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PROBLEM: The current knowledge of evidence-based design for adults is not always implemented when hospital buildings are designed. Scientific data are sparse on the effects of hospital design in pediatric settings on health outcomes in children, parents, and staff. The objective of this review is to determine the evidence-based impact of the built environment in pediatric hospital facilities on health outcomes in children, parents, and staff. ELIGIBILITY CRITERIA: A systematic literature review was carried out on the electronic databases Cochrane Library, Embase, Medline and CINAHL from the period of 2008 to 2019. The review considered studies using either quantitative, qualitative, or mixed methodologies. SAMPLE: Out of 1414 reviewed articles the result is based on eight included articles. RESULTS: Two of these eight articles included health outcomes. The other six articles presented results on measures of perceptions and/or satisfaction for children, parents or staff with the built environment when transitioning to a new or renovated facility. These were generally higher for the new compared to the old facility. CONCLUSIONS: Given the small number of studies addressing the question posed in this review, no firm conclusions can be drawn. IMPLICATIONS: The review illustrates the need for more research in the pediatric setting assessing the evidence-based health outcomes of aspects of physical environmental design in pediatric hospitals or units in children, parents and staff.
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Arquitetura Hospitalar , Hospitais Pediátricos , Adulto , Ambiente Construído , Criança , Prática Clínica Baseada em Evidências , Humanos , Avaliação de Resultados em Cuidados de Saúde , PaisRESUMO
BACKGROUND: Exercise protects against somatic comorbidities and positively affects cognitive function and psychiatric symptoms in patients with severe mental illness. In forensic psychiatry, exercise is a novel concept. Staff at inpatient care facilities may be important resources for successful intervention. Little is known about staff's knowledge, attitudes and behaviors regarding exercise in forensic psychiatric care. AIMS: To translate, culturally adapt and test the feasibility of the Exercise in Mental Health Questionnaire-Health Professionals Version (EMIQ-HP) in the Swedish context, and to use this EMIQ-HP-Swedish version to describe staff's knowledge, attitudes and behaviors regarding exercise. METHOD: The EMIQ-HP was translated, culturally adapted, pilot-tested and thereafter used in a cross-sectional nationwide survey. RESULTS: Ten of 25 clinics and 239 health professionals (50.1%) participated. Two parts of the EMIQ-HP-Swedish version showed problems. Most participants considered exercise to be a low-risk treatment (92.4%) that is beneficial (99.2%). Training in exercise prescription was reported by 16.3%. Half of participants (52.7%) prescribed exercise and 50.0% of those undertook formal assessments prior to prescribing. CONCLUSIONS: Creation of the EMIQ-HP-Swedish version was successful, despite some clarity problems. Exercise appears to be prescribed informally by non-experts in Swedish forensic psychiatric care and does not address treatment goals.
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BACKGROUND: Brief screening instruments focusing on autism spectrum disorder (ASD) that can be administered in primary care are scarce; there is a need for shorter and more precise instruments. The Autism-Tics, AD/HD and other Comorbidities inventory (A-TAC) has previously been validated for ASD reporting excellent validity. This study aims to determine the psychometric properties of each item in the ASD domain (17 items) in the A-TAC using item response theory (IRT), and thereby construct and validate a short form that could be used as a screening instrument in the general population. METHODS: Since 2004, parents of all 9-year-old Swedish twins have been invited to participate in a telephone interview in the Child and Adolescent Twin Study in Sweden (CATSS). The CATSS is linked to the National Patient Register (NPR), which includes data from in- and outpatient care. Data on ASD (A-TAC) collected in CATSS were compared with diagnoses from the NPR. Diagnoses that had been made both before (previous validity) and after (predictive validity) the interviews were included. The sample was divided into a developmental sample and a validation sample. An IRT model was fitted to the developmental sample and item parameters were used to select a subset of items for the short form. The performance of the proposed short form was examined in the validation sample by the use of receiver operation characteristic curves. RESULTS: Four items which were able to discriminate among individuals with more autism traits were deemed sufficient for use in the short form. The values of the area under the receiver operating characteristic curve for a clinical diagnosis of ASD was .95 (previous validity) and .72 (predictive validity). CONCLUSIONS: The proposed short form with 4 out of the original 17 items from A-TAC, showed excellent previous validity while the predictive validity was fair. The validity of the short form was in agreement with previous validations of the full ASD domain. The short form can be a valuable screening instrument in primary care settings in order to identify individuals in need for further assessment and for use in epidemiological studies.
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Transtorno do Espectro Autista/diagnóstico , Doenças em Gêmeos/diagnóstico , Programas de Rastreamento/métodos , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Teoria Psicológica , Gêmeos/psicologia , Adolescente , Criança , Feminino , Humanos , Masculino , Pais , Psicometria , Suécia/epidemiologiaRESUMO
Carbonic anhydrase (CA, EC 4.2.1.1) IX is regarded as a tumour hypoxia marker and CA inhibitors have been proposed as a new class of antitumor agents, with one such agent in Phase II clinical trials. The expression of some CAs, in particular the isoforms CA IX and CA XII, has been correlated with tumour aggressiveness and progression in several cancers. The aim of this study was to evaluate the possibility that CA IX could represent a marker related to clear cell Renal Cell Carcinoma (ccRCC). Bcl-2 and Bax, and the activity of caspase-3, evaluated in tissue biopsies from patients, were congruent with resistance to apoptosis in ccRCCs with respect to healthy controls, respectively. In the same samples, the CA IX and pro-angiogenic factor VEGF expressions revealed that both these hypoxia responsive proteins were strongly increased in ccRCC with respect to controls. CA IX plasma concentration and CA activity were assessed in healthy volunteers and patients with benign kidney tumours and ccRCCs. CA IX expression levels were found strongly increased only in plasma from ccRCC subjects, whereas, CA activity was found similarly increased both in plasma from ccRCC and benign tumour patients, compared to healthy volunteers. These results show that the plasmatic level of CA IX, but not the CA total activity, can be considered a diagnostic marker of ccRCCs. Furthermore, as many reports exist relating CA IX inhibition to a better outcome to anticancer therapy in ccRCC, plasma levels of CA IX could be also predictive for response to therapy.
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Biomarcadores Tumorais , Anidrase Carbônica IX/sangue , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/diagnóstico , Idoso , Western Blotting , Anidrase Carbônica IX/genética , Anidrase Carbônica IX/metabolismo , Carcinoma de Células Renais/enzimologia , Caspase 3/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase em Tempo Real , Regulação para CimaRESUMO
BACKGROUND: Reliable and easy to administer screening instruments focusing on neurodevelopmental disorders and associated conditions are scarce. The Autism-Tics, AD/HD and other Comorbidities inventory (A-TAC) has previously been validated and reporting good- excellent validity for several disorders. This article aims to expand these findings by including more conditions in a substantially larger sample augmented with the Swedish National Patient Register (NPR). METHODS: Since 2004 parents of all 9-year-old Swedish twins have been invited to participate in a telephone interview in the Child and Adolescent Twin Study in Sweden, CATSS. The CATSS is linked to the NPR which includes data from in- and outpatient care. Data on neurodevelopmental disorders (A-TAC) collected in CATSS were compared with diagnoses from the NPR. We investigated diagnoses that had been made both before (previous validity) and after (predictive validity) the interview. RESULTS: Sensitivity and specificity of A-TAC scores for predicting earlier or later clinical diagnoses were mostly good-excellent, with values of the area under the curve for a clinical diagnosis of autism spectrum disorder (ASD) of .98, attention deficit hyperactivity disorder (ADHD) .93, learning disorder (LD) .92, and oppositional defiant disorder (ODD) .99, with small differences in terms of previous and predictive analyses. A-TAC provided little validity for eating disorders. CONCLUSION: The result support previous claims: A-TAC is a broad screening instrument with a particular strength in assessing ASD, ADHD, LD, and ODD at ages 9 and 12, and also provides phenotypic information about other child psychiatric disorders.
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Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno Autístico/diagnóstico , Doenças em Gêmeos/diagnóstico , Testes Neuropsicológicos/normas , Transtornos de Tique/diagnóstico , Adolescente , Área Sob a Curva , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/diagnóstico , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/psicologia , Transtorno Autístico/psicologia , Criança , Comorbidade , Doenças em Gêmeos/psicologia , Feminino , Humanos , Deficiências da Aprendizagem/diagnóstico , Deficiências da Aprendizagem/psicologia , Masculino , Pais , Valor Preditivo dos Testes , Sistema de Registros , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Suécia , Transtornos de Tique/psicologia , Gêmeos/psicologiaRESUMO
Global change is a major threat to the oceans, as it implies temperature increase and acidification. Ocean acidification (OA) involving decreasing pH and changes in seawater carbonate chemistry challenges the capacity of corals to form their skeletons. Despite the large number of studies that have investigated how rates of calcification respond to ocean acidification scenarios, comparatively few studies tackle how ocean acidification impacts the physiological mechanisms that drive calcification itself. The aim of our paper was to determine how the carbonic anhydrases, which play a major role in calcification, are potentially regulated by ocean acidification. For this we measured the effect of pH on enzyme activity of two carbonic anhydrase isoforms that have been previously characterized in the scleractinian coral Stylophora pistillata. In addition we looked at gene expression of these enzymes in vivo. For both isoforms, our results show (1) a change in gene expression under OA (2) an effect of OA and temperature on carbonic anhydrase activity. We suggest that temperature increase could counterbalance the effect of OA on enzyme activity. Finally we point out that caution must, thus, be taken when interpreting transcriptomic data on carbonic anhydrases in ocean acidification and temperature stress experiments, as the effect of these stressors on the physiological function of CA will depend both on gene expression and enzyme activity.
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Antozoários/metabolismo , Carbonatos/metabolismo , Anidrases Carbônicas/metabolismo , Animais , Calcificação Fisiológica/fisiologia , Mudança Climática , Recifes de Corais , Concentração de Íons de Hidrogênio , Oceanos e Mares , Água do Mar , TemperaturaRESUMO
OBJECTIVES: In this study, we explored healthcare workers' (HCWs) worry perception and its association with their work situation during the first wave of the COVID-19 pandemic. DESIGN: A web-based multimethods survey including multiple choice and open-ended questions was used. SETTING: The study was conducted at a university hospital in Sweden. PARTICIPANTS: All HCWs who were working during the first wave of the COVID-19 pandemic in March-June 2020 were eligible. HCWs (n=6484, response rate=41%) from 69 departments fulfilled the study inclusion criteria and responded to the survey. Of them, we analysed data from the 3532 participants who replied to the open-ended questions (54% of the respondents). MAIN OUTCOMES MEASURES: Worry perception and its association with work conditions among HCWs. RESULTS: 29% (n=1822) and 35% (n=2235) of the responding HCWs experienced a daily or more than daily strong worry of being infected or infecting others with SARS-CoV-2. This finding could be further confirmed and explored with themes from the qualitative results: 'ambiguity of feeling safe and secure', 'being obliged to adapt to a new reality' and 'into the unknown'. The themes consisted of 6 main categories and 15 subcategories. The findings revealed that the two main drivers of worry perceived by HCWs were lack of personal protective equipment and fear of bringing the virus home to their families and friends. CONCLUSIONS: Worries of getting infected are common among HCWs during crises such as the COVID-19 pandemic. Several factors are raised that plausibly could minimise the negative effects of worry among HCWs. Thus, effective preventive work plans should be created, promoted and communicated in order to minimise the effects of such crises and support HCWs. By focusing on effective communication and preparedness, including access to relevant protective equipment and providing general support to HCWs, the work environment and patient care could be sustained during a crisis such as the COVID-19 pandemic.
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COVID-19 , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Suécia/epidemiologia , Pandemias , Hospitais Universitários , Pessoal de Saúde , Percepção , InternetRESUMO
Gold nanoparticles (AuNPs) have gained attention for their potential and application in different fields, e.g. nanomedicine. This study explores the surface functionalization of AuNP with inhibitors of carbonic anhydrases (CAs, EC 4.2.1.1). Some CA transmembrane isoforms have been recognized as therapeutic targets for the treatment of hypoxic tumors. Embedding a CA inhibitory function onto a nanosized unit has been proved to enable selective targeting of transmembrane isoforms. We report the preparation in aqueous media, the characterization and CA inhibition tests of AuNPs coated with a sulfonamide (SA) derivative, already known for its inhibitory activity toward CAs. The physico-chemical characterization of SA-coated AuNPs was performed with a combination of scattering and spectroscopic techniques. We detect a threshold effect of the SA concentration on the final hydrodynamic and core sizes of the capped nanoparticles and on their stability over aggregation. These modified nanoparticles were assayed for inhibition of some CA transmembrane isoforms (CA IX and XII) as well as of two cytosolic isoforms (CA I and II), and show interesting inhibitory efficiency in the submicromolar range and some selectivity for transmembrane isoforms.
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Inibidores da Anidrase Carbônica/química , Ouro/química , Nanopartículas Metálicas/química , Sulfonamidas/química , Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/efeitos dos fármacos , Sulfonamidas/farmacologiaRESUMO
BACKGROUND: The aim of this study was to evaluate criminal outcomes of mentally disordered offenders in compulsory forensic psychiatric care during the year 2010 versus 2018. More specifically, we sought to identify the occurrence of new criminal sentences during ongoing treatment and possible factors associated with recidivistic criminality. Another aim was to map previous criminality, types of index crime, and whether there were any changes within this decade. METHODS: Crime-, clinical, and treatment-related variables were collected from the Swedish National Forensic Psychiatric Register for all unique inpatients registered from January 1-December 31 in 2010 (N = 717) and 2018 (N = 757). The mean, frequency, percentage, and standard deviation were calculated per variable and stratified by study year and gender. Between-group comparisons were made using t-tests and Chi-square tests. Binary logistic regression was performed to determine whether variables expected to be associated with recidivism showed any relation to criminal recidivism for each study cohort. RESULTS: Most patients were male and approximately one-quarter and one-half of the men, respectively, had a previous sentence for non-violent and violent crimes. The 2018 cohort showed significantly lower rates of sentences to forensic psychiatry with special court supervision although the numbers were low in both cohorts and for both men and women. Previous violent conviction was associated with criminal recidivism during treatment in 2010, while this was joined by index crime under the influence of alcohol/illicit drugs for the 2018 cohort. CONCLUSIONS: Overall, these results showed more similarities between the 2010 and 2018 cohorts then dissimilarities, while on the other hand some quite substantial differences were described between males versus females. The results of this study indicate that it may be possible to tailor forensic psychiatric treatment to gender as a proxy for other variables related to increased criminal recidivism in offenders sentenced to forensic psychiatric care.
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Criminosos , Transtornos Mentais , Reincidência , Humanos , Masculino , Feminino , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Transtornos Mentais/psicologia , Psiquiatria Legal , Suécia/epidemiologia , Crime/psicologia , Criminosos/psicologiaRESUMO
Background: Healthcare workers (HCWs) at infectious disease departments have held the frontline during the COVID-19 pandemic. This study aimed to identify barriers and facilitators to maintaining the employees' wellbeing that may be used to increase preparedness for future pandemics within ID Departments. Methods: In September 2020, a web-based survey on demographics and work environment was distributed to all HCWs at the Infectious Disease Department at Sahlgrenska University Hospital. Results were compared with a pre-COVID-19 survey from October 2019. A quantitative analysis of the overall effects of the pandemic on the working conditions of HCWs was conducted; in addition, a qualitative content analysis of open-ended responses was performed. Results: In total, 222 and 149 HCWs completed the pre-COVID-19 and COVID-19 surveys (84 and 54% response rate), respectively. Overall, we found significant changes regarding increased workload, lack of emotional support in stressful work situations, and inability to recover after shifts. These factors correlated both with younger age and concern of becoming infected. The open-ended answers (n = 103, 69%) revealed five generic categories (Workload; Organizational support; Worry and ethical stress; Capability; and Cooperation and unity) with a total of 14 identified factors representing plausible individual and organizational-level barriers or facilitators to sustained employee wellbeing. Conclusion: Younger HCWs as well as those expressing worries about contracting the infection were found to be particularly affected during the COVID-19 pandemic and these groups may require additional support in future outbreaks. Factors both increasing and decreasing the pandemic-induced negative health consequences for HCWs were identified; this knowledge may be utilized in the future.
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The members of a focused series of carboxylic acids and of their derivatives (esters, amides and metal complexes) have been investigated as inhibitors of the main cytosolic/transmembrane carbonic anhydrase isoforms, CA I, II, IX and XII, belonging to the mammalian α-class of CAs. These enzymes are present in red blood cells in submillimolar concentration, and typical sulfonamide CA inhibitors do not selectively inhibit any of them. Among such isozymes, the isoform-I is an 'orphan' target that mediates hemorrhagic retinal and cerebral vascular permeability, involved in retinal and cerebral disease. In the present study, we identified the first selective CA I nanomolar inhibitors, that displayed activity against other isozymes in micromolar/millimolar concentration range. Selective CA II over CA I inhibition has also been observed with some diketo acids/metal complexes. Few diketo acid derivatives showed inhibition activities against the fungal ß-class enzymes from Candida albicans and Cryptococcus neoformans in low micromolar concentration range. Prediction of drug-like properties for the most interesting compounds suggests a favorable bioavailability.
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Candida albicans/enzimologia , Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/metabolismo , Ácidos Carboxílicos/farmacologia , Cryptococcus neoformans/enzimologia , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Ácidos Carboxílicos/síntese química , Ácidos Carboxílicos/química , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Human carbonic anhydrase (CA, EC 4.2.1.1) VII is a cytosolic enzyme with high carbon dioxide hydration activity. Here we report an unexpected S-glutathionylation of hCA VII which has also been observed earlier in vivo for hCA III, another cytosolic isoform. Cys183 and Cys217 were found to be the residues involved in reaction with glutathione for hCA VII. The two reactive cysteines were then mutated and the corresponding variant (C183S/C217S) expressed. The native enzyme, the variant and the S-glutathionylated adduct (sgCA VII) as well as hCA III were fully characterized for their CO(2) hydration, esterase/phosphatase activities, and inhibition with sulfonamides. Our findings suggest that hCA VII could use the in vivo S-glutathionylation to function as an oxygen radical scavenger for protecting cells from oxidative damage, as the activity and affinity for inhibitors of the modified enzyme are similar to those of the wild type.
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Inibidores da Anidrase Carbônica/química , Anidrases Carbônicas/metabolismo , Sulfonamidas/química , Sequência de Aminoácidos , Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/genética , Citosol/enzimologia , Ativação Enzimática/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Dados de Sequência Molecular , Isoformas de Proteínas/genética , S-Nitrosoglutationa/química , Alinhamento de Sequência , Espectrometria de Massas por Ionização por Electrospray , Sulfonamidas/farmacologiaRESUMO
A library of 32 novel glycoconjugate thiourea-bridged benzene sulfonamides have been synthesized from the reaction of glycosyl isothiocyanates with a panel of simple benzene sulfonamides comprising either a free amine or hydrazide. All compounds were investigated for their ability to inhibit the enzymatic activity of five human carbonic anhydrase (hCA) isozymes: hCA I, II and membrane-associated isozymes IX, XII and XIV. A physicochemical feature of the free sugar thioureido glycoconjugates was high water solubility (> 20 mg/mL), as well many of these compounds exhibited a desirable potency and CA isozyme selectivity profile. From this library several inhibitors displayed excellent potency-selectivity profiles for transmembrane anchored CAs over off-target CA I and II. These molecules provide potential dual-acting candidates for the development of inhibitors that target the extracellular CAs (IX, XII and XIV)-either directly as free sugars (membrane impermeable) or indirectly as acetylated prodrugs, becoming free sugars upon esterase hydrolysis.
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Inibidores da Anidrase Carbônica/síntese química , Anidrases Carbônicas/química , Desenho de Fármacos , Tioureia/química , Carboidratos/química , Inibidores da Anidrase Carbônica/química , Anidrases Carbônicas/metabolismo , Glicoconjugados/síntese química , Glicoconjugados/química , Humanos , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/metabolismo , Solubilidade , Sulfonamidas/químicaRESUMO
Different natural products and secondary metabolites from mushrooms, teas, honeys, mosses, plants and seaweeds were investigated for their in vitro inhibitory effects on human carbonic anhydrase (hCA, E.C.4.2.1.1) isoforms I and II. Inhibition data were correlated with the total phenol content in the extract and investigated with the pure compounds believed to be responsible for this activity. Methanolic extracts were prepared for 17 such pure chemicals present in the natural products and for 41 diverse natural products. The IC(50) values were in the range of 0.11-66.50 µg/mL against hCA I and of 0.09-54.54 µg/mL against hCA II, respectively. The total phenol content was in the range of 0.02-1318.96 (as milligrams of gallic acid equivalents) per gram of sample. These data offer new insights on possible novel classes of CA inhibitors based on natural products, possessing a range of chemical structures not present in the classical inhibitors with pharmacological applications, such as the sulfonamides and sulfamates.
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Agaricales/química , Produtos Biológicos/farmacologia , Anidrase Carbônica II/antagonistas & inibidores , Anidrase Carbônica I/antagonistas & inibidores , Inibidores da Anidrase Carbônica/farmacologia , Mel , Plantas/química , Biocatálise , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Anidrase Carbônica I/metabolismo , Anidrase Carbônica II/metabolismo , Inibidores da Anidrase Carbônica/química , Inibidores da Anidrase Carbônica/isolamento & purificação , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Enhanced receptor selectivity: carbonic anhydrase inhibitors are relevant for both cancer diagnosis and therapy. Combining non-radioactive Re compounds with their radioactive (99m)Tc homologs enables the use of identical molecules for therapy and imaging (theragnostic). The syntheses and in vitro evaluation of [(Cp-R)M(CO)(3)] (Cp=cyclopentadienyl, M=Re, (99m)Tc) with R being a highly potent carbonic-anhydrase-targeting vector is reported.
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Antígenos de Neoplasias/química , Inibidores da Anidrase Carbônica/química , Anidrases Carbônicas/química , Sulfonamidas/química , Ácidos Sulfônicos/química , Antígenos de Neoplasias/metabolismo , Anidrase Carbônica IX , Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/metabolismo , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Células HEK293 , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Compostos de Organotecnécio/química , Rênio/química , Tamoxifeno/químicaRESUMO
Introduction: The aim of this study is to provide insight into the psychosocial work situation of hospital managers during the first wave of the COVID-19 pandemic. Methods: Mixed-effect modelling was used on survey data on job demands, job resources, job motivation, and work-life balance among over 500 managers working in 55 departments of a large Swedish university hospital in 2019 and 2020. Responses from 6011 employees were then used to stratify the analysis for COVID-19 exposure. Inductive content analysis was applied to open-ended questions on the managers' views on organisational prerequisites during the onset of the pandemic. Results: The proportion of managers reporting difficulties with role clarity, quantitative demands, decision-making authority, and emotional support, time for recovery at work, motivation deficits, or problems with work-life balance clearly increased during the first wave of the pandemic. The proportion of managers reporting negative responses was higher in departments with high COVID-19 exposure. The qualitative analysis shows that overall governance in terms of clear, fair, and well-communicated routines, resource allocation, and division of responsibilities constituted an important framework for managerial during the crisis. First-line managers also require a mandate to re-organize their roles and their teams to successfully adapt to the situation. Organisational and social support was also important resources. Discussion: This is the first study investigating healthcare managers' work situation during the first wave of the COVID-19 pandemic in a Swedish context. As expected, it indicates an increasingly strained work situation during the crisis, but it also provides findings on organisational prerequisites that allow healthcare managers to cope with stressful situations. In line with previous research on organisational resilience, the study provides suggestions for how higher-level managers can act in order to provide front-line managers with the organisational prerequisites they need to adapt, learn and develop successfully during times of unpredictability, insecurity, and rapid change in order to offer the best possible support to health care workers.
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OBJECTIVE: The aim of this study was to investigate how the changed work routines during the COVID-19 pandemic has been affecting the working environment for hospital-based maternity and neonatal health care workers, and to identify preventive measures to be used in future situations when health care organizations are under pressure. METHODS: All maternity and neonatal health care workers in a Swedish university hospital were surveyed during October 2019 and September 2020. The data was analyzed by document analysis of implemented changes in working routines, a quantitative analysis of the overall effects on the working conditions, and a qualitative analysis of open-ended responses. RESULTS: A total of 660 maternity and neonatal health care workers completed the pre-COVID-19 survey (74% response rate) and 382 the COVID-19 survey (35% response rate). Lack of personal protective equipment, worry about becoming infected, uncertainty whether implemented changes were enough, and challenges in communicating updated routines had negative effects on maternity and neonatal health care workers' working conditions. Team spirit and feeling valued by peers had a positive effect. CONCLUSIONS: Results suggest that negative effects on maternity and neonatal health care workers' health can partly be prevented in future critical situations by creating a work climate that acknowledges the employees' worry about being infected, securing adequate pre-conditions for managers, creating a strong psychosocial safety climate and systematically improving the working conditions for the maternity and neonatal health care workers, as well as maintaining the positive perceived effects of increased team spirit and feeling valued by peers.
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COVID-19 , Feminino , Pessoal de Saúde/psicologia , Hospitais , Humanos , Recém-Nascido , Pandemias/prevenção & controle , Gravidez , Local de TrabalhoRESUMO
Carbonic anhydrases (CAs) are enzymes whose endogenous reaction is the reversible hydration of CO(2) to give HCO(3)(-) and a proton. CA are also known to exhibit weak and promiscuous esterase activity toward activated esters. Here, we report a series of findings obtained with a set of CA inhibitors that showed quite unexpectedly that the compounds were both inhibitors of CO(2) hydration and substrates for the esterase activity of CA. The compounds comprised a monosaccharide core with the C-6 primary hydroxyl group derivatized as a sulfamate (for CA recognition). The remaining four sugar hydroxyl groups were acylated. Using protein X-ray crystallography, the crystal structures of human CA II in complex with four of the sulfamate inhibitors were obtained. As expected, the four structures displayed the canonical CA protein-sulfamate interactions. Unexpectedly, a free hydroxyl group was observed at the anomeric center (C-1) rather than the parent C-1 acyl group. In addition, this hydroxyl group is observed axial to the carbohydrate ring while in the parent structure it is equatorial. A mechanism is proposed that accounts for this inversion of stereochemistry. For three of the inhibitors, the acyl groups at C-2 or at C-2 and C-3 were also absent with hydroxyl groups observed in their place and retention of stereochemistry. With the use of electrospray ionization-Fourier transform ion cyclotron resonance-mass spectrometry (ESI-FTICR-MS), we observed directly the sequential loss of all four acyl groups from one of the carbohydrate-based sulfamates. For this compound, the inhibitor and substrate binding mode were further analyzed using free energy calculations. These calculations suggested that the parent compound binds almost exclusively as a substrate. To conclude, we have demonstrated that acylated carbohydrate-based sulfamates are simultaneously inhibitor and substrate of human CA II. Our results suggest that, initially, the substrate binding mode dominates, but following hydrolysis, the ligand can also bind as a pure inhibitor thereby competing with the substrate binding mode.
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Carboidratos/química , Anidrase Carbônica II/antagonistas & inibidores , Inibidores da Anidrase Carbônica/farmacologia , Ésteres/química , Ácidos Sulfônicos/farmacologia , Anidrase Carbônica II/metabolismo , Inibidores da Anidrase Carbônica/química , Humanos , Hidrólise , Modelos Moleculares , Conformação Molecular , Relação Estrutura-Atividade , Ácidos Sulfônicos/químicaRESUMO
A series of compounds incorporating regioisomeric phenylethynylbenzenesulfonamide moieties has been investigated for the inhibition of four human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, hCA I, II, IX and XII. Inhibition between the low nanomolar to the milliomolar range has been observed against them, with several low nanomolar and tumor-CA selective inhibitors detected. The position of the sulfamoyl group with respect to the alkyne functionality, and the nature of the moieties substituting the second aromatic ring were the principal structural features influencing CA inhibition. The para-sulfamoyl-substituted derivatives were effective inhibitors of CA IX and XII, the meta-substituted regioisomers of CA I, IX and XII, whereas the ortho-substituted sulfonamides were weak inhibitors of CA I, II and IX, but inhibited significantly CA XII.
Assuntos
Antígenos de Neoplasias/metabolismo , Anidrases Carbônicas/metabolismo , Isoenzimas/química , Sulfonamidas/síntese química , Sulfonamidas/farmacologia , Antígenos de Neoplasias/química , Anidrase Carbônica I/antagonistas & inibidores , Anidrase Carbônica I/química , Anidrase Carbônica I/metabolismo , Anidrase Carbônica II/antagonistas & inibidores , Anidrase Carbônica II/química , Anidrase Carbônica II/metabolismo , Anidrase Carbônica IX , Inibidores da Anidrase Carbônica/química , Inibidores da Anidrase Carbônica/metabolismo , Anidrases Carbônicas/química , Citosol/enzimologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Isoenzimas/metabolismo , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Estereoisomerismo , Relação Estrutura-Atividade , Sulfonamidas/química , Sulfonamidas/metabolismoRESUMO
The inhibition of the ß-carbonic anhydrases (CAs, EC 4.2.1.1) from the pathogenic fungi Cryptococcus neoformans (Can2) and Candida albicans (Nce103) with a series of 25 branched aliphatic and aromatic carboxylates has been investigated. Human isoforms hCA I and II were also included in the study for comparison. Aliphatic carboxylates were generally millimolar hCA I and II inhibitors and low micromolar/submicromolar ß-CA inhibitors. Aromatic carboxylates were micromolar inhibitors of the four enzymes but some of them showed low nanomolar activity against the fungal pathogenic enzymes. 4-Hydroxy- and 4-methoxy-benzoate inhibited Can2 with K(I)s of 9.5-9.9 nM. The methyl esters, hydroxamates, hydrazides and carboxamides of some of these derivatives were also effective inhibitors of the α- and ß-CAs investigated here.