Cross-cultural adaptation, reliability and validity of the Spanish version of the long-term quality of life questionnaire.

Purpose: The aim of this study was to translate, culturally adapt, and evaluate the psychometric properties of the Spanish Long-Term Quality of Life (LTQL) questionnaire. Methods: The LTQL was initially translated into Spanish and cross-culturally adapted based on established guidelines. The Spanish LTQL was administered to patients with breast cancer who had completed their initial treatment 5 years earlier, along with other self-report measures: Quality of Life in Adult Cancer Survivors (QLACS), Hospital Anxiety and Depression Scale (HADS) and EORT-QLQ-BR23. Reliability was evaluated using internal consistency and test-retest. Convergent and known-groups validity were examined. Structural validity as determined by confirmatory factor analysis (CFA) and Rasch analyses was used to assess the unidimensionality and item-functioning of the LTQL domains. Results: Cronbach's alpha were above 0.7 in all domains. Test-retest coefficients were between 0.72 to 0.96 for LTQL domains. LTQL total score was correlated with others total scores of other measures: QLACS (r=-0.39), HADS depression (r=-0.57), HADS anxiety (-0.45) and EORTC-QLQ-BR23 (r=-0.50). CFA provided satisfactory fit indices, with RMSEA value of 0.077 and TLI and CFI values of 0.901 and 0.909, respectively. All factor loadings were higher than 0.40 and statistically significant (P<0.001). Rasch analysis showed that Somatic Concerns domain had 4 misfitting items, and Philosophical/Spiritual View of Life and social Support domains only 1 misfit item. However, unidimensionality was supported for the four domains. Conclusion: The findings support the validity and reliability of the Spanish version of LTQL questionnaire to be used in long-term cancer female survivors.

Detection of harmful algal blooms from satellite-based inherent optical properties of the ocean in Paracas Bay - Peru.

Harmful algal bloom (HAB) events in front of Pisco River, inside Paracas Bay and Lagunillas inlet on the southern coast of Peru was identified from a satellite index (IOPifa) generated with daily high-resolution satellite data of phytoplankton absorption (aphy,GIOP) and non-algal detrital material plus CDOM (adCDOM,GIOP) from the Generalized Inherent Optical Properties (GIOP) model of Modis-Aqua, Viirs-Snpp and Viirs-Jpss1 satellites were used. Phytoplankton density field data sampling from HAB's monitoring programs of IMARPE of 2018 and 2019 were used to validate and identify the extent and spatio-temporal variability of these events. The satellite index (IOPifa) identified for Modis-Aqua 9 active HABs, 8 events in final conditions and 6 events that do not represent HAB conditions, while for Viirs-Snpp found 14 active HABs, 7 events in decaying bloom conditions and 13 events that do not represent HABs; and for Viirs-Jpss1 the index identified 7 active events, 14 in final bloom conditions and 6 that do not represent HABs conditions. The one-factor anova model was applied (p-value = 0.32 > 0.05), indicating that there is no evidence of a difference in the population means of the indices for each sensor. Subsequently, the pairwise multiple comparisons analysis with a 95 % confidence level of Tukey's test confirmed that there are no significant differences in the satellite index value, the differences could be associated with the spectral characteristics of the cell density of the species community and the oceanographic and environmental conditions. The spatial overlap between the in situ harmful algal blooms areas and the calculated satellite index, shows the capacity of the IOP satellite data for the HABs detection. However, it was also evidenced that some HAB events with high phytoplankton cell density had low IOPifa values, while other events with lower cell density were easily identified by the satellite index. This would indicate the ability of the ocean inherent optical properties to differentiate the phytoplankton types that cause algal blooms.

Eligibility criteria for using menopausal hormone therapy in breast cancer survivors: a safety report based on a systematic review and meta-analysis.

IMPORTANCE: Menopause hormone therapy (MHT) effectively alleviates menopausal symptoms. However, it is generally not recommended for breast cancer survivors, although the scientific evidence is scarce. OBJECTIVE: This study aimed to establish eligibility criteria for use of the MHT in breast cancer survivors based on a systematic review and meta-analysis of the literature. EVIDENCE REVIEW: We conducted exhaustive literature searches until June 2022 in MEDLINE, The Cochrane Library, and EMBASE, using a tailored strategy with a combination of controlled vocabulary and search terms related to breast cancer survivors and MHT. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and assessed the risk of bias using the Cochrane and Risk of Bias in Non-randomized Studies - of Interventions tools. The quality of the evidence was graded according to grading quality of evidence and strength of recommendations criteria (A, high; B, moderate; C, low; and D, very low). We categorized MHT use into four levels: category 1 (no restrictions on use), category 2 (the benefits outweigh the risks), category 3 (the risks generally outweigh the benefits), and category 4 (MHT should not be used). FINDINGS: A total of 12 studies met the eligibility criteria. Analysis of the three randomized clinical trials using combined MHT or tibolone revealed no significant differences concerning tumor recurrence (relative risk [RR], 1.46; 95% CI, 0.99-2.24). A combined analysis of randomized clinical trials, prospective, and retrospective trials found no elevated risk of recurrence (RR, 0.85; 95% CI, 0.54-1.33) or death (RR, 0.91; 95% CI, 0.38-2.19). The eligibility criteria for patients with hormone receptor (HR)-positive tumors fell into categories 3B and 3C for combined MHT or estrogen alone and 4A for tibolone. For HR-negative tumors, the category was 2B and 2C. CONCLUSIONS AND RELEVANCE: Our findings suggest that MHT could be a viable treatment alternative for breast cancer survivors experiencing menopausal symptoms, especially those with HR-negative tumors. Personalized management is recommended for each peri/postmenopausal woman facing a diminished quality of life because of menopause symptoms. Further randomized trials are needed before considering changes to current standards of care.

N-acetylcysteine during critical neurodevelopmental periods prevents behavioral and neurochemical deficits in the Poly I:C rat model of schizophrenia.

Schizophrenia is a chronic neurodevelopmental disorder with an inflammatory/prooxidant component. N-acetylcysteine (NAC) has been evaluated in schizophrenia as an adjuvant to antipsychotics, but its role as a preventive strategy has not been sufficiently explored. We aimed to evaluate the potential of NAC administration in two-time windows before the onset of symptoms in a schizophrenia-like maternal immune stimulation (MIS) rat model. Pregnant Wistar rats were injected with Poly I:C or Saline on gestational day (GD) 15. Three different preventive approaches were evaluated: 1) NAC treatment during periadolescence in the offspring (from postnatal day [PND] 35 to 49); 2) NAC treatment during pregnancy after MIS challenge until delivery (GD15-21); and 3) NAC treatment throughout all pregnancy (GD1-21). At postnatal day (PND) 70, prepulse inhibition (PPI) and anxiety levels were evaluated. In vivo magnetic resonance (MR) imaging was acquired on PND100 to assess structural changes in gray and white matter, and brain metabolite concentrations. Additionally, inflammation and oxidative stress (IOS) markers were measured ex vivo in selected brain regions. MIS offspring showed behavioral, neuroanatomical, and biochemical alterations. Interestingly, NAC treatment during periadolescence prevented PPI deficits and partially counteracted some biochemical imbalances. Moreover, NAC treatments during pregnancy not only replicated the beneficial outcomes reported by the treatment in periadolescence, but also prevented some neuroanatomical deficits, including reductions in hippocampal and corpus callosum volumes. This study suggests that early reduction of inflammation and prooxidation could help prevent the onset of schizophrenia-like symptoms, supporting the importance of anti-IOS compounds in ameliorating this disorder.

THC improves behavioural schizophrenia-like deficits that CBD fails to overcome: a comprehensive multilevel approach using the Poly I:C maternal immune activation.

Prenatal infections and cannabis use during adolescence are well-recognized risk factors for schizophrenia. As inflammation and oxidative stress (OS) contribute to this disorder, anti-inflammatory drugs have been proposed as potential therapies. This study aimed to evaluate the association between delta-9-tetrahydrocannabinol (THC) and schizophrenia-like abnormalities in a maternal immune activation (MIA) model. Additionally, we assessed the preventive effect of cannabidiol (CBD), a non-psychotropic/anti-inflammatory cannabinoid. THC and/or CBD were administered to Saline- and MIA-offspring during periadolescence. At adulthood, THC-exposed MIA-offspring showed significant improvements in sensorimotor gating deficits. Structural and metabolic brain changes were evaluated by magnetic resonance imaging, revealing cortical shrinkage in Saline- and enlargement in MIA-offspring after THC-exposure. Additionally, MIA-offspring displayed enlarged ventricles and decreased hippocampus, which were partially reverted by both cannabinoids. CBD prevented THC-induced reduction in the corpus callosum, despite affecting white matter structure. Post-mortem studies revealed detrimental effects of THC, including increased inflammation and oxidative stress. CBD partially reverted these pro-inflammatory alterations and modulated THC's effects on the endocannabinoid system. In conclusion, contrary to expectations, THC exhibited greater behavioural and morphometric benefits, despite promoting a pro-inflammatory state that CBD partially reverted. Further research is needed to elucidate the underlying mechanisms involved in the observed benefits of THC.

Relationship of arterial stiffness and baseline vascular burden with new lacunes and microbleeds: A longitudinal cohort study.

INTRODUCTION: Arterial stiffness may have a significant impact on the development of cerebral small vessel disease (cSVD). PATIENTS AND METHODS: We obtained pulse wave velocity (24-h PWV) by means of ambulatory blood pressure monitoring (ABPM) in patients with a recent small subcortical infarct (RSSI). Patients with known cardiac or arterial embolic sources were excluded. Lacunes, microbleeds, white matter hyperintensities and enlarged perivascular spaces at baseline were assessed in a brain MRI and included in a cSVD score. A follow-up MRI was obtained 2 years later and assessed for the appearance of new lacunes or microbleeds. We constructed both unadjusted and adjusted models, and subsequently selected the optimal models based on the area under the curve (AUC) of the predicted probabilities. RESULTS: Ninety-two patients (mean age 67.04 years, 69.6% men) were evaluated and 25 had new lacunes or microbleeds during follow-up. There was a strong correlation between 24-h PWV and age (r = 0.942, p < 0.001). cSVD was associated with new lacunes or microbleeds when adjusted by age, 24-h PWV, NT-proBNP and hypercholesterolemia (OR 2.453, CI95% 1.381-4.358). The models exhibiting the highest discrimination, as indicated by their area under the curve (AUC) values, were as follows: 1 (AUC 0.854) - Age, cSVD score, 24-h PWV, Hypercholesterolemia; 2 (AUC 0.852) - cSVD score, 24-h PWV, Hypercholesterolemia; and 3 (AUC 0.843) - Age, cSVD score, Hypercholesterolemia. CONCLUSIONS: cSVD score is a stronger predictor for cSVD progression than age or hemodynamic parameters in patients with a RSSI.

In Silico Analysis of the Dextransucrase Obtained From Leuconostoc mesenteroides Strain IBUN 91.2.98.

The DSR-IBUN dextransucrase produced by Leuconostoc mesenteroides strain IBUN 91.2.98 has a short production time (4.5 hours), an enzymatic activity of 24.8 U/mL, and a specific activity of purified enzyme 2 times higher (331.6 U/mg) than that reported for similar enzymes. The aim of this study was to generate a structural model that, from an in silico approach, allows a better understanding, from the structural point of view, of the activity obtained by the enzyme of interest, which is key to continue with its study and industry application. For this, we translated the nucleotide sequence of the dsr_IBUN gene. With the primary structure of DSR-IBUN, the in silico prediction of physicochemical parameters, the possible subcellular localization, the presence of signal peptide, and the location of domains and functional and structural motifs of the protein were established. Subsequently, its secondary and tertiary structure were predicted and a homology model of the dextransucrase under study was constructed using Swiss-Model, performing careful template selection. The values obtained for the model, Global Model Quality Estimation (0.63), Quality Mean (-1.49), and root-mean-square deviation (0.09), allow us to affirm that the model for the enzyme dextransucrase DSR-IBUN is of adequate quality and can be used as a source of information for this protein.

Aberrant splicing in Huntington's disease via disrupted TDP-43 activity accompanied by altered m6A RNA modification.

Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the first exon of the HTT gene encoding huntingtin. Prior reports have established a correlation between CAG expanded HTT and altered gene expression. However, the mechanisms leading to disruption of RNA processing in HD remain unclear. Here, our analysis of the reported HTT protein interactome identifies interactions with known RNA-binding proteins (RBPs). Total, long-read sequencing and targeted RASL-seq of RNAs from cortex and striatum of the HD mouse model R6/2 reveals increased exon skipping which is confirmed in Q150 and Q175 knock-in mice and in HD human brain. We identify the RBP TDP-43 and the N6-methyladenosine (m6A) writer protein methyltransferase 3 (METTL3) to be upstream regulators of exon skipping in HD. Along with this novel mechanistic insight, we observe decreased nuclear localization of TDP-43 and cytoplasmic accumulation of phosphorylated TDP-43 in HD mice and human brain. In addition, TDP-43 co-localizes with HTT in human HD brain forming novel nuclear aggregate-like bodies distinct from mutant HTT inclusions or previously observed TDP-43 pathologies. Binding of TDP-43 onto RNAs encoding HD-associated differentially expressed and aberrantly spliced genes is decreased. Finally, m6A RNA modification is reduced on RNAs abnormally expressed in striatum from HD R6/2 mouse brain, including at clustered sites adjacent to TDP-43 binding sites. Our evidence supports TDP-43 loss of function coupled with altered m6A modification as a novel mechanism underlying alternative splicing/unannotated exon usage in HD and highlights the critical nature of TDP-43 function across multiple neurodegenerative diseases.

Chemogenetic activation of locus coeruleus neurons ameliorates the severity of multiple sclerosis.

BACKGROUND: Most current disease-modifying therapies approved for multiple sclerosis (MS) are immunomodulatory drugs that counteract the aberrant activity of the immune system. Hence, new pharmacological interventions that drive anti-inflammatory activity and neuroprotection would represent interesting alternative therapeutic approaches or complementary strategies to treat progressive forms of MS. There is evidence of reduced noradrenaline levels and alterations to locus coeruleus (LC) noradrenergic neurons in MS patients, as well as in animal models of this disease, potentially factors contributing to the pathophysiology. Drugs that enhance noradrenaline appear to have some beneficial effects in MS, suggesting their potential to dampen the underlying pathology and disease progression. METHODS: Therefore, we explored the consequences of chronic LC noradrenergic neurons activation by chemogenetics in experimental autoimmune encephalomyelitis (EAE) mice, the most widely used experimental model of MS. LC activation from the onset or the peak of motor symptoms was explored as two different therapeutic approaches, assessing the motor and non-motor behavioral changes as EAE progresses, and studying demyelination, inflammation and glial activation in the spinal cord and cerebral cortex during the chronic phase of EAE. RESULTS: LC activation from the onset of motor symptoms markedly alleviated the motor deficits in EAE mice, as well as their anxiety-like behavior and sickness, in conjunction with reduced demyelination and perivascular infiltration in the spinal cord and glial activation in the spinal cord and prefrontal cortex (PFC). When animals exhibited severe paralysis, LC activation produced a modest alleviation of EAE motor symptoms and it enhanced animal well-being, in association with an improvement of the EAE pathology at the spinal cord and PFC level. Interestingly, the reduced dopamine beta-hydroxylase expression associated with EAE in the spinal cord and PFC was reversed through chemogenetic LC activation. CONCLUSION: Therefore, clear anti-inflammatory and neuroprotective effects were produced by the selective activation of LC noradrenergic neurons in EAE mice, having greater benefits when LC activation commenced earlier. Overall, these data suggest noradrenergic LC neurons may be targets to potentially alleviate some of the motor and non-motor symptoms in MS.

Portable thermal scanners to detect and monitor small endotherms: A comparative assessment of available equipment to guide practitioners.

Detection is essential to studying and monitoring wild animals; however, detection is challenging for small endotherms that are nocturnal or best detected at night. Techniques such as trapping or spotlighting disturb focal species, and the effectiveness of spotlighting can be limited for cryptic species, resulting in low detection rates that hinder our ability to monitor and study some endotherms at night. Thermal scanners detect infrared wavelengths not otherwise visible to humans. With improvements in equipment size and cost, thermal scanners have emerged as a valuable tool for passive detection of endotherms. Here we seek to provide objective guidance on thermal tool selection to practitioners who wish to adopt such tools to detect and monitor small endotherms. We compared the efficacy of three handheld thermal scanners (of varying resolutions) and a traditional spotlight for detecting small, cryptic endotherms at night. Random arrays of artificially heated small bird models (representing small, cryptic endotherms) were established along transects in native grasslands that support a range of small threatened endotherms, including the Critically Endangered Plains-wanderer (Pedionomus torquatus). Transects were independently surveyed by five observers, blind to model locations and model density. Performance measures representing detection capability were assessed for all devices, and usability of each device was assessed with a survey completed by all observers. Detection rates, detection distances, and survey accuracy were greater for thermal scanners with resolutions of 320 × 240 and 640 × 480 than for the spotlight. A low-resolution thermal scope (160 × 120) performed poorly for all performance measures. There was a consensus among users that a video camera-style thermal scanner was most comfortable to hold and view while traversing the transect, as opposed to thermal scopes where users look directly through the lens. These results suggest that high-resolution thermal scanners (≥320 × 240) provide improved detection capabilities compared to traditional spotlights. Higher detection rates provide opportunities for detecting and monitoring small endotherms at night where this was once difficult or impossible.

Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: a real-life multicentre analysis of 162 patients.

BACKGROUND: Anti-CGRP monoclonal antibodies have shown notable effectiveness and tolerability in migraine patients; however, data on their use in elderly patients is still lacking, as clinical trials have implicit age restrictions and real-world evidence is scarce. In this study, we aimed to describe the safety and effectiveness of erenumab, galcanezumab and fremanezumab in migraine patients over 65 years old in real-life. METHODS: In this observational real-life study, a retrospective analysis of prospectively collected data from 18 different headache units in Spain was performed. Migraine patients who started treatment with any anti-CGRP monoclonal antibody after the age of 65 years were included. Primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and medication intake frequencies by months 3 and 6, response rates, changes in patient-reported outcomes and reasons for discontinuation. As a subanalysis, reduction in monthly migraine days and proportion of adverse effects were also compared among the three monoclonal antibodies. RESULTS: A total of 162 patients were included, median age 68 years (range 65-87), 74.1% women. 42% had dyslipidaemia, 40.3% hypertension, 8% diabetes, and 6.2% previous cardiovascular ischaemic disease. The reduction in monthly migraine days at month 6 was 10.1 ± 7.3 days. A total of 25.3% of patients presented adverse effects, all of them mild, with only two cases of blood pressure increase. Headache and medication intake frequencies were significantly reduced, and patient-reported outcomes were improved. The proportions of responders were 68%, 57%, 33% and 9% for reductions in monthly migraine days ≥ 30%, ≥ 50%, ≥ 75% and 100%, respectively. A total of 72.8% of patients continued with the treatment after 6 months. The reduction in migraine days was similar for the different anti-CGRP treatments, but fewer adverse effects were detected with fremanezumab (7.7%). CONCLUSIONS: Anti-CGRP mAbs are safe and effective treatments in migraine patients over 65 years old in real-life clinical practice.

A Procedure for Measuring Anterior Scalene Morphology and Quality with Ultrasound Imaging: An Intra- and Inter-rater Reliability Study.

OBJECTIVE: Ultrasound (US) imaging is an essential tool for clinicians because of its cost-effectiveness and accessibility for assessing multiple muscle metrics including muscle quality, size and shape. Although previous studies highlighted the importance of the anterior scalene muscle (AS) in patients with neck pain, studies analyzing the reliability of US measurements for this muscle are lacking. This study aimed to develop a protocol for assessing AS muscle shape and quality measured with US and investigating its intra- and inter-examiner reliability. METHODS: Through use of a linear transducer, B-mode images of the anterolateral neck region at the C7 level were acquired in 28 healthy volunteers by two examiners (one experienced and one novel). Cross-sectional area, perimeter, shape descriptors and mean echo-intensity were measured twice by each examiner in randomized order. Intra-class correlation coefficients (ICCs), standard errors of measurement and minimal detectable changes were calculated. RESULTS: Results indicated no muscle side-to-side asymmetries (p > 0.05). Gender differences were found for muscle size (p < 0.01), but muscle shape and brightness were comparable (p > 0.05). Intra-examiner reliability was good to excellent for all metrics for the experienced and (ICC >0.846) and novel (ICC >780) examiners. Although inter-examiner reliability was good for most of the metrics (ICC >0.709), the estimates for assessing solidity and circularity were unacceptable (ICC <0.70). CONCLUSION: This study found that the described ultrasound procedure for locating and measuring anterior scalene muscle morphology and quality is highly reliable in asymptomatic individuals.

Mechanism of STMN2 cryptic splice-polyadenylation and its correction for TDP-43 proteinopathies.

Loss of nuclear TDP-43 is a hallmark of neurodegeneration in TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP-43 mislocalization results in cryptic splicing and polyadenylation of pre-messenger RNAs (pre-mRNAs) encoding stathmin-2 (also known as SCG10), a protein that is required for axonal regeneration. We found that TDP-43 binding to a GU-rich region sterically blocked recognition of the cryptic 3' splice site in STMN2 pre-mRNA. Targeting dCasRx or antisense oligonucleotides (ASOs) suppressed cryptic splicing, which restored axonal regeneration and stathmin-2-dependent lysosome trafficking in TDP-43-deficient human motor neurons. In mice that were gene-edited to contain human STMN2 cryptic splice-polyadenylation sequences, ASO injection into cerebral spinal fluid successfully corrected Stmn2 pre-mRNA misprocessing and restored stathmin-2 expression levels independently of TDP-43 binding.

Inter-Examiner Disagreement for Assessing Cervical Multifidus Ultrasound Metrics Is Associated with Body Composition Features.

Ultrasound imaging (US) is a biosensing technique that is widely used in several healthcare disciplines (including physiotherapy) for assessing multiple muscle metrics, such as muscle morphology and quality. Since all biosensors need to be tested in order to demonstrate their reliability, accuracy, sensitivity, and specificity, identifying factors that affect their diagnostic accuracy is essential. Since previous studies analyzed the impact of sociodemographic but not body composition characteristics in US errors, this study aimed to assess whether body composition metrics are associated with ultrasound measurement errors. B-mode images of the lumbar multifidus muscle at the L5 level were acquired and analyzed in 47 healthy volunteers by two examiners (one experienced and one novice). The cross-sectional area, muscle perimeter, and mean echo intensity were calculated bilaterally. A correlation analysis and a multivariate linear regression model were used for assessing the inter-examiner differences with respect to body composition metrics. The results demonstrated good-to-excellent reliability estimates for the cross-sectional area, muscle perimeter, aspect ratio, roundness, circularity, and mean brightness metrics (all ICC > 0.85). However, solidity showed unacceptable reliability (ICC < 0.7). Age, height, total lean mass, trunk lean mass, and water volume were associated with inter-examiner disagreement on mean echo intensity. Cross-sectional area, perimeter, and roundness measurement errors were associated with lean mass and water volume.

Effect of Altitude on Respiratory Functional Status in COVID-19 Survivors: Results from a Latin American Cohort-FIRCOV.

Laura Gochicoa-Rangel, Santiago C. Arce, Carlos Aguirre-Franco, Wilmer Madrid-Mejía, Mónica Gutiérrez-Clavería, Lorena Noriega-Aguirre, Patricia Schonffeldt-Guerrero, Agustín Acuña-Izcaray, Arturo Cortés-Telles, Luisa Martínez-Valdeavellano, Federico Isaac Hernández-Rocha, Omar Ceballos-Zúñiga, Rodrigo Del Rio Hidalgo, Sonia Sánchez, Erika Meneses-Tamayo, and Iván Chérrez-Ojeda; and on Behalf of the Respiratory Physiology Project in COVID-19 (FIRCOV). Effect of altitude on respiratory functional status in COVID-19 survivors: results from a Latin American Cohort-FIRCOV. High Alt Med Biol 24:37-48, 2023. Persistent symptoms and lung function abnormalities are common in COVID-19 survivors. Objectives: To determine the effect of altitude and other independent variables on respiratory function in COVID-19 survivors. Methods: Analytical, observational, cross-sectional cohort study done at 13 medical centers in Latin America located at different altitudes above sea level. COVID-19 survivors were invited to perform pulmonary function tests at least 3 weeks after diagnosis. Results: 1,368 participants (59% male) had mild (20%), moderate (59%), and severe (21%) disease. Restriction by spirometry was noted in 32%; diffusing capacity of the lung for carbon monoxide (DLCO) was low in 43.7%; and 22.2% walked less meters during the 6-minute walk test (6-MWT). In multiple linear regression models, higher altitude was associated with better spirometry, DLCO and 6-MWT, but lower oxygen saturation at rest and during exercise. Men were 3 times more likely to have restriction and 5.7 times more likely to have a low DLCO. Those who had required mechanical ventilation had lower DLCO and walked less during the 6-MWT. Conclusions: Men were more likely to have lower lung function than women, even after correcting for disease severity and other factors. Patients living at a higher altitude were more likely to have better spirometric patterns and walked farther but had lower DLCO and oxygen saturation.

Extra-criteria antiphospholipid antibodies in patients with small vessel brain lesions and clinical manifestations associated with antiphospholipid syndrome.

OBJECTIVES: Neurological manifestations compatible with small vessel brain lesions (SVBL), such as migraine, cognitive impairment, seizures, and transverse myelitis, may be related to antiphospholipid syndrome (APS) and patients could need APS therapies even though they do not fit into thrombosis or obstetric morbidity. Furthermore, extra-criteria antiphospholipid antibodies (aPL) provide an increase in sensitivity in patients with clinical manifestations related to APS but negative for IgG/IgM anticardiolipin (aCL), anti-ß2 glycoprotein I (aß2GPI), and lupus anticoagulant, which are the antibodies included in the classification criteria for APS. METHODS: We determined extra-criteria aPL in 65 SVBL patients with neurological traits and Magnetic Resonance Imaging suggestive of APS but negative for APS classification criteria, 47 of whom were prospectively followed and tested over three years. A group of 95 patients with autoimmune diseases (AD) but without clinical traits of APS was also studied. RESULTS: A persistent presence of extra-criteria aPL was detected in 27.7% of patients: 12.77% IgM anti- prothrombin (PT), 6.38% IgG anti-PT, 6.38% IgM anti-phosphatidylethanolamine (PE), 4.26% IgA aß2GPI, 2.13% IgG anti-phosphatidylserine/prothrombin (PS/PT) and 2.13% IgM anti-PS/PT. There was a tendency towards a higher prevalence of these aPL in SVBL patients than in AD - especially for IgA aß2GPI - and a lack of IgG aPS/PT positivity in the AD group. We found no SVBL patient positive for IgA aCL, IgG anti-PE, annexin V, or aß2GPI domain I. CONCLUSIONS: Extra-criteria aPL can improve sensitivity for APS diagnosis in patients with SVBL, especially IgA aß2GPI and IgG anti-PS/PT antibodies.

Structural Determinants of Indole-2-carboxamides: Identification of Lead Acetamides with Pan Antimycobacterial Activity.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), is one of the leading causes of death in developing countries. Non-tuberculous mycobacteria (NTM) infections are rising and prey upon patients with structural lung diseases such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis. All mycobacterial infections require lengthy treatment regimens with undesirable side effects. Therefore, new antimycobacterial compounds with novel mechanisms of action are urgently needed. Published indole-2-carboxamides (IC) with suggested inhibition of the essential transporter MmpL3 showed good potency against whole-cell M.tb, yet had poor aqueous solubility. This project focused on retaining the required MmpL3 inhibitory pharmacophore and increasing the molecular heteroatom percentage by reducing lipophilic atoms. We evaluated pyrrole, mandelic acid, imidazole, and acetamide functional groups coupled to lipophilic head groups, where lead acetamide-based compounds maintained high potency against mycobacterial pathogens, had improved in vitro ADME profiles over their indole-2-carboxamide analogs, were non-cytotoxic, and were determined to be MmpL3 inhibitors.

NT-proBNP, cerebral small vessel disease and cardiac function in patients with a recent lacunar infarct.

NT-proBNP is produced from both atria and ventricles and it is increased in patients with cardiac disease. NT-proBNP is also associated with cerebral small vessel disease(cSVD) but there are no studies that had carried out a systematic evaluation of cardiac function in this specific setting. We conducted a prospective observational study in 100 patients within 30 days after a recent lacunar infarct by means of brain MRI, 24 h ambulatory blood pressure monitoring, transthoracic echocardiography, and plasmatic NT-proBNP. Global cSVD burden was quantified using a validated visual score (0 to 4) and dichotomized into 2 groups (0-2 or 3-4). Age (73.8 vs 63.5 years) and NT-proBNP (156 vs 76 pg/ml) were increased in patients with SVD 3-4, while daytime augmentation index normalized for the heart rate of 75 bpm (AIx75) (22.5 vs 25.6%) was decreased. The proportion of patients with left atrial enlargement, left ventricular hypertrophy, or septal e' velocity <7 cm/s was not different between both groups. NT-proBNP was increased in patients with left atrial enlargement (126 vs 88 pg/ml). In multivariate analysis, age (OR 1.129 CI 95% 1.054-1.209), daytime AIx75 (OR 0.91 CI 95% 0.84-0.987,) and NT-proBNP (OR 1.007 CI 95% 1.001-1.012,) were independently associated with cSVD score 3-4. In conclusion, as well as in other patients with cSVD we found an association between NT-proBNP and cSVD. This association was independent of cardiac function.

Efectividad del chaleco serigrafiado como medida para disminuir las interrupciones durante la preparación de medicación / Efficacy of the screen printed vest as a measure to reduce interruptions during preparation of medication

Objetivo: evaluar la efectividad del uso de un chaleco serigrafiado en la reducción del número de interrupciones durante la preparación de medicación (PdM) en una unidad de hospitalización del Hospital Santos Reyes (Burgos, España) y la influencia de las medidas adoptadas durante la pandemia por SARS-CoV-2.Metodología: se realizó un estudio cuasiexperimental pre-post de un solo grupo con enfermeras de hospitalización de Medicina Interna. Se recogieron n= 576 preparaciones en tres periodos: antes de usar el chaleco, con chaleco en prepandemia y con chaleco durante la pandemia (con cese de visitas, suspensión de acompañamiento y obligatoriedad de permanecer dentro de la habitación). La variable resultado principal fue el número de interrupciones. Además se recogieron variables demográficas y laborales de las enfermeras, los motivos de las interrupciones y sus consecuencias. Todas fueron autocumplimentadas en hojas tras la PdM.Resultados: se analizaron finalmente 477 hojas de PdM, excluyendo las demás por errores de cumplimentación. En los dos primeros periodos se dieron 159 (86,9%) y 126 (91,9%) interrupciones (p= 0,089) y en el tercero 132 (83,5%), reduciéndose significativamente respecto al prepandemia (p= 0,008). Las principales causas de interrupción fueron el propio personal y tecnológicos (ambos reduciéndose en pandemia; p= 0,043 y p= 0,025 respectivamente). La principal consecuencia de las interrupciones (82-85%) fue repasar la medicación, aumentando significativamente en la pandemia (p= 0,042).Conclusiones: parece que la colocación del chaleco durante la PdM no disminuye el número de interrupciones a los profesionales de Enfermería. Sin embargo, las medidas implantadas durante la pandemia SARS-CoV-2 sí reducen significativamente dichas interrupciones.(AU)

Objective: to assess the efficacy of using a screen printed vest for the reduction in the number of interruptions during preparation of medication (PoM) at a hospitalization unit from the Hospital Santos Reyes (Burgos, Spain), and the influence of the measures taken during the SARS-CoV-2 pandemic.Methodology: a quasi-experimental study with pre-post design was conducted in a single arm with Internal Medicine hospitalization nurses. The study collected n= 576 preparations in three periods: before using the vest, with the vest before the pandemic, and with the vest during the pandemic (with no visitors or persons accompanying patients and enforced stay inside the room). The primary outcome variable was the number of interruptions. Demographical and occupational variables of nurses were also collected, as well as the reasons for the interruptions and their consequences. These were all self-completed in sheets after each PoM.Results: ultimately 477 PoM sheets were analysed; the rest were excluded due to completion errors. In the first two periods, there were 159 (86.9%) and 126 (91.9%) interruptions (p= 0.089), and 132 (83.5%) in the third, with a significant reduction vs. pre-pandemic (p= 0.008). Interruptions were mainly caused by the staff and technological reasons (both were reduced during the pandemic; p= 0.043 and p= 0.025 respectively). The main consequence of interruptions (82-85%) was reviewing the medication, with a significant increase during the pandemic (p= 0.042).Conclusions: apparently using the vest during PoM does not reduce the number of interruptions for Nursing professionals. However, the measures implemented during the SARS-CoV-2 pandemic did lead to a significant reduction in said interruptions.(AU)