Case report: Cytopenias in VEXAS syndrome - a WHO 2022 based approach in a single-center cohort.

VEXAS syndrome is an acquired autoinflammatory disease characterized in most cases by cytopenias and macrocytic anemia. Dyshematopoiesis is a frequent finding in chronic inflammatory conditions and therefore, cytopenias are not easily classified in VEXAS patients. Here we report a series of 7 patients affected by VEXAS associated cytopenias, treated at our center. The use of NGS, together with morphological assays, integrated with the WHO 2022 criteria, allowed to identify three subsets of VEXAS associated cytopenias: ICUS (idiopathic cytopenia of uncertain significance), CCUS (clonal cytopenia of uncertain significance) at high risk of clonal evolution, and MDS. This approach could help to better understand the nature of VEXAS associated cytopenias and to guide the use of specific targeted treatments in order to achieve long lasting responses.

Do non-bovine domestic animals produce A2 milk?: an in silico analysis.

A2 milk is an easily digestible product since it has only A2 beta-casein. In cattle, the A1 and A2 alleles are found in the population and the A2 milk is produced from A2A2 animals. Little is known about these alleles in other domestic dairy species. The present study aims to analyze sequence of genetic material available on public databases and quantify the animals genotyped. Eight domestic species were analyzed. There is strong evidence that domestic non-bovine species only carry A2 beta-casein. The data reported here for goats already confirm it due to the large number of animals genotyped as well as buffaloes. It means that they naturally produce A2 milk and no selection must be done. Thus, the fact that A2 milk is easier to digest can be used to add value to dairy product of these species. It helps to conquer new markets. It also improves people's health and breeder profitability.

Kappa and beta-casein alleles in dairy zebu cattle.

The kappa (CSN3) and beta-casein (CSN2) genes are intensively genotyped in dairy cattle for selection purposes. This information is also generated and disseminated for Zebu breeds adapted to tropical climates. The objective of this work was to gather information on the genotypes for the CSN3 and CSN2 genes in three breeds (Gyr, Guzerat and Sindhi), and to verify the genotypic frequencies in the populations. The genotype AA and allele A frequencies are high for the CSN3 gene, without changes in values over the years, possibly indicating a small gene participation in traits under selection. In addition, the A2A2 frequencies are high for the CSN2 gene (<∼0.80). It is recommended to verify the association and contribution of CSN3 genotypes in productive traits for these breeds. The potential of A2 milk production by these genetic groups is also confirmed.

Investigating the relationship between autistic traits and symptoms and Catatonia Spectrum.

BACKGROUND: In recent years, numerous studies have highlighted the overlap between autism spectrum disorder (ASD) and catatonia, both from a clinical and pathophysiological perspective. This study aimed to investigate the relationship between the autism spectrum (autistic traits and ASD signs, symptoms, and behavioral manifestation) and Catatonia Spectrum (CS). METHODS: A total sample of 376 subjects was distributed in four diagnostic groups. Subjects were assessed with the Structured Clinical Interview for DSM-5, Research Version, the Adult Autism Subthreshold Spectrum (AdAS Spectrum), and CS. In the statistical analyses, the total sample was also divided into three groups according to the degree of autism severity, based on the AdAS Spectrum total score. RESULTS: A statistically significant positive correlation was found between AdAS Spectrum and CS total score within the total sample, the gender subgroups, and the diagnostic categories. The AdAS Spectrum domains found to be significantly and strongly correlated with the total CS score were hyper-hypo reactivity to sensory input, verbal communication, nonverbal communication, restricted interests and rumination, and inflexibility and adherence to routine. The three groups of different autistic severity were found to be distributed across all diagnostic groups and the CS score increased significantly from the group without autistic traits to the group with ASD. CONCLUSIONS: Our study reports a strong correlation between autism spectrum and CS.

Comprehensive Phenotyping in Inflammatory Bowel Disease: Search for Biomarker Algorithms in the Transkingdom Interactions Context.

Inflammatory bowel disease (IBD) is the most common form of intestinal inflammation associated with a dysregulated immune system response to the commensal microbiota in a genetically susceptible host. IBD includes ulcerative colitis (UC) and Crohn's disease (CD), both of which are remarkably heterogeneous in their clinical presentation and response to treatment. This translates into a notable diagnostic challenge, especially in underdeveloped countries where IBD is on the rise and access to diagnosis or treatment is not always accessible for chronic diseases. The present work characterized, for the first time in our region, epigenetic biomarkers and gut microbial profiles associated with UC and CD patients in the Buenos Aires Metropolitan area and revealed differences between non-IBD controls and IBD patients. General metabolic functions associated with the gut microbiota, as well as core microorganisms within groups, were also analyzed. Additionally, the gut microbiota analysis was integrated with relevant clinical, biochemical and epigenetic markers considered in the follow-up of patients with IBD, with the aim of generating more powerful diagnostic tools to discriminate phenotypes. Overall, our study provides new insights into data analysis algorithms to promote comprehensive phenotyping tools using quantitative and qualitative analysis in a transkingdom interactions network context.

Undernutrition risk and nutritional screening implementation in hospitals: Barriers and time trends (2019-2020).

BACKGROUND & AIMS: Undernutrition screening is the starting point for high-quality nutrition care. In Portugal, the systematic nutritional risk assessment became mandatory for every inpatient in hospitals of the National Health System in 2019. The aims of this study were to describe the country's nutritional risk prevalence of hospitalized patients, and the experience of implementing a systematic undernutrition screening method, including time trends, barriers, and facilitators. METHODS: This research was carried out in Portuguese Public Hospitals (n = 49) and included both the analysis of data from health information systems between January 2019 and December 2020 and from an online survey. The performance indicators are described for 38 hospitals that use the SClinico electronic health records software provided by the Ministry of Health. The Nutritional Risk Screening 2002 (NRS 2002) was applied to adult patients and the STRONGkids to paediatric patients. In order to assess barriers and facilitators the online survey was applied to all public hospitals (n = 49), including Hospital Centres and Local Health Units. RESULTS: In 2020, 25.5% of the screened patients were nutritionally at risk. There was a significant increase in the proportion of patients screened from the pre- (10.6 ± 1.9%) to the post-adaptation period of the electronic health record (23.3 ± 4.8%, July-December 2019, and 25.4 ± 2.2%, January-June 2020) (p < 0.001). Data from 41 Hospital Centres and Local Health Units (84%) were obtained from the online survey. The major barriers identified were the lack of human resources (89.7%) and equipment (41.0%), as well as insufficient knowledge about the role of undernutrition screening (35.9%). The most-reported facilitators were the integration of undernutrition screening to electronic health records (22.2%) and good multidisciplinary articulation (36.1%). CONCLUSION: The high prevalence of nutritional risk justifies the mandatory nutritional screening, which leads to the improvement of the quality of hospital care. However, local and national efforts are warranted to adapt nutritional screening policies to local conditions and to increase and improve its implementation.

COVID-19 pandemic as a risk factor for the reactivation of herpes viruses.

The appearance on the skin of herpes virus lesions, concomitantly with the coronavirus disease 2019 (COVID-19) pandemic, leads us to suspect an underlying infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Diagnostic reverse transcriptase polymerase chain reaction tests and immunoglobulin M (IgM) and IgG seroconversion studies have therefore been carried out. We present three cases of herpes virus infections in immunocompetent patients: one of the infections was herpes simplex 1 in a 40-year-old woman, and the other two were herpes varicella-zoster infections in a 62-year-old man and a 25-year-old woman. The patients were in the care of the southern health district of Seville of the SAS (Andalusian Health Service) during the Spanish state of alarm over the COVID-19 pandemic. The SARS-CoV-2 infection was confirmed in only one of the three cases. In this study, we briefly review the etiopathogenic role of the COVID-19 pandemic situation, whereby immunodeficiencies are generated that favour the appearance of other viral infections, such as herpes virus infections.

Clinical characteristics of vulnerable populations hospitalized and diagnosed with COVID-19 in Buenos Aires, Argentina.

There is not in Argentina publications regarding the presentation of patients with COVID-19 requiring hospitalized and emergency care in vulnerable populations (lower incomes and less education tend at greater risk for poor health status and healthcare access), and it has few reports in developing countries. The objective is to determine whether in the care of vulnerable patients, to succeed against COVID-19, multiple public health tools and interventions will be needed to minimize morbidity and mortality. The study is a prospective cohort investigation of patients with lab-confirmed COVID-19, who required to any of the Health Centers response from April 8, 2020, to August 18, 2020. In Buenos Aires Metropolitan Area (AMBA), April 8, 2020 the virus was identified in patients hospitalized in the "Southeast Network" (SN), AMBA. SN covering an area of 661 square kilometers, with 1.8 million inhabitants residing in urban, and rural areas. A total of 14 health centers with different levels of care complexity provide care to patients in the region. The information of each patient with COVID-19 evaluated by SN, was incorporated in an Epidemiological Dashboard. The investigation was designed and reported with consideration of observational studies in epidemiology. We describe the hospitals presentation and care of persons who required SN response and were ultimately diagnosed with COVID-19. From April 8, 2020, to August 18, 2020, were included 1495 patients with lab-confirmed COVID-19 in SN. A total of 58% patients were men, and the mean age (SD) was 48.9 (15.59) years. Eighty one percent patients with pre-existing diseases, most frequent hypertension and diabetes, but hypertension, chronic lung disease, and cardiovascular disease presented higher risk. A total of 13% were hospitalized in Intensive Therapy Unit. The mortality of the cohort was 9.77%. Mortality was higher for patients aged 65 or more (OR 5.09), and for those had some pre-existing disease (OR 2.61). Our observations are consistent with reports demonstrating older persons, and those with comorbidities have the highest risk of mortality related to COVID-19. However, unlike other reports from developed or some developing countries, the mortality in our study is lower. This finding may be related to age of our cohort is younger than other published. Also, the health system was able to respond to the demand.

Audiological outcomes in patients with congenital aural atresia implanted with transcutaneous active bone conduction hearing implant.

OBJECTIVES: The objective of this study is to evaluate the safety and efficacy of the transcutaneous Bone Conduction Implant, the Bonebridge, in patients with congenital aural atresia. METHODS: Audiometry, speech recognition test and free field audiometry were performed. Word recognition scores and speech perception was evaluated using Spanish phonetically-balanced disyllables word list. RESULTS: Fourteen subjects were implanted with the Bonebridge (seven bilateral placements). The study cohort comprised seven males and seven females aged from 3 to 17 years (mean age 9.76yrs). All patients accepted and benefited from the implanted Bonebridge system. The pre-operative PTA4 was 66.4 dB (64.2-68.6, 95-%CI) and improved after activation to 19.2 dB (16.9-21.5, 95%CI), resulting in a mean functional gain of 47,2 dB. Regarding speech discrimination, the pre-operative outcomes of the disyllabic measurements were 34.3% and for monosyllables 27.4%. Following activation the speech discrimination improved to 98.6% and 97.9%, respectively. No infections or adverse device related effects occurred in patient group. CONCLUSION: We have concluded that the Bonebridge implant is an innovative solution for patients with conductive or mixed hearing loss and unilateral loss suffering from congenital atresia. Different surgical techniques may be used for implant placement, based on the patient's anatomy. Studies show improved functional gain, better speech perception, and lower rates of percutaneous complications associated with this implant.

Effect of high-fat and vitamin D deficient diet on rat sperm quality and fertility.

Vitamin D (VD) is involved in many functions of the reproductive system male. The intake of diets high-fat and vitamin D deficiency (VD-) can cause morphological and physiological changes in testis that relate to infertility in the male. However, its effects on sperm quality and in vivo fertility have been little studied. This study analyzed the effects of fat and VD on sperm quality and in vivo fertility in sperm of Sprague-Dawley rats. The rats were divided into four groups: G1: control diet with vitamin D (C/VD+), G2: control diet without vitamin D (C/VD-), G3: high-fat diet with vitamin D (HF/VD+) and G4: high-fat diet without vitamin D (HF/VD-) and were fed for 3 months. Adipose tissue weight and plasma glucose were determined. Sperm quality was analyzed for motility (MO), mitochondrial function and fertilizing capacity. The intake of a high-fat diet caused a significant increase in body weight of rats (P < 0.05). There were fat-by-VD interaction effects (P < 0.05) on MO and MMP. MO and MMP were greater (P < 0.05) in G1 (54 ±â€¯5.5% and 60.5 ±â€¯2.6%) than in G3 and G4 (20 ±â€¯6.0% and 27.7 ±â€¯3.6), whereas G2 (36.7 ±â€¯8.9% and 30.7 ±â€¯4.2%) was intermediate. There was no fat-by-VD interaction for fertilizing capacity. However, fertilizing capacity was greater (P > 0.05) in animals receiving control diet (70 ±â€¯21%); than in animals receiving high-fat diet (20 ±â€¯11%). Our results demonstrated that the high-fat diet and VD- contribute to the decrease in sperm quality (MO, MMP) and consequently could decrease the fertilizing capacity.

Genome-wide scan reveals population stratification and footprints of recent selection in Nelore cattle.

BACKGROUND: This study aimed at (1) assessing the genomic stratification of experimental lines of Nelore cattle that have experienced different selection regimes for growth traits, and (2) identifying genomic regions that have undergone recent selection. We used a sample of 763 animals genotyped with the Illumina BovineHD BeadChip, among which 674 animals originated from two lines that are maintained under directional selection for increased yearling body weight and 89 animals from a control line that is maintained under stabilizing selection. RESULTS: Multidimensional analysis of the genomic dissimilarity matrix and admixture analysis revealed a substantial level of population stratification between the directional selection lines and the stabilizing selection control line. Two of the three tests used to detect selection signatures (FST, XP-EHH and iHS) revealed six candidate regions with indications of selection, which strongly indicates truly positive signals. The set of identified candidate genes included several genes with roles that are functionally related to growth metabolism, such as COL14A1, CPT1C, CRH, TBC1D1, and XKR4. CONCLUSIONS: The current study identified genetic stratification that resulted from almost four decades of divergent selection in an experimental Nelore population, and highlighted autosomal genomic regions that present patterns of recent selection. Our findings provide a basis for a better understanding of the metabolic mechanism that underlies the growth traits, which are modified by selection for yearling body weight.

Identification and characterization of proteolytically resistant gluten-derived peptides.

The lack of digestibility of certain gluten proteins is essential in the development of celiac disease (CD). Gluten proteins are remarkably resistant to luminal and brush-border proteolysis owing to their high proline and glutamine content. Consequently, large fragments remain intact after digestion exerting toxic effects. Intestinal brush-border membrane vesicles (BBMV) have been described as having strong proteolytic activity mainly through prolyl endopeptidase enzymes. The purpose of this work was to monitor the gastrointestinal digestion of specific CD epitopes by means of an in vitro gastrointestinal digestion model that included incubation with brush-border membrane enzymes. Gluten hydrolysates were characterized by mass spectrometry and the immunologic peptides were tracked by searching the main T-cell stimulating epitopes which have been widely described. The immunologic potential of gluten hydrolysates was further analysed by enzyme-linked immunosorbent assay (ELISA). The results showed that the composition of gluten hydrolysates depended on the digestion time and protein structural characteristics. On the other hand, the main T-cell stimulating epitopes formed during hydrolysis depend on the precursor protein. Glutenin oligopeptides were degraded faster whereas gliadin, mainly α-gliadin oligopeptides, remained intact for a long time. MS-based analysis showed that the formation of the epitopes from γ-gliadin and ω-gliadin or glutenin was favoured but they were generally degraded during the gastrointestinal treatment. However, the peptides containing the epitope PFPQPQLPY (α-gliadin) remained intact even after 180 min of digestion time. Overall, from all the epitopes tracked, PFPQPQLPY was the most resistant to in vitro BBMV digestion.

How Thinking About the Donor Influences Post-traumatic Growth in Liver Transplant Recipients.

OBJECTIVE: The aim of this work was to find out whether thinking frequently about the donor influences post-traumatic growth of liver transplant recipients. METHODS: The sample of 240 patients selected was made up of 185 men and 55 women with an overall mean age of 60.21 (SD 9.3) years. All of them had received liver transplants from cadaver donors. Transplant recipients were asked whether they thought frequently about the donor (yes or no) and filled out the Post-traumatic Growth Inventory. The t test for unpaired samples was applied to analyze how thinking frequently about the donor or not influenced post-traumatic growth. We also calculated the effect sizes by means of Cohen d or Cohen w depending on the nature of the variables analyzed (quantitative or qualitative). RESULTS: The liver transplant recipients who thought frequently about the donor, compared with those who did not, had higher total scores on post-traumatic growth (P = .000; d = 0.57; medium effect size). Furthermore, considering the effect sizes, the differences between the subgroups were more relevant on the following subscales: new possibilities (P = .000; d = 0.53; medium effect size), appreciation of life (P = .000; d = 0.60; medium effect size), and spiritual change (P = .000; d = 0.54; medium effect size). CONCLUSIONS: Patients who think frequently about the donor have more post-traumatic growth than those who do not.

Family Caregivers of Liver Transplant Recipients: Coping Strategies Associated With Different Levels of Post-traumatic Growth.

OBJECTIVE: Analyze the influence of 2 variables (post-traumatic growth and time since liver transplantation) on coping strategies used by the transplant recipient's family members. METHODS: In all, 218 family members who were their main caregivers of liver transplant recipients were selected. They were evaluated using the Posttraumatic Growth Inventory and the Brief COPE. A 3 × 3 factorial analysis of variance was used to analyze the influence that post-traumatic growth level (low, medium, and high) and time since transplantation (≤3.5 years, >3.5 to ≤9 years, and >9 years) exerted on caregiver coping strategies. RESULTS: No interactive effects between the two factors in the study were found. The only significant main effect was the influence of the post-traumatic growth factor on the following variables: instrumental support (P = .007), emotional support (P = .005), self-distraction (P = .006), positive reframing (P = .000), acceptance (P = .013), and religion (P = <.001). According to the most relevant effect sizes, low post-traumatic growth compared with medium growth was associated with less use of self-distraction (P = .006, d = -0.52, medium effect size), positive reframing (P = .001, d = -0.62, medium effect size), and religion (P = .000, d = -0.66, medium effect size), and in comparison with high growth, it was associated with less use of positive reframing (P = .002, d = -0.56, medium effect size) and religion (P = .000, d = 0.87, large effect size). CONCLUSION: Regardless of the time elapsed since the stressful life event (liver transplantation), family members with low post-traumatic growth usually use fewer coping strategies involving a positive, transcendent vision to deal with transplantation.

Genomic association for sexual precocity in beef heifers using pre-selection of genes and haplotype reconstruction.

Reproductive traits are of the utmost importance for any livestock farming, but are difficult to measure and to interpret since they are influenced by various factors. The objective of this study was to detect associations between known polymorphisms in candidate genes related to sexual precocity in Nellore heifers, which could be used in breeding programs. Records of 1,689 precocious and non-precocious heifers from farms participating in the Conexão Delta G breeding program were analyzed. A subset of single nucleotide polymorphisms (SNP) located in the region of the candidate genes at a distance of up to 5 kb from the boundaries of each gene, were selected from the panel of 777,000 SNPs of the High-Density Bovine SNP BeadChip. Linear mixed models were used for statistical analysis of early heifer pregnancy, relating the trait with isolated SNPs or with haplotype groups. The model included the contemporary group (year and month of birth) as fixed effect and parent of the animal (sire effect) as random effect. The fastPHASE® and GenomeStudio® were used for reconstruction of the haplotypes and for analysis of linkage disequilibrium based on r2 statistics. A total of 125 candidate genes and 2,024 SNPs forming haplotypes were analyzed. Statistical analysis after Bonferroni correction showed that nine haplotypes exerted a significant effect (p<0.05) on sexual precocity. Four of these haplotypes were located in the Pregnancy-associated plasma protein-A2 gene (PAPP-A2), two in the Estrogen-related receptor gamma gene (ESRRG), and one each in the Pregnancy-associated plasma protein-A gene (PAPP-A), Kell blood group complex subunit-related family (XKR4) and mannose-binding lectin genes (MBL-1) genes. Although the present results indicate that the PAPP-A2, PAPP-A, XKR4, MBL-1 and ESRRG genes influence sexual precocity in Nellore heifers, further studies are needed to evaluate their possible use in breeding programs.

Airway pathology in severe asthma is related to airflow obstruction but not symptom control.

BACKGROUND: Patients with asthma present structural and inflammatory alterations that are believed to play a role in disease severity. However, airway remodeling and inflammation have not been extensively investigated in relation to both symptom control and airflow obstruction in severe asthmatics. We aimed to investigate several inflammatory and structural pathological features in bronchial biopsies of severe asthmatics that could be related to symptom control and airflow obstruction after standardized treatment. METHODS: Fifty severe asthmatics received prednisone 40 mg/d for 2 weeks and maintenance therapy with budesonide/formoterol 400/12 µg twice daily + budesonide/formoterol 200/6 µg as needed for 12 weeks. Endobronchial biopsies were performed at the end of 12 weeks. We performed extensive immunopathological analyses of airway tissue inflammation and remodeling features in patients stratified by asthma symptom control and by airflow obstruction. RESULTS: Airway tissue inflammation and remodeling were not associated with symptom control. Asthmatics with persistent airflow obstruction had greater airway smooth muscle (Asm) area with decreased periostin and transforming growth factor beta-positive cells within Asm bundles, in addition to lower numbers of chymase-positive mast cells in the submucosa compared to patients with nonpersistent obstruction. CONCLUSIONS: Symptom control in severe asthmatics was not associated with airway tissue inflammation and remodeling, although persistent airflow obstruction in these patients was associated with bronchial inflammation and airway structural changes.

Chromatographic and mass spectrometry analysis of wheat flour prolamins, the causative compounds of celiac disease.

Immunogenic gluten peptides trigger Celiac Disease (CD), an adaptive immune response in genetically predisposed individuals. Given the structural similarity between all gluten proteins their individual CD influence is not clear. Hence, the extraction, separation and characterization of wheat gluten proteins have become relevant to measure their individual potential immunoreactivity. Wheat proteins were extracted from commercial wheat flour and further isolated by preparative HPLC. The resulting richest gliadin sub-fractions were characterized by nano-LC-MS/MS following a shotgun proteomic approach in order to identify the prolamins in the original commercial wheat flour. It was found that the gliadin extract was additionally composed of glutenins and avenin-like proteins. Accurate prolamin identification has emerged as a need to delve deep into the influence of each fraction on the onset of celiac disease. After protein characterization, the immunoreactivity towards the main epitope related to CD was verified by ELISA and western blotting for several different gluten fractions.

Concerns, Mental Health, and Quality of Life in Living Kidney Donation-Parent Donor Candidates Worry Less about Themselves.

Even though the majority of living kidney donor candidates appear in good mental health and show few concerns little is known concerning the influence of the type of donor-recipient relationship on donor candidates' specific concerns with regard to kidney donation. 136 donor candidates at Virgen del Rocío University Hospital of Seville filled in the Scale of Concerns Regarding Living Kidney Donation of whom 105 donor candidates and their corresponding recipients (105 patients with End-Stage Renal Disease) were further evaluated with regard to mental health (Hospital Anxiety and Depression Scale, Beck Depression Inventory-II) and quality of life (SF-36 Health Survey). As hypothesized recipients scored higher on depression and lower on quality of life. Donor candidates intending to donate to their children were significantly less concerned about risks of donation for themselves compared to donor candidates donating to siblings. Our findings highlight the importance of the type of donor-recipient relationship to understand specific concerns of donor candidates and optimize psychosocial assessment and support. From an evolutionary perspective parents lack of concern about their own well-being can be seen as an altruistic behavior to increase children's fitness at the (potential) expense of their own fitness.