanto, si la terapia mejora la regulación emocional, también mejorará el malestar psicológico. OBJETIVO: Evaluar y comparar el cambio en la regulación emocional debido al tratamiento psicológico en diferentes terapias. MÉTODO: Se realizó una revisión sistemática y metaanálisis de ECA publicados en las bases de datos PubMed, PsycINFO y Web of Science. Se registró en PROSPERO con el número CRD42023387317. Dos expertos independientes en la materia revisaron los artículos. RESULTADOS: Un total de 18 artículos cumplieron los criterios de inclusión en la revisión. El análisis de estos estudios sugiere que en el Protocolo Unificado, la Terapia Cognitivo Conductual, la Terapia Dialéctica Conductual y terapias basadas en mindfulness existen evidencias que apoyan que se produce un efecto moderado durante el tratamiento. Además, en las terapias basadas en mindfulness y en la Terapia Dialéctica Conductual, el efecto se moduló en el periodo de seguimiento, mientras que en el Protocolo Unificado fue mayor. LIMITACIONES: Dada la heterogeneidad de las intervenciones aplicadas y las limitaciones metodológicas encontradas en los ensayos revisados, los resultados podrán interpretarse con cautela. CONCLUSIONES: UP, CBT, DBT y mindfulness pueden mejorar la ER tras la terapia, mientras que UP, DBT y mindfulness pueden mejorar la recuperación tras un tiempo de seguimiento. Otras terapias, como SKY o Flotation REST, requieren más investigación.

Video assisted retroperitoneal debridement for infected pancreatic necrosis: A two port approach for difficult access.

INTRODUCTION AND IMPORTANCE: The incidence of acute pancreatitis varies globally, and its rates are increasing. Timely intervention in cases of infected necrosis is crucial to effective management. The landscape of acute pancreatitis management has undergone transformation through adopting a "step-up" strategy, accentuating the shift towards minimally invasive techniques. CASE PRESENTATION: A 63-year-old patient with acute pancreatitis and infected pancreatic necrosis underwent a challenging yet successful treatment using video-assisted retroperitoneal debridement employing a two-port approach facilitated access for an intricate area. The procedure, performed 45 days after admission, effectively reduced peripancreatic collections, demonstrating the efficacy of this approach in managing complex cases of infected pancreatic necrosis. CLINICAL DISCUSSION: The management of acute pancreatitis has evolved towards a comprehensive strategy involving early hydration, nutritional support, effective pain management, and interventions. Infected pancreatic necrosis poses a serious complication, with minimally invasive techniques such as video-assisted retroperitoneal debridement (VARD) emerging as preferred options. The efficacy and safety of VARD in complex cases are highlighted, although challenges persist, especially in extensive necrosis. CONCLUSION: The VARD procedure, a key component of the step-up approach, exhibits a remarkable safety profile, substantially reducing postoperative complications and mortality compared to open surgical counterparts. However, challenges persist in managing cases of infected Walled-Off Necrosis with deep extension, necessitating carefully considering a minimal-access approach. We report our experience using the VARD in a two-port approach.

Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease.

Circulating tumour DNA (ctDNA) allows genotyping and minimal residual disease (MRD) detection in lymphomas. Using a next-generation sequencing (NGS) approach (EuroClonality-NDC), we evaluated the clinical and prognostic value of ctDNA in a series of R-CHOP-treated diffuse large B-cell lymphoma (DLBCL) patients at baseline (n = 68) and after two cycles (n = 59), monitored by metabolic imaging (positron emission tomography combined with computed tomography [PET/CT]). A molecular marker was identified in 61/68 (90%) ctDNA samples at diagnosis. Pretreatment high ctDNA levels significantly correlated with elevated lactate dehydrogenase, advanced stage, high-risk International Prognostic Index and a trend to shorter 2-year progression-free survival (PFS). Valuable NGS data after two cycles of treatment were obtained in 44 cases, and 38 achieved major molecular response (MMR; 2.5-log drop in ctDNA). PFS curves displayed statistically significant differences among those achieving MMR versus those not achieving MMR (2-year PFS of 76% vs. 0%, p < 0.001). Similarly, more than 66% reduction in ΔSUVmax by PET/CT identified two subgroups with different prognosis (2-year PFS of 83% vs. 38%; p < 0.001). Combining both approaches MMR and ΔSUVmax reduction, a better stratification was observed (2-year PFS of 84% vs. 17% vs. 0%, p < 0.001). EuroClonality-NDC panel allows the detection of a molecular marker in the ctDNA in 90% of DLBCL. ctDNA reduction at two cycles and its combination with interim PET results improve patient prognosis stratification.

Double Hit of Hydroxichloroquine and Amiodarone Induced Renal Phospholipidosis in a Patient with Monoclonal Gammopathy and Sclerodermiform Syndrome: A Case Report and Review of the Literature.

Phospholipidosis is a rare disorder which consists of an excessive intracellular accumulation of phospholipids and the appearance of zebra bodies or lamellar bodies when looking at them using electron microscopy. This disease is associated with certain genetic diseases or is secondary to drugs or toxins. Drug-induced phospholipidosis encompasses many types of pharmaceuticals, most notably chloroquine, amiodarone or ciprofloxacin. Clinically and histologically, renal involvement can be highly variable, with the diagnosis not being made until the zebra bodies are seen under an electron microscope. These findings may require genetic testing to discount Fabry disease, as its histological findings are indistinguishable. Most of the chemicals responsible are cationic amphiphilic drugs, and several mechanisms have been hypothesized for the formation of zebra bodies and their pathogenic significance. However, the relationship between drug toxicity and phospholipid accumulation, zebra bodies and organ dysfunction remains enigmatic, as do the renal consequences of drug withdrawal. We present, to our knowledge, the first case report of acute renal injury with a monoclonal gammopathy of renal significance, lesions, and sclerodermiform syndrome, with zebra bodies that were associated with the initiation of a hydroxychloroquine and amiodarone treatment, as an example of drug-induced-phospholipidosis.

Development and validation of a clinical decision support system to prevent anticoagulant duplications.

BACKGROUND AND OBJECTIVE: Unintended duplicate prescriptions of anticoagulants increase the risk of serious adverse events. Clinical Decision Support Systems (CDSSs) can help prevent such medication errors; however, sophisticated algorithms are needed to avoid alert fatigue. This article describes the steps taken in our hospital to develop a CDSS to prevent anticoagulant duplication (AD). METHODS: The project was composed of three phases. In phase I, the status quo was established. In phase II, a clinical pharmacist developed an algorithm to detect ADs using daily data exports. In phase III, the algorithm was integrated into the hospital's electronic health record system. Alerts were reviewed by clinical pharmacists before being sent to the prescribing physician. We conducted a retrospective analysis of all three phases to assess the impact of the interventions on the occurrence and duration of ADs. Phase III was analyzed in more detail regarding the acceptance rate, sensitivity, and specificity of the alerts. RESULTS: We identified 91 ADs in 1581 patients receiving two or more anticoagulants during phase I, 70 ADs in 1692 patients in phase II, and 57 ADs in 1575 patients in phase III. Mean durations of ADs were 1.8, 1.4, and 1.1 calendar days during phases I, II, and III, respectively. In comparison to the baseline in phase I, the relative risk reduction of AD in patients treated with at least two different anticoagulants during phase III was 42% (RR: 0.58, CI: 0.42-0.81). A total of 429 alerts were generated during phase III, many of which were self-limiting, and 186 alerts were sent to the respective prescribing physician. The acceptance rate was high at 97%. We calculated a sensitivity of 87.4% and a specificity of 87.9%. CONCLUSION: The stepwise development of a CDSS for the detection of AD markedly reduced the frequency and duration of medication errors in our hospital, thereby improving patient safety.

pH-responsive targeted nanoparticles release ERK-inhibitor in the hypoxic zone and sensitize free gemcitabine in mutant K-Ras-addicted pancreatic cancer cells and mouse model.

Therapeutic options for managing Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest types of aggressive malignancies, are limited and disappointing. Therefore, despite suboptimal clinical effects, gemcitabine (GEM) remains the first-line chemotherapeutic drug in the clinic for PDAC treatment. The therapeutic limitations of GEM are primarily due to poor bioavailability and the development of chemoresistance resulting from the addiction of mutant-K-RAS/AKT/ERK signaling-mediated desmoplastic barriers with a hypoxic microenvironment. Several new therapeutic approaches, including nanoparticle-assisted drug delivery, are being investigated by us and others. This study used pH-responsive nanoparticles encapsulated ERK inhibitor (SCH772984) and surface functionalized with tumor-penetrating peptide, iRGD, to target PDAC tumors. We used a small molecule, SCH772984, to target ERK1 and ERK2 in PDAC and other cancer cells. This nanocarrier efficiently released ERKi in hypoxic and low-pH environments. We also found that the free-GEM, which is functionally weak when combined with nanoencapsulated ERKi, led to significant synergistic treatment outcomes in vitro and in vivo. In particular, the combination approaches significantly enhanced the GEM effect in PDAC growth inhibition and prolonged survival of the animals in a genetically engineered KPC (LSL-KrasG12D/+/LSL-Trp53R172H/+/Pdx-1-Cre) pancreatic cancer mouse model, which is not observed in a single therapy. Mechanistically, we anticipate that the GEM efficacy was increased as ERKi blocks desmoplasia by impairing the production of desmoplastic regulatory factors in PDAC cells and KPC mouse tumors. Therefore, 2nd generation ERKi (SCH 772984)-iRGD-pHNPs are vital for the cellular response to GEM and denote a promising therapeutic target in PDAC with mutant K-RAS.

Perception of photovoltaic energy consumption in the Spanish primary sector. An environmentally profitable alternative.

Agriculture and livestock farming are activities that depend on energy consumption. Photovoltaic self-consumption systems can reduce the production costs of these actors, especially in periods of high-energy price volatility. This work aimed to determine the degree of implementation of photovoltaic self-consumption systems, their relationship with the economic impact of the energy crisis, and the perception of producers to use renewable energy sources in the Spanish agricultural system as it is one of the most important at European level. For this purpose, a survey of the Spanish agricultural and livestock system, involving 396 primary producers, was carried out between December 2022 and March 2023. The results suggest that self-consumption systems are in place in 49.1% of all farms and that these have had a positive effect in alleviating the rising energy costs suffered by the Spanish primary sector. In summary, Spanish primary producers generally have a favorable perception of the use of renewable energies on their farms, especially photovoltaic. However, the cluster analysis shows the fact that there are two types of producers, active and passive, from an environmental point of view. The characterization of this type of producers can help the Spanish Administration to improve the efficiency of its energy strategy, and can be a source of inspiration for the governments of other countries.

Increased threat of urban arboviral diseases from Aedes aegypti mosquitoes in Colombia.

Objectives: Our study targets the potential of the local urban mosquito Aedes aegypti to experimentally transmit chikungunya virus (CHIKV), dengue virus (DENV), yellow fever virus (YFV), and Zika virus (ZIKV). Methods: We collected eggs and adults of Ae. aegypti in Medellín, Colombia (from February to March 2020) for mosquito experimental infections with DENV, CHIKV, YFV and ZIKV and viral detection using the BioMark Dynamic arrays system. Results: We show that Ae. aegypti from Medellín was more prone to become infected, to disseminate and transmit CHIKV and ZIKV than DENV and YFV. Conclusions: Thus, in Colombia, chikungunya is the most serious threat to public health based on our vector competence data.