Obstructive Sleep Apnea: a risk for uncontrolled and more severe asthma in adults that we should keep an eye on.

Summary: Background. Asthma control can be influenced by several factors, including obstructive sleep apnea (OSA). The literature reports variable prevalence and magnitude of OSA impact on asthma outcomes. The aim of our study is to analyze the frequency of high-risk for OSA in asthma patients and its impact on disease severity and control. Methods. We conducted a cross-sectional study at an Allergy Department with adult asthma patients recruited while undergoing routine lung function tests. Data on sex, age, body mass index, allergen sensitization, smoking habits, risk of OSA (using the Berlin questionnaire), rhinitis control (through CARAT), asthma severity (based on GINA 2023), asthma control (using the ACT), adherence to asthma treatment (through Treatment Adherence Measure) and pulmonary function test results were collected. Results. We included 216 patients, predominantly women (70.4%), with a median (P25-P75) age of 29.0 (21.0-45.0) years, of whom 28.2% were on GINA treatment levels 4-5. In 75.5% of cases asthma was controlled. High-risk for OSA was identified in 21.8% of patients. Asthma patients with high-risk for OSA were more likely to have uncontrolled [(47.8%; n = 22) vs (15.8%; n = 26); p less than 0.001] and more severe disease [(44.7%; n = 21) vs (23.7%; n = 40), p = 0.006]. In multivariable analysis, high-risk for OSA (OR 2.81 [95%CI 1.1.28-6.17], p = 0.010), sex (women) (OR 5.21 [95% CI 1.70-15.96], p = 0.004), uncontrolled rhinitis (OR 3.65 [95%CI 1.38-9.64], p = 0.009) and GINA asthma treatment steps 4-5 (OR 2.46 [95%CI 1.15-5.26], p = 0.020) were associated with uncontrolled asthma. Conclusions. It is crucial to actively investigate OSA, especially in patients with uncontrolled and more severe forms of asthma.

The impact of a drug allergy label in an internal medicine ward.

Summary: Background. Drug hypersensitivity reactions are presumably immune-mediated reactions that cause reproducible signs and/or symptoms. Overdiagnosis of drug allergy, frequently self-reported, is common and carries significant limitations. We intended to analyze the frequency and impact of drug allergy in hospitalized patients. Methods. A retrospective study was conducted in an Internal Medicine ward at a tertiary hospital in Portugal. All patients with a drug allergy report admitted within a 3-year period were included. Data were collected from their electronic medical records. Results. We found that 15.4% of patients had a report of drug allergy, with antibiotics being the most common (56.4%), followed by non-steroidal anti-inflammatory drugs (21.7%) and radiocontrast media (7.0%). The allergy report affected the clinical approach of 14.5% of patients by motivating the use of second-line agents, or the eviction of necessary procedures. The usage of alternative antibiotics entailed a cost increase of 2.4 times. There were 14.7% of patients to whom the suspected drug was administered: 87.0% tolerated and 13.0% developed a reaction. Only 1.9% were referred to our Allergy and Clinical Immunology department and proceeded in their allergy study. Conclusions. In this study, a considerable number of patients had a drug allergy label on their records. This label contributed to an increase in the cost of treatment, or the avoidance of necessary exams. However, disregarding an allergy record may lead to potentially life-threatening reactions that proper risk assessment could avoid. Further investigation should always be part of the follow-up routine of these patients, and better articulation between departments should be encouraged.

Pediatric postmortem CT angiography: validation of vascular access for PMCT angiography in stillbirths, babies and toddlers.

PURPOSE: The use of angiography in postmortem CT angiography (PMCTA) has several advantages. In adults, femoral vascular access is well established. Due to the small and specific anatomy in fetuses and infants, the technique has to be adapted, especially regarding the vascular access. The aim of this study was to evaluate vascular access for pediatric PMCTA (pedPMCTA). MATERIALS AND METHODS: Ten pedPMCTAs were performed in stillbirths, babies, and one toddler. A femoral approach by cannulation of the femoral artery and vein, an umbilical approach by cannulation of the umbilical vessels, and an intraosseous approach by an intraosseous needle were evaluated by handling and resulting imaging. RESULTS: The insertion of a cannula with a size of 18-20 G in the femoral vessels was possible in babies. An umbilical access with peripheral venous cannulas with a size of 14-20 G was feasible in stillbirths and newborns. An intraosseous access is advisable as equal alternative to umbilical and in cases where a femoral access is not possible. The most significant problem with the vascular access is the extravasation of contrast media, but this can be reduced significantly with practice. CONCLUSION: When performing pedPMCTA, an umbilical vascular access is recommended if an umbilical cord with open vessels is still present. Otherwise, a bone marrow access should be preferred in the presence of an arteriovenous shunt or if only the venous system needs to be shown. If that is not the case, the femoral access with the possibility to separate venous and arterial scan should be used.

Immunoallergic disorders in the elderly.

Summary: Although allergic diseases have become increasingly prevalent in the elderly, there are few data on this population. Through a retrospective analysis of the electronic medical records of patients aged 65 years and above followed in our Immunoallergology Unit, we aimed to characterize the immunoallergic diseases of the elderly. The most common disorders were respiratory diseases (n = 185; 50%), mucocutaneous diseases (n = 113; 31%), drug allergy (n = 31; 8%), food allergy (n = 9; 2%), and anaphylaxis (n = 9; 2%). Use of specific immunotherapy was residual (n = 2; 1%). There was an association between anaphylaxis and both, drug (p = 0.004) and food (p = 0.013) allergies. Non-allergic rhinitis and bronchial asthma were more frequent in females, and ACE inhibitors/ARB induced-angioedema in males. Recognizing the characteristics of immunoallergic diseases in the elderly and the specificities of this age group is paramount in providing these patients with the best possible care.

Short communication: Socio-psychological factors influencing dairy farmers' intention to adopt high-grain feeding in Brazil.

This study aimed to apply the theory of planned behavior to determine the effects of attitude, perceived behavioral control, and subjective norms on the intention of dairy farmers toward high-grain feeding. Quantitative data were collected through interviews with 150 dairy farmers in Paraná, Brazil. Partial least squares structural equation modeling was used to analyze the data. We observed that farmers with a positive perception of grain feeding (attitude) and a positive perception of their ability to increase the use of grains (perceived behavioral control) had higher intention to increase grain feeding. Social pressure (subjective norm) had no effect on the intention to grain feed. These results can contribute to the development of public strategies and policies that encourage the use of high-grain diets in dairy farms.

The Impact of Prior Season Vaccination on Subsequent Influenza Vaccine Effectiveness to Prevent Influenza-related Hospitalizations Over 4 Influenza Seasons in Canada.

BACKGROUND: Recent studies have demonstrated the possibility of negative associations between prior influenza vaccines and subsequent influenza vaccine effectiveness (VE), depending on season and strain. We investigated this association over 4 consecutive influenza seasons (2011-2012 through 2014-2015) in Canada. METHODS: Using a matched test-negative design, laboratory-confirmed influenza cases and matched test-negative controls admitted to hospitals were enrolled. Patients were stratified into 4 groups according to influenza vaccine history (not vaccinated current and prior season [referent], vaccinated prior season only, vaccinated current season only, and vaccinated both current and prior season). Conditional logistic regression was used to estimate VE; prior vaccine impact was assessed each season for overall effect and effect stratified by age (<65 years, ≥65 years) and type/subtype (A/H1N1, A/H3N2, influenza B). RESULTS: Overall, mainly nonsignificant associations were observed. Trends of nonsignificant decreased VE among patients repeatedly vaccinated in both prior and current season relative to the current season only were observed in the A/H3N2-dominant seasons of 2012-2013 and 2014-2015. Conversely, in 2011-2012, during which B viruses circulated, and in 2013-2014, when A/H1N1 circulated, being vaccinated in both seasons tended to result in a high VE in the current season against the dominant circulating subtype. CONCLUSIONS: Prior vaccine impact on subsequent VE among Canadian inpatients was mainly nonsignificant. Even in circumstances where we observed a trend of negative impact, being repeatedly vaccinated was still more effective than not receiving the current season's vaccine. These findings favor continuation of annual influenza vaccination recommendations, particularly in older adults. CLINICAL TRIALS REGISTRATION: NCT01517191.

Effects of rumen-undegradable protein on intake, performance, and mammary gland development in prepubertal and pubertal dairy heifers.

The objective of this study was to evaluate the influence of different amounts of rumen-undegradable protein (RUP) on intake, N balance, performance, mammary gland development, carcass traits, and hormonal status of Holstein heifers at different physiological stages (PS). Sixteen prepubertal (PRE) heifers (initial BW = 106 ± 7.6 kg; age = 4.3 ± 0.46 mo) and 16 pubertal (PUB) heifers (initial BW = 224 ± 7.9 kg; age = 12.6 ± 0.45 mo) were used in an experiment over a period of 84 d. Four diets with increasing RUP contents (38, 44, 51, and 57% of dietary crude protein) and heifers at 2 PS (PRE or PUB) were used in a 4 × 2 factorial arrangement of treatments in a completely randomized design. Throughout the experiment, 2 digestibility trials were performed over 5 consecutive days (starting at d 36 and 78) involving feed and ort sampling and spot collections of feces and urine. At d 0 and 83, body ultrasound images were obtained for real-time carcass trait evaluation. The mammary gland was ultrasonically scanned at d 0 and every 3 wk during the experiment. Blood samples were taken at d 0 and 84 to determine serum concentrations of progesterone, estrogen, insulin-like growth factor I (IGF-I), and insulin. No interaction between PS and the level of RUP was found for any trait. Apparent digestibility of dry matter, organic matter, and neutral detergent fiber corrected for ash and protein was not affected by RUP level but was lower for PRE compared with PUB heifers. Sorting against neutral detergent fiber corrected for ash and protein (tendency only) and for crude protein was greater for PUB than PRE heifers. Pubertal heifers had greater average daily gain (905 vs. 505 g/d) and N retention (25.9 vs. 12.5 g/d) than PRE heifers. In addition, average daily gain and N retention were greatest at 51% RUP of dietary protein. Mammary ultrasonography indicated no effects of RUP amounts on mammary gland composition, whereas PRE heifers had greater pixel values than PUB, indicating higher contents of fat rather than protein in the mammary glands of PRE heifers. Serum progesterone and IGF-I concentration was affected only by PS, and PRE heifers had greater values of progesterone and IGF-I concentrations than PUB heifers. Serum insulin concentration was unaffected by PS but tended to be higher at 51% of RUP. In conclusion, an RUP level of 51% increases body weight, average daily gain, feed efficiency, and N retention in heifers regardless of the PS. In addition, PRE heifers have a lower sorting ability and reduced intake, total-tract digestibility, and N retention. They also have higher amounts of fat in their mammary glands, even at moderate growth rates.

Colour-Doppler ultrasound imaging as a laparoscopy substitute to count corpora lutea in superovulated sheep.

This study evaluated colour-Doppler ultrasound imaging (UI) as a substitute for laparoscopy to count the corpora lutea (CL) in superovulated sheep. Twenty-five Santa Ines ewes were superovulated three times at 21-day intervals. Corpora lutea were counted by colour-Doppler UI (CLDOPPLER ) 6 days after each superovulation and confirmed by laparoscopy (CLLAP ) 12 hr later. The mean number of CL was similar for both techniques (2.1 ± 2.5 vs. 2.1 ± 2.7 for CLDOPPLER and CLLAP , respectively) with a significant positive correlation (r = .94; r2 =.89). Colour-Doppler UI effectively evaluated the ovarian response in superovulated ewes and efficiently identified animals that did not respond to superovulation.

Candida albicans biofilms: comparative analysis of room-temperature and cryofixation for scanning electron microscopy.

Biofilms are frequently related to invasive fungal infections and are reported to be more resistant to antifungal drugs than planktonic cells. The structural complexity of the biofilm as well as the presence of a polymeric extracellular matrix (ECM) is thought to be associated with this resistant behavior. Scanning electron microscopy (SEM) after room temperature glutaraldehyde-based fixation, have been used to study fungal biofilm structure and drug susceptibility but they usually fail to preserve the ECM and, therefore, are not an optimised methodology to understand the complexity of the fungal biofilm. Thus, in this work, we propose a comparative analysis of room-temperature and cryofixation/freeze substitution of Candida albicans biofilms for SEM observation. Our experiments showed that room-temperature fixative protocols using glutaraldehyde and osmium tetroxide prior to alcohol dehydration led to a complete extraction of the polymeric ECM of biofilms. ECM from fixative and alcohol solutions were recovered after all processing steps and these structures were characterised by biochemistry assays, transmission electron microscopy and mass spectrometry. Cryofixation techniques followed by freeze-substitution lead to a great preservation of both ECM structure and C. albicans biofilm cells, allowing the visualisation of a more reliable biofilm structure. These findings reinforce that cryofixation should be the indicated method for SEM sample preparation to study fungal biofilms as it allows the visualisation of the EMC and the exploration of the biofilm structure to its fullest, as its structural/functional role in interaction with host cells, other pathogens and for drug resistance assays.

Zoledronic acid and alendronate sodium and the implications in orthodontic movement.

OBJECTIVE: To evaluate orthodontic tooth movement (OTM) in rats treated with two types of bisphosphonates (BPs), alendronate sodium (A) and zoledronic acid (Z). DESIGN: In all, 15 male Wistar rats were randomly divided into three groups. Group OTM+A: orthodontic tooth movement and subcutaneous administration of alendronate sodium (2.5 mg/kg); Group OTM+Z: orthodontic tooth movement and subcutaneous administration of zoledronic acid (0.02 mg/kg), and Group OTM: orthodontic tooth movement and subcutaneous injection of saline. The BPs were administered once a day during 25 days before OTM started and during 10 days of OTM. The left upper first molar was moved with a stainless-steel closed coil spring which delivered an initial force of 0.4N. OTM was measured with a digital caliper comparing the moved and the contralateral side. The histomorphometric analysis counted the number of osteoclasts, inflammatory cells, blood vessels and fibroblasts (n/104  m2 ) in periodontal ligament (PDL) of the distobuccal root. RESULTS: A reduction of 58.3% of OTM was found in Group OTM+A and 99.6% in Group OTM+Z, when compared with Group OTM. There was a significant decrease of osteoclasts and inflammatory cells in BP-treated groups. Blood vessels and fibroblastic cells decreased mainly in Group OTM+Z. CONCLUSION: Alendronate sodium and zoledronic acid have similar effects on the periodontal tissue during orthodontic treatment in rats. Especially, zoledronic acid can affect orthodontic tooth movement.

Technical note: Mammary gland ultrasonography to evaluate mammary parenchymal composition in prepubertal heifers.

Bovine mammary gland development studies are often terminal or involve invasive biopsy procedures. Therefore, noninvasive means of assessing mammary development should be considered as alternative methods in live animals. The objective was to test if mammary ultrasonography can be used as a noninvasive way to estimate mammary parenchyma (PAR) composition in prepubertal dairy heifers with different average daily body weight gains. In the 84 d preceding, the ultrasound exam heifers were maintained in 1 of 3 treatment groups. Individual heifers were fed a high gain (1 kg/d; n = 6), low gain (0.5 kg/d, n = 6), or maintenance (n = 6) treatment diet. To achieve desired body weight gains, heifers were fed differing amounts of the same silage-based diet. Mammary glands of 18 crossbred heifers Holstein:Gyr underwent a single mammary ultrasound exam immediately before heifer slaughter, which took place when heifers weighed 142.0 ± 8.0 kg and were 200 d old. The 4 mammary glands of each heifer were evaluated using a real-time B-mode ultrasound machine equipped with a 6.5-MHz micro-convex transducer. Digital images (8-bit) of glands were obtained and PAR was identified within gland. Average pixel values per unit of PAR area were determined for each gland and analyzed at the level of heifer. Pixel results were interpreted on the basis that lower average pixel values reflect PAR with relatively high amounts of protein as opposed to fat. To help validate that the pixel value within PAR is associated with composition of PAR, pixel findings were compared with histological [number of adipocytes in PAR (Nad) and epithelial area in PAR (Ep)] and biochemical [percent crude protein in PAR (%CP), percent ether extract in PAR (%EE), PAR weight (WPAR), and mammary fat pad weight (WFAT)] composition of PAR in these same heifers. Within PAR, %EE and WFAT were positively correlated with pixel values, whereas %CP, Ep, and Nad were negatively correlated. Parenchyma weight did not correlate with pixel values. Regression analyses (fixed effect log-pixel value; random effect treatment) were used to estimate Nad, Ep, %CP, %EE, WPAR, and WFAT. Sensitivity analysis of regression equations revealed that accuracy of tested equations ranged from 0.77 to 0.93 and precision ranged from 0.56 to 0.82. Concordance correlation coefficients of the equations ranged from 0.41 to 0.76. In conclusion, ultrasonography of PAR can accurately measure and predict PAR composition in prepubertal dairy heifers growing at various rates of gain.

Immune response of toddlers with history of prematurity.

BACKGROUND: It is not quite well established how immune responses differ in term and preterm infants beyond the first year of life. This study aimed to evaluate aspects of the innate and adaptive immune responses in a group of preterm infants in comparison with their term peers. METHODS: In this cross-sectional study peripheral blood mononuclear cells (PBMC) were isolated from preterm and term children at age three years. Innate immune response was evaluated by the analysis of TLR receptors expression on CD11c+HLADRhigh cells and inflammatory cytokine production after PBMC stimulation with Toll like receptors (TLR) ligands. Adaptive immune response was evaluated by T cells' phenotyping and function after stimulation with polyclonal conventional T cell stimulus. CONCLUSION: We have found that the patterns of innate and adaptive immune responses at 3 years of age were not affected by the fact of the children having being born preterm or at term.

Effects of tacrolimus and erythropoietin in experimental spinal cord lesion in rats: functional and histological evaluation.

STUDY DESIGN: Experimental study with rats. OBJECTIVE: To evaluate functional and histological effects of tacrolimus (FK 506) and erythropoietin (EPO) after experimental spinal cord contusion injury (SCI). SETTING: Brazil. METHODS: Wistar rats (n=60) were submitted to SCI with the NYU Impactor system. The control group received saline; the EPO group received EPO; the group EPO+FK 506 received EPO associated with tacrolimus and the group FK 506 received tacrolimus only. The Sham group underwent SCI, but did not receive any drug. Locomotor function was evaluated after SCI by BBB (Basso, Beattie and Bresnahan) weekly and by the motor-evoked potential test in 42 days. The spinal cord was histologically evaluated. RESULTS: There was a significant difference between treated and the control groups from the seventh day on for BBB scores, with no difference between the groups EPO and EPO+FK 506 by the end of the study. There were significant differences between groups for necrosis and bleeding, but not for hiperemia, degeneration and cellular infiltrate. Axon neuron count was different between all groups (P=0.001), between EPO+FK 506 and FK 506 (P=0.011) and between EPO+FK 506 and Sham (P=0.002). Amplitude was significantly different between all groups except between control and sham. For latency, there was no difference. CONCLUSIONS: This study did not reveal significant differences in the recovery of locomotor function, or in the histological and electrophysiological analysis in animals treated with EPO and tacrolimus after thoracic SCI.

Milk yield, milk composition, and hepatic lipid metabolism in transition dairy cows fed flaxseed or linola.

The response of transition dairy cows to dietary supplementation with fat sources of various fatty acid profiles could affect hepatic fat metabolism differently. Twenty-eight Holstein cows were blocked for similar calving date 4wk before expected parturition to compare the effects of feeding sources of n-3 and n-6 fatty acids on milk production and composition, plasma metabolites, and liver parameters. Cows within each block were assigned to 1 of 3 isonitrogenous and isoenergetic diets: control with a source of calcium salts of palm oil (MEG; 1.1 and 2.6% of the dry matter in prepartum and postpartum diets, respectively); n-3 fatty acids supplied as whole flaxseed (WFL; 4.8 and 7.7% of the dry matter in prepartum and postpartum diets, respectively); and n-6 fatty acids supplied as whole linola (WLO; 4.8 and 7.7% of the dry matter in prepartum and postpartum diets, respectively). Diets were fed until wk 14 of lactation. Contrasts of WFL versus WLO and polyunsaturated fatty acids versus MEG were compared. Cows fed polyunsaturated fatty acids increased dry matter intake over time at a greater extent than those fed MEG, which resulted in enhanced energy balance. Cows fed MEG produced more milk compared with those fed polyunsaturated fatty acids, and there was no difference between those fed WFL and WLO. We found no effect on body condition score and body weight. Plasma concentrations of glucose, fatty acids, and BHB were similar among diets. There was no effect of diet on concentration of glycogen and activities of superoxide dismutase and glutathione peroxidase in the liver. We observed higher concentrations of hepatic lipids and triacylglycerol in cows fed MEG compared with those fed polyunsaturated fatty acids, and no difference between WFL and WLO. Hepatic catalase activity tended to be higher on wk 4 after calving for cows supplemented with WFL compared with those fed WLO. Feeding linoleic and linolenic acids as unprotected oilseeds increased dry matter intake over time at a greater extent for cows fed MEG, improved the energy status, and lowered hepatic lipids and triacylglycerol contents, which may contribute to enhance the health status of transition dairy cows.

Disrupting membrane raft domains by alkylphospholipids.

Using phase contrast and fluorescence microscopy we study the influence of the alkylphospholipid, ALP, 10-(octyloxy) decyl-2-(trimethylammonium) ethyl phosphate, ODPC, in giant unilamellar vesicles, GUVs, composed of DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine), brain sphingomyelin (SM) and cholesterol (Chol). The results show that adding 100µM ODPC (below CMC) to the outer solution of GUVs promotes DOPC membrane disruption over a period of 1h of continuous observation. On the other hand, the presence of SM and Chol in homogeneous fluid lipid bilayers protects the membrane from disruption. Interestingly, by adding 100µM ODPC to GUVs containing DOPC:SM:Chol (1:1:1), which display liquid ordered (Lo)-liquid disordered (Ld) phase coexistence, the domains rapidly disappear in less than 1min of ODPC contact with the membrane. The lipids are subsequently redistributed to liquid domains within a time course of 14-18min, reflecting that the homogenous phase was not thermodynamically stable, followed by rupture of the GUVs. A similar mechanism of action is also observed for perifosine, although to a larger extent. Therefore, the initial stage of lipid raft disruption by both ODPC and perifosine, and maybe other ALPS, by promoting lipid mixing, may be correlated with their toxicity upon neoplastic cells, since selective (dis)association of essential proteins within lipid raft microdomains must take place in the plasma membrane.

Resonance of vector vortex beams in a triangular optical cavity.

We experimentally demonstrate resonance of first-order vector vortex beams (VVB) with a triangular optical cavity. We also show that, due to their symmetry properties, the VVBs commonly known as radial and azimuthal beams do not resonate at the same cavity length, which could be explored to use the triangular resonator as a mode sorter. In addition, an intracavity Pancharatnam phase shifter (PPS) is implemented in order to compensate for any birefringent phase that the cavity mirrors may introduce.

A facile strategy for tuning the density of surface-grafted biomolecules for melt extrusion-based additive manufacturing applications.

Melt extrusion-based additive manufacturing (ME-AM) is a promising technique to fabricate porous scaffolds for tissue engineering applications. However, most synthetic semicrystalline polymers do not possess the intrinsic biological activity required to control cell fate. Grafting of biomolecules on polymeric surfaces of AM scaffolds enhances the bioactivity of a construct; however, there are limited strategies available to control the surface density. Here, we report a strategy to tune the surface density of bioactive groups by blending a low molecular weight poly(ε-caprolactone)5k (PCL5k) containing orthogonally reactive azide groups with an unfunctionalized high molecular weight PCL75k at different ratios. Stable porous three-dimensional (3D) scaffolds were then fabricated using a high weight percentage (75 wt.%) of the low molecular weight PCL5k. As a proof-of-concept test, we prepared films of three different mass ratios of low and high molecular weight polymers with a thermopress and reacted with an alkynated fluorescent model compound on the surface, yielding a density of 201-561 pmol/cm2. Subsequently, a bone morphogenetic protein 2 (BMP-2)-derived peptide was grafted onto the films comprising different blend compositions, and the effect of peptide surface density on the osteogenic differentiation of human mesenchymal stromal cells (hMSCs) was assessed. After two weeks of culturing in a basic medium, cells expressed higher levels of BMP receptor II (BMPRII) on films with the conjugated peptide. In addition, we found that alkaline phosphatase activity was only significantly enhanced on films containing the highest peptide density (i.e., 561 pmol/cm2), indicating the importance of the surface density. Taken together, these results emphasize that the density of surface peptides on cell differentiation must be considered at the cell-material interface. Moreover, we have presented a viable strategy for ME-AM community that desires to tune the bulk and surface functionality via blending of (modified) polymers. Furthermore, the use of alkyne-azide "click" chemistry enables spatial control over bioconjugation of many tissue-specific moieties, making this approach a versatile strategy for tissue engineering applications. Supplementary Information: The online version contains supplementary material available at 10.1007/s42242-024-00286-2.

The impact of the association between Val16Ala-SOD2 SNP and SOD2 immunohistochemistry expression in the prognosis of patients with esophageal cancer.

INTRODUCTION: Esophageal cancer is an extensive public health issue worldwide, warranting the search for biomarkers related to its risk and progression. Previous studies have indicated an association between Val16AlaSOD2 single nucleotide polymorphism in the gene encoding the enzyme superoxide dismutase 2 and esophageal cancer. However, further investigations are needed to clarify its role in disease risk and progression. OBJECTIVE: To investigate the role of Val16AlaSOD2-SNP in esophageal cancer progression and in the survival of patients METHODS: Tumor samples were utilized for Val16Ala-SNP genotyping, while SOD2 expression levels in tissue were assessed using immunohistochemistry. A SOD2 Val16Ala-SNP database was used to obtain information on the genotype of healthy individuals. Risk and overall survival analyzes were performed. RESULTS: The Val16Ala SNP was associated with an increased risk of esophageal cancer (RR 2.18, 95%CI 1.23-3.86), regardless of age and gender, but did not have a significant effect on patient survival. In contrast, weak SOD2 expression demonstrated a significantly associated with poor overall survival after treatment, independent of other clinicopathological variables (HR, 0.41; 95% CI, 0.22-0.79 P = 0.007). CONCLUSIONS: Val16Ala SNP was positively associated with esophageal cancer, and the expression of SOD2 was an independent prognostic marker.

Different immunosuppressive mechanisms in multi-drug-resistant tuberculosis and non-tuberculous mycobacteria patients.

Previous studies have demonstrated that cells from both multi-drug-resistant tuberculosis (MDR-TB) and non-tuberculous mycobacteria (NTM) patients respond poorly to mycobacterial antigens in vitro. In the present study, we compared the in vitro response of cells isolated from sensitive TB (NR-TB)-, MDR-TB- and NTM-infected patients. Analysis of T cell phenotype ex vivo revealed that both MDR-TB and NTM patients present an increased percentage of CD4(+) CD25(+-) forkhead box protein 3 (FoxP3)(+) and CD4(+) CD25(+) CD127(-) regulatory T (T(reg) ) cells when compared to NR-TB. Increased numbers of T(reg) cells and interleukin (IL)-10 serum levels were detected in MDR-TB, whereas elevated serum transforming growth factor (TGF)-ß was found in the NTM group. Cells of MDR-TB patients stimulated with early secretory antigenic target (ESAT)-6, but not purified protein derivative (PPD), showed a lower frequency of CD4(+) /interferon (IFN)-γ(+) T cells and enhanced CD4(+) CD25(+) FoxP3(+) , CD4(+) CD25(+) CD127(-) and CD4(+) CD25(+) IL-10(+) T cell population. In addition, increased IL-10 secretion was observed in cultured MDR-TB cells following ESAT-6 stimulation, but not in NR-TB or NTM patients. In vitro blockade of IL-10 or IL-10Rα decreased the CD4(+) CD25(+) FoxP3(+) frequencies induced by ESAT-6 in MDR-TB, suggesting a role of IL-10 on impaired IFN-γ responses seen in MDR-TB. Depletion of CD4(+) CD25(+) T lymphocytes restored the capacity of MDR-TB T cells to respond to ESAT-6 in vitro, which suggests a potential role for T(reg) /T regulatory 1 cells in the pathogenesis of MDR-TB. Together, our results indicate that although the similarities in chronicity, NTM- and MDR-TB-impaired antigenic responses involve different mechanisms.