A Single Mindfulness-Based Meditation Session Can Produce Reductions in Cardiovascular Risk in Hypertensive Patients: A Pilot Study.

BACKGROUND: Several non-drug treatment approaches for systemic arterial hypertension have been studied aimed at reducing the adverse effects of this clinical condition. In addition to exercise training, which already has many of its modalities consolidated in the scientific field, body and mind practices have gained strength and deserve attention in the science and treatment of hypertension. The literature shows that meditation practices have numerous health benefits, one of which is blood pressure (BP) control. OBJECTIVE: This study aimed to evaluate the acute effects of a single mindfulness-based meditation on BP in adults with hypertension. METHODS: Research was developed that evaluated the BP of 5 adult women with controlled hypertension. As a data collection instrument, we used 2 sessions of ambulatory BP monitoring (ABPM): the first was a control session and the second a meditation session. Systolic (SBP), diastolic (DBP) and mean blood pressure (MBP) were evaluated at the pre- and post-session in addition to heart rate (HR), with clinical and ambulatorial measurements, during the day, night, morning surge and a 24-hour period. Data analysis was performed using one-way analysis of variance (ANOVA) for the ABPM data and two-way ANOVA to analyze blood pressure. RESULTS: The main results found were a statistically significant reduction in SBP in the morning and a tendency toward a significant decrease in MBP during the same period (P = .057). There were no significant changes in the other variables analyzed. CONCLUSION: Therefore, we concluded that a single meditation session was effective only in reducing morning SBP.

Gonadotroph tumours with a low SF-1 labelling index are more likely to recur and are associated with enrichment of the PI3K-AKT pathway.

AIMS: The gonadotroph tumour (GT) is the most frequently resected pituitary neuroendocrine tumour. Although many symptomatic GT are successfully resected, some recur. We sought to identify histological biomarkers that may predict recurrence and explore biological mechanisms that explain this difference in behaviour. METHODS: SF-1 immunohistochemistry of 51 GT, a subset belonging to a longitudinal prospective cohort study (n = 25), was reviewed. Four groups were defined: Group 1-recently diagnosed GT (n = 20), Group 2-non-recurrent GT with long-term follow up (n = 11), Group 3-initial resections of GT that recur (n = 7) and Group 4-recurrent GT (n = 13). The percentage of SF-1 immunolabelling in the lowest staining fields (SF-1 labelling index (SLI)) was assessed and RNA sequencing was performed on 5 GT with SLI <80% and 5 GT with SLI >80%. RESULTS: Diffuse, strong SF-1 immunolabelling was the most frequent pattern in Groups 1/2, whereas patchy SF-1 staining predominated in Groups 3/4. There was a lower median SLI in Groups 3/4 than 1/2. Overall, GT with SLI <80% recurred earlier than GT with SLI >80%. Differential expression analysis identified 89 statistically significant differentially expressed genes (FDR <0.05) including over-expression of pituitary stem cell genes (SOX2, GFRA3) and various oncogenes (e.g. BCL2, ERRB4) in patchy SF-1 GT. Gene set enrichment analysis identified significant enrichment of genes involved in the PI3K-AKT pathway. CONCLUSIONS: We speculate that patchy SF-1 labelling in GT reflects intratumoural heterogeneity and are less differentiated tumours than diffusely staining GT. SF-1 immunolabelling patterns may have prognostic significance in GT, but confirmatory studies are needed for further validation.

Identification and in silico characterization of structural and functional impacts of genetic variants in milk protein genes in the Zebu breeds Guzerat and Gyr.

Whole genome sequencing of bovine breeds has allowed identification of genetic variants in milk protein genes. However, functional repercussion of such variants at a molecular level has seldom been investigated. Here, the results of a multistep Bioinformatic analysis for functional characterization of recently identified genetic variants in Brazilian Gyr and Guzerat breeds is described, including predicted effects on the following: (i) evolutionary conserved nucleotide positions/regions; (ii) protein function, stability, and interactions; (iii) splicing, branching, and miRNA binding sites; (iv) promoters and transcription factor binding sites; and (v) collocation with QTL. Seventy-one genetic variants were identified in the caseins (CSN1S1, CSN2, CSN1S2, and CSN3), LALBA, LGB, and LTF genes. Eleven potentially regulatory variants and two missense mutations were identified. LALBA Ile60Val was predicted to affect protein stability and flexibility, by reducing the number the disulfide bonds established. LTF Thr546Asn is predicted to generate steric clashes, which could mildly affect iron coordination. In addition, LALBA Ile60Val and LTF Thr546Asn affect exonic splicing enhancers and silencers. Consequently, both mutations have the potential of affecting immune response at individual level, not only in the mammary gland. Although laborious, this multistep procedure for classifying variants allowed the identification of potentially functional variants for milk protein genes.

Morestin Syndrome Beyond Thoracic Trauma.

Morestin syndrome (MS) is a rare clinical manifestation consequent to an acute compression trauma to the thorax. In such an event, the sudden elevated pressure that happens to the airway and the rapid and retrograde blood flow results in capillary rupture in the head and neck vessel territory. This case reports a car accident victim that was dragged by a truck down a road with closed thoracic trauma resulting in MS. The patient presented with ecchymotic mask, neck and facial cyanosis and petechiae, ocular hemorrhage, otorrhagia, left clavicle fracture and spleen laceration that resolved with conservative measures. In this article, the authors present a specific acute syndrome due to trauma, with potential severe complications that should be recognized early and subject to a multidisciplinary and systemic approach in the emergency setting.

The role of Crooke's changes in recurrence and remission after gamma knife radiosurgery.

PURPOSE: The objective of this study is to evaluate the role of Crooke's changes (CC) in normal the peri-tumoral anterior pituitary gland, in patients with Cushing's disease (CD) with a histopathological confirmed corticotroph adenoma, and determine if there is any difference in the recurrence and remission rates in CD patients after treatment with Gamma Knife Radiosurgery (GKRS). METHODS: All patients treated with GKRS for CD from 2005 to 2016 at our institution were identified. Patients had a confirmed adrenocorticotropic (ACTH)-secreting adenoma, i.e. corticotroph adenoma, and normal pituitary gland included in the surgical specimen, and specimens were stained with hematoxylin and eosin and also immunostaining for cytokeratin and ACTH. Statistical analyses were performed in a total of 61 patients who met the inclusion criteria. Additionally, we analyzed 20 patients in each group, with and without CC, after they were matched in a propensity score fashion. RESULTS: Endocrine remission defined as, a normal 24 h urine free cortisol while off suppressive medication, occurred in 48 patients (78.7%), with 76.9% in those with CC and 81.8% in those without CC. There was no statistical significant difference between the two groups in regarding remission (p = 0.312) or recurrence (p = 0.659) in either the unmatched or matched cohorts. CONCLUSION: The presence or absence of CC in normal pituitary gland does not appear to confer a lower rate of remission or a higher rate of recurrence after GKRS. Patients with pituitary corticotroph adenomas that present with CC features may be well served by Stereotactic radiosurgery (SRS).

Increased intratumoral infiltration in IDH wild-type lower-grade gliomas observed with diffusion tensor imaging.

PURPOSE: Diffuse lower grade gliomas (LGG) with isocitrate dehydrogenase (IDH) gene mutations (IDHMUT) have a distinct survival advantage compared with IDH wild-type (IDHWT) cases but the mechanism underlying this disparity is not well understood. Diffusion Tensor Imaging (DTI) has identified infiltrated non-enhancing tumor regions that are characterized by low isotropic (p) and high anisotropic (q) diffusion tensor components that associate with poor survival in glioblastoma. We hypothesized that similar regions are more prevalent in IDHWT (vs. IDHMUT) LGG. METHODS: p and q maps were reconstructed from preoperative DTI scans in N = 41 LGG patients with known IDH mutation and 1p/19q codeletion status. Enhancing and non-enhancing tumor volumes were autosegmented from standard (non-DTI) MRI scans. Percentage non-enhancing tumor volumes exhibiting low p and high q (Vinf) were then determined using threshold values (p = 2 × 10-3mm2/s, q = 3 × 10-4 mm2/s) and compared between IDHWT and IDHMUT LGG, and between IDHMUT LGG with and without 1p/19q codeletion. RESULTS: Vinf volumes were significantly larger in IDHWT LGG than in IDHMUT LGG (35.4 ± 18.3% vs. 15.9 ± 7.6%, P < 0.001). Vinf volumes did not significantly differ between IDHMUT LGG with and without 1p/19q codeletion (17.1 ± 9.5% vs. 14.8 ± 5.8%, P = 1.0). CONCLUSION: IDHWT LGG exhibited larger volumes with suppressed isotropic diffusion (p) and high anisotropic diffusion (q) which reflects regions with increased cell density but non-disrupted neuronal structures. This may indicate a greater prevalence of infiltrative tumor in IDHWT LGG.

Oligodendroglioma confers higher risk of radiation necrosis.

BACKGROUND: Radiation therapy (RT) remains a mainstay for the treatment of lower grade gliomas. Radiation neurotoxicity is a serious complication, carrying high morbidity in the absence of tumor progression. The incidence remains poorly categorized and known risk factors identified are related to the radiation modality. We hypothesized that patients with oligodendroglioma have a higher risk of radiation necrosis (RN) as compared to patients with astrocytoma. METHODS: We conducted a retrospective review of adults with lower grade diffuse gliomas over a 10-year span. The primary outcome was RN, either pathologically confirmed or clinically diagnosed. Cases without pathological confirmation must have been symptomatic, requiring administration of bevacizumab or high-dose steroids. Cox proportional hazard ratios were used for multivariate analyses. RESULTS: In 319 patients, we identified RN in 41 patients (12.9%): 28 patients (21.3%) with oligodendroglioma and 13 (6.9%) with astrocytoma (HR 3.42, p < 0.001). Patients with oligodendroglioma who received > 54 Gy had a higher incidence (31.2%) than those receiving ≤ 54 Gy (14.3%, HR 6.9, p = 0.002). There was no similar correlation among patients with astrocytoma. There was no difference in incidence based on use of concomitant temozolomide. Radiation necrosis appeared within 24 months from radiation in 80.5% of patients. CONCLUSION: Our study suggests that patients with oligodendroglioma are at higher risk of developing RN. The incidence increases with increasing radiation dose in patients with oligodendroglioma but not with astrocytoma. RN usually appears within 24 months from RT. Patients with oligodendroglioma receiving > 54 Gy are at highest risk.

Tumor pharmacokinetics and pharmacodynamics of the CDK4/6 inhibitor ribociclib in patients with recurrent glioblastoma.

INTRODUCTION: We conducted a phase Ib study (NCT02345824) to determine whether ribociclib, an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), penetrates tumor tissue and modulates downstream signaling pathways including retinoblastoma protein (Rb) in patients with recurrent glioblastoma (GBM). METHODS: Study participants received ribociclib (600 mg QD) for 8-21 days before surgical resection of their recurrent GBM. Total and unbound concentrations of ribociclib were measured in samples of tumor tissue, plasma, and cerebrospinal fluid (CSF). We analyzed tumor specimens obtained from the first (initial/pre-study) and second (recurrent/on-study) surgery by immunohistochemistry for Rb status and downstream signaling of CDK4/6 inhibition. Participants with Rb-positive recurrent tumors continued ribociclib treatment on a 21-day-on, 7-day-off schedule after surgery, and were monitored for toxicity and disease progression. RESULTS: Three participants with recurrent Rb-positive GBM participated in this study. Mean unbound (pharmacologically active) ribociclib concentrations in plasma, CSF, MRI-enhancing, MRI-non-enhancing, and tumor core regions were 0.337 µM, 0.632 µM, 1.242 nmol/g, 0.484 nmol/g, and 1.526 nmol/g, respectively, which exceeded the in vitro IC50 (0.04 µM) for inhibition of CDK4/6 in cell-free assay. Modulation of pharmacodynamic markers of ribociclib CDK 4/6 inhibition in tumor tissues were inconsistent between study participants. No participants experienced serious adverse events, but all experienced early disease progression. CONCLUSIONS: This study suggests that ribociclib penetrated recurrent GBM tissue at concentrations predicted to be therapeutically beneficial. Our study was unable to demonstrate tumor pharmacodynamic correlates of drug activity. Although well tolerated, ribociclib monotherapy seemed ineffective for the treatment of recurrent GBM.

Whole genome sequencing of Guzerá cattle reveals genetic variants in candidate genes for production, disease resistance, and heat tolerance.

In bovines, artificial selection has produced a large number of breeds which differ in production, environmental adaptation, and health characteristics. To investigate the genetic basis of these phenotypical differences, several bovine breeds have been sequenced. Millions of new SNVs were described at every new breed sequenced, suggesting that every breed should be sequenced. Guzerat or Guzerá is an indicine breed resistant to drought and parasites that has been the base for some important breeds such as Brahman. Here, we describe the sequence of the Guzerá genome and the in silico functional analyses of intragenic breed-specific variations. Mate-paired libraries were generated using the ABI SOLiD system. Sequences were mapped to the Bos taurus reference genome (UMD 3.1) and 87% of the reference genome was covered at a 26X. Among the variants identified, 2,676,067 SNVs and 463,158 INDELs were homozygous, not found in any database searched, and may represent true differences between Guzerá and B. taurus. Functional analyses investigated with the NGS-SNP package focused on 1069 new, non-synonymous SNVs, splice-site variants (including acceptor and donor sites, and the conserved regions at both intron borders, referred to here as splice regions) and coding INDELs (NS/SS/I). These NS/SS/I map to 935 genes belonging to cell communication, environmental adaptation, signal transduction, sensory, and immune systems pathways. These pathways have been involved in phenotypes related to health, adaptation to the environment and behavior, and particularly, disease resistance and heat tolerance. Indeed, 105 of these genes are known QTLs for milk, meat and carcass, production, reproduction, and health traits. Therefore, in addition to describing new genetic variants, our approach provided groundwork for unraveling key candidate genes and mutations.

The influence of non-steroidal anti-inflammatory drugs and paracetamol used for pain control of orthodontic tooth movement: a systematic review.

The present study aimed to perform a systematic literature review to determine if there is a non-steroidal anti-inflammatory drug (NSAID) that interferes less within tooth movement. This research was performed according to the PRISMA statement. Articles were searched in eight electronic databases (PubMed, Scopus, Embase, Web of Science, LILACS, SciELO, Google Scholar, and Open Grey). Only experimental studies on male Wistar rats were selected, which included experiments related to the influence of NSAIDs on orthodontic movement. Studies in animals with pathological conditions, literature review articles, letters to the editor and/or editorials, case reports, abstracts, books, and book chapters were excluded. Each of the steps of this systematic literature review was performed by two examiners independently. RESULTS: the total sample consisted of 505 articles, from which 6 studies were eligible after a qualitative analysis. From the drugs assessed, paracetamol was unanimous for not interfering within orthodontic movement when compared to the control group. However, drugs such as aspirin, ibuprofen, sodium diclofenac, and selective cyclooxygenase-2 inhibitors caused a reduction in tooth movement when compared to the control group. CONCLUSION: paracetamol could be considered the drug of choice for pain relief because it interferes less within tooth movement.

Atypical Choroid Plexus Tumor of the Cauda Equina With Metastases to the Spinal Cord and Brain.

We report a case of a 57-year-old man with a tumor arising from the cauda equina with spinal cord and intracranial metastases in the basal cisterns and along the cranial nerves. He presented with severe lower back pain and mild gait imbalance. His imaging revealed a large mass in the lumbosacral region with involvement of the cauda equina, intradural extramedullary enhancing metastases in the thoracic spinal canal, and intracranial metastases in the suprasellar cistern and along both trigeminal and facial/vestibulocochlear nerve complexes. Pathological examination of the resected thoracic spinal cord mass showed an atypical papillary proliferation with moderate nuclear pleomorphism and rare mitotic figures. While the morphologic and immunophenotypic features were consistent with the diagnosis of a choroid plexus tumor, the atypical location for this entity required the exclusion of other epithelioid tumors with papillary architecture. Additional immunohistochemical markers were used to exclude a metastatic adenocarcinoma, a papillary variant of a meningioma, and a papillary variant of an ependymoma. Ultimately, methylation-based tumor profiling determined that the methylation class was a match for "plexus tumor" resulting in the integrated diagnosis of the tumor with features of choroid plexus papilloma. This is a unique presentation for both the location and the metastatic spread. The methylation profile was instrumental in establishing this diagnosis.

Wound healing of dehiscence defects following different root conditioning modalities: an experimental study in dogs.

OBJECTIVE: The purpose of this study was to investigate the periodontal healing pattern of dehiscence-type defects following different chemical root conditioning modalities. MATERIALS AND METHODS: Buccal osseous dehiscence defects were created on six teeth of seven dogs. After dental plaque accumulation, defects were treated with sterile saline solution (control group) or one chemical conditioning modality: citric acid (CA group), ethylenediaminetetraacetic acid (EDTA group), tetracycline (TTC group), citric acid + tetracycline (CA + TTC group), or tetracycline + citric acid (TTC + CA group). After 3 months of healing, clinical parameters were evaluated, and the animals were killed. Histological sections were processed, and a computer-assisted histometric analysis was used to evaluate the formation of new cementum, new bone, and epithelial apical migration. RESULTS: All treatments yielded significant improvements in terms of probing depth decrease and clinical attachment level gain compared to baseline values; however, without significant differences among the groups (p > 0.05; one-way ANOVA). The highest amount of new cementum was noted in the EDTA group (3.72 ± 0.83 mm, 77.6 %), while the lowest amount of new bone was observed in the TTC group (0.7 ± 0.94 mm, 14.3 %). However, no statistically significant differences could be observed among the groups regarding epithelial apical migration, new cementum, and alveolar bone formation (p > 0.05). CONCLUSION: Chemical root surface conditioning did not promote any significant improvement in periodontal healing pattern of dehiscence-type defects in dogs. CLINICAL RELEVANCE: Chemical root surface conditioning after surgical debridement did not promote positive or negative effects on periodontal healing pattern of dehiscence-type defects.

Combined Effect of Plasma-Activated Water and Topotecan in Glioblastoma Cells.

The increase in cancer diagnoses and cancer deaths, severe side effects of existing treatments and resistance to traditional treatments have generated a need for new anticancer treatments. Glioblastoma multiforme (GBM) is the most common, malignant and aggressive brain cancer. Despite many innovations regarding GBM treatment, the final outcome is still very poor, making it necessary to develop new therapeutic approaches. Cold atmospheric plasma (CAP) as well as plasma-activated liquids (PAL) are being studied as new possible approaches against cancer. The anticancer activity of PAL such as "plasma-activated water" (PAW) is dependent on the reactive chemical compounds present in the solution. Possible combinatory effects with conventional therapies, such as chemotherapeutics, may expand the potential of PAL for cancer treatment. We aim to explore the therapeutic properties of a combination of PAW and topotecan (TPT), an antineoplastic agent with major cytotoxic effects during the S phase of the cell cycle, on a GBM cancer cell line (U-251mg). Combined treatments with PAW and TPT showed a reduction in the metabolic activity and cell mass, an increase in apoptotic cell death and a reduction in the long-term survival. Single applications of PAW+TPT treatments showed a cytotoxic effect in the short term and an antiproliferative effect in the long term, warranting future exploration of combining PAW with chemotherapeutic agents as new therapeutic approaches.

Pediatric-type diffuse low-grade glioma with MYB/MYBL1 alteration: report of 2 cases.

2016 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) has shown how molecular features can impact the classification of brain tumors. The continued combination of molecular features with histopathology has led to distinguish tumors with similar histopathologic features but distinct clinical prognosis. The 2021 revised 5. edition of the WHO classification further includes molecular features for CNS tumor categorization including MYB/MYBL1 altered diffuse astrocytoma which is a newly recognized type of low-grade pediatric-type brain tumor. We discuss imaging features of two pediatric-type low-grade gliomas with MYB/MYBL1-mutation that encountered at our institution.

Tarballs on the Brazilian coast in late 2022 sustain Lepas anatifera Linnaeus, 1758 (Crustacea: Cirripedia): Occurrence and risk of petroleum hydrocarbon ingestion.

Since the 2019 oil spill on the northeastern coast of Brazil, oil materials have washed up on the beaches. A characteristic of the recent oil spill that began in late August was that some of the oiled material, such as tarballs, contained the goose barnacle species Lepas anatifera (Cirripedia, Lepadomorpha), which is well-known for its cosmopolitan distribution and wide occurrence in the oceans. The findings of this study provide information on the occurrence and contamination of petroleum hydrocarbons in animals adhered to the surfaces of tarballs sampled from beaches in the Brazilian states of Ceará and Rio Grande do Norte, between September and November 2022. The size of the barnacles varied from 0.122 to 2.20 cm, suggesting that the tarballs had been floating in the ocean for at least a month. All groups of L. anatifera collected from the tarballs had polycyclic aromatic hydrocarbons (PAHs) present (∑21PAHs from 476.33 to 3816.53 ng g-1). In comparison to high-molecular-weight PAHs, which are primarily from pyrolytic sources, low-molecular-weight PAHs, such as naphthalene and phenanthrene, which are mostly related to petrogenic sources, were shown to be more abundant. In addition, dibenzothiophene, which is exclusive of petrogenic origin, was found in all samples (30.74-537.76 ng g-1). The aliphatic hydrocarbons (AHs): n-alkanes, pristane, and phytane were also found and displayed petroleum characteristics. These results highlight the danger of increasing the absorption of petrogenic PAHs and AHs by organisms that use tarballs as substrates. L. anatifera is a crucial component of the food chain because many animals such as crabs, starfish, and gastropods consume it.

Characterization of Oral Candida spp. Biofilms in Children and Adults Carriers from Eastern Europe and South America.

BACKGROUND: Candida albicans and non-Candida albicans Candida species (NCACs) are known to colonize and invade various tissues, including the oral mucosa. In this work, we aimed to characterize mature biofilms of several Candida spp. clinical isolates (n = 33) obtained from the oral mucosa of children, adults, and elders of Eastern Europe and South America. METHODS: Each strain was evaluated for its capacity to form biofilms in terms of total biomass using the crystal violet assay and for matrix components production (proteins and carbohydrates) using the BCA and phenol-sulfuric tests, respectively. The effect of different antifungals on biofilm formation was studied. RESULTS: in the children's group, a predominance of C. krusei (81%) was observed, while, among adults, the main species was C. albicans (59%). Most strains showed a reduced response to antimicrobial drugs when in biofilm form (p < 0.01). Moreover, it was observed that strains isolated from children produced more matrix, with higher levels of protein and polysaccharides. CONCLUSIONS: children were more likely to be infected by NCACs than adults. More importantly, these NCACs were able to form biofilms richer in matrix components. This finding is of clinical importance, particularly in pediatric care, since stronger biofilms are highly associated with antimicrobial resistance, recurrent infections, and higher therapeutic failure.

Violacein improves vemurafenib response in melanoma spheroids.

Chemotherapy resistance is one of the main challenges in melanoma treatment. Violacein, a natural pigment produced by Chromobacterium violaceum, induces apoptosis in a variety of tumours, including melanoma. Here, we used BRAF-mutated melanoma spheroids to test the potential of violacein as a sensitizer of cellular viability and levels of the proteins p62 and fatty acid synthase (FASN). Importantly, violacein in combination with vemurafenib (ViVe) was able to interfere with spheroid survival at subtoxic concentrations. The results demonstrated that the ViVe protocol triggered cell death assessed by calcein and ethidium homodimer dyes. Accordingly, melanoma cells in 2D systems also showed a higher apoptosis rate when treated with ViVe. In the current study, we show evidence that ViVe downregulates crucial mediators like FASN, which partially explains how it acts as a sensitizer and ultimately improves the effectiveness of vemurafenib against melanoma cells.

Therapeutic Activity of a Topical Formulation Containing 8-Hydroxyquinoline for Cutaneous Leishmaniasis.

Cutaneous leishmaniasis exhibits a wide spectrum of clinical manifestations; however, only a limited number of drugs are available and include Glucantime® and amphotericin B, which induce unacceptable side effects in patients, limiting their use. Thus, there is an urgent demand to develop a treatment for leishmaniasis. Recently, it was demonstrated that 8-hydroxyquinoline (8-HQ) showed significant leishmanicidal effects in vitro and in vivo. Based on that, this work aimed to develop a topical formulation containing 8-HQ and assess its activity in experimental cutaneous leishmaniasis. 8-HQ was formulated using a Beeler base at 1 and 2% and showed an emulsion size with a D50 of 25 and 51.3 µm, respectively, with a shear-thinning rheological behaviour. The creams were able to permeate artificial Strat-M membranes and excised porcine skin without causing any morphological changes in the porcine skin or murine skin tested. In BALB/c mice infected with L. (L.) amazonensis, topical treatment with creams containing 1 or 2% of 8-HQ was found to reduce the parasite burden and lesion size compared to infected controls with comparable efficacy to Glucantime® (50 mg/kg) administered at the site of the cutaneous lesion. In the histological section of the skin from infected controls, a diffuse inflammatory infiltrate with many heavily infected macrophages that were associated with areas of necrosis was observed. On the other hand, animals treated with both creams showed only moderate inflammatory infiltrate, characterised by few infected macrophages, while tissue necrosis was not observed. These histological characteristics in topically treated animals were associated with an increase in the amount of IFN-γ and a reduction in IL-4 levels. The topical use of 8-HQ was active in decreasing tissue parasitism and should therefore be considered an interesting alternative directed to the treatment of leishmaniasis, considering that this type of treatment is non-invasive, painless, and, importantly, does not require hospitalisation, improving patient compliance by allowing the treatment to be conducted.

Accuracy of two prognostic indexes to predict mortality in older adults with advanced dementia.

Dementia is a cause of disability among older adults. Accessing advanced dementia prognosis is a challenge. Objective: The objective of this study was to evaluate the accuracy of the Charlson and Carey indexes in predicting 3-year survival of older adults with advanced dementia. Methods: This is a retrospective cohort study of 238 patients aged ≥60 years with advanced dementia from an outpatient clinic and classified as stage ≥6A by using the Functional Assessment Staging scale. We excluded patients with missing data. We reviewed the semi-structured interview (clinical, sociodemographic, and functional data) from the baseline visit. This information was used to calculate 3-year mortality risks according to the Charlson and Carey indexes. We used Cox proportional hazard models to evaluate the associations of all-cause mortality with both indexes, adjusted for sociodemographic variables. We used Harrell's C measure to determine the discrimination. We calculated the absolute differences between observed and predicted 3-year mortality risks for each index for calibration. Results: In 238 patients, the average age was 80.5±7.8 years, with 36% being men. The median follow-up time was 1.8 years (0.05-3.0). The 3-year all-cause mortality rate was 50% (119 deaths). The Carey index was associated with mortality, with one point increase related to a 15% increase in the mortality risk (hazard ratio [HR]=1.15, 95% confidence interval (95%CI) 1.06-1.25, p=0.001), even after adjustment. Accuracy for the Charlson index and Carey index was 0.55 (95%CI 0.49-0.60) and 0.60 (95%CI 0.52-0.62), respectively, with no difference between them (p=0.44). Conclusions: Both indexes had poor discrimination and calibration performances in predicting 3-year mortality in patients with advanced dementia.

Demência é uma causa de incapacidade e dependência em idosos. A avaliação prognóstica na fase avançada é desafiadora. Objetivo: Avaliar a acurácia dos índices de Charlson e Carey na predição de mortalidade em até três anos de idosos com demência avançada. Métodos: Estudo de coorte retrospectiva que incluiu 238 pacientes acompanhados em ambulatório especializado em um país de renda média, com idade ≥60 anos e demência avançada classificada como estágio ≥6A pela escala Functional Assessment Staging (FAST). Foram excluídos pacientes com dados incompletos para análise. Realizou-se revisão da primeira consulta, que consiste em entrevista com dados clínicos, sociodemográficos e funcionais utilizados para calcular a probabilidade de óbito em três anos, de acordo com os índices. Foram usados modelos de risco proporcional de Cox para avaliar as associações de mortalidade por todas as causas com os dois índices, ajustados para variáveis sociodemográficas. As discriminações dos dois modelos foram comparadas usando o cálculo C de Harrell. Para a calibração, foram calculadas as diferenças absolutas entre os riscos observados e preditos por cada um dos índices. Resultados: Foram avaliados 238 pacientes, com média de idade de 80,5±7,8 anos, 36% do sexo masculino. A mediana do tempo de acompanhamento foi de 1,8 anos (intervalo interquartil=0,05­3,0). A taxa de mortalidade por todas as causas em três anos foi de 50% (119 óbitos). O índice de Carey foi associado à mortalidade, mas o de Charlson não. Um aumento de 1 ponto no Carey foi relacionado a aumento de 15% no risco de morte (hazard ratio [HR]=1,15, intervalo de confiança [IC95%] 1,06­1,25, p=0,001), mesmo após ajuste para variáveis sociodemográficas. A acurácia do índice de Charlson foi de 0,55 (IC95% 0,49­0,60) e a do índice de Carey de 0,60 (IC95% 0,52­0,62), sem diferença significativa na discriminação (p=0,44). Ambos os índices tiveram performances insatisfatórias na discriminação e na calibração. Conclusões: O índice de Carey foi associado à mortalidade, porém esse resultado não foi encontrado para o índice de Charlson. Ambos os índices tiveram desempenho insatisfatório na discriminação e na calibração para predizer a mortalidade em três anos em pacientes com demência avançada, o que indica que esses escores não são recomendados para predizer a mortalidade nessa população.