Inter- and trans-generational effects of gestational ghrelin imbalance on development and reproduction in the mouse.

CONTEXT AND AIMS: We have demonstrated that ghrelin (Ghrl) participates in fetal programming, since intragestational hyperghrelinaemia increased pup's growth and a Ghrl-receptor antagonist accelerated offspring's sexual maturation and impaired their adult reproductive function. Now, we aim to analyse if these phenotypic changes (found in F1) also occurred in F2 and/or F3 generations. METHODS: We treated mice dams (F0), with 4nmol/animal/day of Ghrl or 6nmol/animal/day of an antagonist [Ant:(d -Lys3)GHRP6] from day 1 of pregnancy until delivery. When F1 female pups reached adulthood, they were paired to obtain F2, and subsequently, F2 females were paired to obtain F3. Parameters evaluated in F2 and F3 pups were: growth, physical development, neurobiological maturation, puberty onset and in adulthood, reproductive function. KEY RESULTS: The F2 and F3 Ant groups showed a significant increase in litter size. Although no differences were detected in the weight of these pups at birth, in adulthood, they were heavier. At F3, pups from the Ant group showed advanced incisors eruption and eye opening compared to controls. Furthermore, F3 male pups from the Ant group showed earlier testis descent, although in adulthood, these males exhibited reduced sperm concentration in comparison to Ghrl. No differences were detected in F2 or F3 females regarding puberty onset or reproduction. CONCLUSIONS AND IMPLICATIONS: Some fetal programming effects of Ghrl seen in F1, also appeared transgenerationally. Since many women at reproductive age suffer from conditions with reduced Ghrl levels (i.e. obesity or polycystic ovarian syndrome), these results could be relevant to the health of their descendants.

Is seminal quality worsening? A 20-year experience in Córdoba, Argentina.

PURPOSE: To assess the possible variations in semen quality during the last 20 years in Córdoba, Argentina, and to identify possible causal lifestyle or genitourinary factors. METHODS: Retrospective study of 23,130 patients attending an andrology laboratory. The 20-year period (2001-2020) was divided into four quinquenniums. Seminal parameters (sperm concentration, motility, morphology, viability, and membrane functional integrity) were classified as normal or abnormal according to WHO, and results were expressed as percentage of patients abnormal for each parameter per quinquennium. In addition, the percentage of patients per quinquennium exposed to the different risk factors (daily alcohol and/or tobacco consumption; occupational exposure to heat or toxics; history of parotitis or varicocele; and high body mass index, BMI) was reported. RESULTS: Patients included in our study did not show impairment in seminal quality over time. Beyond a transient decrease in normozoospermia in the second and third quinquennium, possibly explained by a parallel increase in teratozoospermia, other important parameters of the spermogram did not change. In fact, abnormalities in sperm concentration (oligozoospermia), total sperm count, viability and response to hypoosmotic test showed a decreasing trend over time. On the other hand, parotitis, varicocele, morbid obesity and regular exposition to heat/toxics were the factors more frequently associated with semen abnormalities; the last two increased their frequency over the study period. CONCLUSION: The population included in this study did not show a clear impairment in semen quality during the last 20 years. The decreasing patterns found were associated with high BMI and exposure to heat/toxics.

Do aging, drinking, and having unhealthy weight have a synergistic impact on semen quality?

PURPOSE: To evaluate if age, alcohol consumption, and body mass index (BMI) have synergistic effects on seminal quality, and to rank these factors based on their impact on semen. METHODS: Retrospective study of 9464 patients attending an andrology laboratory. Data on patients' age and daily alcohol intake were provided by the patients. BMI was recorded in the laboratory. Seminal parameters evaluated were volume, sperm concentration and total count, motility, morphology, viability, nuclear maturity, and membrane functional integrity. RESULTS: All the seminal parameters evaluated were affected by the synergistic interaction Age x BMI, suggesting that this combination is more potent in affecting semen quality. The variables sperm morphology and nuclear maturity seemed to be especially susceptible since they were affected by the three synergistic interactions. In the logistic regression analysis, age was the most powerful factor since it impacted first on five of the nine parameters, impacting mainly on sperm motility, viability, and morphology, with no effects on sperm count. On the contrary, BMI impacted first in sperm concentration and total sperm count; which was confirmed also by the logistic predictions analysis. Alcohol consumption impacted first on membrane functional integrity and nuclear maturity. A J-shaped association between BMI or alcohol consumption with semen quality was found in the multivariate analysis. CONCLUSION: The factors considered in this study showed a synergistic negative impact on semen quality, being age and unhealthy weight the most important ones. Reducing the exposure to lifestyle risk factors may be promising for improving sperm quality in infertile patients.

Recategorisation of body mass index to achieve andrological predictive power: a study in more than 20 000 patients.

The aim of this study was to recategorise body mass index (BMI) in order to classify patients according to their risk of semen abnormalities. Patients (n=20563) presenting at an andrology laboratory were classified into five groups according to BMI: underweight (BMI <20kg m-2), normal weight (BMI 20-24.9kg m-2), overweight (BMI 25-29.9kg m-2), obese (BMI 30-39.9kg m-2) and morbidly obese (BMI >40kg m-2). Semen quality was evaluated to determine: (1) differences between groups using analysis of variance (ANOVA); (2) the chances of semen abnormalities (using generalised linear models, Chi-squared tests and odds ratios); (3) reference BMI values with andrological predictive power (multivariate conglomerate analyses and multivariate analysis of variance (MANOVA)); and (4) expected values of abnormalities for each new group resulting from BMI recategorisation. Morbidly obese and underweight patients exhibited the highest decrease in semen quality and had higher chances of semen abnormalities. The smallest number of sperm abnormalities was found at a BMI of 27kg m-2. Four reference values were identified, recategorising BMI into four groups according to their risk of semen abnormalities (from lowest to highest risk): Group1,BMI between 20 and 32kg m-2; Group2, BMI <20 and BMI >32-37kg m-2; Group3, BMI >37-42kg m-2; and Group4, BMI >42kg m-2. A BMI <20 or >32kg m-2 is negatively associated with semen quality; these negative associations on semen quality increase from a BMI >37kg m-2 and increase even further for BMI >42kg m-2. The BMI recategorisation in this study has andrological predictive power.

Association Between Vitamin D Status and Schizophrenia: A First Psychotic Episode Study.

Vitamin D deficiency has been linked with schizophrenia. We aimed to determine whether patients with a first episode of psychosis (FEP) had lower vitamin D levels compared with controls considering their final diagnosis. We conducted a cross-sectional study determining 25-hydroxyvitamin D blood levels. 25-Hydroxyvitamin D levels were considered optimum at 20 ng/mL or greater. A group of 45 adult patients with FEP and a group of 22 healthy controls matched for age were recruited. The patient group was subdivided in two final diagnosis groups (schizophrenia versus other psychoses) after a 6-month follow-up. Average vitamin D values were deficient for FEP patients, especially those 22 with a final diagnosis of schizophrenia. These results relating vitamin D and schizophrenia generate interest to further examine this association.

Milk yield and lactation stage are associated with positive results to ELISA for Mycobacterium avium subsp. paratuberculosis in dairy cows from Northern Antioquia, Colombia: a preliminary study.

Paratuberculosis is a slow-developing infectious disease characterized by chronic granulomatous enterocolitis. This disease has a variable incubation period from 6 months to over 15 years and is caused by Mycobacterium avium subsp. paratuberculosis (MAP). Some studies have been conducted in cattle during the last decades in Colombia. However, those studies were designed using relatively small populations and were not aimed to establish prevalence. This study aimed to determine the MAP seroprevalence in selected dairy herds and to explore risk factors associated with the serology results. Serum samples and related data were collected from 696 randomly selected bovines in 28 dairy herds located in 12 different districts in one of the main dairy municipalities in Colombia (San Pedro de los Milagros). The samples were analyzed using a commercial ELISA kit. The information on risk factors was analyzed using a logistic regression. The apparent seroprevalence was 3.6 % (1/28) at the herd level and 2 % (14/696) at the animal level. The number of days in milk production between 100 and 200 days, and over 200 days as well as the daily milk production between 20 and 40 L/cow, and over 40 L/cow were associated with MAP seropositivity with odds ratios of 4.42, 3.45, 2.53, and 20.38, respectively. This study demonstrates the MAP seroprevalence in dairy herds from Antioquia, Colombia and the possible relationship between MAP seropositivity, milk yield, and lactation stage.

Childhood trauma in Chronic Fatigue Syndrome: focus on personality disorders and psychopathology.

INTRODUCTION: Personality Disorders (PDs) and childhood traumatic experiences have been considered risk factors for Chronic Fatigue Syndrome (CFS). However, the relationship between these factors and their associated psychopathological impact has not been explored in this population. This study was designed to evaluate the association between different childhood traumas and the presence and number of PDs and current psychopathology in a sample of CFS patients. MATERIAL AND METHODS: For this purpose, 166 CFS patients were evaluated with the Personality Diagnostic Questionnaire-4+ (PDQ-4+) and the Child Trauma Questionnaire. Other instruments were used to assess the associated psychopathology and the impact of fatigue. RESULTS: Of the total sample, 55 (33.1%) presented childhood trauma, the most frequent of which were emotional neglect (21.7%) and emotional abuse (18.1%). Considering PD presence, 79 (47.6%) patients presented some PD. There were no differences in frequency of physical childhood trauma in patients with and without PD. However, patients with PD had more frequently experienced emotional childhood trauma (OR=2.18, p=0.034). Severity of childhood trauma was related to a higher number of PDs, more severe depressive symptoms (p=0.025) and suicide risk (p=0.001). Patients with PD and any childhood trauma presented more severe depressive and irritable symptoms and a higher suicide risk than those without any PD and non-childhood traumatic event. These patients' psychopathological symptoms were similar to those of patients with childhood trauma and without PD. CONCLUSIONS: These results suggest that emotional childhood trauma but not physical childhood trauma is related to higher frequency of PD presence. More severe childhood emotional and physical traumas are related to a higher number of PDs and to more severe psychopathological symptoms.

Substance Use in Patients With First-Episode Psychosis: Is Gender Relevant?

OBJECTIVE: Only a few studies in patients with first-episode psychosis have included gender in the study hypothesis or considered this a primary study variable. The aim of this study was to explore the influence of gender in the pattern of substance use in patients with first-episode psychosis. METHODS: This is a sub-analysis of a randomized open clinical trial that compared 1-year treatment retention rates of patients with first-episode psychosis randomized to haloperidol, olanzapine, quetiapine, risperidone, or ziprasidone. Our sub-analysis included 85 men and 29 women. RESULTS: Substance use was relatively high among these patients and differed significantly by gender. Men were more likely to use substances overall than women (89.4% for men vs. 55.2% for women), χ(2) = 16.2, df = 1, p <.001, and were also more likely to use alcohol (χ(2) = 13, df = 1, p <.001), cannabis (χ(2) = 9.9; df = 1, p <.002), and cocaine (χ(2) = 10.3; df = 1, p <.001), compared to women. While there were no gender differences in age at first consumption of alcohol or cocaine, men were significantly younger at first consumption of cannabis (M = 16.08 years, SD = 2.1) than women (M = 18.0 years, SD = 3.8), F(1, 59) = 5, p <.02. When analyzed separately by gender, women showed no significant differences in the influence of number of substances used on age at onset of psychosis, F(3, 29) = 1.2, p =.30. However, there was a significant difference among men, with earlier onset of psychosis noted in men consuming multiple substances; F(4, 85) = 5.8, p <.0001. Regarding prediction of age at onset of psychosis, both male gender and the use of a higher number of substances significantly predicted an earlier age at onset of psychosis. CONCLUSIONS: Our study provides some evidence of gender differences in the pattern of substance use in patients with first-episode psychosis, suggesting the possible need for gender-specific approaches in the interventions performed in these patients. This study is registered as #12610000954022 with the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au).

Prevalence of migraine in patients with restless legs syndrome: a case-control study.

OBJECTIVES: To assess and compare the prevalence of migraine in patients with restless legs syndrome (RLS) and matched controls. BACKGROUND: Recent studies have suggested an association between migraine and RLS. Our work is the first case-control study on this subject performed in an RLS population. METHODS: A case-control study was conducted in 47 RLS patients (27 women and 20 men aged between 18 and 65 years) and 47 age- and sex-matched controls. Validated questionnaires were used to investigate the presence of migraine, anxiety, and depression (Zung Self-Rating Anxiety and Depression scales), sleep quality (Pittsburgh Sleep Quality Index), and RLS severity (International RLS scale). RESULTS: RLS patients had higher lifetime prevalence of migraine than non-RLS controls (53.2% vs. 25.5%, P = .005; matched-OR 1.3 [P = .019]; adjusted odds ratio (OR) 3.8 [P = .03]). No significant associations were found between RLS and active migraine with aura or inactive migraine (no episodes in the previous year). However, active migraine without aura was significantly more prevalent in patients with RLS than in controls (40.4% vs. 12.8%, P = .001; matched OR 1.5 [P = .001]; adjusted OR 2.7 [P = .04]). Within the RLS group, patients with migraine had poorer sleep quality than those without migraine (Pittsburgh Sleep Quality Index >5:100 vs. 80.9%, P = .038) but did not differ in terms of RLS severity, anxiety and depression, use of dopaminergic agonists, and body mass index. CONCLUSION: There appears to be a relationship between RLS and migraine, in particular for active migraine without aura.

Systematic review of the prevalence of paratuberculosis in cattle, sheep, and goats in Latin America and the Caribbean.

Mycobacterium avium subsp. paratuberculosis causes paratuberculosis or Johne's disease (JD) in domestic ruminants and wild species. The aim of the present study was to systematically review the prevalence of paratuberculosis among farmed animals (cattle, sheep, and goats) in Latin America and the Caribbean. The initial search for existing publications reporting systematic reviews and primary studies was carried out by searching the available databases. For the final selection of studies, an initial screen for basic eligibility and a detailed appraisal of quality were performed. After study selection, the relevant data were extracted. The detailed appraisal generated 24 publications that reported 52 studies, of which 73.1, 11.5, and 15.4 % were from cattle, sheep, and goats, respectively. Thirty-three (63.5 %) of the studies were animal level studies, while 19 (36.5 %) were herd-/flock-level studies. No flock-level studies on prevalence in sheep were found. Studies in Latin American and Caribbean countries revealed an overall prevalence of 16.9 (95 % CI (confidence interval) 13.2-20.5) and 75.8 % (95 % CI 50.1-101.5) in cattle at the animal and herd levels, respectively; the prevalence was 16 % (95 % CI 7.9-24.1) in sheep at the animal level and 4.3 % (95 % CI 1.9-6.8) and 3.7 % (95 % CI 0.1-7.4) in goats at the animal and flock levels, respectively. In general, prevalence results reported by the studies were insufficient to accurately determine the prevalence of paratuberculosis in farmed animals in Latin America and the Caribbean. Several flaws in the design of studies limit the quality of evidence regarding the prevalence of paratuberculosis in the region.

Pharmacological Management of Acute and Chronic Insomnia: A Cross-Sectional Study.

OBJECTIVE: Insomnia is a frequent and difficult disease to treat. The objective was to determine the pharmacological management of a group of patients diagnosed with acute and chronic insomnia. METHODS: This is a cross-sectional study that identified patterns of prescription of drugs for outpatient use in patients with insomnia from a population database of 8.5 million individuals in the Health System of Colombia. Sociodemographic and pharmacological variables were considered. RESULTS: A total of 5825 patients with insomnia were identified. Acute insomnia was the most frequent complaint (85.2%). A total of 76.9% received pharmacological treatment, mainly through off-label drugs (70.7%), such as trazodone (20.2%), quetiapine (12.3%), and clonazepam (11.1%). The approved drugs were used in 9.9% of the patients, especially eszopiclone (4.7%) and zopiclone (3.6%). Benzodiazepines and Z compounds predominated in the elderly and individuals with chronic insomnia. CONCLUSIONS: The pharmacological treatment of insomnia in this group of patients is heterogeneous, and medications not approved for this indication are very frequently used.

AI-driven remote sensing enhances Mediterranean seagrass monitoring and conservation to combat climate change and anthropogenic impacts.

Seagrasses are undergoing widespread loss due to anthropogenic pressure and climate change. Since 1960, the Mediterranean seascape lost 13-50% of the areal extent of its dominant and endemic seagrass-Posidonia oceanica, which regulates its ecosystem. Many conservation and restoration projects failed due to poor site selection and lack of long-term monitoring. Here, we present a fast and efficient operational approach based on a deep-learning artificial intelligence model using Sentinel-2 data to map the spatial extent of the meadows, enabling short and long-term monitoring, and identifying the impacts of natural and human-induced stressors and changes at different timescales. We apply ACOLITE atmospheric correction to the satellite data and use the output to train the model along with the ancillary data and therefore, map the extent of the meadows. We apply noise-removing filters to enhance the map quality. We obtain 74-92% of overall accuracy, 72-91% of user's accuracy, and 81-92% of producer's accuracy, where high accuracies are observed at 0-25 m depth. Our model is easily adaptable to other regions and can produce maps in in-situ data-scarce regions, providing a first-hand overview. Our approach can be a support to the Mediterranean Posidonia Network, which brings together different stakeholders such as authorities, scientists, international environmental organizations, professionals including yachting agents and marinas from the Mediterranean countries to protect all P. oceanica meadows in the Mediterranean Sea by 2030 and increase each country's capability to protect these meadows by providing accurate and up-to-date maps to prevent its future degradation.

Chiral Aminoalcohol-Derived δ-Lactams Provide Easy Access to Piperidines and Acyclic Five-Carbon Building Blocks Bearing a Tertiary and a Quaternary Stereocenter.

A procedure for the synthesis of enantiopure piperidines and acyclic building blocks (5-aminopentanols, O-protected 5-hydroxypentanenitriles) containing a tertiary and a quaternary stereocenter has been developed. Starting from a phenylglycinol- or aminoindanol-derived δ-lactam bearing an alkyl substituent at the α-position of the N,O-acetal carbon, easily accessible by a cyclocondensation reaction, the stereoselective dialkylation at the carbonyl α-position generates the quaternary stereocenter and the subsequent two-step reductive removal of the chiral inductor provides enantiopure 3,3,5-trisubstituted piperidines. Alternatively, the simultaneous reductive opening of the oxazolidine and piperidone rings of the dialkylated lactams followed by reductive or oxidative cleavage of the chiral inductor opens access to chiral 2,2,4-trisubstituted 5-amino-1-pentanols or 2,4,4-trisubstituted 5-hydroxypentanenitriles.

Fluctuations in Seminal Quality throughout the Year: How do Temperature, Humidity and Atmospheric Pressure Impact on Human Sperm Quality?

Background: Most studies evaluating the possible seasonal variation of semen quality have considered temperature as the only causal factor. Aims: To assess possible seasonality in sperm quality and associations between semen parameters and several meteorological variables (temperature, humidity, apparent temperature and atmospheric pressure) in a large cohort of andrological patients. Settings and Design: This was a retrospective, cross-sectional and correlational/descriptive study. Materials and Methods: Patients (n: 15665) were categorised into four groups (summer, winter, spring and autumn) according to the date of assistance at the fertility centre. Daily values of temperature, apparent temperature, humidity and atmospheric pressure were provided by the National Weather System and were calculated as the average of the 74 days previous to semen collection (spermatogenic cycle). Statistical Analysis Used: As appropriate, the results were analysed by analysis of variance/Kruskal-Wallis, Chi-square test, t-test/Mann-Whitney, forward conditional regression model and Spearman/Pearson's correlations. Results: We detected seasonality effects on sperm count, total sperm count and total motile sperm count, with the highest values in winter and the lowest in summer. Correlation analysis showed that temperature, apparent temperature and humidity negatively correlated with semen parameters, being humidity the most powerful predictive meteorological variable. Conclusion: Sperm quality is influenced by seasons; increased environmental temperature and humidity negatively affect semen quality.

Natural Language Processing to Automatically Extract the Presence and Severity of Esophagitis in Notes of Patients Undergoing Radiotherapy.

PURPOSE: Radiotherapy (RT) toxicities can impair survival and quality of life, yet remain understudied. Real-world evidence holds potential to improve our understanding of toxicities, but toxicity information is often only in clinical notes. We developed natural language processing (NLP) models to identify the presence and severity of esophagitis from notes of patients treated with thoracic RT. METHODS: Our corpus consisted of a gold-labeled data set of 1,524 clinical notes from 124 patients with lung cancer treated with RT, manually annotated for Common Terminology Criteria for Adverse Events (CTCAE) v5.0 esophagitis grade, and a silver-labeled data set of 2,420 notes from 1,832 patients from whom toxicity grades had been collected as structured data during clinical care. We fine-tuned statistical and pretrained Bidirectional Encoder Representations from Transformers-based models for three esophagitis classification tasks: task 1, no esophagitis versus grade 1-3; task 2, grade ≤1 versus >1; and task 3, no esophagitis versus grade 1 versus grade 2-3. Transferability was tested on 345 notes from patients with esophageal cancer undergoing RT. RESULTS: Fine-tuning of PubMedBERT yielded the best performance. The best macro-F1 was 0.92, 0.82, and 0.74 for tasks 1, 2, and 3, respectively. Selecting the most informative note sections during fine-tuning improved macro-F1 by ≥2% for all tasks. Silver-labeled data improved the macro-F1 by ≥3% across all tasks. For the esophageal cancer notes, the best macro-F1 was 0.73, 0.74, and 0.65 for tasks 1, 2, and 3, respectively, without additional fine-tuning. CONCLUSION: To our knowledge, this is the first effort to automatically extract esophagitis toxicity severity according to CTCAE guidelines from clinical notes. This provides proof of concept for NLP-based automated detailed toxicity monitoring in expanded domains.

Effectiveness, persistence of use, and safety of orlistat and liraglutide in a group of patients with obesity.

BACKGROUND: To determine the effectiveness, persistence of use, adverse reactions, interactions of orlistat and liraglutide taken for weight loss by a group of obese patients in Colombia. RESEARCH DESIGN AND METHODS: A retrospective follow-up study of a cohort of patients with obesity treated with orlistat or liraglutide. Sociodemographic, clinical, and pharmacological variables were identified. The effectiveness for weight loss at 12-16 and 52 weeks, persistence of use, and safety were determined. RESULTS: A total of 294 patients were followed up. At 12-16 weeks after starting orlistat and liraglutide, weight losses of -1.2kg (p=0.002) and -4.1kg (p<0.001) were observed, respectively, and at 52 weeks, reductions of -1.6kg (p=0.208) and -7.8kg (p<0.001) were observed. A total of 8.8% and 31.3% of patients treated with orlistat and liraglutide, respectively, persisted with treatment 1 year after initiation. A total of 17.3% had adverse drug reactions. Older adults with grade II or III obesity who performed physical activity and those treated with liraglutide were more likely to have lost at least 5% of their body weight at 12-16 weeks. CONCLUSION: Orlistat and liraglutide users presented weight loss at 12-16 weeks. However, this effect was greater and sustained with liraglutide, especially when combined with physical activity.

Use of sacubitril/valsartan in patients with heart failure: evidence from the real world.

BACKGROUND: To characterize the use of sacubitril/valsartan in a group of patients with heart failure in Colombia. RESEARCH DESIGN AND METHODS: Follow-up study of patients with heart failure who started sacubitril/valsartan and were affiliated with the Colombian health system between 2019 and 2021. Sociodemographic, clinical, and pharmacological variables and adherence and persistence of use were identified. RESULTS: A total of 514 patients were identified, with a mean age of 65.7 years, 73.7% of whom started sacubitril/valsartan at low doses, and only 12.5% reached the maximum dose. Adherence was 78.2% and persistence was 56.8% at 1 year of follow-up. The increase in systolic blood pressure (odds ratio (OR): 1.01; 95% CI: 1.00-1.03) and the use of ß-blockers (OR: 2.63; 95% CI: 1.42-4.85) were correlated with a greater persistence, while receiving furosemide (OR: 0.59; 95% CI: 0.39-0.89) and not having received renin - angiotensin - aldosterone system inhibitors in the 3 months before starting sacubitril/valsartan (OR: 0.48; 95% CI: 0.31-0.76) were associated with lower persistence. CONCLUSIONS: The persistence of treatment 1 year after starting sacubitril/valsartan was not high, and a small proportion of patients reached the target dose of the drug. Nontitration of the drug dose was common.

Clinical prediction model for pulmonary thrombosis diagnosis in hospitalized patients with SARS-CoV-2 infection.

Background and Aim: We aimed to develop a clinical prediction model for pulmonary thrombosis (PT) diagnosis in hospitalized COVID-19 patients. Methods: Non-intensive care unit hospitalized COVID-19 patients who underwent a computed tomography pulmonary angiogram (CTPA) for suspected PT were included in the study. Demographic, clinical, analytical, and radiological variables as potential factors associated with the presence of PT were selected. Multivariable Cox regression analysis to develop a score for estimating the pre-test probability of PT was performed. The score was internally validated by bootstrap analysis. Results: Among the 271 patients who underwent a CTPA, 132 patients (48.7%) had PT. Heart rate >100 bpm (OR = 4.63 [95% CI: 2.30-9.34]; P < 0.001), respiratory rate >22 bpm (OR = 5.21 [95% CI: 2.00-13.54]; P < 0.001), RALE score ≥4 (OR = 3.24 [95% CI: 1.66-6.32]; P < 0.001), C-reactive protein (CRP) >100 mg/L (OR = 2.10 [95% CI: 0.95-4.63]; P = 0.067), and D-dimer >3.000 ng/mL (OR = 6.86 [95% CI: 3.54-13.28]; P < 0.001) at the time of suspected PT were independent predictors of thrombosis. Using these variables, we constructed a nomogram (CRP, Heart rate, D-dimer, RALE score, and respiratory rate [CHEDDAR score]) for estimating the pre-test probability of PT. The score showed a high predictive accuracy (area under the receiver-operating characteristics curve = 0.877; 95% CI: 0.83-0.92). A score lower than 182 points on the nomogram confers a low probability for PT with a negative predictive value of 92%. Conclusions: CHEDDAR score can be used to estimate the pre-test probability of PT in hospitalized COVID-19 patients outside the intensive care unit. Relevance for Patients: Developing a new clinical prediction model for PT diagnosis in COVID-19 may help in the triage of patients, and limit unnecessary exposure to radiation and the risk of nephrotoxicity due to iodinated contrast.

Asperger syndrome: can the disorder be diagnosed in the adult age?

INTRODUCTION: Asperger Syndrome (AS) is characterized by a qualitative disorder of social interaction, a pattern of restrictive, repetitive and stereotyped behavior, interests and activities, with normal intellectual capacity and normal language skills in the areas of grammar and vocabulary. Since its inclusion in international taxonomies, there has been much controversy regarding its nosological validity. CLINICAL CASE: A patient with a diagnosis of AS in adulthood is described. Results from the psychopathological, personality and cognitive functioning assessment are included. CONCLUSIONS: Asperger Syndrome can also be diagnosed in adulthood and should be suspected whenever retrospective information and clinical assessment point to this diagnosis.

Immobilization strategies of photolyases: Challenges and perspectives for DNA repairing application.

Photolyases are enzymes that repair DNA damage caused by solar radiation. Due to their photorepair potential, photolyases added in topical creams and used in medical treatments has allowed to reverse skin damage and prevent the development of different diseases, including actinic keratosis, premature photoaging and cancer. For this reason, research has been oriented to the study of new photolyases performing in extreme environments, where high doses of UV radiation may be a key factor for these enzymes to have perfected their photorepair potential. Generally, the extracted enzymes are first encapsulated and then added to the topical creams to increase their stability. However, other well consolidated immobilization methods are interesting strategies to be studied that may improve the biocatalyst performance. This review aims to go through the different Antarctic organisms that have exhibited photoreactivation activity, explaining the main mechanisms of photolyase DNA photorepair. The challenges of immobilizing these enzymes on porous and nanostructured supports is also discussed. The comparison of the most reported immobilization methods with respect to the structure of photolyases show that both covalent and ionic immobilization methods produced an increase in their stability. Moreover, the use of nanosized materials as photolyase support would permit the incorporation of the biocatalyst into the target cell, which is a technological requirement that photolyase based biocatalysts must fulfill.