ABSTRACT
INTRODUCTION: Unintentional dural puncture (UDP) occurs in 0.5-1.5% of labour epidural analgesia cases. To date, little is known about evidence of UDP-related complications. This work aimed to assess the incidence of intrapartum and postpartum complications in parturients who experienced UDP. METHODS: This is a 10-year retrospective observational study on parturients admitted to our centre who presented UDP. Data collection gathered UDP-related complications during labour and postpartum. All women who displayed UDP received medical therapy and bed rest. An epidural blood patch (EBP) was not used in this population. Once asymptomatic, patients were discharged from the hospital. RESULTS: Out of 7718 neuraxial analgesia cases, 97 cases of UDP occurred (1.25%). During labour, complications appeared in a small percentage of analgesia procedures performed, including total spinal anaesthesia (1.0%), extended motor block (3%), hypotension (4.1%), abnormal foetal heart rate (2%), inadequate analgesia (14.4%), and general anaesthesia following neuraxial anaesthesia failure (33.3% of emergency caesarean sections). During the postpartum period, 53.6% of parturients exhibited a postdural puncture headache, 13.4% showed neurological symptoms, and 14.4% required neurological consultation and neuroimaging. No patient developed subdural hematoma or cerebral venous sinus thrombosis; one woman presented posterior reversible encephalopathy syndrome associated with eclampsia. Overall, 82.5% of women experienced an extension of hospital stay. CONCLUSION: Major complications occurred in a small percentage of patients during labour. However, since they represent high-risk maternal and neonatal health events, a dedicated anaesthesiologist and a trained obstetric team are essential. No major neurological complications were registered postpartum, and EBP was not performed. Nevertheless, all patients with UDP were carefully monitored and treated until complete recovery before discharge, leading to an extension of their hospitalization.
ABSTRACT
PURPOSE: Patients with Down Syndrome (DS) showed multiple comorbidities, including thyroid disorders, obesity, and metabolic derangement. Different thyroid hormone (THs) patterns and sensitivity to thyroid hormone indices (STHI) seem to be associated with metabolic disorders. The study's aim was to evaluate the prevalence of metabolic syndrome (MS) in pediatric patients affected by DS, taking into consideration the relationship between the metabolic parameters, THs and STHI. METHODS: We enlisted 50 euthyroid patients with DS (9.03 ± 4.46). Clinical parameters, TSH, FT3, FT4 and the presence of MS were recorded. Indexes of peripheral sensitivity (FT3/FT4 ratio) and central sensitivity (TSH index, TSHI; TSH T4 resistance index, TT4RI; TSH T3 resistance index, TT3RI) were also detected. Thirty healthy subjects were included as a control group. RESULTS: MS was detected in 12% of the subjects with DS. FT3, FT4, and TSH levels were higher in DS than in the control group (p < 0.01); higher levels of FT3/FT4 ratio, TSHI and TT3RI and lower TT4RI values (p < 0.01) were also detected. A significant correlation was detected between FT3 and fasting blood glucose (FBG) (R = 0.46), triglyceride (TG) (r = 0.37), total (r = 0.55) and high density lipoprotein-cholesterol (HDL-C) (r = - 0.38), diastolic blood pressure (DBP) (r = - 0.4); FT3/FT4 ratio and waist circumference (WC) (r = 0.36); TSHI and total (r = 0.30) and HDL cholesterol (r = - 0.31); TT4RI and HDL cholesterol (r = - 0.31); TT3RI and total (r = 0.39) and HDL cholesterol (r = - 032). CONCLUSION: We confirmed a higher MS prevalence in children with DS compared to the control group. A significant association between THs, STHI, and the glucose and lipid metabolism parameters was detected supporting their role in metabolic alterations related to the DS.
Subject(s)
Down Syndrome , Metabolic Syndrome , Humans , Adolescent , Child , Metabolic Syndrome/diagnosis , Metabolic Syndrome/epidemiology , Thyroid Gland , Thyroxine , Triiodothyronine , Cholesterol, HDL , Down Syndrome/complications , Down Syndrome/epidemiology , Thyrotropin , Thyroid HormonesABSTRACT
Allergy to natural rubber latex emerged as one of the main allergies at the beginning among some professional groups and the general population. Sensitization and development of latex allergy have been attributed to exposure to products containing residual latex proteins. The prevailing cross-reactivity of latex proteins with other food allergens is of great concern. Numerous purified allergens are currently available, which greatly help in patient management, thus determining their specific profile. We conducted a multicenter study to investigate changes, from the ROC analysis, in the characteristics of patients with latex allergy by measuring its major protein components. Sensitization to latex proteins is crucial because it highlights the cross reactivity to inhalants (pollen) and food (fruit). It is very essential in an accurate and specific clinical setting.
Subject(s)
Food Hypersensitivity , Latex Hypersensitivity , Humans , Latex Hypersensitivity/complications , Latex Hypersensitivity/epidemiology , Allergens , Pollen , Cross ReactionsABSTRACT
BACKGROUND: Epistaxis is the main complaint in patients with Hereditary haemorrhagic telangiectasia (HHT). Even though the role of epistaxis in affecting the quality of life (QoL) is well-known, little is known about epidemiological and clinical factors contributing to epistaxis severity and QoL. METHODOLOGY: This is a cross-sectional study, including adult patients with HHT with epistaxis. All patients underwent an otolaryngological evaluation with nasal endoscopy. Epistaxis severity was graded using the FID score, and QoL was evaluated with the Short-Form Health Survey (SF-36). Descriptive statistics were produced for demographic characteristics; the Shapiro-Wilk test was used to test the normal distribution of quantitative variables. Correlation between the quantitative variables was evaluated with Pearson's correlation coefficient. Both univariate and multivariate linear regression models were fitted to find associations between demographic or clinical factors and the FID score or SF-36. RESULTS: A total of 234 patients with HHT were included in the study. The univariate analysis highlighted the association between high blood pressure, septal perforation, nocturnal epistaxis, surgery, blood transfusion, hormonal therapy and both FID score and QoL. Sex, allergic rhinitis and nasal polyposis were neither related to epistaxis severity nor perceived health. CONCLUSIONS: Epistaxis severity and QoL in patients with HHT are influenced by several clinical factors both dependent and independent from HHT. Some of the results are consistent with those already published, but for the first time, we extended the analysis to different clinical parameters, such as endoscopic findings, never assessed before.
Subject(s)
Quality of Life , Telangiectasia, Hereditary Hemorrhagic , Adult , Cross-Sectional Studies , Endoscopy , Epistaxis/epidemiology , Epistaxis/etiology , Humans , Telangiectasia, Hereditary Hemorrhagic/complicationsABSTRACT
As the SARS-CoV-2 pandemic continues to rage worldwide, the emergence of numerous variants of concern (VOC) represents a challenge for the vaccinal protective efficacy and the reliability of commercially available high-throughput immunoassays. Our study demonstrates the administration of two doses of the BNT162b2 vaccine that elicited a robust SARS-CoV-2-specific immune response which was assessed up to 3 months after full vaccination in a cohort of 37 health care workers (HCWs). SARS-CoV-2-specific antibody response, evaluated by four commercially available chemiluminescence immunoassays (CLIA), was qualitatively consistent with the results provided by the gold-standard in vitro neutralization assay (NTA). However, we could not observe a correlation between the quantity of the antibody detected by CLIA assays and their neutralizing activity tested by NTA. Almost all subjects developed a SARS-CoV-2-specific T-cell response. Moreover, vaccinated HCWs developed a similar protective neutralizing antibodies response against the EU (B.1), Alpha (B.1.1.7), Gamma (P.1), and Eta (B.1.525) SARS-CoV-2 variants, while Beta (B.1.351) and Delta (B.1.617.2) strains displayed a consistent partial immune evasion. These results underline the importance of a solid vaccine-elicited immune response and a robust antibody titre. We believe that these relevant results should be taken into consideration in the definition of future vaccinal strategies.
Subject(s)
BNT162 Vaccine/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , BNT162 Vaccine/administration & dosage , BNT162 Vaccine/genetics , COVID-19/blood , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/genetics , Female , Humans , Immunity, Cellular , Immunity, Humoral , Immunoassay , Longitudinal Studies , Male , Middle Aged , Prospective Studies , SARS-CoV-2/genetics , T-Lymphocytes/immunology , Vaccination , Young AdultABSTRACT
The clinical manifestations of COVID-19 are heterogeneous: 46.4% of patients admitted into hospital reported to have at least one comorbidity. Comorbidities such as COPD, diabetes, hypertension and malignancy predispose patients with Covid-19 to adverse clinical outcomes. Alpha 1-antitrypsin deficiency (AATD) is a genetic disorder caused by pathological mutation(s) in the SERPINA1 gene resulting in an imbalance in proteinase activity which may lead to premature emphysema and COPD. Our aim was to investigate whether people with severe AAT deficiency (AATD) have an increased risk of (severe) COVID-19 infection. We collected data on COVID-19 symptoms, laboratory-confirmed infection, hospitalization and treatment by means of a telephone survey, directly administered to Italian severe AATD subjects in May 2020. We then compared our findings with data collected by the Istituto Superiore di Sanità on the total population in Italy during the same period. We found an higher frequency of SARS-CoV-2 infection in our cohort (3.8%) compared to national data regarding infection, thus giving severe AATD a relative risk of 8. 8 (95%CI 5.1-20,0; p<0.0001) for symptomatic SARS-CoV-2 infection. Moreover, the relative risk (RR) was higher in AATD patients with pre-existing lung diseases (RR 13.9; 95%CI 8.0-33.6; p<0.001), but with a similar death rate (1 in 8, 12.5%) compared to the general population (13.9%; RR 0.9). These preliminary findings highlight the importance of close surveillance in the spread of COVID-19 in patients with severe AATD and underlines the need for further studies into the role of the antiprotease shield in preventing SARS-Cov-2 infection.
Subject(s)
COVID-19/epidemiology , Pandemics , SARS-CoV-2 , alpha 1-Antitrypsin Deficiency/epidemiology , Biomarkers/blood , COVID-19/blood , Comorbidity , Global Health , Humans , Peptide Hydrolases/blood , Severity of Illness Index , alpha 1-Antitrypsin Deficiency/bloodABSTRACT
A highly chemo- and regioselective cyclo(co)trimerization between 3-halopropiolamides and symmetrical internal alkynes is reported. The reaction is catalyzed by CpRuCl(COD) and proceeds under air at ambient temperature in ethanol with no additional precautions. Iodo-, bromo-, and chloropropiolamides, esters, and ketones are viable coupling partners and, in a 2 : 1 stoichiometry relative to internal alkyne, yield fully-substituted arenes in a single step. The highest regioselectivities (96% single isomer) were observed when employing 2° and 3°-halopropiolamides. A mechanistic hypothesis accounting for this selectivity is proposed. Notably, by using 1,4-butynediol as the internal alkyne, in situ lactonization following [2+2+2]-cycloaddition generates therapeutically-relevant phthalide pharmacophores directly.
ABSTRACT
BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is a rare disease characterized by a multisystemic vascular dysplasia and epistaxis, that is the most common cause of disability and social impairment. Patient management strictly depends on the severity of this symptom; therefore, it is of paramount importance for the clinicians to effectively grade epistaxis severity. The aim of this report was to validate the Frequency, Intensity and Duration score (FID) for grading epistaxis severity in patients with HHT; we studied repeatability and external validity comparing FID score with Epistaxis Severity Score (ESS). METHODS: This is a descriptive, observational study that included 264 adult HHT patients with epistaxis. Diagnosis of HHT was established with Curacao criteria or positivity at genetic testing. Nosebleed severity was evaluated according to the FID score and the ESS. The first 30 patients were included in the validation of the FID score, which was graded on days 0, 1, 3 and 7. In the remaining 234 patients, a comparison between the ESS and FID score was performed. RESULTS: The statistical analysis performed in order to validate the FID score showed very good agreement between scores calculated on different days; analysis comparing the FID score with the ESS revealed a high correlation between the two grading systems. CONCLUSIONS: The FID score is a quick, easy and precise tool for evaluating HHT-related epistaxis and could be a possible alternative to the ESS. The FID score meets the need for an intuitive and smart grading system that is easy to manage in cliniciansâ™ hands.
Subject(s)
Epistaxis , Severity of Illness Index , Telangiectasia, Hereditary Hemorrhagic , Adult , Epistaxis/etiology , Humans , Research Design , Telangiectasia, Hereditary Hemorrhagic/complicationsABSTRACT
Multiple Sclerosis (MS) displays a heterogeneous clinical onset and progression, which are mostly unpredictable, but demyelination of the central nervous system (CNS) leads to substantial deficits of sensory, motor, autonomic, and neurocognitive functions. Considering all genetic studies on MS, including the advanced genome-wide association studies, the risk linked to HLA alleles remains the highest among other susceptibility genetic variants. However, given the genetic variability of HLA alleles in different ethnic groups, we conducted a systematic review of reviews and meta-analyses aiming at summarizing all the results on the association between MS and HLA class II genes. We systematically searched meta-analyses and systematic reviews dealing with MS and HLA in all ethnicities. From 154 records, we included 5 articles collecting HLA data from 15,232 MS patients and 24,194 ethnically matched controls. DRB1∗15 (OR ranging from 1.39 in Chinese Han to 2.59 in Caucasians) and DQB1∗06:02 (OR ranging from 1.91 in Caucasians to 2.49 in Colombian) alleles confer an increased risk for MS transethnically (Caucasians, Chinese, South Americans, Carribeans, Middle Easterners, Japanese, and North Africans). DRB1∗01, DRB1∗09, DRB1∗11, DRB1∗12, and DRB1∗16 alleles were protective, in agreement with the type of amino-acidic (aa) residues (ranging from position 9 to 90) included in pockets 1, 4, 6, 7, and 9, which are most involved in peptide presentation. Changes in aa residues affect the capability of HLA molecules in binding myelin peptides. DQB1∗06:02 risk allele seems to be the most interesting target as humanized mice expressing only DQB1∗06:02 develop MS-like disease mediated by autoimmune reactions against myelin oligodendrocytic basic protein that stabilizes the myelin. Our summary of results from a high number of patients and controls suggests that allelic variants from both DQB1 and DRB1 genes are equally involved in MS susceptibility/protection transethnically.
Subject(s)
Genetic Predisposition to Disease , HLA-DQ beta-Chains/genetics , HLA-DRB1 Chains/genetics , Multiple Sclerosis/pathology , Alleles , Animals , Genome-Wide Association Study , Humans , Multiple Sclerosis/genetics , Multiple Sclerosis/immunology , Risk FactorsABSTRACT
Assessment of the risks and environmental impacts of carbon geosequestration requires knowledge about the wetting behavior of mineral surfaces in the presence of CO2 and the pore fluids. In this context, the interfacial tension (IFT) between CO2 and the aqueous fluid and the contact angle, θ, with the pore mineral surfaces are the two key parameters that control the capillary pressure in the pores of the candidate host rock. Knowledge of these two parameters and their dependence on the local conditions of pressure, temperature, and salinity is essential for the correct prediction of structural and residual trapping. We have performed classical molecular dynamics simulations to predict the CO2-water IFT and the CO2-water-calcite contact angle. The IFT results are consistent with previous simulations, where simple point charge water models have been shown to underestimate the water surface tension, thus affecting the simulated IFT values. When combined with the EPM2 CO2 model, the SPC/Fw water model indeed underestimates the IFT in the low-pressure region at all temperatures studied. On the other hand, at high pressure and low temperature, the IFT is overestimated by â¼5 mN/m. Literature data regarding the CO2/water/calcite contact angle on calcite are contradictory. Using our new set of force field parameters, we performed NVT simulations at 323 K and 20 MPa to calculate the contact angle of a water droplet on the calcite {10.4} surface in a CO2 atmosphere. We performed simulations for both spherical and cylindrical droplet configurations for different initial radii to study the size dependence of the water contact angle on calcite in the presence of CO2. Our results suggest that the contact angle of a cylindrical droplet, is independent of droplet size, for droplets with a radius of 50 Å or more. On the contrary, spherical droplets make a contact angle that is strongly influenced by their size. At the largest size explored in this study, both spherical and cylindrical droplets converge to the same contact angle, 38°, indicating that calcite is strongly wetted by water.
ABSTRACT
In this study we investigated fluid displacement water with supercritical (sc) CO2 in chalk under conditions close to those used for geologic CO2 sequestration (GCS), to answer two main questions: How much volume is available for scCO2 injection? And what is the main mechanism of displacement over a range of temperatures? Characterization of immiscible scCO2 displacement, at the pore scale in the complex microstructure in chalk reservoirs, offers a pathway to better understand the macroscopic processes at the continuum scale. Fluid behavior was simulated by solving the Navier-Stokes equations, using finite-volume methods within a pore network. The pore network was extracted from a high resolution 3D image of chalk, obtained using X-ray nanotomography. Viscous fingering dominates scCO2 infiltration and pores remain only partially saturated. The unstable front, developed with high capillary number, causes filling of pores aligned with the flow direction, reaching a maximum of 70% scCO2 saturation. The saturation rate increases with temperature but the final saturation state is the same for all investigated temperatures. The higher the saturation rate, the higher the dynamic capillary pressure coefficient. A higher dynamic capillary pressure coefficient indicates that scCO2 needs more time to reach capillary equilibrium in the porous medium.
ABSTRACT
Germline mutations in the breast cancer susceptibility gene BRCA1, encoding a tumor suppressor protein, greatly enhance the risk of breast and ovarian cancer. This tissue-specificity implicates the role of ovarian hormones. Indeed, BRCA1 has been demonstrated to regulate the signalling axis of the hormone, progesterone, and its receptor, the progesterone receptor (PR), and progesterone action has been implicated in BRCA1-related tumorigenesis. BRCA1 also plays important roles in oxidative stress and activating nuclear factor kappaB (NFκB) signalling pathways. Like wildtype BRCA1 function, PR signalling has also been shown to inhibit NFκB activation. Although PR and BRCA1 networks are known to interact, their interaction at the level of NFκB activation in the human breast is not understood. This study investigates the effect of reduced BRCA1 expression on proliferation and NFκB activation in human breast cells, and the impact of progesterone on these effects. The major findings are that: 1) Reduced BRCA1 levels inhibit cell growth in normal human mammary cells and breast cancer cells; 2) Reduced BRCA1 levels stimulated inflammatory targets and NFκB activity in normal human mammary cells; 3) Wildtype BRCA1 inhibited the pro-proliferative effects of progesterone in normal mammary epithelial cells, and; 4) Progesterone attenuated BRCA1-mediated NFκB activation in normal human mammary cells. These data have important implications for our understanding of progesterone action in BRCA1 mutation carriers, and how inhibition of this action may potentially delay tumorigenesis or impart a more favourable prognosis.
Subject(s)
BRCA1 Protein/metabolism , Breast Neoplasms/pathology , Breast/pathology , Cell Proliferation , Epithelial Cells/metabolism , Gene Expression Regulation/drug effects , NF-kappa B/metabolism , Progesterone/pharmacology , BRCA1 Protein/antagonists & inhibitors , BRCA1 Protein/genetics , Biomarkers, Tumor/genetics , Breast/drug effects , Breast/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Cell Transformation, Neoplastic , Cells, Cultured , Female , Gene Expression Profiling , Humans , NF-kappa B/genetics , Progestins/pharmacology , RNA, Small Interfering/genetics , Signal TransductionSubject(s)
Oropharyngeal Neoplasms/complications , Oropharyngeal Neoplasms/epidemiology , Papillomaviridae/pathogenicity , Papillomavirus Infections/complications , Papillomavirus Infections/epidemiology , Squamous Cell Carcinoma of Head and Neck/complications , Squamous Cell Carcinoma of Head and Neck/epidemiology , Aged , Female , Humans , Incidence , Italy/epidemiology , Male , Middle Aged , Neoplasm Recurrence, Local , Neoplasm Staging , Oropharyngeal Neoplasms/pathology , Oropharyngeal Neoplasms/virology , Papillomavirus Infections/diagnosis , Papillomavirus Infections/virology , Prevalence , Prognosis , Retrospective Studies , Risk Factors , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/virology , Survival AnalysisABSTRACT
STUDY OBJECTIVES: we performed a meta-analysis to assess the usefulness of HLA testing for Narcolepsy diagnosis in four major ethnical groups: Asians, Afro-Americans, Amerindians and Caucasians. METHODS: PubMed, EMBASE, Web of Science, Scopus and Cochrane databases were searched for articles in English and French published before October 2017 on HLA class II alleles in Narcolepsy. We included case-control studies, cross-sectional and retrospective cohort studies with patients diagnosed following the International classifications of sleep disorders (1990-2012) and ethnically matched controls. Following PRISMA guidelines, two investigators independently extracted data according to the inclusion criteria listed in PROSPERO CRD42017058677. A third researcher was consulted for discrepancies. We extracted and pooled adjusted OR using random-effect models. We verified the strength of the association between HLA-DQB1*06:02 and the worldwide distribution of Narcolepsy type 1 (NT1) and type 2 (NT2); furthermore, we pooled the OR measuring the association between HLA-DQB1*06:02 and NT1, NT2 and hypersomniacs. RESULTS: We identified 511 titles. Of these, 12 case-control studies were included, for a total of 2077 NT1 patients, 235 NT2 patients, 161 hypersomniacs and 7802 controls. In the population-stratified analysis, HLA-DQB1*06:02 conferred an increased risk for NT1 (OR: 24.1, IC: 14.6-39.5, p < 0.001) and NT2 (OR: 3.9; IC: 2.2-6.8, p < 0.001). For NT1 the pooled estimated positive Likelihood Ratio (LR+) was 5.94 (IC: 3.71-9.51) and the negative Likelihood Ratio (LR-) was 0.23 (IC: 0.16-0.33); for NT2 LR+ was 3.35 (IC: 2.08-5.38) and LR- 0.72 (IC: 0.63-0.81). Moreover, for hypersomniacs LR+ was 1.436 (IC 0.668-3.089) and LR- 0.903 (IC 0.714-1.142). CONCLUSIONS: Our data support the preponderant role of HLA-DQB1*06:02 in susceptibility to NT1/NT2 across all ethnicities. HLA-DQB1*06:02 negativity should make clinicians cautious in excluding other diagnoses.
Subject(s)
Genetic Testing , HLA-DQ beta-Chains/genetics , Narcolepsy/ethnology , Narcolepsy/genetics , Black or African American/genetics , Asian People/genetics , Cataplexy/genetics , Female , Genetic Predisposition to Disease , Humans , Indians, North American/genetics , Male , Narcolepsy/diagnosis , White People/geneticsABSTRACT
In the biomedical applications of nanoparticles (NPs), the proper choice of surface chemistry is a crucial aspect in their design. The nature of the coating can heavily impact the interaction of NPs with biomolecules, affect the state of aggregation, and ultimately determine their biological fate. As such, protein corona formation and the aggregation behaviour of gold NPs (Au NPs) are studied here. Au NPs are prepared with four distinct surface functionalisations, namely mercaptosuccinic acid (MSA), N-4-thiobutyroil glucosamine, HS-PEG5000 and HS-alkyl-PEG600. Corona formation, aggregation, and the intracellular behaviour of the Au NPs are then investigated by means of Fluorescence Correlation Spectroscopy (FCS) in cell culture media and in live cells. To evaluate the state of aggregation and the formation of a protein corona, the Au NPs are incubated in cell media and the diffusion coefficient is determined via FCS. The in vitro behaviour is compared with the level of aggregation of the NPs in cells. Diffusion times of the NPs are estimated at different positions in the cell after a one hour incubation period. It is found that the majority of MSA and glucose-Au NPs are present inside the cell as slowly diffusing species with diffusion times (τD) greater than 6000 µs (hydrodynamic diameter >250 nm). PEGylated Au NPs adsorb a small amount of protein and manifest low agglomeration both in media and in living cells. In particular, the HS-alkyl-PEG600 coating shows an excellent correlation between lower protein adsorption, 4-fold lower compared to the MSA coated NPs, and limited intracellular aggregation. In the case of single HS-alkyl-PEG600 coated NPs, it is found that typical intracellular τD values range from 500 to 1500 µs, indicating that these particles display reduced aggregation in the intracellular environment.
Subject(s)
Gold , Metal Nanoparticles , Protein Corona , Spectrometry, Fluorescence , A549 Cells , Adsorption , HumansSubject(s)
Blood Donors , Gene Frequency , HLA-B Antigens/genetics , HLA-DRB1 Chains/genetics , Alleles , Female , Fetal Blood , Haplotypes/genetics , Humans , Infant, Newborn , Italy , Male , United KingdomABSTRACT
Knowledge about the interaction between fluids and solids and the interfacial tension (IFT) that results is important for predicting behavior and properties in industrial systems and in nature, such as in rock formations before, during, and after CO2 injection for long-term storage. Many authors have studied the effect of the environmental variables on the IFT in the CO2-H2O system. However, experimental measurements above CO2 supercritical conditions are scarce and sometimes contradictory. Molecular modeling is a valuable tool for complementing experimental IFT determination, and it can help us interpret results and gain insight under conditions where experiments are difficult or impossible. Here, we report predictions for CO2-water interfacial tension performed using density functional theory (DFT) combined with the COSMO-RS implicit solvent model. We predicted the IFT dependence as a function of pressure (0-50 MPa), temperature (273-383 K), and salinity (0-5 M NaCl). The results agree well with literature data, within the estimated uncertainty for experiments and for molecular dynamics (MD) simulations, suggesting that the model can be used as a fast alternative to time-consuming computational approaches for predicting the CO2-water IFT over a range of pressures, temperatures, and salinities.
ABSTRACT
Patients with cystic echinococcosis (CE) can harbour cysts for years or even decades, apparently without effect of the immune system on the metacestode. Although several immune evasion mechanisms by echinococcal cysts have been described, it is unclear whether the human leucocyte antigen (HLA) system plays a role in the susceptibility or resistance to CE in humans. HLA-G molecules are known to exert a suppressive action on dendritic cells maturation and on natural killer (NK) cells functions, therefore hampering T-cell responses and NK cytolysis. HLA-G plays an important role in immune tolerance, is involved in foetus and in allotransplant tolerance, and may be involved in tumoral and viral immune evasion. In this study, we assessed the presence and levels of soluble HLA-G (sHLA-G) in patients with CE using a commercial ELISA kit to determine whether host's HLA-G may have a role in the course of human CE.
Subject(s)
Echinococcosis/immunology , Echinococcus/growth & development , Echinococcus/immunology , HLA-G Antigens/immunology , Immune Evasion , Adult , Animals , Dendritic Cells/immunology , Dendritic Cells/parasitology , Echinococcosis/blood , Echinococcosis/parasitology , Echinococcus/genetics , Enzyme-Linked Immunosorbent Assay , Female , HLA-G Antigens/blood , Humans , Immune Tolerance , Killer Cells, Natural/immunology , Killer Cells, Natural/parasitology , Male , Middle Aged , T-Lymphocytes/immunology , T-Lymphocytes/parasitology , Young AdultABSTRACT
BACKGROUND: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. We previously reported that the prognosis of MF patients is not only related on clinical variables but it is also associated with peculiar HLA alleles. Until today, the association of HLA ligands for KIR with the prognosis of the disease has not yet been analysed. OBJECTIVE: We investigated the frequency of HLA ligands for killer cell Immunoglobulin-like receptors (KIRs) in MF patients, evaluating if the presence of particular HLA alleles that are ligands for KIR may have prognostic value. METHODS: The study includes 46 Caucasian MF patients that, between 1993 and 1997, underwent HLA genomic typing. All patients were diagnosed and followed up from 1977 to 2012 (mean follow-up of 11 years). RESULTS: MF patients have been divided into two groups (long survivors and dead patients). We noticed that the HLA-Bw6/Bw6 specificity increased among the group of seven dead patients compared to the group of 39 long survivors (71.4% vs. 41.0%, P = ns, OR = 3.59), while in the long survivors group the HLA- Bw4/Bw4 specificity increased when compared to dead patients (23.0% vs. 0%, P = ns). Moreover, we observed that six of the seven dead patients had HLA-DQB1*05; the phenotypic frequency of this HLA allele, in dead and long survivors patients, was 85.7% and 23.0% respectively (P = 0.004; OR = 20). CONCLUSION: Our observations suggest that the presence of the HLA-DQB1*05 alleles characterizes the patients with the poorest prognosis in MF. In addition, absence of the KIR-ligand epitope HLA-B Bw4 showed a trend of being more prominent in MF patients with the poorest prognosis.