SYK inhibition thwarts the BAFF - B-cell receptor crosstalk and thereby antagonizes Mcl-1 in chronic lymphocytic leukemia.

Although small molecule inhibitors of B-cell receptor-associated kinases have revolutionized therapy in chronic lymphocytic leukemia (CLL), responses are incomplete. Pro-survival signaling emanating from the microenvironment may foster therapeutic resistance of the malignant B cells resident in the protective lymphoid niches. B-cell activating factor (BAFF) is critical to the survival of both healthy and neoplastic B cells.

The feasibility and benefit of a brief psychosocial intervention in addition to early palliative care in patients with advanced cancer to reduce depressive symptoms: a pilot randomized controlled clinical trial.

Background: The aim of this study was to assess the feasibility and potential benefit of a brief psychosocial intervention based on cognitive-behavioral therapy performed in addition to early palliative care (PC) in the reduction of depressive symptoms among patients with advanced cancer.

Methods: An open-label randomized phase II clinical trial with two intervention arms and one control group. Patients with advanced cancer starting palliative chemotherapy and who met the selection criteria were included.

Ecology and identification of environmental fungi and metabolic processes involved in the biodeterioration of Brazilian soapstone historical monuments.

Unlabelled: This study aimed to evaluate the action of organic acids produced by the fungal population associated with the biodeterioration process of the Twelve Prophets of Aleijadinho, a set of soapstone sculptures in Congonhas, state of Minas Gerais, Brazil. For this, samples of fungi were obtained from the surface of each of the 12 outdoor stone sculptures that comprise the set of Prophets. The identification of the colonizing filamentous fungi was performed by classical microbiology and molecular methods.

TFOS DEWS II Report Executive Summary.

This article presents an Executive Summary of the conclusions and recommendations of the 10-chapter TFOS DEWS II report. The entire TFOS DEWS II report was published in the July 2017 issue of The Ocular Surface. A downloadable version of the document and additional material, including videos of diagnostic and management techniques, are available on the TFOS website: www.

Translation and cultural adaptation of the Functional Assessment of Chronic Illness Therapy - Cervical Dysplasia (FACIT-CD) to evaluate quality of life in women with cervical intraepithelial neoplasia.

Objective: To translate and perform the cultural adaptation of the tool Functional Assessment of Chronic Illness Therapy - Cervical Dysplasia (FACIT-CD) to the Portuguese language.

Methods: A descriptive cross-sectional study, with translation and cultural adaptation of the assessment tool performed according to international guidelines and the Functional Assessment of Chronic Illness Therapy (FACIT) protocol group. It involved eight experts, six from Brazil, one from Portugal and one from the United States.

TFOS DEWS II pathophysiology report.

The TFOS DEWS II Pathophysiology Subcommittee reviewed the mechanisms involved in the initiation and perpetuation of dry eye disease. Its central mechanism is evaporative water loss leading to hyperosmolar tissue damage. Research in human disease and in animal models has shown that this, either directly or by inducing inflammation, causes a loss of both epithelial and goblet cells.

Effect of oil palm on the Plecoptera and Trichoptera (Insecta) assemblages in streams of eastern Amazon.

The production of oil palm is expected to increase in the Amazon region. However, expansion of oil palm plantation leads to significant changes in the physical structure of aquatic ecosystems, mainly through the reduction of riparian vegetation that is essential for aquatic biodiversity. Here, we evaluated the effects of oil palm on the physical habitat structure of Amazonian stream environments and assemblages of Plecoptera and Trichoptera (PT), ​both found in these streams.

Review: MicroRNAS in ocular surface and dry eye diseases.

Since the first description of microRNAs (miRNAs) in the 1990s, more than 60 papers have described the role of miRNAs on the ocular surface and lacrimal gland (LG). MicroRNAs (miRNAs) have a role in several physiological events and in mediation of disease. They inhibit gene expression by blocking messenger RNA.

Goblet Cells Contribute to Ocular Surface Immune Tolerance-Implications for Dry Eye Disease.

Conjunctival goblet cell (GC) loss in dry eye is associated with ocular surface inflammation. This study investigated if conjunctival GCs contribute to ocular surface immune tolerance. Antigens applied to the ocular surface, imaged by confocal microscopy, passed into the conjunctival stroma through goblet cell associated passages (GAPs) in wild type C57BL/6 (WT), while ovalbumin (OVA) was retained in the epithelium of SAM pointed domain containing ETS transcription factor () knockout mice (/) that lack GCs and are a novel model of dry eye.

Depression, anxiety, hopelessness and quality of life in users of cocaine/crack in outpatient treatment.

Objective:: To identify symptoms of anxiety, depression, and feelings of hopelessness in patients in outpatient treatment for substance dependency and to test for correlations with various aspects of their quality of life.

Methods:: A cross-sectional study of a sample of 25 men in recuperation from substance dependency, selected by convenience. We assessed symptoms of depression (Beck Depression Inventory-II), anxiety (Beck Anxiety Inventory), hopelessness (Beck Hopelessness Scale), and quality of life (World Health Organization Quality of Life instrument-Abbreviated version [WHOQOL-Bref]), and also analyzed sociodemographic profile, substance abuse, and family history.

REVIEW-ARTICLE Intermediate alleles of Huntington's disease HTT gene in different populations worldwide: a systematic review.

Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder caused by a dynamic mutation due to the expansion of CAG repeats in the HTT gene (4p16.3). The considered normal alleles have less than 27 CAG repeats.

Chromomycosis, an unusual cause of cicatricial ectropion: a case report.

Chromomycosis is a fungal infection that affects the epidermis, dermis, and subcutaneous tissue and is caused by dematiaceous fungal species that turn black on staining. We report the case of a 50-year-old male patient who was a rural worker and had been treated without success for three decades. Facial lesions progressed and caused severe cicatricial retraction.

Autoantibodies with beta-adrenergic activity from chronic chagasic patients induce cardiac arrhythmias and early afterdepolarization in a drug-induced LQT2 rabbit hearts.

Background: Cardiac arrhythmias are one of the main causes of death in ChCP and other dilated cardiomyopathies. Previous studies demonstrated that ventricular arrhythmias are associated with the presence of autoantibodies with beta-adrenergic activity, Ab-β.

Objectives: The aim of this study was to investigate whether Ab-β, present in chronic chagasic patients (ChCP), induce cardiac arrhythmias in the pharmacological type-2 long QT syndrome model (LQTS-2).

Effects of Aging in Dry Eye.

Dry eye affects millions of people worldwide and causes eye well recognized risk factors for dry eye. Anatomical and inflammation-induced age-related changes affect all components of the lacrimal gland functional unit, inclusive of lacrimal gland, conjunctiva, meibomian gland and compromise ocular surface health. There is increased evidence that inflammation plays a role in dry eye.

Inhibition of NLRP3 Inflammasome Pathway by Butyrate Improves Corneal Wound Healing in Corneal Alkali Burn.

Epithelial cells are involved in the regulation of innate and adaptive immunity in response to different stresses. The purpose of this study was to investigate if alkali-injured corneal epithelia activate innate immunity through the nucleotide-binding oligomerization domain-containing protein (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway. A unilateral alkali burn (AB) was created in the central cornea of C57BL/6 mice.

Mitochondrial DNA oxidation induces imbalanced activity of NLRP3/NLRP6 inflammasomes by activation of caspase-8 and BRCC36 in dry eye.

The concept of innate immunity has been expanded to recognize environmental pathogens other than microbial components. However, whether and how the innate immunity is initiated by epithelium in response to environmental physical challenges such as low humidity and high osmolarity in an autoimmune disease, dry eye, is still largely unknown. Using two experimental dry eye models, primary human corneal epithelial cultures exposed to hyperosmolarity and mouse ocular surface facing desiccating stress, we uncovered novel innate immunity pathway by ocular surface epithelium, where oxidized mitochondrial DNA induces imbalanced activation of NLRP3/NLRP6 inflammasomes via stimulation of caspase-8 and BRCC36 in response to environmental stress.

What are the personal and professional characteristics that distinguish the researchers who publish in high- and low-impact journals? A multi-national web-based survey.

Purpose: This study identifies the personal and professional profiles of researchers with a greater potential to publish high-impact academic articles.

Method: The study involved conducting an international survey of journal authors using a web-based questionnaire. The survey examined personal characteristics, funding, and the perceived barriers of research quality, work-life balance, and satisfaction and motivation in relation to career.

Pevonedistat, a Nedd8-activating enzyme inhibitor, sensitizes neoplastic B-cells to death receptor-mediated apoptosis.

While death receptor ligands (Fas and TRAIL) kill chemoresistant tumor cell lines, related therapies have limited clinical efficacy as single agents. Death receptor signaling is modulated by nuclear factor-κB (NFκB), a family of transcription factors which are constitutively active in B-cell malignancies. We and others have shown that pevonedistat, an investigational inhibitor of the NEDD8-activating enzyme, abrogates NFκB activity in B-cell neoplasia.

Effects of Type 2 Diabetes Mellitus in Patients on Treatment With Glibenclamide and Metformin on Carvedilol Enantiomers Metabolism.

Carvedilol is available in clinical practice as a racemate in which (S)-(-)-carvedilol is a β- and α -adrenergic antagonist and (R)-(+)-carvedilol is only an α -adrenergic antagonist. Carvedilol is mainly metabolized by glucuronidation, by CYP2D6 to hydroxyphenylcarvedilol (OHC), and by CYP2C9 to O-desmethylcarvedilol (DMC). This study evaluated the pharmacokinetics of carvedilol enantiomers and their metabolites OHC and DMC in healthy volunteers (n = 13) and in type 2 diabetes mellitus patients with good glycemic control (n = 13).

Photochemical behavior of biosupramolecular assemblies of photosensitizers, cucurbit[n]urils and albumins.

Biosupramolecular assemblies combining cucurbit[n]urils (CB[n]s) and proteins for the targeted delivery of drugs have the potential to improve the photoactivity of photosensitizers used in the photodynamic therapy of cancer. Understanding the complexity of these systems and how it affects the properties of photosensitizers is the focus of this work. We used acridine orange (AO) as a model photosensitizer and compared it with methylene blue (MB) and a cationic porphyrin (TMPyP).

End-of-life experiences and deathbed phenomena as reported by Brazilian healthcare professionals in different healthcare settings.

Objective: The objectives of the present study were to describe and compare the characteristics and reports of end-of-life experiences (ELEs) by healthcare professionals at different institutions and to investigate the influence of religious beliefs on these reports.

Method: A multicenter study was carried out in Brazil that included six nursing homes (NHs), a cancer hospital (ONC), and a palliative care (PC) unit. Sociodemographic data, ELE reports (Fenwick's questionnaire), religiosity (the Duke Religion Index), spirituality (the Spirituality Self-Rating Scale), and mental health (the DASS-21 questionnaire) were assessed.

Translation and cultural adaptation of the Shame and Stigma Scale (SSS) into Portuguese (Brazil) to evaluate patients with head and neck cancer.

Introduction: Head and neck cancer is the sixth leading cause of death from cancer worldwide and its treatment may involve surgery, chemotherapy and/or radiation therapy. The surgical procedure may cause mutilating sequelae, that can alter patient self-image. Thus, head and neck cancer is often connected to the negative stigma with decreased quality of life.

Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice.

Diabetes mellitus (DM) encompasses a multitude of secondary disorders, including heart disease. One of the most frequent and potentially life threatening disorders of DM-induced heart disease is ventricular tachycardia (VT). Here we show that toll-like receptor 2 (TLR2) and NLRP3 inflammasome activation in cardiac macrophages mediate the production of IL-1β in DM mice.

Resveratrol Reverses Functional Chagas Heart Disease in Mice.

Chronic chagasic cardiomyopathy (CCC) develops years after acute infection by Trypanosoma cruzi and does not improve after trypanocidal therapy, despite reduction of parasite burden. During disease, the heart undergoes oxidative stress, a potential causative factor for arrhythmias and contractile dysfunction. Here we tested whether antioxidants/ cardioprotective drugs could improve cardiac function in established Chagas heart disease.

Single Jejunum Metastasis from Breast Cancer Arising Twelve Years after the Initial Treatment.

Metastatic involvement of gastrointestinal tract from breast cancer is a rare event. We report the case of a 61-year-old woman presenting with bowel obstruction, related to metastasis of a primary breast cancer she had 12 years earlier (a triple-negative invasive ductal carcinoma treated with surgery and chemotherapy). Bowel obstruction was caused by a 20-centimeter tumor in the jejunum, involving also the transverse colon.