Physical Exercise for Treating the Anxiety and Depression Symptoms of Parkinson's Disease: Systematic Review and Meta-Analysis.

BACKGROUND: Depression and anxiety are non-motor symptoms of Parkinson's disease (PD). Physical exercise is a promising approach to reducing neuropsychological burden. We aimed to comprehensively synthesize evidence regarding the use of exercise for treating depression and anxiety symptoms in PD. METHODS: Systematic review and meta-analysis following PRISMA recommendations. Searches on PubMed, Cochrane Library, Scopus, Web of Science, Embase, and Physiotherapy Evidence Database (PEDro) was conducted. The random-effects model was employed for all analyses with the standardized mean difference as the effect estimate. RESULTS: Fifty records were retrieved, but only 17 studies met the criteria for the meta-analyses. A moderate to large effect was observed for depression (-.71 [95% CI = -.96 to -.46], 11 studies, 728 individuals), and a small to moderate effect for anxiety (-.39 [95% CI = -.65 to -.14], 6 studies, 241 individuals), when comparing exercise to non-exercise controls. Subgroup analysis revealed significant effects from aerobic (-.95 [95% CI = -1.60, -.31]), mind-body (-1.85 [95% CI = -2.63, -1.07]), and resistance modalities (-1.61 [95% CI = -2.40, -.83]) for depression, and from mind-body (-.67 [95% CI = -1.19 to -.15]) and resistance exercises (-1.00 [95% CI = -1.70 to -.30]) for anxiety. CONCLUSION: Physical exercise has a relevant clinical impact on depression and anxiety in PD. We discuss the level of the evidence, the methodological limitations of the studies, and give recommendations.

Dipotassium Glycyrrhizininate Improves Skin Wound Healing by Modulating Inflammatory Process.

Wound healing is characterized by a systemic and complex process of cellular and molecular activities. Dipotassium Glycyrrhizinate (DPG), a side product derived from glycyrrhizic acid, has several biological effects, such as being antiallergic, antioxidant, antibacterial, antiviral, gastroprotective, antitumoral, and anti-inflammatory. This study aimed to evaluate the anti-inflammatory effect of topical DPG on the healing of cutaneous wounds by secondary intention in an in vivo experimental model. Twenty-four male Wistar rats were used in the experiment, and were randomly divided into six groups of four. Circular excisions were performed and topically treated for 14 days after wound induction. Macroscopic and histopathological analyses were performed. Gene expression was evaluated by real-time qPCR. Our results showed that treatment with DPG caused a decrease in the inflammatory exudate as well as an absence of active hyperemia. Increases in granulation tissue, tissue reepithelization, and total collagen were also observed. Furthermore, DPG treatment reduced the expression of pro-inflammatory cytokines (Tnf-α, Cox-2, Il-8, Irak-2, Nf-kB, and Il-1) while increasing the expression of Il-10, demonstrating anti-inflammatory effects across all three treatment periods. Based on our results, we conclude that DPG attenuates the inflammatory process by promoting skin wound healing through the modulation of distinct mechanisms and signaling pathways, including anti-inflammatory ones. This involves modulation of the expression of pro- and anti-inflammatory cytokine expression; promotion of new granulation tissue; angiogenesis; and tissue re-epithelialization, all of which contribute to tissue remodeling.

A comprehensive analysis of penile cancer in the region with the highest worldwide incidence reveals new insights into the disease.

BACKGROUND: Although penile cancer (PC) is uncommon in developed countries, it is widespread in developing countries. The state of Maranhão (Northeast, Brazil) has the highest global incidence recorded for PC, and, despite its socioeconomic vulnerability, it has been attributed to human papillomavirus (HPV) infection. This study aimed to determine the histopathological features, the prevalence of HPV infection, and the immunohistochemical profile of PC in Maranhão. METHODS: A retrospective cohort of 200 PC cases were evaluated. HPV detection was performed using nested-PCR followed by direct sequencing for genotyping. Immunohistochemistry (IHC) was performed using monoclonal antibodies anti-p16INK4a, p53, and ki-67. RESULTS: Our data revealed a delay of 17 months in diagnosis, a high rate of penile amputation (96.5%), and HPV infection (80.5%) in patients from Maranhão (Molecular detection). We demonstrated the high rate of HPV in PC also by histopathological and IHC analysis. Most patients presented koilocytosis (75.5%), which was associated with those reporting more than 10 different sexual partners during their lifetime (p = 0.001). IHC revealed frequent p16INK4a overexpression (26.0%) associated with basaloid (p < 0.001) and high-grade tumors (p = 0.008). Interestingly, p16 appears not to be a better prognostic factor in our disease-free survival analysis, as previously reported. We also demonstrated high ki-67 and p53 expression in a subset of cases, which was related to worse prognostic factors such as high-grade tumors, angiolymphatic and perineural invasion, and lymph node metastasis. We found a significant impact of high ki-67 (p = 0.002, log-rank) and p53 (p = 0.032, log-rank) expression on decreasing patients' survival, as well as grade, pT, stage, pattern, and depth of invasion (p < 0.05, log-rank). CONCLUSIONS: Our data reaffirmed the high incidence of HPV infection in PC cases from Maranhão and offer new insights into potential factors that may contribute to the high PC incidence in the region. We highlighted the possible association of HPV with worse clinical prognosis factors, differently from what was observed in other regions. Furthermore, our IHC analysis reinforces p16, ki-67, and p53 expression as important diagnosis and/or prognosis biomarkers, potentially used in the clinical setting in emerging countries such as Brazil.

Dipotassium Glycyrrhizinate on Melanoma Cell Line: Inhibition of Cerebral Metastases Formation by Targeting NF-kB Genes-Mediating MicroRNA-4443 and MicroRNA-3620-Dipotassium Glycyrrhizinate Effect on Melanoma.

Glycyrrhizic acid (GA), a natural compound isolated from licorice (Glycyrrhiza glabra), has exhibited anti-inflammatory and anti-tumor effects in vitro. Dipotassium glycyrrhizinate (DPG), a dipotassium salt of GA, also has shown an anti-tumor effect on glioblastoma cell lines, U87MG and T98G. The study investigated the DPG effects in the melanoma cell line (SK-MEL-28). MTT assay demonstrated that the viability of the cells was significantly decreased in a time- and dose-dependent manner after DPG (IC50 = 36 mM; 24 h). DNA fragmentation suggested that DPG (IC50) induced cellular apoptosis, which was confirmed by a significant number of TUNEL-positive cells (p-value = 0.048) and by PARP-1 [0.55 vs. 1.02 arbitrary units (AUs), p-value = 0.001], BAX (1.91 vs. 1.05 AUs, p-value = 0.09), and BCL-2 (0.51 vs. 1.07 AUs, p-value = 0.0018) mRNA compared to control cells. The proliferation and wound-healing assays showed an anti-proliferative effect on DPG-IC50-treated cells, also indicating an inhibitory effect on cell migration (p-values < 0.001). Moreover, it was observed that DPG promoted a 100% reduction in melanospheres formation (p-value = 0.008). Our previous microRNAs (miRs) global analysis has revealed that DPG might increase miR-4443 and miR-3620 expression levels. Thus, qPCR showed that after DPG treatment, SK-MEL-28 cells presented significantly high miR-4443 (1.77 vs. 1.04 AUs, p-value = 0.02) and miR-3620 (2.30 vs. 1.00 AUs, p-value = 0.01) expression compared to control cells, which are predicted to target the NF-kB, CD209 and TNC genes, respectively. Both genes are responsible for cell attachment and migration, and qPCR revealed significantly decreased CD209 (1.01 vs. 0.54 AUs, p-value = 0.018) and TNC (1.00 vs. 0.31 AUs, p-value = 2.38 × 10−6) mRNA expression levels after DPG compared to untreated cells. Furthermore, the migration of SK-MEL-28 cells stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) was attenuated by adding DPG by wound-healing assay (48 h: p-value = 0.004; 72 h: p-value = 7.0 × 10−4). In addition, the MMP-9 expression level was inhibited by DPG in melanoma cells stimulated by TPA and compared to TPA-treated cells (3.56 vs. 0.99 AUs, p-value = 0.0016) after 24 h of treatment. Our results suggested that DPG has an apoptotic, anti-proliferative, and anti-migratory effect on SK-MEL-28 cells. DPG was also able to inhibit cancer stem-like cells that may cause cerebral tumor formation.

Oral Conditions of Elders and Middle-aged Individuals with Multiple Myeloma.

AIM AND OBJECTIVE: The aim and objective of the present study was to assess the oral conditions of middle-aged and elderly individuals with multiple myeloma. MATERIALS AND METHODS: This cross-sectional, observational study was carried out in the city of Fortaleza, Ceará, in Northeastern Brazil. An oral examination was performed with 19 patients with multiple myeloma, and information on gender, age, diagnosis, diagnosis duration (months/years), and treatment duration (months/years) were collected. The gingival bleeding index (GBI) and probing depth (PD) were measured to check for periodontal disease, and the decayed, missing, and filled teeth (DMFT) index was used to assess dental conditions. Inferential statistics were also used, as well as the Mann-Whitney test to compare genders and continuous variables and the chi-square test for comparisons among the same groups with categorical variables. All statistical tests adopted a significance threshold of p ≤0.05. RESULTS: Among the 19 patients analyzed, 10 (52.6%) were elderly, and 9 (47.4%), middle-aged. The mean age of the participants was 63.4 ± 11.7 years, ranging from 48 to 83 years old. Statistical significance was found regarding missing teeth in the elderly group (p = 0.037), restored teeth in the middle-aged group (p = 0.029), and gingival bleeding among women (p = 0.050). Hyposalivation was observed in 89.5% of the individuals, of which 68.4% were characterized as moderate to severe. CONCLUSION: Better dental conditions were observed in the middle-aged group when compared to the elderly. Men presented the lowest GBI values. The salivary flow of patients with multiple myeloma was reduced, and most of them showed moderate to severe hyposalivation. It can be assumed that such a situation is caused by the action of drugs, chemotherapy, or even age. Improvements in the oral health of these patients are needed in order to promote a better quality of life. CLINICAL SIGNIFICANCE: Knowledge of the oral manifestations of multiple myeloma patients is essential to assist in the early diagnosis of these alterations, as well as to propose an adequate treatment plan, aiming to improve these patients' quality of life.

Evaluation of Budesonide-Hydroxypropyl-ß-Cyclodextrin Inclusion Complex in Thermoreversible Gels for Ulcerative Colitis.

BACKGROUND: New formulations for topical treatment of ulcerative colitis with budesonide inclusion complex (BUDHP-ß-CD) and poloxamers (PL) were developed for future clinical use. AIMS: This study evaluated the efficacy of such novel formulations in a rat model of colitis. METHODS: The PL-BUDHP-ß-CD systems were prepared by direct dispersion of the complex (BUD concentration 0.5 mg mL-1) in solutions with PL407 or PL403. Male Wistar rats underwent TNBS-induced colitis and were treated for 5 days by a rectal route, as follows: BUD 1: BUDHP-ß-CD + PL407 (18%); BUD 2: BUDHP-ß-CD + PL407 (20%); BUD 3: BUDHP-ß-CD + PL407 (18%) + PL403 (2%); BUD 4: plain BUD; BUD 5: BUDHP-ß-CD; C1: HP-ß-CD + PL407 (18%); C2: HP-ß-CD + PL407 (20%); C3: HP-ß-CD + PL407 (18%) + PL403 (2%); C4: saline. A negative control group without colitis was also used. Colitis was assessed via myeloperoxidase (MPO) activity, and macroscopic and microscopic damage score in colon tissues. Protein levels of TNF-α, IL-1ß, IL-10 and endogenous glucocorticoids were obtained using ELISA. RESULTS: BUDHP-ß-CD poloxamer formulations had similar MPO activity when compared with the negative control group. All formulations presented lower MPO activity than BUDHP-ß-CD and plain BUD (p < 0.001). BUD 2 produced lower microscopic score values than plain BUD and BUDHP-ß-CD (p < 0.01). All formulations with BUDHP-ß-CD poloxamers reduced TNF-α levels (p < 0.05). CONCLUSION: Novel budesonide inclusion complex formulations improved microscopic damage and reduced colonic MPO activity and TNF-α levels.

Neurotoxicity of Tityus bahiensis (brown scorpion) venom in sympathetic vas deferens preparations and neuronal cells.

Systemic scorpion envenomation is characterized by massive neurotransmitter release from peripheral nerves mediated primarily by scorpion venoms neurotoxins. Tityus bahiensis is one of the medically most important species in Brazil, but its venom pharmacology, especially regarding to peripheral nervous system, is poorly understood. Here, we evaluated the T. bahiensis venom activity on autonomic (sympathetic) neurotransmission by using a variety of approaches, including vas deferens twitch-tension recordings, electrophysiological measurements (resting membrane potentials, spontaneous excitatory junctional potentials and whole-cell patch-clamp), calcium imaging and histomorphological analysis. Low concentrations of venom (≤ 3 µg/mL) facilitated the electrically stimulated vas deferens contractions without affecting postsynaptic receptors or damaging the smooth muscle cells. Transient TTX-sensitive sustained contractions and resting membrane depolarization were mediated mainly by massive spontaneous ATP release. High venom concentrations (≥ 10 µg/mL) blocked the muscle contractions and induced membrane depolarization. In neuronal cells (ND7-23wt), the venom increased the peak sodium current, modified the current-voltage relationship by left-shifting the Nav-channel activation curve, thereby facilitating the opening of these channels. The venom also caused a time-dependent increase in neuronal calcium influx. These results indicate that the sympathetic hyperstimulation observed in systemic envenomation is presynaptically driven, probably through the interaction of α- and ß-toxins with neuronal sodium channels.

Alcohol consumption is associated with DXA measurement of adiposity: the Pró-Saúde Study, Brazil.

PURPOSE: Evaluate the association between alcohol consumption and body adiposity. METHODS: We analyzed cross-sectional data from a longitudinal investigation (Pró-Saúde Study), comprising a sample of 514 civil servants of both sexes (35-64 years). Daily alcohol consumption (wine, beer, and other alcoholic drinks) over the previous 6 months was assessed via food frequency questionnaire and categorized as no doses, up to 1 dose, and ≥1 dose. The total body mass, total fat mass (TFM), android fat mass (AFM), and gynoid fat mass (GFM) were measured via dual-energy X-ray absorptiometry. AFM (AFM%) and GFM (GFM%) were expressed as percentages relative to TFM. The ratio of AFM% and GFM% was calculated. Multiple linear regression analyses were performed after adjusting for age, calories not originating from alcohol, leisure-time physical activity and education. RESULTS: Among nondrinkers, 59 % were women, and the age range between 45 and 54 years was predominant (44.3 %); 63.7 % of the nondrinkers were overweight/obese. Among drinkers of 1 dose or more/day, 67 % were males aged between 45 and 54 years (43.7 %); 69.1 % were overweight/obese. Among men, the daily consumption of ≥1 alcohol dose (13 g) was associated with an approximately 2 % (ß = 2.2, IC = 0.077; 4.303) adjusted for age, calories not originated from alcohol, leisure-time physical activity and education, increase in TFM, compared to those who reported no alcohol consumption during the previous 6 months. This association was not observed among women. In both sexes, no associations were observed between alcohol consumption and the other evaluated parameters of adiposity. CONCLUSION: Among men only, daily consumption of ≥1 alcohol dose was associated with increased adiposity, despite the relatively low average alcohol consumption in this study population.

Perception of food consumed at home and dietary intake: A nationwide study from Brazil.

Perception of food consumed is a key factor in acknowledging the need for behavioral change to improve diet quality. We analyzed family dietary intake according to the head of household's perception of satisfaction with food consumed by the family. Households (n = 13,351) that participated in the Brazilian Household Budget Survey and the National Dietary Survey were classified as satisfied or dissatisfied with the food consumed in the home. We compared the family dietary intake of the two groups considering their socio-demographic characteristics. Satisfied families (n = 4429) reported statistically higher intake (in grams/1000 kcal) of vegetables (47.3 vs 33.7), fruits (46.9 vs 21.4), sugar-sweetened beverages (118 vs 71.7), milk and dairy (57.9 vs 34.6), and ultra-processed products (18.6 vs 9.8); and lower intake of rice (86.2 vs 112), beans (91.7 vs 136), and meat (76.5 vs 84.0) when compared to dissatisfied families (n = 1717). Among satisfied families, in the youngest group we found lower consumption of fruits and higher intake of sugar-sweetened beverages and ultra-processed products when compared to the oldest group. Also among satisfied families, those in the highest per capita income group presented higher intake of fruits and lower intake of beans than those in the lowest income group. Satisfied families in the highest income group also consumed more fruits and less beans than dissatisfied families in the same income group. Socio-demographic characteristics may influence perception of satisfaction with food consumed and potentially influence the success of public health efforts to offer nutrition guidance for families satisfied with diets that may or may not be comprised of healthy food and beverages.

Effects of pneumoperitoneum and of an alveolar recruitment maneuver followed by positive end-expiratory pressure on cardiopulmonary function in sheep anesthetized with isoflurane-fentanyl.

OBJECTIVE: To investigate the effects of pneumoperitoneum alone or combined with an alveolar recruitment maneuver (ARM) followed by positive end-expiratory pressure (PEEP) on cardiopulmonary function in sheep. STUDY DESIGN: Prospective, randomized, crossover study. ANIMALS: A total of nine adult sheep (36-52 kg). METHODS: Sheep were administered three treatments (≥10-day intervals) during isoflurane-fentanyl anesthesia and volume-controlled ventilation (tidal volume: 12 mL kg-1) with oxygen: CONTROL (no intervention); PNEUMO (120 minutes of CO2 pneumoperitoneum); PNEUMOARM/PEEP (PNEUMO protocol with an ARM instituted after 60 minutes of pneumoperitoneum). The ARM (5 cmH2O increases in PEEP of 1 minute duration until 20 cmH2O of PEEP) was followed by 10 cmH2O of PEEP until the end of anesthesia. Cardiopulmonary data were recorded until 30 minutes after abdominal deflation. RESULTS: PaO2 was decreased from 435-462 mmHg (58.0-61.6 kPa) (range of mean values in CONTROL) to 377-397 mmHg (50.3-52.9 kPa) in PNEUMO (p < 0.05). Quasistatic compliance (Cqst, mL cmH2O-1 kg-1) was decreased from 0.85-0.92 in CONTROL to 0.52-0.58 in PNEUMO. PaO2 increased from 383-385 mmHg (51.1-51.3 kPa) in PNEUMO to 429-444 mmHg (57.2-59.2 kPa) in PNEUMOARM/PEEP (p < 0.05) and Cqst increased from 0.52-0.53 in PNEUMO to 0.70-0.74 in PNEUMOARM/PEEP. Abdominal deflation in PNEUMO did not restore PaO2 and Cqst to control values. Cardiac index (L minute-1 m2) decreased from 4.80-4.70 in CONTROL to 3.45-3.74 in PNEUMO and 3.63-3.76 in PNEUMOARM/PEEP. Compared with controls, ARM/PEEP with pneumoperitoneum decreased mean arterial pressure from 81 to 68 mmHg and increased mean pulmonary artery pressure from 10 to 16 mmHg. CONCLUSIONS AND CLINICAL RELEVANCE: Abdominal deflation did not reverse the pulmonary function impairment associated with pneumoperitoneum. The ARM/PEEP improved respiratory compliance and reversed the oxygenation impairment induced by pneumoperitoneum with acceptable hemodynamic changes in healthy sheep.

Effects of tretinoin on wound healing in aged skin.

Aged and adult populations have differences in the structural, biological, and healing properties of skin. Comparative studies of healing under the influence of retinoids in both these populations are very important and, to the best of our knowledge, have not been performed to date. The purpose of this study was to compare the activities of topical tretinoin in aged and adult animal models of wound healing by secondary intention. Male aged rats (24 months old, n = 7) and adult rats (6 months old, n = 8) were used. The rats were assigned to the following groups according to the dates on which wound samples were excised (day 14 or 21 after model creation): treated group, control group, and naive group. Topical application of tretinoin cream was used only on the proximal wound and was applied daily for 7 days. Wound healing areas were measured using metal calipers, and morphological analysis was performed. Slides were stained with Hematoxylin and Eosin, Masson's trichrome, and periodic acid-Schiff stains. Statistical analysis adopted a 5% coefficient for rejection of the null hypothesis. Although aged animals showed skin repair, complete reepithelialization was found on day 21 in some animals of both groups (treated and control). In aged rats, the wound area was significantly smaller in treated wounds than in untreated wounds, resulting in a larger scar area compared with the adult group. When treated wounds were compared, no differences were found between the wound areas in adult and aged rats. As expected, the collagen concentration was higher in normal skin from adult rats than in normal skin from aged animals, but there was no difference when aged skin was treated with tretinoin. These results indicate that tretinoin increases collagen synthesis in aged skin and returns the healing process to a normal state of skin healing.

An Experiment Using Functional Near-Infrared Spectroscopy and Robot-Assisted Multi-Joint Pointing Movements of the Lower Limb.

Stroke affects approximately 17 million individuals worldwide each year and is a leading cause of long-term disability. Robotic therapy has shown promise in helping stroke patients regain lost motor functions. One potential avenue for increasing the understanding of how motor recovery occurs is to study brain activation during the movements that are targeted by therapy in healthy individuals. Functional Near-Infrared Spectroscopy (fNIRS) has emerged as a promising neuroimaging technique for examining neural underpinnings of motor function. This study aimed to investigate fNIRS neural correlates of complex lower limb movements in healthy subjects. Participants were asked to perform cycles of rest and movement for 6 min using a robotic device for motor rehabilitation. The task required coordinated knee and ankle joint movements to point to targets displayed on a computer screen. Two experimental conditions with different levels of movement assistance provided by the robot were explored. The results showed that the fNIRS protocol effectively detected brain regions associated with motor control during the task. Notably, all subjects exhibited greater activation in the contralateral premotor area during the no-assistance condition compared to the assisted condition. In conclusion, fNIRS appears to be a valuable approach for detecting changes in oxyhemoglobin concentration associated with multi-joint pointing movements of the lower limb. This research might contribute to the understanding of stroke motor recovery mechanisms and might pave the way for improved rehabilitation treatments for stroke patients. However, further research is needed to fully elucidate the potential of fNIRS in studying motor function and its applications in clinical settings.

Physical exercise for treating non-motor symptoms assessed by general Parkinson's disease scales: systematic review and meta-analysis of clinical trials.

Introduction: Parkinson's disease is a movement disorder that also manifests non-motor symptoms (NMS). Physical exercise is a prominent strategy that can have an impact on NMS; however, the evidence is limited. Our aim was to verify the effects of exercise on NMS, as assessed using general NMS scales. Methods: This study is a systematic review and meta-analysis. Two searches were conducted on the PubMed, Cochrane Library, Scopus, Web of Science, Embase, Science Direct and PEDro databases from September to December 2022. The PEDro scale was used to assess the methodological quality of the studies. Results: Twenty-three studies were included. The interventions were classified as multimodal, aerobic, resistance, dance, conventional physical therapy and other types. Five studies had high risk of bias. Eight studies were included in the meta-analyses. According to the criteria, four studies compared exercise with non-exercise (n=159), two compared multimodal exercise with cognitive/leisure approaches (n=128), and two compared aerobic with conventional exercise (n=40). No statistical differences were observed between exercise and non-exercise (-0.26 (-0.58 to 0.05)) and between multimodal and cognitive approaches (0.21 (-0.14 to 0.55)). However, trends were observed in the direction of exercise and cognitive approaches. A significant difference was observed favouring aerobic over conventional exercise (-0.72 (-1.36 to -0.08)). Conclusions: Our findings suggest that exercise may have an effect on general NMS compared with non-exercise, although only a trend was observed. It was also observed for cognitive approaches over multimodal exercises. Aerobic exercise showed near-large effects compared with conventional exercise.

Sevoflurane and isoflurane anesthesia induce redox imbalance, but only sevoflurane impairs vascular contraction.

Volatile anesthetics may cause vascular dysfunction; however, underlying effects are unclear. The aim of the present study was to investigate whether sevoflurane and isoflurane affect vascular function, nitric oxide (NO) bioavailability, and biomarkers of oxidative stress and inflammation. Wistar rats were divided into three experimental groups: Not anesthetized (control group) or submitted to anesthesia with isoflurane (Iso group) or sevoflurane (Sevo group). Hemodynamic parameters were monitored during anesthesia, and blood gas values and biochemical determinants were analyzed. Isometric contractions were recorded in aortic rings. Vasoconstriction induced by potassium chloride (KCl) and phenylephrine (Phe) were measured. No differences in hemodynamic parameters and blood gasses variables were observed. Impaired KCl and Phe-induced contractions were observed in endothelium-intact aorta of Sevo compared to Iso and Control groups. Redox imbalance was found in Sevo and Iso groups. Reduced NO bioavailability and increased activity of matrix metalloproteinase 2 (MMP-2) were observed in Sevo, but not in the Iso group. While reduced IL-10 and IL-1ß were observed in Sevo, increases in IL-1ß in the Iso group were found. Sevoflurane, but not isoflurane, anesthesia impairs vasocontraction, and reduced NO and cytokines and increased MMP-2 activity may be involved in vascular dysfunction after sevoflurane anesthesia.

Biochemical and Toxinological Characterization of Venom from Macrorhynchia philippina (Cnidaria, Hydrozoa).

Macrorhynchia philippina is a colonial benthic hydroid from the Class Hydrozoa (Phylum Cnidaria) distributed in the tropical and subtropical marine waters from Atlantic Ocean, Indo-Pacific, and Mozambique. Its colonies somewhat resemble plants, causing confusion in the bathers who accidentally touch the animal. Acute burning/local pain, edema, erythema, and pruritus were symptoms already described, but its venom composition is unknown, as well as the participation of toxins for the symptom's development. Thus, herein, we show the biochemical composition and toxic effects of M. philippina venom. Colonies were collected and processed for histological analysis; alternatively, they were immersed into methanol containing 0.1% acetic acid for venom attainment, which was analyzed by mass spectrometry and submitted to edema and nociception evaluation in mice, hemolysis and antimicrobial assays in vitro. Before the molecule's extraction, it was possible to see the inoculation structures (hydrocladiums and hydrotheca) containing venom, which was released after the immersion of the animal in the solvents. The venom was composed mainly by low molecular mass compounds, able to cause significant reduction of the paw withdrawal latency from the hot plate test, 30 minutes after the injection. Moreover, significant edema was observed 10 and 30 minutes after the injection, indicating the activity of at least two inflammatory mediators. The venom caused no hemolytic activity but reduced the growth of A. baumannii and K. pneumoniae strains. This study is the first biochemical description of M. philippina venom, with molecules that cause fast inflammatory and painful effects, characteristic of the envenomation.

Anti-Migratory Effect of Dipotassium Glycyrrhizinate on Glioblastoma Cell Lines: Microarray Data for the Identification of Key MicroRNA Signatures.

The nuclear factor kappa B (NF-κB) pathway has been reported to be responsible for the aggressive disease phenomenon observed in glioblastoma (GBM). Dipotassium glycyrrhizinate (DPG), a dipotassium salt of glycyrrhizic acid isolated from licorice, has recently demonstrated an anti-tumoral effect on GBM cell lines U87MG and T98G through NF-κB suppression by IRAK2- and TRAF6-mediating microRNA (miR)-16 and miR-146a, respectively. Thus, the present study aimed to evaluate the expression profiles of miRNAs related to NF-κB suppression in T98G GBM cell line after DPG exposure using miRNA microarray (Affymetrix Human miRNA 4.0A), considering only predicted miRNAs as NF-κB regulator genes. Additional assays using U251 and U138MG cells were performed to validate the array results. DPG cytotoxicity was determined by (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and cellular apoptosis was quantified by DNA fragmentation and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. The anti-proliferative effect was observed by cell proliferation and wound-healing assays, and the sphere formation assay examined whether DPG reduced stem cell subpopulation formation. The most over-expressed miRNAs were miR-4443 and miR-3620. The cytotoxic effect of DPG in U251 and U138MG was observed with an IC50 of 32 and 20 mM for 48 h, respectively. The IC50 of each cell line was used in all further assays. DPG treatment-induced apoptosis is observed by DNA fragmentation and increased TUNEL-positive cells. Cell proliferation and wound-healing assays showed an anti-proliferative and anti-migratory effect by DPG on the evaluated cell lines. In addition, DPG treatment led to a 100% reduction in sphere formation. The qPCR results in U251 and U138MG cells showed that DPG increased miR-4443 (2.44 vs. 1.11, p-value = 0.11; 8.27 vs. 1.25, p-value = 0.04) and miR-3620 expression (1.66 vs. 1.00, p-value = 0.03; 8.47 vs. 1.01, p-value = 0.03) and decreased CD209 (0.44 vs. 1.10, p-value = 0.03; 0.49 vs. 1.07, p-value = 0.04) and TNC (0.20 vs. 1.03, p-value = 0.001; 0.39 vs. 1.06, p-value = 0.01) mRNA levels compared to controls. Our results suggest that DPG inhibits cell viability by activating apoptosis and inhibiting cell proliferation and stem cell subpopulation formation through miR-4443 and miR-3620 upregulation. Both miRNAs are responsible for the post-transcriptional inhibition of NF-κB by CD209 and TNC modulation.

Non-Coding RNA in Penile Cancer.

Penile cancer (PC) still presents a health threat for developing countries, in particular Brazil. Despite this, little progress has been made on the study of markers, including molecular ones, that can aid in the correct management of the patient, especially concerning lymphadenectomy. As in other neoplasms, non-coding RNAs (ncRNAs) have been investigated for penile cancer, with emphasis on microRNAs, piRNAs (PIWI-interacting small RNAs), and long non-coding RNAs (LncRNAs). In this context, this review aims to assemble the available knowledge on non-coding RNA linked in PC, contributing to our understanding of the penile carcinogenesis process and addressing their clinical relevance. ncRNAs are part of the novel generation of biomarkers, with high potential for diagnosis and prognosis, orientating the type of treatment. Furthermore, its versatility regarding the use of paraffin samples makes it possible to carry out retrospective studies.

Primary Leiomyosarcoma of the Glans.

Penile leiomyosarcoma isz an extremely uncommon entity that rarely occurs in the glans. Due to the limited number of cases described in literature, guidelines regarding non-surgical treatment, prognosis, and management remain equivocal. Among the mesenchymal tumors of the penis, leiomyosarcoma has the highest propensity for recurrence. It originates in the smooth muscle cells from two distinct locations: superficial and deep. The deep subtype is the most aggressive and has the highest potential for metastasis. Surgical treatment should be implemented early and must be locally aggressive. Herein, we present a rare case of a 54-year-old patient with deep localized leiomyosarcoma of the glans, albeit with superficial characteristics. A review of the main histopathological, clinical, immunohistochemical, and therapeutic aspects of this unusual entity is presented.

The greater black krait (Bungarus niger), a newly recognized cause of neuro-myotoxic snake bite envenoming in Bangladesh.

Prospective studies of snake bite patients in Chittagong, Bangladesh, included five cases of bites by greater black kraits (Bungarus niger), proven by examination of the snakes that had been responsible. This species was previously known only from India, Nepal, Bhutan and Burma. The index case presented with descending flaccid paralysis typical of neurotoxic envenoming by all Bungarus species, but later developed generalized rhabdomyolysis (peak serum creatine kinase concentration 29,960 units/l) with myoglobinuria and acute renal failure from which he succumbed. Among the other four patients, one died of respiratory paralysis in a peripheral hospital and three recovered after developing paralysis, requiring mechanical ventilation in one patient. One patient suffered severe generalized myalgia and odynophagia associated with a modest increase in serum creatine kinase concentration. These are the first cases of Bungarus niger envenoming to be reported from any country. Generalized rhabdomyolysis has not been previously recognized as a feature of envenoming by any terrestrial Asian elapid snake, but a review of the literature suggests that venoms of some populations of Bungarus candidus and Bungarus multicinctus in Thailand and Vietnam may also have this effect in human victims. To investigate this unexpected property of Bungarus niger venom, venom from the snake responsible for one of the human cases of neuro-myotoxic envenoming was injected into one hind limb of rats and saline into the other under buprenorphine analgesia. All animals developed paralysis of the venom-injected limb within two hours. Twenty-four hours later, the soleus muscles were compared histopathologically and cytochemically. Results indicated a predominantly pre-synaptic action (ß-bungarotoxins) of Bungarus niger venom at neuromuscular junctions, causing loss of synaptophysin and the degeneration of the terminal components of the motor innervation of rat skeletal muscle. There was oedema and necrosis of extrafusal muscle fibres in envenomed rat soleus muscles confirming the myotoxic effect of Bungarus niger venom, attributable to phospholipases A2. This study has demonstrated that Bungarus niger is widely distributed in Bangladesh and confirms the risk of fatal neuro-myotoxic envenoming, especially as no specific antivenom is currently manufactured. The unexpected finding of rhabdomyolysis should prompt further investigation of the venom components responsible. The practical implications of having to treat patients with rhabdomyolysis and consequent acute renal failure, in addition to the more familiar respiratory failure associated with krait bite envenoming, should not be underestimated in a country that is poorly equipped to deal with such emergencies.

Food consumption patterns, overweight and cardiovascular risk: a cross-sectional analysis of the Pró-Saúde Study, Brazil, 2013. / Padrão de consumo de alimentos, excesso de peso e risco cardiovascular: uma análise transversal do Estudo Pró-Saúde, 2013.

OBJECTIVE: To identify food consumption patterns and association between overweight and risk of cardiovascular disease. METHODS: This was a cross-sectional study with staff of the Universidade do Estado do Rio de Janeiro, Brazil, who took part in the Pró-Saúde Study. Food consumption was investigated using a food frequency questionnaire. Association between dietary patterns (exposure) and overweight and cardiovascular risk (outcomes) was estimated using linear regression. RESULTS: Among the 520 staff assessed, four dietary patterns were found: 'ultra-processed', 'healthy', 'meat' and 'traditional'. After adjustment, the 'meat' pattern was inversely associated with waist circumference (ß=-1.52 - 95%CI -2.66;-0.39), body mass index (ß=-0.56 - 95%CI -1.01;-0.11), and the Framingham Risk Score (ß=-0.36 - 95%CI -0.64;-0.09). CONCLUSION: In view of excess weight, risk of cardiovascular disease and inverse association between the 'meat' food consumption pattern and BMI, it is important to conduct further investigations, with non-working groups, with the aim of gaining greater understanding of the health-disease process related to food consumption.