Anti-inflammatory, ulcerogenic and platelet activation evaluation of novel 1,4-diaryl-1,2,3-triazole neolignan-celecoxib hybrids.

This study reports the synthesis of novel neolignans-celecoxib hybrids and the evaluation of their biological activity. Analogs8-13(L13-L18) exhibited anti-inflammatory activity, inhibited glycoprotein expression (P-selectin) related to platelet activation, and were considered non- ulcerogenic in the animal model, even with the administration of 10 times higher than the dose used in reference therapy. In silico drug-likeness showed that the analogs are compliant with Lipinski's rule of five. A molecular docking study showed that the hybrids8-13(L13-L18) fitted similarly with celecoxib in the COX-2 active site. According to this data, it is possible to infer that extra hydrophobic interactions and the hydrogen interactions with the triazole core may improve the selectivity towards the COX-2 active site. Furthermore, the molecular docking study with P-selectin showed the binding affinity of the analogs in the active site, performing important interactions with amino acid residues such as Tyr 48. Whereas the P-selectin is a promising target to the design of new anti-inflammatory drugs with antithrombotic properties, a distinct butterfly-like structure of 1,4-diaryl-1,2,3-triazole neolignan-celecoxib hybrids synthesized in this work may be a safer alternative to the traditional COX-2 inhibitors.

Infection in Hospitalized Patients With Systemic Lupus Erythematosus: Proposal of an Algorithm for Diagnosis.

BACKGROUND: Identification of infection in patients with systemic lupus erythematosus (SLE) is a major challenge in clinical practice. OBJECTIVE: This medical records review study evaluated clinical markers, including the performance of C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) in the diagnosis of infection in SLE patients. METHODS: One hundred four SLE patients hospitalized between 2014 and 2018 were allocated into 3 groups, namely, infection, infection and disease activity, and isolated disease activity. Groups were compared in relation to clinical and laboratory variables. Accuracy measures were calculated for CRP, NLR, and PLR. RESULTS: C-reactive protein, NLR, and PLR differed between the groups with higher values observed in the infected group, intermediate values in the mixed group, and lower values in the group with isolated activity-CRP (56 vs 26 vs 15 mg/dL, p = 0.002), NLR (7.9 vs 4.0 vs 3.1, p = 0.005), and PLR (270 vs 227 vs 134, p = 0.025). Fever, tachypnea, and PLR were independently associated with infection. The cutoff points of the CRP of 20 mg/L, NLR of 3.5, and PLR of 151.4 presented values of sensitivity and specificity for the prediction of infection equal to 67% and 67%, 65% and 58%, and 71% and 53%, respectively. The developed algorithm showed a sensitivity of 86.6% and specificity of 81% for the diagnosis of infection. CONCLUSIONS: The combined use of clinical and laboratory markers presented superior accuracy than their isolated use, suggesting a great potential for the application of the algorithm in clinical practice.

Bilateral multiple oncocytic cysts of the parotid gland in type 2 diabetes patients.

AIMS: The hallmarks of type 2 diabetes (T2D) are hyperglycaemia and insulin resistance. These factors, at the cellular level, are associated with mitochondrial dysfunction and increased glucose uptake. Such events are poorly explored in the context of the salivary glands. In this study, we present a series of eight cases of a distinct salivary gland lesion characterised by multiple oncocytic cysts, and we provide new pathological insights regarding its pathogenesis. METHODS AND RESULTS: Seven patients (87.5%) had confirmed T2D, and obesity was identified in five (62.5%) patients. Clinically, the patients showed bilateral parotid gland swelling with recurrent episodes of pain and enlargement. Imaging examination revealed multiple cystic lesions in both parotid glands. Microscopically, the parotid glands showed multiple cysts of different sizes, lined by oncocytic epithelial cells. Intraluminally, strongly eosinophilic glass-like crystalloid material was observed. Immunohistochemical studies were performed, and the most notable finding was glucose transporter 1 (GLUT1) overexpression in the oncocytic cysts which is not observed in any other oncocytic lesion of patients without T2D. In addition, high expressions of mitochondrial antigen, fission 1 protein and mitofusin-2 were observed in the oncocytic epithelium of the cysts. Furthermore, most of the oncocytic cysts showed a pattern of cytokeratin expression consistent with striated ducts. CONCLUSIONS: These results strongly suggest that T2D is associated with alterations in GLUT1 expression in the cells of striated ducts with mitochondrial dysfunction, causing a hyperplastic process characterised by multiple oncocytic cysts. For this lesion, the designation of 'diabetes-associated-bilateral multiple oncocytic cysts of the parotid gland' is proposed.

Dried blood spots for Streptococcus pneumoniae and Haemophilus influenzae detection and serotyping among children < 5 years old in rural Mozambique.

BACKGROUND: Dried blood spots (DBS) have been proposed as potentially tool for detecting invasive bacterial diseases. METHODS: We evaluated the use of DBS for S. pneumoniae and H. influenzae detection among children in Mozambique. Blood for DBS and nasopharyngeal (NP) swabs were collected from children with pneumonia and healthy aged < 5 years. Bacterial detection and serotyping were performed by quantitative PCR (qPCR) (NP and DBS; lytA gene for pneumococcus and hpd for H. influenzae) and culture (NP). Combined detection rates were compared between children with pneumonia and healthy. RESULTS: Of 325 children enrolled, 205 had pneumonia and 120 were healthy. Pneumococci were detected in DBS from 20.5 and 64.2% of children with pneumonia and healthy, respectively; NP specimens were positive for pneumococcus in 80.0 and 80.8%, respectively. H. influenzae was detected in DBS from 22.9% of children with pneumonia and 59.2% of healthy; 81.4 and 81.5% of NP specimens were positive for H. influenzae, respectively. CONCLUSION: DBS detected pneumococcal and H. influenzae DNA in children with pneumonia and healthy. Healthy children were often DBS positive for both bacteria, suggesting that qPCR of DBS specimens does not differentiate disease from colonization and is therefore not a useful diagnostic tool for children.

FGF-2 and FGFR-1 might be independent prognostic factors in oral tongue squamous cell carcinoma.

AIMS: Fibroblast growth factor (FGF)-2 and fibroblast growth factor receptor (FGFR)-1 are associated with tumour invasiveness, cell proliferation, angiogenesis, and metastasis. The aims of this study were to investigate FGF-2 expression and FGFR-1 expression in oral epithelial dysplasia (OED) and oral tongue squamous cell carcinoma (OTSCC), and their correlation with OTSCC patients' prognosis. METHODS AND RESULTS: One hundred and sixty-seven cases were retrospectively selected, including 85 surgical specimens of patients with OTSCC, 46 incisional biopsies of OTSCC, and 36 incisional biopsies of OED. Tissue sections were subjected to immunohistochemical staining for FGF-2 and FGFR-1, and digitally scored. Elevated scores of FGF-2 and FGFR-1 immunostaining were associated with high-grade OEDs. FGF-2 positivity in the stroma was associated with vascular invasion and a worse prognosis, in both overall survival (OS) and disease-free survival (DFS) analyses, in univariate and multivariate models. FGFR-1 positivity in the stroma was correlated with lymph node metastasis and distant metastasis. FGFR-1 expression in either the malignant cells or the stroma was strongly correlated with shorter OS and DFS. CONCLUSIONS: Taken together, our findings suggest that increased FGF-2 expression and increased FGFR-1 expression are associated with high-grade OEDs, and are correlated with the presence of metastasis and adverse outcomes in OTSCC patients.

Sebaceous adenocarcinomas of the major salivary glands: a clinicopathological analysis of 10 cases.

AIMS: Sebaceous carcinomas are uncommon malignant cutaneous tumours originating from the pilosebaceous unit. Although its occurrence is mostly common in peri-ocular glands, other anatomical regions of the head and neck may be affected, including major and minor salivary glands. METHODS AND RESULTS: We describe a series of sebaceous adenocarcinomas of the parotid and submandibular glands. The mean age was 62.1 (range = 31-90) years. Two patients (20%) presented regional or distant metastasis to mandible and lungs. All cases were positive for cytokeratins (AE1AE3 and CK-5), epithelial membrane antigen and adipophilin and negative for androgen receptor, Factor XIIIa, S-100, vimentin and perforin. MLH1 and MSH2 were expressed in the nuclei of most tumour cells, and one case showed loss of MSH2 expression. Proliferative index (assessed by Ki-67 expression) and microvessel density (CD34-positive vessels) were higher in metastasis-associated cases. P63 expression was noted in the periphery of the tumour nests, in the basaloid cells, with a mean of 69.2% nuclear positivity. CONCLUSIONS: The sebaceous adenocarcinoma of salivary glands is rare and may show an unfavourable outcome; therefore, its correct diagnosis may be challenging. For this reason, immunohistochemical studies, including adipophilin in particular, constitute an important diagnostic tool.

Expression of FGF-2/FGFR-1 in normal mucosa, salivary gland, preneoplastic, and neoplastic lesions of the oral cavity.

Fibroblast growth factor 2 (FGF-2) is a multifunctional cytokine expressed in several tissues and involved in a wide variety of biologic activities, with one low molecular weight (LMW) protein present in the cytosol, which is secreted, acting via its receptors (FGFRs), and four high molecular weight (HMW) proteins located in the nucleus. Fibroblast growth factor receptor (FGFR) family has four (FGFR1-4) transmembrane tyrosine kinase receptors expressed on several cell types, and FGFR-1 has been indicated as a potential molecular target in several types of cancer, including oral squamous cell carcinoma (OSCC). The FGF-2/FGFR-1 expression has been studied in the oral cavity, and it was associated with the wound repair process, the development of benign and malignant salivary gland tumors, besides being related to oral potentially malignant disorders (OPMDs) and OSCC. Hence, we critically review the currently available data on FGF-2/FGFR-1 expression in the normal mucosa and lesions of the oral cavity.

Polymorphisms in cytokine genes influence cognitive and functional performance in a population aged 75 years and above.

OBJECTIVE: To investigate the frequency of the cytokine single nucleotide polymorphisms (SNPs) tumor necrosis factor (TNF)-α -308G > A, tumor growth factor (TGF)-ß1 codon +10C > T, TGF-ß1 codon +25G > C, interleukin (IL)-10 -1082A > G, IL-10 -819C > T, IL-10 -592C > A, IL-6 -174G > C, and IFN-γ +874T > A in a sample of healthy and cognitively impaired elderlies and to verify the probable association between these SNPs and cognitive and functional performance of subjects aged 75 years and above. METHODS: 259 Brazilian subjects were included, comprising 81 with cognitive impairment no dementia (CIND) and 54 demented seniors (together made up the cognitively impaired group, CI) and 124 age-matched and gender-matched cognitively healthy controls (CHS). The genotyping was performed by multiplex polymerase chain reaction. The cognitive performance was evaluated by Mini-Mental State Examination Brief Cognitive Screening Battery. The functional performance was accessed by Functional Activities Questionnaire. RESULTS: The CClower genotype of TGF-ß1 codon +25G > C was frequent in both patient groups. The TThigher genotype of INF-γ +874T > A was less frequent in the dementia group. IL-10 haplotypes of lower expression were more frequent among CIND and demented patients. In CI, individuals with genetic variants that produce higher expression of TGF-ß1, INF-γ, and IL-10 showed better normalized cognitive performance. Additionally, the Alower allele of INF-γ +874T > A was related to worse functional performance in CI, while the Alower allele of TNF-α -308G > A was associated with better cognitive and functional scores in the CIND group. CONCLUSIONS: Our findings suggest a potential role for certain cytokine SNPs in the development of CIND and dementia, which may influence the functional and cognitive performance of these patients. Copyright © 2016 John Wiley & Sons, Ltd.

Cortisol, HDL-c, VLDL-c, and APOE Polymorphisms as Laboratorial Parameters Associated to Cognitive Impairment No Dementia (CIND) and Dementia.

BACKGROUND: Population aging is a global phenomenon whose main consequence is the increase of chronic degenerative diseases, including dementia. The aim of this case-control study was to evaluate the laboratorial parameters lipid profile, cortisol, and apolipoprotein E (APOE) gene genotype, comparing cognitively healthy controls and subjects with cognitive impairment no dementia (CIND) and dementia in a group of elderly people. METHODS: Three hundred and nine individuals enrolled in the Pietà Study (Brazil) were divided into three groups: control (n = 158), CIND (n = 92), and dementia (n = 59). Participants were interviewed, went through examination, and had blood samples taken. RESULTS: Age and APOE showed significant differences among the groups, while sex and lipid profile did not. According to multivariate regression logistic analyses, higher cortisol levels, lower high-density lipoprotein (HDL-c) and very low-density lipoprotein (VLDL-c), presence of ε4 allele of APOE, and aging were associated with CIND and dementia. CONCLUSION: These laboratorial parameters are risk factors associated to CIND and dementia in the elderly people and should be investigated in order to develop strategies to prevent or delay the onset of dementia in the oldest-old populations.

Haemophilus influenzae type b disease among children in rural Mozambique: impact of vaccine introduction.

OBJECTIVE: Haemophilus influenzae type b (Hib) conjugate vaccine has dramatically reduced invasive Hib disease worldwide. Yet, data on protection against pneumonia and among children with HIV are limited. We evaluated the impact of Hib conjugate vaccine introduction in 2009 in a rural, high-HIV prevalence area in Mozambique. STUDY DESIGN: From 2006-2011, we conducted hospital-based surveillance for invasive Hib disease and clinical pneumonia (classified as severe and very severe) among children <5 years of age. Incidences calculated using population denominators were compared between baseline (2006-2008) and post-Hib conjugate vaccine (2010-2011) periods. Surveillance data for radiologically-confirmed pneumonia among children <2 years of age in 2011 were compared with baseline data from 2004-2006. RESULTS: Among 50 cases of invasive Hib disease, 5 occurred after Hib conjugate vaccine introduction; 1 case-patient was age-eligible for Hib conjugate vaccine (and had received 3 doses). Four post-Hib conjugate vaccine case-patients (including Hib conjugate vaccine failure) had HIV. Among children <1 and <5 years of age, significant reductions occurred in rates of invasive Hib disease (91% and 85%, respectively) and very severe pneumonia (29% and 34%, respectively). Radiologically-confirmed pneumonia incidence fell significantly (33%) in children <2 years of age. Severe pneumonia incidence did not decline. CONCLUSIONS: We demonstrate important reductions in invasive disease and pneumonia following Hib conjugate vaccine introduction in a high-HIV area. Continued surveillance is needed to monitor long-term Hib conjugate vaccine effects, particularly among children with HIV.

Impact of Haemophilus influenzae Type b conjugate vaccine in Mongolia: prospective population-based surveillance, 2002-2010.

OBJECTIVES: Bacterial meningitis is associated with high mortality and long-term complications. This study assessed the impact of Haemophilus influenzae type b (Hib) conjugate vaccine on childhood bacterial meningitis in Ulaanbaatar, Mongolia. STUDY DESIGN: Prospective, active, population-based surveillance for suspected meningitis in children aged 2-59 months was conducted (February 2002-January 2011) in 6 hospitals. Clinical data, blood, and cerebrospinal fluid were collected. The impact of Hib conjugate vaccine was assessed by comparing Hib and all cause meningitis data in the 3 years preceding pentavalent conjugate vaccine implementation (2002-2004) with 3 years postimplementation (2008-2010). RESULTS: Five hundred eleven cases of suspected meningitis were identified from 2002-2011. Pentavalent conjugate vaccine coverage in December 2005 in Ulaanbaatar city was 97%. The proportion of suspected cases confirmed as Hib meningitis decreased from 25% (50/201) in the prevaccination era to 2% (4/193) in the postvaccination era (P < .0001). The annual incidence of Hib decreased from 28 cases per 100,000 children in 2002-2005 to 2 per 100,000 in 2008-2010 (P < .0001). CONCLUSIONS: This article demonstrates the marked impact of Hib conjugate vaccine introduction on meningitis in Mongolia. It is important to sustain this surveillance system to monitor the long-term impact of Hib conjugate vaccine, as well as other interventions such as pneumococcal and meningococcal vaccines.

Antithrombotic potential of Lippia alba: A mechanistic approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Lippia alba (Mill.) N.E.Br. ex Britton & P. Wilson is traditionally used in Brazil as an adjunct in the relief of mild anxiety, as an antispasmodic, and as an antidyspeptic. This medicinal species was included in the Phytotherapeutic Form of the Brazilian Pharmacopeia 2nd edition (2021) and has already been described as the most used medicinal plant in a study with patients from an Anticoagulation Clinic in Brazil. Meanwhile, no studies were found that support the safety of the use of L. alba in patients using anticoagulants, a drug with several safety limitations. AIM OF THE STUDY: Provide scientific evidence to ensure the safety of the concomitant use of L. alba and warfarin and support the management of these patients by evaluating its in vitro anticoagulant effect and chemical composition. And, as a timely complementation, evaluate the potential of this medicinal species in the development of new antithrombotics. METHODS: The chemical profile of L. alba derivatives was analyzed by chromatographic methods such as Ultra-Performance Liquid Chromatography (UPLC) coupled with electrospray ionization mass spectrometry (ESI-MS), qualitative UPLC using Diode-Array Detection, and Thin Layer Chromatography. The anticoagulant activity was evaluated by the innovative Thrombin Generation Assay by Calibrated Automated Thrombogram method and using traditional coagulometric tests: prothrombin time, activated partial thromboplastin time, and plasma fibrinogen measurement. RESULTS: Extracts and fractions prolonged the coagulation time in all the tests and reduced thrombin formation in thrombin generation assay. Coagulation times with the addition of ethanloic extract (2.26 mg/mL) was 17.78s, 46.43s and 14.25s respectively in prothrombin time, activated partial thromboplastin time and fibrinogren plasma measurement. In thrombin generation test, this same extract showed ETP as 323 nM/min compared to control (815 nM/min) with high tissue factor and 582 nM/min compared to control (1147 nM/min) using low tissue factor. Presence of flavonoids, phenylpropanoids, and triterpenes were confirmed by chromatographic methods and 13 compounds were identified by UPLC-ESI-MS. Based on these results and on the scientific literature, it is possible to propose that phenylpropanoids and flavonoids are related to the anticoagulant activity observed. CONCLUSION: The results demonstrate the in vitro anticoagulant activity of L. alba, probably due to the activation of intrinsic and extrinsic pathways. It is concluded, then, that there is a potential for interaction, which needs to be further studied, between L. alba and warfarin. Also, this medicinal species shows a great potential for use in the development of new antithrombotics.

Are gastric cancer resection margin proteomic profiles more similar to those from controls or tumors?

A strategy for treating cancer is to surgically remove the tumor together with a portion of apparently healthy tissue surrounding it, the so-called "resection margin", to minimize recurrence. Here, we investigate whether the proteomic profiles from biopsies of gastric cancer resection margins are indeed more similar to those from healthy tissue than from cancer biopsies. To this end, we analyzed biopsies using an offline MudPIT shotgun proteomic approach and performed label-free quantitation through a distributed normalized spectral abundance factor approach adapted for extracted ion chromatograms (XICs). A multidimensional scaling analysis revealed that each of those tissue-types is very distinct from each other. The resection margin presented several proteins previously correlated with cancer, but also other overexpressed proteins that may be related to tumor nourishment and metastasis, such as collagen alpha-1, ceruloplasmin, calpastatin, and E-cadherin. We argue that the resection margin plays a key role in Paget's "soil to seed" hypothesis, that is, that cancer cells require a special microenvironment to nourish and that understanding it could ultimately lead to more effective treatments.

ADAMTS13 and Von Willebrand factor in patients undergoing hemodialysis.

Hemodialysis (HD) is associated with increasing thrombotic trend. Vascular access thrombosis (VAT) increases morbidity in HD patients. The aim of this study was to evaluate ADAMTS13 and VWF plasma levels from patients undergoing HD as putative biomarkers of the hypercoagulability state, as well the association between these markers and VAT occurrence. This study included 195 patients on HD for more than 6 months. HD patients were allocated into two groups according to the occurrence or not of previous episode of VAT; HD with VAT (N = 46) and HD without VAT (N = 149). ADAMTS13 and VWF were performed by ELISA. There was no significant difference between HD patients with and without VAT for ADAMTS13 and VWF levels. However, VWF levels were higher (P < 0.001) and ADAMTS13 were lower (P < 0.001) in HD patients, comparing to the control group composed by healthy subjects without kidney disease, age and sex-matched (N = 80). Taken together our data suggest a potential role of the kidneys function compromised on ADAMTS13 synthesis or metabolism, regardless other known sources of ADAMTS13. The imbalance between ADAMTS13 and VWF levels does not explain the development of VAT in HD patients by itself, although it should contribute for the hypercoagulability state. Therefore, additional studies to identify other risk factors are warranted and essential for better management of HD patients.

Relationship between ABO blood groups and von Willebrand factor, ADAMTS13 and factor VIII in patients undergoing hemodialysis.

Several studies have demonstrated that non-O blood groups subjects present an increased VTE risk as compared to those carrying O blood group. The aim of this study was to investigate the ABO blood groups influence on factor VIII (FVIII) activity, von Willebrand factor (VWF), and ADAMTS13 plasma levels in patients undergoing hemodialysis (HD). Patients undergoing HD (N=195) and 80 healthy subjects (control group) were eligible for this cross-sectional study. The ABO blood group phenotyping was performed by the reverse technique. FVIII activity was measured through coagulometric method, and VWF and ADAMTS13 antigens were assessed by ELISA. FVIII activity and VWF levels were significantly higher and ADAMTS13 levels was decreased in HD patients, as compared to healthy subjects (P < 0.001, in three cases). HD patients carrying non-O blood groups showed a significant increase in FVIII activity (P = 0.001) and VWF levels (P < 0.001) when compared to carriers of O blood group. However, no significant difference was observed in ADAMTS13 levels (P = 0.767). In the control group, increased in FVIII activity (P = 0.001) and VWF levels (P = 0.002) and decreased in ADAMTS13 levels (P = 0.005) were observed in subjects carrying non-O blood groups as compared to carriers of O blood group.Our data confirmed that ABO blood group is an important risk factor for increased procoagulant factors in plasma, as FVIII and VWF. Admitting the possible role of kidneys in ADAMTS13 synthesis or on its metabolism, HD patients were not able to increase ADAMTS13 levels in order to compensate the increase of VWF levels mediated by ABO blood groups. Considering that non-O blood groups constitute a risk factor for thrombosis, it is reasonable to admit that A, B and AB HD patients need a careful and continuous follow-up in order to minimize thrombotic events.

Unfractionated heparin versus low molecular weight heparin for avoiding heparin-induced thrombocytopenia in postoperative patients.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction presenting as a prothrombotic disorder related to antibody-mediated platelet activation. It is a poorly understood paradoxical immune reaction resulting in thrombin generation in vivo, which leads to a hypercoagulable state and the potential to initiate venous or arterial thrombosis. A number of factors are thought to influence the incidence of HIT including the type and preparation of heparin (unfractionated heparin (UFH) or low molecular weight heparin (LMWH)) and the heparin-exposed patient population, with the postoperative patient population presenting a higher risk.Although LMWH has largely replaced UFH as a front-line therapy, there is evidence supporting a lack of superiority of LMWH compared with UFH regarding prevention of deep vein thrombosis and pulmonary embolism following surgery, and similar frequencies of bleeding have been described with LMWH and UFH. The decision as to which of these two preparations of heparin to use may thus be influenced by adverse reactions such as HIT. We therefore sought to determine the relative impact of UFH and LMWH specifically on HIT in postoperative patients receiving thromboembolism prophylaxis. OBJECTIVES: The objective of this review was to compare the incidence of HIT and HIT complicated by thrombosis in patients exposed to UFH versus LMWH in randomised controlled trials (RCTs) of postoperative heparin therapy. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (March 2012) and CENTRAL (2012, Issue 2). In addition, the authors searched LILACS (March 2012) and additional trials were sought from reference lists of relevant publications. SELECTION CRITERIA: We were interested in comparing the incidence of HIT occurring during exposure to UFH or LMWH after any surgical intervention. Therefore, we studied RCTs in which participants were postoperative patients allocated to receive UFH or LMWH, in a blinded or unblinded fashion. Eligible studies were required to have as an outcome clinically diagnosed HIT, defined as a relative reduction in the platelet count of 50% or greater from the postoperative peak (even if the platelet count at its lowest remained > 150 x 10(9)/L) occurring within five to 14 days after the surgery, with or without a thrombotic event occurring in this timeframe. Additionally, circulating antibodies associated with the syndrome were required to have been investigated through laboratory assays. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias. Disagreements were resolved by consensus with participation of a third author. MAIN RESULTS: In total two studies involving 923 participants met all the inclusion criteria and were included in the review. Pooled analysis showed a statistically significant reduction in the risk of HIT with LMWH compared with UFH (risk ratio (RR) 0.24, 95% confidence interval (CI) 0.07 to 0.82; P = 0.02). This result suggests that patients treated with LMWH would have a relative risk reduction (RRR) of 76% in the probability of developing HIT compared with patients treated with UFH.Venous thromboembolism (VTE) complicating HIT occurred in 12 of 17 patients who developed HIT. Pooled analysis showed a statistically significant reduction in HIT complicated by VTE with LMWH compared with UFH (RR 0.20, 95% CI 0.04 to 0.90; P = 0.04). This result indicates that patients using LMWH would have a RRR of 80% for developing HIT complicated by VTE compared with patients using UFH. Arterial thrombosis occurred in only one patient who received UFH and there were no amputations or deaths documented. AUTHORS' CONCLUSIONS: There was a lower incidence of HIT and HIT complicated by VTE in postoperative patients undergoing thromboprophylaxis with LMWH compared with UFH. This is consistent with the current clinical use of LMWH over UFH as front-line heparin therapy. However, conclusions are limited by a scarcity of high quality evidence. We did not expect the paucity of RCTs including HIT as an outcome as heparin is one of the most commonly used drugs worldwide and HIT is a life-threatening adverse drug reaction. To address the scarcity of clinically-relevant information on the topic of HIT as a whole, HIT should be included as an outcome in future RCTs of heparin, and HIT as an adverse drug reaction should be considered in clinical recommendations regarding monitoring of the platelet count for HIT.

High-performance delignification of invasive tree species wood with ionic liquid and deep eutectic solvent for the production of cellulose-based polyelectrolytes.

An efficient and eco-friendly process for lignocellulosic biomass fractionation is essential for the production of high value-added bioproducts from biomass. The present work aimed to obtain cellulose-rich materials from the wood of an invasive tree species (Acacia dealbata) using an appropriate choice of ionic liquids (ILs) and deep eutectic solvents (DESs), and of the processing conditions, for the subsequent production of cationic wood-based polyelectrolytes. In the pretreatment step, the 1-butyl-3-methylimidazolium methyl sulfate (IL) + H2O and choline chloride + imidazole (DES) systems demonstrated a remarkable ability to remove lignin from acacia, reaching up to 92.4 and 90.2% of delignification, respectively. However, the DES pretreatment revealed to be more selective for lignin removal with lower cellulose losses (less than 15%) than the IL treatment (up to 30%) and less cellulose depolymerization. The hemicellulose was also removed but in a lesser extent with the DES treatment. Both systems could provide treated materials with a very high cellulose content (≥89%). Afterwards, cationic polyelectrolytes having a considerable content of quaternary ammonium groups (up to 3.6 mmol g-1) were obtained directly from the IL- and DES-pretreated woods. The treated woods, when used as raw materials for cationization reaction, allow to synthesize water-soluble polyelectrolytes with potential to be applied in wastewater treatment, pharmaceutical or cosmetic products.

Oral Manifestations of Coronavirus Disease 2019 (COVID-19): A Comprehensive Clinicopathologic and Immunohistochemical Study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents rapid transmission and significant mortality worldwide. It is responsible for coronavirus disease 2019 (COVID-19). The disease presents diverse clinical symptoms, including fever, cough, dyspnea, and pneumonia. However, other manifestations associated with COVID-19 need to be clarified, leading specialists to an early diagnosis and better prognosis. We describe the spectrum of clinicopathologic COVID-19-related oral lesions that can be the first and/or the unique manifestation of the disease. Fourteen patients with a mean age of 58 years (range: 23 to 88 y) with oral lesions were included. All patients were confirmed to be infected with SARS-CoV-2 by reverse transcription polymerase chain reaction testing. Patients demonstrated mild symptoms, including dysgeusia, anosmia, fever, and headache. The lesions were recognized and classified into 2 groups: (1) lesions caused by ischemia and/or hemorrhage and (2) lesions secondary to inflammatory events associated with viral load. The palate was most affected (n=8), followed by the tongue (n=4), and both the lip and palate (n=2). Histologic analysis demonstrated thrombosis of small arteries and capillaries, associated with areas of hemorrhage and chronic inflammatory infiltrate. Immunohistochemistry showed positive staining for spike protein (SARS-CoV and SARS-CoV-2) and angiotensin-converting enzyme 2 in the surface epithelium, salivary glands, inflammatory cells, and endothelial cells. Although the incidence of oral lesions among patients infected with SARS-CoV-2 appears to be uncommon, these findings suggest that the oral mucosa can also be a target organ for SARS-CoV-2.

HFE, MTHFR, and FGFR4 genes polymorphisms and breast cancer in Brazilian women.

Genetic factors related to cancer have been extensively studied and several polymorphisms have been associated to breast cancer. The FGFR4, MTHFR, and HFE genes have been associated with neoplastic diseases development. The current report outlines the analysis of the polymorphisms G388A (FGFR4), C677T (MTHFR), C282Y, and H63D (HFE) in Brazilian breast cancer patients. We studied 68 patients with invasive ductal and operable breast carcinoma and 85 women as a control group. The polymorphism frequencies in the breast cancer and control groups were analyzed, but no significant difference was observed by comparing the two groups. The presence of each polymorphism was analyzed according to the clinical features and markers already established as prognostic in the breast cancer group. The C677T, H63D, and G388A polymorphisms were not associated to histological grade, age of diagnosis, expression of HER2 receptor, or estrogen and progesterone receptor. The H63D polymorphism showed a significant association (P = 0.02) with the presence of p53 mutations, and C667T showed association to lymph node involvement (P = 0.05). Lymph node involvement, G388A polymorphism, and histological grade were independently associated to metastasis/death. Our data suggests that the polymorphisms G388A, C677T, and H63D are not useful in breast cancer diagnosis, but they may be significant additional prognostic markers related to breast cancer survival.