Genetic risk score for insulin resistance based on gene variants associated to amino acid metabolism in young adults.

Circulating concentration of arginine, alanine, aspartate, isoleucine, leucine, phenylalanine, proline, tyrosine, taurine and valine are increased in subjects with insulin resistance, which could in part be attributed to the presence of single nucleotide polymorphisms (SNPs) within genes associated with amino acid metabolism. Thus, the aim of this work was to develop a Genetic Risk Score (GRS) for insulin resistance in young adults based on SNPs present in genes related to amino acid metabolism. We performed a cross-sectional study that included 452 subjects over 18 years of age. Anthropometric, clinical, and biochemical parameters were assessed including measurement of serum amino acids by high performance liquid chromatography. Eighteen SNPs were genotyped by allelic discrimination. Of these, ten were found to be in Hardy-Weinberg equilibrium, and only four were used to construct the GRS through multiple linear regression modeling. The GRS was calculated using the number of risk alleles of the SNPs in HGD, PRODH, DLD and SLC7A9 genes. Subjects with high GRS (≥ 0.836) had higher levels of glucose, insulin, homeostatic model assessment- insulin resistance (HOMA-IR), total cholesterol and triglycerides, and lower levels of arginine than subjects with low GRS (p < 0.05). The application of a GRS based on variants within genes associated to amino acid metabolism may be useful for the early identification of subjects at increased risk of insulin resistance.

High resting energy expenditure, less fat-free mass, and less muscle strength in HIV-infected children: a matched, cross-sectional study.

Background and aims: Many improvements have been made in the treatment of human immunodeficiency virus (HIV) in pediatric patients; however, challenges remain in terms of achieving normal growth, body composition, and metabolism during treatment, etc. Current nutritional recommendations are based on studies performed in adults, with limited data on the HIV-infected pediatric population. Therefore, this study aimed to compare the resting energy expenditure (REE) of asymptomatic HIV-infected pediatric patients with healthy counterparts and to compare body composition, dietary intake, and physical activity between the two groups. Methods: This was a cross-sectional study of asymptomatic HIV-infected children who were receiving antiretroviral therapy; the infected group was compared with the uninfected group, matched by age (± 6 months), sex, and body mass index (± 0.5 z-score). Participants were recruited between 2021 and 2022, as outpatients. In both groups, REE was determined by indirect calorimetry and body composition by bioelectrical impedance analysis and hand strength, measured using a hydraulic hand dynamometer. Results: Seventy-eight participants were enrolled, where n = 39 HIV-infected children and n = 39 controls, with a mean age of 11.6 ± 3.4 years old. REE was significantly higher in the HIV group (1254.4 ± 334.7 kcal/day vs. 1124.7 ± 321 kcal/day, p = 0.013) than in the control group. Fat-free mass (FFM) was lower in the HIV group (28.2 ± 10.5 kg vs. 32 ± 11.2 kg, p = 0.001); this trend continued when the index skeletal muscle was evaluated (7.2 ± 1.2 vs. 7.6 ± 1.5, p = 0.04). The strength of the dominant hand was also lower in the HIV group (12 (8-18) kg vs. 20 (10.5-26) kg, p < 0.0001). Conclusions: Children with asymptomatic HIV infection have higher REE than their uninfected peers. They also present decreased FFM, skeletal muscle mass index, and muscle strength. These parameters should be considered during nutritional assessment in this population to have a favorable impact on nutritional status and growth.

Management of a Right Heart Intracavitary Thrombus in Transit in a Patient With Gastric Cancer in a Resource-Limited Setting: A Case Report.

A right atrial thrombus is an unusual source of imminent massive saddle pulmonary embolism (PE) . A hypercoagulable state secondary to gastric cancer (GC) can result in deep vein thrombosis (DVT) with a resultant right-sided heart thrombus in transit. Here, we present a case of a young male patient from Honduras with DVT and multiple venous thrombi extending from the external iliac veins to the suprahepatic left vein, inferior vena cava, and right atrium of the heart, secondary to a hypercoagulable state from GC, adenocarcinoma type. We describe the approach of treating a right heart intracavitary thrombus with imminent risk for saddle PE and sudden cardiac death with thrombolysis through a central venous catheter (CVC) in a resource-limited setting.

Prostatic Abscess Secondary to Staphylococcus haemolyticus and Escherichia coli: A Case Report.

A prostate abscess is a rare clinical entity with an incidence of 0.2%-0.5% in males. No case reports exist of Staphylococcus haemolyticus as an etiologic bacterial agent. We report a 59-year-old man with a past medical history of poorly controlled diabetes mellitus and benign prostatic hyperplasia who was hospitalized due to urosepsis and obstruction. A prostatic abscess was discovered and initially treated with intravenous vancomycin and ertapenem. Clinical improvement was apparent within two days following transrectal prostatic abscess drainage. Four weeks of intravenous antibiotics followed. Prostatic abscess cultures grew Staphylococcus haemolyticus and Escherichia coli following tube deployment. To the best of our knowledge, this is the first case reporting Staphylococcus haemolyticus as an organism in a prostate abscess. We regard this as another example of the rising incidence of gram-positive organisms in prostatic abscesses in the post-antibiotic era.

Impact of COVID-19 on the Care of Patients with HIV Infection.

The COVID-19 pandemic and associated lockdown measures have been associated with substantial disruptions to health care services, including screening for human immunodeficiency virus (HIV) and management of people living with HIV (PLWH). Data from 3265 patients were examined in a retrospective cohort study. We compared outpatient follow-up for PLWH, the number of new patients, treatment adherence, hospitalizations, and deaths during the "pandemic period" (March 2020 to February 2021), the "pre-pandemic period" (the equivalent time frame in 2019), and the "post-pandemic period" (March to September 2021). During the pandemic period, the number of new patients seen at the HIV clinic (116) as well as the requested viral load tests (2414) decreased significantly compared to the pre-pandemic (204 and 2831, respectively) and post-pandemic periods (146 and 2640, respectively) (p < 0.01 for all the comparisons). However, across the three study periods, the number of drug refills (1385, 1330, and 1411, respectively), the number of patients with undetectable viral loads (85%, 90%, and 93%, respectively), and the number of hospital admissions among PLWH remained constant. Despite the COVID-19 pandemic's impact, our findings show stability in the retention of clinical care, adherence to treatment, and viral suppression of PLWH, with no significant impact on hospitalization rates or all-cause mortality.

Enfermedad de Crohn en paciente con artritis idiopática juvenil de inicio sistémico: ¿asociación o complicación asociada al tratamiento? / Crohn's Disease in a Patient with Systemic Onset Juvenile Idiopathic Arthritis. Association or Associated Side Effect of Treatment?

La evolución de la artritis idiopática juvenil de inicio sistémico (AIJs) hacia las diferentes formas de presentación de enfermedad inflamatoria intestinal es extremadamente infrecuente. Presentamos la que, hasta ahora, es la primera comunicación de un paciente con AIJs con evolución a enfermedad de Crohn en el que se han detectado mutaciones en genes responsables de la adecuada regulación del sistema inmune innato.(AU)

The progression of systemic-onset juvenile idiopathic arthritis (JIAs) to the different forms of presentation of inflammatory bowel disease is extremely rare. We present the first report of a patient with SJIA that progressed to Crohn's disease in which mutations have been detected in genes responsible for the adequate regulation of the innate immune system.(AU)

Sensitisation to Pollen Allergens in Children and Adolescents of Different Ancestry Born and Living in the Same Area.

Background: Allergy can start at early ages, with genetic and environmental factors contributing to its development. Aim: The study aimed to describe the pattern of sensitisation and allergy in children and adolescents of Spanish versus Moroccan ancestry but born in the same rural area of Spain. Methods: Participants were children and adolescents (3-19 years) of Spanish or Moroccan descent, born in Blanca, Murcia (Spain). A detailed questionnaire was completed, and skin prick tests were performed to assess reactions to the most prevalent pollen allergens (O. europaea, P. pratense, S. kali, C. arizonica, P. acerifolia, A. vulgaris and P. judaica) plus molecular components Ole e 1 and Ole e 7. The association with ancestry was verified by studying participants' parents. Results: The study included 693 participants: 48% were aged 3-9 years and 52%, 10-19 years; 80% were of Spanish descent and 20% of Moroccan descent. Sensitisation to Olea europaea, Phleum pratense, Salsola kali and Cupressus arizonica were slightly higher in the Spanish group. The only significant differences were observed in sensitisation to Ole e 1 (p=0.02). Rhinitis, conjunctivitis, and rhinitis plus asthma were significantly higher in the Spanish group (p=0.03, p=0.02, p=0.007, respectively). The sensitisation pattern differed between Spanish and Moroccan parents, and between Moroccan parents and their children, but not between Spanish parents and their children. Conclusion: Both environment and ancestry may influence sensitisation and symptoms. Although the environment seems to have a stronger influence, other factors may contribute to the differences in prevalence and in the clinical entities in people of Spanish versus Moroccan descent.

Allergenic Properties and Molecular Characteristics of PR-1 Proteins.

Only a small fraction of proteins in plants and animals are classified as allergens. The allergenic properties are frequently attributed to certain functional characteristics of the proteins, such as a role in the plant defense against biotic and abiotic stress, to achieve the systematic acquired resistance. In line with this, eight members out of 17 functional pathogenesis-related (PR) protein families have been characterized as allergens. The present review summarizes the molecular features and allergenic significance of allergens of the PR-1 family. Not many allergens have been identified as belonging to this protein family, with most of them having a pollen origin, like mugwort or Bermuda grass. Molecular and structural features of allergenic PR-1 proteins are discussed and attributed to their IgE-reactive properties, clinical manifestation, and cross-reactivity among different foods and inhalants.

Plasma miRNA profile at COVID-19 onset predicts severity status and mortality.

BACKGROUND: MicroRNAs (miRNAs) have a crucial role in regulating immune response against infectious diseases, showing changes early in disease onset and before the detection of the pathogen. Thus, we aimed to analyze the plasma miRNA profile at COVID-19 onset to identify miRNAs as early prognostic biomarkers of severity and survival. METHODS AND RESULTS: Plasma miRNome of 96 COVID-19 patients that developed asymptomatic/mild, moderate and severe disease was sequenced together with a group of healthy controls. Plasma immune-related biomarkers were also assessed. COVID-19 patients showed 200 significant differentially expressed (SDE) miRNAs concerning healthy controls, with upregulated putative targets of SARS-CoV-2, and inflammatory miRNAs. Among COVID-19 patients, 75 SDE miRNAs were observed in asymptomatic/mild compared to symptomatic patients, which were involved in platelet aggregation and cytokine pathways, among others. Moreover, 137 SDE miRNAs were identified between severe and moderate patients, where miRNAs targeting the SARS CoV-2 genome were the most strongly disrupted. Finally, we constructed a mortality predictive risk score (miRNA-MRS) with ten miRNAs. Patients with higher values had a higher risk of 90-days mortality (hazard ratio = 4.60; p-value < 0.001). Besides, the discriminant power of miRNA-MRS was significantly higher than the observed for age and gender (AUROC = 0.970 vs. 0.881; p = 0.042). CONCLUSIONS: SARS-CoV-2 infection deeply disturbs the plasma miRNome from an early stage of COVID-19, making miRNAs highly valuable as early predictors of severity and mortality.

The Impact of COVID-19 in the Latinx Community.

Description The COVID-19 pandemic has intensified the existing health and social disparities that affect minority groups in the United States (US), including the Latinx community. This situation has been reflected in many aspects of health, including increased morbi-mortality and reduced adherence to medical and scientific recommendations. Limited access to health care, financial challenges, migrant status, and health literacy, or lack thereof, have all hampered the Latinx community's ability to seek aid quickly and to be tested or treated effectively for this disease. This pandemic has shown that the Latinx community's socioeconomic status correlates with greater mortality rates when compared to other ethnic groups, which runs counter to historical norms. Furthermore, morbi-mortality in Latinx people has been disproportionately greater. Beyond the systematic barriers that the Latinx community has had to face to access care during the pandemic, there were also perception barriers that increased the gap and further complicated the situation. Latinxs were more likely to be exposed due to a decreased compliance with physical distancing. When it was suggested to avoid crowds, many people started using delivery services; however, many Latinxs found the cost and requirements of reliable internet to be a barrier to using these services. Currently, COVID-19 vaccines are broadly available in the US but there has been skepticism from marginalized communities, including the Latinx population, about getting vaccinated. Integrating this population into a welcoming healthcare system, safeguarding their immigration and work status, providing more accessible vaccination locations, and promoting health equality and education would all assist to lessen the impact of this illness on the Latinx community.

Are Physicochemical Properties Shaping the Allergenic Potency of Plant Allergens?

This review searched for published evidence that could explain how different physicochemical properties impact on the allergenicity of food proteins and if their effects would follow specific patterns among distinct protein families. Owing to the amount and complexity of the collected information, this literature overview was divided in two articles, the current one dedicated to protein families of plant allergens and a second one focused on animal allergens. Our extensive analysis of the available literature revealed that physicochemical characteristics had consistent effects on protein allergenicity for allergens belonging to the same protein family. For example, protein aggregation contributes to increased allergenicity of 2S albumins, while for legumins and cereal prolamins, the same phenomenon leads to a reduction. Molecular stability, related to structural resistance to heat and proteolysis, was identified as the most common feature promoting plant protein allergenicity, although it fails to explain the potency of some unstable allergens (e.g. pollen-related food allergens). Furthermore, data on physicochemical characteristics translating into clinical effects are limited, mainly because most studies are focused on in vitro IgE binding. Clinical data assessing how these parameters affect the development and clinical manifestation of allergies is minimal, with only few reports evaluating the sensitising capacity of modified proteins (addressing different physicochemical properties) in murine allergy models. In vivo testing of modified pure proteins by SPT or DBPCFC is scarce. At this stage, a systematic approach to link the physicochemical properties with clinical plant allergenicity in real-life scenarios is still missing.

Are Physicochemical Properties Shaping the Allergenic Potency of Animal Allergens?

Key determinants for the development of an allergic response to an otherwise 'harmless' food protein involve different factors like the predisposition of the individual, the timing, the dose, the route of exposure, the intrinsic properties of the allergen, the food matrix (e.g. lipids) and the allergen modification by food processing. Various physicochemical parameters can have an impact on the allergenicity of animal proteins. Following our previous review on how physicochemical parameters shape plant protein allergenicity, the same analysis was proceeded here for animal allergens. We found that each parameter can have variable effects, ranging on an axis from allergenicity enhancement to resolution, depending on its nature and the allergen. While glycosylation and phosphorylation are common, both are not universal traits of animal allergens. High molecular structures can favour allergenicity, but structural loss and uncovering hidden epitopes can also have a similar impact. We discovered that there are important knowledge gaps in regard to physicochemical parameters shaping protein allergenicity both from animal and plant origin, mainly because the comparability of the data is poor. Future biomolecular studies of exhaustive, standardised design together with strong validation part in the clinical context, together with data integration model systems will be needed to unravel causal relationships between physicochemical properties and the basis of protein allergenicity.

Skin Testing With Peach Peel Extract Versus Serum IgE to Pru p 3 as a Stronger Predictor of Peach-Induced Anaphylaxis.

The most important peach fruit allergen is Pru p 3, followed by Pru p 1, Pru p 4, and Pru p 7. We aimed to assess their role in subjects with peach fruit-induced allergy (anaphylaxis and OAS) and compare skin prick tests (SPT) vs. specific immunoglobulin E (sIgE) for predicting anaphylaxis. We also selected a control group. SPT included prevalent inhalant and plant food allergens plus peach peel extract. The sIgE to Pru p 1, Pru p 3, Pru p 4, and Pru p 7 were quantified. Compared with controls (n = 42), cases (n = 41) were younger (P = 0.003), more frequently female (P < 0.05) and had higher SPT positivity to peach peel (44% vs. 2.4%, P < 0.0001). There were significant differences in sensitization to several pollens: Olea europaea, Artemisia vulgaris, Prunus persica, Platanus acerifolia (all P < 0.001); and fruits: apple (P < 0.04), peanut (P < 0.002), tomato (P < 0.005), and melon (P < 0.05). Pru p 3 sIgE was detected in 61% of all cases (85% anaphylaxis and 38% OAS; P < 0.01 each) and 5% of controls (P < 0.001). Pru p 4 sIgE was present in 19% of cases and 7% of controls. The sIgE to Pru p 1 and Pru p 7 were not found. The odds ratio to predict anaphylaxis for peach peel SPT was 113 (confidence interval [CI], 20-613; P < 0.0001); for sIgE to Pru p 3, 22 (CI, 5.3-93; P < 0.0001); and for SPT positivity to selected plant food allergens, 5 (CI, 1-19; P < 0.05). In our study group, SPT with peel peach extract was a better predictor of anaphylaxis than Pru p 3 sIgE or other variables considered. The role of sIgE to Pru p 1, Pru p 4, and Pru p 7 seemed negligible.

Subjects develop tolerance to Pru p 3 but respiratory allergy to Pru p 9: A large study group from a peach exposed population.

Peach tree allergens are present in fruit, pollen, branches, and leaves, and can induce systemic, respiratory, cutaneous, and gastrointestinal symptoms. We studied the capacity of peach fruit/Pru p 1, Pru p 3, Pru p 4, Pru p 7 and peach pollen/Pru p 9 for inducing symptoms following oral or respiratory exposure in a large group of subjects. We included 716 adults (aged 21 to 83 y.o.) exposed to peach tree pollen and fruit intake in the study population. Participants completed a questionnaire and were skin tested with a panel of inhalant and food allergens, including peach tree pollen, Pru p 9 and peach fruit skin extract. Immunoglobulin E antibodies (SIgE) to Pru p 1, Pru p 3, Pru p 4 and Pru p 7 were quantified. Sensitised subjects underwent oral food challenge with peach fruit and nasal provocation test with peach tree pollen and Pru p 9. The prevalence of sensitisation to peach fruit was 5% and most of these had SIgE to Pru p 3, with a very low proportion to Pru p 4 SIgE and no SIgE to Pru p 1 and Pru p 7. In only 1.8%, anaphylaxis was the clinical entity induced. Cases with positive skin tests to peach and SIgE to Pru p 3 presented a good tolerance after oral challenge with peach fruit. The prevalence of skin sensitisation to peach tree pollen was 22%, with almost half recognising Pru p 9. This induced respiratory symptoms in those evaluated by nasal provocation. In a large population group exposed to peach fruit and peach tree pollen, most individuals were tolerant, even in those with SIgE to Pru p 3. A positive response to Pru p 9 was associated with respiratory allergy.

Characterization of Relevant Biomarkers for the Diagnosis of Food Allergies: An Overview of the 2S Albumin Family.

2S albumins are relevant and often major allergens from several tree nuts and seeds, affecting mainly children and young people. The present study aims to assess how the structural features of 2S albumins could affect their immunogenic capacity, which is essential to comprehend the role of these proteins in food allergy. For this purpose, twelve 2S albumins were isolated from their respective extracts by chromatographic methods and identified by MALDI-TOF mass-spectrometry. Their molecular and structural characterization was conducted by electrophoretic, spectroscopic and in silico methods, showing that these are small proteins that comprise a wide range of isoelectric points, displaying a general high structure stability to thermal treatment. Despite low amino acid sequence identity, these proteins share structural features, pointing conformational epitopes to explain cross-reactivity between them. Immunoblotting with allergic patients' sera revealed those possible correlations between evolutionarily distant 2S albumins from different sources. The availability of a well-characterized panel of 2S albumins from plant-derived sources allowed establishing correlations between their structural features and their allergenic potential, including their role in cross-reactivity processes.

IgE-Reactivity Pattern of Tomato Seed and Peel Nonspecific Lipid-Transfer Proteins after in Vitro Gastrointestinal Digestion.

The influence of gastrointestinal digestion on the immunological properties of three different nonspecific lipid-transfer proteins (nsLTPs) described in tomato fruit has been assessed using an in vitro system mimicking the stomach and intestine digestion conditions. Tomato peel/pulp nsLTP, Sola l 3, was degraded after digestion, although the immunoglobulin E (IgE) recognition of intact protein and a 10 kDa band were still observed after 30 min of duodenal digestion in the presence of phosphatidylcholine. The tomato seed nsLTP, Sola l 7, showed a higher stability than the other seed allergen, Sola l 6, during digestion. Sola l 7 showed an IgE immunoreactive 6.5 kDa band in immunoblotting analysis, retaining up to 7% of its IgE-binding capacity in inhibition ELISA test after 60 min of duodenal digestion and keeping intact its ability to activate basophils after digestion. These results suggest that the tomato seed allergen Sola l 7 might be considered as an important allergen in the induction of allergic responses to tomato due to its high stability against gastrointestinal digestion.

Prunus persica 9, a new occupational allergen from peach tree pollen involved in rhinitis and asthma.

OBJECTIVES: Several studies have described peach tree (PT) as an occupational allergen. The aim of this work was to assess the effect of Prunus persica 9 (Pru p 9), a recently identified allergen from PT pollen, in exposed workers. METHODS: The study included people who reported respiratory symptoms after handling PT in orchards during the flowering period (Blanca village, Murcia region, south-east Spain). After completing a detailed questionnaire, participants underwent skin prick test (SPT) and nasal provocation test (NPT). The IgE response was analysed by SDS-PAGE and immunoblotting assays. RESULTS: A total of 21 cases were included (mean age 45 years; 57% women). Most were polysensitised to common pollens, although one person was sensitised only to PT pollen. All cases had a positive SPT to this pollen, and 43% also to Pru p 9. All participants reported having rhinitis, and six participants reported having also asthma. Immunoblotting showed a heterogeneous IgE pattern for several proteins, with Pru p 9 recognised in nine cases. Most participants sensitised to PT pollen and Pru p 9 had positive NPTs, while those who were not sensitised to Pru p 9 tested negative. CONCLUSIONS: We demonstrate for the first time that Pru p 9, an allergen from PT pollen, can induce respiratory symptoms following occupational exposure. This must be considered a relevant allergen when people working with PT cultivars develop respiratory symptoms.

Rapid Assessment at Hospital Admission of Mortality Risk From COVID-19: The Role of Functional Status.

OBJECTIVE: To evaluate the role of functional status along with other used clinical factors on the occurrence of death in patients hospitalized with COVID-19. DESIGN: Prospective cohort study. SETTING: Public university hospital (Madrid). PARTICIPANTS AND METHODS: A total of 375 consecutive patients with COVID-19 infection, admitted to a Public University Hospital (Madrid) between March 1 and March 31, 2020, were included in the Prospective Cohort study. Death was the main outcome. The main variable was disability in activities of daily living (ADL) assessed with the Barthel Index. Covariates included sex, age, severity index (Quick Sequential Organ Failure Assessment, qSOFA), polypharmacy (≥5 drugs in the month before admission), and comorbidity (≥3 diseases). Multivariable logistic regression was used to identify risk factors for adverse outcomes. Estimated model coefficients served to calculate the expected probability of death for a selected combination of 5 variables: Barthel Index, sex, age, comorbidities, and severity index (qSOFA). RESULTS: Mean age was 66 years (standard deviation 15.33), and there were 207 (55%) men. Seventy-four patients died (19.8%). Mortality was associated with low Barthel Index (odds ratio per 5-point decrease 1.11, 95% confidence interval 1.03-1.20), male sex (0.23, 0.11-0.47), age (1.07, 1.03-1.10), and comorbidity (2.15, 1.08-4.30) but not with qSOFA (1.29, 0.87-1.93) or polypharmacy (1.54, 0.77-3.08). Calculated mortality risk ranged from 0 to 0.78. CONCLUSIONS AND IMPLICATIONS: Functional status predicts death in hospitalized patients with COVID-19. Combination of 5 variables allows to predict individual probability of death. These findings provide useful information for the decision-making process and management of patients.