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1.
Int J Biol Macromol ; 277(Pt 4): 134250, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39089541

ABSTRACT

The current treatments for wounds often fail to induce adequate healing, leaving wounds vulnerable to persistent infections and development of drug-resistant microbial biofilms. New natural-derived nanoparticles were studied to impair bacteria colonization and hinder the formation of biofilms in wounds. The nanoparticles were fabricated through polyelectrolyte complexation of chitosan (CS, polycation) and hyaluronic acid (HA, polyanion). UV-induced photo-crosslinking was used to enhance the stability of the nanoparticles. To achieve this, HA was methacrylated (HAMA, degree of modification of 20 %). Photo-crosslinked nanoparticles obtained from HAMA and CS had a diameter of 478 nm and a more homogeneous size distribution than nanoparticles assembled solely through complexation (742 nm). The nanoparticles were loaded with the antimicrobial agent bacitracin (BC), resulting in nanoparticles with a diameter of 332 nm. The encapsulation of BC was highly efficient (97 %). The BC-loaded nanoparticles showed significant antibacterial activity against gram-positive bacteria Staphylococcus aureus, Methicillin-resistant S. aureus and S. epidermidis. Photo-crosslinked HAMA/CS nanoparticles loaded with BC demonstrated inhibition of biofilm formation and a positive effect on the proliferation of mammalian cells (L929). These crosslinked nanoparticles have potential for the long-term treatment of wounds and controlled antibiotic delivery at the location of a lesion.

2.
Int J Mol Sci ; 24(22)2023 Nov 15.
Article in English | MEDLINE | ID: mdl-38003521

ABSTRACT

Over the past decades, the problem of bacterial resistance to most antibiotics has become a serious threat to patients' survival. Nevertheless, antibiotics of a novel class have not been approved since the 1980s. The development of antibiotic potentiators is an appealing alternative to the challenging process of searching for new antimicrobials. Production of H2S-one of the leading defense mechanisms crucial for bacterial survival-can be influenced by the inhibition of relevant enzymes: bacterial cystathionine γ-lyase (bCSE), bacterial cystathionine ß-synthase (bCBS), or 3-mercaptopyruvate sulfurtransferase (MST). The first one makes the main contribution to H2S generation. Herein, we present data on the synthesis, in silico analyses, and enzymatic and microbiological assays of novel bCSE inhibitors. Combined molecular docking and molecular dynamics analyses revealed a novel binding mode of these ligands to bCSE. Lead compound 2a manifested strong potentiating activity when applied in combination with some commonly used antibiotics against multidrug-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. The compound was found to have favorable in vitro absorption, distribution, metabolism, excretion, and toxicity parameters. The high effectiveness and safety of compound 2a makes it a promising candidate for enhancing the activity of antibiotics against high-priority pathogens.


Subject(s)
Hydrogen Sulfide , Methicillin-Resistant Staphylococcus aureus , Humans , Anti-Bacterial Agents/pharmacology , Hydrogen Sulfide/metabolism , Cystathionine gamma-Lyase/metabolism , Methicillin-Resistant Staphylococcus aureus/metabolism , Pyrroles/pharmacology , Molecular Docking Simulation , Bacteria/metabolism , Indoles/pharmacology , Cystathionine beta-Synthase/metabolism
3.
Cureus ; 15(5): e38995, 2023 May.
Article in English | MEDLINE | ID: mdl-37323325

ABSTRACT

Introduction The prevalence of obesity is steadily increasing worldwide. Obesity is one of the most potent risk factors for various diseases and is simultaneously a heterogeneous condition. Different types of obesity could be identified according to body mass index (BMI), waist circumference, and visceral fat level; these conditions may present individually or in combination and pose a risk of developing certain comorbidities. However, the current obesity classification systems do not allow for accurate diagnosis and prediction of the comorbidity risk of patients, which is crucial for their clinical management. This points to the importance of studying obesity phenotyping in the context of body composition. Our study aimed to determine the contribution of obesity phenotypes in forming various comorbidities. Materials and methods This case-control study was conducted at the Clinical and Diagnostic Center of the Aviastroitelny District, Kazan. Patients were selected based on BMI per inclusion and exclusion criteria. A total of 151 patients with a median age of 43 [34.5-50] years were included in the study. The participants were distributed into six groups according to BMI and a combination of abdominal obesity (AO) and excess visceral fat. Results The participants were distributed in the following phenogroups: The first group - normal BMI without AO and excess visceral fat (n=47; 31.1%); the second group - overweight without AO and excess visceral fat (n=26; 17.2%); the third group - normal BMI with AO and without excess visceral fat (n=11; 7.3%); fourth group - overweight with AO and without excess visceral fat (n=34; 22.5%); fifth group - general obesity with AO and without excess visceral fat (n=20; 13.2%); sixth group - general obesity with AO and excess visceral fat (n=13; 8.6%). The five most frequently observed conditions in the general cohort were dyslipidemia (71.5%; n=108), disorders of the gastrointestinal tract (53.0%; n=80), cardiovascular disease (46.4%; n=70), musculoskeletal diseases (40.4%; n=61) and impaired carbohydrate metabolism (25.2%; n=38). The median number of pathological combinations in the general cohort was 5 [IQR: 3-7]. As the group number increased, the median number of comorbidities also increased. While BMI was significantly associated only with arterial hypertension, the level of visceral fat was associated with most comorbidities (obstructive sleep apnea syndrome, non-alcoholic fatty liver disease, chronic pancreatitis, hypertriglyceridemia, and prediabetes), followed by abdominal obesity (gastroesophageal reflux disease, hypertriglyceridemia, arterial hypertension, hypercholesterolemia). Conclusions In working-age people, group 1 and 4 phenotypes were more frequent than others. Abdominal obesity and visceral fat were associated with the most comorbid conditions. However, the individual types of these comorbidities were not the same.

4.
Int J Mol Sci ; 25(1)2023 Dec 20.
Article in English | MEDLINE | ID: mdl-38203233

ABSTRACT

The minor secreted proteinase of B. pumilus 3-19 MprBp classified as the unique bacillary adamalysin-like enzyme of the metzincin clan. The functional role of this metalloproteinase in the bacilli cells is not clear. Analysis of the regulatory region of the mprBp gene showed the presence of potential binding sites to the transcription regulatory factors Spo0A (sporulation) and DegU (biodegradation). The study of mprBp activity in mutant strains of B. subtilis defective in regulatory proteins of the Spo- and Deg-systems showed that the mprBp gene is partially controlled by the Deg-system of signal transduction and independent from the Spo-system.


Subject(s)
Bacillus pumilus , Bacillus , Lacticaseibacillus casei , Bacillus pumilus/genetics , Metalloendopeptidases , Biodegradation, Environmental , Firmicutes
5.
Biomaterials ; 290: 121829, 2022 11.
Article in English | MEDLINE | ID: mdl-36194954

ABSTRACT

Recombinant spider silk materials with antimicrobial peptides are a promising new class of drug-free antimicrobial materials capable of preventing surgical site infections (SSI), but their potential to impede infections is unclear. Herein, we aimed to unravel the biological and inflammatory potential of bioengineered spider silk materials to prevent SSI using an infection animal model. Silk-like fibers made of silk fibroin and spider silk proteins with antimicrobial peptides (6mer-HNP1) held improved stiffness (2.9 GPa) and had a slow biodegradation profile while inhibiting bacterial adherence in vitro by 5-log and 6-log reduction on Methicillin-Resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli), respectively. In vivo studies showed that fibers with 6mer-HNP1 elicited a short-term low to mild local inflammatory response, similar to implanted commercial sutures. In the presence of a bacterial infection, the mediators related to infection and inflammation were downregulated suggesting that the fibers maintained a low but active response to bacterial infection. Thus, the presence of 6mer-HNP1 helped the host maintain an active response to bacterial infection, impairing the development of an acute infection. Our findings further support the use of bioengineered spider silk proteins to develop drug-free antimicrobial sutures capable to impair SSI.


Subject(s)
Anti-Infective Agents , Bacterial Infections , Methicillin-Resistant Staphylococcus aureus , Spiders , Animals , Escherichia coli , Sutures , Silk/chemistry , Surgical Wound Infection/prevention & control , Anti-Bacterial Agents/pharmacology
6.
Antibiotics (Basel) ; 11(9)2022 Sep 05.
Article in English | MEDLINE | ID: mdl-36139977

ABSTRACT

Since the discovery of streptomycin, actinomycetes have been a useful source for new antibiotics, but there have been diminishing rates of new finds since the 1960s. The decreasing probability of identifying new active agents led to reduced interest in soil bacteria as a source for new antibiotics. At the same time, actinomycetes remain a promising reservoir for new active molecules. In this work, we present several reporter plasmids encoding visible fluorescent protein genes. These plasmids provide primary information about the action mechanism of antimicrobial agents at an early stage of screening. The reporters and the pipeline described have been optimized and designed to employ citizen scientists without specialized skills or equipment with the aim of essentially crowdsourcing the search for new antibiotic producers in the vast natural reservoir of soil bacteria. The combination of mechanism-based approaches and citizen science has proved its effectiveness in practice, revealing a significant increase in the screening rate. As a proof of concept, two new strains, Streptomyces sp. KB-1 and BV113, were found to produce the antibiotics pikromycin and chartreusin, respectively, demonstrating the efficiency of the pipeline.

7.
J Psychiatr Res ; 154: 117-122, 2022 10.
Article in English | MEDLINE | ID: mdl-35933855

ABSTRACT

Individuals with obsessive-compulsive disorder (OCD) more often think about, attempt, and die by suicide than individuals from the general population. Sexual and religious obsessions (i.e., taboo obsessions) have been linked to increased risk of suicidality, but it is unclear if they explain additional risk over and above other risk factors. We refined the recently proposed multidimensional hierarchical model of OCD and explored how each symptom dimension in the model was associated with suicidality in a random half (n = 500) of a well-characterized cohort of patients with OCD. Symptom dimensions and other risk factors significantly associated with suicidality were included in a confirmatory multivariable model conducted with the other half of the sample (n = 501). The predictive confirmatory model accounted for 19% of the variance in suicidality. Taboo obsessions, the general OCD factor (i.e., having many different OCD symptoms at the same time), lifetime major depression, and lifetime substance use disorders significantly predicted suicidality in this model. Lifetime major depression explained most unique variance in suicidality (5.6%) followed by taboo obsessions and the general OCD factor (1.9% each). Taboo obsessions explain a small but significant proportion of variance in suicidality and should be considered an independent risk factor for suicidality in patients with OCD.


Subject(s)
Obsessive-Compulsive Disorder , Suicide , Humans , Obsessive Behavior/epidemiology , Obsessive-Compulsive Disorder/diagnosis , Obsessive-Compulsive Disorder/epidemiology , Suicidal Ideation , Taboo
8.
Biochemistry (Mosc) ; 87(3): 215-224, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35526850

ABSTRACT

Color vision sensitivity is crucial for fish adaptation during migration and reproduction. Prolactin and prolactin-like hormone are important regulators in both these processes. We hypothesized that prolactin influences the color vision sensitivity during freshwater migrations in fish. We studied the effects of prolactin and freshwater adaptation during the spawning period on the expression of opsin genes (SWS1, SWS2, RH2, LWS) in the retina of female and male three-spined sticklebacks Gasterosteus aculeatus L. Expression of the prolactin gene increased in the brain of females, but not males, while expression of the prolactin-like hormone decreased in the brain of both male and female sticklebacks during freshwater adaptation. Expression of the SWS2 gene decreased in the retina of females and males during freshwater adaptation and after prolactin administration. Expression of the SWS1 gene decreased in the retina of male sticklebacks after prolactin administration, but not during freshwater adaptation. Expression of the RH2 and LWS genes did not depend on prolactin administration in male and female sticklebacks. We conclude that expression of some opsin genes in the retina of sticklebacks is regulated by prolactin and depends on sex and freshwater adaptation. This expands our knowledge of the adaptive effects of prolactin on fish during freshwater migrations.


Subject(s)
Opsins , Smegmamorpha , Animals , Female , Fresh Water , Male , Opsins/genetics , Opsins/metabolism , Prolactin/genetics , Prolactin/pharmacology , Retina/metabolism , Smegmamorpha/genetics , Smegmamorpha/metabolism
9.
Psychiatry Res ; 312: 114567, 2022 06.
Article in English | MEDLINE | ID: mdl-35490573

ABSTRACT

This study aimed to identify the factors associated with a delay in treatment-seeking among patients with obsessive-compulsive disorder (OCD), a disabling neuropsychiatric disorder. To achieve this purpose, we conducted a cross-sectional study examining latency to treatment (LTT) and its associated correlates in 863 patients with OCD. We defined LTT as the time lag between the awareness of discomfort and/or impairment caused by symptoms and the beginning of OCD-specific treatment. To determine the socio-demographic and clinical characteristics associated with LTT, we built an interval-censored survival model to simultaneously assess the relationship between all variables, representing the best fit to our data format. The results of our study showed that approximately one-third of OCD patients sought treatment within two years of symptom awareness, one-third between two and nine years, and one-third after ten or more years. Median LTT was 4.0 years (mean = 7.96, SD = 9.54). Longer LTT was associated with older age, early onset of OCD symptoms, presence of contamination/cleaning symptoms and full-time employment. Shorter LTT was associated with the presence of aggression symptoms and comorbidity with hypochondriasis. The results of our study confirm the understanding that LTT in OCD is influenced by several interdependent variables - some of which are modifiable. Strategies for reducing LTT should focus on older patients, who work in a full-time job, and on individuals with early onset of OCD and contamination/cleaning symptoms.


Subject(s)
Obsessive-Compulsive Disorder , Comorbidity , Cross-Sectional Studies , Humans , Hypochondriasis/epidemiology , Obsessive-Compulsive Disorder/diagnosis
10.
Biomolecules ; 12(2)2022 02 10.
Article in English | MEDLINE | ID: mdl-35204789

ABSTRACT

Endophytic plant-growth-promoting microorganisms can protect plants against pathogens, but they have rarely been investigated as potential biocontrol agents and triggers of induced systemic resistance (ISR), regulated by phytohormones, against viruses. We studied the role of endophytic strains Bacillus subtilis 26D and B. subtilis Ttl2, which secrete ribonucleases and phytohormones, in the induction of tomato plant resistance against potato virus X and potato virus Y in a greenhouse condition. The endophytes reduced the accumulation of viruses in plants, increased the activity of plant ribonucleases and recovered the fruit yield of infected tomato plants. Both the 26D and Ttl2 strains induced ISR by activating the transcription of genes related to salicylate- and jasmonate-dependent responses. The 26D and Ttl2 strains increased the content of cytokinins and decreased the level of indolacetic acid in plants infected with PVX or PVY. PVY led to an increase of the abscisic acid (ABA) content in tomato plants, and PVX had the opposite effect. Both strains reduced the ABA content in plants infected with PVY and induced ABA accumulation in plants infected with PVX, which led to an increase in the resistance of plants. This is the first report of the protection of tomato plants against viral diseases by foliar application of endophytes.


Subject(s)
Potexvirus , Potyvirus , Solanum lycopersicum , Bacillus subtilis , Solanum lycopersicum/genetics , Plant Diseases , Potyvirus/physiology , Ribonucleases
11.
Molecules ; 26(6)2021 Mar 20.
Article in English | MEDLINE | ID: mdl-33804712

ABSTRACT

Pathogenic microbes are a major source of health and environmental problems, mostly due to their easy proliferation on most surfaces. Currently, new classes of antimicrobial agents are under development to prevent microbial adhesion and biofilm formation. However, they are mostly from synthetic origin and present several disadvantages. The use of natural biopolymers such as cellulose, hemicellulose, and lignin, derived from lignocellulosic materials as antimicrobial agents has a promising potential. Lignocellulosic materials are one of the most abundant natural materials from renewable sources, and they present attractive characteristics, such as low density and biodegradability, are low-cost, high availability, and environmentally friendly. This review aims to provide new insights into the current usage and potential of lignocellulosic materials (biopolymer and fibers) as antimicrobial materials, highlighting their future application as a novel drug-free antimicrobial polymer.


Subject(s)
Anti-Infective Agents/chemistry , Lignin/chemistry
12.
Adv Healthc Mater ; 10(6): e2001692, 2021 03.
Article in English | MEDLINE | ID: mdl-33448144

ABSTRACT

Lesions involving the osteochondral unit are difficult to treat. Biomimetic scaffolds are previously shown as promising alternative. Such devices often lack multiple functional layers that mimic bone, cartilage, and the interface. In this study, multilayered scaffolds are developed based on the use of natural extracellular matrix (ECM)-like biopolymers. Particular attention is paid to obtain a complex matrix that mimics the native osteochondral transition. Porous, sponge-like chitosan-collagen-octacalcium phosphate (OCP) scaffolds are obtained. Collagen content increases while the amount of OCP particles decreases toward the cartilage layer. The scaffolds are bioactive as a mineral layer is deposited containing hydroxyapatite at the bony side. The scaffolds stimulate proliferation of human adipose-derived mesenchymal stem cells, but the degree of proliferation depends on the cell seeding density. The scaffolds give rise to a zone-specific gene expression. RUNX2, COL1A1, BGLAP, and SPP1 are upregulated in the bony layer of the scaffold. SOX9 is upregulated concomitant with COL2A1 expression in the cartilage zone. Mineralization in presence of the cells is prominent in the bone area with Ca and P steadily increasing over time. These results are encouraging for the fabrication of biomimetic scaffolds using ECM-like materials and featuring gradients that mimic native tissues and their interface.


Subject(s)
Stem Cells , Tissue Scaffolds , Calcium Phosphates , Cell Differentiation , Humans , Porosity , Tissue Engineering
13.
Proc Natl Acad Sci U S A ; 118(2)2021 01 12.
Article in English | MEDLINE | ID: mdl-33419921

ABSTRACT

Terrestrial ecosystems are increasingly enriched with resources such as atmospheric CO2 that limit ecosystem processes. The consequences for ecosystem carbon cycling depend on the feedbacks from other limiting resources and plant community change, which remain poorly understood for soil CO2 efflux, JCO2, a primary carbon flux from the biosphere to the atmosphere. We applied a unique CO2 enrichment gradient (250 to 500 µL L-1) for eight years to grassland plant communities on soils from different landscape positions. We identified the trajectory of JCO2 responses and feedbacks from other resources, plant diversity [effective species richness, exp(H)], and community change (plant species turnover). We found linear increases in JCO2 on an alluvial sandy loam and a lowland clay soil, and an asymptotic increase on an upland silty clay soil. Structural equation modeling identified CO2 as the dominant limitation on JCO2 on the clay soil. In contrast with theory predicting limitation from a single limiting factor, the linear JCO2 response on the sandy loam was reinforced by positive feedbacks from aboveground net primary productivity and exp(H), while the asymptotic JCO2 response on the silty clay arose from a net negative feedback among exp(H), species turnover, and soil water potential. These findings support a multiple resource limitation view of the effects of global change drivers on grassland ecosystem carbon cycling and highlight a crucial role for positive or negative feedbacks between limiting resources and plant community structure. Incorporating these feedbacks will improve models of terrestrial carbon sequestration and ecosystem services.


Subject(s)
Carbon Dioxide/chemistry , Poaceae/chemistry , Soil/chemistry , Atmosphere , Biodiversity , Biomass , Carbon Cycle/physiology , Climate Change , Ecosystem , Feedback , Grassland , Nitrogen/chemistry , Nitrogen/pharmacology , Nitrogen Fixation , Plants , Soil Microbiology , Texas , Water/analysis
14.
J Clin Med ; 10(2)2021 Jan 13.
Article in English | MEDLINE | ID: mdl-33451078

ABSTRACT

Background: Obsessive-compulsive disorder (OCD) is a very heterogeneous condition that frequently includes symptoms of the "symmetry dimension" (i.e., obsessions and/or compulsions of symmetry, ordering, repetition, and counting), along with aggressive, sexual/religious, contamination/cleaning, and hoarding dimensions. Methods: This cross-sectional study aimed to investigate the prevalence, severity, and demographic and clinical correlates of the symmetry dimension among 1001 outpatients from the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders. The main assessment instruments used were the Dimensional Yale-Brown Obsessive-Compulsive Scale, the Yale-Brown Obsessive-Compulsive Scale, the USP-Sensory Phenomena Scale, the Beck Depression and Anxiety Inventories, the Brown Assessment of Beliefs Scale, and the Structured Clinical Interview for DSM-IV Axis I Disorders. Chi-square tests, Fisher's exact tests, Student's t-tests, and Mann-Whitney tests were used in the bivariate analyses to compare patients with and without symptoms of the symmetry dimension. Odds ratios (ORs) with confidence intervals and Cohen's D were also calculated as effect size measures. Finally, a logistic regression was performed to control for confounders. Results: The symmetry dimension was highly prevalent (86.8%) in this large clinical sample and, in the logistic regression, it remained associated with earlier onset of obsessive-compulsive symptoms, insidious onset of compulsions, more severe depressive symptoms, and presence of sensory phenomena. Conclusions: A deeper knowledge about specific OCD dimensions is essential for a better understanding and management of this complex and multifaceted disorder.

15.
J Psychiatr Res ; 130: 187-193, 2020 11.
Article in English | MEDLINE | ID: mdl-32828024

ABSTRACT

BACKGROUND: While stressful life events increase the risk of developing a range of psychiatric disorders, including obsessive-compulsive disorder (OCD), their ability to precipitate specific obsessive-compulsive symptoms' dimensions is unknown. Here we aimed to evaluate the potential role of three different types of stressful life events, herein termed losses (death of a loved one, termination of a romantic relationship and severe illness) in predicting the speed of progression from subclinical to clinical OCD and the severity of specific OCD dimensions in a large multicentre OCD sample. METHODS: Nine hundred and fifty-four OCD outpatients from the Brazilian OCD Research Consortium were included in this study. Several semi-structured and structured instruments were used, including the Structured Clinical Interview for DSM-IV Axis I Disorders, the Yale-Brown Obsessive-Compulsive Scale, the Dimensional Yale-Brown Obsessive-Compulsive Scale, the Brown Assessment of Beliefs Scale, the Beck Depression Inventory, the Beck Anxiety Inventory and the Yale OCD Natural History Questionnaire. Regression models investigated the interaction between types of loss and gender to predict speed of progression from subclinical obsessive-compulsive symptoms to OCD, and the severity of five symptom dimensions. RESULTS: While termination of a relationship was associated with a faster speed of progression from subthreshold to clinical OCD, the death of a loved one was associated with increased severity of hoarding symptoms. There was also an interaction between gender and experiences of death, which predicted a faster speed of progression to OCD in males. CONCLUSIONS: Stressful life events have the ability to accelerate the progression from subclinical to clinical OCD, as well as impact the severity of specific OCD dimensions. Gender also plays a role in both the progression and severity of symptoms. These findings suggest that stressful life events may represent a marker to identify individuals at risk of progressing to clinical OCD.


Subject(s)
Obsessive-Compulsive Disorder , Psychiatric Status Rating Scales , Brazil , Diagnostic and Statistical Manual of Mental Disorders , Female , Humans , Male , Obsessive-Compulsive Disorder/diagnosis , Obsessive-Compulsive Disorder/epidemiology , Severity of Illness Index , Surveys and Questionnaires
16.
J Affect Disord ; 264: 181-186, 2020 03 01.
Article in English | MEDLINE | ID: mdl-32056748

ABSTRACT

BACKGROUND: There is current interest in the elaboration of early intervention programs for obsessive-compulsive disorder (OCD). To this end, it is important to investigate the speed of progression from subthreshold symptoms to diagnosable OCD. In this study, we have retrospectively investigated the speed of progression towards full-blown OCD and sociodemographic and clinical factors associated with a faster transition. METHODS: Patients enrolled in the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders (N = 954) were interviewed with a comprehensive assessment battery that included the interval (in years) between the onset of subthreshold OCD symptoms and the onset of full-blown OCD. RESULTS: It took a median of 7 years (interquartile range: 2-13 years) for subthreshold symptoms to convert to diagnosable OCD. Faster OCD onset was associated with lower age at the time of assessment, male gender, being in new romantic states as precipitants for compulsions, greater severity of sexual/religious symptoms and lower severity of hoarding and YBOCS compulsions severity scores, greater rates of generalized anxiety disorder and agoraphobia without panic disorder, and negative family history for OCD. LIMITATIONS: The retrospective design of this study allowed for susceptibility to memory bias about age at onset of OCD symptoms. We were unable to capture progressions taking less than 12 months. CONCLUSIONS: We could identify a specific phenotype that was more likely to escalate rapidly to clinical levels within this large clinical sample. This phenomenon may be particularly relevant in the context of selecting individuals for early intervention initiatives in situations when resources are scarce.


Subject(s)
Obsessive-Compulsive Disorder , Anxiety Disorders/epidemiology , Brazil , Comorbidity , Compulsive Personality Disorder , Humans , Male , Obsessive-Compulsive Disorder/diagnosis , Obsessive-Compulsive Disorder/epidemiology , Retrospective Studies
17.
Acta Biomater ; 99: 236-246, 2019 11.
Article in English | MEDLINE | ID: mdl-31505301

ABSTRACT

Microbial infections from post-surgery or other medical-related procedure is a serious health problem. Nowadays, the research is focused on the development of new drug-free materials with antibacterial properties to prevent or minimize the risk of infections. Spider silk is known for its unique biomechanical properties allied with biocompatibility. Recombinant DNA technology allows to bioengineering spider silk with antimicrobial peptides (AMP). Thus, our goal was to bioengineered spider silk proteins with AMP (6mer-HNP1) as an antibacterial drug-free coating for commercial silk sutures (Perma-Hand®) for decreasing bacterial infections. Perma-Hand® sutures were coated with 6mer-HNP1 by dip coating. In vitro tests, using human fetal lung fibroblasts (MRC5), showed that coated sutures sustained cell viability, and also, the contact with red blood cells (RBCs) demonstrate blood compatibility. Also, the coatings inhibited significantly the adherence and formation of biofilm, where sutures coated with 6mer-HNP1 produced a 1.5 log reduction of Methicillin-Resistant Staphylococcus aureus (MRSA) and a 2 log reduction of Escherichia coli (E. coli) compared to the uncoated Perma-Hand® suture. The mechanical properties of Perma-Hand® sutures were not affected by the presence of bioengineered spider silk proteins. Thus, the present work demonstrated that using spider silk drug-free coatings it is possible to improve the antibacterial properties of the commercial sutures. Furthermore, a new class of drug-free sutures for reducing post-implantation infections can be developed. STATEMENT OF SIGNIFICANCE: Microbial infections from post-surgery or other medical-related procedure is a serious health problem. Developing new drug-free materials with antibacterial properties is an approach to prevent or minimize the risk of infections. Spider silk is known for its unique biomechanical properties allied with biocompatibility. Recombinant DNA technology allow to bioengineering spider silk with antimicrobial peptides (AMP). Our goal is bioengineered spider silk proteins with AMP as an antibacterial coating for silk sutures. The coatings showed exceptional antibacterial properties and maintained intrinsic mechanical features. In vitro studies showed a positive effect of the coated sutures on the cell behavior. With this new drug-free bioengineered spider silk coating is possible to develop a new class of drug-free sutures for reducing post-implantation infections.


Subject(s)
Anti-Bacterial Agents/chemistry , Bacterial Infections/prevention & control , Coated Materials, Biocompatible/chemistry , Silk/chemistry , Sutures/adverse effects , Animals , Anti-Bacterial Agents/pharmacology , Bacterial Adhesion/drug effects , Biofilms , Biomechanical Phenomena , Coated Materials, Biocompatible/pharmacology , Escherichia coli/drug effects , Humans , Methicillin-Resistant Staphylococcus aureus/drug effects , Silk/pharmacology , Spiders , Surface Properties , Surgical Wound Infection/prevention & control , Tensile Strength , alpha-Defensins/metabolism
18.
J Affect Disord ; 256: 324-330, 2019 09 01.
Article in English | MEDLINE | ID: mdl-31201983

ABSTRACT

BACKGROUND: Patients with obsessive-compulsive disorder (OCD) often present with comorbidities, mainly anxiety and affective disorders, which may influence OCD course, help-seeking and treatment response. Some authors have studied bipolar disorder (BD) comorbidity in patients with OCD, but usually in small samples. The objective was to estimate the lifetime prevalence of BD in a large clinical sample of OCD patients, and to compare demographic and clinical features of patients with and without BD comorbidity. METHOD: This cross-sectional study with 955 adult OCD patients from the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders (C-TOC) used several assessment instruments, including the Yale-Brown Obsessive-Compulsive Scale, the Dimensional Yale-Brown Obsessive-Compulsive Scale, the Beck Depression and Anxiety Inventories, and the Structured Clinical Interview for DSM-IV Axis I Disorders. Descriptive and bivariate analyses were followed by logistic regression. RESULTS: The lifetime prevalence of BD was 7.75% (N = 74). The variables that were independently associated with BD comorbidity were: panic disorder with agoraphobia, impulse control disorders, and suicide attempts. LIMITATIONS: The cross-sectional design does not permit causal inferences; the external validity may be limited, as the participants were from tertiary services. Despite the large sample size, some analyses may have been underpowered due to the relatively low prevalence of the outcome and of some explanatory variables. CONCLUSIONS: Patients with OCD comorbid with BD have some clinical features indicative of greater severity, including higher suicide risk, and require a careful therapeutic approach for the appropriate treatment of both disorders.


Subject(s)
Bipolar Disorder/epidemiology , Bipolar Disorder/psychology , Obsessive-Compulsive Disorder/epidemiology , Obsessive-Compulsive Disorder/psychology , Adult , Agoraphobia/epidemiology , Anxiety/psychology , Anxiety Disorders/epidemiology , Brazil/epidemiology , Comorbidity , Compulsive Personality Disorder , Cross-Sectional Studies , Depression/epidemiology , Diagnostic and Statistical Manual of Mental Disorders , Female , Humans , Logistic Models , Male , Middle Aged , Panic Disorder/epidemiology , Prevalence , Suicide, Attempted , Young Adult
19.
Depress Anxiety ; 36(6): 533-542, 2019 06.
Article in English | MEDLINE | ID: mdl-30990937

ABSTRACT

BACKGROUND: Recent findings suggest an association between attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). Thus, we evaluated the clinical associated features of ADHD in a large sample of adult OCD patients. METHODS: A cross-sectional study including 955 adult patients with OCD from the Brazilian Research Consortium of Obsessive-Compulsive Spectrum Disorders (C-TOC). Clinical characteristics in adult OCD patients with and without comorbid ADHD were compared using Fisher's exact test, t-tests or Mann-Whitney tests. Bivariate analyses were followed by logistic regression analysis to identify clinical characteristics independently associated with ADHD comorbidity. RESULTS: The lifetime prevalence of ADHD in adult OCD patients was 13.7%. The current results indicate that OCD + ADHD patients were more severe, had an earlier onset of the obsessive-compulsive symptoms, a higher history of rheumatic fever, with higher frequencies of sensory phenomena and comorbidity with Tourette syndrome. They also had an increased risk for academic impairment and suicide attempts. CONCLUSION: Adult OCD patients with ADHD present some specific clinical features and may represent a special subgroup of adult OCD. Future studies should focus on the development of interventions more tailored to the phenotype of this subgroup of patients.


Subject(s)
Attention Deficit Disorder with Hyperactivity/epidemiology , Attention Deficit Disorder with Hyperactivity/psychology , Obsessive-Compulsive Disorder/epidemiology , Obsessive-Compulsive Disorder/psychology , Academic Success , Adolescent , Adult , Aged , Aged, 80 and over , Brazil/epidemiology , Comorbidity , Correlation of Data , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Phenotype , Prevalence , Suicide, Attempted/statistics & numerical data , Tourette Syndrome/epidemiology , Young Adult
20.
New Phytol ; 222(1): 183-192, 2019 04.
Article in English | MEDLINE | ID: mdl-30367488

ABSTRACT

Atmospheric CO2 enrichment usually increases the aboveground net primary productivity (ANPP) of grassland vegetation, but the magnitude of the ANPP-CO2 response differs among ecosystems. Soil properties affect ANPP via multiple mechanisms and vary over topographic to geographic gradients, but have received little attention as potential modifiers of the ANPP-CO2 response. We assessed the effects of three soil types, sandy loam, silty clay and clay, on the ANPP response of perennial C3 /C4 grassland communities to a subambient to elevated CO2 gradient over 10 yr in Texas, USA. We predicted an interactive, rather than additive, effect of CO2 and soil type on ANPP. Contrary to prediction, CO2 and soil additively influenced grassland ANPP. Increasing CO2 by 250 µl l-1 increased ANPP by 170 g m-2 across soil types. Increased clay content from 10% to 50% among soils reduced ANPP by 50 g m-2 . CO2 enrichment increased ANPP via a predominant direct effect, accompanied by a smaller indirect effect mediated by a successional shift to increased dominance of the C4 tallgrass Sorghastrum nutans. Our results indicate a large, positive influence of CO2 enrichment on grassland productivity that resulted from the direct physiological benefits of CO2 augmented by species succession, and was expressed similarly across soils of differing physical properties.


Subject(s)
Carbon Dioxide/metabolism , Grassland , Soil/chemistry , Carbon Dioxide/pharmacology , Models, Biological , Poaceae/drug effects , Poaceae/physiology , Time Factors , Water
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