Brazilian berry extract (Myrciaria jaboticaba): A promising therapy to minimize prostatic inflammation and oxidative stress.

BACKGROUND: Brazilian berry is a fruit popularly known as "Jaboticaba," rich in bioactive compounds with antioxidant and anti-inflammatory properties. Senescence and overweight are increasing worldwide and are considered risk factors to prostatic pathogenesis mainly due to oxidative and inflammatory processes induction. Thus, this study aimed to evaluate the effect of two increasing doses of the patented jaboticaba peel extract (PJE) on oxidative-stress and inflammation in the prostate of aging or high-fat-fed aging mice. METHODS: PJE and/or high-fat diet (HFD) treatments started with 11-month-old mice and lasted 60 days. The levels or the immunoexpression of different inflammatory (nuclear factor κB [NFκB], CD3+, cyclooxygenase 2 [COX-2], toll-like receptor 4 [TLR4], phosphorylated signal transducers and activators of transcription 3 [pSTAT-3], tumor necrosis factor α [TNF-α], interleukin 6 [IL-6], and IL-1ß) and oxidative-stress (catalase, superoxide dismutase 2 [SOD2], glutathione reductase [GSR], reduced glutathione, and glutathione peroxidase 3 [GPx3]) related molecules were analyzed by western-blotting, immunohistochemistry, and enzyme-linked immunosorbent assays. RESULTS: Both PJE doses reduced the levels of oxidative-stress-related molecules (GPx3, GSR, catalase), lipid peroxidation (4-hydroxynonenal), inflammatory mediators (COX-2, TNF-α, and pSTAT-3) and CD3+ T cells number, which were associated with the maintenance of the glandular morphological integrity in aging and HFD-fed-aging mice. Nevertheless, only the high PJE dose reduced the NFκB and TLR4 levels in aging mice; and SOD2, IL-6, and IL-1ß levels in HFD-aging mice. Aging itself promoted an oxidative inflammation in the prostate, interfering in the levels of the different oxidative-stress, lipid peroxidation, and inflammatory mediators evaluated, in association with high incidence of prostate epithelial and stromal damages. The HFD intake intensified aging alterations, showing an unfavorable prostatic microenvironment prone to oxidative and inflammatory damages. CONCLUSIONS: PJE exerted a dose-dependent effect controlling inflammation and oxidative-stress in aging and HFD-fed aging mice prostate. This fact contributed to prostate microenvironment balance recovery, preserving the tissue architecture of this gland. Thus, the PJE emerges as a potential therapy to prevent inflammation and oxidative stress in the prostate.

High-fat diet effects on the prostatic adenocarcinoma model and jaboticaba peel extract intake: protective response in metabolic disorders and liver histopathology.

Prostate cancer (PCa), overweight and obesity are frequent worldwide health problems. Clinical studies have shown that increased high-fat diet (HFD) consumption is associated with higher incidence of PCa. Brazilian berries, such as Myrciaria jaboticaba (Vell.) Berg, present high polyphenol concentration in the peel and exhibit positive effects on metabolic disorders and hepatic lesions. Therefore, the aim of the study herein was to investigate the patented jaboticaba peel extract effects (PJE) on different metabolic parameters and liver histopathology in the transgenic adenocarcinoma of the mouse prostate model, receiving a either normolipid diet or HFD for 8 weeks. The results showed that PJE reduced insulin resistance and glucose intolerance, decreased hepatic lipid accumulation, and inflammatory markers such as PPARγ and TNFα, respectively. In conclusion, the PJE treatment promoted protective effects in the metabolism of insulin and glucose and liver imbalance caused by HFD intake in the PCa model, suggesting that it may be a good protector against metabolic disorders present in overweight and associated with PCa.

Novel synthetic peptide derived from Porphyromonas gingivalis Lys-gingipain detects IgG-mediated host response in periodontitis.

Porphyromonas gingivalis is a keystone pathogen in periodontitis. Analysis of the immunogenicity of its virulence factors may provide insight into the host response to this infection. The Kgp12 (IEDB Epitope ID 763561), an epitope of Lys-gingipain (Kgp) virulence factor from P. gingivalis ATCC 33277, elicits an immunoglobulin G (IgG) immunoreactivity with low cross-reactivity and, therefore, more specificity. The aim of the present study was to determine in silico the localization of Kgp12 within the protein and to evaluate the IgG host response to this novel Kgp peptide through its capacity to differentiate individuals with different periodontal status. Sera of 71 volunteers were tested by indirect ELISA to detect the IgG immunoreactivity specific to Kgp12, as well as to the protein HmuY and to the sonicated total extract of P. gingivalis ATCC33277, both used as gold standard. The participants had no systemic disease and were classified according to periodontal clinical parameters to comparison, firstly, into periodontitis (P) and without periodontitis (WP) groups and, secondly, into periodontitis (P), gingivitis (G) and clinically health (CH) ones. All the antigens tested, Kgp12 (p = 0.02), HmuY (p = 0.00) and P. gingivalis extract (p = 0.03), could differentiate P from WP groups considering IgG serum levels. P group also had higher IgG levels specific to Kgp12 (p = 0.03), HmuY (p < 0.01) and P. gingivalis extract (p = 0.01) when compared to G group. We conclude that the Kgp12 synthetic peptide was useful to detect the IgG-mediated host response signaling that it is a promising epitope to analyze the immunogenicity of P. gingivalis.

Design, Synthesis and Biological Evaluation of Novel Triazole N-acylhydrazone Hybrids for Alzheimer's Disease.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that involves different pathogenic mechanisms. In this regard, the goal of this study was the design and synthesis of new compounds with multifunctional pharmacological activity by molecular hybridization of structural fragments of curcumin and resveratrol connected by an N-acyl-hydrazone function linked to a 1,4-disubstituted triazole system. Among these hybrid compounds, derivative 3e showed the ability to inhibit acetylcholinesterase activity, the intracellular formation of reactive oxygen species as well as the neurotoxicity elicited by Aß42 oligomers in neuronal SH-SY5Y cells. In parallel, compound 3e showed a good profile of safety and ADME parameters. Taken together, these results suggest that 3e could be considered a lead compound for the further development of AD therapeutics.

Dissociation between decision making under ambiguity and risk in patients with juvenile myoclonic epilepsy.

INTRODUCTION: Decision making (DM) is one aspect of impulsivity that can be defined by the ability to decide between two or more options in a given situation. To date, there are at least two types of DM that differ in the level of uncertainty, and how much information about consequences is provided. In this study, we aimed to evaluate the two domains of DM - under risk and ambiguous - with a comprehensive evaluation in a group of patients with juvenile myoclonic epilepsy (JME), and correlate with patients' characteristics, clinical variables, and neuropsychological evaluation for executive functions. METHODS: We evaluated 35 patients with JME and 39 healthy controls using the Iowa Gambling Task for DM under ambiguity and the Game Dice Task for DM under risk. We assessed the performance in Iowa Gambling Task and Game Dice Task through net scores, safe and risky choices, besides the type of decisions across time. RESULTS: Patients with JME had a higher number of risky choices compared to controls in the Game Dice Task. There was no significant difference between patients and controls in the Iowa Gambling Task. However, patients with higher seizure frequency had worse scores on decks C and D (safe choices) from the Iowa Gambling Task. CONCLUSION: Patients with JME have worse performance on DM under risk. The same was not observed for DM under ambiguity. Epilepsy-related factors and the presence of psychiatric disorders, but not executive dysfunction, were associated with a lower tendency for safe choices. These findings showed a dissociation between DM processes in patients with JME and a tendency to make disadvantageous decisions with measurable risks.

The relevance of attention deficit hyperactivity disorder in self-limited childhood epilepsy with centrotemporal spikes.

In this study, we aimed to evaluate the attentional and executive functions in patients with benign childhood epilepsy with centrotemporal spikes (BCECTS) with and without attention-deficit hyperactivity disorder (ADHD) compared with controls and compared with patients with ADHD without epilepsy. We evaluated 12 patients with BCECTS and ADHD (66.7% boys; mean age of 9.67years); 11 children with non-ADHD BCECTS (63.6% boys; mean age of 11.91years); 20 healthy children (75% boys; mean age of 10.15years); and 20 subjects with ADHD without epilepsy (60% boys; mean age of 10.9years). We used a comprehensive battery of neuropsychological tests to evaluate attentional and executive functions in their broad domains. Patients with BCECTS and ADHD had worse performance in Conners' Continuous Performance Test II (reaction time standard error [p=0.008], variability [p=0.033], perseverations [p=0.044] and in reaction time interstimuli interval [p=0.016]). Patients with ADHD showed worse performance in Trail Making Test B errors [p=0.012]. In conclusion, patients with BCECTS and ADHD had worse executive and attentional performance compared with controls than non-ADHD patients with BCECTS. Regardless of the presence of epilepsy, ADHD also negatively impacted executive and attentional functions but in different executive subdomains compared with patients with epilepsy.

The executive profile of children with Benign Epilepsy of Childhood with Centrotemporal Spikes and Temporal Lobe Epilepsy.

RATIONALE: Benign Epilepsy of Childhood with Centrotemporal Spikes (BECTS) and temporal lobe epilepsy (TLE) represent two distinct models of focal epilepsy of childhood. In both, there is evidence of executive dysfunction. The purpose of the present study was to identify particular deficits in the executive function that would distinguish children with BECTS from children with TLE. METHODS: We prospectively evaluated 19 consecutive children and adolescents with TLE with hippocampal sclerosis (HS) (57.9% male; mean 11.74years [SD 2.05]; mean IQ 95.21 [SD 15.09]), 19 with BECTS (36.8% male; mean 10.95years [SD 2.33]; mean IQ 107.40 [SD 16.01]), and 21 age and gender-matched controls (33.3% male; mean 11.86years [SD 2.25]; mean IQ 108.67 [15.05]). All participants underwent a neuropsychological assessment with a comprehensive battery for executive and attentional functions. We used ANOVA and chi-square to evaluate differences on demographic aspects among groups (BECTS, TLE-HS, and control groups). Group comparisons on continuous variables were complemented by MANOVA and Bonferroni posthoc comparisons. RESULTS: Patients with BECTS had worse performance than controls in: Matching Familiar Figures Test, time (p=0.001); Matching Familiar Figures Test, time×errors index (p<0.001); Verbal Fluency for foods (p=0.038); Trail Making Test, part B time (p=0.030); Trail Making Test, part B number of errors (p=0.030); and WCST, number of categories achieved (p=0.043). Patients with BECTS had worse performance than patients with TLE-HS on Matching Familiar Figures Test, time (p=0.004), and Matching Familiar Figures Test, time×errors index (p<0.001). Patients with TLE-HS had worse performance than controls on the following tests: Verbal Fluency for foods (p=0.004); Wisconsin Card Sorting Test, the number of categories achieved (p<0.001); and Wisconsin Card Sorting Test, the number of perseverative errors (p=0.028). Patients with TLE-HS had worse performance than patients with BECTS on Digit Backward (p=0.002); and the Wisconsin Card Sorting Test, the number of perseverative errors (p<0.001). CONCLUSIONS: Patients with TLE and BECTS present distinct cognitive profiles. Patients with TLE-HS had worse performance in mental flexibility, concept formation, and working memory compared to BECTS. Patients with BECTS had worse inhibitory control compared to children with TLE-HS. Both TLE-HS and BECTS had a higher number of errors on an inhibitory control test. However, patients with BECTS had a slower mental processing even when compared to patients with TLE-HS. Rehabilitation programs for children with epilepsy must include children with benign epilepsies and must take into account the epileptic syndrome and its particular neurocognitive phenotype.

Everyday memory impairment in patients with temporal lobe epilepsy caused by hippocampal sclerosis.

OBJECTIVE: Patients with temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS) have episodic memory impairment. Memory has rarely been evaluated using an ecologic measure, even though performance on these tests is more related to patients' memory complaints. We aimed to measure everyday memory of patients with TLE-HS to age- and gender-matched controls. METHODS: We evaluated 31 patients with TLE-HS and 34 healthy controls, without epilepsy and psychiatric disorders, using the Rivermead Behavioral Memory Test (RBMT), Visual Reproduction (WMS-III) and Logical Memory (WMS-III). We evaluated the impact of clinical variables such as the age of onset, epilepsy duration, AED use, history of status epilepticus, and seizure frequency on everyday memory. Statistical analyses were performed using MANCOVA with years of education as a confounding factor. RESULTS: Patients showed worse performance than controls on traditional memory tests and in the overall score of RBMT. Patients had more difficulties to recall names, a hidden belonging, to deliver a message, object recognition, to remember a story full of details, a previously presented short route, and in time and space orientation. Clinical epilepsy variables were not associated with RBMT performance. Memory span and working memory were correlated with worse performance on RBMT. SIGNIFICANCE: Patients with TLE-HS demonstrated deficits in everyday memory functions. A standard neuropsychological battery, designed to assess episodic memory, would not evaluate these impairments. Impairment in recalling names, routes, stories, messages, and space/time disorientation can adversely impact social adaptation, and we must consider these ecologic measures with greater attention in the neuropsychological evaluation of patients with memory complaints.

Decision-making in patients with temporal lobe epilepsy: Delay gratification ability is not impaired in patients with hippocampal sclerosis.

BACKGROUND: Decision-making abilities have rarely been examined in patients with temporal lobe epilepsy related to hippocampal sclerosis (TLE-HS). We aimed to investigate the ability to delay gratification, a decision-making subdomain, in patients with intractable TLE-HS and to verify the association of delay gratification performance and cool executive function tests. METHODS: We evaluated 27 patients with TLE-HS (mean age: 35.46 [±13.31] years; 7 males) and their cognitive performance was compared with that of 27 age- and gender-matched healthy controls (mean age: 35.33 [±12.05] years; 7 males), without epilepsy and psychiatric disorders. Patients were assessed using the delay discounting task (DDT) and tests of attention, shifting, inhibitory control, and concept formation. Results were correlated with clinical epilepsy variables such as age of onset, epilepsy duration, AED use, history of status epilepticus, febrile seizures, and the presence of generalized seizures. Statistical analysis was performed using one-way ANCOVA with years of education as a confounding factor. RESULTS: Patients and controls demonstrated similar performance on DDT, showing similar discount rate (p=0.935) and probability rate (p=0.585). Delay gratification was not related to cool executive function tests (Digit Span, Stroop Color Test, Trail Making Test, Wisconsin Card Sorting Test, and Connors' CPT). History of status epilepticus, presence of generalized seizures and higher seizure frequency, age at onset, and epilepsy duration had a significant impact on DDT. CONCLUSION: Patients with intractable TLE-HS showed unimpaired delay gratification abilities, being able to accept a higher delay and a lower amount of chance for receiving a higher reward in the future. Clinical variables related to the epilepsy severity impacted the performance on delay gratification. Impairment on cool aspects of executive function was unrelated to this decision-making domain.

Humoral and cellular immune responses in mice against secreted and somatic antigens from a Corynebacterium pseudotuberculosis attenuated strain: Immune response against a C. pseudotuberculosis strain.

BACKGROUND: Corynebacterium pseudotuberculosis is the etiologic agent of caseous lymphadenitis (CL), a chronic disease that affects goats and sheep. CL is characterized by the formation of granulomas in lymph nodes and other organs, such as the lungs and liver. Current knowledge of CL pathogenesis indicates that the induction of humoral and cellular immune responses are fundamental to disease control. The aim of this study was to evaluate the humoral and cellular immune responses in BALB/c mice inoculated with a C. pseudotuberculosis strain isolated in the state of Bahia, Brazil. RESULTS: The lymphocyte proliferation and in vitro production of IFN-γ, IL-4, IL-10, IL-12 and nitric oxide by spleen cells stimulated with secreted and somatic antigens from the studied strain were evaluated. IgG subclasses were also analyzed. Results showed a significant increase of Th1-profile cytokines after 60 days post-inoculation, as well as an important humoral response, represented by high levels of IgG2a and IgG1 against C. pseudotuberculosis. CONCLUSION: The T1 strain of C. pseudotuberculosis was shown to induce humoral and cellular immune responses in BALB/c mice, but, even at a dosage of 1x10(7) CFU, no signs of the disease were observed.

Distinct domains of impulsivity are impaired in juvenile myoclonic epilepsy but not in temporal lobe epilepsy.

OBJECTIVE: The Barratt Impulsiveness Scale (BIS-11) is the most widely used questionnaire to study impulsivity in persons with psychiatric disorders, but it has rarely been applied to persons with epilepsy. The present study aimed to evaluate the usefulness of BIS-11 as a tool to explore impulsivity in two distinct epilepsy syndromes. METHOD: The BIS-11 was applied to 20 patients with juvenile myoclonic epilepsy (JME) (32.5±8.95years old), 20 patients with temporal lobe epilepsy (TLE) (37.7±13.25years old), and 26 healthy controls (31.86±11.25years old). The scores in motor, attentional, and lack of planning impulsivity were compared between groups. RESULTS: Patients with JME showed higher scores than patients with TLE and controls in all domains: motor (JME vs TLE: 28.60 vs 13.25 (mean score), p<0.001 and JME vs controls: 28.60 vs 14.12, p<0.001), attentional (JME vs TLE: 21.55 vs 13.45, p<0.001 and JME vs controls: 21.55 vs 14.88, p<0.001) and nonplanning (JME vs TLE: 28.05 vs 13.10, p<0.001 and JME vs controls: 28.05 vs 16.15, p<0.001). CONCLUSION: Higher BIS-11 scores in all domains of impulsivity [i.e., motor, attentional, and lack of planning] corroborated previous findings described in patients with JME. On the other hand, BIS-11 could not demonstrate problem solving and inhibitory control deficits related to impulsive behavior, which were described in patients with TLE. Other behavioral measures may be more sensitive to some aspects of impulsivity in TLE. Our results reinforce the concept that distinct epileptic syndromes require different neuropsychological approaches, especially considering a complex construct such as impulsivity.

Tetrandrine for Targeting Therapy Resistance in Cancer.

During the last five decades, there has been tremendous development in our understanding of cancer biology and the development of new and novel therapeutics to target cancer. However, despite these advances, cancer remains the second leading cause of death across the globe. Most cancer deaths are attributed to the development of resistance to current therapies. There is an urgent and unmet need to address cancer therapy resistance. Tetrandrine, a bis-benzyl iso-quinoline, has shown a promising role as an anti-cancer agent. Recent work from our laboratory and others suggests that tetrandrine and its derivatives could be an excellent adjuvant to the current arsenal of anti-cancer drugs. Herein, we provide an overview of resistance mechanisms to current therapeutics and review the existing literature on the anti-cancer effects of tetrandrine and its potential use for overcoming therapy resistance in cancer.

18F-Fluoride PET/CT-Updates.

Sodium Fluoride-18 production started in the 1940s and was described clinically for the first time in 1962 as a bone-imaging agent. However, its use became dormant with the development of conventional bone scintigraphy, especially due to its low cost. Conventional bone scintigraphy has been the most utilized Nuclear Medicine technique for identifying osteoblastic bone metastases, especially in prostate and breast cancers for decades and is also employed to identify benign bone disease, especially in the orthopedic setting. While bone scintigraphy is highly sensitive, it lacks adequate specificity. With the advent of high-quality 3D Whole-Body Positron Emission Tomography combined with computed tomography (PET/CT), images, Sodium Fluoride-18 imaging with PET/CT (Fluoride PET/CT) re-emerged. This PET/CT bone-imaging agent provides higher sensitivity and specificity to detect bone lesions in both the oncological scenario as well as to identify benign bone and joint disorders. PET/CT bone-imaging provides a precise view of the bone metabolism remodeling processes at a molecular level, throughout the skeleton, and combines anatomical information, enhancing diagnostic specificity and accuracy. This article review will explore the updates on clinical applications of Fluoride PET/CT in oncology and benign conditions encompassing orthopedic, inflammatory and cardiovascular conditions and treatment response assessment.

Sleep quality and circadian rhythm profile of persons with juvenile myoclonic epilepsy in a tertiary epilepsy center: A case-control study.

PURPOSE: This study evaluated sleep quality, chronotype, and excessive diurnal somnolence in persons with Juvenile Myoclonic Epilepsy (JME) and their possible association with clinical variables. METHODS: This cross-sectional controlled study evaluated 49 consecutive patients (65% females, mean age 27.53 years) with an electroclinical diagnosis of JME and 49 healthy controls (55% females, mean age 28.55 years). The Pittsburgh Sleep Quality Inventory (PSQI) was used to assess sleep quality and the Epworth Sleepiness Scale (ESS) to evaluate excessive daytime sleepiness. The patients' chronotype was evaluated by the Morningness-Eveningness Questionnaire (MEQ). Epilepsy-related factors gathered from the medical chart and personal interview were epilepsy duration, age at onset, frequency of myoclonic (Mcl), generalized tonic-clonic (GTC) and absence (ABS) seizures, pharmacoresponse, and current antiseizure medication (ASM). RESULTS: Persons with JME did not differ from the control group regarding daytime sleepiness (p=0.840); however, the JME group had worse sleep quality (p=0.01) than the controls. Persons with JME presented a more evening chronotype than controls (p = 0.003). The age at onset, epilepsy duration, frequency of Mcl seizure, frequency of GTC seizure, frequency of ABS seizure, and drug response did not predict ESS and MEQ scales. Pharmacoresponsive patients had lower PSQI scores compared with pharmacoresistant patients (p=0.036). CONCLUSION: Persons with JME have worse sleep quality and a more evening chronotype. Notably, pharmacoresistant patients present a worse sleep quality that deserves attention and special care due to the relationship between sleep deprivation and seizure worsening.

A synthetic resveratrol-curcumin hybrid derivative exhibits chemopreventive effects on colon pre-neoplastic lesions by targeting Wnt/ß-catenin signaling, anti-inflammatory and antioxidant pathways.

ABSTRACT: Based on the effectiveness of resveratrol and curcumin in carcinogenesis, (E)-3-(4-hydroxy-3-methoxyphenyl)-N'-((E)-4-methoxybenzylidene) acrylohydrazide (PQM-162), curcumin-resveratrol hybrid derivative, was designed by molecular hybridization using a hydrazone functionality as a spacer moiety between pharmacophoric fragments inspired by the parent compounds. OBJECTIVES: The present study aimed to evaluate the chemopreventive effects of the hybrid against pre-neoplastic lesions induced in the colon of rodents. METHODS: The doses were determined based on the reduction in DNA damage induced by doxorubicin [15 mg/kg body weight (b.w.)] in peripheral blood of Swiss mice. Doses of 8, 16, 32, and 64 mg/kg b.w. were antimutagenic. For the evaluation of pre-neoplastic lesions in the colon, Wistar rats were treated with PQM-162 at doses of 0.5, 1, and 2 mg/kg b.w. for 6 weeks using three approaches: simultaneous treatment, pre-treatment, and post-treatment. Pre-neoplastic lesions were induced with 1,2 dimethylhydrazine (160 mg/kg b.w.). KEY FINDINGS: PQM-162 reduced the formation of aberrant crypt foci in the simultaneous treatment and post-treatment. TNF-α and COX-2 mRNA levels decreased, while Nrf2 mRNA levels increased. PQM-162 also reduced the expression of COX-2, PCNA, and ß-catenin protein markers and increased Nrf2 expression. CONCLUSION: Our findings suggest a chemopreventive potential of PQM-162 in colorectal carcinogenesis, which acts on anti-inflammatory, antioxidant, and cell proliferation pathways.

Different biological effects of exposure to far-UVC (222 nm) and near-UVC (254 nm) irradiation.

Ultraviolet C (UVC) light has long been used as a sterilizing agent, primarily through devices that emit at 254 nm. Depending on the dose and duration of exposure, UV 254 nm can cause erythema and photokeratitis and potentially cause skin cancer since it directly modifies nitrogenated nucleic acid bases. Filtered KrCl excimer lamps (emitting mainly at 222 nm) have emerged as safer germicidal tools and have even been proposed as devices to sterilize surgical wounds. All the studies that showed the safety of 222 nm analyzed cell number and viability, erythema generation, epidermal thickening, the formation of genetic lesions such as cyclobutane pyrimidine dimers (CPDs) and pyrimidine-(6-4)-pyrimidone photoproducts (6-4PPs) and cancer-inducing potential. Although nucleic acids can absorb and be modified by both UV 254 nm and UV 222 nm equally, compared to UV 254 nm, UV 222 nm is more intensely absorbed by proteins (especially aromatic side chains), causing photooxidation and cross-linking. Here, in addition to analyzing DNA lesion formation, for the first time, we evaluated changes in the proteome and cellular pathways, reactive oxygen species formation, and metalloproteinase (MMP) levels and activity in full-thickness in vitro reconstructed human skin (RHS) exposed to UV 222 nm. We also performed the longest (40 days) in vivo study of UV 222 nm exposure in the HRS/J mouse model at the occupational threshold limit value (TLV) for indirect exposure (25 mJ/cm2) and evaluated overall skin morphology, cellular pathological alterations, CPD and 6-4PP formation and MMP-9 activity. Our study showed that processes related to reactive oxygen species and inflammatory responses were more altered by UV 254 nm than by UV 222 nm. Our chronic in vivo exposure assay using the TLV confirmed that UV 222 nm causes minor damage to the skin. However, alterations in pathways related to skin regeneration raise concerns about direct exposure to UV 222 nm.

Factors associated with caregiver burden of adults with epilepsy in a middle-income country.

PURPOSE: Despite the relevance of socio-economic background in burden of caregivers of persons with epilepsy (PWE), there is a dearth of knowledge about this topic in low-resource settings. Here we attempt to identify the extent of the burden in caregivers of adults with epilepsy in a middle-income country and the factors associated with it. METHODS: In this cross-sectional study, we evaluated the level of burden with the Zarit Caregiver Burden Inventory. A comprehensive questionnaire was developed to assess the demographics of patients and caregivers. Epilepsy-related factors were obtained by interview and file review. Depressive, anxiety symptoms, and sleep quality were evaluated by Beck Depression Inventory, State and Trait Anxiety Inventory, and Pittsburgh Sleep Quality Index. Stigma was evaluated by the Stigma Scale of Epilepsy. RESULTS: The caregiver's burden was mild to moderate in our sample. The factors most strongly associated with the higher caregiver burden were age-onset of epilepsy, PWE years of schooling, needs for assistance in daily life, disabilities, and caregiver's bad-quality of sleep and higher depressive and anxiety symptoms. CONCLUSION: Caregivers of PWE deserve special attention regarding mental health and other health aspects, such as sleep quality.

Anxiety symptoms are the strongest predictor of quality of life in temporal lobe epilepsy.

PURPOSE: It is established that the severity of depressive and anxiety symptoms is associated with poorer quality of life (QOL) in persons with drug-resistant epilepsy. We aimed to verify the presence of subsyndromic depressive episodes (SDEs) and subsyndromic anxiety episodes (SAEs) in persons with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) compared to healthy controls and to determine the impact of depressive and anxiety symptoms on patients' QOL. METHODS: We prospectively evaluated 35 persons with TLE-HS and 90 healthy controls. QOL was assessed by the Epilepsy Surgery Inventory (ESI) and QOL in Epilepsy Inventory-31 (QOLIE-31). The Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI-X) were used to assess symptoms, and SDEs and SAEs diagnosis were made considering the total scores of BDI (<9) and STAI-Trait (<49), respectively. RESULTS: Persons with TLE-HS had higher symptoms on BDI, STAI-S, and STAI-T. They have 3.011 greater odds of presenting SDEs and 7.056 times odds, SAEs. The depressive and anxiety symptoms, added in the model with epilepsy-related factors, accounted for a significant increase in the variance in several aspects of QOL. Anxiety-trait symptoms are the most critical individual determinant of the QOL. CONCLUSION: Our results demonstrated that persons with TLE-HS had greater odds of presenting SDE and SAE than healthy controls. Besides, there was a relationship between anxiety and depressive symptoms and worse QOL in TLE-HS. It is essential to be aware of psychiatric symptoms, even though these symptoms do not meet the criteria to be considered a "disorder."

Enhancing the Anticancer Activity and Selectivity of Goniothalamin Using pH-Sensitive Acetalated Dextran (Ac-Dex) Nanoparticles: A Promising Platform for Delivery of Natural Compounds.

Goniothalamin (GTN), a natural compound isolated from Goniothalamus species, has previously demonstrated cytotoxic activity against several cancer cell lines. However, similarly to many natural and synthetic anticancer compounds, GTN presents toxicity toward some healthy cells and low aqueous solubility, decreasing its bioavailability and precluding its application as an antineoplastic drug. In our efforts to improve the pharmacokinetic behavior and selectivity of GTN against cancer cells, we developed a polymeric nanosystem, in which rac-GTN was encapsulated in pH-responsive acetalated dextran (Ac-Dex) nanoparticles (NPs) with high loadings of the bioactive compound. Dynamic light scattering (DLS) analysis showed that the nanoparticles obtained presented a narrow size distribution of around 100 nm in diameter, whereas electron microscopy (EM) images showed nanoparticles with a regular spherical morphology in agreement with the size range obtained by DLS. Stability and release studies indicated that the GTN@Ac-Dex NPs presented high stability under physiological conditions (pH 7.4) and disassembled under slightly acidic conditions (pH 5.5), releasing the rac-GTN in a sustained manner. In vitro assays showed that GTN@Ac-Dex NPs significantly increased cytotoxicity and selectivity against cancer cells when compared with the empty Ac-Dex NPs and the free rac-GNT. Cellular uptake and morphology studies using MCF-7 cells demonstrated that GTN@Ac-Dex NPs are rapidly internalized into the cancer cells, causing cell death. In vivo investigation confirmed the efficient release of rac-GTN from GTN@Ac-Dex NPs, resulting in the delay of prostate cancer progression in transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Furthermore, liver histopathology evaluation after treatment with GTN@Ac-Dex NPs showed no evidence of toxicity. Therefore, the in vitro and in vivo findings suggest that the Ac-Dex NPs are a promising nanosystem for the sustained delivery of rac-GTN into tumors.

Social cognition in childhood epilepsy with centrotemporal spikes.

PURPOSE: Social cognition is involved in the perception, processing, and interpretation of social information. For this reason, social cognition is a crucial domain for successful communication and interpersonal relationships. With this in mind, we aimed to assess social cognition in children with Self-Limited Childhood Epilepsy with Centrotemporal Spikes (CECTS) and its association with traditional executive function tests and clinical variables of epilepsy. METHODS: We evaluated 23 patients with CECTS (65% male, mean age of 10.64 years) and 20 healthy children (75% male, mean age of 10.15 years). We used the Faux-Pas Child Task (FP) to analyze social cognition and a comprehensive battery of neuropsychological tests to evaluate domains of classic executive functions. RESULTS: Patients with CECTS had impairments in FP compared to healthy children [p < 0.001]. Impairments in some areas of traditional executive functions were related to worse social cognition in patients with CECTS. Epilepsy-related factors did not impair the performance on FP, except for the number of antiseizure medication [p = 0.016]. CONCLUSIONS: Social cognition is impaired in children and adolescents with CECTS. The presence of ongoing seizures and frequent epileptiform activity were not correlated with social cognition. Therefore, epilepsy per se was more relevant for social cognition than its severity.