Integrated post-genomic cell wall analysis reveals floating biofilm formation associated with high expression of flocculins in the pathogen Pichia kudriavzevii.

The pathogenic yeast Pichia kudriavzevii, previously known as Candida krusei, is more distantly related to Candida albicans than clinically relevant CTG-clade Candida species. Its cell wall, a dynamic organelle that is the first point of interaction between pathogen and host, is relatively understudied, and its wall proteome remains unidentified to date. Here, we present an integrated study of the cell wall in P. kudriavzevii. Our comparative genomic studies and experimental data indicate that the general structure of the cell wall in P. kudriavzevii is similar to Saccharomyces cerevisiae and C. albicans and is comprised of ß-1,3-glucan, ß-1,6-glucan, chitin, and mannoproteins. However, some pronounced differences with C. albicans walls were observed, for instance, higher mannan and protein levels and altered protein mannosylation patterns. Further, despite absence of proteins with high sequence similarity to Candida adhesins, protein structure modeling identified eleven proteins related to flocculins/adhesins in S. cerevisiae or C. albicans. To obtain a proteomic comparison of biofilm and planktonic cells, P. kudriavzevii cells were grown to exponential phase and in static 24-h cultures. Interestingly, the 24-h static cultures of P. kudriavzevii yielded formation of floating biofilm (flor) rather than adherence to polystyrene at the bottom. The proteomic analysis of both conditions identified a total of 33 cell wall proteins. In line with a possible role in flor formation, increased abundance of flocculins, in particular Flo110, was observed in the floating biofilm compared to exponential cells. This study is the first to provide a detailed description of the cell wall in P. kudriavzevii including its cell wall proteome, and paves the way for further investigations on the importance of flor formation and flocculins in the pathogenesis of P. kudriavzevii.

The impact of the COVID-19 pandemic on people living with HIV: a cross-sectional study in Caracas, Venezuela.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has disrupted multiple health services, including human immunodeficiency virus (HIV) testing, care, and treatment services, jeopardizing the achievement of the Joint United Nations Programme on HIV/AIDS 90-90-90 global target. While there are limited studies assessing the impact of the COVID-19 pandemic on people living with HIV (PLHIV) in Latin America, there are none, to our knowledge, in Venezuela. This study aims to assess the impact of the COVID-19 pandemic among PLHIV seen at the outpatient clinic of a reference hospital in Venezuela. METHODS: We conducted a cross-sectional study among PLHIV aged 18 years and over seen at the Infectious Diseases Department of the University Hospital of Caracas, Venezuela between March 2021 and February 2022. RESULTS: A total of 238 PLHIV were included in the study. The median age was 43 (IQR 31-55) years, and the majority were male (68.9%). Most patients (88.2%, n = 210) came for routine check-ups, while 28 (11.3%) were newly diagnosed. The majority of patients (96.1%) were on antiretroviral therapy (ART), but only 67.8% had a viral load test, with almost all (95.6%) being undetectable. Among those who attended regular appointments, 11.9% reported missing at least one medical consultation, and 3.3% reported an interruption in their ART refill. More than half of the patients (55.5%) had received at least one dose of the COVID-19 vaccine, while the rest expressed hesitancy to get vaccinated. Most patients with COVID-19 vaccine hesitancy were male (65.1%), younger than 44 years (57.5%), employed (47.2%), and had been diagnosed with HIV for less than one year (33%). However, no statistically significant differences were found between vaccinated patients and those with COVID-19 vaccine hesitancy. Older age was a risk factor for missing consultations, while not having an alcoholic habit was identified as a protective factor against missing consultations. CONCLUSION: This study found that the COVID-19 pandemic had a limited impact on adherence to medical consultations and interruptions in ART among PLHIV seen at the University Hospital of Caracas, Venezuela.

Low HDL-C/ApoA-I index is associated with cardiometabolic risk factors and coronary artery calcium: a sub-analysis of the genetics of atherosclerotic disease (GEA) study.

BACKGROUND: The high-density lipoprotein cholesterol to apolipoprotein A-I index (HDL-C/ApoA-I) may be practical and useful in clinical practice as a marker of atherosclerosis. This study aimed to investigate the association between the HDL-C/ApoA-I index with cardiometabolic risk factors and subclinical atherosclerosis. METHODS: In this cross-sectional sub-analysis of the GEA study, 1,363 individuals, women (51.3%) and men (48.7%) between 20 and 75 years old, without coronary heart disease or diabetes mellitus were included. We defined an adverse cardiometabolic profile as excess adipose tissue metrics, non-alcoholic liver fat measured by non-contrasted tomography, metabolic syndrome, dyslipidemias, and insulin resistance. The population was stratified by quartiles of the HDL-C/Apo-AI index, and its dose-relationship associations were analysed using Tobit regression, binomial, and multinomial logistic regression analysis. RESULTS: Body mass index, visceral and pericardial fat, metabolic syndrome, fatty liver, high blood pressure, and CAC were inversely associated with the HDL-C/ApoA-I index. The CAC > 0 prevalence was higher in quartile 1 (29.2%) than in the last quartile (22%) of HDL-C/ApoA-I index (p = 0.035). The probability of having CAC > 0 was higher when the HDL-C/ApoA-I index was less than 0.28 (p < 0.001). This association was independent of classical coronary risk factors, visceral and pericardial fat measurements. CONCLUSION: The HDL-C/ApoA-I index is inversely associated with an adverse cardiometabolic profile and CAC score, making it a potentially useful and practical biomarker of coronary atherosclerosis. Overall, these findings suggest that the HDL-C/ApoA-I index could be useful for evaluating the probability of having higher cardiometabolic risk factors and subclinical atherosclerosis in adults without CAD.

A novel class of Candida glabrata cell wall proteins with ß-helix fold mediates adhesion in clinical isolates.

Candida glabrata is an opportunistic pathogenic yeast frequently causing infections in humans. Though it lacks typical virulence factors such as hyphal development, C. glabrata contains a remarkably large and diverse set of putative wall adhesins that is crucial for its success as pathogen. Here, we present an analysis of putative adhesins from the homology clusters V and VI. First, sequence similarity network analysis revealed relationships between cluster V and VI adhesins and S. cerevisiae haze protective factors (Hpf). Crystal structures of A-regions from cluster VI adhesins Awp1 and Awp3b reveal a parallel right-handed ß-helix domain that is linked to a C-terminal ß-sandwich. Structure solution of the A-region of Awp3b via single wavelength anomalous diffraction phasing revealed the largest known lanthanide cluster with 21 Gd3+ ions. Awp1-A and Awp3b-A show structural similarity to pectate lyases but binding to neither carbohydrates nor Ca2+ was observed. Phenotypic analysis of awp1Δ, awp3Δ, and awp1,3Δ double mutants did also not confirm their role as adhesins. In contrast, deletion mutants of the cluster V adhesin Awp2 in the hyperadhesive clinical isolate PEU382 demonstrated its importance for adhesion to polystyrene or glass, biofilm formation, cell aggregation and other cell surface-related phenotypes. Together with cluster III and VII adhesins our study shows that C. glabrata CBS138 can rely on a set of 42 Awp1-related adhesins with ß-helix/α-crystallin domain architecture for modifying the surface characteristics of its cell wall.

Suicidal ideation among people with Parkinson's disease and comparison with a control group.

BACKGROUND: Detection of suicidal ideation (SI) is key for trying to prevent suicide. The aim of this study was to analyze the frequency of SI and related factors in Spanish people with Parkinson's Disease (PwPD) and to compare them with a control group. METHODS: PD patients and controls recruited from the Spanish cohort COPPADIS from January 2016 to November 2017 were included. Two visits were conducted: V0 (baseline); V2 (2-year ± 1 month follow-up). SI was defined as a score ≥1 on item nine of the Beck Depression Inventory-II (BDI-II). Regression analyses were conducted to identify factors related to SI. RESULTS: At baseline, 693 PwPD (60.2% males; 62.59 ± 8.91 years old) and 207 controls (49.8% males; 60.99 ± 8.32 years old) were included. No differences between PwPD and controls were detected in SI frequency at either V0 (5.1% [35/693] vs. 4.3% [9/207]; p = 0.421) or at V2 (5.1% [26/508] vs. 4.8% [6/125]; p = 0.549). Major depression (MD) and a worse quality of life were associated with SI at both visits in PwPD: V0 (MD, OR = 5.63; p = 0.003; PDQ-39, OR = 1.06; p = 0.021); V2 (MD, OR = 4.75; p = 0.027; EUROHIS-QOL8, OR = 0.22; p = 0.006). A greater increase in the BDI-II total score from V0 to V2 was the only factor predicting SI at V2 (OR = 1.21; p = 0.002) along with an increase in the total number of non-antiparkinsonian drugs (OR = 1.39; p = 0.041). CONCLUSION: The frequency of SI (5%) in PwPD was similar to in controls. Depression, a worse quality of life, and a greater comorbidity were related to SI.

Chromosome-level assemblies from diverse clades reveal limited structural and gene content variation in the genome of Candida glabrata.

BACKGROUND: Candida glabrata is an opportunistic yeast pathogen thought to have a large genetic and phenotypic diversity and a highly plastic genome. However, the lack of chromosome-level genome assemblies representing this diversity limits our ability to accurately establish how chromosomal structure and gene content vary across strains. RESULTS: Here, we expanded publicly available assemblies by using long-read sequencing technologies in twelve diverse strains, obtaining a final set of twenty-one chromosome-level genomes spanning the known C. glabrata diversity. Using comparative approaches, we inferred variation in chromosome structure and determined the pan-genome, including an analysis of the adhesin gene repertoire. Our analysis uncovered four new adhesin orthogroups and inferred a rich ancestral adhesion repertoire, which was subsequently shaped through a still ongoing process of gene loss, gene duplication, and gene conversion. CONCLUSIONS: C. glabrata has a largely stable pan-genome except for a highly variable subset of genes encoding cell wall-associated functions. Adhesin repertoire was established for each strain and showed variability among clades.

Oligodendrocytes regulate the adhesion molecule ICAM-1 in neuroinflammation.

Recently, oligodendrocytes (Ol) have been attributed potential immunomodulatory effects. Yet, the exact mode of interaction with pathogenic CNS infiltrating lymphocytes remains unclear. Here, we attempt to dissect mechanisms of Ol modulation during neuroinflammation and characterize the interaction of Ol with pathogenic T cells. RNA expression analysis revealed an upregulation of immune-modulatory genes and adhesion molecules (AMs), ICAM-1 and VCAM-1, in Ol when isolated from mice undergoing experimental autoimmune encephalomyelitis (EAE). To explore whether AMs are involved in the interaction of Ol with infiltrating T cells, we performed co-culture studies on mature Ol and Th1 cells. Live cell imaging analysis showed direct interaction between both cell types. Eighty percentage of Th1 cells created contacts with Ol that lasted longer than 15 min, which may be regarded as physiologically relevant. Exposure of Ol to Th1 cells or their supernatant resulted in a significant extension of Ol processes, and upregulation of AMs as well as other immunomodulatory genes. Our observations indicate that blocking of oligodendroglial ICAM-1 can reduce the number of Th1 cells initially contacting the Ol. These results suggest that AMs may play a role in the interaction between Ol and Th1 cells. We identified Ol interacting with CD4+ cells in vivo in spinal cord tissue of EAE diseased mice indicating that our in vitro findings are of interest to further scientific research in this field. Further characterization and understanding of Ol interaction with infiltrating cells may lead to new therapeutic strategies enhancing Ol protection and remyelination potential. Oligodendrocytes regulate immune modulatory genes and adhesion molecules during autoimmune neuroinflammation Oligodendrocytes interact with Th1 cells in vitro in a physiologically relevant manner Adhesion molecules may be involved in Ol-Th1 cell interaction.

Pessimistic cognitive bias is associated with enhanced reproductive investment in female zebrafish.

Optimistic and pessimistic cognitive biases have been described in many animals and are related to the perceived valence of the environment. We, therefore, hypothesize that such cognitive bias can be adaptive depending on environmental conditions. In reward-rich environments, an optimistic bias would be favoured, whereas in harsh environments, a pessimistic one would thrive. Here, we empirically investigated the potential adaptive value of such bias using zebrafish as a model. We first phenotyped female zebrafish in an optimistic/pessimistic axis using a previously validated judgement bias assay. Optimistic and pessimistic females were then exposed to an unpredictable chronic stress protocol for 17 days, after which fish were euthanized and the sectional area of the different ovarian structures was quantified in both undisturbed and stressed groups. Our results show that zebrafish ovarian development responded to chronic stress, and that judgement bias impacted the relative area of the vitellogenic developmental stage, with pessimists showing higher vitellogenic areas as compared with optimists. These results suggest that pessimism maximizes reproductive investment, through increased vitellogenesis, indicating a relationship between cognitive bias and life-history organismal decisions.

Validation of a commercial allergen microarray platform for specific immunoglobulin E detection of respiratory and plant food allergens.

BACKGROUND: As the use of multiplex-specific immunoglobulin E (sIgE) detection methods becomes increasingly widespread, proper comparative validation assessments of emerging new platforms are vital. OBJECTIVE: To evaluate the clinical and technical performance of a newly introduced microarray platform, Allergy Explorer (ALEX) (MacroArray Diagnostics), in the diagnosis of pollen (cypress, grass, olive), dust mite (Dermatophagoides pteronyssinus), mold (Alternaria alternata), fruit (apple, peach), and nut (walnut, hazelnut and peanut) allergies and to compare it with those of the ImmunoCAP Immuno Solid-phase Allergen Chip (ISAC) 112 microarray and the ImmunoCAP singleplex method (ThermoFisher Scientific). METHODS: We enrolled 153 patients with allergy and 16 controls without atopy. The sIgE assays were conducted using ISAC112, ALEX version 2 (ALEX2), and ImmunoCAP for whole extracts and major components. Technical validation of ALEX2 was performed by measuring repeatability and interassay, interbatch, and interlaboratory reproducibility. RESULTS: When measured globally (detection by 1 or more allergen components), ALEX2 had adequate sensitivity and specificity for most of the allergens studied, comparable in general with that of ISAC112 (except for olive pollen and walnut) and similar to that of ImmunoCAP whole extract measurements. Component-by-component analysis revealed comparable results for all techniques, except for Ole e 1 and Jug r 3, in both ISAC112 and ImmunoCAP comparisons, and Alt a 1, when compared with ISAC112. Continuous sIgE levels correlate with sIgE by ImmunoCAP. Good reproducibility and repeatability were observed for ALEX2. CONCLUSION: ALEX2 has sound technical performance and adequate diagnostic capacity, comparable in general with that of ISAC112 and ImmunoCAP.

Predictors of the change in burden, strain, mood, and quality of life among caregivers of Parkinson's disease patients.

BACKGROUND AND OBJECTIVE: Caregiver burden in Parkinson's disease (PD) has been studied in many cross-sectional studies but poorly in longitudinal ones. The aim of the present study was to analyze the change in burden, strain, mood, and quality of life (QoL) after a 2-year follow-up in a cohort of caregivers of patients with PD and also to identify predictors of these changes. PATIENTS AND METHODS: PD patients and their caregivers who were recruited from January/2016 to November/2017 from 35 centers of Spain from the COPPADIS cohort were included in the study. They were evaluated again at 2-year follow-up. Caregivers completed the Zarit Caregiver Burden Inventory (ZCBI), Caregiver Strain Index (CSI), Beck Depression Inventory-II (BDI-II), and EUROHIS-QOL 8-item index (EUROHIS-QOL8) at baseline (V0) and at 2-year follow-up (V2). General linear model repeated measure and lineal regression models were applied. RESULTS: Significant changes, indicating an impairment, were detected on the total score of the ZCBI (p < 0.0001), CSI (p < 0.0001), BDI-II (p = 0.024), and EUROHIS-QOL8 (p = 0.002) in 192 PD caregivers (58.82 ± 11.71 years old; 69.3% were females). Mood impairment (BDI-II; ß = 0.652; p < 0.0001) in patients from V0 to V2 was the strongest factor associated with caregiver's mood impairment after the 2-year follow-up. Caregiver's mood impairment was the strongest factor associated with an increase from V0 to V2 on the total score of the ZCBI (ß = 0.416; p < 0.0001), CSI (ß = 0.277; p = 0.001), and EUROHIS-QOL (ß = 0.397; p = 0.002). CONCLUSION: Burden, strain, mood, and QoL were impaired in caregivers of PD patients after a 2-year follow-up. Mood changes in both the patient and the caregiver are key aspects related to caregiver burden increase.

Cutaneous leishmaniosis due to Leishmania mexicana in a cat treated with cryotherapy.

We report the novel use of cryosurgery to treat cutaneous feline leishmaniosis (FeL) in a domestic cat from mid-western Venezuela. Amastigotes, evident by microscopy in aspirates from the nodular, erythematous nose lesions, were identified as Leishmania mexicana by cytochrome b gene sequence analysis. Lesions resolved completely without relapse after 14 months.

Nous décrivons une nouvelle utilisation de la cryochirurgie pour traiter la leishmaniose féline cutanée (FeL) chez un chat domestique du centre-ouest du Venezuela. Les amastigotes, observés par microscopie dans les cytoponctions des lésions nodulaires et érythémateuses du nez, ont été identifiés comme Leishmania mexicana par analyse de la séquence du gène du cytochrome b. Les lésions ont complètement disparu sans rechute après 14 mois.

Describimos el uso novedoso de la criocirugía para tratar la leishmaniosis cutánea felina (FeL) en un gato doméstico del medio oeste de Venezuela. Los amastigotes, evidentes por microscopía en los aspirados de las lesiones nasales nodulares eritematosas, se identificaron como Leishmania mexicana mediante el análisis de la secuencia del gen del citocromo b. Las lesiones se resolvieron completamente sin recidiva tras 14 meses.

Neste estudo, relatamos a utilização inédita de criocirurgia para tratar leishmaniose felina cutânea (FeL) em um gato doméstico no centro-oeste da Venezuela. Amastigotas, evidentes à microscopia de aspirados da lesão nodular e eritematosa na região nasal, foram identificadas como Leishmania Mexicana por sequenciamento do gene do citocromo b. As lesões se resolveram completamente sem recidiva após 14 meses.

Identification of Candida auris and related species by multiplex PCR based on unique GPI protein-encoding genes.

BACKGROUND: The pathogen Candida auris is rapidly gaining clinical importance because of its resistance to antifungal treatments and its persistence in hospital environments. Early and accurate diagnosis of C. auris infections is crucial, and however, the fungus has often been misidentified by commercial systems. OBJECTIVES: To develop conventional and real-time PCR methods for accurate and rapid identification of C. auris and its discrimination from closely related species by exploiting the uniqueness of certain glycosylphosphatidylinositol (GPI)-modified protein-encoding genes. METHODS: Species-specific primers for two unique putative GPI protein-encoding genes per species were designed for C. auris, C. haemulonii, C. pseudohaemulonii, C. duobushaemulonii, C. lusitaniae and C. albicans. Primers were blind tested for their specificity and efficiency in conventional and real-time multiplex PCR set-up. RESULTS: All primers combinations showed excellent species specificity. In multiplex mode, correct identification was aided by different-sized amplicons for each species. Efficiency of the C. auris primers was validated using a panel of 155 C. auris isolates, including all known genetically diverse clades. In real-time multiplex PCR, different melting points of the amplicons allowed the distinction of C. auris from four related species. C. auris limit of detection was 5 CFU/reaction with a threshold value of 32. The method was also able to detect C. auris in spiked blood and serum. CONCLUSIONS: PCR identification based on unique GPI protein-encoding genes allows for accurate and rapid species identification of C. auris and related species without need for expensive equipment when applied in conventional PCR set-up.

Reduction in concentration of chromium (VI) by Lysinibacillus macroides isolated from sediments of the Chapala Lake, Mexico.

The Chapala Lake is one of the most polluted lakes in Mexico, due to the in flow of effluents from several industrial plants, the lake accumulates pollutants such as chromium(VI) which is considered important for aquatic ecosystem. This study aimed was to evaluate the ability to decrease the concentration of chromium (VI) by Lysinibacillus macroides 2(1B)104A, isolated from sediments of the Chapala Lake. The strain was identified through 16S rRNA sequencing and phylogenetic analysis. Results showed that this strain grows in concentrations of 50, 100, 200 and 300 mgL-1 Cr(VI), in pH ranging 6 to 7, showing 79.508% reduction in concentration 50 mgL-1, determining that the reduction occurs extracellularly. Likewise, it was observed that Lysinibacillus macroides reduced the concentration of Cr(IV) in the broth, it was not observed that the bacteria could sequester Cr(VI) in the membrane or intracellularly. However, it reduced the concentration of Cr(VI) in the broth. Lysinibacillus macroides 2(1B)104A isolate showed having the ability that decrease the concentration of Cr(VI), which makes it a viable options for bioremediation of water polluted with this metal.

Distribution, treatment outcome and genetic diversity of Leishmania species in military personnel from Colombia with cutaneous leishmaniasis.

BACKGROUND: Leishmaniasis is one of the most important infectious diseases affecting the Colombian National Army due to the high number of reported cases and exposure throughout military operations in endemic areas. The main aim of this study was to estimate the geographical distribution along with the genetic diversity and treatment outcome of Leishmania species in Colombian military personnel. METHODS: Skin lesion samples by smear and aspirate were collected in 136 patients having parasitological cutaneous leishmaniasis (CL) diagnosis. DNA was extracted, the nuclear marker heat shock protein 70 (HSP70) was amplified by PCR and sequenced. Leishmania species were identified by BLASTn. The geo-spatial distribution of the identified parasites was determined according to the possible site of infection. Gene tree was constructed by maximum likelihood (ML), diversity indices (π, h) were estimated and haplotype network was constructed under the Templeton-Crandall-Sing algorithm in order to determine the geographic relationships of the genetic variants of Leishmania species circulating in Colombian military population. RESULTS: The species were identified in 77.94% of the samples, with a predominance of L. braziliensis (65.09%), followed by L. panamensis (31.13%), L. naiffi by the first time reported in Colombia in two patients (1.89%) as well as L. lindenbergi in a single patient (0.945%) with possible infection in the municipality of Miraflores, Guaviare and L. infantum in a single patient (0.945%) notified with CL in the municipality of Tumaco, Nariño. The phylogenetic analysis was consistent according to bootstrap, showing four strongly differentiated clades. CONCLUSIONS: The geo-spatial distribution suggested that L. braziliensis has a greater abundance, while L. panamensis has a greater dispersion. The phylogenetic relationships of Leishmania species in Colombian military personnel was estimated with the confirmation of two new species circulating without prior report in the country and a species with no background for CL in the Colombian army. A substantial genetic diversity of Leishmania braziliensis was defined. This study contributes through the understanding of the molecular epidemiology to the CL transmission in Colombia.

Tolerance of torasemide in cats with congestive heart failure: a retrospective study on 21 cases (2016-2019).

BACKGROUND: In dogs with congestive heart failure (CHF), the efficacy of torasemide, a loop diuretic, has been demonstrated. However, unlike in dogs and humans little has been described about the use of torasemide in the cat with spontaneous CHF. The objectives of this retrospective study were therefore to describe the therapeutic use of oral torasemide in cats with spontaneous CHF, document its potential adverse effects while reporting the clinical course of this feline population following torasemide administration in addition to standard medical therapy. RESULTS: Medical records of 21 client-owned cats with CHF (median age = 10.6 years [interquartile range (IQR) = 6.5-11.2]) receiving torasemide were reviewed. Data collected included torasemide dosages, other concurrent medications, physical examination features, echocardiographic data, and potential adverse effects during follow-up. A survival analysis was performed to estimate the time from diagnosis to cardiac death. Dyspnea related to CHF was identified in all cats (pleural effusion [8/21], pulmonary edema [5/21] or both [8/21]), associated with ascites in 4/21 cats. The CHF cause was determined by echocardiography in all cats: hypertrophic (n = 10), restrictive (n = 6), arrhythmogenic right ventricular (n = 3), dilated (n = 1) cardiomyopathies, and aortic valve abnormality (n = 1). At initiation, median torasemide dosage was 0.21 mg/kg [IQR = 0.17-0.23] q24h. Clinical signs declined in most cats (20/21) during the first 2 weeks with no remarkable adverse events. Median survival time after torasemide prescription was 182 days [IQR = 46-330]. A contemporary control group including 54 cats with CHF, receiving furosemide as sole loop diuretic treatment was compared with the study group. Median (IQR) survival time of cats in the control group was not significatively different (p = 0.962) from that of the torasemide group, i.e., 148 days (9-364), although the torasemide group included significantly more cats with recurrent episodes of CHF (52%) that the control group (19%). CONCLUSIONS: This case series demonstrates that torasemide can be used in cats with spontaneous CHF. This therapeutic interest needs to be confirmed by prospective clinical trials.

Profilin-mediated food-induced allergic reactions are associated with oral epithelial remodeling.

BACKGROUND: In areas of high exposure to grass pollen, allergic patients are frequently sensitized to profilin, and some experience severe profilin-mediated food-induced reactions. This specific population of patients is ideal to study the relationship between respiratory and food allergies. OBJECTIVE: We sought to determine the role of oral mucosal epithelial barrier integrity in profilin-mediated allergic reactions. METHODS: Thirty-eight patients with profilin allergy stratified into mild or severe according to their clinical history and response to a profilin challenge test and 6 nonallergic subjects were recruited. Oral mucosal biopsies were used for measurement of CD11c, CD3, CD4, tryptase, claudin-1, occludin, E-cadherin, and vascular endothelial growth factor A levels; Masson trichrome staining; and POSTN, IL33, TPSAB, TPSB, and CMA gene expression analysis by using quantitative RT-PCR. Blood samples were used for basophil activation tests. RESULTS: Distinct features of the group with severe allergy included the following: (1) impaired epithelial integrity with reduced expression of claudin-1, occludin, and E-cadherin and decreased numbers of epithelial cells, which is indicative of acanthosis, higher collagen deposition, and angiogenesis; (2) inflammatory immune response in the mucosa, with an increased number of CD11c+ and CD4+ infiltrates and increased expression of the cytokine genes POSTN and IL33; and (3) a 10-fold increased sensitivity of basophils to profilin. CONCLUSIONS: Patients with profilin allergy present with significant damage to the oral mucosal epithelial barrier, which might allow profilin penetration into the oral mucosa and induction of local inflammation. Additionally, severely allergic patients presented with increased sensitivity of effector cells.

Multi-omics analysis points to altered platelet functions in severe food-associated respiratory allergy.

BACKGROUND: Prevalence and severity of allergic diseases have increased worldwide. To date, respiratory allergy phenotypes are not fully characterized and, along with inflammation progression, treatment is increasingly complex and expensive. Profilin sensitization constitutes a good model to study the progression of allergic inflammation. Our aim was to identify the underlying mechanisms and the associated biomarkers of this progression, focusing on severe phenotypes, using transcriptomics and metabolomics. METHODS: Twenty-five subjects were included in the study. Plasma samples were analyzed using gas and liquid chromatography coupled to mass spectrometry (GC-MS and LC-MS, respectively). Individuals were classified in four groups-"nonallergic," "mild," "moderate," and "severe"-based on their clinical history, their response to an oral challenge test with profilin, and after a refinement using a mathematical metabolomic model. PBMCs were used for microarray analysis. RESULTS: We found a set of transcripts and metabolites that were specific for the "severe" phenotype. By metabolomics, a decrease in carbohydrates and pyruvate and an increase in lactate were detected, suggesting aerobic glycolysis. Other metabolites were incremented in "severe" group: lysophospholipids, sphingosine-1-phosphate, sphinganine-1-phosphate, and lauric, myristic, palmitic, and oleic fatty acids. On the other hand, carnitines were decreased along severity. Significant transcripts in the "severe" group were found to be downregulated and were associated with platelet functions, protein synthesis, histone modification, and fatty acid metabolism. CONCLUSION: We have found evidence that points to the association of severe allergic inflammation with platelet functions alteration, together with reduced protein synthesis, and switch of immune cells to aerobic glycolysis.

Fetal hydrometrocolpos and congenital imperforate hymen: Prenatal and postnatal imaging features.

Congenital imperforate hymen is probably the most common obstructive anomaly of the female reproductive tract. The accumulation of fluid in the genital tract leads to a distended uterus and vagina, causing hydrometrocolpos. Prenatal diagnosis of fetal hydrometrocolpos is uncommon, with only 22 cases reported in the literature and only a few cases of prenatal imaging of this condition available to date. The main ultrasound finding is a fetal pelvic mass posterior to the bladder and anterior to the rectum. We present the case of a 37-week female fetus with a fetal pelvic mass detected in a routine obstetric ultrasound examination, and the correlation between the prenatal and postnatal findings.

Biochemical and Molecular Characterization of a Native Haloalkalophilic Tolerant Strain from the Texcoco Lake.

In the last decade several new genera have been isolated in alkaline and halophile growth conditions. The studies conducted in the Texcoco Lake soils have shown a generalized microbial adaptation to the specific conditions. In this research work, morphological and phylogenetic characterization of the HN31(22) strain that was isolated from the cited soil is presented. The strain was identified as a Gram-positive halophile and alkaline tolerant bacteria from the Nesterenkonia genus, which uses different substrates in metabolic processes.

A clinical trial comparing propofol versus propofol plus midazolam in diagnostic endoscopy of patients with a low anesthetic risk.

BACKGROUND AND OBJECTIVES: propofol and midazolam are two of the most commonly used sedatives in upper gastrointestinal endoscopy (UGE). The objective of this study was to evaluate these two sedation regimens administered to patients who underwent an UGE with regard to security, efficiency, quality of exploration and patient response. PATIENTS AND METHODS: a prospective, randomized and double-blind study was performed which included 83 patients between 18 and 80 years of age of a low anesthetic risk (ASA - American Society of Anesthesiologists- I-II) who underwent a diagnostic UGE. Patients were randomized to receive sedation with either placebo plus propofol (group A) or midazolam plus propofol (group B). RESULTS: in group A, 42 patients received a placebo bolus (saline solution) and on average up to 115 mg of propofol in boluses of 20 mg. In group B, 41 patients received 3 mg of midazolam and an average of up to 83 mg of propofol in boluses of 20 mg. There were no significant differences in the adverse effects observed in either group and all adverse events were treated conservatively. The patients in group B (midazolam plus propofol) entered the desired sedated state more quickly with no variation in the overall time of the exploration. The quality of the endoscopic evaluation was similar in both groups and the patients were equally satisfied regardless of the sedatives they received. CONCLUSIONS: the use of midazolam plus propofol as a sedative does not affect the overall exploration time, a lower dose of propofol can be used and it is as safe as administering propofol as a monotherapy while providing the same level of both exploration quality and patient approval.