Synthesis and Medicinal Applications of N-Heterocyclic Carbene Complexes Based on Caffeine and Other Xanthines.

Xanthines are purine derivatives predominantly found in plants. These include compounds such as caffeine, theophylline, and theobromine and exhibit a variety of pharmacological properties, demonstrating efficacy in treating neurodegenerative disorders, respiratory dysfunctions, and also cancer. The versatile attributes of these materials render them privileged scaffolds for the development of compounds for various biological applications. Xanthines are N-heterocyclic carbene precursors that combine a pyrimidine and an imidazole ring. Owing to their biological relevance, xanthines have been employed as N-heterocyclic carbenes in the development of metallodrugs for anticancer and antimicrobial purposes. In this conceptual review, we examine key examples of N-heterocyclic carbene complexes derived from caffeine and other xanthines, elucidating their synthetic methods and describing their pertinent medicinal applications.

Exploring the potential of fully automated LUMIPULSE G plasma assays for detecting Alzheimer's disease pathology.

BACKGROUND: LUMIPULSE G-automated immunoassays represent a widely used method for the quantification of Alzheimer's disease (AD) biomarkers in the cerebrospinal fluid (CSF). Less invasive blood-based markers confer a promising tool for AD diagnosis at prodromal stages (mild cognitive impairment (MCI)). Highly sensitive assays for the quantification of amyloid-beta (Aß) and phosphorylated Tau-181 (p-Tau181) in the blood are showing promising results. In this study, we evaluated the clinical performance of the recently available fully automated LUMIPULSE plasma marker assays for detecting brain AD pathology and for predicting progression from MCI to AD dementia stage. METHODS: A retrospective exploratory cohort of 138 individuals (22 neurological controls [NC], 72 MCI, and 44 AD dementia patients) was included. Data regarding baseline CSF concentrations of Aß42, Aß40, t-Tau, and p-Tau181 was available and used to establish the presence of AD brain pathology. Baseline Aß42, Aß40, and p-Tau181 concentrations were determined in stored plasma samples using high-throughput fully automated LUMIPULSE assays. Progression from MCI to AD dementia was evaluated during follow-up (mean 6.4 ± 2.5 years). Moreover, a prospective validation cohort of 72 individuals with memory complaints underwent AD biomarker quantification, closely mirroring typical clinical practice. This cohort aimed to confirm the study's main findings. RESULTS: In the exploratory cohort, correlations between CSF and plasma were moderate for p-Tau181 (ρ = 0.61, p < 0.001) and weak for Aß42/Aß40 ratio (ρ = 0.39, p < 0.001). Plasma p-Tau181 and p-Tau181/Aß42 concentrations were significantly increased while Aß42/Aß40 was significantly decreased (p < 0.001) in patients with AD dementia and prodromal AD, as well as in individuals with CSF abnormal amyloid concentrations (A +). Plasma p-Tau181 showed a robust performance in differentiating patients clinically diagnosed as AD (AUC = 0.89; 95% CI 0.83-0.94); A + vs. A - (AUC = 0.84, 95% CI 0.77-0.91) and also in predicting conversion to AD dementia in MCI patients (AUC = 0.89, 95% CI 0.81-0.96). When tested in the validation cohort, plasma p-Tau181 displayed 83.3% of the overall percentage of agreement according to amyloid status. CONCLUSIONS: Our results show that the measurement of p-Tau181 in plasma has great potential as a non-invasive prognostic screening tool for implementation in a clinical setting.

The relationship between obesity-related H19DMR methylation and H19 and IGF2 gene expression on offspring growth and body composition.

Background and objective: Imprinted genes are important for the offspring development. To assess the relationship between obesity-related H19DMR methylation and H19 and IGF2 gene expression and offspring growth and body composition. Methods: Thirty-nine overweight/obese and 25 normal weight pregnant women were selected from the "Araraquara Cohort Study" according to their pre-pregnancy BMI. Fetal growth and body composition and newborn growth were assessed, respectively, by ultrasound and anthropometry. The methylation of H19DMR in maternal blood, cord blood, maternal decidua and placental villi tissues was evaluated by methylation-sensitive restriction endonuclease qPCR, and H19 and IGF2 expression by relative real-time PCR quantification. Multiple linear regression models explored the associations of DNA methylation and gene expression with maternal, fetal, and newborn parameters. Results: H19DMR was less methylated in maternal blood of the overweight/obese group. There were associations of H19DMR methylation in cord blood with centiles of fetal biparietal diameter (BPD) and abdominal subcutaneous fat thickness and newborn head circumference (HC); H19DMR methylation in maternal decidua with fetal occipitofrontal diameter (OFD), HC, and length; H19DMR methylation in placental villi with fetal OFD, HC and abdominal subcutaneous fat thickness and with newborn HC. H19 expression in maternal decidua was associated with fetal BPD and femur length centiles and in placental villi with fetal OFD and subcutaneous arm fat. IGF2 expression in maternal decidua was associated with fetal BPD and in placental villi with fetal OFD. Conclusion: To our knowledge, this is the first study to demonstrate associations of imprinted genes variations at the maternal-fetal interface of the placenta and in cord blood with fetal body composition, supporting the involvement of epigenetic mechanisms in offspring growth and body composition.

Synthesis, Base Pairing Properties, and Biological Activity Studies of Platinum(II) Complexes Based on Uracil Nucleosides.

The synthesis and base pairing properties of platinum complexes based on uridine and deoxyuridine nucleosides and preliminary studies of their antiproliferative activity are described. Platinum(II) uridine and deoxyuridine complexes were synthesized by C-I oxidative addition to Pt(0)(PPh3)4. First, the synthesis was performed with protected nucleosides to generate complexes 1 and 2, which were deprotected under basic conditions, affording complexes 3 and 4 in good yields. The synthesis with the unprotected nucleosides was also performed and provided complexes 3 and 4 effectively. Base pairing interactions were measured for complex 1, either for self-base pairing or for the Watson-Crick base pair. Complex 1 undergoes self-base pairing in CDCl3, and this aggregation was found not to be dependent on metalation. Contrastingly, for the Watson-Crick base pair with adenine, base pairing was also observed, but metalation was found to affect hydrogen bonding considerably. Complexes 3 and 4 and the corresponding ligand precursors were evaluated for their antiproliferative activity against human glioblastoma cell line U-251. The compounds showed IC50 values of 3.30 (3) and 1.84 (4) µM but are also toxic for nontumorous cell lines.

Serum Neurofilament Light Chain in the Diagnostic Evaluation of Patients with Cognitive Symptoms in the Neurological Consultation of a Tertiary Center.

Serum light-chain neurofilaments (sNfL) have been investigated as a potential minimally invasive biomarker that could help in the diagnosis of patients with cognitive symptoms. We assessed the correlation between sNfL and cerebrospinal fluid (CSF) biomarkers (sNfL versus CSF NfL, ρ= 0.70, p < 0.001), the performance of sNfL in distinguishing controls from patients (controls versus frontotemporal dementia, area under curve 0.86), and sNfL differences in mild cognitive impairment according to amyloid-ß (Aß) deposition (Aß versus non-Aß, p = 0.017). Our results support the role of this biomarker in the screening and risk stratification of patients followed in a neurological consultation of a tertiary center.

Maternal plasma transforming growth factor-β1 (TGF-β1) and newborn size: the Araraquara Cohort Study

Abstract Objective To investigate associations of maternal and cord blood cytokine patterns with newborn size and body composition. Methods This cross-sectional study involved 70 pregnant women and their healthy newborns selected from the "Araraquara Cohort Study". Newborn anthropometric measurements were recorded at birth. Body composition was evaluated by air displacement plethysmography. Maternal blood samples were collected from pregnant women between 30 and 36 weeks of gestation, and umbilical cord blood samples were collected immediately after placenta discharge. The concentrations of the cytokines were determined in plasma by ELISA. Multiple linear regression models were used to assess associations between maternal and cord blood cytokine concentrations and newborn anthropometry and body composition measurements. Results Maternal plasma TGF-β1 concentration was inversely associated with newborn weight (β= -43.0; p= 0.012), length (β= -0.16, p= 0.028), head circumference (β= -0.13, p= 0.004), ponderal index (β= -0.32, p= 0.011) and fat-free mass (β= -0.05, p= 0.005). However, the association persisted just for head circumference (β= -0.26; p= 0.030) and ponderal index (β= - 0.28; p= 0.028), after adjusting for pre-gestational BMI, gestational weight gain, gestational age, hours after delivery, newborn sex, smoking and alcohol consumption. Conclusions Maternal plasma TGF-β1 concentration may be involved in the regulation of newborn size, mainly head circumference and ponderal index. Further cohort studies are necessary to investigate the role of TGF-β1 in different trimesters of pregnancy and its effect during the early stages of fetal development.

Antitumor Activity and Reductive Stress by Platinum(II) N-Heterocyclic Carbenes based on Guanosine.

Platinum(II) complexes bearing N-heterocyclic carbenes based guanosine and caffeine have been synthesized by unassisted C-H oxidative addition, leading to the corresponding trans-hydride complexes. Platinum guanosine derivatives bearing triflate as counterion or bromide instead of hydride as co-ligand were also synthesized to facilitate correlation between structure and activity. The hydride compounds show high antiproliferative activity against all cell lines (TC-71, MV-4-11, U-937 and A-172). Methyl Guanosine complex 3, bearing a hydride ligand, is up to 30 times more active than compound 4, with a bromide in the same position. Changing the counterion has no significant effect in antiproliferative activity. Increasing bulkiness at N7, with an isopropyl group (compound 6), allows to maintain the antiproliferative activity while decreasing toxicity for non-cancer cells. Compound 6 leads to an increase in endoplasmic reticulum and autophagy markers on TC71 and MV-4-11 cancer cells, induces reductive stress and increases glutathione levels in cancer cells but not in non-cancer cell line HEK-293.

Blood biomarkers in mild cognitive impairment patients: Relationship between analytes and progression to Alzheimer disease dementia.

BACKGROUND AND PURPOSE: Blood-based biomarkers are promising tools for the diagnosis of Alzheimer disease (AD) at prodromal stages (mild cognitive impairment [MCI]) and are hoped to be implemented as screening tools for patients with cognitive complaints. In this work, we evaluated the potential of peripheral neurological biomarkers to predict progression to AD dementia and the relation between blood and cerebrospinal fluid (CSF) AD markers in MCI patients referred from a general neurological department. METHODS: A group of 106 MCI patients followed at the Neurology Department of Coimbra University Hospital was included. Data regarding baseline neuropsychological evaluation, CSF levels of amyloid ß 42 (Aß42), Aß40, total tau (t-Tau), and phosphorylated tau 181 (p-Tau181) were available for all the patients. Aß42, Aß40, t-Tau, p-Tau181, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) levels were determined in baseline stored serum and plasma samples by commercial SiMoA (Single Molecule Array) assays. Progression from MCI to AD dementia was assessed at follow-up (mean = 5.8 ± 3.4 years). RESULTS: At baseline, blood markers NfL, GFAP, and p-Tau181 were significantly increased in patients who progressed to AD at follow-up (p < 0.001). In contrast, plasma Aß42/40 ratio and t-Tau showed no significant differences between groups. NfL, GFAP, and p-Tau181 demonstrated good diagnostic accuracy to identify progression to AD dementia (area under the curve [AUC] = 0.81, 0.80, and 0.76, respectively), which improved when combined (AUC = 0.89). GFAP and p-Tau181 were correlated with CSF Aß42. Association of p-Tau181 with NfL was mediated by GFAP, with a significant indirect association of 88% of the total effect. CONCLUSIONS: Our findings highlight the potential of combining blood-based GFAP, NfL, and p-Tau181 to be applied as a prognostic tool in MCI.

Maternal plasma transforming growth factor-ß1 (TGF-ß1) and newborn size: the Araraquara Cohort Study.

OBJECTIVE: To investigate associations of maternal and cord blood cytokine patterns with newborn size and body composition. METHODS: This cross-sectional study involved 70 pregnant women and their healthy newborns selected from the "Araraquara Cohort Study". Newborn anthropometric measurements were recorded at birth. Body composition was evaluated by air displacement plethysmography. Maternal blood samples were collected from pregnant women between 30 and 36 weeks of gestation, and umbilical cord blood samples were collected immediately after placenta discharge. The concentrations of the cytokines were determined in plasma by ELISA. Multiple linear regression models were used to assess associations between maternal and cord blood cytokine concentrations and newborn anthropometry and body composition measurements. RESULTS: Maternal plasma TGF-ß1 concentration was inversely associated with newborn weight (ß = -43.0; p = 0.012), length (ß = -0.16, p = 0.028), head circumference (ß = -0.13, p = 0.004), ponderal index (ß = -0.32, p = 0.011) and fat-free mass (ß = -0.05, p = 0.005). However, the association persisted just for head circumference (ß = -0.26; p = 0.030) and ponderal index (ß = - 0.28; p = 0.028), after adjusting for pre-gestational BMI, gestational weight gain, gestational age, hours after delivery, newborn sex, smoking and alcohol consumption. CONCLUSIONS: Maternal plasma TGF-ß1 concentration may be involved in the regulation of newborn size, mainly head circumference and ponderal index. Further cohort studies are necessary to investigate the role of TGF-ß1 in different trimesters of pregnancy and its effect during the early stages of fetal development.

Alzheimer's Disease Diagnosis Based on the Amyloid, Tau, and Neurodegeneration Scheme (ATN) in a Real-Life Multicenter Cohort of General Neurological Centers.

BACKGROUND: The ATN scheme was proposed as an unbiased biological characterization of the Alzheimer's disease (AD) spectrum, grouping biomarkers into three categories: brain Amyloidosis-A, Tauopathy-T, Neurodegeneration-N. Although this scheme was mainly recommended for research, it is relevant for diagnosis. OBJECTIVE: To evaluate the ATN scheme performance in real-life cohorts reflecting the inflow of patients with cognitive complaints and different underlying disorders in general neurological centers. METHODS: We included patients (n = 1,128) from six centers with their core cerebrospinal fluid-AD biomarkers analyzed centrally. A was assessed through Aß42/Aß40, T through pTau-181, and N through tTau. Association between demographic features, clinical diagnosis at baseline/follow-up and ATN profiles was assessed. RESULTS: The prevalence of ATN categories was: A-T-N-: 28.3%; AD continuum (A + T-/+N-/+): 47.8%; non-AD (A- plus T or/and N+): 23.9%. ATN profiles prevalence was strongly influenced by age, showing differences according to gender, APOE genotype, and cognitive status. At baseline, 74.6% of patients classified as AD fell in the AD continuum, decreasing to 47.4% in mild cognitive impairment and 42.3% in other neurodegenerative conditions. At follow-up, 41% of patients changed diagnosis, and 92% of patients that changed to AD were classified within the AD continuum. A + was the best individual marker for predicting a final AD diagnosis, and the combinations A + T+ (irrespective of N) and A + T+N+ had the highest overall accuracy (83%). CONCLUSION: The ATN scheme is useful to guide AD diagnosis in real-life neurological centers settings. However, it shows a lack of accuracy for patients with other types of dementia. In such cases, the inclusion of other markers specific for non-AD proteinopathies could be an important aid to the differential diagnosis.

Genetic Polymorphisms as Predictors of Survival in Breast Cancer: Future Lessons in Historical Data.

Introduction Breast cancer is the most common cancer among women worldwide and one of the main causes of death in the female sex. Genetic polymorphisms in the mu-opioid receptor (OPRM1) and catechol-o-methyltransferase (COMT) genes have been shown to increase breast cancer risk. Variants in these genes may carry a prognostic impact in breast cancer. Long follow-up intervals are critical to adequately analyze prognosis in diseases with prolonged survival times and late relapses. Objective To analyze the impact of genetic polymorphisms on the survival of a cohort of breast cancer patients with very long follow-up. Methods This was a retrospective study of patients treated at Portuguese Oncology Institute of Porto (IPO Porto), a Portuguese comprehensive cancer center, with invasive carcinoma of the breast with very long follow-up, with analysis of genetic polymorphisms OPMR1 rs1799971 (AA vs. G allele) and COMT rs4680 (CC vs T allele) on biological samples. Statistical analysis of survival was performed using the Kaplan-Meier method, log-rank test, and Cox regression method. Results A total of 143 patients with invasive breast cancer were included, with a median follow-up of 21.5 years. There was a statistically significant difference in overall survival (OS) at 30 years according to the OPMR1 polymorphism, with lower survival in patients with the AA genotype (p<0.05). The difference in OS according to the COMT polymorphism was also statistically significant, with worse survival in patients with genotype T allele (p<0.05). The genetic variants were not associated with patient age, stage at diagnosis, or tumor grade. Discussion The genetic polymorphisms of OPRM1 and COMT affected the overall survival of breast cancer patients, in concordance with previous research. Further investigation is needed in order to clarify the prognostic impact of these genetic alterations on breast cancer.

Serum neurofilament light chain as a surrogate of cognitive decline in sporadic and familial frontotemporal dementia.

BACKGROUND AND PURPOSE: Neurofilament light chain (NfL) has recently been proposed as a promising biomarker in frontotemporal dementia (FTD). We investigated the correlation of both cerebrospinal fluid (CSF) and serum NfL with detailed neuropsychological data and cognitive decline in a cohort of sporadic and familial FTD. METHODS: CSF and serum NfL, as well as conventional CSF Alzheimer's disease (AD) biomarkers (Aß42, t-Tau, p-Tau181), were determined in 63 FTD patients (30 sporadic-FTD, 20 with progranulin (GRN) mutations [FTD-GRN], 13 with chromosome 9 open reading frame 72 [C9orf72] expansions [C9orf72-FTD]), 37 AD patients, and 31 neurologic controls. Serum NfL was also quantified in 37 healthy individuals. Correlations between baseline CSF and serum NfL levels, standardized neuropsychological tests, and the rate of cognitive decline in FTD patients were assessed. RESULTS: CSF and serum NfL presented with significantly higher levels in FTD than in AD patients and both control groups. Within FTD subtypes, genetic cases, and particularly FTD-GRN, had higher CSF and serum NfL levels. Significant correlations between NfL levels and overall cognitive function, abstract reasoning (CSF and serum), executive functions, memory, and language (serum) were found. A relationship between increased baseline CSF and serum NfL and a decay in cognitive performance over time was also observed. CONCLUSIONS: Our findings highlight the potential of serum NfL as a useful surrogate end point of disease severity in upcoming targeted treatments.

Development of Triazoles and Triazolium Salts Based on AZT and Their Anti-Viral Activity against HIV-1.

We report herein a set of 3'-azido-3'-deoxythymidine (AZT) derivatives based on triazoles and triazolium salts for HIV-1 infection. The compounds were synthesized via click chemistry with Cu(I) and Ru(II) catalysts. Triazolium salts were synthesized by reaction with methyl iodide or methyl triflate in good yields. The antiviral activity of the compounds was tested using two methodologies: In method one the activity was measured on infected cells; in method two a pre-exposure prophylaxis experimental model was employed. For method one the activity of the compounds was moderate, and in general the triazolium salts showed a decreased activity in relation to their triazole precursors. With method two the antiviral activity was higher. All compounds were able to decrease the infection, with two compounds able to clear almost all the infection, while a lower antiviral activity was noted for the triazolium salts. These results suggest that these drugs could play an important role in the development of pre-exposure prophylaxis therapies.

Synthesis of Platinum(II) N-Heterocyclic Carbenes Based on Adenosine.

Organometallic derivatization of nucleosides is a highly promising strategy for the improvement of the therapeutic profile of nucleosides. Herein, a methodology for the synthesis of metalated adenosine with a deprotected ribose moiety is described. Platinum(II) N-heterocyclic carbene complexes based on adenosine were synthesized, namely N-heterocyclic carbenes bearing a protected and unprotected ribose ring. Reaction of the 8-bromo-2',3',5'-tri-O-acetyladenosine with Pt(PPh3)4 by C8-Br oxidative addition yielded complex 1, with a PtII centre bonded to C-8 and an unprotonated N7. Complex 1 reacted at N7 with HBF4 or methyl iodide, yielding protic carbene 2 or methyl carbene 3, respectively. Deprotection of 1 to yield 4 was achieved with NH4OH. Deprotected compound 4 reacted at N7 with HCl solutions to yield protic NHC 5 or with methyl iodide yielding methyl carbene 6. Protic N-heterocyclic carbene 5 is not stable in DMSO solutions leading to the formation of compound 7, in which a bromide was replaced by chloride. The cis-influence of complexes 1-7 was examined by 31P{1H} and 195Pt NMR. Complexes 2, 3, 5, 6 and 7 induce a decrease of 1JPt,P of more than 300 Hz, as result of the higher cis-influence of the N-heterocyclic carbene when compared to the azolato ligand in 1 and 4.

Intimate Relationships as Perceived by Adolescents: Concepts and Meanings.

Adolescence is a period of great changes and the assumption of risk behaviours at the level of sexuality may have implications for health and well-being. Nowadays, adolescents live free from constraints and prioritise freedom, using their own terminology to label their relationships, it becoming in turn important to conceptualise intimacy relationships from their perspective. Therefore, a qualitative, descriptive, and exploratory study was performed. Participants included 109 adolescents aged 14 and 18 years old from public schools in central Portugal. Data were collected using 12 focus groups and a content analysis was undertaken. These terms attributed to intimate relationships by adolescents are, for the most part, mutual for both genders: crush, friendzone, friends with benefits, making out, dating, and similar in terms of meaning. In an intimate relationship, adolescents give priority to factors such as respect, trust, and love. The fear of loneliness, obsession, and low self-esteem are reasons pointed out by adolescents for maintaining an unhealthy intimate relationship. Adolescents' knowledge of language about their intimate relationships is essential to establish effective communication and to build intervention programs in the healthy intimacy relationships field.

Podemos falar de segurança do paciente durante uma pandemia? Uma experiência portuguesa / Can we talk about patient safety during a pandemia? A portuguese experience / ¿Podemos hablar sobre seguridad del paciente durante una pandemia? Una experiencia portuguesa

Objetivo: enumerar medidas governativas e de saúde pública implementadas em Portugal decorrentes da pandemia pelo vírus SARS-CoV-2 e descrever a atuação do Gabinete de Segurança do Paciente do Centro Hospitalar Universitário de Lisboa Central (CHULC), referência nacional na resposta à situação de emergência de saúde pública. Métodos: utilizou-se como método a análise normativa, documental, além de relato de caso por pesquisa-ação. Resultados: em Portugal, documentaram-se os primeiros casos de infeção por SARS-CoV-2 a 2 de março de 2020. Os processos assistenciais são geridos pelo Ministério da Saúde e Direção Geral da Saúde, abrangendo o Sistema Nacional de Saúde (universal) e o sector privado. O Gabinete de Segurança do Doente do CHULC, participou na redefinição dos processos, criação de vias alternativas de informação entre as várias estruturas, implementação de inovações no uso de tecnologias e vigilância clínica, gestão dos equipamentos de proteção, motivação e suporte emocional dos profissionais e na consolidação das principais metas de segurança do doente (ex. identificação do doente, medicação e cirurgia segura). A aprendizagem feita com os erros contribui para a melhoria contínua dos processos. Conclusão: em Portugal e no mundo a pandemia por COVID-19 não terminou. Compreendemos que é tempo de refletir e voltar aos princípios básicos da segurança, como a higiene das mãos, a etiqueta respiratória e o controlo ambiental. Na gestão do risco e segurança do paciente em situação de crise, é necessário, mais do que nunca, inovar e aprender com os erros.

Objective: to enumerate governmental and public health measures implemented in Portugal resulting from the SARS-CoV-2 virus pandemic and describe the work of the Patient Safety Office of the Centro Hospitalar Universitário de Lisboa Central (CHULC), a national reference in the response to the situation of public health emergency. Methods: normative, documentary analysis was used as a method, in addition to case reports by action research. Results: in Portugal, the first cases of SARS-CoV-2 infection were documented on March 2, 2020. Assistance processes are managed by the Ministry of Health and the General Directorate of Health, covering the National Health System (universal) and the private sector. The CHULC Patient Safety Office, participated in the redefinition of processes, creation of alternative information routes between the various structures, implementation of innovations in the use of technologies and clinical surveillance, management of protective equipment, motivation and emotional support from professionals and consolidating the main patient safety goals (eg patient identification, medication and safe surgery). Learning from mistakes contributes to the continuous improvement of processes. Conclusion: In Portugal and in the world, the COVID-19 pandemic has not ended. We understand that it is time to reflect and return to the basic principles of safety, such as hand hygiene, respiratory etiquette and environmental control. In the management of risk and safety of patients in crisis situations, it is necessary, more than ever, to innovate and learn from mistakes.

Objetivo: enumerar las medidas gubernamentales y de salud pública implementadas en Portugal como resultado de la pandemia del virus SARS-CoV-2 y describir el trabajo de la Oficina de Seguridad del Paciente del Centro Hospitalar Universitário de Lisboa Central (CHULC), una referencia nacional en la respuesta a la situación de emergencia de salud pública. Métodos: se utilizó como método el análisis documental, normativo, además de los reportes de casos por investigación-acción. Resultados: en Portugal se documentaron los primeros casos de infección por SARS-CoV-2 el 2 de marzo de 2020. Los procesos de atención son gestionados por el Ministerio de Salud y la Dirección General de Salud, abarcando el Sistema Nacional de Salud (universal) y el privado. sector. La Oficina de Seguridad del Paciente del CHULC, participó en la redefinición de procesos, creación de rutas alternativas de información entre las distintas estructuras, implementación de innovaciones en el uso de tecnologías y vigilancia clínica, manejo de equipos de protección, motivación y apoyo emocional de los profesionales y consolidando las principales objetivos de seguridad del paciente (por ejemplo, identificación del paciente, medicación y cirugía segura). Aprender de los errores contribuye a la mejora continua de los procesos. Conclusión: En Portugal y en el mundo, la pandemia de COVID-19 no ha terminado. Entendemos que es hora de reflexionar y volver a los principios básicos de seguridad, como la higiene de manos, la etiqueta respiratoria y el control ambiental. En la gestión del riesgo y la seguridad de los pacientes en situaciones de crisis, es necesario, más que nunca, innovar y aprender de los errores.

Long-term impacts of nutrient control, climate change, and invasive clams on phytoplankton and cyanobacteria biomass in a large temperate river.

Recent studies suggest that climate change, with warmer water temperatures and lower and longer low flows, may enhance harmful planktic cyanobacterial growth in lakes and large rivers. Concomitantly, controlling nutrient loadings has proven effective in reducing phytoplankton biomass especially in North America and Western Europe. In addition, the impact of invasive benthic filter-feeder species such as Corbicula on phytoplankton has largely been overlooked in large rivers, leading to even more uncertainty in predicting future trajectories in river water quality. To investigate how nutrient control, climate change and invasion of benthic filter-feeders may affect phytoplankton biomass and composition, we assembled a large database on the entire water course of the River Loire (France) over three decades (1991-2019). We focus on cyanobacteria to provide an in-depth analysis of the 30-year trend and insights on future possible trajectories. Since 1991, total phytoplankton and cyanobacteria biomasses have decreased 10-fold despite warmer water temperature (+0.23 °C·decade-1) and lower summer flow (-0.25 L·s-1·km-2·decade-1). In the long-term, the contribution of planktic cyanobacteria to total biomass was on average 2.8%. The main factors driving total phytoplankton and cyanobacteria biomasses were total phosphorus (4-fold decrease), the abundance of Corbicula clams (from absence before 1998 to 250-1250 individuals·m-2 after 2010), the duration of summer low flows and the intensity of summer heatwaves. The River Loire constitutes an example in Europe of how nutrient control can be an efficient mitigation strategy, counteracting already visible effects of climate change on the thermal regime and flow pattern of the river. This may hold true under future conditions, but further work is needed to account for the climate trajectory, land and water use scenarios, the risk of enhanced benthic biofilm and macrophyte proliferation, together with the spread of invasive filter-feeding bivalves.

On the reactivity of mRNA Cap0: C-H oxidative addition of 7-methylguanosine to Pt0 and base pairing studies.

7-Methylguanosine, whose lability to form an ylide/NHC has been known for decades, reacts with [Pt(PPh3)4] via C-H oxidative addition to yield a hydrido-PtII carbene complex. 1H NMR studies on Watson-Crick base-pairs showed no significant effect of metallation.

C-reactive protein as a predictor of mild cognitive impairment conversion into Alzheimer's disease dementia.

BACKGROUND AND AIMS: Increasing evidence suggests that inflammation plays an important role in brain aging and neurodegeneration. Pathological studies demonstrate the presence of C-reactive protein (CRP) in the senile plaques and neurofibrillary tangles in Alzheimer's disease (AD) brain tissue suggesting that CRP may play a role in its neuropathological processes. Some findings suggest that midlife elevations of serum CRP are a risk factor for AD. However, others found lower CRP levels in mild or moderate AD than in controls, suggesting that CRP levels could be different in different stages of disease. We aimed to assess the role of CRP as a predictor of Mild cognitive impairment (MCI) conversion into AD dementia. METHODS: We retrospectively reviewed the cohort of MCI patients followed at the Dementia Clinic, Neurology Department of University Hospital of Coimbra. We collected demographical, neuropsychological, genetic and laboratorial variables (including serum CRP measurements at the time of baseline laboratory tests). A Cox regression model was performed adjusted for the collected variables preconsidered to be predictors of dementia and the variable being studied (CRP) to assess for independent predictors of conversion. RESULTS: We included 130 patients, 58.5% female, with a mean age of onset of 65.5 ± 9.1 years and age at first assessment of 69.3 ± 8.5 years. The mean CRP was 0.33 ± 0.58 mg/dl. At follow-up (mean, 36.9 ± 27.0 months) 42.3% of MCI patients converted to dementia. Lower CSF Aß42 (HR = 0.999, 95%CI = [0.997, 1.000], p = 0.015), lower MMSE score (HR = 0.864, 95%CI = [0.510, 1.595], p = 0.008) and lower CRP quartile (HR = 0.597, 95%CI = [0.435, 0.819], p = 0.001) were independent predictors of conversion. CONCLUSION: CRP may add information of risk of conversion in MCI patients. Patients with lower CRP levels appear to have a more rapid conversion to AD dementia.