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1.
An. Fac. Cienc. Méd. (Asunción) ; 55(2): 88-91, 20220801.
Artigo em Espanhol | LILACS | ID: biblio-1380445

RESUMO

El fenómeno de Lucio es un estado reaccional grave, poco frecuente, mediado por inmunocomplejos que se observa típicamente en los casos de lepra lepromatosa difusa. En Paraguay, corresponde aproximadamente al 2% de los casos de lepra diagnosticados en la mayoría de los casos, se presenta como debut de la enfermedad. Se manifiesta con lesiones en la piel de tipo máculas y placas purpúricas poligonales, generalmente sin compromiso visceral. El diagnóstico lo confirma el estudio histopatológico y es fundamental realizar el diagnóstico diferencial con vasculitis de otras etiologías.


Lucio's phenomenon is a rare and severe reactional state mediated by immune complexes that is commonly seen in cases of diffuse lepromatous leprosy. In Paraguay, it represents approximately 2% of leprosy diagnosed cases, mainly as a debut of the disease. It manifests with macule-type skin lesions and polygonal purpuric plaques, generally without visceral involvement. The diagnosis is confirmed by the histopathological study and it is essential to consider differential diagnosis such as vasculitis of other etiologies.


Assuntos
Hanseníase , Hanseníase Virchowiana
2.
Int J Dermatol ; 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35913701

RESUMO

BACKGROUND: Leprosy is a chronic infectious disease that causes disabilities and deformities. Early detection is a major strategy for leprosy control. This study reported a new practice of suspicious symptom monitoring for early detection of leprosy. METHODS: A descriptive and comparative analysis between a non-strategy group of pre-implementation of suspicious symptom monitoring in 2005-2011 and a strategy group of strategy implementation in 2012-2018 was conducted through indicators of the number of times of misdiagnoses, delayed period, proportion of early detected cases, and proportion of disabilities. RESULT: Compared with the non-strategy group in 2005-2011, the median number of times of misdiagnoses was decreased from two times to zero times (z = 4.387, P < 0.001), and the median delayed period of newly detected cases were shortened from 24 months to 13 months (z = 2.381, P < 0.001), the proportion of early detected cases was increased from 43.7% to 75.2% (χ2 = 29.464, P < 0.001), the proportion of grade 2 disabilities was decreased from 28.6% in the highest year of 2005 to 4.0% in the lowest year of 2014, and the average proportion of disabilities was decreased from 33.5% to 17.6% (χ2 = 9.421, P = 0.002) in the strategy group in 2012-2018, respectively. CONCLUSION: Suspicious symptom monitoring promoted early detection of cases by reducing the number of times misdiagnosis of leprosy patients, shortening the delayed period, increasing the proportion of early detection, and decreasing the proportion of disabilities. It is an important and recommendable public health strategy for leprosy prevention and control in a low epidemic condition.

3.
IDCases ; 29: e01574, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35923859

RESUMO

We describe a case of sarcoid-like cutaneous paracoccidioidomycosis in a 26-year-old male, with a 10-year evolution, wrongly diagnosed as granulomatous rosacea. The correct diagnosis was only possible after the appearance of a new skin lesion with a more typical characteristic of the dermatosis, correlated with anatomopathological, laboratory and imaging exams. The clinical presentation of paracoccidioidomycosis is diverse, and the sarcoid-like form can mimic several chronic granulomatous diseases, such as sarcoidosis, tuberculoid leprosy, leishmaniasis, or tuberculosis. This presentation of cutaneous paracoccidioidomycosis is rare, and its diagnosis depends on the clinicopathological correlation, which can be a challenge for the dermatologist.

4.
Infect Drug Resist ; 15: 4029-4036, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35924023

RESUMO

Purpose: Reports on antimicrobial resistance (AMR) of Mycobacterium leprae (M. leprae) in Zhejiang Province are limited. Thus, this study aimed to investigate the drug resistance of new leprosy cases within several years and analyse the emergence of AMR mutations from Zhejiang Province. Methods: This study enrolled 34 leprosy cases in Zhejiang Province, China, from 2018 to 2021. Gene mutation of WHO-recommended DRDRs (folP1, rpoB and gyrA) and genes of compensatory AMR-associated DRDRs, including nth, rpoA, rpoC, gyrB and 23S rRNA, were detected by amplification. Clinical data analysis was performed to investigate the epidemiological association of leprosy. Results: Of the 34 samples, 2 (5.9%) strains showed drug resistance, which were mutated to dapsone and ofloxacin, separately. Two single mutations in gyrB were detected in different strains (5.9%), whereas one of the rpoC mutation was also detected in one strain each (2.9%), which were proved to be polymorphs. No correlation of drug resistance proportion was identified in male vs female, nerve vs no nerve involvement, deformity vs no deformity and reaction vs non-reaction cases. Conclusion: Results showed well control of leprosy patients in Zhejiang Province. Gene mutations of WHO-recommended DRDRs folP1 and gyrA confirmed the resistance to dapsone and ofloxacin. Compensatory AMR-associated mutations confirmed to be polymorphs still require further study to determine their phenotypic outcomes in M. leprae. The results demonstrated that drug-resistant strains are not epidemic in this area. Given the few cases of leprosy, analysing the AMR of M. leprae in Zhejiang Province more comprehensively is difficult. However, regular MDT treatment and population management in the early stage may contribute to the low prevalence of leprosy.

5.
Front Med (Lausanne) ; 9: 865330, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35924037

RESUMO

Leprosy reactions are an acute and systemic manifestation, which occurs suddenly, can be severe and lead leprosy patients to disability. Reactional episodes are observed among half of the multibacillary patients, mainly in borderline lepromatous and lepromatous forms. They may begin at any time during multidrug therapy, and even before the treatment. Physical disabilities, which are the source of extreme suffering and pain for patients, occur in progression of the cellular immune response associated with a reaction and are still poorly understood. Thus, this work aimed to phenotypically and functionally characterize CD4+ and CD8+ Treg cells ex vivo and in response to Mycobacterium leprae (ML). We studied 52 individuals, including 18 newly diagnosed and untreated multibacillary leprosy patients, 19 reactional multibacillary patients (Type I or Type II episodes) and 15 healthy volunteers, included as controls, all residents of the city of Rio de Janeiro. The functional activity and frequencies of these cells were evaluated through multiparametric flow cytometry. In addition, the production of cytokines in supernatant from peripheral blood mononuclear cell cultures was also investigated against ML by enzyme-linked immunosorbent assay. Our results showed a decrease in CD4+TGF-ß+ Treg and CD8+ TGF-ß+ Treg in leprosy multibacillary patients during both types of reactional episodes. Alterations in the cytokine profile was also observed in Type II reactions, along with upregulation of IL-17 and IL-6 in supernatant. Thus, our study suggests that downregulation of Treg cells is related with both classes of reactional episodes, improving our understanding of immune hyporesponsiveness in multibacillary patients and hyperesponsiveness in both reactions.

6.
Int J Dermatol ; 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35924464

RESUMO

BACKGROUND: Corticosteroids remain the main therapy in erythema nodosum leprosum (ENL), and long-term usage in chronic or recurrent ENL is a cause of significant morbidity and mortality. Thalidomide exerts dramatic effect in controlling ENL and helps reduce the dose of steroids, but the cost is a hindrance to its usage. METHODS: Patients of ENL (steroid naïve and steroid-dependent) were recruited over a 1-year period. An escalating dose of low-dose thalidomide with a reducing dose of prednisolone was titrated depending on the control of disease activity. The primary aim was to reduce the dose of steroids to the lowest effective dose, and the secondary aim was to stop. RESULTS: Sixteen patients of ENL were studied (mean duration of ENL 22.1 months, 15 severe ENL), and a majority (11/16, 68%) were on steroids with a mean duration of 11.27 months. All patients had steroid-related side effects (cushingoid habitus 81.8%, weight gain 54.5%, diabetes mellitus 9%, hyperlipidemia 18.18%, cataract 18.1%, osteoporosis 36.3%, striae 36.3%, acneiform eruptions 18.1%, and myopathy 9%). Steroids could be tapered in a majority of patients (n = 9) within 3 months (mean 2.44 months) with a low dose of thalidomide (25-150 mg/day, mean 78.3 mg) achieving a significant reduction in prednisolone dose (33.16 mg at baseline; 4.28 mg at 3 months, P < 0.05). Steroids could be stopped in 92% of patients by 3.03 months, and both drugs could be stopped in 80% of cases by 5.83 months. CONCLUSION: The rapid and effective control of ENL with low-dose thalidomide in our series is comparable to the historical efficacy of high-dose thalidomide regimens, making it an affordable therapy in resource-constrained settings and an excellent steroid-sparing agent. The rapid onset of disease control is likely attributable to its action via neutrophils.

7.
Front Vet Sci ; 9: 934789, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35928109

RESUMO

Dachshunds are at significant risk of experiencing thoracolumbar intervertebral disk herniation (IVDH) during their lifetimes. Standard of care includes advanced imaging, surgical intervention, and postoperative rehabilitation. Conservative management is commonly recommended for cases where the standard of care is declined, and little is known about the prognosis of treatment with conservative management and rehabilitation (nonsurgical rehabilitation). This retrospective cohort study assessed 12-week functional outcome and recurrence of clinical signs in 40 dachshunds with T3-L3 myelopathy presumed to be due to Hansen's Type I disc herniation, treated with nonsurgical rehabilitation. The overall prognosis was good with 34 of 40 (85.0%, 95% CI 70.2-94.2) dachshunds achieving functional pet status by 12 weeks postinjury. Modified Frankel Score at presentation was significantly (p < 0.001) higher in dogs with a positive 12-week outcome compared to dogs that did not recover by 12 weeks. All 27 dogs with motor function at presentation had a positive outcome. Of the 9 dogs exhibiting paraplegia with intact deep nociception at presentation, 7 dogs (77.8%) had achieved a positive outcome by 12 weeks. None of the 4 dogs persistently lacking deep nociception had a positive outcome. Among 27 dogs with a positive outcome for whom follow-up records were available, the 1- and 2-year recurrence rates for T3-L3 myelopathy were 5 and 11%, respectively. Nonsurgical rehabilitation should be considered in dachshunds with mild to moderate T3-L3 myelopathy or in severe cases when advanced imaging and surgical intervention are not possible.

8.
Mech Ageing Dev ; : 111713, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35931241

RESUMO

Inflammaging is a low-grade inflammatory state generated by the aging process that can contribute to frailty and age-related diseases in the elderly. However, it can have distinct effects in the elderly living in endemic areas for infectious diseases. An increased inflammatory response may confer protection against infectious agents in these areas, although this advantage can cause accelerating epigenetic aging. In this study, we evaluated the inflammatory profile and the epigenetic age of infected and noninfected individuals from an endemic area in Brazil. The profile of cytokines, chemokines and growth factors analyzed in the sera of the two groups of individuals showed similarities, although infected individuals had a higher concentration of these mediators. A significant increase in IL-1ra, CXCL8, CCL2, CCL3 and CCL4 production was associated with leprosy infection. Notably, elderly individuals displayed distinct immune responses associated with their infection status when compared to adults suggesting an adaptive remodelling of their immune responses. Epigenetic analysis also showed that there was no difference in epigenetic age between the two groups of individuals. However, individuals from the endemic area had a significant accelerated aging when compared to individuals from São Paulo, a non-endemic area in Brazil. Moreover, the latter cohort was also epigenetically aged in relation to an Italian cohort. Our data shows that living in endemic areas for chronic infectious diseases results in remodelling of inflammaging and acceleration of epigenetic aging in individuals regardless of their infectious status. It also highlights that geographical, genetic and environmental factors influence aging and immunosenescence in their pace and profile.

9.
Biomater Adv ; 138: 212941, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35913257

RESUMO

To design new material for blood-related applications one needs to consider various factors such as cytotoxicity, platelet adhesion, or anti-thrombogenic properties. The aim of this work is the design of new, highly effective materials possessing high blood compatibility. To do this, the new composites based on the poly(vinylidene fluoride) (PVDF) support covered with a single-walled carbon nanohorns (CNHs) layer were prepared. The PVDF-CNHs composites were subsequently used for the first time in the hemocompatibility studies. To raise the hemocompatibility a new, never applied before for CNHs, plasma-surface modifications in air, nitrogen and ammonia were implemented. This relatively cheap, facile and easy method allows generating the new hybrid materials with high effectiveness and significant differences in surface properties (water contact angle, surface ζ-potential, and surface functional groups composition). Changing those properties made it possible to select the most promising samples for blood-related applications. This was done in a fully controlled way by applying Taguchi's "orthogonal array" procedure. It is shown for the first time that nitrogen plasma treatment of new surfaces is the best tool for hemocompatibility rise and leads to very low blood platelet adhesion, no cytotoxicity, and excellent performance in thromboelastometry and hemolysis tests. We propose a possible mechanism explaining this behavior. The optimisation results are coherent with biological characterisation and are supported with Hansen Solubility Parameters. New surfaces can find potential applications in cardiological and circulatory system implants as well as other blood-related biomaterials.


Assuntos
Carbono , Sistema Cardiovascular , Polímeros de Fluorcarboneto , Teste de Materiais/métodos , Nitrogênio , Polivinil
10.
Environ Microbiol ; 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35920032

RESUMO

If life exists on Mars, it would face several challenges including the presence of perchlorates, which destabilize biomacromolecules by inducing chaotropic stress. However, little is known about perchlorate toxicity for microorganism on the cellular level. Here we present the first proteomic investigation on the perchlorate-specific stress responses of the halotolerant yeast Debaryomyces hansenii and compare these to generally known salt stress adaptations. We found that the responses to NaCl and NaClO4 -induced stresses share many common metabolic features, e.g., signaling pathways, elevated energy metabolism, or osmolyte biosynthesis. Nevertheless, several new perchlorate-specific stress responses could be identified, such as protein glycosylation and cell wall remodulations, presumably in order to stabilize protein structures and the cell envelope. These stress responses would also be relevant for life on Mars, which - given the environmental conditions - likely developed chaotropic defense strategies such as stabilized confirmations of biomacromolecules and the formation of cell clusters. This article is protected by copyright. All rights reserved.

11.
J Physiol ; 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35930370

RESUMO

Over the last 100 years, high-altitude researchers have amassed a comprehensive understanding of the global cardiac responses to acute, prolonged and lifelong hypoxia. When lowlanders are exposed to hypoxia, the drop in arterial oxygen content demands an increase in cardiac output, which is facilitated by an elevated heart rate while ventricular volumes are maintained. As exposure is prolonged, haemoconcentration restores arterial oxygen content while left ventricular filling and stroke volume are lowered due to a combination of reduced blood volume and hypoxic pulmonary vasoconstriction. Populations native to high-altitude, such as the Sherpa in Asia, exhibit unique lifelong or generational adaptations to hypoxia. For example, smaller left ventricular volumes compared to lowlanders despite having larger total blood volume. More recent investigations have begun to explore the mechanisms underlying such adaptive responses by combining novel imaging techniques with interventions that manipulate cardiac preload, afterload, and/or contractility. This work has revealed the contributions and interactions of (i) plasma volume constriction, (ii) sympathoexcitation and (iii) hypoxic pulmonary vasoconstriction in altering cardiac loading, or otherwise preserving or enhancing biventricular systolic and diastolic function even amongst high altitude natives with excessive erythrocytosis. Despite these advances, various areas of investigation remain understudied, including potential sex-related differences in response to high altitude. Collectively, the available evidence supports the conclusion that the human heart successfully adapts to hypoxia over the short- and long-terms, without signs of myocardial dysfunction in healthy humans, except in very rare cases of maladaptation. Abstract figure legend Responses of key cardio-autonomic parameters to acute, prolonged and lifelong hypoxia. Relative changes are plotted for lowlanders across the timelines of 0 to 12 hours (left panel) and 1 day to 6 months (middle panel) and compared to observations in select populations residing at high altitude in Asia and South America (right panel). Where divergent adaptations occur, Andean and Sherpa data are represented with dashed and dotted lines, respectively. Generally, increasing exposure durations to hypoxia are characterized by substantial increases to sympathetic neural activation (SNA) (Duplain et al., 22; Hansen & Sander, 38; Simpson et al., 98) and pulmonary arterial systolic pressure (PASP) (Swenson, 110), with afterload-induced expansion of right ventricular end-diastolic area (RV EDA) (Kjaergaard et al., 48; Stembridge, Ainslie et al., 101) and consequent reductions to left ventricular (LV) end-diastolic volume (EDV) (Goebel et al., 33; Stembridge et al., 104, 101). Total blood volume (BV) is initially lowered with prolonged exposure due to plasma volume constriction but over several months returns to or above sea level values and is notably higher in high-dwelling Sherpa and Andeans compared to acclimatized lowlanders when expressed as relative to body size (Ryan et al., 89; Stembridge, Williams et al., 106). This article is protected by copyright. All rights reserved.

12.
JMIR Res Protoc ; 2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35922062

RESUMO

BACKGROUND: The prevalence of skin diseases is extremely high in sub-Saharan Africa, among which are skin neglected tropical diseases (skin NTDs) that could lead to life-long disabilities and deformities if not diagnosed and treated early. To achieve early detection and early treatment of these skin diseases, we developed a mobile health application (mHealth app): 'eSkinHealth.' OBJECTIVE: This paper outlines a protocol for evaluating the effect of our eSkinHealth app in the early detection and effective management of skin diseases in Côte d'Ivoire. METHODS: A mixed-methods pilot trial will be conducted in Côte d'Ivoire and will consist of 3 phases: phase 1, the development and improvement of the eSkinHealth app; phase 2, a pilot trial to evaluate the usability of the eSkinHealth app for local medical staff in Côte d'Ivoire; and phase 3, a pilot trial to evaluate the effectiveness of early detection and case management of targeted skin NTDs (Buruli ulcer, leprosy, yaws, and lymphatic filariasis) with the eSkinHealth app in Côte d'Ivoire. The pilot study will be implemented as a 2-arm trial with local healthcare providers and patients with skin NTDs over a 3-month follow-up period. The local healthcare providers will be assigned to an intervention group receiving the eSkinHealth app to be used in their daily practices or a control group. Training will be provided on the usage and implementation of the app and diagnostic pipeline to the intervention group only, while both groups will receive training on skin diseases. Our primary outcome is to evaluate the early detection and effective management of skin diseases using the eSkinHealth app in Côte d'Ivoire by number of cases diagnosed and managed. Additionally, we will evaluate the eSkinHealth app with validated questionnaires and in-depth interviews. Procedures of our methods have been reviewed and approved by the IRB of the Ministry of Health, Côte d'Ivoire and by Tulane University in 2021. RESULTS: This study was funded in 2021. We started enrolment of patients in February 2022, and data collection is currently underway. We expect the first results to be submitted for publication in 2023. CONCLUSIONS: Our 'eSkinHealth' is a field-adapted platform that could both provide direct diagnostic and management assistance to health workers in remote settings. The study will provide evidence for the usability and the effectiveness of the eSkinHealth app to improve the early detection and case management of skin NTDs in Côte d'Ivoire; and further, are expected to contribute to knowledge on mobile health approaches in the control of skin NTDs. CLINICALTRIAL: 2020-2054 (Clinicaltrials.gov).

13.
Infect Dis Poverty ; 11(1): 88, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35932055

RESUMO

BACKGROUND: Neglected tropical diseases (NTDs) affect poor populations with little or no 'political voice' to influence control activities. While most NTDs have interventions that work, the biggest challenge remains in delivering targeted interventions to affected populations residing in areas experiencing weak health systems. Despite the upward development trends in most countries of sub-Saharan Africa (SSA), the healthcare worker to population ratio remains exceptionally low, with some areas not served at all; thus, there is a need to involve other personnel for school and community-based healthcare approaches. Nonetheless, the current community-based programs suffer from inconsistent community participation due to a lack of coordinated response, and an expanded intervention agenda that lacks context-specific solutions applicable to rural, urban, and marginalized areas. METHODS: This research investigated the capacity of local communities to address the burden of NTDs. Informed by the social theory of human capability, the research collected primary qualitative data by conducting key informant interviews and focus group discussions of people infected or affected by NTDs. The interview data were collected and transcribed verbatim for thematic analysis using Nvivo version 12. RESULTS: Our findings reveal, first, a need for intersectoral collaboration between governments and affected populations for inclusive and sustainable NTD solutions. Second, a 'bottom-up' approach that enhances capacity building, sensitization, and behaviour change for improved uptake of NTD interventions. Third, the enforcement of Public Health Legislative Acts that mandates the reporting and treatment of NTDs such as leprosy. Fourth, the establishment of support groups and counseling services to assist persons suffering from debilitating and permanent effects of NTDs. CONCLUSIONS: Our research demonstrates the importance of human agency in encouraging new forms of participation leading to the co-production of inclusive and sustainable solutions against NTDs.


Assuntos
Doenças Negligenciadas , Medicina Tropical , Fortalecimento Institucional , Serviços de Saúde Comunitária , Humanos , Quênia , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/prevenção & controle , Saúde Pública
14.
Curr Res Microb Sci ; 3: 100129, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909624

RESUMO

Yeasts of the genus Hanseniaspora gained notoriety in the last years due to their contribution to wine quality, and their loss of several genes, mainly related to DNA repair and cell cycle processes. Based on genomic data from many members of this genus, they have been classified in two well defined clades: the "faster-evolving linage" (FEL) and the "slower-evolving lineage" (SEL). In this context, we had detected that H. vineae exhibited a rapid loss of cell viability in some conditions during the stationary phase compared to H. uvarum and S. cerevisiae. The present work aimed to evaluate the viability and cell cycle progression of representatives of Hanseniaspora species along their growth in an aerobic and discontinuous system. Cell growth, viability and DNA content were determined by turbidity, Trypan Blue staining, and flow cytometry, respectively. Results showed that H. uvarum and H. opuntiae (representing FEL group), and H. osmophila (SEL group) exhibited a typical G1/G0 (1C DNA) arrest during the stationary phase, as S. cerevisiae. Conversely, the three strains studied here of H. vineae (SEL group) arrested at G2/M stages of cell cycle (2C DNA), and lost viability rapidly when enter the stationary phase. These results showed that H. vineae have a unique cell cycle behavior that will contribute as a new eukaryotic model for future studies of genetic determinants of yeast cell cycle control and progression.

15.
Cureus ; 14(6): e26251, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35911269

RESUMO

Non-tuberculous mycobacterial infections (mycobacterium other than Mycobacterium tuberculosis and Mycobacterium leprae) are organisms that are commonly found in the environment such as water, soil, and dust. They may form difficult to eliminate biofilms and have been reported to cause significant infections in humans, especially in immunocompromised hosts. This article describes an interesting case of Mycobacterium abscessus in the lung.

16.
PLoS Negl Trop Dis ; 16(7): e0010641, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35867720

RESUMO

BACKGROUND: The numbers of circulating regulatory T cells (Tregs) are increased in lepromatous leprosy (LL) but reduced in erythema nodosum leprosum (ENL), the inflammatory complication of LL. It is unclear whether the suppressive function of Tregs is intact in both these conditions. METHODS: A longitudinal study recruited participants at ALERT Hospital, Ethiopia. Peripheral blood samples were obtained before and after 24 weeks of prednisolone treatment for ENL and multidrug therapy (MDT) for participants with LL. We evaluated the suppressive function of Tregs in the peripheral blood mononuclear cells (PBMCs) of participants with LL and ENL by analysis of TNFα, IFNγ and IL-10 responses to Mycobacterium leprae (M. leprae) stimulation before and after depletion of CD25+ cells. RESULTS: 30 LL participants with ENL and 30 LL participants without ENL were recruited. The depletion of CD25+ cells from PBMCs was associated with enhanced TNFα and IFNγ responses to M. leprae stimulation before and after 24 weeks treatment of LL with MDT and of ENL with prednisolone. The addition of autologous CD25+ cells to CD25+ depleted PBMCs abolished these responses. In both non-reactional LL and ENL groups mitogen (PHA)-induced TNFα and IFNγ responses were not affected by depletion of CD25+ cells either before or after treatment. Depleting CD25+ cells did not affect the IL-10 response to M. leprae before and after 24 weeks of MDT in participants with LL. However, depletion of CD25+ cells was associated with an enhanced IL-10 response on stimulation with M. leprae in untreated participants with ENL and reduced IL-10 responses in treated individuals with ENL. The enhanced IL-10 in untreated ENL and the reduced IL-10 response in prednisolone treated individuals with ENL was abolished by addition of autologous CD25+ cells. CONCLUSION: The findings support the hypothesis that the impaired cell-mediated immune response in individuals with LL is M. leprae antigen specific and the unresponsiveness can be reversed by depleting CD25+ cells. Our results suggest that the suppressive function of Tregs in ENL is intact despite ENL being associated with reduced numbers of Tregs. The lack of difference in IL-10 response in control PBMCs and CD25+ depleted PBMCs in individuals with LL and the increased IL-10 response following the depletion of CD25+ cells in individuals with untreated ENL suggest that the mechanism of immune regulation by Tregs in leprosy appears independent of IL-10 or that other cells may be responsible for IL-10 production in leprosy. The present findings highlight mechanisms of T cell regulation in LL and ENL and provide insights into the control of peripheral immune tolerance, identifying Tregs as a potential therapeutic target.


Assuntos
Eritema Nodoso , Hanseníase Virchowiana , Hanseníase , Anti-Inflamatórios/uso terapêutico , Quimioterapia Combinada , Humanos , Interleucina-10 , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Hanseníase Virchowiana/complicações , Leucócitos Mononucleares , Estudos Longitudinais , Mycobacterium leprae , Prednisolona/farmacologia , Prednisolona/uso terapêutico , Linfócitos T Reguladores , Fator de Necrose Tumoral alfa
17.
J Colloid Interface Sci ; 626: 178-192, 2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35785603

RESUMO

HYPOTHESIS: Strikingly, Kraft lignin nanoparticles (KLNPs) can substitute polluting nanoparticles in diverse applications. An attractive method for synthesizing KLNPs is Solvent shifting. We hypothesized that by a detailed understanding of the solvent properties and influence of the process parameters, one could derive new fundamental and technical information about the lignin nanoparticle formation process. EXPERIMENTS: DMSO and THF were chosen best solvents based on the Hansen solubility parameter of lignin. The four synthesis parameters such as lignin concentration, (anti-solvent) water volume, temperature, and stirring speed were used to investigate the size, polydispersity index (PDI), morphology as well as the thermal, mechanical and optical properties of KLNPsDMSO & KLNPsTHF. FINDINGS: KLNPsTHF follows the well-known nucleation and growth (NG) mechanism, resulting in spherical KLNPs (43 ± 12 nm: 0.20 PDI). Surprisingly, KLNPsDMSO follows a unique mechanism resembling spinodal decomposition (SD), which generates rare bicontinuous-to-spherical KLNPs (17 ± 8 nm: 0.20 PDI). Remarkably, we show that the difference in the KLNPs mechanism modulates their intrinsic properties, such as glass transition temperature (Tg), specific surface area (SSA), elastic modulus (EM) and optical properties. Beyond the new mechanism, our synthesis resulted in reproducible ultra-small KLNPs with an excellent % yield. Such findings have vast implications in high-performance nanocomposites.

18.
BMJ Open ; 12(7): e058397, 2022 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-35851027

RESUMO

INTRODUCTION: Malaria is one of the major public health problems in sub-Saharan Africa. It contributes significantly to maternal and fetal morbidity and mortality in affected countries. This study aims to evaluate the impact of enhanced case detection using molecular testing called loop-mediated isothermal amplification (LAMP) on birth outcomes in a prospective study design. METHODS AND ANALYSIS: A pragmatic randomised diagnostic outcomes trial will be conducted in several health institutes in different Ethiopian regions. Women (n=2583) in their first and second trimesters of pregnancy will be included in the study and individually randomised to the standard of care or enhanced case detection arms, and followed until delivery. Enrolment will encompass the malaria peak transmission seasons. In the standard of care arm, a venous blood sample will be collected for malaria diagnosis only in symptomatic patients. In contrast, in the intervention arm, mothers will be tested by a commercially available Conformité Européene (CE)-approved LAMP malaria test, microscopy and rapid diagnostic test for malaria regardless of their symptoms at each antenatal care visit. The primary outcome of the study is to measure birth weight. ETHICS AND DISSEMINATION: The study was approved by the following ethical research boards: Armauer Hansen Research Institute/ALERT Ethics Review Committee (FORM AF-10-015.1, Protocol number PO/05/20), the Ethiopia Ministry of Science and Higher Education National Research Ethics Review Committee (approval SRA/11.7/7115/20), the Ethiopia Food and Drug Administration (approval 02/25/33/I), UCalgary Conjoint Health Research Ethics Board (REB21-0234). The study results will be shared with the institutions and stakeholders such as the Ethiopia Ministry of Health, the Foundation for Innovative Diagnostics, WHO's Multilateral initiative on Malaria - Tropical Diseases Research (TDR-MIM), Roll Back Malaria and the Malaria in Pregnancy Consortium. The study results will also be published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT03754322.


Assuntos
Malária , Programas de Rastreamento , Complicações Parasitárias na Gravidez , Feminino , Humanos , Malária/diagnóstico , Malária/terapia , Programas de Rastreamento/métodos , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Ensaios Clínicos Pragmáticos como Assunto , Gravidez , Complicações Parasitárias na Gravidez/diagnóstico , Complicações Parasitárias na Gravidez/terapia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Tecnologia
19.
Int J Dermatol ; 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35775153

RESUMO

BACKGROUND: The implications of COVID-19 co-infection in patients under treatment for Hansen's disease (HD, leprosy) remain uncertain. We aimed to describe clinical characteristics, treatments, and outcomes in patients with HD and COVID-19 in Brazil. METHODS: Cross-sectional study recruiting adult HD patients with PCR-confirmed COVID-19 from five HD treatment centers in Brazil between March 1, 2020, and March 31, 2021. At the time of this study, no patient had received COVID-19 vaccine. RESULTS: Of 1377 patients under treatment for HD, 70 (5.1%) were diagnosed with COVID-19. Of these, 41 (58.6%) had PCR-confirmed COVID-19, comprising 19 men and 22 women, aged 24-67 (median 45) years. HD was multibacillary in 39/41 patients. Eight patients ceased WHO Multi-Drug Therapy for HD, three for lack of drugs, two because of COVID-19, and three for other reasons. Of the 33 who continued treatment, 26 were on the standard regimen and seven an alternative regimen. Seventeen patients were receiving oral prednisone, including nine patients with type 1 reaction, four with type 2 reaction, three with neuritis, and one with rheumatologic disease. Twelve patients were hospitalized for COVID-19, and six patients died, of whom three had hypertension and one also had type 2 diabetes and obesity. CONCLUSIONS: COVID-19 and Hansen's disease co-infection did not appear to change the clinical picture of either disease in this cross-sectional study. The wider impact of the pandemic on persons affected by HD requires follow-up and monitoring.

20.
Biomacromolecules ; 23(8): 3174-3185, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-35792377

RESUMO

The use of lignin as a functional additive has long been a promising topic in both industry and academia, but the development of such systems is still limited by the considerable challenges posed by the incompatibility of lignin with common polymers. Herein, we designed modified silicone (MS) sealants with enhanced UV and thermal stability by incorporating molecularly engineered lignin bio-additives while establishing robust design principles to finely adjust the morphology of such blends by tailoring the molecular structures of lignin fractions. To that end, we first constructed a library of lignin fractions with various molecular weights (obtained by fractionating Kraft lignin and by using a lignin model compound) and with several chemical modifications (acetylation, butyrylation, and silylation). The lignin bio-additives were then melt-blended with MS polyethers. The experimental phase diagrams of the resulting blends were established and rationalized with a thermodynamic framework combining Hansen solubility parameters and Flory-Huggins theory, unraveling fascinating insights into the complex solubility behavior of lignin fractions and notably, for the first time, the subtle interplay between molecular weight (entropic effects) and chemical modifications (enthalpic effects). A molecularly optimized lignin additive was then selected to achieve full solubility while providing better thermal stability and UV-blocking properties to the resulting MS material. Overall, this article provides robust design principles for the elaboration of functional biomaterials with optimized morphologies based on rationally engineered lignin fractions.


Assuntos
Adesivos , Lignina , Entropia , Lignina/química , Solubilidade , Termodinâmica
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