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IntroductionPrimary ciliary dyskinesia (PCD) is a rare genetic disorder that can result in significant morbidity and mortality if left untreated. Clinical manifestations of PCD include recurrent respiratory infections, laterality defects, and infertility, all of which arise from impaired or absent ciliary motility. Diagnostic approaches for PCD may include high-speed video microscopy, measurement of nasal nitric oxide levels, and genetic testing; however, no single definitive diagnostic test exists. The present study aims to highlight the lack of standardized diagnostic and treatment guidelines for PCD in Latin America (Central and South America, and the Caribbean). To this effect, we compared North American and European recommendations for the diagnosis and management of PCD and found that certain diagnostic tools and treatment options mentioned in these guidelines are not readily accessible in many Latin American countries.Methods & ResultsThis review gathers disease information in North America, Europe, and Latin America organizing guideline results into tables for clarity and potential interventions. Management information for Latin America is inferred from case reports, as most findings are from North American recommendations and studies on PubMed, Google Scholar, and Scopus. Treatment and management information is based on North American and European standards.Among 5,774 publications reviewed, only 15 articles met the inclusion criteria (focused on PCD management, peer-reviewed, and located in America). No clinical guideline for PCD in Latin America was found, but recommendations on respiratory management from Colombia and Chile were discovered. The lack of guidelines in Latin America may originate from limited resources and research on the disease in those countries.DiscussionPCD lacks documentation, research, and recommendations regarding its prevalence in Latin America, likely due to unfavorable economic conditions. This disadvantage results in limited access to diagnostic tests available in North America and Europe. The PICADAR score, discussed in this review, can be used in low-income nations as a screening tool for the disorder.

Forecasting electricity spot prices holds paramount significance for informed decision-making among energy market stakeholders. This study introduces a methodology utilizing a multilayer perceptron (MLP) neural network for multivariate electricity spot price prediction. The model underwent a feature selection process to identify the most influential predictors. In the validation phase, the model’s performance was evaluated using key metrics, including trend accuracy percentage index (TAPI), normalized root mean squared error (NRMSE), and mean absolute percentage error (MAPE). The results were obtained for a four-week forecast horizon in order to serve as an auxiliary tool to facilitate decision-making processes in the short-term energy market. The relevance of short-term electricity spot price forecasting lies in its direct impact on pricing strategies during energy contract negotiations, which allows for the making of assertive decisions in the energy trading landscape.

Context: Modern medicine aims to ensure a world in which all people experience a good end of life as an integral part of their life journey. A good end-of-life experience means dying with dignity and receiving the best healthcare based on scientific evidence., Objective: This study aims to reach a consensus about the contents of a comprehensive instrument based on the 10/40 Model of the International Collaborative for the Best Care for the Dying Person for evaluating inpatients facing imminent death in Portuguese internal medicine wards and a proposal for anticipatory medication for symptom control in inpatient and home care settings., Methods: We employed the Delphi method and conducted various rounds of questionnaire administration to 23 Portuguese internists competent in palliative medicine. Data were obtained in July and September of 2022., Results: Consensus was reached among the expert panel on the diagnostic, initial assessment, monitoring, and after-death care items of the tool, with minor adjustments to wording or content. However, it was not possible to reach a consensus on most of the proposals presented for anticipatory medication for symptomatic control., Conclusion: We present the consensus about the contents of a comprehensive instrument for evaluating inpatients facing imminent death in Portuguese internal medicine wards. Best practices in this setting were defined from the point of view of internists with expertise in palliative care. However, the best pharmacological practices still require further reviews of the literature and consensus.

Background : Oral anticoagulation (OAC) is pivotal in the clinical management of atrial fibrillation (AF) patients. Vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) prevent thromboembolic events, but information about the quality of life (QoL) and patient satisfaction in relation with the anticoagulant treatment is limited. Methods : REGUEIFA is a prospective, observational, and multicentre study that included patients with AF treated by cardiologists. We included patients treated with VKAs or DOACs. The EuroQol-5D (EQ-5D) questionnaire evaluated QoL, and the Anti-Clot Treatment Scale (ACTS) questionnaire investigated patient satisfaction with OAC. Results : A total of 904 patients were included (532 on VKA and 372 on DOACs). A total of 846 patients completed the EQ-5D questionnaire, with results significantly worse in patients on VKAs than on DOACs: more mobility limitations (37.6% vs. 24.2%, p < 0.001), more restriction in usual activities (24.7% vs. 18.3%, p = 0.026), more pain/discomfort (31.8% vs. 24.2%, p = 0.015), a lower visual analogue scale (VAS) score (66.4 ± 16.21 vs. 70.8 ± 15.6), and a lower EQ-D5 index (0.79 ± 0.21 vs. 0.85 ± 0.2, p < 0.001). After adjusting for baseline characteristics, VKA treatment was not an independent factor towards worse EQ-5D results. Also, 738 patients completed the ACTS questionnaire, and burden and profit scores were lower in patients on VKAs than for DOACs (52.1 ± 8.4 vs. 55.5 ± 6.8, p < 0.001 and 11.1 ± 2.4 vs. 11.8 ± 2.6, p < 0.001, respectively). The negative impact score was higher for VKAs than for DOACs (1.8 ± 1.02 vs. 1.6 ± 0.99, p < 0.001), with a general positive impact score lower for VKAs than for DOACs (3.6 ± 0.96 vs. 3.8 ± 1.02, p < 0.001). Conclusions : Patients on VKA have more comorbidity and worse EQ-5D and VAS scores than those on DOACs. VKA has a greater burden and higher negative impact on the patient's life than DOACs.

For irreversible denaturation transitions such as those exhibited by monoclonal antibodies, differential scanning calorimetry provides the denaturation temperature, T m , the rate of denaturation at T m , and the activation energy at T m . These three quantities are essential but not sufficient for an accurate extrapolation of the rate of denaturation to temperatures of 25 °C and below. We have observed that the activation energy is not constant but temperature dependent due to the existence of an activation heat capacity, C p,a . It is shown in this paper that a model that incorporates C p,a is able to account for previous observations like, for example, that increasing the T m does not always improve the stability at low temperatures; that some antibodies exhibit lower stabilities at 5 °C than at 25 °C; or that low temperature stabilities do not follow the rank order derived from T m values. Most importantly, the activation heat capacity model is able to reproduce time dependent stabilities measured by size exclusion chromatography at low temperatures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We present a flora and fauna dataset for the Mira-Mataje binational basins. This is an area shared between southwestern Colombia and northwestern Ecuador, where both the Chocó and Tropical Andes biodiversity hotspots converge. We systematized data from 120 sources in the Darwin Core Archive (DwC-A) standard and geospatial vector data format for geographic information systems (GIS) (shapefiles). Sources included natural history museums, published literature, and citizen science repositories across 13 countries. The resulting database has 33,460 records from 6,821 species, of which 540 have been recorded as endemic, and 612 as threatened. The diversity represented in the dataset is equivalent to 10% of the total plant species and 26% of the total terrestrial vertebrate species in both hotspots. The dataset can be used to estimate and compare biodiversity patterns with environmental parameters and provide value to ecosystems, ecoregions, and protected areas. The dataset is a baseline for future assessments of biodiversity in the face of environmental degradation, climate change, and accelerated extinction processes., (© 2024. The Author(s).)

Introduction: In Brazil, approximately 5% are born with a congenital disorder, potentially fatal without surgery. This study aims to evaluate the relationship between gastrointestinal congenital malformation (GICM) mortality, health indicators, and socioeconomic factors in Brazil., Methods: GICM admissions (Q39-Q45) between 2012 and 2019 were collected using national databases. Patient demographics, socioeconomic factors, clinical management, outcomes, and the healthcare workforce density were also accounted for. Pediatric Surgical Workforce density and the number of neonatal intensive care units in a region were extracted from national datasets and combined to create a clinical index termed ' NeoSurg'. Socioeconomic variables were combined to create a socioeconomic index termed ' SocEcon'. Simple linear regression was used to investigate if the temporal changes of both indexes were significant. The correlation between mortality and the different indicators in Brazil was evaluated using Pearson's correlation coefficient., Results: Over 8 years, Brazil recorded 12804 GICM admissions. The Southeast led with 6147 cases, followed by the Northeast (2660), South (1727), North (1427), and Midwest (843). The North and Northeast reported the highest mortality, lowest NeoSurg, and SocEcon Index rates. Nevertheless, mortality rates declined across regions from 7.7% (2012) to 3.9% (2019), a 51.7% drop. The North and Midwest experienced the most substantial reductions, at 63% and 75%, respectively. Mortality significantly correlated with the indexes in nearly all regions ( p <0.05)., Conclusion: Our study highlights the correlation between social determinants of health and GICM mortality in Brazil, using two novel indexes in the pediatric population. These findings provide an opportunity to rethink and discuss new indicators that could enhance our understanding of our country and could lead to the development of necessary solutions to tackle existing challenges in Brazil and globally., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The DYSCOVER study was a phase 3b, open-label, randomized trial (NCT02799381) that evaluated levodopa-carbidopa intestinal gel (LCIG) versus optimized medical treatment (OMT) in patients with Parkinson's disease (PD) and a high burden of dyskinesia at baseline (defined as Unified Dyskinesia Rating Scale [UDysRS] total score ≥ 30). At week 12, patients receiving LCIG versus OMT experienced significant improvements in dyskinesia, pain, and health-related outcomes. The objective of this analysis was to examine correlations between dyskinesia, pain, and health-related outcomes in PD., Methods: This post hoc analysis assessed correlations between UDysRS, King's Parkinson's Disease Pain Scale (KPPS), 8-item Parkinson's Disease Questionnaire (PDQ-8), Unified Parkinson's Disease Rating Scale part II, Clinical Global Impression of Severity (CGI-S) or Change (CGI-C), and "On" time without troublesome dyskinesia at baseline and after 12 weeks of LCIG or OMT. Correlations were assessed by Pearson correlation coefficients (categorization: weak, r = 0.20-0.39; moderate, r = 0.40-0.59; strong, r ≥ 0.60)., Results: Among 61 patients, moderate-to-strong positive and significant correlations were observed between UDysRS and KPPS scores (baseline, r = 0.47; week 12 change from baseline [CFB], r = 0.63; all p < 0.001). UDysRS and KPPS scores had moderate-to-strong positive and highly significant correlations with PDQ-8 scores (baseline, r = 0.45 and 0.46, respectively; CFB, r = 0.54 and 0.64, respectively; all p < 0.001). Moderate positive and significant correlations were observed between UDysRS and CGI-S/CGI-C scores (baseline, r = 0.41; CFB, r = 0.47; all p < 0.001)., Conclusions: In patients with high dyskinesia burden, positive correlations were observed between dyskinesia, pain, and health-related quality of life (HRQoL) at baseline. Improvements in dyskinesia and pain were associated with improvements in HRQoL, demonstrating the clinical burden of troublesome dyskinesia., Trial Registration Number: Clinicaltrials.gov identifier NCT02799381., (© 2024. The Author(s).)

Background: As Parkinson's disease (PD) advances, management is challenged by an increasingly variable and inconsistent response to oral dopaminergic therapy, requiring special considerations by the provider. Continuous 24 h/day subcutaneous infusion of foslevodopa/foscarbidopa (LDp/CDp) provides steady dopaminergic stimulation that can reduce symptom fluctuation., Objective: Our aim is to review the initiation, optimization, and maintenance of LDp/CDp therapy, identify possible challenges, and share potential mitigations., Methods: Review available LDp/CDp clinical trial data for practical considerations regarding the management of patients during LDp/CDp therapy initiation, optimization, and maintenance based on investigator clinical trial experience., Results: LDp/CDp initiation, optimization, and maintenance can be done without hospitalization in the clinic setting. Continuous 24 h/day LDp/CDp infusion can offer more precise symptom control than oral medications, showing improvements in motor fluctuations during both daytime and nighttime hours. Challenges include infusion-site adverse events for which early detection and prompt management may be required, as well as systemic adverse events (eg, hallucinations) that may require adjustment of the infusion rate or other interventions. A learning curve should be anticipated with initiation of therapy, and expectation setting with patients and care partners is key to successful initiation and maintenance of therapy., Conclusion: Continuous subcutaneous infusion of LDp/CDp represents a promising therapeutic option for individuals with PD. Individualized dose optimization during both daytime and nighttime hours, coupled with patient education, and early recognition of certain adverse events (plus their appropriate management) are required for the success of this minimally invasive and highly efficacious therapy., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Anna Jeong is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Agnita J. W. Boon is a study investigator and has served as an advisory board member for AbbVie Inc., Stada, and Ever Pharma. She has received a research grant from Stichting ParkinsonFonds and the Erasmus Trust Fund. Amy M. Spiegel is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Arjun Tarakad declarations of interest: none. Eric Freire-Alvarez has received advisory, consulting, and lectures fees from AbbVie Inc., Teva, Bial, Zambon, Esteve, UCB, and Neuraxpharm; and is an investigator on studies funded by AbbVie Inc., Neuroderm, Cerevel, Roche, Anavex, Bial, Zambon, Impax, and Irlab. Enrique Urrea-Mendoza has received advisory/consulting fees from: AbbVie Inc., Defeat MSA USA, and Medtronic. Filip Bergquist has received advisory and lecture fees from AbbVie Inc., GKC, and Britannia; and research support in kind from GKC. He is a board member of Arvid Carlsson Research AB and receives salary from the University of Gothenburg and Sahlgrenska University Hospital. Jason Aldred is a member of the faculty of the University of Washington and Washington State University. He is a study investigator and has received honorarium from AbbVie Inc., Allergan (now AbbVie Inc.), Teva, US WorldMeds, Medtronic, and Abbott. He is an investigator in studies sponsored by AbbVie Inc., Biogen, Acadia, Northwestern University, Neuroderm, Massachusetts General Hospital, and AstraZeneca. He is also a scientific advisor for AbbVie Inc. He has a clinical practice through Selkirk Neurology. Jia Jia is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Jorge Zamudio is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Manon Bouchard has received honoraria for consultancy, lectures, and advisory boards from AbbVie Inc., Allergan (now AbbVie Inc.), Merz, Ipsen, Lilly, Novartis, Paladin, Sunovion, and UCB. She is an investigator for AbbVie Inc., ES-therapeutics, Biohaven, and Pfizer. Maurizio F. Facheris is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Michael J. Soileau has received advisory/consulting fees from: AbbVie Inc., Abbott, Mertz Therapeutics, Medtronic, and Supernus. He has received research support from: AbbVie Inc., Cerevel Therapeutics, CND Lifesciences, Praxis Precision Medicine, and Teva. He has served on the speaking bureau for: AbbVie Inc., Amneal Pharmaceuticals, Kyowa Kirin, and Neurocrine Pharmaceuticals. Martha P. Arroyo is a study investigator with Leo Pharma and Allakos, and has received honoraria and consultant fees from AbbVie Inc. and BMS. She has a clinical practice through Lakeside Dermatology. Nahome Fisseha is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Pavnit Kukreja is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Robert A. Hauser serves on a scientific advisory board for Inhibikase and Stoparkinson. He has received consulting fees from AbbVie Inc., Amneal Pharmaceuticals, Avanex, Biogen, BlueRock Therapeutics, Forsee Pharmaceuticals, Global Kinetics, Inhibikase, Jazz Pharmaceuticals, Kyowa Kirin, MDCE Suzhou, MedRhythms, Merck, Merz, Neurocrine, Neuroderm, Ovid Therapeutics, PD Neurotechnology, Pharma Two B, Regenxbio, Revance, Sage Therapeutics, Scion NeuroStim, Stoparkinson, Sunovion, Supernus Pharmaceuticals, Tolmar, Tremor Research Group, Tris Pharma, UCB, and Vivifi Biotech. He has received speaking fees from Acorda, Amneal Pharmaceuticals, Cerevel, Inhibikase, Kyowa Kirin, Neurocrine Biosciences, Sunovion, and Supernus. His University has received research support from AbbVie Inc., Aeon Biopharma, Annovis Bio Inc., Artizan Biosciences, Biogen MA, Bukwang Pharmaceutical Co. Ltd., Cavion Inc., Cerevance Inc., Cerevel Therapeutics, Cynapsus Therapeutics, Enterin Inc., Genetech, Global Kinetics Corporation, Hoffman-La Roche Inc., Impax Laboratories, Inhibikase Therapeutics, Integrative Research Laboratories Sweden, Lundbeck Inc., Michael J. Fox Foundation for Parkinson’s Research, National Parkinson’s Foundation, Neuraly Inc., Neurocrine Biosciences, Neuroderm, Parkinson’s & Movement Disorder Alliance, Pharma Two B Ltd., Revance Therapeutics, Sage Therapeutics, Sanofi Pharmaceuticals, Scion NeuroStim, SunPharma, and UCB BioPharma. He holds stock options in Axial Therapeutics, Enterin, and Inhibikase as well as holds stock in Revance Therapeutics. He has received intellectual property interests from a Parkinson’s Disease Diary through his University. He acknowledges a Center of Excellence grant from the Parkinson Foundation. Rajesh Pahwa serves as a consultant for Abbott, AbbVie Inc., ACADIA, Acorda, Adamas, Amneal, CalaHealth, Global Kinetics, Impel, Neuropharma, Kyowa, Lundbeck, Mitsubishi, Neurocrine, Orbis Bioscience, PhotoPharmics, Prilenia, Sunovion, Teva Neuroscience, and US WorldMeds. He receives research support from Abbott, AbbVie Inc., Addex, Biogen, Biohaven, Boston Scientific, EIP, Global Kinetics, Impax, Intec, Lilly, Neuroderm, Neuraly, Parkinson’s Foundation, Pharma 2B, Prelinia, Roche, SIS, Sun Pharma, Sunovion, Theranexus, Theravance, US WorldMeds, and Voyager. He is also an investigator for AbbVie Inc. Sarah Bray has received advisory fees from AbbVie Inc., receives a salary from NSW Health, and is a Nurse Coordinator on studies funded by AbbVie Inc. Sara Dhanani received advisory honoraria from Amneal and AbbVie Inc., and is an investigator on studies funded by AbbVie Inc. Saritha Talapala is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Victor S. C. Fung receives a salary from NSW Health; has received unrestricted research grants from the Michael J. Fox Foundation, AbbVie Inc., and Merz; and receives royalties from Health Press Ltd. and Taylor and Francis Group LLC., (© 2024 AbbVie Inc.)

Objectives: Identifying the prevalence of palliative care (PC) needs among patients who die at the emergency department (ED) and to assess symptom control and aggressiveness of care., Methods: We conducted a decedent cohort study of adults deceased at the ED of a Portuguese teaching hospital in 2016. PC needs were identified using the National Hospice Organization terminality criteria and comorbidities measurement by the Charlson's Index., Results: 384 adults died at the ED (median age 82 (IQR 72-89) years) and 78.4% (95% CI 73.9% to 82.2%) presented PC needs. Only 3.0% (n=9) were referred to the hospital PC team. 64.5%, 38.9% and 57.5% experienced dyspnoea, pain and confusion, respectively. Dyspnoea was commonly medicated (92%), against 56% for pain and 8% for confusion. Only 6.3% of the patients were spared from aggressive interventions, namely blood collection (86.0%) or intravenous fluid therapy (63.5%). The burden of aggressive interventions was similar between those with or without withhold cardiopulmonary resuscitation order (median 3 (2-4) vs 3 (2-5)), p=0.082., Conclusions: Nearly four out of five adults who died at the ED had PC needs at the time of admission. Most experienced poor symptom control and care aggressiveness in their last hours of life and were mostly unknown to the PC team. The findings urge improvements in the care provided to patients with PC needs at the ED, focusing on patient well-being and increased PC referral., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Foslevodopa/foscarbidopa, a soluble formulation of levodopa/carbidopa (LD/CD) prodrugs for the treatment of Parkinson's disease (PD), is administered as a 24-hour/day continuous subcutaneous infusion (CSCI) with a single infusion site. The efficacy and safety of foslevodopa/foscarbidopa versus oral immediate-release LD/CD was previously demonstrated in patients with PD in a 12-week, randomized, double-blind, phase 3 trial (NCT04380142). We report the results of a separate 52-week, open-label, phase 3 registrational trial (NCT03781167) that evaluated the safety/tolerability and efficacy of 24-hour/day foslevodopa/foscarbidopa CSCI in patients with advanced PD., Methods: Male and female patients with levodopa-responsive PD and ≥ 2.5 hours of "Off" time/day received 24-hour/day foslevodopa/foscarbidopa CSCI at individually optimized therapeutic doses (approximately 700-4250 mg of LD per 24 hours) for 52 weeks. The primary endpoint was safety/tolerability. Secondary endpoints included changes from baseline in normalized "Off" and "On" time, percentage of patients reporting morning akinesia, Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Parkinson's Disease Sleep Scale-2 (PDSS-2), 39-item Parkinson's Disease Questionnaire (PDQ-39), and EuroQol 5-dimension questionnaire (EQ-5D-5L)., Results: Of 244 enrolled patients, 107 discontinued, and 137 completed treatment. Infusion site events were the most common adverse events (AEs). AEs were mostly nonserious (25.8% of patients reported serious AEs) and mild/moderate in severity. At week 52, "On" time without troublesome dyskinesia and "Off" time were improved from baseline (mean [standard deviation (SD)] change in normalized "On" time without troublesome dyskinesia, 3.8 [3.3] hours; normalized "Off" time, -3.5 [3.1] hours). The percentage of patients experiencing morning akinesia dropped from 77.7% at baseline to 27.8% at week 52. Sleep quality (PDSS-2) and quality of life (PDQ-39 and EQ-5D-5L) also improved., Conclusion: Foslevodopa/foscarbidopa has the potential to provide a safe and efficacious, individualized, 24-hour/day, nonsurgical alternative for patients with PD., Trial Registration Number: ClinicalTrials.gov identifier NCT03781167., (© 2023. The Author(s).)

Introduction: Parkinson's Disease (PD) is a progressive age-related neurodegenerative condition requiring new therapeutic alternatives. Safinamide, a novel levodopa add-on therapy, positively affects disease fluctuations by modulating both dopaminergic and glutamatergic systems. To further investigate the use of safinamide in European routine clinical practice, the present post-hoc analysis aimed to understand safinamide's safety profile within the Spanish study population., Patients and Methods: Five hundred eleven Spanish patients with PD were evaluated at baseline, four (±1), eight (±1), and 12 (±1) months after initiating safinamide treatment. Unified Parkinson's Disease Rating Scale (UPDRS) total score and UPDRS part III score during on time were used to measure the overall severity of PD and motor complications, respectively, while the severity of adverse events was evaluated following the investigators' criteria., Results: Safinamide showed a favourable safety profile within the Spanish study population, although prescription to patients with psychiatric conditions and off-label use were more frequent than in the European study population. In Spain, clinically meaningful improvements were observed in UPDRS scores when safinamide was used as the only add-on therapy to levodopa (57.4% and 53.7% of patients) and when switching from rasagiline (55.1% of patients). Motor complications were reduced from 83.2% to 63.3% after the study period. Increased safety concerns were undetected in any patient subgroup, although patients with cognitive impairment showed a slightly higher frequency of adverse events., Conclusions: This subanalysis further supports safinamide use as a safe and efficacious option for the management of motor fluctuations in different subgroups of levodopa-treated patients. However, safinamide should be used with caution in patients with cognitive impairment.

Introduction: Primary ciliary dyskinesia (PCD) is a rare genetic disorder that can result in significant morbidity and mortality if left untreated. Clinical manifestations of PCD include recurrent respiratory infections, laterality defects, and infertility, all of which arise from impaired or absent ciliary motility. Diagnostic approaches for PCD may include high-speed video microscopy, measurement of nasal nitric oxide levels, and genetic testing; however, no single definitive diagnostic test exists. The present study aims to highlight the lack of standardized diagnostic and treatment guidelines for PCD in Latin America (Central and South America, and the Caribbean). To this effect, we compared North American and European recommendations for the diagnosis and management of PCD and found that certain diagnostic tools and treatment options mentioned in these guidelines are not readily accessible in many Latin American countries., Methods & Results: This review gathers disease information in North America, Europe, and Latin America organizing guideline results into tables for clarity and potential interventions. Management information for Latin America is inferred from case reports, as most findings are from North American recommendations and studies on PubMed, Google Scholar, and Scopus. Treatment and management information is based on North American and European standards.Among 5,774 publications reviewed, only 15 articles met the inclusion criteria (focused on PCD management, peer-reviewed, and located in America). No clinical guideline for PCD in Latin America was found, but recommendations on respiratory management from Colombia and Chile were discovered. The lack of guidelines in Latin America may originate from limited resources and research on the disease in those countries., Discussion: PCD lacks documentation, research, and recommendations regarding its prevalence in Latin America, likely due to unfavorable economic conditions. This disadvantage results in limited access to diagnostic tests available in North America and Europe. The PICADAR score, discussed in this review, can be used in low-income nations as a screening tool for the disorder., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Castillo, Freire and Romero.)

The estimative of the leaf area using a nondestructive method is paramount for successive evaluations in the same plant with precision and speed, not requiring high-cost equipment. Thus, the objective of this work was to construct models to estimate leaf area using artificial neural network models (ANN) and regression and to compare which model is the most effective model for predicting leaf area in sesame culture. A total of 11,000 leaves of four sesame cultivars were collected. Then, the length (L) and leaf width (W), and the actual leaf area (LA) were quantified. For the ANN model, the parameters of the length and width of the leaf were used as input variables of the network, with hidden layers and leaf area as the desired output parameter. For the linear regression models, leaf dimensions were considered independent variables, and the actual leaf area was the dependent variable. The criteria for choosing the best models were: the lowest root of the mean squared error (RMSE), mean absolute error (MAE), and absolute mean percentage error (MAPE), and higher coefficients of determination (R 2 ). Among the linear regression models, the equation y ˆ = 0.515 + 0.584 * L W was considered the most indicated to estimate the leaf area of the sesame. In modeling with ANNs, the best results were found for model 2-3-1, with two input variables (L and W), three hidden variables, and an output variable (LA). The ANN model was more accurate than the regression models, recording the lowest errors and higher R 2 in the training phase (RMSE: 0.0040; MAE: 0.0027; MAPE: 0.0587; and R 2 : 0.9834) and in the test phase (RMSE: 0.0106; MAE: 0.0029; MAPE: 0.0611; and R 2 : 0.9828). Thus, the ANN method is the most indicated and accurate for predicting the leaf area of the sesame., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Joao Everthon da Silva Ribeiro reports administrative support, article publishing charges, equipment, drugs, or supplies, statistical analysis, travel, and writing assistance were provided by 10.13039/100017134Federal Rural University of the Semi-Arid. There was no financial interest., (© 2023 The Author(s).)

Background and Aims: End-stage liver disease (ESLD) is an important cause of morbidity and mortality, comparable to a large extent to other organ insufficiencies. The need for palliative care (PC) in patients with ESLD is high. In Portugal, in the only identified study, more than 80% of patients hospitalized with ESLD had criteria for PC. No results specified which needs they identified or their transplantation prospect status., Methods: Prospective observational study including 54 ESLD patients who presented to a university hospital and transplantation center, between November 2019 and September 2020. Assessment of their PC needs through the application of NECPAL CCOMS-ICO © and IPOS, considering their transplantation perspective status., Results: Of the 54 patients, 5 (9.3%) were on active waiting list for transplantation and 8 (14.8%) under evaluation. NECPAL CCOMS-ICO © identified 23 patients (n = 42.6%) that would benefit from PC. Assessment of PC needs by clinicians, functional markers and significant comorbidities were the most frequent criteria (47.8%, n = 11). IPOS also revealed a different sort of needs: on average, each patient identified about 9 needs (8.9 ±2.8). Among the symptoms identified, weakness (77.8%), reduced mobility (70.3%), and pain (48.1%) stood out, as well as the psychoemotional symptoms of depression (66.7%) and anxiety (77.8%). There were no significant differences between the subgroups of patients analyzed. Only 4 patients (7.4%) were followed by the PC team., Conclusion: All the ESLD patients included, independently of the group they belonged to, presented with PC needs. No significant differences between the subgroups of patients were identified, confirming that even patients with a transplantation prospect have important needs for PC., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)

In hospitalized patients the prevalence of constipation is high, especially among elderly patients. Constipation impacts significantly the quality of life of patients and is associated with increased morbidity and length of hospital stay. This retrospective observational study intended to identify the prevalence of constipation in patients hospitalized in an internal medicine ward. In a sample of 80 patients, the median age was 79 years and 53% ( n  = 42) were women. We identified constipation in 68% ( n  = 56) of the patients during hospitalization. The medical team prescribed treatment only to 70% of those patients. Constipation was responsible for delirium in 11% of patients and 5% suffered urinary retention. This study shows constipation is prevalent among patients admitted in an internal medicine ward. Systematic assessment of this problem can improve the overall care of the patients, alleviate symptoms, and prevent complications., Competing Interests: None to declare., (© 2023 The Authors. Aging Medicine published by Beijing Hospital and John Wiley & Sons Australia, Ltd.)

A series of six new Cu(i) complexes with ([Cu( N -{4- R }pyridine-2-yl-methanimine)(PPh 3 )Br]) formulation, where R corresponds to a donor or acceptor p -substituent, have been synthesized and were used to study self-association effects on their structural and electrochemical properties. X-ray diffraction results showed that in all complexes the packing is organized from a dimer generated by supramolecular π stacking and hydrogen bonding. 1 H-NMR experiments at several concentrations showed that all complexes undergo a fast-self-association monomer-dimer equilibrium in solution, while changes in resonance frequency towards the high or low field in specific protons of the imine ligand allow establishing that dimers have similar structures to those found in the crystal. The thermodynamic parameters for this self-association process were calculated from dimerization constants determined by VT- 1 H-NMR experiments for several concentrations at different temperatures. The values for K D (4.0 to 70.0 M -1 range), Δ H (-1.4 to -2.6 kcal mol -1 range), Δ S (-0.2 to 2.1 cal mol -1 K -1 range), and Δ G 298 (-0.8 to -2.0 kcal mol -1 range) are of the same order and indicate that the self-dimerization process is enthalpically driven for all complexes. The electrochemical profile of the complexes shows two redox Cu(ii)/Cu(i) processes whose relative intensities are sensitive to concentration changes, indicating that both species are in chemical equilibrium, with the monomer and the dimer having different electrochemical characteristics. We associate this behaviour with the structural lability of the Cu(i) centre that allows the monomeric molecules to reorder conformationally to achieve a more adequate assembly in the non-covalent dimer. As expected, structural properties in the solid and in solution, as well as their electrochemical properties, are not correlated with the electronic parameters usually used to evaluate R substituent effects. This confirms that the properties of the Cu(i) complexes are usually more influenced by steric effects than by the inductive effects of substituents of the ligands. In fact, the results obtained showed the importance of non-covalent intermolecular interactions in the structuring of the coordination geometry around the Cu centre and in the coordinative stability to avoid dissociative equilibria., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Recently, a novel simple classification called MNCD, based on 4 axes (Motor; Non-motor; Cognition; Dependency) and 5 stages, has been proposed to classify Parkinson's disease (PD)., Objective: Our aim was to apply the MNCD classification in a cohort of PD patients for the first time and also to analyze the correlation with quality of life (QoL) and disease severity., Methods: Data from the baseline visit of PD patients recruited from 35 centers in Spain from the COPPADIS cohort fromJanuary 2016 to November 2017 were used to apply the MNCD classification. Three instruments were used to assess QoL:1) the 39-item Parkinson's disease Questionnaire [PDQ-39]); PQ-10; the EUROHIS-QOL 8-item index (EUROHIS-QOL8)., Results: Four hundred and thirty-nine PD patients (62.05±7.84 years old; 59% males) were included. MNCD stage was:stage 1, 8.4% (N = 37); stage 2, 62% (N = 272); stage 3, 28.2% (N = 124); stage 4-5, 1.4% (N = 6). A more advancedMNCD stage was associated with a higher score on the PDQ39SI (p < 0.0001) and a lower score on the PQ-10 (p< 0.0001) and EUROHIS-QOL8 (p< 0.0001). In many other aspects of the disease, such as disease duration, levodopa equivalent daily dose, motor symptoms, non-motor symptoms, and autonomy for activities of daily living, an association between the stage and severity was observed, with data indicating a progressive worsening related to disease progression throughout the proposed stages., Conclusion: Staging PD according to the MNCD classification correlated with QoL and disease severity. The MNCD could be a proper tool to monitor the progression of PD.

Background: Oesophageal cancer patients have poor survival, and most are unfit for curative or systemic palliative treatment. This article aims to review the best supportive care for oesophageal cancer, focusing on the management of its most frequent or distinctive symptoms and complications., Methods: Evidence-based review on palliative supportive care of oesophageal cancer, based on Pubmed search for relevant clinical practice guidelines, reviews and original articles, with additional records collected from related articles suggestions, references and societies recommendations., Results: We identified 1075 records, from which we screened 138 records that were related to oesophageal cancer supportive care, complemented with 48 additional records, finally including 60 records. This review summarizes the management of oesophageal cancer-related main problems, including dysphagia, malnutrition, pain, nausea and vomiting, fistula and bleeding. In recent years, several treatments have been developed, while optimal management is not yet standardized., Conclusion: This review contributes toward improving supportive care and decision making for oesophageal cancer patients, presenting updated summary recommendations for each of their main symptoms. A robust body of evidence is still lacking, and the best supportive care decisions should be individualized and shared.

The genus Kalanchoe , mostly indigenous from Madagascar and Tropical Africa, is widely traded for ornamental value. In this study, we provided an updated list of wild and cultivated Kalanchoe taxa in Ecuador; we analyzed the temporal-spatial pattern of their records, and we categorized the invasion status for each taxon and its environment preferences. The records of any taxa belonging to this genus were compiled from an extensive search using various information sources. Our results confirmed the presence of 16 taxa of Kalanchoe in the country. Seven species and a hybrid were detected in the wild. Kalanchoe densiflora , K. laxiflora , K. pinnata , K. tubiflora , and K. × houghtonii were categorized as invasive. We detected invasive records of some of these plants in protected areas. Almost all taxa had at least one record as cultivated, suggesting that the invasion pathway is ornamental trade. Kalanchoe pinnata individuals in the wild were recorded in the four biogeographic regions of Ecuador, which could be associated with the wide range of precipitations and temperatures in which the species may dwell. Our study highlights the importance of reducing the ornamental value and limiting the use of Kalanchoe taxa with invasive potential in horticulture and promoting, instead, the use of indigenous species.

The economically important cotton and cacao family (Malvaceae sensu lato) have long been recognized as a monophyletic group. However, the relationships among some subfamilies are still unclear as discordant phylogenetic hypotheses keep arising when different sources of molecular data are analyzed. Phylogenetic discordance has previously been hypothesized to be the result of both introgression and incomplete lineage sorting (ILS), but the extent and source of discordance have not yet been evaluated in the context of loci derived from massive sequencing strategies and for a wide representation of the family. Furthermore, no formal methods have been applied to evaluate if the detected phylogenetic discordance among phylogenomic datasets influences phylogenetic dating estimates of the concordant relationships. The objective of this research was to generate a phylogenetic hypothesis of Malvaceae from nuclear genes, specifically we aimed to (1) investigate the presence of major discordance among hundreds of nuclear gene histories of Malvaceae; (2) evaluate the potential source of discordance; and (3) examine whether discordance and loci heterogeneity influence on time estimates of the origin and diversification of subfamilies. Our study is based on a comprehensive dataset representing 96 genera of the nine subfamilies and 268 nuclear loci. Both concatenated and coalescence-based approaches were followed for phylogenetic inference. Using branch lengths and topology, we located the placement of introgression events to directly evaluate whether discordance is due to introgression rather than ILS. To estimate divergence times, concordance and molecular rate were considered. We filtered loci based on congruence with the species tree and then obtained the molecular rate of each locus to distribute them into three different sets corresponding to shared molecular rate ranges. Bayesian dating was performed for each of the different sets of loci with the same parameters and calibrations. Phylogenomic discordance was detected between methods, as well as gene histories. At deep coalescent times, we found discordance in the position of five subclades probably due to ILS and a relatively small proportion of introgression. Divergence time estimation with each set of loci generated overlapping clade ages, indicating that, even with different molecular rate and gene histories, calibrations generally provide a strong prior., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hernández-Gutiérrez, van den Berg, Granados Mendoza, Peñafiel Cevallos, Freire M., Lemmon, Lemmon and Magallón.)

Voltage-gated sodium channels, Na V s, are responsible for the rapid rise of action potentials in excitable tissues. Na V channel mutations have been implicated in several human genetic diseases, such as hypokalemic periodic paralysis, myotonia, and long-QT and Brugada syndromes. Here, we generated high-affinity anti-Na V nanobodies (Nbs), Nb17 and Nb82, that recognize the Na V 1.4 (skeletal muscle) and Na V 1.5 (cardiac muscle) channel isoforms. These Nbs were raised in llama (Lama glama) and selected from a phage display library for high affinity to the C-terminal (CT) region of Na V 1.4. The Nbs were expressed in Escherichia coli, purified, and biophysically characterized. Development of high-affinity Nbs specifically targeting a given human Na V isoform has been challenging because they usually show undesired crossreactivity for different Na V isoforms. Our results show, however, that Nb17 and Nb82 recognize the CTNa V 1.4 or CTNa V 1.5 over other CTNav isoforms. Kinetic experiments by biolayer interferometry determined that Nb17 and Nb82 bind to the CTNa V 1.4 and CTNa V 1.5 with high affinity (K D ∼ 40-60 nM). In addition, as proof of concept, we show that Nb82 could detect Na V 1.4 and Na V 1.5 channels in mammalian cells and tissues by Western blot. Furthermore, human embryonic kidney cells expressing holo Na V 1.5 channels demonstrated a robust FRET-binding efficiency for Nb17 and Nb82. Our work lays the foundation for developing Nbs as anti-Na V reagents to capture Na V s from cell lysates and as molecular visualization agents for Na V s., Competing Interests: Conflict of interest S. B. G. is a founder and holds equity in Advanced Molecular Sciences LLC. S. B. G. is consultant to Genesis Therapeutics and Xinthera, Inc. All other authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and objective : Parkinson's disease (PD) is a clinically heterogeneous disorder in which the symptoms and prognosis can be very different among patients. We propose a new simple classification to identify key symptoms and staging in PD. Patients and Methods : Sixteen movement disorders specialists from Spain participated in this project. The classification was consensually approved after a discussion and review process from June to October 2021. The TNM classification and the National Institutes of Health Stroke Scale (NIHSS) were considered as models in the design. Results : The classification was named MNCD and included 4 major axes: (1) motor symptoms; (2) non-motor symptoms; (3) cognition; (4) dependency for activities of daily living (ADL). Motor axis included 4 sub-axes: (1) motor fluctuations; (2) dyskinesia; (3) axial symptoms; (4) tremor. Four other sub-axes were included in the non-motor axis: (1) neuropsychiatric symptoms; (2) autonomic dysfunction; (3) sleep disturbances and fatigue; (4) pain and sensory disorders. According to the MNCD, 5 stages were considered, from stage 1 (no disabling motor or non-motor symptoms with normal cognition and independency for ADL) to 5 (dementia and dependency for basic ADL). Conclusions : A new simple classification of PD is proposed. The MNCD classification includes 4 major axes and 5 stages to identify key symptoms and monitor the evolution of the disease in patients with PD. It is necessary to apply this proof of concept in a properly designed study.