Translation and validation into Brazilian Portuguese of the English version of the International Consultation on Incontinence Modular Questionnaire for Male Lower Urinary Tract Symptoms (ICIQ-MLUTS).

OBJECTIVES: To translate and cross-culturally adapt the English version of the International Consultation on Incontinence Modular Questionnaire for Male Lower Urinary Tract Symptoms (ICIQ-MLUTS) into Brazilian Portuguese and evaluate its psychometric properties. INTRODUCTION: Male lower urinary tract symptoms (LUTS) are frequent and commonly assessed with questionnaires. The ICIQ-MLUTS is a robust instrument that investigates the main aspects of LUTS in men and their impact on quality of life. Although highly recommended, Grade A is not as popular as the International Prostate Symptom Score (IPSS) and remained untranslated and unvalidated for Brazilian Portuguese. METHODS: After authorization by the Advisory Board of the International Consultation on Incontinence (ICIQ) the translation process was conducted according to the standard guidelines and the ICIQ validation protocol. Internal consistency was assessed using Cronbach's ⍺ coefficient and values > 0.7 were considered satisfactory. To assess test-retest reliability and reproducibility, Spearman's correlation coefficient and intraclass correlation coefficient were used. For group data, a Spearman correlation coefficient or an intraclass correlation coefficient of at least 0.70 demonstrates good test-retest reliability. A p < 0.05 was considered significant. RESULTS: One hundred and eighty-six, aged 61.41 ± 11.01 years, suffering from LUTS participated in the study between January 2021 and October 2022. Cronbach's ⍺, 0.875, demonstrated the internal consistency of the Portuguese version of ICIQ-MLUTS. The intraclass correlation coefficient of 0.912 (0.882; 0.935 - 95% CI) for the test-retest evidenced the stability and validity of the instrument. Likewise, Spearman's correlation coefficient highlighted the agreement between IPSS and ICIQ-MLUTS, 0.906, <0.001. DISCUSSION: The Portuguese version of the ICIQ-MLUTS demonstrated internal consistency, stability, and validity, in addition to agreement with the IPSS. CONCLUSION: The ICIQ-MLUTS, translated and validated into Brazilian Portuguese, is a robust and reliable instrument to assess LUTS in Brazilian men and can be used in the evaluation of treatment and research.

Syagrus coronata fixed oil prevents rotenone-induced movement disorders and oxidative stress in Drosophila melanogaster.

One prominent aspect of Parkinson's disease (PD) is the presence of elevated levels of free radicals, including reactive oxygen species (ROS). Syagrus coronata (S. coronata), a palm tree, exhibits antioxidant activity attributed to its phytochemical composition, containing fatty acids, polyphenols, and flavonoids. The aim of this investigation was to examine the potential neuroprotective effects of S. coronata fixed oil against rotenone-induced toxicity using Drosophila melanogaster. Young Drosophila specimens (3-4 d old) were exposed to a diet supplemented with rotenone (50 µM) for 7 d with and without the inclusion of S. coronata fixed oil (0.2 mg/g diet). Data demonstrated that rotenone exposure resulted in significant locomotor impairment and increased mortality rates in flies. Further, rotenone administration reduced total thiol levels but elevated lipid peroxidation, iron (Fe) levels, and nitric oxide (NO) levels while decreasing the reduced capacity of mitochondria. Concomitant administration of S. coronata exhibited a protective effect against rotenone, as evidenced by a return to control levels of Fe, NO, and total thiols, lowered lipid peroxidation levels, reversed locomotor impairment, and enhanced % cell viability. Molecular docking of the oil lipidic components with antioxidant enzymes showed strong binding affinity to superoxide dismutase (SOD) and glutathione peroxidase (GPX1) enzymes. Overall, treatment with S. coronata fixed oil was found to prevent rotenone-induced movement disorders and oxidative stress in Drosophila melanogaster.

Dry residue of cassava on slow-growing broiler diets, with or without the addition of carbohydrases.

Dry residue of cassava was studied on the digestibility, performance, intestinal measurements, with or without inclusion of carbohydrases, of slow-growing broilers. 160 Label Rouge broiler chickens, 21-d-old, were distributed in a randomized, 2x5 factorial arrangement (male and female x 0, 10, 20, 30 and 40% residue) (metabolism trial). 1,100 male chicks were distributed in a 2x5 factorial arrangement (with/without carbohydrases x 0; 2.5; 5.0; 7.5; and 10.0% residue), with five replicates (performance trial). Increasing residue levels led to increases in energetic values. Feed intake from 1-21-d-old and 1-63-d-old decreased linearly. At 42 d-old, feed intake and weight gain levels exhibited a quadratic response, which predicted a highest value at 3.32% and 4.77%, respectively, for diets without carbohydrases. For 21- and 42-d-old chickens, the inclusion of carbohydrases reduced the weight and length of the small intestine. The energetic values of the diets were positively influenced by the residue and had similar digestibility values for both sexes. Inclusion of up to 10% of residue in slow-growing broiler diets does not impaired performance and intestinal morphology. The addition of carbohydrases reduced the viscosity of the digesta but it was not enough to improve the performance of the birds.

Performance and bone characteristics of broilers fed diets supplemented with vitamin A at different concentrations.

This work evaluated the influence of vitamin A on performance, organ weight, and bone and skin characteristics in broilers (Cobb 500) at 21 and 42 days of age. A total of 1920 chickens were distributed in a randomised design, considering six vitamin A supplementation levels (0, 6000, 16,000, 26,000, 36,000, and 46,000 IU kg-1 ), with 16 replicates and 20 chickens per experimental unit, established due to rising the range of vitamin levels observed in the literature to evaluate the effect of vitamin A on broilers. At 22 days, half of the replicates from each treatment continued receiving the initial diet, and the other eight repetitions received diets without vitamin A (0 IU kg-1 ) until 42 days. The level of vitamin A influenced feed intake (FI) and body weight gain (BWG) until 21 days for all treatments. Broilers at 21 days of age had a more significant BWG at a vitamin A supplementation level of 28,209 IU kg-1 . At 42 days, vitamin A influenced the BWG and FI of broilers at treatments that were not supplemented after 21 days. Treatments supplemented up to 42 days showed quadratic responses to vitamin A for BWG, FI, and feed conversion. The vitamin A levels influenced the relative weights of the small intestine, pancreas, gizzard, abdominal fat, Seedor index, and breaking strength at 42 days, where the adequate supplementation of vitamin A improved these characteristics in broilers. Vitamin A supplementation from 22 to 42 days old did not affect broiler performance. An increased BWG was obtained when vitamin A supplementation occurred until 42 days, with supplementation of 29,375 IU kg-1 and a lower response of feed conversion with the addition of 27,775 IU kg-1 .

Therapeutic hypothermia is limited in preventing developmental impairments after neonatal hypoxia-ischemia.

The only current treatment for neonatal hypoxia-ischemia (HI) is therapeutic hypothermia (TH), which still shows some limitations. Specific effects of TH in the several processes involved in brain injury progression remain unclear. In this study, the effects of TH treatment on developmental parameters, behavioral outcomes, and peripheral leukocytes were evaluated in neonatal male and female rats. In P7, animals were submitted to right common carotid artery occlusion followed by hypoxia (8% oxygen). TH was performed by reducing the animal scalp temperature to 32°C for 5 h. Behavioral parameters and developmental landmarks were evaluated. Animals were euthanized at P9 or P21, and cerebral hemispheres, spleen, and thymus were weighed. White blood cells (WBC) were counted in blood smears. There was a reduction in the weight of the brain hemisphere ipsilateral to the carotid occlusion in HI and TH groups, as well as a reduction in body weight gain and a delay in the opening of the ipsilateral eye. Latency in negative geotaxis was increased by HI at P12. TH did not prevent brain weight loss, developmental impairments, or WBC number changes but prevented negative geotaxis impairment and spleen weight reduction. These data reinforce that a better understanding of the events that occur after HI and TH in both males and females is necessary and would allow the development of more adequate and sex-specific therapeutic approaches.

Structural and thermodynamic properties of quasi-2D Mo(1-x)Wx(S, Se, Te)2monolayer alloys: a statistical first principle study.

In this work, we report anab initiostudy of the structural and thermodynamic properties of two-dimensional transition-metal dichalcogenides (2D-TMDC) alloys, Mo(1-x)Wx(S, Se, Te)2, using the cluster expansion framework to compute the Helmholtz free energy of alloys as a function of alloy composition and temperature, in the framework of the generalized quasi-chemical approximation. We consider alloying only on the metal sublayer. Our results indicate a weak dependence of the structural properties (lattice constants, nearest-neighbor bond lengths, and layer width) on the alloy composition (i.e. concentrations of W and Mo atoms), in line with the very similar values of the atomic radii of Mo and W atoms. A stronger dependence on the chalcogen is obtained, a trend that reflects the larger variations in atomic radii among the three chalcogen species. As a function of composition, the structural parameters we examined show similar trends, with negligible bowing (i.e. deviations from a Vegard's law interpolation between end compounds), for the three alloys. Moreover, already at 300 K the behavior of these structural features as a function of composition is very similar to that of the standard-regular-solution (SRS) high-temperature limit. In contrast, the electronic band gaps of the the three alloys as a function of composition show small but significant bowing, as high as -1% to -2% near thex= 0.5 alloy composition. Similarly to the structural features, the band gaps attain the high-temperature SRS limit already at 300 K. Regarding thermodynamic properties, we obtain negative values of the internal energy of mixing for the three alloys over the full range of compositions. Therefore, the theoretical alloying phase diagram for the three alloys is featureless, with stability of a fully-mixed alloy at all temperatures and compositions, with no miscibility gap (hence no bimodal nor spinodal decomposition lines). The thermodynamic potentials (mixing internal energy, mixing entropy, and mixing free energy) reach the high-temperature limit at ∼1000 K, the temperature range of synthesis of 2D-TMDC alloys. These trends of structural and electronic properties of the 2D-TMDC alloys are due to the very similar atomic radii and the nearly identical coordination chemistry of Mo and W. Our results are in agreement with experimental work on the alloying of Mo and W atoms, for samples of Mo(1-x)WxS2monolayer alloys, that found that the random mixed alloy is the thermodynamically stable state for this alloy, with no segregation or phase separation.

AbobotulinumtoxinA is effective in patients with urinary incontinence due to neurogenic detrusor overactivity regardless of spinal cord injury or multiple sclerosis etiology: Pooled analysis of two phase III randomized studies (CONTENT1 and CONTENT2).

BACKGROUND: Neurogenic detrusor overactivity incontinence (NDOI) is often inadequately managed with oral therapy. OBJECTIVE: To assess efficacy and safety of abobotulinumtoxinA (aboBoNT-A; Dysport®; Ipsen Ltd.) according to etiology of NDOI. DESIGN, SETTING, AND PARTICIPANTS: Two phase III, randomized, double-blind studies (CONTENT1 [NCT02660138] conducted in Asia, Europe and North America; CONTENT2 [NCT02660359] conducted in the Americas, Asia, Europe and Oceania) both included patients with spinal cord injury (SCI) or multiple sclerosis (MS), with inadequately managed NDOI, regularly performing clean intermittent catheterization (CIC). INTERVENTION: Patients in CONTENT1 and CONTENT2 received aboBoNT-A injections 600 U (n = 162)/800 U (n = 161), or placebo (n = 162) into the detrusor muscle. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary endpoint: mean change from baseline in number of NDOI episodes/week at Week 6. Secondary endpoints: proportion of patients with no NDOI episodes; incontinence-related quality of life (I-QoL); urodynamic parameters; and time-to-retreatment. Safety was also assessed. Statistical analyses were conducted for pooled populations by etiology (aboBoNT-A doses vs. placebo). RESULTS AND LIMITATIONS: Of 485 randomized patients, 341 (70%) and 144 (30%) had SCI and MS etiologies, respectively. A significant reduction was observed in mean NDOI episodes/week at Week 6 with both aboBoNT-A doses versus placebo in the SCI (all p < 0.001) and MS (all p < 0.01) groups, as well as significant improvements in I-QoL and urodynamic parameters. Median time-to-retreatment was longer in patients with MS (48-62 weeks across doses) than those with SCI (39-44 weeks). Safety data were similar between etiologies. Urinary tract infection was the most frequent adverse event; similar numbers were reported across treatment groups. CONCLUSIONS: AboBoNT-A was well tolerated and significantly improved continence and bladder function, and QoL, in patients with SCI or MS with NDOI performing regular CIC. PATIENT SUMMARY: AboBoNT-A injections improved QoL, symptoms, and bladder function in patients with SCI or MS with bladder muscle overactivity that causes incontinence.

Effects of feeding diets with zinc-l-selenomethionine on growth performance of broilers subjected to cyclic heat stress.

Limited information exists on the use of zinc-l-selenomethionine (Zn-L-SeMet) in broiler diets and its effects on the growth performance, body temperature, mortality rates, blood profile, and gene expression, especially when animals are reared under cyclic heat stress conditions. This study aimed to investigate the impact of Zn-L-SeMet in broiler diets from 1 to 42 days of age reared under cyclic heat stress and its effects on growth performance, cloacal temperatures, mortality rate, blood parameters, and insulin-like growth factor 1 (IGF-1) and growth hormone receptor (GHR) gene expression in the breast muscle. A total of 1000 male Cobb 500® broiler chicks were randomly assigned to five treatments: 0, 0.15, 0.23, 0.47, and 1.30 mg/kg of Zn-L-SeMet. Each treatment consisted of 10 replicates with 20 birds each. No statistically significant differences in growth performance were observed from 1 to 21 days of age (P > 0.05). However, from 1 to 42 days, feed intake (FI) and feed conversion ratio (FCR) decreased linearly (P < 0.05). Cloacal temperatures showed no significant effects (P > 0.05), while overall mortality rate exhibited a quadratic response (P < 0.05), with the optimal inclusion level predicted to reduce broiler mortality at 0.71 mg/kg. Triglyceride (TRG) levels increased with 0.97 mg/kg (P < 0.05), and gama-glutamil transferase (GGT) levels decreased with the inclusion of 1.19 mg/kg (P < 0.05). No significant effects on IGF-1 and GHR gene expression were found (P > 0.05). In conclusion, the inclusion of 1.30 mg/kg of Zn-L-SeMet in diets of heat-stressed broilers improved growth performance from 1 to 42 days of age. An inclusion of 0.71 mg/kg reduced mortality rate, while 0.97 mg and 1.19 mg increased and reduced TRG and GGT levels, respectively.

Therapeutic hypothermia for the treatment of neonatal hypoxia-ischemia: sex-dependent modulation of reactive astrogliosis.

Therapeutic hypothermia (TH) is the standard treatment for neonatal hypoxia-ischemia (HI) with a time window limited up to 6 h post injury. However, influence of sexual dimorphism in the therapeutic window for TH has not yet been elucidated in animal models of HI. Therefore, the aim of this study was to investigate the most effective time window to start TH in male and female rats submitted to neonatal HI. Wistar rats (P7) were divided into the following groups: NAÏVE and SHAM (control groups), HI (submitted to HI) and TH (submitted to HI and TH; 32ºC for 5 h). TH was started at 2 h (TH-2 h group), 4 h (TH-4 h group), or 6 h (TH-6 h group) after HI. At P14, animals were subjected to behavioural tests, volume of lesion and reactive astrogliosis assessments. Male and female rats from the TH-2 h group showed reduction in the latency of behavioral tests, and decrease in volume of lesion and intensity of GFAP immunofluorescence. TH-2 h females also showed reduction of degenerative cells and morphological changes in astrocytes. Interestingly, females from the TH-6 h group showed an increase in volume of lesion and in number of degenerative hippocampal cells, associated with worse behavioral performance. Together, these results indicate that TH neuroprotection is time- and sex-dependent. Moreover, TH started later (6 h) can worsen volume of brain lesion in females. These data indicate the need to develop specific therapeutic protocols for each sex and reinforce the importance of early onset of the hypothermic treatment.

Toxicological assessment of a bioactive extract from Triplaris gardneriana Wedd. seeds using alternative models.

The Triplaris gardneriana Wedd. seeds extract has great therapeutic potential due to numerous biological activities such as antioxidant, antibacterial and anti-inflammatory, which are associated with phenolic content. Although this herbal preparation has shown many benefits, recently their toxicity profile has begun to be explored. In this present study, the toxic effects of T. gardneriana seeds ethanolic extract (EETg) on biological systems of different taxonomical groups and levels of complexity (from cell culture to lower vertebrates) were assessed, through a variety of viability and toxicological assays. It was found that EETg did not impair the Saccharomyces cerevisiae growth at the highest tested concentration (200 µg/mL), and no toxicant evidence was observed in Aedes aegypti larvae or in Drosophila melanogaster adult stage. Contrarily, the extract reduced the viability of undifferentiated Caco-2 cells (250 µg/mL, 40% of viable cells), but did not affect differentiated ones. The embryotoxicity in Danio rerio model showed a LC50 of 7.41 mg/L (95% confidence interval, 4.78 - 11.49 mg/L). EETg did not show signs of toxicity in the majority of the models used, but lethality and malformations in zebrafish embryos occurred. Further analyses are needed to better understand the selective toxicity mechanism of EETg on zebrafish, as well as whether the toxic effects happen in higher vertebrates.

Pouteria macrophylla Fruit Extract Microemulsion for Cutaneous Depigmentation: Evaluation Using a 3D Pigmented Skin Model.

Here, we verify the depigmenting action of Pouteria macrophylla fruit extract (EXT), incorporate it into a safe topical microemulsion and assess its effectiveness in a 3D pigmented skin model. Melanocytes-B16F10- were used to assess the EXT effects on cell viability, melanin synthesis, and melanin synthesis-related gene transcription factor expression, which demonstrated a 32% and 50% reduction of intra and extracellular melanin content, respectively. The developed microemulsion was composed of Cremophor EL®/Span 80 4:1 (w/w), ethyl oleate, and pH 4.5 HEPES buffer and had an average droplet size of 40 nm (PdI 0.40 ± 0.07). Skin irritation test with reconstituted epidermis (Skin Ethic RHETM) showed that the formulation is non-irritating. Tyrosinase inhibition was maintained after skin permeation in vitro, in which microemulsion showed twice the inhibition of the conventional emulsion (20.7 ± 2.2% and 10.7 ± 2.4%, respectively). The depigmenting effect of the microemulsion was finally confirmed in a 3D culture model of pigmented skin, in which histological analysis showed a more pronounced effect than a commercial depigmenting formulation. In conclusion, the developed microemulsion is a promising safe formulation for the administration of cutite fruit extract, which showed remarkable depigmenting potential compared to a commercial formulation.

Performance, metabolism, and meat quality of broilers fed dry brewery residue.

A study was conducted to assess the chemical composition and apparent metabolizable energy (AME), nitrogen-corrected AME (AMEn), and their respective coefficients of dry brewery residue (DBR) for broilers. A second study was conducted to evaluate the increasing inclusions of DBR in broiler diets and its effects on growth performance, carcass traits, blood metabolites, and meat quality. In the first trial (metabolism assay), a total of 250 male broilers were assigned to 5 diets (0, 100, 200, 300, and 400 g DBR/kg) composed by 5 replications with 10 animals per cage in a completely randomized design in the period from days 11 to 21. There was an increasing linear effect for AME, AMEn, metabolizable coefficient of gross energy (MCGE), and MCGE corrected for N (MCGEn). In the second experiment, a total of 840 one-day-old male broiler chickens were assigned to 6 treatments (0, 20, 40, 60, 80, and 100 g DBR/kg) with 7 replications and 20 animals per pen, from days 0 to 42. Growth performance was determined at days 21 and 42. There was an increasing linear effect for weight gain in the period from days 0 to 21 and for feed intake from days 0 to 42. A linear decreasing effect was observed at day 21 for cholesterol and quadratic effect for uric acid (UA), aspartate aminotransferase, and albumin. At day 42, there was a quadratic effect for UA and creatinine. At day 21, an increasing linear effect was observed for protein deposition rate. In conclusion, the inclusion of DBR up to 100 g/kg improved WG in the starter phase and did not negatively affect the productive parameters of broilers from days 0 to 42.

Influence of dietary corn distillers' dried grains with solubles on nutrient digestibility, growth performance, and carcass traits in rabbits.

Two experiments were performed to evaluate the digestibility and growth performance of New Zealand White rabbits fed corn distillers' dried grains with solubles (DDGS). For the digestibility trial, 20 rabbits were housed in metabolic cages. The animals were distributed in two treatments, T1 (control diet without inclusion of DDGS) and T2 (control diet + 300 g kg-1 DDGS). For the growth performance trial, 100 rabbits (50 males and 50 females) were assigned in a factorial design 2 × 5 (2 gender × 5 inclusions of DDGS) and five replicates. The treatments were composed of diets with inclusions of 0, 60, 120, 180, and 240 g kg-1 of DDGS. The rabbits were housed at 35 days old, and the experiment lasted 35 days. The DDGS showed high digestibility for protein (74.10%) and lipids (81.51%) and a high content of digestible energy (2979 kcal kg-1). In the second trial, growth performance and carcass yield and organ relative weights were evaluated. There were no interactions between gender and DDGS inclusions (P > 0.05). A linear decrease was observed for feed intake (FI) for the period from days 35 to 50 (FI, P = 0.001) and FI and FCR from days 35 to 70 (FI, P = 0.004; FCR, P = 0.001) with the increasing levels of DDGS. Rabbits supplemented with 240 g kg-1 had lower (P < 0.05) whole carcass yield (WCY) and carcass without head yield compared with the control rabbits. DDGS is highly digestible in rabbits, and when supplemented up to 240 g kg-1 in diets, it improved FCR but reduced FI and WCY.

A new case of osteogenesis imperfecta type VIII and retinal detachment.

Osteogenesis imperfecta (OI) type VIII (OMIM: 610915) is a rare autosomal recessive disorder characterized by white sclerae, severe growth deficiency, and bone fragility. This condition results from pathogenic variants of P3H1, a gene that codes for P3H1, an important protein involved in the prolyl-3-hydroxylation complex required for collagen type I folding. Here, we described a woman with OI type VIII due to a homozygous mutation of c.1914+1G>C (NM_001243246.1) in P3H1 and retinal detachment. We compared our case to five severe OI and retinal detachment cases reported in the literature. The only case previously reported with a molecular diagnosis had a similar mutation in P3H1 c.1914+1G>A and a giant retinal detachment. We suggest that individuals with OI type VIII should be submitted to careful fundoscopic examination.

Impact of a 1-day urodynamic course on knowledge, perceptions, and attitudes of urology residents.

AIMS: No evidence-informed educational curriculum is available for designing urodynamics (UDS) courses. We evaluated the learning outcomes of a short-lasting urodynamic course for urology residents. METHODS: Urology residents of postgraduate years 4 and 5 (n = 13 and n = 1316, respectively) attended a 1-day urodynamic course. Learning objectives included patient preparation, indication and technique, terminology, trace interpretation, and impact on patient management. Instructional methods consisted of short lectures (3 h) and case-based discussions (7.5 h). Learners' reactions, modifications of perceptions and attitudes, and acquisition of knowledge and skills were assessed by three written tests with a single group, pretest, posttest 1, and posttest 2 design. Tests were conducted precourse, 1 week after, and 4 months after the course. RESULTS: All participants felt more confident in several urodynamic competencies after the course, including patient preparation, urodynamic indication and technique, terminology, trace interpretation, and impact for patient management. These perceptions remained unchanged after 4 months. Most became stricter in the indication of UDS, including 20 (87.0%) at posttest 1 and 8 (66.7%) at posttest 2. The mean number of correct answers in the knowledge evaluation was 52.2% versus 61.4% versus 56.7%, respectively at pretest, posttest 1, and posttest 2; p = 0.535). All participants rated the course as very useful or useful in both posttest evaluations. CONCLUSIONS: Our study demonstrates that a 1-day urodynamic course can promote lasting improvements in self-reported perceptions, attitudes, and urodynamic-related competencies of urology residents. Further studies using evidence-informed educational principles are needed to determine the effect of specific educational interventions on urodynamic competencies in different contexts.

Synthesis of a novel glibenclamide-pioglitazone hybrid compound and its effects on glucose homeostasis in normal and insulin-resistant rats.

A new library of hybrid compounds that combine the functional parts of glibenclamide and pioglitazone was designed and developed. Compounds were screened for their antihyperglycemic effects on the glucose tolerance curve. This approach provided a single molecule that optimizes the pharmacological activities of two drugs used for the treatment of diabetes mellitus type 2 (DM2) and that have distinct biological activities, potentially minimizing the adverse effects of the original drugs. From a total of 15 compounds, 7 were evaluated in vivo; the compound 2; 4- [2- (2-phenyl-4-oxo-1,3-thiazolidin-3-yl) ethyl] benzene-1-sulfonamide (PTEBS) was selected to study its mechanism of action on glucose and lipid homeostasis in acute and chronic animal models related to DM2. PTEBS reduced glycemia and increased serum insulin in hyperglycemic rats, and elevated in vitro insulin production from isolated pancreatic islets. This compound increased the glycogen content in hepatic and muscular tissue. Moreover, PTEBS stimulated the uptake of glucose in soleus muscle through a signaling pathway similar to that of insulin, stimulating translocation and protein synthesis of glucose transporter 4 (GLUT4). PTEBS was effective in increasing insulin sensitivity in resistance rats by stimulating increased muscle glucose uptake, among other mechanisms. In addition, this compound reduced total triglycerides in a tolerance test to lipids and reduced advanced glycation end products (AGES), without altering lactate dehydrogenase (LDH) activity. Thus, we suggest that PTEBS may have similar effects to the respective prototypes, which may improve the therapeutic efficacy of these molecules and decrease adverse effects in the long-term.

Synthesis of chalcones derived from 1-naphthylacetophenone and evaluation of their cytotoxic and apoptotic effects in acute leukemia cell lines.

Chalcones and their derivatives have been described as promising compounds with antiproliferative activity against leukemic cells. This study aimed to investigate the cytotoxic effect of three synthetic chalcones derived from 1-naphthylacetophenone (F07, F09, and F10) in acute leukemia cell lines (K562 and Jurkat) and examine the mechanisms of cell death induced by these compounds. The three compounds were cytotoxic to K562 and Jurkat cells, with IC50 values ranging from 1.03 to 31.66 µM. Chalcones induced intrinsic and extrinsic apoptosis, resulting in activation of caspase-3 and DNA fragmentation. F07, F09, and F10 were not cytotoxic to human peripheral blood mononuclear cells, did not produce any significant hemolytic activity, and did not affect platelet aggregation after ADP stimulation. These results, combined with calculations of molecular properties, suggest that chalcones F07, F09, and F10 are promising molecules for the development of novel antileukemic drugs.

Cell Cycle Arrest and Apoptosis Induction by a New 2,4-Dinitrobenzenesulfonamide Derivative In Acute Leukemia Cells.

BACKGROUND: Current therapies for acute leukemias (ALs) are associated with severe adverse reactions and high relapse rates, which makes the search for new antileukemic agents a necessity. Therefore, the aim of this study was to evaluate the effects of a new sulfonamide, S1, in AL cells K562 and Jurkat. METHODS: The cytotoxic activity of S1 was assessed using MTT method. The involvement of apoptosis in the mechanism of cell death was assessed by flow cytometry and fluorescence microscopy. RESULTS: Our results demonstrated that S1 induced morphological changes suggestive of apoptosis in both K562 and Jurkat cells. Additionally, S1 was not cytotoxic to normal erythrocytes and mononuclear cells and had a highly selective cytotoxicity for AL lineages. The mechanisms of cell death induced by S1 in K562 cells involves cell cycle arrest at G2/M phase and the activation of both extrinsic and intrinsic apoptosis, with an increased FasR and AIF expression and the loss of mitochondrial potential. As for Jurkat, we observed cell cycle blockade at G0/G1 phase, phosphatidylserine exposure and the involvement of intrinsic apoptosis only, with mitochondrial potential loss and a reduced expression of Survivin.  Although sulfonamide S1 did not altered Bcl-2 and Bax expression in AL cell lines, it was able to activate caspase-3 in K562 cells. CONCLUSION: Our results suggest that sulfonamide S1 may be a promising candidate for the development of new drugs for the treatment of ALs.

A Soft Tactile Sensor Based on Magnetics and Hybrid Flexible-Rigid Electronics.

Tactile sensing is crucial for robots to manipulate objects successfully. However, integrating tactile sensors into robotic hands is still challenging, mainly due to the need to cover small multi-curved surfaces with several components that must be miniaturized. In this paper, we report the design of a novel magnetic-based tactile sensor to be integrated into the robotic hand of the humanoid robot Vizzy. We designed and fabricated a flexible 4 × 2 matrix of Si chips of magnetoresistive spin valve sensors that, coupled with a single small magnet, can measure contact forces from 0.1 to 5 N on multiple locations over the surface of a robotic fingertip; this design is innovative with respect to previous works in the literature, and it is made possible by careful engineering and miniaturization of the custom-made electronic components that we employ. In addition, we characterize the behavior of the sensor through a COMSOL simulation, which can be used to generate optimized designs for sensors with different geometries.

A chalcone derivative binds a putative allosteric site of YopH: Inhibition of a virulence factor of Yersinia.

Identification of allosteric inhibitors of PTPs has attracted great interest as a new strategy to overcome the challenge of discover potent and selective molecules for therapeutic intervention. YopH is a virulence factor of the genus Yersinia, validated as an antimicrobial target. The finding of a second substrate binding site in YopH has revealed a putative allosteric site that could be further exploited. Novel chalcone compounds that inhibit PTPs activity were designed and synthesized. Compound 3j was the most potent inhibitor, interestingly, with different mechanisms of inhibition for the panel of enzymes evaluated. Further, our results showed that compound 3j is an irreversible non-competitive inhibitor of YopH that binds to a site different than the catalytic site, but close to the well-known second binding site of YopH.