Insight into the esterase like activity demonstrated by an imidazole appended self-assembling hydrogelator

A low molecular weight hydrogelator with a covalently appended imidazole moiety is reported. Capable of percolating water in the pH range of 6 to 8, it proves to be an efficient catalyst upon self-assembly, showing Michaelis-Menten type kinetics. Activities at different pH values correlated with dramatic structural changes were observed. It can hydrolyse p-nitrophenyl acetate (pNPA) as well as inactivated esters, and l and d-phenylalanine methyl esters. The enhanced activity can be related to the conglomeration of catalytic groups upon aggregation resulting in their close proximity and the formation of hydrophobic pockets

Performance and costs of a rapid syphilis test in an urban population at high risk for sexually transmitted infections

Introduction. Rapid syphilis screening could facilitate caseidentification in populations at high risk for sexually transmitted infections (STI). The aim of this study was to compare the performance and the cost-effectiveness of a rapid immunochromatography syphilis test with a traditional ELISA screening test in patients with suspected infectious syphilis or patients at high risk for STI/syphilis. Methods. Consecutive patients attending a STI clinic cosensually underwent serological testing with two different tests. Sensitivity, specificity, Positive Predictive Values, Negative Predictive Values and effectiveness of the two tests were evaluated with respect to definitive diagnosis. Results. In our population, the immunochromatography essay (Abbott Determine Syphilis TP) had a sensitivity of 95.0% (95% CI 88.7-97.8) and a specificity of 97.7% (95% CI 94.7-99.0). The ELISA test had a sensitivity of 95.0% (95% CI 88.8-97.9) and a specificity of 97.2% (95% CI 94.1-98.7). The Positive Predictive Value for ELISA was 94.1% (95% CI 87.6-97.3) and 95.0% (95% CI 88.7-97.8) for the rapid test. The Negative Predictive Value was 97.7% (95% CI 94.7-99) for both ELISA and the rapid tests. The cost-effectiveness analysis showed that the rapid test was less expensive than ELISA (? 26.46 vs ? 40.57) and yielded a similar number of right diagnoses. Conclusions. The Abbott Determine Syphilis TP test is an accurate, easy and inexpensive test that could facilitate the rapid detection of syphilis in high-risk urban patients

Assessment of the Psychometric Characteristics of the Italian Version of the Nurse Manager Actions Scale

Nurse managers play a vital role in healthcare organizations, wielding the ability to substantially enhance work environments, foster nurses’ autonomy, and bolster retention within workplaces. In this context, this study focuses on the Nurse Manager Actions scale, aiming to evaluate its items’ scalability as well as the scale’s validity and reliability among nurses and nurse managers operating within the Italian healthcare context. The study protocol was not registered. To ensure linguistic and cultural alignment, an iterative and collaborative translation process was undertaken. Subsequently, a multi-center cross-sectional design was adopted. Using a web-survey approach, data were collected among 683 nurses and 188 nurse managers between August 2022 and January 2023. The Nurse Manager Actions scale was found to be a valid and reliable instrument in Italian after a Mokken Scale Analysis. For nurses (HT = 0.630, Molenaar–Sijtsma rho = 0.890), the scale included 6 items, while 11 items were confirmed for nurse managers (HT = 0.620, Molenaar–Sijtsma rho = 0.830). Nurse Manager Actions scale scores were correlated with increased satisfaction and decreased intention to leave for both nurses and nurse managers. The employed validation process enhanced the scale validity for use in Italy and provided a model for other researchers to follow when assessing similar measures in different populations. Measuring and empowering nurse manager actions in work contexts is essential to improve the general well-being and retention of nurses, especially in the current nursing shortage

Solution structure of the SGTA dimerisation domain and investigation of its interactions with the ubiquitin-like domains of BAG6 and UBL4A

BACKGROUND: The BAG6 complex resides in the cytosol and acts as a sorting point to target diverse hydrophobic protein substrates along their appropriate paths, including proteasomal degradation and ER membrane insertion. Composed of a trimeric complex of BAG6, TRC35 and UBL4A, the BAG6 complex is closely associated with SGTA, a co-chaperone from which it can obtain hydrophobic substrates. METHODOLOGY AND PRINCIPAL FINDINGS: SGTA consists of an N-terminal dimerisation domain (SGTA_NT), a central tetratricopeptide repeat (TPR) domain, and a glutamine rich region towards the C-terminus. Here we solve a solution structure of the SGTA dimerisation domain and use biophysical techniques to investigate its interaction with two different UBL domains from the BAG6 complex. The SGTA_NT structure is a dimer with a tight hydrophobic interface connecting two sets of four alpha helices. Using a combination of NMR chemical shift perturbation, isothermal titration calorimetry (ITC) and microscale thermophoresis (MST) experiments we have biochemically characterised the interactions of SGTA with components of the BAG6 complex, the ubiquitin-like domain (UBL) containing proteins UBL4A and BAG6. We demonstrate that the UBL domains from UBL4A and BAG6 directly compete for binding to SGTA at the same site. Using a combination of structural and interaction data we have implemented the HADDOCK protein-protein interaction docking tool to generate models of the SGTA-UBL complexes. SIGNIFICANCE: This atomic level information contributes to our understanding of the way in which hydrophobic proteins have their fate decided by the collaboration between SGTA and the BAG6 complex

A critical analysis of building sustainability assessment methods for healthcare buildings

The healthcare building project contains different aspects from the most common projects. Designing a healthcare environment is based on a number of criteria related to the satisfaction and well-being of the professional working teams, patients and administrators. Mostly due to various design requirements, these buildings are rarely designed and operated in a sustainable way. Therefore, the sustainable development is a concept whose importance has grown significantly in the last decade in this sector. The worldwide economic crisis reinforces the growing environmental concerns as well as raising awareness among people to a necessary and inevitable shift in the values of their society. To support sustainable building design, several building sustainability assessment (BSA) methods are being developed worldwide. Since healthcare buildings are rather complex systems than other buildings, so specific methods were developed for them. These methods are aimed to support decision-making towards the introduction of the best sustainability practices during the design and operation phases of a healthcare environment. However, the comparison between the results of different methods is difficult, if not impossible, since they address different environmental, societal and economic criteria, and they emphasize different phases of the life cycle. Therefore, the aim of this study was to clarify the differences between the main BSA methods for healthcare buildings by analysing and categorizing them. Furthermore, the benefits of these methods in promoting a more sustainable environment will be analysed, and the current situation of them within the context of standardization of the concept sustainable construction will be discussed.The authors acknowledge the Portuguese Foundation for Science and Technology and POPH/FSE for the financial support for this study under the Reference SFRH/BD/77959/2011

Protein kinase C theta (PKCθ) modulates the ClC-1 chloride channel activity and skeletal muscle phenotype: a biophysical and gene expression study in mouse models lacking the PKCθ

In skeletal muscle, the resting chloride conductance (gCl), due to the ClC-1 chloride channel, controls the sarcolemma electrical stability. Indeed, loss-of-function mutations in ClC-1 gene are responsible of myotonia congenita. The ClC-1 channel can be phosphorylated and inactivated by protein kinases C (PKC), but the relative contribution of each PKC isoforms is unknown. Here, we investigated on the role of PKCθ in the regulation of ClC-1 channel expression and activity in fast- and slow-twitch muscles of mouse models lacking PKCθ. Electrophysiological studies showed an increase of gCl in the PKCθ-null mice with respect to wild type. Muscle excitability was reduced accordingly. However, the expression of the ClC-1 channel, evaluated by qRT-PCR, was not modified in PKCθ-null muscles suggesting that PKCθ affects the ClC-1 activity. Pharmacological studies demonstrated that although PKCθ appreciably modulates gCl, other isoforms are still active and concur to this role. The modification of gCl in PKCθ-null muscles has caused adaptation of the expression of phenotype-specific genes, such as calcineurin and myocyte enhancer factor-2, supporting the role of PKCθ also in the settings of muscle phenotype. Importantly, the lack of PKCθ has prevented the aging-related reduction of gCl, suggesting that its modulation may represent a new strategy to contrast the aging process

Cerebral Small Vessel Disease Burden and Longitudinal Cognitive Decline from age 73 to 82: the Lothian Birth Cohort 1936

Slowed processing speed is considered a hallmark feature of cognitive decline in cerebral small vessel disease (SVD); however, it is unclear whether SVD’s association with slowed processing might be due to its association with overall declining general cognitive ability. We quantified the total MRI-visible SVD burden of 540 members of the Lothian Birth Cohort 1936 (age: 72.6 ± 0.7 years; 47% female). Using latent growth curve modelling, we tested associations between total SVD burden at mean age 73 and changes in general cognitive ability, processing speed, verbal memory and visuospatial ability, measured at age 73, 76, 79 and 82. Covariates included age, sex, vascular risk and childhood cognitive ability. In the fully adjusted models, greater SVD burden was associated with greater declines in general cognitive ability (standardised β: −0.201; 95% CI: [−0.36, −0.04]; pFDR = 0.022) and processing speed (−0.222; [−0.40, −0.04]; pFDR = 0.022). SVD burden accounted for between 4 and 5% of variance in declines of general cognitive ability and processing speed. After accounting for the covariance between tests of processing speed and general cognitive ability, only SVD’s association with greater decline in general cognitive ability remained significant, prior to FDR correction (−0.222; [−0.39, −0.06]; p = 0.008; pFDR = 0.085). Our findings do not support the notion that SVD has a specific association with declining processing speed, independent of decline in general cognitive ability (which captures the variance shared across domains of cognitive ability). The association between SVD burden and declining general cognitive ability supports the notion of SVD as a diffuse, whole-brain disease and suggests that trials monitoring SVD-related cognitive changes should consider domain-specific changes in the context of overall, general cognitive decline

Investigation of 15q11-q13, 16p11.2 and 22q13 CNVs in Autism Spectrum Disorder Brazilian Individuals with and without Epilepsy

Copy number variations (CNVs) are an important cause of ASD and those located at 15q11-q13, 16p11.2 and 22q13 have been reported as the most frequent. These CNVs exhibit variable clinical expressivity and those at 15q11-q13 and 16p11.2 also show incomplete penetrance. In the present work, through multiplex ligation-dependent probe amplification (MLPA) analysis of 531 ethnically admixed ASD-affected Brazilian individuals, we found that the combined prevalence of the 15q11-q13, 16p11.2 and 22q13 CNVs is 2.1% (11/531). Parental origin could be determined in 8 of the affected individuals, and revealed that 4 of the CNVs represent de novo events. Based on CNV prediction analysis from genome-wide SNP arrays, the size of those CNVs ranged from 206 kb to 2.27 Mb and those at 15q11-q13 were limited to the 15q13.3 region. In addition, this analysis also revealed 6 additional CNVs in 5 out of 11 affected individuals. Finally, we observed that the combined prevalence of CNVs at 15q13.3 and 22q13 in ASD-affected individuals with epilepsy (6.4%) was higher than that in ASD-affected individuals without epilepsy (1.3%; p<0.014). Therefore, our data show that the prevalence of CNVs at 15q13.3, 16p11.2 and 22q13 in Brazilian ASD-affected individuals is comparable to that estimated for ASD-affected individuals of pure or predominant European ancestry. Also, it suggests that the likelihood of a greater number of positive MLPA results might be found for the 15q13.3 and 22q13 regions by prioritizing ASD-affected individuals with epilepsy.Support was provided by FAPESP-INCT - grant number: 2008/57899-7; FAPESP-CEPID - grant number: 2013/08028-1; CNPq [http://www.fapesp.br/]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

AMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell migration

Cell migration is crucial for cancer dissemination. We find that AMP-activated protein kinase (AMPK) controls cell migration by acting as an adhesion sensing molecular hub. In 3-dimensional matrices, fast-migrating amoeboid cancer cells exert low adhesion/low traction linked to low ATP/AMP, leading to AMPK activation. In turn, AMPK plays a dual role controlling mitochondrial dynamics and cytoskeletal remodelling. High AMPK activity in low adhering migratory cells, induces mitochondrial fission, resulting in lower oxidative phosphorylation and lower mitochondrial ATP. Concurrently, AMPK inactivates Myosin Phosphatase, increasing Myosin II-dependent amoeboid migration. Reducing adhesion or mitochondrial fusion or activating AMPK induces efficient rounded-amoeboid migration. AMPK inhibition suppresses metastatic potential of amoeboid cancer cells in vivo, while a mitochondrial/AMPK-driven switch is observed in regions of human tumours where amoeboid cells are disseminating. We unveil how mitochondrial dynamics control cell migration and suggest that AMPK is a mechano-metabolic sensor linking energetics and the cytoskeleton. Cell metabolism must adapt to the energy needs of migrating cells. This study finds that fast amoeboid migrating cells harbor high AMPK activity, which controls both mitochondrial dynamics and cytoskeletal remodeling, enabling reduced energy needs