Integrated management of residues from tomato production: Recovery of value-added compounds and biogas production in the biorefinery context.

The biorefinery approach must be boosted in the management of agro-residues in the future. The present study aims to investigate the valorization of tomato production residues, namely rotten tomato (unfit for consumption - RT), green tomato (GT), and tomato branches (TB). The assessment involves the recovery of value-added compounds through the extraction process followed by biogas production through anaerobic digestion. A thorough characterization of the three residues (RT, GT, and TB) was carried out, including the identification of volatile compounds by solid-phase microextraction (SPME) and gas chromatography/mass spectrometry (GC/MS). The volatiles analysis revealed the presence of flavor enhancer compounds and molecules with insecticidal properties. A solid-liquid extraction with ethanol allowed the recovery of value-added compounds in the extracts, in particular phenolic compounds, ß-carotene, and lycopene, which contributed to the antioxidant activity. RT and TB extracts were found to be richer in total phenolic compounds (~27 mg GAE/gdb dry basis) and exhibited higher antioxidant activity (IC50 = 0.911 and 0.745 mg/mL). The tomato branches extract had the highest concentration of carotenoids with 37.23 and 3.08 mg/kgdb of ß-carotene and lycopene, respectively. The biochemical methane potential (BMP) was assessed in sealed reactors operating in anaerobic conditions for all the raw (RT, GT, and TB) and extracted substrates waste (RTe, GTe, and TBe). While the BMP of RT and GT was in the range of 232-285 mL CH4/g VS, a lower value of 141 mL CH4/g VS was obtained for TB. The methane production for each pair of raw and extracted substrates (RT/RTe, GT/GTe, and TB/TBe) was considered statistically similar at a 95 % confidence level. Overall, the value-added compounds recovery through ethanolic extraction did not compromise the methane production of the materials.

Futility of abdominal drain in elective laparoscopic splenectomy.

PURPOSE: Despite the implementation of minimally invasive surgery and enhanced recovery protocols, the use of drain in elective splenectomy is still controversial. The aim of this study was to assess whether the abdominal drain can impact on short-term outcome after elective laparoscopic splenectomy. METHODS: This is a retrospective analysis of a consecutively collected database including all patients who underwent elective laparoscopic splenectomy in our institution between January 2001 and June 2019. Postoperative complications were defined according to a priori criteria and graded according to Clavien-Dindo classification. All complications that occurred during hospitalization or within 30 days after discharge were considered. Primary endpoint was postoperative morbidity, and secondary endpoint was postoperative hospital length of stay. RESULTS: One hundred and sixty-one patients were analysed. Intraperitoneal drain was placed in 75 (46.6%) patients. Postoperative complications occurred in 36 (22.4%) patients, while 8 (4.9%) patients had major complications. Median postoperative length of stay was 4 days. At multivariate analysis, only malignancy was significantly associated with the onset of complications (OR 3.50; 95% CI 1.1-11.0; p = 0.032). Malignancy, ASA > 2, conversion to open surgery, presence of drain and longer operation were significantly associated with prolonged length of stay. Patients with drain showed a greater unadjusted risk of abdominal collections (RR 10.32; 95% CI 1.3-79.6; p = 0.006). CONCLUSION: Abdominal drain did not reduce morbidity and prolonged the length of stay following elective laparoscopic splenectomy. Therefore, the present study does not support the routine use of drain in such procedure.

Can immunohistochemical biomarkers distinguish epithelial dysplasia degrees in actinic cheilitis? A systematic review and meta-analysis.

BACKGROUND: Actinic cheilitis (AC) is a potentially malignant disorder of the lip, characterized by epithelial and connective tissue alterations caused by chronic exposure to ultraviolet radiation. In the past decades, diverse studies have been conducted in lip carcinogenesis and many biomarkers have been identified in lip lesions, yet there is no scientific evidence that determines its usefulness in the clinical setting or in histopathological routine. Therefore, we conducted the first systematic review in this field to summarize the results of published studies on immunohistochemical biomarkers in lip carcinogenesis, to evaluate if there is a marker than can distinguish the different histological grades of AC. MATERIAL AND METHODS: Retrospective studies that investigated immunohistochemical biomarkers in AC defined on standardised histological assessment were gathered from five databases and evaluated. Each study was qualitatively evaluated using the Critical Appraisal Tools from SUMARI. RESULTS: The proliferation marker Ki-67 was the most studied biomarker and we observed, through meta-analysis, that it was differently expressed between AC and lip cancer, but not in AC subgroups. Most articles had a high risk of bias. CONCLUSIONS: In summary, the literature lacks quality follow up studies in actinic cheilitis. Multi-centre cohort studies, with patients stratified by treatment type and the use of image analysis software, could be the solution to further address the issues of investigating potentially malignant lesions and help change clinical practice, in terms of individualizing patients' treatment and prognosis prediction.

Extraordinary Dielectric Properties at Heterojunctions of Amorphous Ferroelectrics.

Materials having a high dielectric constant are needed for a variety of electrical applications from transistors to capacitors. Ferroelectric amorphous-oxide (glass) alkali-ion electrolytes of composition A2.99Ba0.005ClO (A = Li, Na) are shown by two different types of measurement and different consistent analyses to have extraordinarily high dielectric constants, varying from 109 at 25 °C to 1010 at 220 °C if the glass is properly conditioned. These anomalously high dielectric properties coexist with alkali-ion conductivities at 25 °C that are equivalent to those of the best organic-liquid electrolytes of a Li-ion cell, and cyclic voltammetry (CV) in a Au/glass electrolyte/Au cell is stable from -10 to +10 V. A model to interpret microscopically all the key features of the CV curves shows that the electric-double-layer capacitors that form at the gold/electrolyte interfaces in the Au/glass electrolyte/Au heterojunction reverse polarization at an applied voltage V = ±2.1 V, resulting in three almost equivalent discharging capacitances for a single physical capacitor from -10 to +10 V.

The effect of adjusting the pH of local anaesthetics in dentistry: a systematic review and meta-analysis.

The acidic nature of commercial local anaesthetics (LAs) can cause pain during infiltration and delay the onset of anaesthesia. It is suggested that adjusting the pH of anaesthetic agents could minimize these effects. This systematic review aimed to evaluate the efficacy of buffered LAs in reducing infiltration pain and onset time during dental procedures. MEDLINE, Embase, Scopus and Scielo databases were searched up to April 2017. Randomized controlled trials comparing buffered and unbuffered LAs for intraoral injections were included. Risk of bias was assessed using the Cochrane Collaboration tool. Data upon injection pain and onset time were pooled in a random-effects model. Subgroup analyses compared normal and inflamed tissues, and terminal infiltrations and inferior alveolar nerve (IAN) blocks. Meta-regressions were performed to explain heterogeneity. Fourteen articles were included in this review. Lidocaine with epinephrine was the most used anaesthetic combination. Nonlidocaine studies (n = 2) were not pooled in the meta-analysis. Buffered lidocaine did not result in less pain during intraoral injections: mean difference -6.4 (95% CI -12.81 to 0.01) units in a 0-100 scale. Alkalinized lidocaine did not reduce the onset time in normal tissues when terminal infiltration techniques were used, but resulted in a more rapid onset for IAN blocks (-1.26 min) and in inflamed tissues (-1.37 min); however, this change may not be clinically relevant, considering the time required to prepare the buffered agent. Studies performed using other anaesthetic salts did not show robust and clinically significant results in favour of alkalinization.

Effect of sarcopenia and visceral obesity on mortality and pancreatic fistula following pancreatic cancer surgery.

BACKGROUND: Analytical morphometric assessment has recently been proposed to improve preoperative risk stratification. However, the relationship between body composition and outcomes following pancreaticoduodenectomy is still unclear. The aim of this study was to assess the impact of body composition on outcomes in patients undergoing pancreaticoduodenectomy for cancer. METHODS: Body composition parameters including total abdominal muscle area (TAMA) and visceral fat area (VFA) were assessed by preoperative staging CT in patients undergoing pancreaticoduodenectomy for cancer. Perioperative variables and postoperative outcomes (mortality or postoperative pancreatic fistula) were collected prospectively in the institutional pancreatic surgery database. Optimal stratification was used to determine the best cut-off values for anthropometric measures. Multivariable analysis was performed to identify independent predictors of 60-day mortality and pancreatic fistula. RESULTS: Of 202 included patients, 132 (65·3 per cent) were classified as sarcopenic. There were 12 postoperative deaths (5·9 per cent), major complications developed in 40 patients (19·8 per cent) and pancreatic fistula in 48 (23·8 per cent). In multivariable analysis, a VFA/TAMA ratio exceeding 3·2 and American Society of Anesthesiologists grade III were the strongest predictors of mortality (odds ratio (OR) 6·76 and 6·10 respectively; both P < 0·001). Among patients who developed major complications, survivors had a significantly lower VFA/TAMA ratio than non-survivors (P = 0·017). VFA was an independent predictor of pancreatic fistula (optimal cut-off 167 cm(2) : OR 4·05; P < 0·001). CONCLUSION: Sarcopenia is common among patients undergoing pancreaticoduodenectomy. The combination of visceral obesity and sarcopenia was the best predictor of postoperative death, whereas VFA was an independent predictor of pancreatic fistula.

Brazilian Pampa Biome Honey Protects Against Mortality, Locomotor Deficits and Oxidative Stress Induced by Hypoxia/Reperfusion in Adult Drosophila melanogaster.

We aimed to investigate the potential beneficial effects of the Brazilian Pampa biome honey in a Drosophila-based hypoxia model. Adult flies were reared in standard medium in the presence or absence of honey (at a final concentration of 10 % in medium). Then, control flies (4 % sucrose in medium) and honey-treated flies were submitted to hypoxia. Subsequently, flies were analyzed for mortality, neurolocomotor behavior (negative geotaxis), mitochondrial/oxidative stress parameters and expression of hypoxia/stress related genes by RT-qPCR. The HPLC analysis revealed the presence of phenolics and flavonoids in the studied honey. Caffeic acid was the major compound followed by p-coumaric acid and kaempferol. The presence of such compounds was correlated with a substantial antioxidant activity in vitro. Flies subjected to hypoxia presented marked mortality, locomotor deficits and changes in oxidative stress and mitochondrial activity parameters. Honey treatment was able to completely block mortality and locomotor phenotypes. In addition, honey was able to reverse ROS production and hypoxia-induced changes in mitochondrial complex I and II activity. Hypoxia also induced an up-regulation in mRNA expression of Sima (HIF-1), NFκß, NRF2, HOX, AKT-1, InR, dILP2, dILP5 and HSP27. Honey treatment was not able to modulate changes in the tested genes, indicating that its protective effects involve additional mechanisms other than transcriptional activity of hypoxia-driven adaptive responses in flies. Our results demonstrated, for the first time, the beneficial effects of honey against the deleterious effects of hypoxia/reperfusion processes in a complex organism.

How different do visuo-tactile criteria assess caries lesions activity status on occlusal surfaces?

OBJECTIVES: We tested the association between active caries lesions assessed by two different criteria and clinical features of these caries lesions. MATERIALS AND METHODS: Three examiners examined forty-nine 3- to 12-year-old children: one examiner used the Nyvad criteria, another examiner used the International Caries Detection and Assessment System with an additional criteria--Lesion Activity Assessment (ICDAS + LAA), and a reference examiner classified lesions regarding plaque stagnation, colour, lustre, cavities, depth and texture. Logistic regressions were used to test associations. For analyses, we grouped sound sites and inactive lesions vs active caries lesions, but also considering only inactive vs active lesions. RESULTS: Active lesions scored by both criteria were similarly associated with different clinical parameters tested, except when the sound sites were excluded from the analysis. In these cases, active lesions according to ICDAS + LAA were associated only with cavitation and texture. Texture was associated with divergences between criteria when differentiating sound or inactive lesions from active ones. Fewer divergences in differentiating active from inactive lesions were observed when lesions present lustre. CONCLUSION: Most clinical signs associated with active caries lesions were similar, but texture and severity tend to have a greater importance when using ICDAS + LAA for distinguishing caries activity status. Attention should be given to differences due to texture and lustre when using different indices.

Ecotoxicological effect of zinc pyrithione in the freshwater fish Gambusia holbrooki.

Currently diverse biocidal agents can be used for distinct applications, such as personal hygiene, disinfection, antiparasitic activity, and antifouling effects. Zinc pyrithione is an organometallic biocide, with bactericidal, algicidal and fungicidal activities. It has been recently incorporated in antifouling formulas, such as paints, which prevent the establishment of a biofilm on surfaces exposed to the aquatic environment. It has also been used in cosmetics, such as anti-dandruff shampoos and soaps. Previously reported data has shown the presence of this substance in the aquatic compartment, a factor contributing to the potential exertion of toxic effects, and there is also evidence that photodegradation products of zinc pyrithione were involved in neurotoxic effects, namely by inhibiting cholinesterases in fish species. Additional evidence points to the involvement of zinc pyrithione in alterations of metal homeostasis and oxidative stress, in both aquatic organisms and human cell models. The present work assesses the potential ecotoxicity elicited by zinc pyrithione in the freshwater fish Gambusia holbrooki after an acute (96 h) exposure. The oxidative stress was assessed by the quantification of the activities of specific enzymes from the antioxidant defense system, such as catalase, and glutathione-S-transferases; and the extent of peroxidative damage was quantified by measuring the thiobarbituric acid reactive substances levels. Neurotoxicity was assessed through measurement of acetylcholinesterase activity; and a standardized method for the description and assessment of histological changes in liver and gills of was also used. Zinc pyrithione caused non-specific and reversible tissue alterations, both in liver and gills of exposed organisms. However, histopathological indices were not significantly different from the control group. In terms of oxidative stress biomarkers, none of the tested biomarkers indicated the occurrence of pro-oxidative effects, suggesting that the oxidative pathway is not the major toxicological outcome of exposure to zinc pyrithione.

Acute effects of tetracycline exposure in the freshwater fish Gambusia holbrooki: antioxidant effects, neurotoxicity and histological alterations.

A large body of evidence was compiled in the recent decades showing a noteworthy increase in the detection of pharmaceutical drugs in aquatic ecosystems. Due to its ubiquitous presence, chemical nature, and practical purpose, this type of contaminant can exert toxic effects in nontarget organisms. Exposure to pharmaceutical drugs can result in adaptive alterations, such as changes in tissues, or in key homeostatic mechanisms, such as antioxidant mechanisms, biochemical/physiological pathways, and cellular damage. These alterations can be monitored to determine the impact of these compounds on exposed aquatic organisms. Among pharmaceutical drugs in the environment, antibiotics are particularly important because they include a variety of substances widely used in medical and veterinary practice, livestock production, and aquaculture. This wide use constitutes a decisive factor contributing for their frequent detection in the aquatic environment. Tetracyclines are the individual antibiotic subclass with the second highest frequency of detection in environmental matrices. The characterization of the potential ecotoxicological effects of tetracycline is a much-required task; to attain this objective, the present study assessed the acute toxic effects of tetracycline in the freshwater fish species Gambusia holbrooki by the determination of histological changes in the gills and liver, changes in antioxidant defense [glutathione S-transferase (GST), catalase (CAT), and lipoperoxidative damage] as well as potential neurotoxicity (acetylcholinesterase activity). The obtained results suggest the existence of a cause-and-effect relationship between the exposure to tetracycline and histological alterations (more specifically in gills) and enzymatic activity (particularly the enzyme CAT in liver and GST in gills) indicating that this compound can exert a pro-oxidative activity.

Consensus guidelines for enhanced recovery after gastrectomy: Enhanced Recovery After Surgery (ERAS®) Society recommendations.

BACKGROUND: Application of evidence-based perioperative care protocols reduces complication rates, accelerates recovery and shortens hospital stay. Presently, there are no comprehensive guidelines for perioperative care for gastrectomy. METHODS: An international working group within the Enhanced Recovery After Surgery (ERAS®) Society assembled an evidence-based comprehensive framework for optimal perioperative care for patients undergoing gastrectomy. Data were retrieved from standard databases and personal archives. Evidence and recommendations were classified according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system and were discussed until consensus was reached within the group. The quality of evidence was rated 'high', 'moderate', 'low' or 'very low'. Recommendations were graded as 'strong' or 'weak'. RESULTS: The available evidence has been summarized and recommendations are given for 25 items, eight of which contain procedure-specific evidence. The quality of evidence varies substantially and further research is needed for many issues to improve the strength of evidence and grade of recommendations. CONCLUSION: The present evidence-based framework provides comprehensive advice on optimal perioperative care for the patient undergoing gastrectomy and facilitates multi-institutional prospective cohort registries and adequately powered randomized trials for further research.

The catalytic reactions in the Cu-Li-Mg-H high capacity hydrogen storage system.

A family of hydrides, including the high capacity MgH2 and LiH, is reported. The disadvantages these hydrides normally display (high absorption/desorption temperatures and poor kinetics) are mitigated by Cu-hydride catalysis. This paper reports on the synthesis of novel CuLi0.08Mg1.42H4 and CuLi0.08Mg1.92H5 hydrides, which are structurally and thermodynamically characterized for the first time. The CuLi0.08Mg1.42H4 hydride structure in nanotubes is able to hold molecular H2, increasing the gravimetric and volumetric capacity of this compound. The catalytic effect these compounds show on hydride formation and decomposition of CuMg2 and Cu2Mg/MgH2, Li and LiH, Mg and MgH2 is analyzed. The Gibbs energy, decomposition temperature, and gravimetric capacity of the reactions occurring within the Cu-Li-Mg-H system are presented for the first time. First principles and phonon calculations are compared with experiments, including neutron spectroscopy. It is demonstrated that the most advantageous sample contains CuLi0.08Mg1.92 and (Li) ∼ Li2Mg3; it desorbs/absorbs hydrogen according to the reaction, 2CuLi0.08Mg1.42H4 + 2Li + 4MgH2 ↔ 2CuLi0.08Mg1.92 + Li2Mg3 + 8H2 at 114 °C (5.0 wt%) - 1 atm, falling within the proton exchange membrane fuel cell applications window. Finally the reaction 2CuLi0.08Mg1.42H4 + MgH2 ↔ 2CuLi0.08Mg1.92 + 5H2 at 15 °C (4.4 wt%) - 1 atm is found to be the main reaction of the samples containing CuLi0.08Mg1.92 that were analyzed in this study.

Diagnostic Strategies for Restorations Management: A 70-Month RCT.

We aimed to evaluate the impact of 2 visual diagnostic strategies for assessing secondary caries and managing permanent posterior restorations on long-term survival. We conducted a diagnostic cluster-randomized clinical trial with 2 parallel groups using different diagnostic strategies: (C+AS) based on caries assessment, marginal adaptation, and marginal staining aspects of the FDI (World Dental Federation) criteria and (C) based on caries assessment using the Caries Associated with Restorations or Sealants (CARS) criteria described by the International Caries Detection and Assessment System (ICDAS). The treatment for the restoration was conducted based on the decision made following the allocated diagnostic strategy. The restorations were then clinically reevaluated for up to 71 mo. The primary outcome was restoration failure (including tooth-level failure: pain, endodontic treatment, and extraction). Cox regression analyses with shared frailty were conducted in the intention-to-treat population, and hazard ratios (HRs) and 95% confidence intervals (95% CIs) were derived. We included 727 restorations from 185 participants and reassessed 502 (69.1%) restorations during follow-up. The evaluations occurred between 6 and 71 mo. At baseline, C led to almost 4 times fewer interventions compared with the C+AS strategy. A total of 371 restorations were assessed in the C group, from which 31 (8.4%) were repaired or replaced. In contrast, the C+AS group had 356 restorations assessed, from which 113 (31.7%) were repaired or replaced. During follow-up, 34 (9.2%) failures were detected in the restorations allocated to the C group and 30 (8.4%) allocated to the C+AS group in the intention-to-treat population, with no significant difference between the groups (HR = 0.83; 95% CI = 0.51 to 1.38; P = 0.435, C+AS as reference). In conclusion, a diagnostic strategy focusing on marginal defects results in more initial interventions but does not improve longevity over the caries-focused strategy, suggesting the need for more conservative approaches.

Oxidative stress specifically downregulates survivin to promote breast tumour formation.

BACKGROUND: Breast cancer, a heterogeneous disease has been broadly classified into oestrogen receptor positive (ER+) or oestrogen receptor negative (ER-) tumour types. Each of these tumours is dependent on specific signalling pathways for their progression. While high levels of survivin, an anti-apoptotic protein, increases aggressive behaviour in ER- breast tumours, oxidative stress (OS) promotes the progression of ER+ breast tumours. Mechanisms and molecular targets by which OS promotes tumourigenesis remain poorly understood. RESULTS: DETA-NONOate, a nitric oxide (NO)-donor induces OS in breast cancer cell lines by early re-localisation and downregulation of cellular survivin. Using in vivo models of HMLE(HRAS) xenografts and E2-induced breast tumours in ACI rats, we demonstrate that high OS downregulates survivin during initiation of tumourigenesis. Overexpression of survivin in HMLE(HRAS) cells led to a significant delay in tumour initiation and tumour volume in nude mice. This inverse relationship between survivin and OS was also observed in ER+ human breast tumours. We also demonstrate an upregulation of NADPH oxidase-1 (NOX1) and its activating protein p67, which are novel markers of OS in E2-induced tumours in ACI rats and as well as in ER+ human breast tumours. CONCLUSION: Our data, therefore, suggest that downregulation of survivin could be an important early event by which OS initiates breast tumour formation.

Systemic nickel allergy syndrome: nosologic framework and usefulness of diet regimen for diagnosis.

Systemic (gastrointestinal and skin) reactions to ingestion of nickel rich foods in patients with nickel allergic contact dermatitis characterize Systemic Nickel Allergy Syndrome (SNAS). The objective of the study was to describe the nosologic framework of the syndrome and to compare sensibility and specificity for SNAS diagnosis between two different low nickel diets - BraMa-Ni and the usually prescribed list of forbidden foods - along with patient adherence to diet. One hundred forty-five patients with suspected SNAS (by history and benefit from nickel dietary restrictions) were selected and orally challenged with nickel for a definite diagnosis. Specificity and sensibility of the diets were calculated in relation to the results of nickel challenges. The nosologic framework of SNAS was deduced from the clinical pictures of 98 patients with positive nickel challenge and characterized essentially by skin and gastrointestinal symptoms, whereas all other symptoms (dizziness, headache etc.) were never elicited by the oral nickel challenge. The specificity and sensibility of BraMa-Ni in detecting SNAS were significantly higher than the forbidden food list diet, with an excellent patient adherence. Therefore, BraMa-Ni diet can be prescribed for the treatment of the syndrome other than for the diagnosis, the gold standard of which remains the oral nickel challenge.

Root canal filling materials for endodontic treatment of necrotic primary teeth: a network meta-analysis.

PURPOSE: To investigate the effect of different root canal filling materials on the change of failure of the endodontic treatment of necrotic primary teeth. METHODS: A literature search was carried out in PubMed/MEDLINE, CENTRAL, Scopus databases, and grey literature up to July 2022 selecting randomised clinical trials related to research question. Two reviewers independently selected the studies, extracted the data, and assessed the bias risk. Root canal filling materials were grouped according to the main component [iodoform (IOD), calcium hydroxide (CAOH), zinc oxide (ZO) or mix (IOD plus CAOH plus ZO) pastes]. Pairwise and network meta-analyses using the mixed treatment comparisons method were performed to compare the number of events (failure) among treatments. Odds ratio and 95% confidence intervals (CI) for calculated. Post-probabilities among treatments were also calculated and interpreted. RESULTS: From 1186 potentially relevant studies, 17 were selected for full-text analysis, and 7 were included in the meta-analysis, totalizing 263 teeth. In the direct evidence, ZO pastes resulted in a higher chance of failure than IOD pastes (OR 7.07 95% CI 1.02, 62.59). In the indirect evidence, there was no difference between the materials. The IOD pastes presented a high probability (81%) of being the treatment associated to lowest number of failures among all treatments. The CAOH pastes presented the highest probability of being the worst option. Studies showed high bias risk. CONCLUSION: There is currently no scientific evidence of the superiority of any one root canal filling material for endodontic treatment of necrotic primary teeth.

Influence of class I and II HLA alleles on inhibitor development in severe haemophilia A patients from the south of Brazil.

Congenital haemophilia A is a chromosome-linked recessive disorder caused by the deficiency or reduction of factor VIII (FVIII) pro-coagulant activity. During treatment, some patients develop alloantibodies (FVIII inhibitors) that neutralize the action of exogenously administered FVIII. Currently, the presence of these inhibitors is the most serious adverse event found in replacement therapy. Some studies have suggested that genetic factors influence the development of the FVIII coagulation inhibitors. To identify the class I and II alleles that may be influencing the formation of inhibitors in severe haemophilic patients. Genotyping of the class I (HLA-A, -B and -C) and class II (HLA-DRB1, -DQA1 and -DQB1) alleles of 122 patients with severe haemophilia A, including 36 who had developed antibodies to factor VIII, was performed. After the comparison of the group without inhibitors and the group with inhibitors, HLA-C*16 [Odds ratio (OR) = 7.73; P = 0.0092] and HLA-DRB1*14 (OR = 4.52; P = 0.0174) were found to be positively associated with the formation of the inhibitors. These results confirm that HLA alleles are involved in inhibitor production and could be used as a tool for recognition of groups at high risk of possible inhibitor development in Southern Brazilian haemophilic patients.

Dose-dependent clinical and immunological efficacy of sublingual immunotherapy with mite monomeric allergoid.

Sublingual immunotherapy with monomeric carbamylated allergoid (LAIS) is an effective and well tolerated treatment of respiratory allergy. The aim of the present study was to correlate the efficacy of two maintenance doses (1000 AU vs 3000 AU) of LAIS with the immunological modulation of allergen-driven Th1, Th2 and T regulatory cytokines produced in vitro by PBMCs, in patients suffering from mite allergic rhinitis. Forty-eight consecutive patients with mite allergic rhinitis were recruited. Patients were randomly assigned to group A (n=24) or group B (n=24), respectively receiving 1000 AU or 3000 AU weekly during one-year maintenance phase. Each patient was evaluated for rhinitis severity (ARIA protocol), and for drug consumption at the time of the inclusion and after 6 and 12 months of treatment. Patients were also asked to report the perceived severity of the disease and the tolerability of the treatment in a visual analogical scale (VAS). Before and at the end of the treatment allergen-driven release of cytokines by PBMCs in vitro was measured. After 1-year treatment, a statistically significant reduction of all clinical parameters was observed in all patients, associated with reduction of IL-4 and increase of INF-γ secreted in vitro by mite-challenged PBMCs. Notably, the group treated with the higher dose showed significantly better clinical and immunological results. The efficacy of LAIS is correlated to the immune modulation in a clear dose-dependent effect.

Frequencies of MICA alleles in patients from southern Brazil with multibacillary and paucibacillary leprosy.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which mainly affects the skin and nervous system. The disease has several clinical forms. This study investigated the MICA and HLA-B genes in 223 samples from leprosy patients and 201 samples from healthy individuals matched for age, gender and ethnical background. Of the patients, 153 had multibacillary, 45 paucibacillary and 25 indeterminate leprosy. The aim of this case-control study was to assess whether the MICA alleles influence susceptibility for leprosy or affect the subtype of the disease in a population of southern Brazil. There were significant differences in frequencies of the MICA*027 allele (4.7% vs 1.8%, P-value = 0.01, OR = 0.37; 95% CI = 0.16-0.85) between leprosy patients and controls, and of the MICA*010 (4.5% vs 1.6%, P-value = 0.05, OR = 0.35, 95% CI = 0.13-0.97) and MICA*027 alleles (4.7% vs 1.3%, P-value = 0.01; OR = 0.27; 95% CI = 0.09-0.79) between multibacillary leprosy patients and the control group. There were no significant differences in the frequency of MICA alleles between paucibacillary leprosy patients and controls. Thus, the MICA*027 allele is associated with a protective effect for leprosy per se, while the MICA*010 and MICA*027 alleles are associated with protection against multibacillary leprosy, the most severe clinical subtype.