Viral-based animal models in polyglutamine disorders.

Polyglutamine disorders are a complex group of incurable neurodegenerative disorders caused by an abnormal expansion in the trinucleotide cytosine-adenine-guanine tract of the affected gene. To better understand these disorders, our dependence on animal models persists, primarily relying on transgenic models. In an effort to complement and deepen our knowledge, researchers have also developed animal models of polyglutamine disorders employing viral vectors. Viral vectors have been extensively used to deliver genes to the brain, not only for therapeutic purposes but also for the development of animal models, given their remarkable flexibility. In a time- and cost-effective manner, it is possible to use different transgenes, at varying doses, in diverse targeted tissues, at different ages, and in different species, to recreate polyglutamine pathology. This paper aims to showcase the utility of viral vectors in disease modelling, share essential considerations for developing animal models with viral vectors, and provide a comprehensive review of existing viral-based animal models for polyglutamine disorders.

Enhancing Bystander Intervention: Insights from the Utstein Analysis of Out-of-Hospital Cardiac Arrests in Slovenia.

Background and Objectives: Out-of-hospital cardiac arrest (OHCA) and survival is a pressing matter all around the world. Despite years of research and great strides and advancements, survival remains alarmingly low. The aim of this study was to measure the survival and characteristics of patients having an OHCA in Slovenia, with an in-depth look at how the bystanders affect the return of spontaneous circulation (ROSC) and survival of OHCA. Materials and Methods: In this observational cross-sectional prospective study, we enrolled patients between 1 September 2022 and 30 November 2022, with a follow-up period of 1 month. All OHCAs attended by the emergency medical services were included. Data were collected and analyzed according to the Utstein 2015 reporting template. Independent predictors of ROSC and 30-day survival or survival were explored using ridge regression. Results: ROSC was achieved in 41% of cases where resuscitation was attempted. The overall 30-day survival rate where resuscitation was attempted was 14%. In 13% of all cases where resuscitation was attempted, patients had a favorable neurological outcome. Using our prediction model, we found that defibrillation under 20 min and ventricular fibrillation as an initial rhythm improves survival, whilst no defibrillation and bystander full cardiopulmonary resuscitation negatively predicted survival. Conclusions: Slovenia has OHCA 30-day survival comparable to the rest of the European Union. The favorable neurological outcome is high. Our data show that bystanders do not significantly improve survival. This represents an untapped potential of general public education in cardiopulmonary resuscitation and automatic external defibrillator use. Following good practices from abroad and improving layperson CPR knowledge could further improve OHCA survival.

ULK overexpression mitigates motor deficits and neuropathology in mouse models of Machado-Joseph disease.

Machado-Joseph disease (MJD) is a fatal neurodegenerative disorder clinically characterized by prominent ataxia. It is caused by an expansion of a CAG trinucleotide in ATXN3, translating into an expanded polyglutamine (polyQ) tract in the ATXN3 protein, that becomes prone to misfolding and aggregation. The pathogenesis of the disease has been associated with the dysfunction of several cellular mechanisms, including autophagy and transcription regulation. In this study, we investigated the transcriptional modifications of the autophagy pathway in models of MJD and assessed whether modulating the levels of the affected autophagy-associated transcripts (AATs) would alleviate MJD-associated pathology. Our results show that autophagy is impaired at the transcriptional level in MJD, affecting multiple AATs, including Unc-51 like autophagy activating kinase 1 and 2 (ULK1 and ULK2), two homologs involved in autophagy induction. Reinstating ULK1/2 levels by adeno-associated virus (AAV)-mediated gene transfer significantly improved motor performance while preventing neuropathology in two in vivo models of MJD. Moreover, in vitro studies showed that the observed positive effects may be mainly attributed to ULK1 activity. This study provides strong evidence of the beneficial effect of overexpression of ULK homologs, suggesting these as promising instruments for the treatment of MJD and other neurodegenerative disorders.

How Can Out-of-Hospital Cardiac Arrest (OHCA) Data Collection in Slovenia Be Improved?

Background and Objectives: The prevalence of out-of-hospital cardiac arrest (OHCA) has been established as a significant contributor to mortality rates in developed nations. Due to the challenges associated with conducting controlled randomized trials, there exists a necessity for the collection of high-quality data to enhance the comprehension of the impact of interventions. Several nations have initiated efforts to gather information pertaining to out-of-hospital cardiac arrest (OHCA). The Republic of Slovenia has been collecting data from interventions; however, the variables and data attributes have not yet been standardized to comply with international standards. This lack of conformity poses a challenge in making comparisons or drawing inferences. The aim of this study is to identify how to better gather OHCA data in Slovenia. Materials and methods: The Utstein resuscitation registry protocol (UP) was compared to the Slovenian data points that must be gathered in accordance with the Rules on Emergency Medical Service (REMS) during interventions. In addition, we have proposed alternative measures of digitization to enhance pre-hospital data. Results: Missing data points and attribute mismatches were detected in Slovenia. Eight data points necessitated by the UP are gathered in several databases (hospitals, the National Institute of Public Health, dispatch services, intervention reports from first responders, and defibrillator files), but not in the mandated protocols based on REMS. Two data points have variables that do not match those of the UP. A total of 16 data points according to UP are currently not being collected in Slovenia. The advantages and potential drawbacks of digitizing emergency medical services have been discussed. Conclusions: The study has identified gaps in the methods employed for collecting data on OHCA in Slovenia. The assessment conducted serves as a basis for enhancing the process of data collection, integrating quality control measures across the nation, and establishing a nationwide registry for out-of-hospital cardiac arrest (OHCA) in Slovenia.

A new protocol for whole-brain biodistribution analysis of AAVs by tissue clearing, light-sheet microscopy and semi-automated spatial quantification.

Recombinant adeno-associated virus (rAAV) has become one of the most promising gene delivery systems for both in vitro and in vivo applications. However, a key challenge is the lack of suitable imaging technologies to evaluate delivery, biodistribution and tropism of rAAVs and efficiently monitor disease amelioration promoted by AAV-based therapies at a whole-organ level with single-cell resolution. Therefore, we aimed to establish a new pipeline for the biodistribution analysis of natural and new variants of AAVs at a whole-brain level by tissue clearing and light-sheet fluorescence microscopy (LSFM). To test this platform, neonatal C57BL/6 mice were intravenously injected with rAAV9 encoding EGFP and, after sacrifice, brains were processed by standard immunohistochemistry and a recently released aqueous-based clearing procedure. This clearing technique required no dedicated equipment and rendered highly cleared brains, while simultaneously preserving endogenous fluorescence. Moreover, three-dimensional imaging by LSFM allowed the quantitative analysis of EGFP at a whole-brain level, as well as the reconstruction of Purkinje cells for the retrieval of valuable morphological information inaccessible by standard immunohistochemistry. In conclusion, the pipeline herein described takes the AAVs to a new level when coupled to LSFM, proving its worth as a bioimaging tool in tropism and gene therapy studies.

Changing perspectives in times of crisis. The impact of COVID-19 on territorial accessibility.

The link between transport and land use in urban areas has always been characterized by a slow evolution process. COVID-19 brought, suddenly and unexpectedly, severe changes to the trip structure within urban areas, as several restrictions were combined with individual health fears. This study addresses the impact of the COVID-19 pandemic in the territory of Porto Greater Urban Area, in Portugal, measured under a structural accessibility approach. This was evaluated through a simulation model, combining different destination restrictions in three alternative scenarios during the pandemic and post-COVID, as well as the definition of four different personas, with distinct risk aversion to infections and telecommuting patterns. The results, presented as the spatial configuration of different mobility environments, foster a critical reflection on their implication for future transportation and land use policies. This pandemic has shown that the territory behaves differently under a critical lockdown scenario, where active modes gain predominance to satisfy most travel needs, signalling a potential ability to enforce more sustainable mobility habits. Still, as the territorial configuration tends to the previous state of equilibrium as restrictions are lifted, particularly for non-telecommuters, the need for acting quickly is reinforced. While the growth of telecommuting can induce additional challenges to the management of urban mobility systems, most policy recommendations that were valid in the past will maintain its relevance, as non telecommuters will retain previous travel habits.

Combined transcriptome and proteome profiling of the pancreatic ß-cell response to palmitate unveils key pathways of ß-cell lipotoxicity.

BACKGROUND: Prolonged exposure to elevated free fatty acids induces ß-cell failure (lipotoxicity) and contributes to the pathogenesis of type 2 diabetes. In vitro exposure of ß-cells to the saturated free fatty acid palmitate is a valuable model of lipotoxicity, reproducing features of ß-cell failure observed in type 2 diabetes. In order to map the ß-cell response to lipotoxicity, we combined RNA-sequencing of palmitate-treated human islets with iTRAQ proteomics of insulin-secreting INS-1E cells following a time course exposure to palmitate. RESULTS: Crossing transcriptome and proteome of palmitate-treated ß-cells revealed 85 upregulated and 122 downregulated genes at both transcript and protein level. Pathway analysis identified lipid metabolism, oxidative stress, amino-acid metabolism and cell cycle pathways among the most enriched palmitate-modified pathways. Palmitate induced gene expression changes compatible with increased free fatty acid mitochondrial import and ß-oxidation, decreased lipogenesis and modified cholesterol transport. Palmitate modified genes regulating endoplasmic reticulum (ER) function, ER-to-Golgi transport and ER stress pathways. Furthermore, palmitate modulated cAMP/protein kinase A (PKA) signaling, inhibiting expression of PKA anchoring proteins and downregulating the GLP-1 receptor. SLC7 family amino-acid transporters were upregulated in response to palmitate but this induction did not contribute to ß-cell demise. To unravel critical mediators of lipotoxicity upstream of the palmitate-modified genes, we identified overrepresented transcription factor binding sites and performed network inference analysis. These identified LXR, PPARα, FOXO1 and BACH1 as key transcription factors orchestrating the metabolic and oxidative stress responses to palmitate. CONCLUSIONS: This is the first study to combine transcriptomic and sensitive time course proteomic profiling of palmitate-exposed ß-cells. Our results provide comprehensive insight into gene and protein expression changes, corroborating and expanding beyond previous findings. The identification of critical drivers and pathways of the ß-cell lipotoxic response points to novel therapeutic targets for type 2 diabetes.

Coracohumeral distance and coracoid overlap as predictors of subscapularis and long head of the biceps injuries.

BACKGROUND: Subscapularis (SS) lesions are often underdiagnosed because of an incomplete understanding of contributing factors but also because of a greater difficulty in SS tear diagnosis with magnetic resonance imaging or physical examination. In this setting, predicting factors can be useful tools in these injuries' management. The goal of this study was to determine the influence of the coracohumeral distance (CHD) and coracoid overlap (CO) in anterior rotator cuff lesions, as well as to determine the CHD and CO values that can accurately predict SS and long head of the biceps (LHB) injuries. METHODS: We performed a retrospective, controlled, single-blinded study. We analyzed 301 patients with rotator cuff pathology and magnetic resonance imaging studies; patients with SS lesions represented the study group. The CHD and CO were measured. RESULTS: We found that lower CHD and higher CO values were progressively related to more serious injuries of the SS and LHB. The CHD was a very strong predictor of SS injury and tear and a good predictor of LHB injuries. A CHD of 7.6 mm had a sensitivity of 84.4% and specificity of 88.6% for SS tears. The CO was also a very strong predictor of SS tears and a good predictor of LHB injury, with a CO of 16.6 mm reaching a sensitivity of 77.8% and specificity of 68.3% for SS tears. CONCLUSIONS: The CHD is an excellent predictor of SS tears and a good predictor of LHB lesions, with the CO also being a very strong predictor of SS tears and a good model for LHB injuries.

Msx1 and Msx2 act as essential activators of Atoh1 expression in the murine spinal cord.

Dorsal spinal neurogenesis is orchestrated by the combined action of signals secreted from the roof plate organizer and a downstream transcriptional cascade. Within this cascade, Msx1 and Msx2, two homeodomain transcription factors (TFs), are induced earlier than bHLH neuralizing TFs. Whereas bHLH TFs have been shown to specify neuronal cell fate, the function of Msx genes remains poorly defined. We describe dramatic alterations of neuronal patterning in Msx1/Msx2 double-mutant mouse embryos. The most dorsal spinal progenitor pool fails to express the bHLH neuralizing TF Atoh1, which results in a lack of Lhx2-positive and Barhl2-positive dI1 interneurons. Neurog1 and Ascl1 expression territories are dorsalized, leading to ectopic dorsal differentiation of dI2 and dI3 interneurons. In proportion, the amount of Neurog1-expressing progenitors appears unaffected, whereas the number of Ascl1-positive cells is increased. These defects occur while BMP signaling is still active in the Msx1/Msx2 mutant embryos. Cell lineage analysis and co-immunolabeling demonstrate that Atoh1-positive cells derive from progenitors expressing both Msx1 and Msx2. In vitro, Msx1 and Msx2 proteins activate Atoh1 transcription by specifically interacting with several homeodomain binding sites in the Atoh1 3' enhancer. In vivo, Msx1 and Msx2 are required for Atoh1 3' enhancer activity and ChIP experiments confirm Msx1 binding to this regulatory sequence. These data support a novel function of Msx1 and Msx2 as transcriptional activators. Our study provides new insights into the transcriptional control of spinal cord patterning by BMP signaling, with Msx1 and Msx2 acting upstream of Atoh1.

Evaluation of a series of 2-napthamide derivatives as inhibitors of the drug efflux pump AcrB for the reversal of antimicrobial resistance.

Drug efflux pumps confer multidrug resistance to dangerous pathogens which makes these pumps important drug targets. We have synthesised a novel series of compounds based on a 2-naphthamide pharmacore aimed at inhibiting the efflux pumps from Gram-negative bacteria. The archeatypical transporter AcrB from Escherichia coli was used as model efflux pump as AcrB is widely conserved throughout Gram-negative organisms. The compounds were tested for their antibacterial action, ability to potentiate the action of antibiotics and for their ability to inhibit Nile Red efflux by AcrB. None of the compounds were antimicrobial against E. coli wild type cells. Most of the compounds were able to inhibit Nile Red efflux indicating that they are substrates of the AcrB efflux pump. Three compounds were able to synergise with antibiotics and reverse resistance in the resistant phenotype. Compound A3, 4-(isopentyloxy)-2-naphthamide, reduced the MICs of erythromycin and chloramphenicol to the MIC levels of the drug sensitive strain that lacks an efflux pump. A3 had no effect on the MIC of the non-substrate rifampicin indicating that this compound acts specifically through the AcrB efflux pump. A3 also does not act through non-specific mechanisms such as outer membrane or inner membrane permeabilisation and is not cytotoxic against mammalian cell lines. Therefore, we have designed and synthesised a novel chemical compound with great potential to further optimisation as inhibitor of drug efflux pumps.

Cytokines induce endoplasmic reticulum stress in human, rat and mouse beta cells via different mechanisms.

AIMS/HYPOTHESIS: Proinflammatory cytokines contribute to beta cell damage in type 1 diabetes in part through activation of endoplasmic reticulum (ER) stress. In rat beta cells, cytokine-induced ER stress involves NO production and consequent inhibition of the ER Ca(2+) transporting ATPase sarco/endoplasmic reticulum Ca(2+) pump 2 (SERCA2B). However, the mechanisms by which cytokines induce ER stress and apoptosis in mouse and human pancreatic beta cells remain unclear. The purpose of this study is to elucidate the role of ER stress on cytokine-induced beta cell apoptosis in these three species and thus solve ongoing controversies in the field. METHODS: Rat and mouse insulin-producing cells, human pancreatic islets and human EndoC-ßH1 cells were exposed to the cytokines IL-1ß, TNF-α and IFN-γ, with or without NO inhibition. A global comparison of cytokine-modulated gene expression in human, mouse and rat beta cells was also performed. The chemical chaperone tauroursodeoxycholic acid (TUDCA) and suppression of C/EBP homologous protein (CHOP) were used to assess the role of ER stress in cytokine-induced apoptosis of human beta cells. RESULTS: NO plays a key role in cytokine-induced ER stress in rat islets, but not in mouse or human islets. Bioinformatics analysis indicated greater similarity between human and mouse than between human and rat global gene expression after cytokine exposure. The chemical chaperone TUDCA and suppression of CHOP or c-Jun N-terminal kinase (JNK) protected human beta cells against cytokine-induced apoptosis. CONCLUSIONS/INTERPRETATION: These observations clarify previous results that were discrepant owing to the use of islets from different species, and confirm that cytokine-induced ER stress contributes to human beta cell death, at least in part via JNK activation.

Polymorphisms in the mitochondrial ribosome recycling factor EF-G2mt/MEF2 compromise cell respiratory function and increase atorvastatin toxicity.

Mitochondrial translation, essential for synthesis of the electron transport chain complexes in the mitochondria, is governed by nuclear encoded genes. Polymorphisms within these genes are increasingly being implicated in disease and may also trigger adverse drug reactions. Statins, a class of HMG-CoA reductase inhibitors used to treat hypercholesterolemia, are among the most widely prescribed drugs in the world. However, a significant proportion of users suffer side effects of varying severity that commonly affect skeletal muscle. The mitochondria are one of the molecular targets of statins, and these drugs have been known to uncover otherwise silent mitochondrial mutations. Based on yeast genetic studies, we identify the mitochondrial translation factor MEF2 as a mediator of atorvastatin toxicity. The human ortholog of MEF2 is the Elongation Factor Gene (EF-G) 2, which has previously been shown to play a specific role in mitochondrial ribosome recycling. Using small interfering RNA (siRNA) silencing of expression in human cell lines, we demonstrate that the EF-G2mt gene is required for cell growth on galactose medium, signifying an essential role for this gene in aerobic respiration. Furthermore, EF-G2mt silenced cell lines have increased susceptibility to cell death in the presence of atorvastatin. Using yeast as a model, conserved amino acid variants, which arise from non-synonymous single nucleotide polymorphisms (SNPs) in the EF-G2mt gene, were generated in the yeast MEF2 gene. Although these mutations do not produce an obvious growth phenotype, three mutations reveal an atorvastatin-sensitive phenotype and further analysis uncovers a decreased respiratory capacity. These findings constitute the first reported phenotype associated with SNPs in the EF-G2mt gene and implicate the human EF-G2mt gene as a pharmacogenetic candidate gene for statin toxicity in humans.

Temporal profiling of cytokine-induced genes in pancreatic ß-cells by meta-analysis and network inference.

Type 1 Diabetes (T1D) is an autoimmune disease where local release of cytokines such as IL-1ß and IFN-γ contributes to ß-cell apoptosis. To identify relevant genes regulating this process we performed a meta-analysis of 8 datasets of ß-cell gene expression after exposure to IL-1ß and IFN-γ. Two of these datasets are novel and contain time-series expressions in human islet cells and rat INS-1E cells. Genes were ranked according to their differential expression within and after 24 h from exposure, and characterized by function and prior knowledge in the literature. A regulatory network was then inferred from the human time expression datasets, using a time-series extension of a network inference method. The two most differentially expressed genes previously unknown in T1D literature (RIPK2 and ELF3) were found to modulate cytokine-induced apoptosis. The inferred regulatory network is thus supported by the experimental validation, providing a proof-of-concept for the proposed statistical inference approach.

Msx genes define a population of mural cell precursors required for head blood vessel maturation.

Vessels are primarily formed from an inner endothelial layer that is secondarily covered by mural cells, namely vascular smooth muscle cells (VSMCs) in arteries and veins and pericytes in capillaries and veinules. We previously showed that, in the mouse embryo, Msx1(lacZ) and Msx2(lacZ) are expressed in mural cells and in a few endothelial cells. To unravel the role of Msx genes in vascular development, we have inactivated the two Msx genes specifically in mural cells by combining the Msx1(lacZ), Msx2(lox) and Sm22α-Cre alleles. Optical projection tomography demonstrated abnormal branching of the cephalic vessels in E11.5 mutant embryos. The carotid and vertebral arteries showed an increase in caliber that was related to reduced vascular smooth muscle coverage. Taking advantage of a newly constructed Msx1(CreERT2) allele, we demonstrated by lineage tracing that the primary defect lies in a population of VSMC precursors. The abnormal phenotype that ensues is a consequence of impaired BMP signaling in the VSMC precursors that leads to downregulation of the metalloprotease 2 (Mmp2) and Mmp9 genes, which are essential for cell migration and integration into the mural layer. Improper coverage by VSMCs secondarily leads to incomplete maturation of the endothelial layer. Our results demonstrate that both Msx1 and Msx2 are required for the recruitment of a population of neural crest-derived VSMCs.

A microbial spoilage profile of half shell Pacific oysters (Crassostrea gigas) and Sydney rock oysters (Saccostrea glomerata).

This study aimed to assess bacterial spoilage of half shell Pacific and Sydney rock oysters during storage using microbial culture and 16S rRNA pyrosequencing. Odour and pH of oyster meats were also investigated. Estimation of microbiological counts by microbial culture highlighted growth of psychrotrophic bacteria. During storage, odour scores (a score describing deterioration of fresh odours where a score of 1 is fresh and 4 is completely spoiled) increased from 1.0 to 3.0 for Pacific oysters and from 1.3 to 3.4 for Sydney rock oysters. pH results obtained for both species fluctuated during storage (range 6.28-6.73) with an overall increase at end of storage. Pyrosequencing revealed that the majority of bacteria at Day 0 represented taxa from amongst the Proteobacteria, Tenericutes and Spirochaetes that have not been cultured and systematically described. During storage, Proteobacteria became abundant with Pseudoalteromonas and Vibrio found to be dominant in both oyster species at Day 7. Analysis of the pyrosequencing data showed significant differences in bacterial profiles between oyster species and storage time (both P = 0.001). As oysters spoiled, bacterial profiles between oyster species became more similar indicating a common spoilage profile. Data presented here provides detailed insight into the changing bacterial profile of shucked oysters during storage and has identified two genera, Pseudoalteromonas and Vibrio, as being important in spoilage of shucked oysters.

Cabo Verde telemedicine program: initial results of nationwide implementation.

BACKGROUND: Telemedicine and e-health have been suggested as one solution for closing the health disparity gap between the developed world and the developing world. Yet evidence is lacking from current successful programs in the developing world and, in particular, from sub-Saharan Africa. The primary objective of our study was to present the preliminary results of our efforts in building the Integrated Telemedicine and e-Health Program for Cabo Verde (ITeHP-CV), with an emphasis on initial utilization and results. MATERIALS AND METHODS: This is a prospective study of data collected while we worked to establish a fully functional, integrated national telemedicine network and virtual education network in Cabo Verde. We used the International Virtual e-Hospital Foundation strategic approach known as "initiate-build-operate-transfer" over a 26-month period (November 2011-December 2013). We describe herein the five main pillars of this process that have been implemented: (1) capacity building; (2) network development and deployment of equipment; (3) implementation of clinical telemedicine; (4) implementation of activities related to continuing medical education, delivered from within the country and from abroad; and (5) establishment and use of the electronic virtual library. RESULTS: Based on comprehensive technical and medical assessment of the country's needs, 10 fully functional telemedicine centers in all nine inhabited islands of the Republic of Cabo Verde have been established. RESULTS are presented under the five main pillars of capacity building, network deployment, implementation of clinical telemedicine, implementation of continuing medical education activities, and establishment of the electronic virtual library. CONCLUSIONS: The ITeHP-CV has been successfully launched, and the initial results are encouraging. The continuity of the program and sustainability are primary goals once the program is transferred fully to the Ministry of Health of Cabo Verde. A long-term follow-up study is required in order to ensure sustainability and continuity goals are met.

F-waves responses derived from low-intensity electrical stimulation: A method to explore split-hand pathogenesis.

OBJECTIVES: The "split-hand syndrome" is a common clinical sign in amyotrophic lateral sclerosis (ALS), being characterized by more severe atrophy of the hand muscles on the radial side of the hand compared to the ulnar side. We aimed to investigate possible physiological differences between relevant hand muscles using low-intensity F-wave stimulation to assess spinal motoneuron excitability. METHODS: We recruited 36 healthy volunteers. F-waves were recorded from the abductor pollicis brevis (APB), first dorsal interosseous (FDI) and abductor digiti minimi (ADM), using 20 supramaximal stimuli followed by 20 stimuli at a low-intensity required to obtain M-waves with 10 % amplitude of maximal CMAP. We evaluated the following F-wave parameters: F-M latency, chronodispersion, persistence, amplitude, F/CMAP amplitude ratio and number of F-wave repeaters (with low-intensity). In 10 subjects, low-intensity stimulation F-waves were compared after 20 and 50 stimuli in each muscle. RESULTS: Low-intensity stimulation resulted in lower F-wave amplitude and persistence and higher F/CMAP amplitude ratios. There were no significant differences in F-wave latencies and chronodispersion. When comparing the three muscles, we found higher F-wave persistence and F/CMAP amplitude ratios when recording over the ADM and APB compared to the FDI. We also found a higher number of F-wave repeaters in the ADM with low-intensity stimulation. Results from 20 to 50 low-intensity stimuli were similar. DISCUSSION: A small number of low-intensity stimuli is appropriate to study F-wave latencies and chronodispersion. We found differences in some physiological properties of the ADM spinal motoneuron pool compared to other hand muscles.

Improving Organizational Commitment among Healthcare Employees in Angola: The Role of Psychological Capital and Perceived Transformational Leadership.

While previous studies conducted in sub-Saharan African countries have focused on verifying standards of clinical care and assessing challenges faced by healthcare professionals, the present study fills a gap in the literature in that it explores the factors that may drive the organizational commitment of healthcare professionals in Angola. This study aimed to analyze the relationship between psychological capital and organizational commitment through perceived transformational leadership. Therefore, using the quantitative methodology, a self-report questionnaire was applied to 342 healthcare professionals (174 male, 168 female) from different public and private hospitals located in three large cities in Angola. The results confirmed that psychological capital is positively related to affective commitment and that perceived transformational leadership is a mediating variable of this relationship. Therefore, this study highlights the role of psychological capital and perceived transformational leadership in improving affective commitment in challenging environments.

Portuguese Global Medicines Access Index 2021: An Indicator to Measure Access to Hospital Medicines.

OBJECTIVES: Access to innovative and effective medication is a citizen's right. The main objectives of this study were to build an indicator to measure access to medicines within hospitals, the Global Medicines Access Index, and to identify the main existing barriers. METHODS: Cross-sectional study carried out in Portuguese National Health Service hospitals. A consensus methodology (expert panel of 7 members) was used to define which dimensions should be included in the index and the weighting that each should take. The panel identified 6 dimensions: access to innovative medicines, proximity distribution, shortages, access to medicines before financing decision, value-based healthcare, and access to medication depending on cost/funding. Data were collected through an electronic questionnaire (September 2021). RESULTS: The response rate was 61.2%. Most hospitals used medicines with and without marketing authorization before the funding decision. Monitoring and generating evidence of new therapies results is still insufficient. The identified barriers were the administrative burden as the major barrier in purchasing medicines, with a relevant impact on shortages of medicines. Most respondents (87%) had a proximity distribution program, mainly implemented in the pandemic context, and the price/funding model was only identified by 10% as a barrier to access. The 2021 Global Medicines Access Index was 66%. Shortages and value-based use of medicines were the dimensions that had more influence in lowering the index value. CONCLUSIONS: The new formula used to obtain a unique and multidimensional index for access to hospital medicines seems to be more sensitive and objective and will be used to monitor access.