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Abstract Background To provide evidence-based, up-to-date recommendations for physicians in primary and specialist healthcare setting in diagnosing and treating patients with polymyalgia rheumatica (PMR). Methods The PMR working group conducted a narrative review of the available evidence in the field and wrote the draft guidelines. These guidelines were discussed and revised according to the standard operating procedures within the Norwegian Society of Rheumatology. The European Alliance of Associations for Rheumatology (EULAR) and American College of Rheumatology (ACR) recommendations for the management of PMR, the British Society for Rheumatology (BSR) guidelines for the management for PMR, the treat-to-target recommendations in giant cell arteritis and PMR and the 2023 recommendations for early referral of individuals with suspected polymyalgia rheumatica were used in particular for purpose of harmonization. Results A total of 10 recommendations have been formulated covering initial diagnostic investigations, comorbidity assessment, imaging, specialist referral criteria, treatment involving glucocorticoids and steroid-sparing agents and follow-up care. Conclusion Norwegian recommendations for diagnostics and treatment to improve management and outcome in patients with PMR were developed.

Se describe la experiencia en 10 años en el tratamiento de los traumatismos graves de hígado con la oclusión selectiva arterial extrahepátlca como alternativa de hemostasia. En 13 pacientes se efecutaron 12 oclusiones satisfactorias y hubo fracaso en 1. Las complicaciones hepáticas post-operatorias relacionadas a la aplicación del método fue de 23%; dentro de las extrahepáticas, las respiratorias alcanzan el 61.3%. La mortalidad relacionada con la lesión del higado fue por hemorragia hepática persistente en el 7.6%; la extrahepática por pancreatitis y lesión neurológica en el 15,2%. Esta experiencia demuestra que este procedimiento de excepción de hemostasia hepática es altamente confiable, de baja morbimortalidad, rápido, aplicable en lesiones penetrantes o no, poco visibles o Inaccesibles o en las que existe además lesiones de viscera hueca. Se puede aplicar tambien este procedimiento cuando fallan otros métodos de hemostasia hepática. Está al alcance de cuulquler cirujano entrenado y no requiere de Instrumental especializado. No se puede aplicar en hemorragias provenientes de lesiones de venas perihepáticas y en hemorragias no mecanicas.

Introducción: Los tumores intracraneales son la segunda patología más frecuente en pacientes entre 0 y 19 años de vida. En edades más tempranas son más frecuentes los tumores de origen embrionario, con una localización infratentorial. Presentan una gran morbimortalidad dada por el efecto de masa que genera el tumor, y también por los tratamientos disponibles, presentando un gran desafío para la toma de decisiones. El método ideal para la caracterización de los mismos y seguimiento es la resonancia magnética (RM) con contraste endovenoso. Objetivo: Analizar las características imagenológicas de los tumores intracraneales en pacientes menores de 1 año y su relación con la agresividad tumoral. Método: Estudio de cohorte retrospectivo. Se incluyeron pacientes de hasta 1 año de edad con diagnóstico de tumor intracraneal y resonancia magnética disponible, evaluados entre los años 2010 y 2022. Se obtuvo la información clínica y las características imagenológicas de los tumores. Se incluyeron 11 pacientes. Los motivos de consulta más frecuentes fueron aumento del perímetro cefálico (27,3%) y vómitos (27,3%). Resultados: Encontramos seis tumores supratentoriales y cinco infratentoriales. Siete tumores tenían restricción en difusión, nueve reforzaban con contraste intravenoso y dos presentaban diseminación leptomeníngea. Se observó desviación de la línea media en ocho pacientes e hidrocefalia en seis. Encontramos seis tumores gliales (54,5%), dos tumores teratoides rabdoides, dos tumores neurales y un ependimoma anaplásico. Cinco pacientes recibieron tratamiento quirúrgico y tres tratamiento quimioterápico; los restantes no recibieron tratamiento oncológico. Siete pacientes tuvieron sobrevida a 5 años, tres con desarrollo neurológico normal y cuatro con secuelas neurológicas. Conclusiones: La detección de las lesiones y sus características radiológicas, en especial la localización, pueden asistir en el manejo de los pacientes con tumores intracraneales en el primer año de vida.

Introduction Vaccination is an effective, relatively inexpensive, and easy to deliver approach to combating infectious diseases. Widespread vaccination of children has led to the eradication of smallpox and allowed for regional elimination or control of diseases like polio, measles, mumps, tetanus, diphtheria, and whooping cough. But, as we learned from efforts to combat the COVID-19 pandemic, a successful global vaccination program must overcome several hurdles. Failure at any stage can limit vaccine uptake and disease control. Areas covered In this review, we break down the vaccine journey from research and development to delivery into several steps. We also list all the important international organizations trying to support this ecosystem. Then we identify the role of each of these organizations in supporting each of the necessary steps for a successful vaccination program. Expert opinion The bottlenecks in vaccination can be different for different countries, based on their income and geography. Policy makers need to identify the weaknesses of this ecosystem in different regions of the world and make sure there is adequate global and local support to fill the gaps in the system.

Pitch spaces allow pitch relations to be expressed through geometrical representations for many different purposes. The Tonnetz is a well-known pitch space in the field of music theory; equivalent representations have been described in the field of cognitive science, especially Krumhansl's model of perceived triadic distance. Despite her empirical approach, we know very little about the way people interact, cognitively speaking, with Tonnetz -based computational platforms involving multimodal stimuli. Our study has approached this issue by means of empirical experimentation for the first time. A total of 88 participants, with varying backgrounds in music and mathematics, were asked to interact with a Tonnetz interface; they did not have prior knowledge of this pitch space. Results of our experiment confirmed our main hypotheses. On the one hand, strong skills in music theory are needed to partially grasp the overall structure of the Tonnetz at first sight; this aspect is mainly related to the quality recognition of triads and the detection of shared pitch classes in harmonic motions. On the other hand, the particular geometry of the Tonnetz may bias this understanding when non-functional harmonic sequences are displayed on it.

El Cromolín Sódico 4% gotas nasales es un antinflamatorio bronquial e inhibidor de los mastocitos en el tratamiento de la rinitis alérgica. En el presente estudio se validó un método por cromatografía líquida de alta resolución para evaluar el comportamiento analítico y la estabilidad del Cromolín Sódico 4 % gotas nasales. El método se basó en la separación del principio activo a través una columna cromatográfica Apollo-C8; 5 µm; 150 mm x 4,6 mm; con detección ultravioleta a 326 nm, para lo cual se preparó la fase móvil A y B; consistentes en fase móvil A: disolución de hidrógeno sulfato de tetrabutilamonio (10 g/L), acetonitrilo (95:5) y fase móvil B: disolución de hidrógeno sulfato de tetrabutilamonio (10 g/L), acetonitrilo, metanol (50: 25:25); con una velocidad de flujo de 1,5 mL/min. La curva de calibración se realizó en el intervalo de concentración de 1,25 a 1,87 10-4 mol/L, (del 80% hasta el 120%) del ingrediente farmacéutico activo en el producto terminado. El método fue lineal, preciso y exacto en el intervalo de concentraciones estudiadas. Además, fue específico frente a los restantes componentes de la matriz y a los posibles productos de degradación obtenidos en condiciones de estrés

Acquiring information on consumer preferences for the sensory properties of pomegranates is a cue for breeding programmes to set their quality targets and promote the consumption of this particularly healthy fruit. In this study, a total of 12 pomegranate varieties were evaluated, including commercial (Valenciana, Illina, Tastem, Rugalate, Wonderful, Mollar 49 y Mollar 45) and new varieties (Ref 102, Ref 383, H3/27, and D27/12). For the first time, consumers not only scored their acceptance of different pomegranate varieties but also described their sensory properties using CATA questions. This approach allowed us to identify the main drivers of liking, preference patterns, and the relationship between sensory and physico-chemical properties. Of all the sensory attributes, acidity intensity was revealed as the main driver of liking/disliking, and two different consumer preference patterns were identified: ‘low acid pomegranate lovers’ and ‘acid pomegranate lovers’. Seed properties like the intensity of woody flavour and seed/aril ratio were also key drivers for preferences. A relationship between sensory and physico-chemical properties was also established. Interestingly, sweetness perception correlated more strongly with low titratable acidity levels than with high total soluble solids levels, corroborating that acidity level is a key measurement for quality assessments. ‘H3/27’ was the most promising of the new varieties for having the well-appreciated internal properties of the ‘Mollar’ varieties and external and internal red colouration, which makes it much more appealing to consumers. This study shows that there is still room on the market for pomegranate varieties with very different sensory properties and highlights the need to develop sensory labels that help consumers make the right choices.

Teleost IgT/Z plays a principal role in the defense mechanisms against infectious agents in the mucosal compartments and in systemic immunity. Previously, Nile tilapia (Oreochromis niloticus) IgT was discovered and characterized at transcription level. In this work, we generated a monoclonal antibody (mAb) that specifically recognized the Nile tilapia IgT. BALB/c mice were immunized with three synthetic peptides conjugated to KLH. The sequences of these peptides derived from the constant region of the Nile tilapia IgT heavy chain. ELISA and Western blotting confirmed the specificity of the polyclonal sera and the culture supernatant from a positive hybridoma clone. We observed immunoreactivity against a recombinant IgT fragment and native IgT in skin mucus. The anti-IgT mAb did not cross-react with purified tilapia IgM. Direct ELISA analysis allowed the quantification of skin mucus IgM and IgT concentrations. Flow cytometry analysis revealed differences in the percentage of IgT+ B cell populations between juveniles and adults in peripheral blood, head kidney and spleen lymphocytes and among the tissues analyzed. For further validation of the anti-IgT mAb utility, a recombinant vaccine candidate against sea lice (TT-P0 Ls) was injected into juvenile tilapia. Direct ELISA results revealed a differential secretion of skin mucus IgT and IgM after immunostimulation. In addition, the percentages of IgT+ B cells were determined at 7 days after booster and ex-vivo stimulation by flow cytometry. This mAb constitutes an important immunological tool to study the biological function and structural characteristics of tilapia IgT.

Kluyveromyces marxianus is an emerging host for metabolic engineering. This thermotolerant yeast is the fastest growing eukaryote, has high flux through the TCA cycle, and can metabolize a broad range of C5, C6, and C12 carbon sources. In comparison to the common host Saccharomyces cerevisiae, this non-conventional yeast suffers from a lack of metabolic engineering tools to control gene expression over a wide transcriptional range. To address this issue, we designed a library of 25 native-derived promoters from K. marxanius CBS6556 that spans 87-fold transcriptional strength under glucose metabolism. Six promoters from the library were further characterized in both glucose and xylose as well as across various temperatures from 30 to 45 ​°C. The temperature study revealed that in most cases EGFP expression decreased with elevating temperature; however, two promoters, P SSA3 and P ADH1 , increased expression above 40 ​°C in both xylose and glucose. The six-promoter set was also validated in xylose for triacetic acid lactone (TAL) production. By controlling the expression level of heterologous 2-pyrone synthase (2-PS), the specific TAL titer increased over 8-fold at 37 ​°C. Cultures at 41 ​°C exhibited a similar TAL biosynthesis capability, while at 30 ​°C TAL levels were lower. Taken together, these results advance the metabolic engineering tool set in K. marxianus and further develop this new host for chemical biosynthesis.

In response to the challenges introduced by global warming and increased eutrophication, this paper presents an innovative modeling and simulation (M&S)-driven model for developing an automated inland water monitoring system. This system is grounded in a layered Internet of Things (IoT) architecture and seamlessly integrates cloud, fog, and edge computing to enable sophisticated, real-time environmental surveillance and prediction of harmful algal and cyanobacterial blooms (HACBs). Utilizing autonomous boats as mobile data collection units within the edge layer, the system efficiently tracks algae and cyanobacteria proliferation and relays critical data upward through the architecture. These data feed into advanced inference models within the cloud layer, which inform predictive algorithms in the fog layer, orchestrating subsequent data-gathering missions. This paper also details a complete development environment that facilitates the system lifecycle from concept to deployment. The modular design is powered by Discrete Event System Specification (DEVS) and offers unparalleled adaptability, allowing developers to simulate, validate, and deploy modules incrementally and cutting across traditional developmental phases.

Mid-gesture interfaces have become popular for specific scenarios, such as interactions with augmented reality via head-mounted displays, specific controls over smartphones, or gaming platforms. This article explores the use of a location-aware mid-air gesture-based command triplet syntax to interact with a smart space. The syntax, inspired by human language, is built as a vocative case with an imperative structure. In a sentence like “Light, please switch on!”, the object being activated is invoked via making a gesture that mimics its initial letter/acronym (vocative, coincident with the sentence’s elliptical subject). A geometrical or directional gesture then identifies the action (imperative verb) and may include an object feature or a second object with which to network (complement), which also represented by the initial or acronym letter. Technically, an interpreter relying on a trainable multidevice gesture recognition layer makes the pair/triplet syntax decoding possible. The recognition layer works on acceleration and position input signals from graspable (smartphone) and free-hand devices (smartwatch and external depth cameras), as well as a specific compiler. On a specific deployment at a Living Lab facility, the syntax has been instantiated via the use of a lexicon derived from English (with respect to the initial letters and acronyms). A within-subject analysis with twelve users has enabled the analysis of the syntax acceptance (in terms of usability, gesture agreement for actions over objects, and social acceptance) and technology preference of the gesture syntax within its three device implementations (graspable, wearable, and device-free ones). Participants express consensus regarding the simplicity of learning the syntax and its potential effectiveness in managing smart resources. Socially, participants favoured the Watch for outdoor activities and the Phone for home and work settings, underscoring the importance of social context in technology design. The Phone emerged as the preferred option for gesture recognition due to its efficiency and familiarity. The system, which can be adapted to different sensing technologies, addresses the scalability concerns (as it can be easily extended for new objects and actions) and allows for personalised interaction.

Objetivo: En pacientes con enfermedad de Alzheimer (EA) se han descrito cambios neuropatológicos tempranos en la corteza entorrinal, que anteceden el compromiso temporomesial. La evaluación de la atrofia hipocampal mediante escalas visuales y volumetría son herramientas útiles en la valoración de pacientes con deterioro cognitivo. Nuestro objetivo es establecer la correlación entre la evaluación visual de la atrofia de la corteza entorrinal (ACE), la atrofia temporomesial (ATM) y el volumen hipocampal. Material y métodos: Estudio retrospectivo de corte transversal. Se incluyeron pacientes con queja cognitiva y resonancia magnética (RM) cerebral. Se utilizaron escalas visuales de ACE y ATM. Se midió el volumen hipocampal mediante el software volBrain 1.0. Resultados: Se incluyeron 48 pacientes, 31 eran mujeres (64,6%). Mediana de edad: 76,5 (RIQ: 69-83). La correlación entre las escalas visuales ACE y la ATM del lado derecho fue de 0,67 p < 0,0001) y del lado izquierdo de 0,69 (p < 0,0001). Encontramos correlación negativa moderada entre la ACE y el volumen hipocampal, del lado derecho fue de –0,59 (p < 0,0001) y del lado izquierdo de –0,42 (p = 0,003). Conclusión: La escala de ACE muestra moderada correlación con la escala de ATM y con el volumen hipocampal. Su uso podría aportar información valiosa para valoración de trastornos cognitivos.

IntroductionThe antinociceptive and pharmacological activities of C-Phycocyanin (C-PC) and Phycocyanobilin (PCB) in the context of inflammatory arthritis remain unexplored so far. In the present study, we aimed to assess the protective actions of these compounds in an experimental mice model that replicates key aspects of human rheumatoid arthritis.MethodsAntigen-induced arthritis (AIA) was established by intradermal injection of methylated bovine serum albumin in C57BL/6 mice, and one hour before the antigen challenge, either C-PC (2, 4, or 8 mg/kg) or PCB (0.1 or 1 mg/kg) were administered intraperitoneally. Proteome profiling was also conducted on glutamate-exposed SH-SY5Y neuronal cells to evaluate the PCB impact on this key signaling pathway associated with nociceptive neuronal sensitization.Results and discussionC-PC and PCB notably ameliorated hypernociception, synovial neutrophil infiltration, myeloperoxidase activity, and the periarticular cytokine concentration of IFN-γ, TNF-α, IL-17A, and IL-4 dose-dependently in AIA mice. In addition, 1 mg/kg PCB downregulated the gene expression for T-bet, RORγ, and IFN-γ in the popliteal lymph nodes, accompanied by a significant reduction in the pathological arthritic index of AIA mice. Noteworthy, neuronal proteome analysis revealed that PCB modulated biological processes such as pain, inflammation, and glutamatergic transmission, all of which are involved in arthritic pathology.ConclusionsThese findings demonstrate the remarkable efficacy of PCB in alleviating the nociception and inflammation in the AIA mice model and shed new light on mechanisms underlying the PCB modulation of the neuronal proteome. This research work opens a new avenue to explore the translational potential of PCB in developing a therapeutic strategy for inflammation and pain in rheumatoid arthritis.

Este artículo presenta el laboratorio remoto diseñado en la Universidad Complutense de Madrid (UCM) para dar acceso remoto, a través de Internet, al robot educativo Dobot Magician. El software del laboratorio remoto está formado por el servidor web ReNoLabs (programado en Node.js) que gestiona el acceso al laboratorio, despliega sus páginas web, y sirve como pasarela de comunicación entre el software de control (programado en Python) que interactúa directamente con el robot) y la interfaz gráfica web de la experiencia (diseñada en EJsS). EJsS también se utiliza para gestionar de forma centralizada el laboratorio, al haber ampliado su funcionalidad mediante un Plugin. Además, el software anterior, creado con herramientas software gratuitas, se ejecuta sobre una Raspberry Pi y el interfaz web de la experiencia puede integrarse, si así se desea, en un sistema de gestión de aprendizaje general como Moodle. Finalmente, el artículo también presenta un par de ejemplos de uso del laboratorio remoto.

Objetivo: El objetivo del tratamiento en accidente cerebrovascular (ACV) isquémico agudo es restablecer la circulación en el área de la penumbra isquémica. La secuencia de susceptibilidad (SWI) puede detectar cambios en el calibre de las venas intracraneanas cuando se altera la relación desoxiHb/oxiHb en áreas hipoperfundidas, lo que permitiría una detección temprana de penumbra isquémica. Material y métodos: Estudio de cohorte retrospectivo. Se incluyeron pacientes con infartos agudos en territorio de la arteria cerebral media. Se evaluaron las secuencias difusión y SWI iniciales y un estudio de control a los siete días. La extensión del ACV se midió con la escala ASPECT en difusión y SWI del ingreso, y en el estudio de control. Se estableció una discordancia SWI/difusión > 2 puntos como variable predictora y la extensión final del infarto como variable de resultado. Resultados: Se incluyeron 31 pacientes, mediana de edad de 72 años (RIC: 61-81). En 13 pacientes se detectó una oclusión vascular proximal, ocho de los cuales tenían discordancia SWI/difusión > 2 puntos (p < 0,0001). En cinco pacientes encontramos incremento del infarto, cuatro con discordancia SWI/difusión (p = 0,01). Conclusión: La presencia de discordancia SWI/difusión puede ser un biomarcador de penumbra isquémica en pacientes con oclusión vascular proximal.

During mammalian embryogenesis, de novo hematopoiesis occurs transiently in multiple anatomical sites including the yolk sac, dorsal aorta, and heart tube. A long-unanswered question is whether these local transient hematopoietic mechanisms are essential for embryonic growth. Here, we show that endocardial hematopoiesis is critical for cardiac valve remodeling as a source of tissue macrophages. Colony formation assay from explanted heart tubes and genetic lineage tracing with the endocardial specific Nfatc1-Cre mouse revealed that hemogenic endocardium is a de novo source of tissue macrophages in the endocardial cushion, the primordium of the cardiac valves. Surface marker characterization, gene expression profiling, and ex vivo phagocytosis assay revealed that the endocardially derived cardiac tissue macrophages play a phagocytic and antigen presenting role. Indeed, genetic ablation of endocardially derived macrophages caused severe valve malformation. Together, these data suggest that transient hemogenic activity in the endocardium is indispensable for the valvular tissue remodeling in the heart.

This article aims to show how some elements of musical self-analysis may reveal significant cognitive issues about composition. For this purpose, I first draft a methodological framework that mainly borrows from some considerations about semiology in neuroscience and cognitive linguistics fields applied to music by Stefan Koelsch and Lawrence M. Zbikowski. Next, I use this framework for scrutinizing José Manuel López López’s Viento de otoño [Autumn wind] (1998) alongside disparate sources by the composer directly related to its composition. This case study analysis entails a better grasping of the composer’s creative practices and an evaluation of the potential and limits of my methodological framework.

This paper summarizes in depth the state of the art of aerial swarms, covering both classical and new reinforcement-learning-based approaches for their management. Then, it proposes a hybrid AI system, integrating deep reinforcement learning in a multi-agent centralized swarm architecture. The proposed system is tailored to perform surveillance of a specific area, searching and tracking ground targets, for security and law enforcement applications. The swarm is governed by a central swarm controller responsible for distributing different search and tracking tasks among the cooperating UAVs. Each UAV agent is then controlled by a collection of cooperative sub-agents, whose behaviors have been trained using different deep reinforcement learning models, tailored for the different task types proposed by the swarm controller. More specifically, proximal policy optimization (PPO) algorithms were used to train the agents’ behavior. In addition, several metrics to assess the performance of the swarm in this application were defined. The results obtained through simulation show that our system searches the operation area effectively, acquires the targets in a reasonable time, and is capable of tracking them continuously and consistently.

In a prepurchase situation, consumers base their choice decision on external fruit characteristics, from which they infer internal characteristics. This study investigates consumer preference for pomegranate appearance using a choice-based conjoint analysis with 320 participants. We created 27 images of pomegranates that differed in varietal characteristics: colour (yellow, bicoloured, and red), shape (round, oval, and flattened), and calyx shape (open, semi-open, and closed). Colour was by far the most important factor for consumers, followed by fruit shape and calyx shape. Two preference profiles were identified. Most consumers liked bicolour and red pomegranates equally, and rejected yellow ones, while a smaller group concentrated their choice on bicolour pomegranates. In terms of fruit and calyx shape, oval and flattened fruit and open calyx were the most preferred by both consumer groups. Barriers and drivers for consumption were also investigated. There is still plenty of room to increase pomegranate consumption. Greater availability of pomegranates and ready-to-eat arils in grocery shops, obtaining new unseeded/easier-to-peel varieties, and providing a sensory label would help to overcome current barriers. Marketing campaigns should focus on a pomegranate’s health benefits and its versatility in consumption.

Abstract Background Perinatal mental health problems, defined as mental health problems occurring from the start of pregnancy to one year after birth, substantially affect women's and children's quality of life in low- and middle-income countries. In South Africa, despite high prevalence and documented negative impacts, most women do not receive any care. Methods A modelling study examined the costs of perinatal mental health problems, namely depression and anxiety, for a hypothetical cohort of women and their children in South Africa over part of their life course (10 years for women, 40 years for children). In sensitivity analysis, additional impacts of post-traumatic stress disorder (PTSD) and completed suicide were included. Data sources were published findings from cohort studies, as well as epidemiological and economic data from South Africa. Data from international studies were considered where no data from South Africa were available. Results Lifetime costs of perinatal depression and anxiety in South Africa amount to USD 2.8 billion per annual cohort of births. If the impacts of PTSD and suicide are included, costs increase to USD 2.9 billion. This includes costs linked to losses in quality of life (USD 1.8 billion), losses in income (USD 1.1 billion) and public sector costs (USD 3.5 million). Conclusions Whilst important progress has been made in South Africa with regards to mental health policies and interventions that include assessment and management of perinatal mental health problems, substantial underinvestment prevents progress. Findings from this study strengthen the economic case for investing in perinatal mental health care.

Abstract Background Primary care services in South Africa have been challenged by increasing numbers of people with communicable and non-communicable chronic diseases. There was a need to develop alternative approaches for stable patients to access medication. With the onset of the coronavirus pandemic there was an urgent need to decongest facilities and protect people from infection. In this crisis the Metro Health Services rapidly implemented home delivery of medication by community health workers. This study aimed to evaluate the implementation of home delivery of medication by community health workers during the coronavirus pandemic in Cape Town, South Africa. Methods A convergent mixed methods study evaluated six implementation outcomes: adoption, feasibility, fidelity, coverage, cost, and sustainability of the initiative. Data sources included routinely collected data, a telephonic survey of 138 patients, an analysis of set-up and recurrent costs as well as 17 descriptive exploratory qualitative semi-structured interviews with 68 key informants. Results Over a 6-month period 1,054,657 pre-packaged parcels were sent to primary care facilities, 819,649 (77.7%) were delivered and of those 97,297 (11.9%) returned. The additional costs were estimated as 1.3% of a total health budget of R2,2 billion. The initiative was rapidly adopted as it decongested facilities and protected vulnerable patients. Although it was feasible to implement at scale, numerous challenges were encountered, such as incorrect addresses and contact details, transporting parcels, communicating with patients, having a reliable audit trail, and handling out-of-area patients. All role players thought the service should continue and 42.3% of patients reported better adherence to their medication. Conclusion Home delivery of medication by community health workers is feasible at scale and affordable. It should continue, but as one of a menu of options for alternative delivery of medication. The following need to be improved: efficiency of the system, the audit trail, adequate support and resources for community health workers, transport of medication, communication with patients, empanelment of patients, governance of the system and training of the community health workers.

Introduction: Helicobacter pylori is the main risk factor for the development of chronic atrophic gastritis and intestinal-type gastric cancer. Objective: Identify preneoplastic gastric lesions in patients with Helicobacter pylori. Methods: A descriptive, cross-sectional study was carried out, which included 167 patients with Helicobacter pylori infection, diagnosed by endoscopy with gastric biopsy in the antrum and body (anterior and posterior sides) and in the angular notch. The variables included were: Helicobacter pylori infection and preneoplastic gastric lesions. Absolute frequency and percentage were used as summary measures for qualitative variables. To evaluate the association between qualitative variables, the chi-square test (χ2) was applied, with a level of statistical significance p≤ 0,05. Development: Of 167 patients evaluated, 150 (89,82 %) had gastric atrophy, 42 (25,14 %) intestinal metaplasia, and 66 (39,52 %) low-grade dysplasia. No patients with high-grade dysplasia were found. Moderate chronic gastritis prevailed (83; 49,7 %). Of the 22 patients in stage III, 17 (10,2 %) had severe chronic gastritis. Lymphoepithelial reaction was found in 138 (83 %) patients with gastric atrophy. Conclusions: Gastric atrophy is the most common preneoplastic lesion in patients with Helicobacter pylori and non-advanced stages of it predominate. Intestinal metaplasia and dysplasia occur less frequently.

Abstract Background Failure to take medicines for diabetes as prescribed contributes to poor outcomes from the condition. Mobile phones are ubiquitous and short message service (SMS) texts have shown promise as a low-cost intervention. We tested the effectiveness of SMS-text messaging in improving outcomes in adults with type 2 diabetes. Methods StAR2D was a 12-month two-arm randomised trial of SMS-text messaging and usual care in Cape Town, South Africa and Lilongwe, Malawi. Messages used behaviour change theory and were developed with patients and staff. The intervention group received four messages each week. The primary outcome was change in HbA1c. Secondary outcomes were the proportion of patients who collected > 80% medication and changes in systolic blood pressure, lipids, cardiovascular risk, and the proportion of the participants reaching treatment goals. Results The trial took place between 1 October, 2016 and 1 October 2018, 1186 participants were randomised to intervention (593) and control (593) groups. 91% of participants completed follow-up. There was a reduction in HbA1c (DCCT) in both groups but not in mean change (95% CI) between groups (− 0.08% (− 0.31 to 0.16) (IFCC − 0.82 mmol/mol (− 3.44 to 1.79). There was a small but not significant increase in the proportions of participants likely to have collected 80% or more of medication (Relative risk 1.11 (0.84 to 1.47; P = 0.47). There was a significant difference between groups in change in systolic blood pressure from baseline of 3.46 mmHg (1.48 to 5.44, P = 0.001) in favour of the intervention group. The between group difference in change in 10-year risk of coronary heart disease was − 0.71% (− 1.46 to 0.04, P = 0.064). The proportion of participants meeting treatment goals in the intervention group was 36.0% and in the control group 26.8% (Relative risk 1.36 (1.13 to 1.63, P = 0.001). Participants reported many challenges to adherence despite finding messages acceptable and useful. Conclusions Whilst SMS text messages do not lead to improved glycaemia in these low-resource settings there appeared to be an impact on blood pressure and achievement of treatment goals but the mechanisms for this are unclear. Text messages alone, may be unsuccessful unless accompanied by health system strengthening and other forms of self-management support for type 2 diabetes. Trial registration Trial registration: ISRCTN, ISRCTN70768808. Registered 1 July 2015, http://www.isrctn.com/I ISRCTN70768808.

Introducción: El sistema OLGA considera a la atrofia gástrica como la lesión histopatológica representativa de progresión de la gastritis crónica, que es el denominador común en la inducción del cáncer. Objetivo: Identificar lesiones precursoras de cáncer gástrico. Métodos: Se realizó un estudio descriptivo, que incluyó 190 pacientes con dispepsia. Los resultados se expresaron en números absolutos y porcientos. Para evaluar la asociación de la atrofia gástrica con el reflujo duodenogástrico y la infección por Helicobacter pylori se aplicó el test ji cuadrado (χ2). Se aceptó un nivel de significación estadística p≤ 0,05. Resultados: El 94,2 % de los pacientes tenía gastritis eritematosa. El estadio II fue el más frecuente en los menores de 50 años (54,1 %) y en los mayores (48,5 %). En ambos grupos de edad se encontraron pacientes en estadio III (10,7 % en los menores de 50 años y 16,1 % en los mayores de 50 años). En el estadio II, 27 (62,8 %) pacientes tenían metaplasia intestinal. La displasia de bajo grado fue encontrada con mayor frecuencia en el estadio II (46; 54,2 %). De los pacientes con atrofia 11 (91,7 %; p= 0,75626) y 159 (89,4 %; p= 0,43719) presentaban reflujo duodenogástrico e infección por Helicobacter pylori, respectivamente. Conclusiones: La prevalencia de etapas avanzadas de atrofia gástrica es baja. La metaplasia intestinal y la displasia de bajo grado son más frecuentes en el estadio II de OLGA. No se detectan pacientes con displasia de alto grado.

Valorization of persimmon discards is a current challenge for the food industry. Obtaining dehydrated persimmon products can be a good option, but studies are necessary to predict consumer responses before placing new products on the market. In this study, we produced dried slices, chips, leathers and powder from persimmons that were discarded at harvest. A consumer study was performed with 100 participants. For a realistic context, the four products were presented to the participants in specifically designed packages to simulate commercial packages. The participants were asked about their interest in having each product available on the market. Then, they were asked to taste the samples and to state their acceptance and purchase intention. The participants characterized the main sensory properties of the samples using the CATA questions. The consumption contexts evoked by each product were also investigated based on the item-by-use method, plus the CATA questions. Our results revealed that, before tasting the samples, the participants showed special interest in having chips and slices available on the market. After tasting, the participants reported very good acceptance of chips, slices and powder, but leathers were less liked. According to the consumer characterizations, slices had the most intense persimmon taste and a succulent texture, while powder was characterized by its caramel taste. Chips were differentiated from the other samples, mainly for their crispy texture, while leathers were sticky and tasteless, which explained their poor acceptance. By evaluating the data on acceptance and the evoked consumption contexts together, we conclude that persimmon consumption could be enhanced by commercializing slices, chips and powder. The participants described chips and slices as healthy snacks in different daily situations, while powder could be used as a sweetener for yoghurts or hot drinks and as an ingredient for baking desserts. These are all contexts in which fresh persimmon would be not consumed as reported by the participants.

Background: Diabetic nephropathy is considered one of the most common microvascular complications. Insulin resistance and impaired insulin secretion are very important in the pathogenesis, It can be suggested that increased platelet volume may be an important factor in the enhanced risk of vascular complications. Patients and Method: This study included 50 diabetic patients, 50 diabetic patients with nephropathy & 50 healthy age and sex-matched subjects as controls. Blood samples were obtained for CBC, Anticoagulated blood (ethylene diamine tetracetic acid) was collected and analyzed in an automated blood cell counter for platelet count and indices (MPV, PDW, P-LCC & P-LCR), Glucose, HbA1c, Kidney function (creatinine & urea), Albumin/creatinine ratio & lipid profile (cholesterol, triglyceride, HDL, LDL & VLDL) were also done. Results: MPV, PDW and P-LCR were all significantly higher in diabetic patients compared to the control subjectswith (P= 0.001, 0.05, 0.02 respectively). Among the diabetics, MPV was higher in diabetic patient with nephropathy as compared to those without nephropathy (P= 0.001). Conclusions:Platelet indices, especially MPV were different between diabetics and controls as well as diabetic nephropathy. Discriminant analysis using MPV and PDW could classify majority of patients with nephropathy.

Abstract Background Despite existing research on text mining and machine learning for title and abstract screening, the role of machine learning within systematic literature reviews (SLRs) for health technology assessment (HTA) remains unclear given lack of extensive testing and of guidance from HTA agencies. We sought to address two knowledge gaps: to extend ML algorithms to provide a reason for exclusion—to align with current practices—and to determine optimal parameter settings for feature-set generation and ML algorithms. Methods We used abstract and full-text selection data from five large SLRs (n = 3089 to 12,769 abstracts) across a variety of disease areas. Each SLR was split into training and test sets. We developed a multi-step algorithm to categorize each citation into the following categories: included; excluded for each PICOS criterion; or unclassified. We used a bag-of-words approach for feature-set generation and compared machine learning algorithms using support vector machines (SVMs), naïve Bayes (NB), and bagged classification and regression trees (CART) for classification. We also compared alternative training set strategies: using full data versus downsampling (i.e., reducing excludes to balance includes/excludes because machine learning algorithms perform better with balanced data), and using inclusion/exclusion decisions from abstract versus full-text screening. Performance comparisons were in terms of specificity, sensitivity, accuracy, and matching the reason for exclusion. Results The best-fitting model (optimized sensitivity and specificity) was based on the SVM algorithm using training data based on full-text decisions, downsampling, and excluding words occurring fewer than five times. The sensitivity and specificity of this model ranged from 94 to 100%, and 54 to 89%, respectively, across the five SLRs. On average, 75% of excluded citations were excluded with a reason and 83% of these citations matched the reviewers’ original reason for exclusion. Sensitivity significantly improved when both downsampling and abstract decisions were used. Conclusions ML algorithms can improve the efficiency of the SLR process and the proposed algorithms could reduce the workload of a second reviewer by identifying exclusions with a relevant PICOS reason, thus aligning with HTA guidance. Downsampling can be used to improve study selection, and improvements using full-text exclusions have implications for a learn-as-you-go approach.

Introducción. El CIGB-300 es un péptido antitumoral inhibidor de la fosforilación de los sus- tratos de la proteína quinasa CK2. El presente trabajo persigue como objetivo fundamental exponer nuevos elementos vinculados al mecanismo antineoplásico del CIGB-300 relacio- nados con el modo de inhibición de dicha fosforilación y la sinergia del péptido con drogas anticáncer. Métodos. Se realizaron ensayos de fosforilación mediada por la subunidad cata- lítica CK2α o la holoenzima en presencia o no del CIGB-300. La interacción CIGB-300/CK2 se verificó mediante ensayos de pull-down, colocalización in situ y además se realizó un análisis fosfoproteómico en células de cáncer de pulmón tratadas con el péptido. El sinergismo del CIGB-300 y las drogas anticáncer se evaluó in vitro y en el caso del cisplatino también in vivo. Además, se realizó un estudio de proteómica comparativa de la combinación del CIGB-300 con el cisplatino.Resultados. El CIGB-300 interaccionó directamente con la subunidad CK2α e inhibió la actividad de la holoenzima en diferentes condiciones experimentales. Asimismo, el análisis de fosfoproteómica y Western blot permitió conocer el perfil de inhibición tempra- na de CK2 por el CIGB-300 a los 10 min y 30 min Adicionalmente, el CIGB-300 sinergizó con quimioterapéuticos e inhibidores del receptor del factor de crecimiento epidérmico (EGFR) y se conocieron los eventos moleculares que pueden sustentar la sinergia del péptido con las drogas anticáncer estudiadas. Como conclusiones, el CIGB-300 inhibe la fosforilación mediada por CK2 a través de un mecanismo alternativo de interacción directa con la enzima. Además, sinergiza con quimioterapéuticos e inhibidores del EGFR, modulando diferentes proteínas relacionadas con la resistencia a dichas drogas.

Objetivo: Describir los hallazgos en resonancia magnética (RM) en lesiones intralaberínticas. Método: Se incluyeron pacientes evaluados entre enero de 2012 y marzo de 2019 que se sometieron a una RM del oído interno. Se recogieron datos demográficos y de imagen. Las RM incluyeron secuencias ponderadas en T2 de alta resolución (T2 AR), secuencias ponderadas en T1 sin contraste (T1 SC) y secuencias ponderadas en T1 con contraste (T1 CC). Resultados: Se analizaron las imágenes de RM de 23 pacientes con una mediana de edad de 60 años (rango: 43-73). Encontramos 8 (34,8%) pacientes con neurinoma intralaberíntico, 7 (30,4%) con laberintitis inflamatoria, 5 (21,7%) con laberintitis osificante y 3 (13%) con hemorragia intralaberíntica. Todos los pacientes con neurinoma intralaberíntico tenían una baja señal en la secuencias T2 AR, ligera hiperseñal en las secuencias T1 SC y realce poscontraste. Tres pacientes (42,5%) con laberintitis inflamatoria tenían baja señal en las secuencias T2 AR y 5 (71%) tenían realce en las secuencias T1 CC. Los pacientes con laberintitis osificante tenían una baja señal en las secuencias T2 AR y los pacientes con hemorragia tenían una señal alta en las secuencias T1 SC. Los pacientes con neurinoma intralaberíntico tenían señal más baja en T2 AR que los pacientes con laberintitis inflamatoria (p = 0,026). Conclusiones: Existen diferentes condiciones que pueden alterar la señal del laberinto en la RM. El patrón radiológico permite establecer su diagnóstico. La investigación proporciona información relevante para la interpretación de las alteraciones de la señal del laberinto membranoso en la RM.

Introducción: El esófago de Barrett es una lesión del esófago con elevado potencial degenerativo; para su diagnóstico se requiere la confirmación histológica de metaplasia intestinal en el esófago. Objetivo: Determinar la prevalencia del esófago de Barrett y las características epidemiológicas de los pacientes con esta afección. Métodos: Se realizó un estudio observacional descriptivo, entre enero del 2018 y junio del 2019, en 14 pacientes con diagnóstico histológico de esófago de Barrett. Las variables estudiadas fueron: edad, sexo, color de la piel, antecedentes epidemiológicos, síntomas y signos, longitud del segmento, de acuerdo con la clasificación de Sharma y presencia de hernia hiatal. Se realizó el diagnóstico histológico según la clasificación de Viena. Se determinó la prevalencia respecto del total de endoscopias digestivas altas realizadas en el periodo; emplearon de estadísticas descriptivas. Resultados: Se obtuvo una prevalencia de 0,37 %. El sexo masculino (78,6 %) y el color de piel blanca (71,4 %) predominaron; la edad media fue de 51,64 años. El consumo de tabaco fue referido por el 50 % de los pacientes. Los síntomas típicos de reflujo gastroesofágico, regurgitación (64,3 %) y pirosis (42,9 %) fueron los más frecuentes. La variedad de segmento corto fue la más observada y la hernia hiatal se encontró en 28,6 % de los casos. Conclusiones: Predominan las características epidemiológicas de ser pacientes masculinos, color de piel blanca, entre la 5ta y 6ta décadas de la vida y síntomas típicos de enfermedad por reflujo gastroesofágico. La prevalencia de la afección es baja.

Protein kinase CK2 is a highly pleiotropic and ubiquitously expressed Ser/Thr kinase with instrumental roles in normal and pathological states, including neoplastic phenotype in solid tumor and hematological malignancies. In line with previous reports, CK2 has been suggested as an attractive prognostic marker and molecular target in acute myeloid leukemia (AML), a blood malignant disorder that remains as an unmet medical need. Accordingly, this work investigates the complex landscape of molecular and cellular perturbations supporting the antileukemic effect exerted by CK2 inhibition in AML cells. To identify and functionally characterize the proteomic profile differentially modulated by the CK2 peptide-based inhibitor CIGB-300, we carried out LC-MS/MS and bioinformatic analysis in human cell lines representing two differentiation stages and major AML subtypes. Using this approach, 109 and 129 proteins were identified as significantly modulated in HL-60 and OCI-AML3 cells, respectively. In both proteomic profiles, proteins related to apoptotic cell death, cell cycle progression, and transcriptional/translational processes appeared represented, in agreement with previous results showing the impact of CIGB-300 in AML cell proliferation and viability. Of note, a group of proteins involved in intracellular redox homeostasis was specifically identified in HL-60 cell-regulated proteome, and flow cytometric analysis also confirmed a differential effect of CIGB-300 over reactive oxygen species (ROS) production in AML cells. Thus, oxidative stress might play a relevant role on CIGB-300-induced apoptosis in HL-60 but not in OCI-AML3 cells. Importantly, these findings provide first-hand insights concerning the CIGB-300 antileukemic effect and draw attention to the existence of both common and tailored response patterns triggered by CK2 inhibition in different AML backgrounds, a phenomenon of particular relevance with regard to the pharmacologic blockade of CK2 and personalized medicine.

Persimmon cultivation has significantly grown in the Mediterranean Region in recent years. The production concentrates mainly in three astringent cultivars: Kaki Tipo in Italy, Triumph in Israel, and Rojo Brillante in Spain. Therefore, the varietal range expansion is one of the current challenges for persimmon producers in this area. Moreover, the introduction of nonastringent persimmon cultivars is particularly interesting because they can be commercialized immediately after harvest without applying deastringency treatment before commercialization. This study evaluated the harvest period and the postharvest response of six Japanese nonastringent cultivars (Kanshu, Shinshu, Soshu, Suruga, Youhou, Izu). During two seasons, fruit from each cultivar were harvested at two maturity stages. Fruit quality (external color, firmness, and total soluble solids) was evaluated after harvest and after different commercial scenarios (domestic market: 7 days at 20 °C, market to European Union (EU): 5 days at 5 °C plus 5 days at 20 °C, and market to countries with cold-quarantine treatment requirements: 21 days at 0 °C plus 5 days at 20 °C). Cultivars Kanshu, Shinshu, Soshu, and Izu were identified as early cultivars, and Soshu was the earliest one, which reached commercial maturity at the beginning of September. These four cultivars showed good quality after simulating commercialization on domestic and EU markets. Cultivars Suruga and Youhou overlapped the current harvest window, but their low chilling injury sensitiveness is highlighted, so they are of special interest to be cold-stored at the end of the season to be commercialized in overseas markets.