Search

Purpose: Magnetic resonance imaging (MRI) is useful for interpreting temporomandibular joint (TMJ) disorders including disc displacement. This study aimed to evaluate the relationship between TMJ sounds and disc displacement with and without reduction by clinical examination and MRI. Methods: A sample of 58 patients was clinically examined when after being referred to MRI due to signs and symptoms of unilateral or bilateral TMJ disc displacement. The diagnosis obtained using MRI was compared with the clinical findings for the presence or absence of articular sounds. Results: Most patients (n=39; 67%) had joint sounds manifested as clicking; the other 19 patients (33%) did not present sounds. Among the 39 patients with sounds, bilateral clicking was observed in 29 (74%), and unilateral clicking in 10 (26%) patients. Unilateral clicking was equally observed on the right and left sides, each occurring in 5 five patients (13%). Conclusion: The results suggest that articular sounds do not occur exclusively in TMJ with disc displacement with reduction. The presence or absence of joint sounds will not suffice as the only aspect criterion to be considered in the differential diagnosis of disc displacement with and without reduction. [ABSTRACT FROM AUTHOR]

Background Aims: Adequate re-establishment of thymopoiesis is critical for long-term immune reconstitution after hematopoietic cell transplantation (HCT), potentially impacting patient survival rates. This study aimed to evaluate immune reconstitution in pediatric HCT recipients by quantifying recent thymic emigrants (RTEs), specifically CD3 + CD31 + CD45RA + cells., Methods: We conducted a retrospective analysis of 186 pediatric patients transplanted between 2013 and 2020, undergoing their first allogeneic HCT, who were alive in the first 100 days after transplantation with immune recovery evaluation at three time points: day 100, day 180 and day 360 after HCT. We analyzed the distribution of peripheral blood subsets of T, B and natural killer lymphocytes and assessed the impact of underlying disease, HCT type, stem cell source, recipient age, conditioning regimen, graft-versus-host disease (GVHD) occurrence and cytomegalovirus (CMV) reactivation on immune recovery., Results: At day 100, patients under 10 years exhibited higher RTE CD4 + and CD8 + CD31 + CD45RA + counts compared with older patients (5.3 versus 2.2 cells/µL, P = 0.022 and 48 versus 72.8 cells/µL, P = 0.049, respectively). Patients with haploidentical HCT had lower RTE CD4 + counts compared with those with unrelated or related donors (2.4 versus 4.4 versus 7.9 cells/µL, P = 0.024). Administration of rabbit anti-thymocyte globulin negatively impacted RTE CD4 + production (median, 6.5 versus 2.4 cells/µL, P = 0.007). At day 180, the presence of GVHD had a negative influence on RTE production (11.7 versus 56.8 cells/µL, P < 0.001), particularly higher-grade acute GVHD (without, 56.8 cells/µL, grade 1-2, 28.1 cells/µL, grade 3-4, 6.0 cells/µL, P < 0.001). Patients with CMV reactivation had higher CD8 + CD31 + CD45RA + compared with those without reactivation (median, 204.6 versus 100.2 cells/µL, P = 0.022). At day 360, no variables significantly affected RTE recovery. Overall survival at 5-year follow-up was 87.7%, with a median of 1170 days (range, 122-3316). Multivariate analysis showed that age >10 years (P = 0.038), negative CMV donor serology (P = 0.0029) and acute GVHD (P = 0.0026) had a negative impact on survival., Conclusions: This study highlights variations in RTE production based on patient age, donor type and immunosuppression regimen employed., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the quality of life in patients diagnosed as having tuberculous uveitis and its association with sociodemographic, clinical, and psychosocial aspects., Method: By conducting standardized interviews, clinical and demographic data were collected using a measure developed in this study. This measure was applied in addition to other measures, namely SF-12, Hospital Anxiety and Depression Scale, and NEI-VFQ-39, which were used to assess health-related quality of life, anxiety and depression symptoms, and visual functioning., Results: The study included 34 patients [mean age: 46.5 ± 15.1 years, female patients: 21 (61.8%)]. The mean of the VFQ-39 score was 74.5 ± 16.6 and that of SF-12 physical and mental component scores were 45.8 ± 10.1 and 51.6 ± 7.5, respectively, for the health-related quality of life. Anxiety symptoms were the most prevalent compared with depression symptoms and were found in 35.3% of the participants., Conclusion: Tuberculous uveitis affects several scales of quality of life, thereby affecting a population economically active with a social, psychological, and economic burden.

Background: In the squat movement, the use of constant resistance (CR) generates greater compression and shear forces close to 90° of knee flexion, increasing joint overload. However, when used variable resistance (VR) there is no consensus about the effect of knee joint load. The aim of this study was to compare knee torques using constant or variable resistance during the squat exercise., Methods: Twenty-one healthy male subjects (mean age, 24 [SD, 3] years; height, 1.76 [SD, 0.04] m), who practice squats during strength training routine. Were simultaneously record data from the platform force and tridimensional kinematic to obtain torques around knee. 15 repetitions were performed up to maximum knee flexion with the use of variable (RV) or constant (CR) resistance in a single session., Results: Significant differences regarding the angles only in the sagittal plane at the end of the ascending phase of the squat, with less knee extension in the VR condition. In the sagittal and frontal planes, lower values of extensor and abductor torque were found in the VR condition at the angles of greater knee flexion., Conclusion: The use of variable resistance compared to constant resistance seems to be an alternative to be considered when the objective is to minimize the internal loads on the knee joint in exercises such as the squat in amplitudes of greater flexion. This study indicated that VR helps subjects who are learning the squat movement, enabling the application of this knowledge in physical therapy or physical training clinics., Competing Interests: Declaration of competing interest There are no known conflicts of interest associated with this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Frontline healthcare workers providing care for COVID-19 are more likely to get infected and die compared with other professionals. Deaths or sick leaves due to COVID-19 can affect the smooth operation of health services in areas with shortage of workers., Objectives: To analyze factors associated with the death of healthcare workers due to COVID-19 in the state of Amapá, Brazil., Methods: Analytical cross-sectional study using COVID-19 data from Amapá between March 2020 and January 2021. The association of independent variables (sex, race/color, age group, region of residence, comorbidity) with death was analyzed by logistic regression., Results: Data from 1,258 workers were analyzed. The majority were women (67.7%; 852/1,258), multiracial (66.9%; 759/1,135), aged between 18 and 64 (98.3%; 1,226/1,247), with no comorbidity (86.6%; 1,090/1,258), from the Macapá metropolitan area (56.7%; 713/1,258). The mortality rate was 1.59%. Factors associated with death were: age group = 65 years (odds ratio = 10.43; 95% confidence interval [CI] = 2.78-39.11), comorbidity (odds ratio = 4.52; 95%CI = 1.74-11.74), and residence in the Macapá metropolitan area (odds ratio = 4.37; 95%CI = 1.25-15.29)., Conclusions: The recognition of factors that may have caused the death of healthcare workers in Amapá can support the recommendation of protective measures for the most susceptible, such as switching to activities with lower exposure to the virus or teleworking., Competing Interests: Conflicts of interest: None

Introduction: The state of Amapá is located in Brazil's Legal Amazon and comprises 16 municipalities. Its history is marked by social vulnerability and industrial mining; therefore, its current socioeconomic and occupational context should be analyzed considering possible sociohistorical and geographic influences., Objectives: To analyze and/or describe the epidemiological profile of workers, occupational accidents, the socioeconomic context, and time evolution of the number of workers in the state and their relationship with the state's gross domestic product., Methods: This is an analytic time series study based on official public data. We used a simple regression test to analyze the relationship between the number of workers and gross domestic product and to assess the time trend of the number of workers. The studied period was from 2007 to 2017., Results: The number of workers presented an increasing trend over time (R 2 = 0.902; p < 0.001), with a relative increase of 49.8% between 2007 and 2017. We observed a positive relationship between the annual increase in the number of workers and the state's gross domestic product (R 2 = 0.899; p < 0.001). The economic activity with the highest mean number of workers was public administration, defense, and social security. The highest socioeconomic indicators were observed in the state capital Macapá. Non-hazardous waste management was the activity concentrating the highest absolute number of occupational accidents., Conclusions: This study highlighted important socioeconomic contrasts within the state. The significant increases in the gross domestic product and number of workers are signs of development, but the high number of occupational accidents represents a serious public health problem., Competing Interests: Conflicts of interest: None

Objective: Nanotechnology has progressed significantly and particles as small as 3 nm are being employed in resin-based restorative materials to improve clinical performance. The goal of this review is to report the progress of nanotechnology in Restorative Dentistry by reviewing the advantages, limitations, and applications of resin-based restorative materials with nanoparticles., Materials and Methods: A literature review was conducted using PubMed/Medline, Scopus and Embase databases. In vitro, in vivo and in situ research studies published in English between 1999 and 2020, and which focused on the analysis of resin-based restorative materials containing nanoparticles were included., Results: A total of 140 studies were included in this review. Studies reported the effect of incorporating different types of nanoparticles on adhesive systems or resin composites. Mechanical, physical, and anti-bacterial properties were described. The clinical performance of resin-based restorative materials with nanoparticles was also reported., Conclusions: The high surface area of nanoparticles exponentially increases the bioactivity of materials using bioactive nanofillers. However, the tendency of nanoparticles to agglomerate, the chemical instability of the developed materials and the decline of rheological properties when high ratios of nanoparticles are employed are some of the obstacles to overcome in the near future., Clinical Significance: In spite of the recent advancements of nanotechnology in resin-based restorative materials, some challenges need to be overcome before new nano-based restorative materials are considered permanent solutions to clinical problems., (© 2020 Wiley Periodicals LLC.)

Leptospirosis is a global disease that affects humans and animals, impacting public health and the economy. The symptoms caused by Leptospira infection can vary from mild to severe, affecting liver, lungs, and kidneys. The host-pathogen interaction in leptospirosis is still poorly understood, but there is evidence for the role of the host immune response in the pathogenesis. Chemokines are a family of structurally-related low-molecular-mass proteins (8-14 kDa) that signal the recruitment of leukocytes. In this study the profile of 22 chemokines were evaluated in liver and kidney of three mice strains with different phenotypes of susceptibility to leptospirosis. We extended our previously reported observations showing that expression of chemokines with homeostatic function, activation and chemotaxis of leukocytes are essential to modulate and to induce resistance to leptospirosis. Our findings support that an early induction of CXC chemokines in resistant BALB/c mice can be associated with the control of the infection. The correlation of chemokine expression between liver and kidney observed in BALB/c suggests that a balance of chemokine induction in the organs may contribute to resistance to leptospirosis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective  The present study verified, through a systematic review with meta-analysis, the effects of a rehabilitation, physical training program for the treatment of pain and muscle strength in knee osteoarthritis (OA). Methods  We analyzed studies published between 2008 and 2018 referenced at the Medline (National Library of Medicine) database, selecting 7 randomized controlled clinical trials about exercise programs to improve pain and muscle strength in patients with knee OA with Physiotherapy Evidence Database (PeDro) score higher than 8. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) systematization was used to prepare this review, and a meta-analysis was carried out to obtain mathematical evidence the outcomes of physical exercise on pain. Results  The studies included in the analysis contained a total of 934 participants aged 40 to 73 years-old, with 34.90% males. Most of the exercise sets offered in OA treatment had a significantly positive outcome result in both criteria, but mainly for pain relief (statistically significant difference, p  < 0.003). Conclusion  We infer that there was an improvement of pain in all articles that performed muscle strengthening, but there is still an obstacle to the protocols used., Competing Interests: Conflicts of Interest The authors declare that there is no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Zika virus (ZIKV) has caused an explosive epidemic linked to severe clinical outcomes in the Americas. As of June 2018, 4,929 ZIKV suspected infections and 46 congenital syndrome cases had been reported in Manaus, Amazonas, Brazil. Although Manaus is a key demographic hub in the Amazon region, little is known about the ZIKV epidemic there, in terms of both transmission and viral genetic diversity. Using portable virus genome sequencing, we generated 59 ZIKV genomes in Manaus. Phylogenetic analyses indicated multiple introductions of ZIKV from northeastern Brazil to Manaus. Spatial genomic analysis of virus movement among six areas in Manaus suggested that populous northern neighborhoods acted as sources of virus transmission to other neighborhoods. Our study revealed how the ZIKV epidemic was ignited and maintained within the largest urban metropolis in the Amazon. These results might contribute to improving the public health response to outbreaks in Brazil., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Reflecting on the role of the nursing staff in civil construction has paramount importance, because it enables improving knowledge and making discoveries. Such reflection is further useful for managers and workers to jointly develop disease prevention and health promotion strategies. The aim of the present study is to describe a nurse's contributions to a civil construction company. It consists of an experience report according to Callista Roy's adaptation theory. The analyzed experience took place from August 2017 through March 2018. We describe the activities carried out by the nurse jointly with other healthcare workers. We believe that the present study evidences the significance of occupational health nursing actions, particularly within civil construction, as well as the relevance of providing theoretical scientific grounds to such actions to contribute to make working environments healthier for all the involved actors without neglecting the aspect of productivity.

Leptospirosis is globally widespread neglected disease, affecting most mammalian species. Clinical signs can be confused with other diseases which make the diagnosis and treatment difficult. Chemokines and cytokines are known for their role in the inflammatory and immune response to infections. The profile determination of chemokines' expressions in the course of infection may elucidate the defense mechanisms of the host and support the search for effective treatment strategies. We investigated the mechanisms of innate immunity through the comparison of chemokines induced during infection with L. interrogans in mice with different levels of susceptibility. We used lung and spleen tissues samples of mice from C3H/HeJ, C3H/HePas and Balb/c, respectively sensitive, intermediate susceptibility and resistant to the pathogen. The inoculation of L. interrogans in C3H/HeJ mice led a comparatively smaller change in chemokines expression in both spleen and lung tissues. In samples from spleens and lungs of C3H/HePas and Balb/c the higher increases occurred on CXCL9, CXCL16, CXCL5, CCL8 and CCL5 in Balb/c. Given the same genetic background, the differences in the responses of C3H/HePas compared to C3H/HeJ mice strongly suggest the role of chemokines for the survival of parental strain. Therefore, the greatest increase in CXC chemokines appears to be efficient to induce migration of cells to the secondary lymphoid organs and affected tissues, which is important to control infection. Overall, CXC chemokines are important for the activation and attraction of T cell and may influence the course and control of the infection in resistant Balb/c mice., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Objective: Attention deficit hyperactivity disorder (ADHD) is characterized by a persistent pattern of inattention or hyperactivity. This study aimed to investigate the relationship between ADHD and drug dependence., Methods: The presence and severity of ADHD and substance use were evaluated through questionnaires in 80 adult patients in therapeutic communities., Results: No difference in drug use or dependence prevalence between ADHD and non-ADHD patients was found. However, ADHD patients had lower ages on admission (p = 0.004) and at first contact with cocaine (p = 0.033). In ADHD patients, there was a negative correlation between the age at first use of cannabis and the subsequent severity of cannabis use (p = 0.017) and cocaine use (p = 0.033)., Conclusions: Though there was no difference in prevalence of drug use among groups, results show that ADHD in patients in therapeutic communities may cause different addiction patterns, such as earlier use of cocaine and admission, and a more severe use of cocaine correlated to earlier contact with cannabis.

Objective: to assess in-hospital care for patients with Acute Coronary Syndrome according to quality indicators., Method: a longitudinal quantitative study was performed between November 2012 and March 2013 with 94 patients, including interviews and medical records., Results: a total of 39.4% of patients had unstable angina and 60.6% had myocardial infarction, of which 34% had ST segment elevation. Patients with TIMI and GRACE scores higher than four and 140 (p<0.05) respectively died. Admission to the intensive care unit totaled 2.1%; assessment of left ventricular (LV) ejection fraction, 83.0%; ASA within 24 hours of admission, 77.8%; statins, 72.7%; angiotensin-converting enzyme inhibitor, 62.8%; anti-smoking counseling, 53.3%; and timely reperfusion, 62.5%. Of all participants, 12.0% underwent an invasive strategy in 24h and 50.0% in 72h. Door-to-ECG time was 68.3±104.3 min and door-to-balloon time, 122±54.5 min., Conclusions: health care protocols are required to standardize practice and improve these indicators.

Objective: to assess quality indicators related to the pre-hospital time for patients with acute coronary syndrome., Method: collection took place at a tertiary hospital in Paraná between 2012 and 2013, through interviews and a medical record review. 94 patients participated, 52.1% male, 78.7% who were over 50 years old, 46.9% studied until the fourth grade, 60.6% were diagnosed with acute myocardial infarction., Results: the outcomes were the time between the onset of symptoms and the decision to seek help with an average of 1022 min±343.13, door-to-door 805 min±181.78; and reperfusion, 455 min±364.8. The choice to seek out care within 60 min occurred in patients who were having a heart attack, and longer than 60 min in those with a history of heart attack or prior catheterization., Conclusion: We concluded that the pre-hospital indicators studied interfered with the quality of care.

l-Arginine is an essential amino acid in Leishmania (Leishmania) amazonensis metabolism. A key enzyme for parasite l-arginine metabolism is arginase (ARG) that uses arginine to produce urea and ornithine, a precursor of polyamine pathway guaranteeing parasite replication in both insect and mammal hosts. There is an alternative pathway to produce ornithine via l-proline and glutamate, but this mechanism is not described in Leishmania. In the mammal host, two enzymes can use l-arginine as substrate, the host ARG and the induced nitric oxide synthase that produces nitric oxide. The competition between induced nitric oxide synthase and both parasite and host ARG can favor the success of the infection or its control. Here, we established the metabolomics profile of the polyamine pathway of wild type (WT) L. (L.) amazonensis, submitted or not to l-arginine starvation, and compared to the ARG-knockout mutant (arg - ). Our results indicated that arginine starvation induces a decrease in arginine, ornithine, and putrescine, but we could not detect the significative level changes of spermidine, spermine, or agmatine. However, the absence of ARG on the arg - induced an increase of arginine and citrulline levels, but decreased the levels of ornithine and putrescine. Similarly to the WT arginine-starved parasites, the arg - parasites presented lower levels of proline when compared to the WT ones. This could be indicative of an alternative pathway to surpass the enzyme or its substrate absence., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

There is a rising resistance against antimony drugs, the gold-standard for treatment until some years ago. That is a serious problem due to the paucity of drugs in current clinical use. In a research to reveal how these drugs affect the parasite during treatment and to unravel the underlying basis for their resistance, we have employed metabolomics to study treatment in Leishmania infantum promastigotes. This was accomplished first through the untargeted analysis of metabolic snapshots of treated and untreated parasites both resistant and responders, utilizing a multiplatform approach to give the widest as possible coverage of the metabolome, and additionally through novel monitoring of the origin of the detected alterations through a 13C traceability experiment. Our data stress a multi-target metabolic alteration with treatment, affecting in particular the cell redox system that is essential to cope with detoxification and biosynthetic processes. Additionally, relevant changes were noted in amino acid metabolism. Our results are in agreement with other authors studying other Leishmania species.

Factor VIII (FVIII) is a glycoprotein that plays an essential role in blood coagulation cascade. Purification of plasma-derived coagulation FVIII by direct application of plasma to a chromatographic column is a method of choice. Anion exchange column is a very powerful method because FVIII is strongly adsorbed, resulting in good activity recovery and high purification factor. However, vitamin-K-dependent coagulation factors coelute with FVIII. In the present study, we report the separation of vitamin-K-dependent coagulation proteins from FVIII using immobilized metal affinity chromatography (IMAC) with Cu(2+) as the metal ligand. Plasma was directly loaded to a Q Sepharose Big Beads column, and FVIII was recovered with 65% activity and a purification factor of approximately 50 times. Then, the Q Sepharose eluate was applied to the IMAC-Cu(2+) column, and FVIII was eluted with 200 mM imidazole, with up to 85% recovery of activity. The mass recovery in this fraction was less than 10% of the applied mass of protein. Vitamin-K-dependent proteins elute with imidazole concentrations of lower than 60 mM. Because of the difference in affinity, FVIII could be completely separated from the vitamin-K-dependent proteins in the IMAC column., (© 2014 International Union of Biochemistry and Molecular Biology, Inc.)

Genetically attenuated microorganisms, pathogens, and some commensal bacteria can be engineered to deliver recombinant heterologous antigens to stimulate the host immune system, while still offering good levels of safety. A key feature of these live vectors is their capacity to stimulate mucosal as well as humoral and/or cellular systemic immunity. This enables the use of different forms of vaccination to prevent pathogen colonization of mucosal tissues, the front door for many infectious agents. Furthermore, delivery of DNA vaccines and immune system stimulatory molecules, such as cytokines, can be achieved using these special carriers, whose adjuvant properties and, sometimes, invasive capacities enhance the immune response. More recently, the unique features and versatility of these vectors have also been exploited to develop anti-cancer vaccines, where tumor-associated antigens, cytokines, and DNA or RNA molecules are delivered. Different strategies and genetic tools are constantly being developed, increasing the antigenic potential of agents delivered by these systems, opening fresh perspectives for the deployment of vehicles for new purposes. Here we summarize the main characteristics of the different types of live bacterial vectors and discuss new applications of these delivery systems in the field of vaccinology.

Background. Orthostatic hypotension (OH) is an important nonmotor manifestation of Parkinson's disease (PD). Changes in cerebrovascular reactivity may contribute to this manifestation and can be monitored using transcranial Doppler. Objective. To identify possible changes in cerebrovascular reactivity in patients with OH. Methods. Twenty-two individuals were selected and divided into three groups: with and without OH and controls. Transcranial Doppler was used to assess basal mean blood flow velocity, postapnea mean blood flow velocity, percentage increase in mean blood flow velocity, and cerebrovascular reactivity as measured by the breath-holding index. Results. PD patients had lower values of basal velocity (p = 0.019), postapnea velocity (p = 0.0015), percentage increase in velocity (p = 0.039), and breath-holding index (p = 0.04) than the controls. Patients with OH had higher values of basal velocity (p = 0.09) and postapnea velocity (p = 0.19) but lower values of percentage increase in velocity (p = 0.22) and breath-holding index (p = 0.32) than patients without OH. Conclusions. PD patients present with abnormalities in a compensatory mechanism that regulates cerebral blood flow. OH could be an indicator of these abnormalities.

The Schistosoma mansoni transcriptome revealed new members of the dynein light chain family (DLC/LC8). The antigenicity and immunogenicity of these proteins, and their potential as vaccine candidates were investigated. Two DLC genes (DLC12&#95;JI392413.1 and DLC13&#95;JI387686.1) were cloned and the recombinant proteins produced in E. coli. The immunization of mice with the rDLCs, using alhydrogel as adjuvant, resulted in high titers of antibodies, indicated that these proteins are highly immunogenic. The anti-DLCs antibodies presented cross reactivity with both recombinant antigens and also recognized proteins from S. mansoni adult worm extracts. The DLC12 and DLC13 immunized animals were challenged by infection with cercariae and a protective profile was observed in three different assays, with a significant decreased in worm burden, of 43% and 51% respectively, when compared to the non-vaccinated group. The granulomas formation due to egg retention in the hepatic tissues was evaluated 45 days after infection. Smaller granulomas were observed in the liver of DLC immunized animals, up to 70% reduction in comparison to the granulomas size in the non-vaccinated animals. Fifty-five days after infection, the average size of the hepatic granulomas was still 25-35% smaller in the DLCs vaccinated groups. The interference of DLC immunization on the hepatic granuloma formation may reflect the lower worm burden and consequent decrease on the number of eggs retained in the liver, resulting in lower pro-inflammatory level in the tissue. The protective effect of DLCs immunization, decreasing the worm burden and delaying the rate of granuloma formation, suggests that these antigens should be further studied as potential vaccine candidates., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The paper describes the construction of a questionnaire to assess the quality of care of a Rapid Response Team at the University Hospital of Londrina, based on the conceptual model of Donabedian (structure-process-outcome). Data collection occurred in March 2012 and the process of adjusting the questionnaire was developed with the application of the Delphi technique involving 15 experts. At the end of the study the questionnaire contained 37 statements, achieving final compliance level higher than 80% in all concepts. It is hoped that the contributions of the expert group produce a more reliable questionnaire to be applied in other similar services. Future applications of this instrument may provide information to better assess the quality of teams of Rapid Response services.

Background: Articular cartilage, because of its avascular nature, has little capacity for spontaneous healing, and tissue engineering approaches, employing different biomaterials and cells, are under development. Among the investigated biomaterials are the chitosan-based hydrogels. Although thoroughly studied in other mammalian species, studies are scarce in equines. So, the aim of the present study was to investigate the biocompatibility of chitosan-GP in horse joints submitted to high mechanical loads., Results: An osteochondral defect was created by arthroscopy in the medial surface of lateral trochlea of talus of left or right leg, randomly selected, from six healthy geldings. The defect was filled up with chitosan-GP. The contralateral joint received an identical defect with no implant. The chondral fragment removed to produce the defect was collected, processed and used as the "Initial" sample (normal cartilage) for histology, immunohistochemistry, and metabolic labelling of PGs. After 180 days, the repair tissues were collected, and also analyzed. At the end of the experiment (180 days after lesion), the total number of cells per field in repair tissues was equal to control, and macrophages and polymorphonuclear cells were not detected, suggesting that no significant inflammation was present. These cells were able to synthesize type II collagen and proteoglycans (PGs). Nevertheless, the cell population in these tissues, both in presence of chitosan-GP and in untreated controls, were heterogeneous, with a lower proportion of type II collagen-positives cells and some with a fibroblastic aspect. Moreover, the PGs synthesized in repair tissues formed in presence or absence of chitosan-GP were similar to those of normal cartilage. However, the chitosan-GP treated tissue had an disorganized appearance, and blood vessels were present., Conclusions: Implanted chitosan-GP did not evoke an important inflammatory reaction, and permitted cell growth. These cells were able to synthesize type II collagen and PGs similar to those synthesized in normal cartilage and in healing tissue without implant, indicating its chondrocyte nature.

Synaptic transmission is an essential process for neuron physiology. Such process is enabled in part due to modulation of neurotransmitter release. Adenosine is a synaptic modulator of neurotransmitter release in the Central Nervous System, including neurons of medulla oblongata, where several nuclei are involved with neurovegetative reflexes. Adenosine modulates different neurotransmitter systems in medulla oblongata, specially glutamate and noradrenaline in the nucleus tractussolitarii, which are involved in hypotensive responses. However, the intracellular mechanisms involved in this modulation remain unknown. The adenosine A2a receptor modulates neurotransmitter release by activating two cAMP protein effectors, the protein kinase A and the exchange protein activated by cAMP. Therefore, an in vitro approach (cultured cells) was carried out to evaluate modulation of neurotransmission by adenosine A2a receptor and the signaling intracellular pathway involved. Results show that the adenosine A2a receptor agonist, CGS 21680, increases neurotransmitter release, in particular, glutamate and noradrenaline and such response is mediated by protein kinase A activation, which in turn increased synapsin I phosphorylation. This suggests a mechanism of A2aR modulation of neurotransmitter release in cultured cells from medulla oblongata of Wistar rats and suggest that protein kinase A mediates this modulation of neurotransmitter release via synapsin I phosphorylation., (Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

The prokaryotic ubiquitous Toxin-Antitoxin (TA) operons encode a stable toxin and an unstable antitoxin. The most accepted hypothesis of the physiological function of the TA system is the reversible cessation of cellular growth under stress conditions. The major TA family, VapBC is present in the spirochaete Leptospira interrogans. VapBC modules are classified based on the presence of a predicted ribonucleasic PIN domain in the VapC toxin. The expression of the leptospiral VapC in E. coli promotes a strong bacterial growth arrestment, making it difficult to express the recombinant protein. Nevertheless, we showed that long term induction of expression in E. coli enabled the recovery of VapC in inclusion bodies. The recombinant protein was successfully refolded by high hydrostatic pressure, providing a new method to obtain the toxin in a soluble and active form. The structural integrity of the recombinant VapB and VapC proteins was assessed by circular dichroism spectroscopy. Physical interaction between the VapC toxin and the VapB antitoxin was demonstrated in vivo and in vitro by pull down and ligand affinity blotting assays, respectively, thereby indicating the ultimate mechanism by which the activity of the toxin is regulated in bacteria. The predicted model of the leptospiral VapC structure closely matches the Shigella's VapC X-ray structure. In agreement, the ribonuclease activity of the leptospiral VapC was similar to the activity described for Shigella's VapC, as demonstrated by the cleavage of tRNAfMet and by the absence of unspecific activity towards E. coli rRNA. This finding suggests that the cleavage of the initiator transfer RNA may represent a common mechanism to a larger group of bacteria and potentially configures a mechanism of post-transcriptional regulation leading to the inhibition of global translation.

Miltefosine (MT) (hexadecylphosphocholine) was implemented to cope with resistance against antimonials, the classical treatment in Leishmaniasis. Given the scarcity of anti- Leishmania (L) drugs and the increasing appearance of resistance, there is an obvious need for understanding the mechanism of action and development of such resistance. Metabolomics is an increasingly popular tool in the life sciences due to it being a relatively fast and accurate technique that can be applied either with a particular focus or in a global manner to reveal new knowledge about biological systems. Three analytical platforms, gas chromatography (GC), liquid chromatography (LC) and capillary electrophoresis (CE) have been coupled to mass spectrometry (MS) to obtain a broad picture of metabolic changes in the parasite. Impairment of the polyamine metabolism from arginine (Arg) to trypanothione in susceptible parasites treated with MT was in some way expected, considering the reactive oxygen species (ROS) production described for MT. Importantly, in resistant parasites an increase in the levels of amino acids was the most outstanding feature, probably related to the adaptation of the resistant strain for its survival inside the parasitophorous vacuole.

Schistosomiasis is an important parasitic disease, with about 240 million people infected worldwide. Humans and animals can be infected, imposing an enormous social and economic burden. The only drug available for chemotherapy, praziquantel, does not control reinfections, and an efficient vaccine for prophylaxis is still missing. However, the tegumental protein Sm29 of Schistosoma mansoni was shown to be a promising antigen to compose an anti-schistosomiasis vaccine. Though, recombinant Sm29 is expressed in Escherichia coli as insoluble inclusion bodies requiring an efficient process of refolding, thus, hampering its production in large scale. We present in this work studies to refold the recombinant Sm29 using high hydrostatic pressure, a mild condition to dissociate aggregated proteins, leading to refolding on a soluble conformation. Our studies resulted in high yield of rSm29 (73%) as a stably soluble and structured protein. The refolded antigen presented protective effect against S. mansoni development in immunized mice. We concluded that the refolding process by application of high hydrostatic pressure succeeded, and the procedure can be scaled-up, allowing industrial production of Sm29., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Metabolomics has become an invaluable tool to unveil biology of pathogens, with immediate application to chemotherapy. It is currently accepted that there is not one single technique capable of obtaining the whole metabolic fingerprint of a biological system either due to their different physical-chemical properties or concentrations. In this work, we have explored the capability of capillary electrophoresis mass spectrometry with a sheathless interface with electrospray ionization (CE-ESI-TOF-MS) to separate metabolites in order to be used as a complementary technique to LC. As proof of concept, we have compared the metabolome of Leishmania infantum promastigotes BCN 150 (Sb (III) IC(50) = 20.9 μM) and its variation when treated with 120 μM of Sb(III) potassium tartrate for 12 h, as well as with its Sb(III) resistant counterpart obtained by growth of the parasites under increasing Sb(III) in a step-wise manner up to 180 μM. The number of metabolites compared were of 264 for BCN150 Sb(III) treated versus nontreated and of 195 for Sb(III) resistant versus susceptible parasites. After successive data filtering, differences in seven metabolites identified in databases for Leishmania pathways, showed the highest significant differences, corresponding mainly to amino acids or their metabolite surrogates. Most of them were assigned to sulfur containing amino acids and polyamine biosynthetic pathways, of special relevance considering the deterioration of the thiol-dependent redox metabolism in Leishmania by Sb(III). Given the low concentrations typical for most of these metabolites, the assay can be considered a success that should be explored for new biological questions., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The role of innate immune response in protection against leptospirosis is poorly understood. We examined the expression of the chemokine CXCL2/MIP-2 and the cytokine TNF-α in experimental resistant and susceptible mice models, C3H/HeJ, C3H/HePas and BALB/c strains, using a virulent strain of Leptospira interrogans serovar Copenhageni. Animals were infected intraperitoneally with 10(7) cells and the development of the disease was followed. Mortality of C3H/HeJ mice was observed whereas C3H/HePas presented jaundice and BALB/c mice remained asymptomatic. The infection was confirmed by the presence of leptospiral DNA in the organs of the animals, demonstrated by PCR. Sections of the organs were analyzed, after H&E stain. The relative expression of mRNA of chemokine CXCL2/MIP-2 and cytokine TNF-α was measured in lung, kidney and liver of the mice by qPCR. The concentrations of these proteins were measured in extracts of tissues and in serum of the animals, by ELISA. Increasing levels of transcripts and protein CXCL2/MIP-2 were detected since the first day of infection. The highest expression was observed at third day of infection in kidney, liver and lung of BALB/c mice. In C3H/HeJ the expression of CXCL2/MIP-2 was delayed, showing highest protein concentration in lung and kidney at the 5th day. Increasing in TNF-α transcripts were detected after infection, in kidney and liver of animals from the three mice strains. The expression of TNF-α protein in C3H/HeJ was also delayed, being detected in kidney and lung. Our data demonstrated that Leptospira infection stimulates early expression of CXCL2/MIP-2 and TNF-α in the resistant strain of mice. Histological analysis suggests that the expression of those molecules may be related to the influx of distinct immune cells and plays a role in the naturally acquired protective immunity., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Leishmania (L.) amazonensis uses arginine to synthesize polyamines to support its growth and survival. Here we describe the presence of two gene copies, arranged in tandem, that code for the arginine transporter. Both copies show similar Open Reading Frames (ORFs), which are 93% similar to the L. (L.) donovani AAP3 gene, but their 5' and 3' UTR's have distinct regions. According to quantitative RT-PCR, the 5.1 AAP3 mRNA amount was increased more than 3 times that of the 4.7 AAP3 mRNA along the promastigote growth curve. Nutrient deprivation for 4 hours and then supplemented or not with arginine (400 µM) resulted in similar 4.7 AAP3 mRNA copy-numbers compared to the starved and control parasites. Conversely, the 5.1 AAP3 mRNA copy-numbers increased in the starved parasites but not in ones supplemented with arginine (p<0.05). These results correlate with increases in amino acid uptake. Both Meta1 and arginase mRNAs remained constant with or without supplementation. The same starvation experiment was performed using a L. (L.) amazonensis null knockout for arginase (arg(-)) and two other mutants containing the arginase ORF with (arg(-)/ARG) or without the glycosomal addressing signal (arg(-)/argΔSKL). The arg(-) and the arg(-)/argΔSKL mutants did not show the same behavior as the wild-type (WT) parasite or the arg(-)/ARG mutant. This can be an indicative that the internal pool of arginine is also important for controlling transporter expression and function. By inhibiting mRNA transcription or/and mRNA maturation, we showed that the 5.1 AAP3 mRNA did not decay after 180 min, but the 4.7 AAP3 mRNA presented a half-life decay of 32.6 +/- 5.0 min. In conclusion, parasites can regulate amino acid uptake by increasing the amount of transporter-coding mRNA, possibly by regulating the mRNA half-life in an environment where the amino acid is not present or is in low amounts.

Coagulation factor VIII (FVIII) concentrates are used in the treatment of patients with Hemophilia A. Human FVIII was purified directly from plasma using anion exchange chromatography followed by gel filtration. Three Q-Sepharose resins were tested, resulting in 40% recovery of FVIII activity using Q-Sepharose XL resin, about 80% using Q-Sepharose Fast Flow and 70% using the Q-Sepharose Big Beads. The vitamin K-dependent coagulation factors co-eluted with FVIII from the anion exchange columns. In the second step of purification, when Sepharose 6FF was used, 70% of FVIII activity was recovered free from vitamin K-dependent factors.

Leptospira is the etiological agent of leptospirosis, a life-threatening disease that affects human populations worldwide. Available vaccines have demonstrated limited effectiveness, and therapeutic interventions are complicated by the difficulty of establishing an early diagnosis. The genome of Leptospira strains was sequenced, and bioinformatic analyses revealed potential vaccine and serodiagnosis candidates. The present work studied OmpA70, a putative outer membrane protein from Leptospira interrogans serovar Copenhageni that combines structural features of Loa22, the first genetically defined virulence factor in Leptospira, and Lp49, a protein that reacts with sera from early and convalescent patients. Recombinant OmpA was produced in Escherichia coli in an insoluble form. Considering the importance of the structural integrity of a protein to confer immune protection, high hydrostatic pressure (HHP) was used to refold OmpA70 aggregated as inclusion bodies. HHP was applied in association with redox-shuffling reagents (oxidized and reduced glutathione) and guanidine hydrochloride or l-arginine. About 40% of the protein was refolded by applying 200MPa for 16h in concentrations of l-arginine above 0.4M. Circular dichroism revealed the presence of secondary structure. OmpA70 has immunogenic and antigenic properties as high antibody titers were seen after immunization with this protein, and sera from infected hamsters reacted with soluble OmpA70., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Background: The aim of this study was to examine whether neem Azadirachta indica possesses regenerative potential on the stomach and ileum at 500 mg/kg dose given every 12 hours after mucosa lesion was brought by the administration of 1 ml of 50% ethanol for 21 consecutive days in adult Wistar rats., Methods: Adult male Wistar rats used in the study were divided into 3 groups: group A received oral normal saline and served as control; group B received 1.0 ml of 50% ethanol orally every 12 hours; and group C received neem extract (500 mg/kg) orally 12 hours after ethanol (50%, 1.0 ml) administration to verify its regenerative potential. The experiment lasted for 21 days after which the animals were sacrificed following chloroform inhalation and the stomach and ileum excised and processed for histological and morphometric examinations., Results: Ethanol treated rats showed marked gross mucosal lesions in the stomach and ileum. Ulcerated mucosa with marked apoptotic bodies and destruction of glandular elements were evident in the animals (group B). Neem extract administered 12 hours after the ethanol administration showed regenerative potential against ethanol-induced mucosal damage. This was characterized by mild restoration of the ulcerated mucosa epithelium and reorganization of the cyto-architechtural outline in group C., Conclusions: Our investigation suggests that neem extract has a regenerative potential and may be adopted in the management of gastrointestinal disorders such as ulcer.

The role of innate immune responses in protection against leptospirosis remains unclear. We examined the expression of the chemokines CCL2/JE (MCP-1), CCL3/MIP-1 alpha (MIP-1 alpha) and CXCL1/KC (IL-8) regarding resistance and susceptibility to leptospirosis in experimental mice models BALB/c and C3H/HeJ, respectively. A virulent strain of Leptospira interrogans serovar Copenhageni was used in this study. Twenty-five animals of each mouse strain of C3H/HeJ and BALB/c, were infected intraperitoneally with 10(6) cells. Five un-infected animals of each strain were kept as control. Mortality of C3H/HeJ mouse was observed while BALB/c mice were asymptomatic. The presence of leptospire DNA in tissues of infected animals was demonstrated by PCR. Chemokines were measured in serum, spleen, liver, kidney and lung of both strains of animals using immunoenzymatic assay (ELISA). Elevations in the levels of chemokines MCP-1 and IL-8 occurred in all organs and sera of C3H/HeJ and BALB/c infected mice. The levels of MIP-1 alpha were lower when compared to MCP-1 and IL-8 in all analyzed organs, with a slight increase in liver and kidney. Our results indicate that the expression of inflammatory mediators can vary greatly, depending on the tissue and mouse strains. It is possible that the resistance to Leptospira can be partially correlated to the increase of MIP-1 alpha observed in BALB/c mice, while an increasing and a sustained expression of MCP-1 and IL-8 in the lungs of C3H/HeJ mice can be correlated to the severity and progression of leptospirosis.

A controlled study was designed in order to evaluate the effects of medial patellar desmotomy (MPD), combined with exercise restriction, on clinically and radiographically normal femoropatellar joints, and to identify the patellar instability by radiographic examination. MPD was performed on the right hind limb and the horses were rested for 120 days. Both hind limbs were radiographed before surgery and at 15, 30, 60, 90, and 120 days after MPD, obtaining lateromedial, flexed lateromedial, caudocranial and cranioproximal-craniodistal (skyline) views. The femorotibial and femoropatellar angles were assessed on the lateromedial views, and the distance between the medial and lateral cortex of the femur, and the distance between the medial cortex of the femur and the lateral border of the patella were evaluated in the caudocranial views. An increase in the angle between the proximal articular surface of the patella and the cranial distal surface of the femur along with enthesophyte formation and lateral deviation of the patella were found on the radiographs of the right stifles after MPD. Therefore, MPD leads to patellar instability, which can be demonstrated by the radiographic changes. The 120 days rest did not prevent the lesions caused by postsurgical patellar instability.

Objective: The effect of quinine commonly used for the treatment of Chloroquine resistant malaria and cerebral malaria on the population and transverse diameters of Purkinje cells in the cerebellar cortex was investigated., Methods: Twenty-seven adult male wistar rats weighing between 150 g and 190 g were separated into three groups, each containing nine rats. The rats in group I were injected intramuscularly with equivalent volume of physiological saline, while group II rats were injected intramuscularly with an initial 20 mg/kg body weight dose of quinine followed by a 10 mg/kg body weight dose given 8 hourly for 7 days. The group III rats received the same treatment as group II, but were subjected to a withdrawal period of one week. The cerebellum of each rat was removed and fixed in 10% formol saline for routine histological procedures., Results: The Purkinje cell population reduced significantly (P < 0.05) from the mean value of 363 +/- 5.2 cells/mm2 in group I to a mean value of 239 +/- 9.5 cells/mm2 in group II and 220 +/- 6.6 cells/mm2 in group III rats. The transverse diameters of the Purkinje cells also reduced significantly (p < 0.05) from the mean value of 1.20 +/- 0.02 microm in the group I to a mean value of 1.09 +/- 0.1 microm in group II and 0.75 +/- 0.03 microm in group III., Conclusion: The observed decrease in population and diameters of Purkinje cells in the treatment groups may impair cerebellar functions since they are the principal neurons of the cerebellum.

This observational and sectional study analyzed the quality of the wound dressing procedure performed on hospitalized patients at a medical surgical unit of a University Hospital, based on their classification according to the degree of care dependency and activity performance phases. Using a check list, 168 wound dressings were observed between October and December 2005. Procedure quality was analyzed based on the Positivity Index (IP) and values >70% were considered satisfactory. For the preparation, the IP was 68%, 63%, 73% and 75% for patients with degrees I, II, III and IV, respectively; for execution, 70%, 69%, 71% and 75% and, for unit organization, it was >70% for all degrees. However, the items: validity time frame checking, respect for aseptic principles and maintenance of logical sequence of procedures were compromised. Rigorous execution of procedures allows for risk decrease and assures beneficial results for patients, conferring quality to nursing actions.

This was a clinical-epidemiological and mycological study on 184 patients at the university hospital: 200 samples, 142 positive samples, 98 yeasts and 68 filamentous fungi. Candida parapsilosis (47%) and Trichophyton rubrum (38%) were prevalent. They were 100% sensitive to ketoconazole and 99% sensitive to amphotericin B. The highest prevalences were among women (80%), adults (62%) and toes (84%).

This study was undertaken to investigate the protective effects of quercetin (QCT) on the morphology of pancreatic beta-cells against diabetes mellitus and oxidative stress experimentally-induced by streptozotocin (STZ) treatment in Wistar rats. Fifty male and female Wistar rats (200-250 g) were randomly divided into three experimental groups (i. e., control, STZ-treated, and STZ + Quercetin-treated groups). Diabetes was induced in the diabetic groups (B and C) of animals, by a single intraperitoneal injection of STZ (75 mg/kg), while each of the rats in the 'control' group received equal volume of citrate buffer (pH 6.3) solution intraperitoneally. In group C rats, quercetin (QCT, 25 mg/kg/day i.p.) was injected daily for 3 days prior to STZ treatment, and QCT administration continued until the end of the study period (30 days). Diabetes mellitus was confirmed by using Bayer's Glucometer Elite and compatible blood glucose test strips. The rats were sacrificed serially until the end of the study period (after 30 days). The pancreases of the sacrificed rats were excised and randomly processed for histological staining and biochemical assays for antioxidant enzymes [such as glutathione peroxidase (GSHPx), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and serum nitric oxide (NO)]. In the diabetic state, pancreatic beta-cells of STZ-treated group B rats histologically demonstrated an early chromatin aggregation, cytoplasmic vesiculation in the central beta-cells, nuclear shrinkage, and lysis of beta-cells with distortion of granules. The morphology of QCT-treated rats' pancreases showed viable cellularity with distinct beta-cell mass. STZ treatment significantly decreased (p<0.05) GSHPx, SOD, CAT and pancreatic insulin content. However, STZ treatment increased blood glucose concentrations, MDA and serum NO. The QCT-treated group of animals showed a significant decrease (p<0.05) in elevated blood glucose, MDA and NO. Furthermore, QCT treatment significantly increased (p<0.05) antioxidant enzymes' activities, as well as pancreatic insulin contents. Quercetin (QCT) treatment protected and preserved pancreatic beta-cell architecture and integrity. In conclusion, the findings of the present experimental animal study indicate that QCT treatment has beneficial effects on pancreatic tissues subjected to STZ-induced oxidative stress by directly quenching lipid peroxides and indirectly enhancing production of endogenous antioxidants.