Spirituality in Coping with Pain in Cancer Patients: A Cross-Sectional Study.

Spirituality has been identified as an adaptive coping strategy and a predictor of better quality of life in cancer patients. Despite the relevance of spirituality in the health-disease process, it is noted that the assessment of the impact of spirituality in coping with pain is still incipient. The objective of this study is to assess the impact of spirituality in coping with pain in cancer patients. This quantitative cross-sectional study was carried out in a medium-sized hospital and a cancer patient support institution located in northeastern Brazil. A questionnaire with sociodemographic and clinical variables was used and the following instruments were applied: Visual Analogue Scale (VAS); Short-Form McGill Pain Questionnaire (SF-MPQ); Neuropathic Pain 4 Questions (DN4); Spiritual Wellbeing Scale (SWBS); WHOQOL Spirituality, Religiousness and Personal Beliefs (WHOQOL-SRPB). Most people with no pain had higher scores on the SWBS. Neuropathic pain was identified in 23 patients and was associated with the highest level of spirituality used as a way of coping with pain. As faith increases, pain decreases in intensity by 0.394 points. On the other hand, as inner peace increases, pain increases by 1.485 points. It is concluded that faith is a strategy for coping with pain, in particular neuropathic pain, minimizing its intensity. On the other hand, greater levels of inner peace allow to increase the awareness of the painful sensation. It is expected that these findings may be useful to integrate spirituality care in healthcare facilities as a resource for positive coping for people in the process of becoming ill, contributing to the therapeutic path and favouring a new meaning to the experience of the disease.

Factors associated with knowledge of the disease in people with type 2 diabetes mellitus.

OBJECTIVES: To identify factors associated with the level of knowledge of the disease in people with type 2 Diabetes. METHODS: A cross-sectional study carried out with 412 people with diabetes registered in the Primary Health Care network of a Brazil Northeast municipality. For data collection, we used a questionnaire with sociodemographic and clinical variables and to identify the level of knowledge, we used the Diabetes Knowledge Questionnaire. RESULTS: Insufficient knowledge prevailed in 54.7% of the participants, associated in significant bivariate analysis (p < 0.05) with the sociodemographic variables: age (≥ 60 years old), marital status (without a partner), education (up to complete / incomplete elementary school), family income (≤ 1 minimum wage). For clinical variables, the level of insufficient knowledge was significantly associated with not participating in an educational group, not using insulin, and not practicing physical activity. In logistic regression, we observed that the factors that increase the risk for insufficient knowledge were: never having participated in an educational group (OR=2.0), age ≥ 60 years old (OR=2.2), illiterate and primary education (OR=8.3) and income less than or equal to 1 minimum wage (OR = 2.4). CONCLUSIONS: The level of knowledge of people with type 2 diabetes mellitus about their disease is insufficient, with socioeconomic and educational characteristics being the factors that increase the odds of having this level of knowledge.

Factors associated with knowledge of the disease in people with type 2 diabetes mellitus

Objective. To identify factors associated with the level of knowledge of the disease in people with type 2 Diabetes. Methods. A cross-sectional study carried out with 412 people with diabetes registered in the Primary Health Care network of a Brazil Northeast municipality. For data collection, we used a questionnaire with sociodemographic and clinical variables and to identify the level of knowledge, we used the Diabetes Knowledge Questionnaire. Results. Insufficient knowledge prevailed in 54.7% of the participants, associated in significant bivariate analysis (p<0.05) with the sociodemographic variables: age (≥ 60 years old), marital status (without a partner), education (up to complete / incomplete elementary school), family income (≤ 1 minimum wage). For clinical variables, the level of insufficient knowledge was significantly associated with not participating in an educational group, not using insulin, and not practicing physical activity. In logistic regression, we observed that the factors that increase the risk for insufficient knowledge were: never having participated in an educational group (OR=2.0), age ≥ 60 years old (OR=2.2), illiterate and primary education (OR=8.3) and income less than or equal to 1 minimum wage (OR = 2.4). Conclusion. The level of knowledge of people with type 2 diabetes mellitus about their disease is insufficient, with socioeconomic and educational characteristics being the factors that increase the odds of having this level of knowledge

Objetivo. Identificar los factores asociados al nivel de conocimiento de la enfermedad en personas con Diabetes Mellitus Tipo 2. Métodos. Estudio transversal realizado con 413 personas con diabetes inscritas en la red de Atención Primaria de Salud de un municipio del Nordeste de Brasil. Para la recolección de los datos, se utilizó un cuestionario con variables sociodemográficas y clínicas y, para identificar el nivel de conocimiento, se utilizó el Diabetes Knowledge Questionnaire. Resultados. Prevaleció el conocimiento insuficiente en el 54.7% de los participantes, asociándose significativamente en el análisis bivariado (p<0.05) con las variables sociodemográficas: edad (≥ 60 años), estado civil (sin pareja), escolaridad (hasta primaria completa / incompleta) e ingreso familiar (≤1 salario mínimo). En cuanto a las variables clínicas, el nivel de conocimiento insuficiente se asoció significativamente con no participar en un grupo educativo, no usar insulina y no practicar actividad física. En la regresión logística, se observó que los factores que incrementan el riesgo de conocimiento insuficiente fueron: nunca haber participado en un grupo educativo (OR=2.0), edad ≥ 60 años (OR=2.2), nivel educativo de analfabetismo o de educación primaria (OR=8.3) e ingresos menores o iguales a 1 salario mínimo (OR=2.4). Conclusión. El nivel de conocimiento sobre su enfermedad de las personas con Diabetes Mellitus Tipo 2 es insuficiente, siendo las características socioeconómicas y educativas los factores que más aumentan la probabilidad de tener este nivel de conocimiento.

Objetivo. Identificar os fatores associados ao nível de conhecimento da doença em pessoas com Diabetes Mellitus tipo 2. Métodos. Estudo transversal realizado com 413 pessoas com diabetes cadastradas na rede de Atenção Primária a Saúde de um município do Nordeste do Brasil. Para coleta de dados foi utilizado questionário com variáveis sociodemográficas e clínicas e para identificar o nível de conhecimento foi utilizado o instrumento Diabetes Knowledge Questionnaire. Resultados. Prevaleceu o nível de conhecimento insuficiente em 54.7% dos participantes, associando-se em uma análise bivariada de forma significativa (p<0.05) com as variáveis sociodemográficas: idade (≥ 60 anos), situação conjugal (sem companheiro), escolaridade (até o ensino fundamental completo/incompleto), renda familiar (≤ 1 salário mínimo). Quanto as variáveis clínicas, o nível de conhecimento insuficiente se associou de forma significativa com a não participação em grupo educativo, não utilização de insulina e não praticar atividade física. Em regressão logística se observou que os fatores que aumentam o risco para o conhecimento insuficientes foram: nunca ter participado de grupo educativo (OR=2.0), idade ≥ 60 anos (OR=2.2), escolaridade analfabeto e primário (OR=8.3) e renda menor ou igual a 1 salário mínimo (OR=2.4). Conclusão. O nível de conhecimento das pessoas com diabetes mellitus tipo 2 acerca de sua doença é insuficiente, sendo as características socioeconômicas e educacionais os fatores que aumentam as razões de chances do conhecimento insuficiente.

Anti-Leishmania amazonensis activity of the terpenoid fraction from Eugenia pruniformis leaves.

Leishmaniasis is caused by protozoan parasites belonging to the genus Leishmania and includes cutaneous, mucocutaneous and visceral clinical forms. Drugs currently available for leishmaniasis treatment present high toxicity, and development of parasite resistance. Plants constitute an important source of compounds with leishmanicidal potential. This study aimed to evaluate the anti-Leishmania amazonensis activity of the terpenoid fraction of Eugenia pruniformis leaves (TF-EpL). TF-EpL was active against the promastigote and intracellular amastigote forms of L. amazonensis with IC50(24h) value of 43.60µg/mL and 44.77µg/mL, respectively. TF-EpL altered the cell cycle of the parasite, increasing 2.32-fold the cells in the Sub-G0/G1 phase. TF-EpL also changed the ΔΨm and increased ROS and the number of annexin-V-PI positive promastigotes, which suggests incidental death. ß-sitosterol, ursolic acid, corosolic acid and asiatic acid were isolated from TF-EpL. The results showed the antileishmanial activity of E. pruniformis terpenoids and its potential for further studies as a source of new drugs for leishmaniasis.

Spirituality in coping with pain in oncological patients: systematic review / A espiritualidade no enfrentamento da dor em pacientes oncológicos: revisão sistemática

ABSTRACT BACKGROUND AND OBJECTIVES: The relationship between spirituality and cancer coping is still a challenge for comprehensive health care. Therefore, it is necessary to analyze whether the level of spirituality directly interferes with clinical markers, such as pain intensity in people with cancer. The present study aims to investigate the relationship between spirituality and pain coping and the strategies used in adult cancer patients. CONTENTS: This is a systematic review, registered in the International Prospective Register of Systematic Reviews: CRD42018108835. The search was performed in Pubmed, Medline, LILACS, Scielo, and ScienceDirect databases until May 2019, available in all languages. The search strategy was defined for the PubMed database as a parameter: (neoplasms or cancer) AND (spirituality) AND (pain). Adults patients with cancer of both genders who faced pain were studied. Studies that did not address the pain associated with spirituality were excluded. Of the 588 studies found, 13 were eligible. Among these, nine studies showed that spirituality contributes to positive pain coping. Regarding the level of spirituality, higher spiritual well-being was associated with lower pain intensity in three studies. The spiritual strategies used were mindfulness, meditation, relaxation, prayer, support from religious leaders and members. CONCLUSION: Despite the few studies found, the findings broaden the knowledge about the positive relationship between spirituality and pain coping and underline the spiritual strategies for the management of this health condition in cancer patients.

RESUMO JUSTIFICATIVA E OBJETIVOS: A relação entre espiritualidade e enfrentamento do câncer ainda é um desafio para o cuidado integral em saúde. Portanto, é necessário analisar se o nível de espiritualidade interfere diretamente nos marcadores clínicos, como na intensidade da dor em pessoas com câncer. O presente estudo teve como objetivo analisar a relação da espiritualidade com o enfrentamento da dor e as estratégias utilizadas em pacientes adultos oncológicos. CONTEÚDO: Trata-se de uma revisão sistemática, com registro na base International Prospective Register of Systematic Reviews: CRD42018108835. A busca foi realizada nas bases: Pubmed, Medline, LILACS, Scielo e ScienceDirect até maio de 2019, disponíveis em todos os idiomas. A estratégia de pesquisa foi definida para o banco de dados Pubmed como um parâmetro: (neoplasms or cancer) AND (spirituality) AND (pain). Foram estudados adultos com neoplasias, de ambos os sexos, que enfrentam a dor. Os estudos que não abordaram a dor associada à espiritualidade foram excluídos. Foram encontrados 588 estudos, sendo 13 elegíveis. Entre esses, nove estudos mostraram que a espiritualidade contribuiu no enfrentamento positivo da dor. Com relação ao nível de espiritualidade, o maior bem-estar espiritual esteve associado com menor intensidade da dor em três estudos. As estratégias espirituais utilizadas foram, mindfulness, meditação, relaxamento, oração, suporte de líderes e membros religiosos. CONCLUSÃO: Apesar dos poucos estudos encontrados, os achados ampliam o conhecimento sobre a relação positiva da espiritualidade com o enfrentamento da dor e evidencia as estratégias espirituais para o manejo dessa condição de saúde em pacientes oncológicos.

Leishmania amazonensis infection induces behavioral alterations and modulates cytokine and neurotrophin production in the murine cerebral cortex.

Neurological symptoms have been associated with Leishmania infection, however little is known about how the nervous system is affected in leishmaniasis. This work aimed to analyze parasitic load, production of cytokines/neurotrophins in the prefrontal cortex and behavioral changes in BALB/c mice infected with Leishmania amazonensis. At 2 and 4months post-infection, infected mice showed a decrease in IFN-γ, IL-1, IL-6, IL-4, IL-10 cytokines and BDNF and NGF neurotrophins in prefrontal cortex associated with increased anxiety behavior. Parasite DNA was found in brain of all animals at 4months post-infection, when the levels of IBA-1 (activated macrophage/microglia marker) and TNF-α was increased in the prefrontal cortex. However TNF-α returned to normal levels at 6months post-infection suggesting a neuroprotective mechanism.

The histopathological and immunological pattern of CBA mice infected with Leishmania amazonensis after treatment with pyrazole carbohydrazide derivatives.

Because there is no vaccine in clinical use, control of Leishmaniasis relies almost exclusively on chemotherapy and the conventional treatments exhibit high toxicity for patients and emerging drug resistance. Recently, we showed that oral treatment with synthetic pyrazole carbohydrazide compounds induced lower parasite load in draining lymph nodes and reduced skin lesion size without causing any toxic effects in an experimental murine infection model with Leishmania amazonensis. In this study, CBA mice were infected in the footpad with L. amazonensis and then orally treated with pyrazole carbohydrazides derivatives, such as BrNO(2), NO(2)Cl and NO(2)Br and their histopathological and immunological effects were then investigated. Epidermis and dermis had lower levels of inflammatory infiltration compared to the infected untreated control mice. In the dermis of treated animals, the numbers of vacuolated macrophages containing intracellular parasites were far lower than in infected untreated animals. In addition to dermal macrophages, we also observed a mixed inflammatory infiltrate containing lymphocytes and granulocyte cells. Lower numbers of B cells (B220+) and T lymphocytes (CD3+) were identified in the lesions of treated mice compared with the untreated, infected mice. In draining lymph node cells, the number of T lymphocytes (CD3+) was decreased, and the numbers of B cells (CD19+) and CD8+ T cells were increased in infected mice, when compared with the non-infected control group. In additional, we have shown that infected treated and untreated lymph node cells had similar levels of TGF-ß and IFN-γ mRNA expression, whereas IL-4 was expressed at a lower level in the treated group. Increased levels of the specific anti-Leishmania IgG2a or IgG3 antibody subclass were observed in NO(2)Cl or BrNO(2)-treated group, respectively. Overall, our experimental findings suggest that pyrazole carbohydrazides exert modulation of IL-4 expression and B cell levels; however, further evaluation is required to determine the optimal treatment regime.

4-(1H-Pyrazol-1-yl) benzenesulfonamide derivatives: identifying new active antileishmanial structures for use against a neglected disease.

Leishmaniasis is a neglected disease responsible for about 56,000 deaths every year. Despite its importance, there are no effective, safe and proper treatments for leishmaniasis due to strain resistance and/or drug side-effects. In this work we report the synthesis, molecular modeling, cytotoxicity and the antileishmanial profile of a series of 4-(1H-pyrazol-1-yl)benzenesulfonamides. Our experimental data showed an active profile for some compounds against Leishmania infantum and Leishmania amazonensis. The profile of two compounds against L. infantum was similar to that of pentamidine, but with lower cytotoxicity. Molecular modeling evaluation indicated that changes in electronic regions, orientation as well as lipophilicity of the derivatives were areas to improve the interaction with the parasitic target. Overall the compounds represent feasible prototypes for designing new molecules against L. infantum and L. amazonensis.

The in vivo activity of 1,3,4-thiadiazolium-2-aminide compounds in the treatment of cutaneous and visceral leishmaniasis.

OBJECTIVES: Researchers have recently investigated the biological activities of mesoionic (MI) compounds, which have shown in vitro activity against many species of Leishmania, as well as Trypanosoma cruzi. The main goal of this study was to evaluate and compare the activity of three MI compounds against Leishmania amazonensis and Leishmania infantum infection in vivo. METHODS: The experiments were carried out using BALB/c mice infected with L. amazonensis or L. infantum as a highly sensitive murine model. The infected mice were treated with MI-HH, MI-4-OCH(3), MI-4-NO(2) or meglumine antimoniate by different routes (intralesional, topical or intraperitoneal). RESULTS: Treatment with MI-4-OCH(3) and MI-4-NO(2) efficiently contained the progression of cutaneous and visceral leishmaniasis in comparison with the control group or mice treated with meglumine antimoniate. Interestingly, these MI compounds did not produce toxicological effects after treatment. Furthermore, treatment with these compounds led to a modulation of the immune response that was correlated with disease control. In this study, MI compounds, and MI-4-NO(2) in particular, exhibited high activity in the L. infantum murine model. In the L. amazonensis model, intralesional treatment with MI-4-OCH(3) or MI-4-NO(2) showed greater therapeutic efficacy than treatment with meglumine antimoniate, and the new topical formulations of these compounds also displayed great activity in the cutaneous leishmaniasis model. CONCLUSIONS: Upon comparison of each MI compound, MI-4-NO(2) was clearly the compound with the greatest activity in these two in vivo infection models by each administration route tested.

Synthesis and antileishmanial evaluation of 1-aryl-4-(4,5-dihydro-1H-imidazol-2-yl)-1H-pyrazole derivatives.

A series of 1-aryl-4-(4,5-dihydro-1H-imidazol-2-yl)-1H-pyrazoles (4a-g) and 5-amino-1-aryl-4-(4,5-dihydro-1H-imidazol-2-yl)-1H-pyrazoles (5a-g) were synthesized and evaluated in vitro against three Leishmania species: L. amazonensis, L. braziliensis and L. infantum (L. chagasi syn.). The cytotoxicity was assessed. Among the derivatives examined, six compounds emerged as the most active on promastigotes forms of L. amazonensis with IC(50) values ranging from 15 to 60 µM. The reference drug pentamidine presented IC(50)=10 µM. However, these new compounds were less cytotoxic than pentamidine. Based on these results, the more promising derivative 5d was tested further in vivo. This compound showed inhibition of the progression of cutaneous lesions in CBA mice infected with L. amazonensis relative to an untreated control.

Effect of oral treatment with pyrazole carbohydrazide derivatives against murine infection by Leishmania amazonensis.

Newly synthesized pyrazole carbohydrazide derivatives with substituents X = Br/Y = NO(2) and X = NO(2)/Y = Cl were independently investigated in the CBA mouse model of cutaneous leishmaniasis. Animals were infected with Leishmania amazonensis and treated two weeks after the parasitic infection with the pyrazole carbohydrazides for 45 days. Oral treatment with both compounds controlled evolution of footpad cutaneous lesions and dissemination of parasites to draining lymph nodes. Nitric oxide generation was observed in supernatants of lymph node cells from infected CBA mice that were treated with these compounds. The pyrazole carbohydrazide derivatives did not show any toxicity or cause alterations in body weight, plasma concentrations of alanine aminotransferase and aspartate aminotransferase, and urinary creatinine levels, but promoted a small decrease in blood neutrophils. These results provide new perspectives on the development of drugs with activities against leishmaniasis.

Antileishmanial activity of 1,3,4-thiadiazolium-2-aminide in mice infected with Leishmania amazonensis.

The efficacy of two mesoionic derivatives (MI-H-H and MI-4-OCH(3)) was evaluated in CBA/J mice infected with Leishmania amazonensis. Treatment with these compounds demonstrated that the MI-4-OCH(3) derivative and the reference drug meglumine antimoniate (Glucantime) presented significant activity relative to an untreated control. No apparent hepatic or renal toxicity due to these mesoionic compounds was found.

A comparative study of mesoionic compounds in Leishmania sp. and toxicity evaluation.

In this first study, a series of mesoionic compounds like 1,3,4-thiadiazolium-2-phenylamine derivatives were synthesized and studied in Leishmania amazonensis. The cytotoxic effects of these compounds on the host cells were investigated and the antileishmanial in vitro activity was compared with other species of Leishmania (Leishmania chagasi and Leishmania braziliensis). The compounds presented lower toxicity in murine macrophages than the reference drug pentamidine. The halogen derivatives 5, 6, 8 and 13 (4-F, 4-Cl, 4-Br and 3-Cl) were the most active compounds among all the species tested.

Synthesis and leishmanicidal activities of 1-(4-X-phenyl)-N'-[(4-Y-phenyl)methylene]-1H-pyrazole-4-carbohydrazides.

1H-pyrazole-4-carbohydrazides were synthesized and their leishmanicidal in vitro activities and cytotoxic effects were investigated. The drugs prototypes of these new compounds (ketoconazole, benznidazole, allopurinol and pentamidine) were also tested. It was found that among all the 1H-pyrazole-4-carbohydrazides derivatives examined, the most active compounds were those with X = Br, Y = NO2 (27) and X = NO2, Y = Cl (15) derivatives which showed to be most effective on promastigotes forms of L. amazonensis than on L. chagasi and L. braziliensis species. When tested against murine peritoneal macrophages as mammalian host cell controls of toxicity, 1-(4-Br-phenyl)-N'-[(4-NO(2)-phenyl)methylene]-1H-pyrazole-4-carbohydrazides (27) (EC50 = 50 microM l(-1)) and 1-(4-NO2-phenyl)-N'-[(4-Cl-phenyl)methylene]-1H-pyrazole-4-carbohydrazides (15) EC50 = 80 microM l(-1))] was reasonably toxic. However, both compounds were less toxic than pentamidine and ketoconazole. These results provide new perspectives on the development of drugs with activities against Leishmania parasite.

Cross-immunity experiments between different species or strains of Leishmania in rhesus macaques (Macaca mulatta).

This study evaluates cross-immunity in rhesus monkeys (Macaca mulatta) previously infected with one species of Leishmania and have had self-cured disease or were cured by antimony-based therapy upon development of full-blown disease. We found that a self-healing cutaneous leishmaniasis (CL) following experimental infection with Leishmania (Leishmania) major induces significant protection for L. (L.) amazonensis and L. (Viannia) guyanensis, and was dependent on time of re-challenge by L (L.) amazonensis after animals had recovered from primary lesions, but lacked protection against L. (V.) braziliensis. In contrast, monkeys that recovered from L. (V.) braziliensis CL or L. (L.) chagasi visceral leishmaniasis following chemotherapeutic intervention were protected by challenge with L. (V.) braziliensis and L (L.) amazonensis. These findings indicate the relative variability in protection after self-cure or drug-cured experimental leishmaniasis to challenge by heterologous leishmanial parasites. Further studying the immune response may provide information regarding relevant factors influencing cross-protective immunity.