Towards carotenoid biofortification in wheat: identification of XAT-7A1, a multicopy tandem gene responsible for carotenoid esterification in durum wheat.

Yellow pigment content, mainly due to the accumulation of carotenoids, is a quality trait in durum wheat grain as it confers the bright yellow color to pasta preferred by consumers. Also, carotenoids are essential nutrients exerting important biological functions in human health. Consequently, biofortification strategies have been developed in many crops to increase carotenoid content. In this context, carotenoid esterification is emerging as a new breeding target for wheat biofortification, as carotenoid esters have been found to promote both carotenoid accumulation and stability. Until recently, no carotenoid esters have been identified in significant proportions in durum wheat grains, and interspecific breeding programs have been started to transfer esterification ability from common wheat and Hordeum chilense.In this work, XAT-7A1 is identified as the gene responsible for carotenoid esterification in durum wheat. Sequencing, copy number variation and mapping results show that XAT-7A1 is organized as tandem or proximal GDSL esterase/lipase copies in chromosome 7A. Three XAT-7A1 haplotypes are described: Type 1 copies, associated with high levels of carotenoid esters (diesters and monoesters) production and high expression in grain development; Type 2 copies, present in landraces with low levels of carotenoid esters (monoesters) or no esters; and Type 3 copies, without the signal peptide, resulting in zero-ester phenotypes.The identification of XAT-7A1 is a necessary step to make the carotenoid esterification ability available for durum and bread wheat breeding, which should be focused on the Type 1 XAT-7A1 haplotype, which may be assessed as a single gene since XAT-7A1 copies are inherited together.

A Systematic Review of the Factors Associated with Post-Traumatic Growth in Parents Following Admission of Their Child to the Intensive Care Unit.

This systematic review aims to identify the demographic, clinical and psychological factors associated with post-traumatic growth (PTG) in parents following their child's admission to the intensive care unit (ICU). Papers published up to September 2021 were identified following a search of electronic databases (PubMed, Medline, Web of Science, PsycINFO, CINAHL, PTSDpubs and EMBASE). Studies were included if they involved a sample of parents whose children were previously admitted to ICU and reported correlational data. 1777 papers were reviewed. Fourteen studies were eligible for inclusion; four were deemed to be of good methodological quality, two were poor, and the remaining eight studies were fair. Factors associated with PTG were identified. Mothers, and parents of older children, experienced greater PTG. Parents who perceived their child's illness as more severe had greater PTG. Strong associations were uncovered between PTG and post-traumatic stress, psychological well-being and coping. PTG is commonly experienced by this population. Psychological factors are more commonly associated with PTG in comparison with demographic and clinical factors, suggesting that parents' subjective ICU experience may be greater associated with PTG than the objective reality.

Chatbots to Support People With Dementia and Their Caregivers: Systematic Review of Functions and Quality.

BACKGROUND: Over the past decade, there has been an increase in the use of information technologies to educate and support people with dementia and their family caregivers. At the same time, chatbot technologies have become increasingly popular for use by the public and have been identified as having benefits for health care delivery. However, little is known about how chatbot technologies may benefit people with dementia and their caregivers. OBJECTIVE: This study aims to identify the types of current commercially available chatbots that are designed for use by people with dementia and their caregivers and to assess their quality in terms of features and content. METHODS: Chatbots were identified through a systematic search on Google Play Store, Apple App Store, Alexa Skills, and the internet. An evidence-based assessment tool was used to evaluate the features and content of the identified apps. The assessment was conducted through interrater agreement among 4 separate reviewers. RESULTS: Of the 505 initial chatbots identified, 6 were included in the review. The chatbots assessed varied significantly in terms of content and scope. Although the chatbots were generally found to be easy to use, some limitations were noted regarding their performance and programmed content for dialog. CONCLUSIONS: Although chatbot technologies are well established and commonly used by the public, their development for people with dementia and their caregivers is in its infancy. Given the successful use of chatbots in other health care settings and for other applications, there are opportunities to integrate this technology into dementia care. However, more evidence-based chatbots that have undergone end user evaluation are needed to evaluate their potential to adequately educate and support these populations.

Survival in adult inpatients with COVID-19.

BACKGROUND: The mortality of the coronavirus disease 2019 (COVID-19) pandemic is high, and data regarding its prognosis are scarce. We aimed to assess the survival experience and determining factors in adult inpatients with laboratory-confirmed COVID-19. METHODS: We conducted a nationwide and retrospective cohort study. Data from 66,123 individuals were analyzed using the Kaplan-Meier method, and a multivariate Cox proportional hazard regression model was fitted. RESULTS: The 7-day survival was 72.2% and went to 47.6%, 35.0%, and 23.9% on days 15, 21, and 30 of hospital stay, respectively. In the multiple analysis, factors associated with an increased risk of dying were male gender, age, pneumonia at hospital admission, immunosuppression, and personal history of chronic non-communicable diseases. Reduced risk of a fatal outcome was observed among patients with asthma history. CONCLUSIONS: To the best of our knowledge, this is the largest study analyzing the survival probability in a large subset of Latin-American adults with COVID-19, in whom the disease burden has been high. Our results contribute to achieving a better understanding of disease evolution.

Predictors of severe symptomatic laboratory-confirmed SARS-CoV-2 reinfection.

OBJECTIVE: The aim of the study was to evaluate factors predicting severe symptomatic laboratory-confirmed (via Reverse transcription polymerase chain reaction, RT-PCR polymerase chain reaction) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection. STUDY DESIGN: This is a nationwide retrospective cohort study that was conducted in Mexico. METHODS: Data from 258 reinfection cases (at least 28 days between both episodes onset) were analyzed. We used risk ratios (RRs) and 95% confidence intervals (CIs) to evaluate predictors of severe (dyspnea requiring hospital admission) secondary SARS-CoV-2 infection. RESULTS: The risk of severe disease was 14.7%, and the observed overall fatality rate was 4.3%. Patients with more serious primary disease were more likely to develop severe symptoms (39.5% vs. 5.5%, P < 0.001) during reinfection. In multiple analysis, factors associated with an increased risk of severe symptomatic SARS-CoV-2 reinfection were increasing age (RRper year = 1.007, 95% CI = 1.003-1.010), comorbidities (namely, obesity [RR = 1.12, 95% CI = 1.01-1.24], asthma [RR = 1.26, 95% CI = 1.06-1.50], type 2 diabetes mellitus [RR = 1.22, 95% CI = 1.07-1.38]), and previous severe laboratory-confirmed coronavirus disease 2019 (RR = 1.20, 95% CI = 1.03-1.39). CONCLUSIONS: To the best of our knowledge, this is the first study evaluating disease outcomes in a large set of laboratory-positive cases of symptomatic SARS-CoV-2 reinfection, and factors associated with illness severity were characterized. Our results may contribute to the current knowledge of SARS-CoV-2 pathogenicity and to identify populations at increased risk of a poorer outcome after reinfection.

Survival in adult pneumonia inpatients fulfilling suspected COVID-19 criteria and baseline negative RT-qPCR.

OBJECTIVES: The objective of this study was to evaluate the survival experience of suspicion COVID-19 hospitalized patients with pneumonia and negative baseline reverse-transcription quantitative polymerase chain reaction (RT-qPCR) test results. STUDY DESIGN: We conducted a nationwide retrospective cohort study in Mexico. METHODS: Adult pneumonia inpatients fulfilling suspected COVID-19 criteria, and hospital entry from March to August 2020, were enrolled. The Kaplan-Meier method was to use to compare survival estimates among patients with negative RT-qPCR nasopharyngeal or oropharyngeal swabs and those with a baseline positive test. RESULTS: Data from 64,624 individuals fulfilling suspected COVID-19 criteria were analyzed and 1.6% of them had negative RT-qPCR tests. The overall mortality rate was higher among laboratory-positive patients (48.5% vs. 34.2%, P < 0.001) and, at any given threshold, the survival estimates were higher among RT-qPCR-negative pneumonia inpatients. CONCLUSIONS: The pathogenic mechanism of COVID-19 remains poorly understood and suspected cases with pneumonia and negative laboratory results represent a major challenge for healthcare systems. Our findings suggest that RT-qPCR-negative inpatients may have an improved disease prognosis, but the in-hospital mortality was still high among them. However, further research is needed to clarify the clinical and epidemiological implications of our results.

[Performance of the case definition of suspected influenza before and during the COVID-19 pandemic]. / Desempeño de la definición de caso sospechoso de influenza antes y durante la pandemia por COVID-19.

OBJECTIVE: This study aimed to evaluate the performance, before and during the COVID-19 pandemic, of the case definition of suspected influenza used in community surveillance in Mexico. METHODS: A cross-sectional analysis of a cohort study was perfomed and cases that met the suspected case criteria (n = 20,511) and that had laboratory-conclusive evidence (quantitative real-time polymerase chain reaction) to confirm or discard influenza virus infection, were analysed. RESULTS: A high sensitivity and modest specificity were documented, which later decreased during the COVID-19 outbreak, as well as its diagnostic accuracy. However, no significant differences were observed in the area under the receiver operating characteristics curve among the analysed periods. CONCLUSION: The evaluated case definition remains to be a cost-effective alternative for identifying patients who may benefit from influenza-specific antiviral drugs, even during the global COVID-19 outbreak.

Predictors of laboratory-positive COVID-19 in children and teenagers.

OBJECTIVE: The aim of the study was to identify factors predicting laboratory-positive coronavirus disease 2019 (COVID-19) in pediatric patients with acute respiratory symptoms. STUDY DESIGN: We conducted a cross-sectional analysis of a prospective cohort study. METHODS: Data from 1849 individuals were analyzed. COVID-19 was confirmed (reverse transcription-quantitative polymerase chain reaction) in 15.9% of patients, and factors predicting a positive test result were evaluated through prevalence odds ratios and 95% confidence intervals. RESULTS: Increasing age, personal history of obesity, and household contact with a case were found to be associated, in the multiple regression model, with increased odds of a positive test result. Young patients residing in areas with higher population sizes, as well as those with severe respiratory symptoms, were less likely to be laboratory confirmed. CONCLUSIONS: Early identification and isolation of children and teenagers with suggestive symptoms of COVID-19 is important to limit viral spread. We identified several factors predicting the laboratory test result. Our findings are relevant from a public health policy perspective, particularly after the restart of in-person academic activities.

Characteristics of adults with Down syndrome hospitalised in Spanish internal medicine departments during 2005-2014. / Características de los adultos con síndrome de Down ingresados en los servicios de medicina interna españoles en el periodo 2005-2014.

INTRODUCTION AND OBJECTIVES: The clinical problems of adults with Down syndrome seem to differ from those of the general population. To better understand these differences, we list the demographic and clinical characteristics of adults with Down syndrome admitted to Spanish internal medicine departments during 2005-2014. PATIENTS AND METHODS: We conducted an observational retrospective study using data collected from the minimum basic data set on hospitalisation episodes of adults with Down syndrome in the internal medicine departments of Spain's National Health System from 2005 to 2014. We analysed the patients' epidemiological, clinical and societal data. RESULTS: A total of 7548 hospitalisation episodes from 3786 patients were recorded. Some 56.6% of the patients were male with a mean age (±SD) of 47±13 years, and 715 of the patients died (18.9%). The age-adjusted mortality was 26.6%, and the mean stay was 9.6±12 days. The hospitalisation was for respiratory disease in 3684 episodes (48.8%) and for cardiac origin in 760 (10%). The most common comorbidities were hypothyroidism (27.1%, 2043 episodes), epilepsy (24.1%, 1819 episodes) and dementia (15.4%, 1162 episodes). CONCLUSIONS: The hospitalisation of adults with Down syndrome in internal medicine departments has increased in the past decade. Although the reasons for hospitalisation, mean stay and cost per episode for this population are similar to those of the general population treated by internal medicine departments, the age-adjusted hospital mortality was significantly greater.

Assessing the relationship between markers of glycemic control through flexible copula regression models.

Glycated haemoglobin (HbA1c) is a sensitive marker of blood glucose in patients with diabetes. However, levels can vary considerably, even amongst individuals with similar mean blood glucose concentrations. Other glycated proteins, such as fructosamine, can also act as blood sugar markers, but estimating HbA1c and fructosamine via independent models may lead to errors of interpretation regarding disease severity. From a clinical standpoint, it would be of great interest to know the factors that affect the mean concentration of both HbA1c and fructosamine, which influence the variability in the concentrations of these glycated markers and cause HbA1c/fructosamine discordance. Flexible models are required to illustrate the behaviour of these variables as well as the association between them. This work reviews existing models that might serve in this regard. Flexible copula regression models using splines were used to provide a better understanding of the behaviour of both glycated proteins and the relationship between them under the possible influence of different covariates. This work shows the usefulness of this type of models in practise and provides a basis for their clinical interpretation by means of an understandable case study. Ultimately, to better understand the effects of each continuous covariate, they are represented at the true scale of the response variables.

Design and development of low cost polyurethane biopolymer based on castor oil and glycerol for biomedical applications.

In the current study, we present the synthesis of novel low cost bio-polyurethane compositions with variable mechanical properties based on castor oil and glycerol for biomedical applications. A detailed investigation of the physicochemical properties of the polymer was carried out by using mechanical testing, ATR-FTIR, and X-ray photoelectron spectroscopy (XPS). Polymers were also tested in short term in-vitro cell culture with human mesenchymal stem cells to evaluate their biocompatibility for potential applications as biomaterial. FTIR analysis confirmed the synthesis of castor oil and glycerol based PU polymers. FTIR also showed that the addition of glycerol as co-polyol increases crosslinking within the polymer backbone hence enhancing the bulk mechanical properties of the polymer. XPS data showed that glycerol incorporation leads to an enrichment of oxidized organic species on the surface of the polymers. Preliminary investigation into in vitro biocompatibility showed that serum protein adsorption can be controlled by varying the glycerol content with polymer backbone. An alamar blue assay looking at the metabolic activity of the cells indicated that castor oil based PU and its variants containing glycerol are non-toxic to the cells. This study opens an avenue for using low cost bio-polyurethane based on castor oil and glycerol for biomedical applications.

Interindividual differences in the clinical effectiveness of liraglutide in Type 2 diabetes: a real-world retrospective study conducted in Spain.

AIMS: To study the response of clinical variables (HbA1c , body weight, lipid profile and blood pressure) over 24 months of liraglutide treatment in a real-world clinical setting, and to describe the evolution of HbA1c and body weight reduction in response to liraglutide treatment by employing generalized additive mixed models (GAMMs). METHODS: We included people aged ≥ 18 years with Type 2 diabetes mellitus that initiated liraglutide treatment between November 2011 and May 2015. Demographic and clinical data were retrieved retrospectively over 24 months from electronic medical records with a median duration of observation of 7.0 (IQR 3.0-12.0) months. RESULTS: Individuals that initiated liraglutide therapy were obese (BMI 39.1 kg/m2 ), with inadequate HbA1c (68 mmol/mol [8.4%]), blood pressure and lipid levels. Upon liraglutide treatment, HbA1c , body weight, mean systolic and diastolic blood pressure, and lipid levels decreased gradually. GAMMs demonstrated that longer treatment with liraglutide was a predictor of improved HbA1c response, whereas higher baseline HbA1c , longer Type 2 diabetes duration and treatment with insulin were predictors of worse HbA1c response. Higher baseline weight, longer treatment with liraglutide and the interaction between metformin and time were predictors of improved weight response. CONCLUSIONS: In this real-world study, we showed the effectiveness of liraglutide in improving body weight, HbA1c , mean systolic and diastolic blood pressure, and lipid levels. GAMMs indicated that baseline HbA1c and weight, time of treatment with liraglutide, diabetes duration and the use of metformin or insulin are predictors of clinical response to liraglutide.

Comparisons of the topographic characteristics and electrical charge distributions among Babesia-infected erythrocytes and extraerythrocytic merozoites using AFM.

Tick-borne Babesia parasites are responsible for costly diseases worldwide. Improved control and prevention tools are urgently needed, but development of such tools is limited by numerous gaps in knowledge of the parasite-host relationships. We hereby used atomic force microscopy (AFM) and frequency-modulated Kelvin probe potential microscopy (FM-KPFM) techniques to compare size, texture, roughness and surface potential of normal and infected Babesia bovis, B. bigemina and B. caballi erythrocytes to better understand the physical properties of these parasites. In addition, AFM and FM-KPFM allowed a detailed view of extraerythrocytic merozoites revealing shape, topography and surface potential of paired and single parasites. B. bovis-infected erythrocytes display distinct surface texture and overall roughness compared to noninfected erythrocytes. Interestingly, B. caballi-infected erythrocytes do not display the surface ridges typical in B. bovis parasites. Observations of extraerythrocytic B. bovis, B. bigemina and B. caballi merozoites using AFM revealed differences in size and shape between these three parasites. Finally, similar to what was previously observed for Plasmodium-infected erythrocytes, FM-KPFM images reveal an unequal electric charge distribution, with higher surface potential above the erythrocyte regions that are likely associated with Babesia parasites than over its remainder regions. In addition, the surface potential of paired extraerythrocytic B. bovis Mo7 merozoites revealed an asymmetric potential distribution. These observations may be important to better understand the unique cytoadhesive properties of B. bovis-infected erythrocytes, and to speculate on the role of differences in the distribution of surface charges in the biology of the parasites.

Recommendations for the management of comorbidity in hidradenitis suppurativa.

BACKGROUND: The association between hidradenitis suppurativa (HS) and some diseases is becoming relevant in recent years. Providing appropriate management of HS from an early stage requires to include prompt diagnosis and treatment of concomitant diseases and to prevent any potential comorbidity. This approach should consider the adverse events of the drugs used to treat HS potentially related to the onset of a comorbidity. OBJECTIVE: To provide the dermatologist with an accurate, easily used tool that will inform the diagnosis of HS comorbidity, and to facilitate decision-making regarding the referral and treatment of patient with HS-associated comorbidity. METHODS: These recommendations have been developed by a working group composed of seven experts (three dermatologists, a cardiovascular specialist internist, a rheumatologist expert in spondyloarthritis, a gastroenterologist and a psychiatrist) and a team of three methodologist researchers. The expert group selected the HS comorbidities considered in these recommendations through a literature review. The recommendations on diagnostic criteria are based on the relevant clinical practice guidelines for each of the comorbidities and on the recommendations of the experts. The information regarding the repercussion of HS medical treatments on associated comorbid diseases was obtained from the summary of product characteristics of each drug. RESULTS: The comorbidities considered in this guide are as follows: cardiovascular risk factors (diabetes, dyslipidaemia, obesity, hypertension and metabolic syndrome), inflammatory bowel disease, inflammatory joint disorders and psychological disorders (anxiety and depression). In addition, the association between HS and the consumption of alcohol and tobacco is included. The tables and figures are a precise, easy-to-use tool to systematize the diagnosis of comorbidity in patients with HS and facilitate the decision-making process regarding referral and treatment of patients with an associated disease. CONCLUSION: The application of these recommendations will facilitate the dermatologist practice and benefit HS patients' health and quality of life.

Optimum Sample Size to Estimate Mean Parasite Abundance in Fish Parasite Surveys.

To reach ethically and scientifically valid mean abundance values in parasitological and epidemiological studies this paper considers analytic and simulation approaches for sample size determination. The sample size estimation was carried out by applying mathematical formula with predetermined precision level and parameter of the negative binomial distribution estimated from the empirical data. A simulation approach to optimum sample size determination aimed at the estimation of true value of the mean abundance and its confidence interval (CI) was based on the Bag of Little Bootstraps (BLB). The abundance of two species of monogenean parasites Ligophorus cephali and L. mediterraneus from Mugil cephalus across the Azov-Black Seas localities were subjected to the analysis. The dispersion pattern of both helminth species could be characterized as a highly aggregated distribution with the variance being substantially larger than the mean abundance. The holistic approach applied here offers a wide range of appropriate methods in searching for the optimum sample size and the understanding about the expected precision level of the mean. Given the superior performance of the BLB relative to formulae with its few assumptions, the bootstrap procedure is the preferred method. Two important assessments were performed in the present study: i) based on CIs width a reasonable precision level for the mean abundance in parasitological surveys of Ligophorus spp. could be chosen between 0.8 and 0.5 with 1.6 and 1x mean of the CIs width, and ii) the sample size equal 80 or more host individuals allows accurate and precise estimation of mean abundance. Meanwhile for the host sample size in range between 25 and 40 individuals, the median estimates showed minimal bias but the sampling distribution skewed to the low values; a sample size of 10 host individuals yielded to unreliable estimates.

[Conservative management of traumatic priapism in paediatric patients]. / Manejo conservador del priapismo traumático en la edad pediátrica.

INTRODUCTION: High-flow priapism is infrequent in pediatric patients. It is mostly secondary to perineal trauma resulting in laceration of a penile artery and the formation of an arterio-cavernous fistula. It does not constitute a medical emergency in itself, and allows conservative management awaiting spontaneous resolution. CLINICAL CASE: A six-year-old boy with painless persistent erection preceded by perineal trauma. Ultrasound imaging confirmed the clinical suspicion of high flow priapism secondary to arterio-cavernous fistula. After adopting a conservative approach, the patient presented progressive detumescence, as well as ultrasound resolution one month after the episode. COMMENTS: In high-flow priapism, venous drainage of the penis is preserved. The classical approach in adults is based on therapeutic angiography, which presents greater technical complexity and the risk of iatrogenic hypoxia in pediatric patients.

INTRODUCCION: El priapismo de alto flujo es una entidad infrecuente en la edad pediátrica. Es, en su mayoría, secundario a traumatismo perineal que provoca la laceración de una arteria peneana y formación de una fístula arterio-cavernosa. No constituye una emergencia médica, permitiendo un manejo conservador a la espera de su resolución espontánea. CASO CLINICO: Niño de seis años con erección persistente e indolora tras traumatismo perineal. El diagnóstico ecográfico confirma la sospecha de priapismo de alto flujo secundario a fístula arteria-cavernosa. Tras manejo conservador, presenta detumescencia progresiva y resolución ecográfica al mes del episodio. COMENTARIOS: En el priapismo de alto flujo el drenaje venoso del pene se encuentra conservado. El manejo clásico en adultos se fundamenta en la angiografía terapéutica, de mayor complejidad técnica y riesgo de hipoxia iatrogénica en el paciente pediátrico.

New advances in genitourinary cancer: evidence gathered in 2014.

This review provides updated information published in 2014 regarding advances and major achievements in genitourinary cancer. Sections include the best in prostate cancer, renal cancer, bladder cancer, and germ cell tumors. In the field of prostate cancer, data related to treatment approach of hormone-sensitive disease, castrate-resistant prostate cancer, mechanisms of resistance, new drugs, and molecular research are presented. In relation to renal cancer, relevant aspects in the treatment of advanced renal cell carcinoma, immunotherapy, and molecular research, including angiogenesis and von Hippel-Lindau gene, molecular biology of non-clear cell histologies, and epigenetics of clear renal cell cancer are described. New strategies in the management of muscle-invasive localized bladder cancer and metastatic disease are reported as well as salient findings of biomolecular research in urothelial cancer. Some approaches intended to improve outcomes in poor prognosis patients with metastatic germ cell cancer are also reported. Results of clinical trials in these areas are discussed.

Clinical Pathway for Patients with Acute or Chronic Urticaria: A Consensus Statement of the Andalusian Section of the Spanish Academy of Dermatology and Venereology (AEDV). / Proceso de atención al paciente con urticaria aguda y crónica. Documento de consenso de la sección territorial andaluza de la Academia Española de Dermatología y Venereología.

Attention has been focused on new ways to understand and manage urticaria ever since the recent addition of novel drugs to the therapeutic arsenal, the updating of clinical practice guidelines, and the publication of pathophysiologic insights. The Andalusian Section of the Spanish Academy of Dermatology and Venereology (AEDV) has developed a clinical pathway that defines quality-of-care characteristics and makes recommendations on decision-making affecting patients with urticaria. We present a patient-centered approach to care, in which the patient's clinical pathway through the health care system includes links between primary and hospital care to ensure continuity-a key feature of quality.