TB treatment non-adherence in São Tomé and Príncipe.

SETTING: Sao Tomé and Principe (STP) is a lower middle-income country in the Gulf of Guinea that has a persistent high loss of TB patients on treatment. OBJECTIVE: To investigate factors associated with patient loss to follow-up (LTFU) and to assess health worker perceptions on non-adherence. DESIGN: A retrospective cohort study was conducted using data from the national database. Factors associated with LTFU were investigated using univariable and multivariable logistic regression. In-depth interviews were conducted with TB health workers to identify perceived barriers for treatment completion. RESULTS: A total of 822 registered patients with drug-susceptible TB were included, of whom 82 (10.0%) were lost to follow-up. Male sex (adjusted OR [aOR] 1.7, 95% CI 1.0-3.0; P = 0.048), as well as living in the Mé-Zóchi and Caué Districts (aOR 2.60, 95% CI 1.58-4.26; P < 0.001) were associated with an increased odds of LTFU. The main barriers to treatment completion were related to lack of food, stigma, and lack of patient information and personal support. CONCLUSION: The study indicates the need to address multiple issues related to LTFU during TB treatment. Enhanced efforts to personalise care, especially for information, nutrition and encouragement will better support patients in STP.

CONTEXTE: Sao Tomé-et-Principe (STP) est un pays à revenu moyen inférieur situé dans le golfe de Guinée qui présente une perte élevée et persistante de patients tuberculeux sous traitement. OBJECTIF: Étudier les facteurs associés à la perte de patients en cours de suivi (LTFU) et évaluer les perceptions des travailleurs de la santé sur la non-observance. MÉTHODE: Une étude de cohorte rétrospective a été réalisée à partir des données de la base nationale. Les facteurs associés à la LTFU ont été étudiés au moyen d'une régression logistique univariable et multivariable. Des entrevues en profondeur ont été menées auprès de travailleurs de la santé spécialisés dans la TB afin de déterminer les obstacles perçus à l'achèvement du traitement. RÉSULTATS: Au total, 822 patients enregistrés atteints de TB pharmacosensible ont été inclus, dont 82 (10,0%) ont été perdus de vue. Le sexe masculin (OR ajusté [ORa] 1,7 ; IC 95% 1,0­3,0 ; P = 0,048), ainsi que le fait de vivre dans les districts de Mé-Zóchi et de Caué (ORa 2,60 ; IC 95% 1,58­4,26 ; P < 0,001) étaient associés à une probabilité accrue d'abandon du traitement. Les principaux obstacles à l'achèvement du traitement étaient liés au manque de nourriture, à la stigmatisation et au manque d'information et de soutien personnel des patients. CONCLUSION: L'étude indique qu'il est nécessaire de s'attaquer aux multiples problèmes liés à LTFU pendant le traitement de la TB. Des efforts accrus pour personnaliser les soins, notamment en matière d'information, de nutrition et d'encouragement, permettront de mieux soutenir les patients en STP.

Renoprotective Effects of Luteolin: Therapeutic Potential for COVID-19-Associated Acute Kidney Injuries.

Acute kidney injury (AKI) has been increasingly reported in critically-ill COVID-19 patients. Moreover, there was significant positive correlation between COVID-19 deaths and renal disorders in hospitalized COVID-19 patients with underlying comorbidities who required renal replacement therapy. It has suggested that death in COVID-19 patients with AKI is 3-fold higher than in COVID-19 patients without AKI. The pathophysiology of COVID-19-associated AKI could be attributed to unspecific mechanisms, as well as COVID-19-specific mechanisms such as direct cellular injury, an imbalanced renin-angiotensin-aldosterone system, pro-inflammatory cytokines elicited by the viral infection and thrombotic events. To date, there is no specific treatment for COVID-19 and its associated AKI. Luteolin is a natural compound with multiple pharmacological activities, including anticoronavirus, as well as renoprotective activities against kidney injury induced by sepsis, renal ischemia and diverse nephrotoxic agents. Therefore, in this review, we mechanistically discuss the anti-SARS-CoV-2 and renoprotective activities of luteolin, which highlight its therapeutic potential in COVID-19-AKI patients.

Nitric oxide and immune response in infection control of Caseous Lymphadenitis / Óxido nítrico e resposta imune no controle de infecção da Linfadenite Caseosa

This study aimed to evaluate aspects of host immune response using an experimental infection model of Corynebacterium pseudotuberculosis (CP) in C57/Black6 wild-type and knockout for nitric oxide (KO-NO) mice. 28 mice were evaluated: 4 wild-type controls; 10 wild-type infected with CP; 4 KO-NO controls; 10 KO-NO infected with CP. Infection procedures were carried out by intraperitoneal inoculation using 107. Infected C57/Black6 KO-NO mice began to die after the 5° day post-inoculation, up until the 14º day. Neutrophils were found in increased numbers in the infiltrate of KO-NO murine peritoneal cavities. Examination of splenic tissue revealed an accumulation of lymphocytes, predominantly CD8 T-cells, in experimental animal groups. KO-NO animals were found to have a predominance of granulomas 7 days post-inoculation, primarily in the lymph nodes. In addition, greater amounts of bacteria were recovered from the mesenteric lymph nodes of KO-NO mice. There was no statistically significant difference in the levels of total IgG and its subclasses 14 days post-inoculation between KO-NO and wild groups. The results suggest the importance of nitric oxide in the process of controlling CP infection, as KO-NO animals were observed to be markedly more affected by infection with this bacterium.(AU)

O objetivo deste estudo foi avaliar os aspectos da resposta imune do hospedeiro, mediante o uso de um modelo experimental de infecção de Corynebacterium pseudotuberculosis (CP) em camundongos C57/Black6 do tipo selvagem e em C57/Black6 knockout para o óxido nítrico (KO-NO). Foram avaliados 28 camundongos: quatro controles de tipo selvagem; 10 do tipo selvagem infectados com CP; quatro controles KO-NO; e 10 KO-NO infectados com CP. A infecção foi realizada via intraperitoneal, usando-se 107. Os animais C57/Black6 KO-NO infectados começaram a vir a óbito no quinto dia pós-inoculação, o que aconteceu até o 14º dia. Um número maior de neutrófilos foi encontrado na sua cavidade peritoneal. O exame do baço revelou um acúmulo de linfócitos, predominantemente células T CD8, nos grupos de animais experimentais. Nos animais KO-NO, foi observada a presença de granulomas, sete dias pós-inoculação, principalmente nos gânglios linfáticos. Além disso, uma maior quantidade de bactérias foi detectada dos linfonodos mesentéricos desses animais. Não houve diferença estatisticamente significante nos níveis séricos IgG total e em suas subclasses aos 14 dias pós-inoculação nos grupos KO-NO e selvagem. Os resultados obtidos sugerem a importância do óxido nítrico no processo de controle da infecção por CP.(AU)

Role of Porphyromonas gingivalis HmuY in Immunopathogenesis of Chronic Periodontitis.

Periodontitis is a multifactorial disease, with participation of bacterial, environmental, and host factors. It results from synergistic and dysbiotic multispecies microorganisms, critical "keystone pathogens," affecting the whole bacterial community. The purpose of this study was to review the role of Porphyromonas gingivalis in the immunopathogenesis of chronic periodontitis, with special attention paid to HmuY. The host response during periodontitis involves the innate and adaptive immune system, leading to chronic inflammation and progressive destruction of tooth-supporting tissues. In this proinflammatory process, the ability of P. gingivalis to evade the host immune response and access nutrients in the microenvironment is directly related to its survival, proliferation, and infection. Furthermore, heme is an essential nutrient for development of these bacteria, and HmuY is responsible for its capture from host heme-binding proteins. The inflammatory potential of P. gingivalis HmuY has been shown, including induction of high levels of proinflammatory cytokines and CCL2, decreased levels of IL-8, and increased levels of anti-HmuY IgG and IgG1 antibodies in individuals with chronic periodontitis. Therefore, the HmuY protein might be a promising target for therapeutic strategies and for development of diagnostic methods in chronic periodontitis, especially in the case of patients with chronic periodontitis not responding to treatment, monitoring, and maintenance therapy.

Osteoporosis/osteopenia as an independent factor associated with periodontitis in postmenopausal women: a case-control study.

UNLABELLED: This study investigated whether osteoporosis/osteopenia has an influence on the progression of periodontitis in postmenopausal women. The findings highlight that postmenopausal women with osteoporosis/osteopenia had a greater chance of presenting periodontitis than those with normal bone mineral density, particularly among nonusers of osteoporosis medications and women with a greater number of remaining teeth, showing that osteoporosis/osteopenia has had an influence on the progression of periodontitis. INTRODUCTION: This study investigated whether osteoporosis/osteopenia has an influence on the progression of periodontitis in postmenopausal women and explored the effects of use of osteoporosis medication and tooth loss on this association. METHODS: This case-control study involved 521 postmenopausal women, with minimum age of 50 years, in Feira de Santana, Bahia, Brazil. Sociodemographic characteristics, health conditions/medications, and lifestyle habits were recorded. A complete periodontal examination was performed and periodontitis was diagnosed. Bone mineral density was evaluated through lumbar spine and femoral bone densitometry, obtained using dual-energy X-ray absorptiometry. Logistic regression was used to calculate the strength of association between the occurrences of osteoporosis/osteopenia and periodontitis. RESULTS: Women with osteoporosis/osteopenia were twice as likely to present periodontitis, as were those with normal bone mineral density, even after adjusting for smoking, age, family income, and last visit to dentist (odds ratios (OR)adjusted=2.24, 95% CI [1.24-4.06], p=0.008). Among nonusers of osteoporosis medication (ORadjusted=2.51, 95% CI [1.33-4.73], p=0.004) and women with at least 10 remaining teeth (ORadjusted=2.50 95% CI [1.18-5.27], p=0.02), the odds ratio was higher and statistically significant. CONCLUSIONS: These findings highlight that postmenopausal women with osteoporosis/osteopenia had a greater chance of presenting periodontitis than those with normal bone mineral density, particularly among nonusers of osteoporosis medications and women with a greater number of remaining teeth.

Induction of interleukin (IL)-1ß, IL-10, IL-8 and immunoglobulin G by Porphyromonas gingivalis HmuY in humans.

BACKGROUND AND OBJECTIVE: Porphyromonas gingivalis, an anaerobic gram-negative bacterium, is associated with chronic periodontitis. This study was undertaken to evaluate the production of interleukin (IL)-1ß, IL-8 and IL-10 by human peripheral blood mononuclear cells (PBMC) stimulated with P. gingivalis antigens and to assess the levels of serum immunoglobulin (Ig)G, IgA and IgG subclasses raised against P. gingivalis HmuY protein. MATERIAL AND METHODS: PBMC from patients with chronic periodontitis (CP) and from nonperiodontitis (NP) control subjects were stimulated with P. gingivalis antigens, and the cytokine levels in the culture supernatants were determined by ELISA. The specificity of serum antibodies raised against HmuY was analyzed by Western blotting and by ELISA. RESULTS: Compared with the NP controls, the CP patients produced higher levels of total serum IgG and IgG1 specific for P. gingivalis HmuY. No differences were found between CP and NP groups in the production of IL-1ß and IL-8 by PBMC stimulated with total P. gingivalis antigens. Only P. gingivalis lipopolysaccharide (LPS) induced higher levels of IL-10 in the CP group. Higher levels of IL-1ß and IL-10 were induced by HmuY than by other antigens derived from the wild-type P. gingivalis strains. In contrast, total antigens derived from the hmuY-deletion mutant strain induced the production of significantly higher levels of IL-8 and significantly lower levels of IL-1ß. CONCLUSION: Our data suggest that P. gingivalis HmuY may be considered an immunogenic protein associated with host-pathogen interactions.

Genotoxic effects of X-rays on keratinized mucosa cells during panoramic dental radiography.

OBJECTIVES: The aim of this study was to evaluate the genotoxic effects of X-rays on epithelial gingival cells during panoramic dental radiography using a differentiated protocol for the micronucleus test. METHODS: 40 healthy individuals who underwent this procedure for diagnostic purposes on request from their dentists agreed to participate in this study. All of them answered a questionnaire before the examination. Epithelial gingival cells were obtained from the keratinized mucosa of the upper dental arcade by gentle scraping with a cervical brush immediately before exposure and 10 days later. Cytological preparations were stained according to the Feulgen-Rossenbeck reaction, counterstained with fast green 1% for 1 min and analysed under a light microscope. Micronuclei, nuclear projections (broken eggs) and degenerative nuclear alterations (pyknosis, karyolysis, karyorrhexis and condensed chromatin) were scored. RESULTS: The frequency of micronuclei was significantly higher after exposure (P < 0.05), as were the frequencies of nuclear alterations indicative of apoptosis (P < 0.001). CONCLUSIONS: These results indicate that X-ray radiation emitted during panoramic dental radiography induces a genotoxic effect on epithelial gingival cells that increases the frequency of chromosomal damage and nuclear alterations indicative of apoptosis.

Radiographic features of periodontal bone defects: evaluation of digitized images.

OBJECTIVES: Radiographic evaluation of periodontal conditions is a difficult process because of the many limitations inherent to this complementary examination and the lack of image specificity for different types of bone defects. The objectives of this study are to utilize digitized imaging resources to describe the radiographic features of different types of periodontal bone defects produced artificially in dry mandibles. METHODS: 14 dry mandibles were utilized, in which periodontal bone defects were produced. Digital photographs and conventional radiographs of each site were obtained in a standardized manner, before and after producing these defects. The radiographs were then digitized, displayed on the screen and evaluated by three examiners. RESULTS: Most of the bone defects presented distinct imaging characteristics that allowed them to be identified, with the exception of one-, two- and three-wall infrabony defects. The defects that were most easily interpreted were horizontal and vertical defects and the most difficult were defects in the radicular septum. CONCLUSIONS: Despite the importance of imaging diagnoses in reaching clinical decisions regarding treatment, such diagnoses for different types of periodontal bone defects are extremely difficult to make. In the present study, the utilization of digital tools for interpreting digitized radiographic images facilitated the process.

Genetic damage in exfoliated cells from oral mucosa of individuals exposed to X-rays during panoramic dental radiographies.

The genotoxic effects of X-ray emitted during dental panoramic radiography were evaluated in exfoliated cells from oral epithelium through a differentiated protocol of the micronucleus test. Thirty-one healthy individuals agreed to participate in this study and were submitted to this procedure for diagnosis purpose after being requested by the dentist. All of them answered a questionnaire before the examination. Cells were obtained from both sides of the cheek by gentle scrapping with a cervical brush, immediately before the exposure and after 10 days. Cytological preparations were stained according to Feulgen-Rossenbeck reaction and analyzed under light and laser scanning confocal microscopies. Micronuclei, nuclear projections (buds and broken eggs) and degenerative nuclear alterations (condensed chromatin, karyolysis and karyorrhexis) were scored. The frequencies of micronuclei, karyolysis and pycnosis were similar before and after exposure (P > 0.90), whereas the condensation of the chromatin and the karyorrhexis increased significantly after exposure (P < 0.0001). In contrast, both bud and broken egg frequencies were significantly higher before the examination (P < 0.005), suggesting that these structures are associated to the normal epithelium differentiation. The results suggest that the X-ray exposure during panoramic dental radiography induces a cytotoxic effect by increasing apoptosis. We also believe that the score of other nuclear alterations in addition to the micronucleus improves the sensitivity of genotoxic effects detection.