Randomized, double-blind, sham-controlled trial to evaluate the efficacy and tolerability of electroconvulsive therapy in patients with clozapine-resistant schizophrenia.

There is no established treatment for patients with clozapine-resistant schizophrenia (CRS). Clozapine augmentation strategies with antipsychotics or others substances are effective in comparison with placebo while and Electroconvulsive therapy (ECT) showed to be effective in comparison with treatment as usual (TAU) but not with placebo (sham-ECT). In the present double- blind randomized controlled trial, we compared 40 outpatients who received 20 sessions of ECT (n = 21) or sham-ECT (n = 19) (age = 37.40 ± 9.62, males = 77.5 %, illness duration = 14.95 ± 8.32 years, mean total Positive and Negative Syndrome Scale (PANSS) = 101.10 ± 24.91) who fulfilled well-defined CRS criteria including baseline clozapine plasma levels ≥350 ng/mL. The primary outcome was the ≥50 % PANSS Total Score reduction; secondary outcomes were the scores of the PANSS subscales, PANSS five-factor dimensions, PANSS-6 and the Calgary Depression Rating Scale (CDRS). Treatment response was analyzed by percentage reduction, Linear Mixed Models and effect sizes. At baseline both groups showed no differences except for years of school education (included as a covariate). At endpoint, only 1/19 of the completers (5.26 %) in the ECT group and 0/17 in the sham-ECT group showed a ≥50 % total PANSS score reduction. Both groups showed no significant differences of the total PANSS score (F = 0.12; p = 0.73), Positive (F = 0.27, p = 0.61), Negative (F = 0.25, p = 0.62), and General Psychopathology scores (F = 0.01, p = 0.94) as well for all PANSS five factors, the PANSS-6 and CDRS. Thus, the present study found no evidence that ECT is better than Sham-ECT in patients with CRS. Future sham-ECT controlled studies with larger sample sizes are warranted to test the efficacy of ECT for patients with CRS.

A multicenter, open-label, randomized, phase II study of cediranib with or without lenalidomide in iodine 131-refractory differentiated thyroid cancer.

BACKGROUND: Multitargeted tyrosine kinase inhibitors (TKIs) of the vascular endothelial growth factor receptor (VEGFR) pathway have activity in differentiated thyroid cancer (DTC). Lenalidomide demonstrated preliminary efficacy in DTC, but its safety and efficacy in combination with VEGFR-targeted TKIs is unknown. We sought to determine the safety and efficacy of cediranib, a VEGFR-targeted TKI, with or without lenalidomide, in the treatment of iodine 131-refractory DTC. PATIENTS AND METHODS: In this multicenter, open-label, randomized, phase II clinical trial, 110 patients were enrolled and randomized to cediranib alone or cediranib with lenalidomide. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate, duration of response, toxicity, and overall survival (OS). Patients (≥18 years of age) with DTC who were refractory to further surgical or radioactive iodine (RAI) therapy as reviewed at a multispecialty tumor board conference, and evidence of disease progression within the previous 12 months and no more than one prior line of systemic therapy were eligible. RESULTS: Of the 110 patients, 108 started therapy and were assessable for efficacy. The median PFS was 14.8 months [95% confidence interval (CI) 8.5-23.8 months] in the cediranib arm and 11.3 months (95% CI 8.7-18.9 months) in the cediranib with lenalidomide arm (P = 0.36). The 2-year OS was 64.8% (95% CI 43.3% to 86.4%) and 75.3% (95% CI 59.4% to 91.0%), respectively (P = 0.80). The serious adverse event rate was 41% in the cediranib arm and 46% in the cediranib with lenalidomide arm. CONCLUSIONS: Single-agent therapy with cediranib showed promising efficacy in RAI-refractory DTC similar to other VEGFR-targeted TKIs, while the addition of lenalidomide did not result in clinically meaningful improvements in outcomes.

Magnetism in a 2D Hybrid Ruddlesden-Popper Perovskite through Charge Redistribution Driven by an Organic Functional Spacer.

Two-dimensional Ruddlesden-Popper (RP) perovskites are emerging materials offering great synthetic versatility and remarkable features due to the tunability of their crystal structure. We present a novel strategy to provide magnetism in a 2D RP perovskite using histidine molecules as a spacer, which could induce charge rebalancing at the interface of the inorganic layer. We observe that the amide and imidazole groups are close to Pb ions. The interaction with the imidazole indicates that this functional group, possibly assisted by the carboxyl close to the vicinity of the amine terminal, is inducing charge rearrangement from Pb2+ to paramagnetic Pb3+ ions, resulting in a positive magnetic moment. This magnetized 2D hybrid perovskites can be classified as a novel class of promising materials showing a magnetic moment at their interface, which may result in intriguing physical properties due to a delicate balance between magnetism and a quantum well confinement effect in the inorganic layer.

Proinflammatory circulating markers: new players for evaluating asymptomatic acute cardiovascular toxicity in breast cancer treatment.

PURPOSE: This study aimed to evaluate markers of cardiac damage (total CK, CKMB and CRP), inflammatory markers (free iron, homocysteine and TNF-α) as well as lipidogram in breast cancer patients undergoing acute cycles of doxorubicin (DOX), paclitaxel (PTX) or trastuzumab (TZ) and to verify if there is an association between these markers and the toxicity of the chemotherapeutic treatment. Methods: Included in the study were 120 breast cancer patients and 50 healthy controls. All analyzes were performed on automated systems. For the statistical analysis, each group was compared with the controls according to their normality by Student's t-test and Mann-Whitney test. Results: Our results showed that DOX treatment led to increased hsCRP (4.80 ± 1.23 mg/dL, p = 0.0005), triglycerides (187.6 ± 25.06, p = 0.0231), TNF-α (42.31 ± 17.96 pg/mL, p = 0.01) and Fe levels (138.8 ± 18.6 µg/dL, p = 0.0193). In the meantime, PTX induced changes in CK-MB (8.78 ± 4.2 U/L, p = 0.0361), hsCRP (7.12 ± 1.87 mg/dL, p = 0.0006), cholesterol (201.7 ± 19.54, p = 0.05), triglycerides (201.7 ± 19.54, p = 0.0277), TNF-α (38.27 ± 9.12 pg/mL, p = 0.023), homocysteine (10.95 ± 0, 86 µmol/L, p = 0.005), and free iron (113 ± 18 6 µg/dL, p = 0.045) while TZ augmented CK-MB (6.9 ± 1.97 U/L, p < 0.00), hsPCR (3.12 ± 0.68 mg/dL, p = 0.095), cholesterol (218.3 ± 16.79, p = 0.0317), triglycerides (218.3 ± 16.79, p = 0.0127), TNF-α (89.6 ± 12.11, p = 0.032), homocysteine (9.95 ± 1.15 µmol/L, p = 0.0396), free iron (120.5 ± 4.64 µg/dl, p = 0.0058) as well. Conclusions: Our data demonstrated the existence of a proinflammatory net triggered by breast cancer chemotherapy that could increase cardiomyocytes permeability and allow the leakage of circulating proteins as CK-MB and induce the production of hsCRP.

Eficiência de duas técnicas de recuperação de espermatozoides epididimários de cães e avaliação seminal pós-criopreservação / [Efficiency of two techniques for recovering epididymal spermatozoids from dogs and seminal evaluation post cryopreservation]

O objetivo deste trabalho foi avaliar a recuperação de espermatozoides epididimários de cães castrados, utilizando as técnicas de fluxo retrógrado (FR) e flutuação (FL) em diluidor Tris-gema, antes e após a criopreservação. Foram coletados 30 complexos testículo-epididímos (CTE), sendo 15 para FR e 15 para FL, e, logo após a recuperação dos espermatozoides, foram analisadas as alterações morfológicas nessas células espermáticas. Após a adição do diluidor, foram avaliados os parâmetros de motilidade total (MOT) e vigor (V) espermáticos. O sêmen pós-criopreservado foi submetido ao teste de termorresistência nos tempos T0, T30, T60 e T90 minutos, além da avaliação das membranas plasmática e acrossomal por sondas fluorescentes. Não houve diferença estatística entre as técnicas quanto à MOT e ao vigor no sêmen diluído (FR-MOT: 82,3% e V: 3,4; FL-MOT: 79,6% e V: 3,2) e pós-criopreservado (FR-MOT: 34% e V: 2,8; FL-MOT: 30% e V: 2,7). A partir do T30, houve diferença significativa quanto à MOT e ao vigor nas técnicas utilizadas, e o tempo também prejudicou o acrossoma espermático a partir do T30. Conclui-se que as técnicas de recuperação de espermatozoides epididimários de cães castrados, testadas neste trabalho, podem ser utilizadas para refrigeração e criopreservação de sêmen.(AU)

The objective of this work was to evaluate the recovery of epididymal spermatozoa from castrated dogs using retrograde flow (FL) and flotation (FL) techniques in Tris-egg yolk diluent, before and after cryopreservation. Thirty testicle-epididymal complexes (CTE) were collected, 15 for FR and 15 for FL and soon after spermatozoid recovery, morphological changes in these spermatic cells were analyzed. After addition of the diluent, the parameters of total motility (MOT) and vigor (V) were evaluated. The post-cryopreserved semen was submitted to thermoresistance (TTR) test at T0, T30, T60 and T90 minutes, as well as the plasma and acrosomal membrane evaluation by fluorescent probes. There was no statistically significant difference between techniques tested for MOT and vigor in the diluted semen (FR-MOT: 82.3% and V: 3.4, FL-MOT: 79.6% and V: 3.2) and post-cryopreserved (FR-MOT: 34% and V: 2.8, FL-MOT: 30% and V: 2.7). From the T30 there was a significant difference regarding MOT and vigor in the used techniques, and the time also damaged the spermatic acrosome from the T30. It is concluded that the epididymal spermatozoa recovering techniques from castrated dogs, tested in this study, can be used for semen refrigeration and cryopreservation.(AU)

Transcranial Doppler could help to differentiate the types of dementia? A pilot study when CSF biomarkers are not available.

Our objective was to find a mean flow velocity (MFV) cut-off point to differentiate between normal and cognitive impaired patients using Clinical Dementia Rating (CDR) as a comparison method. To evaluate MFV (in cm/s) and pulsatility index (PI) from the left middle cerebral artery (MCA) and basilar artery using transcranial Doppler in a pilot study from an outpatient cognition unit and compare with cognitively normal older adults (at the age of sixty or older) from the Geriatric Ambulatory of Fluminense Federal University. We hypothesized that there is a MFV and PI cut-off point to potentially distinguish between normal and impaired cognition. Sixty-one patients with cognitive decline, including 18 with amnestic mild cognitive impairment (aMCI), 31 with probable Alzheimer disease (AD), 12 with vascular dementia (VD), and 10 cognitively normal older adults were included in the study. Patients with dementia (both AD and VD, p < 0.01) and aMCI (p < 0.05) had lower MFV than the control group in the MCA (32.2 cm/s, 31.9 cm/s, and 36.6 cm/s, respectively) and dementia patients had higher PI compared to control (AD and VD, both p < 0.05). Basilar MFV showed to be no difference between the patients and the control group. A cut off value of 39.1 cm/s was found in a ROC curve (area under de curve value 0.85, 95% CI 0.75-0.95) for mean MCA MFV to be predictive of cognitive impairment (CDR ≥ 0.5). In this study, the values of MCA MFV below 39.1 cm/s were predictive of cognitive impairment according to CDR. TCD is an inexpensive method that could be used in a clinical scenario to help differentiate normal cognition from cognitive decline. Multicentric and longitudinal studies should be done to validate that.

Effect of urine contamination on stallion semen freezing ability.

Urospermia is a common ejaculatory dysfunction of stallions. Current practice suggests that urine contaminated semen should not be used for cryopreservation. The aim of this study was to determine effects of urine contamination on semen freezing. Sixty-five ejaculates from eight stallions were divided into no urine (CONT), low (20% urine, LOW), and high (50% urine, HIGH) samples. Semen was extended with a commercial cooling extender, cushion-centrifuged, resuspended to 200 million/mL in a commercial egg-yolk based extender, and cryopreserved in liquid nitrogen. A subset of ejaculates (n = 20) were split in two after cushion-centrifugation, and one half of the ejaculate was submitted to a single-layer gradient centrifugation before cryopreservation. Sperm motility parameters were assessed pre- and post-freezing with an automated sperm analyzer. Semen pH, creatinine, and urea concentrations were assessed in raw samples, after urine contamination and after centrifugation and extension. Statistical analyses were performed with ANOVA and Tukey's posthoc. There were significant reductions in total and progressive sperm motilities (i.e., %TM and %PM, respectively) with increasing urine contamination pre-freezing (%TM 67 ±â€¯1.7, %PM 50 ±â€¯2.2, CONT), (%TM 60.3 ±â€¯1.7, % PM 42.5 ±â€¯2.1, LOW), and (%TM 41.3 ±â€¯2, %PM 21.3 ±â€¯1.5, HIGH). Post-thaw motilities for CONT (%TM 54 ±â€¯2.3, %PM 40.8 ±â€¯3.3) and LOW (%TM 51.7 ±â€¯1.8, %PM 36.2 ±â€¯2.1) were not different, but were higher than the HIGH (%TM 31.5 ±â€¯1.2, %PM 17.1 ±â€¯1.0) (p < 0.05). Post-thaw sperm viability was significantly lower in the HIGH (54.7 ±â€¯2.4) than in the CONT (63.8 ±â€¯2.3) or LOW (64.6 ±â€¯3.4) groups. Semen creatinine and urine levels were significantly higher with increasing urine contamination and were significantly decreased after centrifugation and resuspension in freezing extender. Pre-treatment semen pH was significantly lower than semen contaminated with low or high amounts of urine, and pH decreased significantly after centrifugation and resuspension. Gradient centrifugation did not improve %TM in the control group, but it did improve pre-freeze %TM and %PM in the low and high groups and improved significantly post freezing %TM and %PM in the high urine contaminated group. Semen contaminated with a small amount of urine may be suitable for freezing, whereas highly contaminated semen might not be usable. Although urine was mostly removed in this fashion, the initial exposure to high quantities was sufficient to decrease sperm motility pre- and post-freezing, whereas low urine contamination was not as detrimental.

Treatment with ascorbic acid and α-tocopherol modulates oxidative-stress markers in the spinal cord of rats with neuropathic pain.

Vitamin E (vit. E) and vitamin C (vit. C) are antioxidants that inhibit nociception. The effect of these vitamins on oxidative-stress markers in the spinal cord of rats with chronic constriction injury (CCI) of the sciatic nerve is unknown. This study investigated the effect of intraperitoneal administration of vit. E (15 mg·kg-1·day-1) and vit. C (30 mg·kg-1·day-1), given alone or in combination, on spinal cord oxidative-stress markers in CCI rats. Adult male Wistar rats weighing 200-250 g were divided equally into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve), which received injections of vitamins or vehicle (saline containing 1% Tween 80) for 3 or 10 days (n=6/each group). The vitamins prevented the reduction in total thiol content and the increase in superoxide-anion generation that were found in vehicle-treated CCI rats. While nitric-oxide metabolites increased in vehicle-treated CCI rats 3 days after surgery, these metabolites did not show significant changes in vitamin-treated CCI rats. In all rats, total antioxidant capacity and hydrogen-peroxide levels did not change significantly. Lipid hydroperoxides increased 25% only in vehicle-treated CCI rats. These changes may contribute to vit. C- and vit. E-induced antinociception, because scavenging reactive oxygen species seems to help normalize the spinal cord oxidative status altered by pain.

Effects of N-acetylcysteine on spinal cord oxidative stress biomarkers in rats with neuropathic pain.

N-acetylcysteine (NAC) inhibits nociceptive transmission. This effect has been associated partly with its antioxidant properties. However, the effect of NAC on the levels of lipid hydroperoxides (a pro-oxidant marker), content of ascorbic acid (a key antioxidant molecule of nervous tissue) and total antioxidant capacity (TAC) is unknown. Thus, our study assessed these parameters in the lumbosacral spinal cord of rats with chronic constriction injury (CCI) of the sciatic nerve, one of the most commonly employed animal models of neuropathic pain. Thirty-six male Wistar rats weighing 200-300 g were equally divided into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve). All rats received intraperitoneal injections of NAC (150 mg·kg-1·day-1) or saline for 1, 3, or 7 days. Rats were killed 1, 3, and 7 days after surgery. NAC treatment prevented the CCI-induced increase in lipid hydroperoxide levels only at day 1, although the amount was higher than that found in naive rats. NAC treatment also prevented the CCI-induced increase in ascorbic acid content, which occurred at days 1, 3, and 7. No significant change was found in TAC with NAC treatment. The changes observed here may be related to the antinociceptive effect of NAC because modulation of oxidative-stress parameters seemed to help normalize the spinal cord oxidative status altered by pain.

Plasminogen activator inhibitor 1 and Antipain preserve acrosome integrity of bovine spermatozoa during cryopreservation / Inibidor do ativador do plasminogênio 1 e antipaína preservam a integridade do acrossoma de espermatozoides bovinos durante a criopreservação

Seminal plasma contains serine proteases and serine protease inhibitor, which are involved in mammalian fertilization, and the inhibitors can be applied to prevent cold-induced sperm capacitation. The effects of different concentrations of two serine protease inhibitors were analyzed, Plasminogen activator inhibitor 1 - PAI-1 (70ƞg, 140ƞg and 210 ƞg) and Antipain (10µg, 50µg and 100µg) as supplementation to bovine semen cryopreservation extender. The effects of the inhibitors on the sperm parameters (sperm kinetics - CASA, acrosome integrity, plasma membrane integrity, mitochondrial membrane potential, sperm defects and acrosome reaction rate) were evaluated in the post-thaw semen. Cryopreservation of sperm with Antipain decreased post-thaw kinetic parameters of MP, VSL, LIN, SRT and the percentage of hyper-activated sperm while PAI-1 (210 ƞg) decreased VSL and LIN. Antipain and PAI-1 had no effect on the integrity parameters of the plasma membrane, mitochondrial membrane potential and sperm defects. Sperm cryopreserved in the presence of Antipain and PAI-1 (70 and 140 ƞg) preserved acrosome integrity, as they were able to complete the in vitro acrosome reaction. In conclusion, the serine protease inhibitors, Antipain and PAI-1 (70 and 140ƞg) are able to preserve the acrosome integrity of cryopreserved bovine sperm.(AU)

A criopreservação é parcialmente prejudicial à fertilidade do sêmen de bovinos e induz mudanças semelhantes à capacitação em espermatozoides. O plasma seminal contém serina-proteases e inibidores de serina-proteases que estão envolvidos na fertilização de mamíferos, e os inibidores podem ser aplicados para evitar uma capacitação espermática induzida pelo frio. Analisaram-se os efeitos de diferentes concentrações de dois inibidores de serina-proteases, inibidor do ativador do plasminogênio 1 - PAI-1 (70ƞg, 140ƞg e 210ƞg) e antipaína (10µg, 50µg e 100µg) na suplementação ao diluidor de criopreservação de sêmen bovino. Trinta e seis ejaculados de quatro bovinos Curraleiro Pé-Duro foram usados para criopreservação. Os efeitos dos inibidores sobre os parâmetros dos espermatozoides (cinética espermática - CASA, integridade acrossomal, integridade da membrana plasmática, potencial de membrana mitocondrial, defeitos espermáticos e taxa de reação acrossomal) foram avaliados no sêmen pós-descongelamento. A criopreservação de espermatozoides com antipaína diminuiu os parâmetros cinéticos pós-descongelamento de MP, VSL, LIN, SRT e a porcentagem de espermatozoides hiperativados, PAI-1 (210ƞg) diminuiu VSL e LIN. Antipaína e PAI-1 não tiveram efeitos nos parâmetros de integridade da membrana plasmática, no potencial de membrana mitocondrial e nos defeitos espermáticos. Espermatozoides criopreservados na presença de antipaína e PAI-1 (70 e 140ƞg) preservaram a integridade acrossomal, assim como foram capazes de completar a reação acrossômica in vitro. Em conclusão, os inibidores de serina-proteases, antipaína e PAI-1 (70 e 140ƞg) são capazes de preservar a integridade acrossomal de espermatozoides criopreservados de bovinos.(AU)

N-acetylcysteine downregulates phosphorylated p-38 expression but does not reverse the increased superoxide anion levels in the spinal cord of rats with neuropathic pain.

We determined the effect of N-acetylcysteine (NAC) on the expression of the phosphorylated p38 (p-p38) protein and superoxide anion generation (SAG), two important players in the processing of neuropathic pain, in the lumbosacral spinal cord of rats with chronic constriction injury (CCI)-induced neuropathic pain. The sciatic functional index (SFI) was also measured to assess the functional recovery post-nerve lesion. Thirty-six male Wistar rats were divided equally into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve), which received 2, 4, or 8 intraperitoneal injections of NAC (150 mg·kg-1·day-1) or saline beginning 4 h after CCI. Rats were sacrificed 1, 3, and 7 days after CCI. The SFI was measured on these days and the lumbosacral spinal cord was used for analysis of p-p38 expression and SAG. CCI induced a decrease in SFI as well as an increase in p-p38 expression and SAG in the spinal cord. The SFI showed a partial recovery at day 7 in saline-treated CCI rats, but recovery was improved in NAC-treated CCI rats. NAC induced a downregulation in p-p38 expression at all time-points evaluated, but did not reverse the increased SAG induced by CCI. Since p-p38 is a mediator in neuropathic pain and/or nerve regeneration, modulation of this protein may play a role in NAC-induced effects in CCI rats.

Leiomiossarcoma gástrico associado a hérnia de hiato em cão da raça Shar-pei: relato de caso / Gastric leiomyosarcoma associated with hiatal hernia in a Shar-pei: a case report

Os tumores do sistema digestório não são comuns na medicina veterinária e as neoplasias de estômago representam menos de 1% de todos os tumores malignos. O leiomiossarcoma é o segundo tumor que mais acomete o trato gastrointestinal de cães, com predisposição para as regiões de jejuno e ceco, mas qualquer porção pode ser afetada, desde o esôfago até o reto. O presente trabalho relata um caso em um canino da raça Shar-pei, macho, com 13 anos de idade e histórico de episódios eméticos pós- prandiais e emagrecimento progressivo havia oito meses. Após avaliação radiográfica e endoscópica, foi indicada intervenção cirúrgica e observada tumoração gástrica associada a hérnia de hiato. O diagnóstico de leiomiossarcoma gástrico foi estabelecido por meio de análise histopatológica. O paciente apresentou pouco tempo de sobrevida, entretanto destaca-se a raridade desse tipo de neoplasia gástrica e da associação desse tipo tumoral com hérnias de hiato, assim como a importância da análise histopatológica para o correto diagnóstico desse tipo de patologia.(AU)

Gastrointestinal system tumors are not common in Veterinary Medicine and stomach neoplasia represents less than 1% of all malignant tumors. Among digestive neoplasias, the leiomyosarcoma is the second most common with predisposition to the regions of the jejunum and cecum, but any portion from the esophagus to rectum can be potentially affected. This is a case report of a 13-year-old male Shar-pei dog with medical history of post prandial emetic episodes and progressive weight loss lasting eight months. Surgical intervention was indicated after radiographs and endoscopic evaluation, where a gastric mass and hiatal hernia were found. The diagnosis of gastric leiomyosarcoma was established only after histopathological analysis. Despite the patient having little survival time, this clinical presentation of a gastric tumor associated with hiatal hernia is rare, and exalts the importance of histopathological studies as a tool for the correct diagnosis in these unusual diseases.(AU)

Toothpaste with Nanosized Trimetaphosphate Reduces Enamel Demineralization.

This double-blind crossover study assessed the effects of a low-fluoride (low-F) dentifrice containing nanosized sodium trimetaphosphate (TMP) on enamel demineralization in situ. Nineteen subjects wore palatal appliances containing 4 blocks of bovine enamel and were randomly assigned to brush their teeth with placebo (without F/TMP), 250-ppm F (250F), 250F plus 0.05% nanosized TMP (250F-TMPnano), and 1,100-ppm F (1,100F) dentifrices during 7 d, under cariogenic challenge. Enamel surface hardness and cross-sectional hardness (ΔKHN [Knoop hardness number]), as well as F, calcium (Ca), and phosphorus (P) concentrations, were determined. Also, biofilm that formed on the blocks was analyzed for F, Ca, P, and insoluble extracellular polysaccharide concentrations. Data were submitted to analysis-of-variance models and Student-Newman-Keuls test ( P < 0.05). The 250F-TMPnano dentifrice promoted the lowest ΔKHN among all groups ( P < 0.001), while the percentage of surface hardness loss was similar to 1,100F. Also, similar F, Ca, and P concentrations in enamel were observed for 1,100F and 250F-TMPnano. In the biofilm, the highest F content was observed for 1,100F; Ca content was similar between 1,100F and 250F-TMPnano; and P content was similar among all groups. Similar extracellular polysaccharide values were observed for 250F-TMPnano and 1,100F ( P < 0.001), ionic activity of CaHPO40, CaF+, and HF0 ( P < 0.05) and degree of saturation of hydroxyapatite and CaF2 ( P < 0.05). It was concluded that the protective effect of 250F-TMPnano dentifrice was similar to a conventional dentifrice for most of the variables studied, having a more pronounced effect on the subsurface lesion when compared with the conventional toothpaste (1,100F). Knowledge Transfer Statement: Although toothpastes containing ≥1,000-ppm fluoride are more effective than low-fluoride formulations against dental caries, their early use can lead to side effects. This has prompted intensive research on alternatives to increase the anticaries effect of low-fluoride toothpastes. The present in situ study demonstrated that the addition of sodium trimetaphosphate nanoparticles to toothpastes containing 250-ppm fluoride significantly enhances the protective effect of this formulation against enamel demineralization to levels comparable to a 1,100-ppm fluoride toothpaste in terms of most of the variables studied. Most important, this formulation promoted the lowest loss of subsurface hardness among all groups, suggesting that caries lesions would take longer to develop under clinical conditions when compared with a conventional (1,100-fluoride) toothpaste.

Provável extrusão de núcleo pulposo aguda e não compressiva em um cão: relato de caso / Probable acute non-compressive nucleus pulposus extrusion in a dog: case report

A extrusão discal aguda e não compressiva é caracterizada pela extrusão de caráter agudo/hiperagudo e não compressivo do núcleo pulposo de um disco intervertebral não degenerado. Pode ser chamada de hérnia de disco de baixo volume e alta velocidade ou explosões discais e geralmente está associado a exercícios intensos ou episódios traumáticos. O núcleo pulposo é fortemente forçado através de uma pequena fissura no ânulo fibroso dorsal, provocando uma contusão espinhal. Este relato tem como objetivo apresentar um caso de provável extrusão aguda de núcleo pulposo não compressiva. Foi atendido um cão macho, três anos e seis meses de idade, maltês, pesando 4,1kg. Como queixa principal, o proprietário relatou dificuldade locomotora e dor à manipulação há um dia, sem histórico de trauma. Foi constatada paraparesia não ambulatória de início agudo com ausência de propriocepção e dor superficial em membros pélvicos e dor à palpação epaxial da coluna toracolombar. A ressonância magnética (RM) evidenciou extensa área de hipersinal em segmento toracolombar da medula espinhal, sem sinais de compressão medular e de atenuação da intensidade do núcleo pulposo do disco intervertebral L1-L2. Foi feito diagnóstico presuntivo de mielopatia focal não compressiva com edema medular de todo segmento toracolombar, característico de uma extrusão aguda de núcleo pulposo não compressiva. Foi prescrito tratamento com anti-inflamatório esteroidal, analgésico, repouso absoluto e protocolo de reabilitação com acupuntura e fisioterapia. Após sete dias de tratamento, o animal recuperou a sensibilidade dolorosa superficial em membros pélvicos e evoluiu para paraparesia ambulatória. Os resultados deste relato sugerem que a RM pode ser útil para fazer um diagnóstico presuntivo em cães com histórico e sinais clínicos compatíveis. Além disso, o tratamento conservativo em extrusões discais não compressivas é preconizado e o paciente pode apresentar boa recuperação.(AU)

Acute and non-compressive disc extrusion is characterized by the acute character of extrusion of the nucleus pulposus without real compression of the spine. It has been called low-volume and high speed disc herniation or disc explosions, and usually is associated with an intense exercise or traumatic episode. This report aims to present a case of an acute extrusion of nucleus pulposus with no compression of the spinal cord. A 3.5 year-old male dog of the Maltes breed, weighing 4.1kg was presented at the Veterinary Hospital with locomotion disorders and pain during manipulation with no history of trauma. At the physical and neurological examination, non-ambulatory paraparesis of acute onset with absence of proprioception and superficial pain in hind limbs was found, as well as pain on palpation of epaxial thoracolumbar spine. Magnetic resonance imaging (MRI) showed extensive hyper intense area in the thoracolumbar spinal cord, with no signs of spinal cord compression, and decreased intensity of the nucleus pulposus of the L1-L2 intervertebral disc. Additionally, a spinal cord edema in all thoracolumbar segments was seen that is characteristic of an acute extrusion of non-compressive nucleus pulposus. A presumptive diagnosis of non-compressive myelopathy was assumed. The dog was prescribed steroidal anti-inflammatory, analgesic, absolute rest and rehabilitation protocol, including acupuncture and physiotherapy. The patient recovered superficial pain in the pelvic limbs and evolved into ambulatory paraparesis after seven days. The results of this report suggested that MRI can be useful for making a presumptive diagnosis in dogs with a history of compatible clinical signs. Moreover, the conservative treatment in non-compressive disc extrusions can be feasible.(AU)

New route for hollow materials.

Hollow micro/nano structures form an important family of functional materials. We have used the thermal oxidation process combined with the passage of electric current during a structural phase transition to disclose a colossal mass diffusion transfer of Ti ions. This combination points to a new route for fabrication of hollow materials. A structural phase transition at high temperature prepares the stage by giving mobility to Ti ions and releasing vacancies to the system. The electric current then drives an inward delocalization of vacancies, condensing into voids, and finally turning into a big hollow. This strong physical phenomenon leading to a colossal mass transfer through ionic diffusion is suggested to be driven by a combination of phase transition and electrical current followed by chemical reaction. We show this phenomenon for Ti leading to TiO2 microtube formation, but we believe that it can be used to other metals undergoing structural phase transition at high temperatures.

Avaliação in vitro do sêmen criopreservado de cães naturalmente infectados por Leishmania sp / In vitro evaluation of cryopreserved semen of dogs naturally infected by Leishmania sp

O objetivo deste trabalho foi avaliar a qualidade in vitro do sêmen criopreservado de cães naturalmente infectados por Leishmania sp. Foram coletadas amostras de sêmen de 12 cães, sendo seis positivos (GI) e seis negativos (GII) para leishmaniose visceral (LV), semanalmente, totalizando quatro coletas por animal. O sêmen criopreservado foi avaliado pelo teste de termorresistência rápida (TTR), nos tempos zero, 30 e 60 minutos, pela análise computadorizada (CASA) e por meio de sondas fluorescentes; esta última técnica com o intuito de avaliar a integridade das membranas espermáticas. Houve diferença estatística pela técnica de TTR no parâmetro motilidade progressiva, no tempo 0min (68,33% GI e 72,50% GII), e no vigor espermático (2,67 GI e 3,0 GII), no tempo 30min. Quanto ao CASA, houve diferença estatística apenas na motilidade total (27,50% GI e 57,08% GII), embora os demais parâmetros seminais tenham apresentado valores relativos diminuídos nos cães do GI. Nas análises com sondas fluorescentes, foram observadas diferenças estatísticas entre os grupos quanto à integridade das membranas plasmática e acrossomal e ao potencial mitocondrial das células espermáticas. Concluiu-se que a LV pode comprometer a qualidade do sêmen criopreservado de cães parasitados.(AU)

The aim of this study was to evaluate the in vitro quality of cryopreserved semen of dogs naturally infected by Leishmania sp. 12 dog semen samples were collected, with 06 positive (GI) and 06 negative (GII) for Visceral Leishmaniasis (LV), weekly, totaling 04 collections per animal. The cryopreserved semen was evaluated by the Rapid Termorresistência Test (TTR), at 0, 30 and 60 minutes by computer analysis (CASA) and by means of fluorescent probes, the latter technique in order to assess the integrity of the sperm membrane. There was no statistical difference for the TTR technique in the progressive motility parameter, at time 0min (68.33% GI and GII 72.50%), and sperm vigor (2.67 GI and GII 3.0), time 30min. As for the CASA, there was statistical difference only in total motility (27.50% GI and GII 57.08%), although other semen parameters have submitted lower figures for GI dogs. In the analyzes with fluorescent probes statistical differences were noted between the groups in terms of plasma membrane integrity and acrosomal and mitochondrial potential of sperm cells. It was concluded that LV can compromise the quality of cryopreserved semen of infected dogs.(AU)

Response-adapted volume de-escalation (RAVD) in locally advanced head and neck cancer.

BACKGROUND: Efforts to reduce the late toxicity associated with chemoradiation (CRT) for locally advanced head and neck squamous cell cancer (LA-HNSCC) have focused on radiotherapy (RT) dose de-escalation. In this phase I/II protocol investigating the addition of everolimus to induction chemotherapy (IC), we incorporated a novel response-adapted volume de-escalation (RAVD) approach using IC response to guide the extent of RT volume reduction. PATIENTS AND METHODS: Patients with measurable LA-HNSCC received two cycles of IC (cisplatin, paclitaxel, cetuximab ± everolimus). Patients with ≥50% reduction in the sum of tumor diameters [good response (GR)] received TFHX (paclitaxel, fluorouracil, hydroxyurea, and 1.5 Gy twice daily RT every other week) to a dose of 75 Gy with the single planning target volume (PTV1) encompassing exclusively gross disease. Patients with <50% response [non-response (NR)] were treated with TFHX encompassing PTV1 and the next nodal station at risk (PTV2) to a dose of 45 Gy followed by a sequential boost to PTV1 to a dose of 75 Gy. RESULTS: Ninety-four patients were enrolled. Randomization to everolimus was discontinued on interim analysis after 50 patients due to futility. IC response was evaluable in 89 patients. Thirty-seven patients (41.6%) had GR and 52 (58.4%) had NR. There was a trend for improved progression-free (P = 0.086) but not overall survival (P = 0.94) for GR versus NR. The 2-year PFS and OS were 86.0% and 83.5% for GR and 68.7% and 85.4% for NR, respectively. NR were significantly more likely to undergo G-tube placement during treatment (50.0% GR versus 73.5% NR, P = 0.040) and be G-tube dependent at 6-month follow-up (5.7% GR versus 32.6% NR, P = 0.005). CONCLUSIONS: The addition of everolimus to IC was not beneficial. The elimination of elective nodal coverage in patients with GR to IC did not appear to compromise outcomes and resulted in significantly decreased late toxicity. Further investigation of RAVD is warranted. CLINICALTRIALSGOV: NCT01133678.

Effect of avocado/soybean unsaponifiables on ligature-induced bone loss and bone repair after ligature removal in rats.

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the effects of administration of avocado/soybean unsaponifiable (ASU), a drug that is commonly used in the treatment of rheumatoid arthritis, on ligature-induced bone loss and bone repair after ligature removal in rats. MATERIAL AND METHODS: Eighty-four rats were randomly assigned to four groups of equal size and received a daily gavage of either sterile saline [control (CTR)] or ASU (0.6 mg/kg), starting 7 d before (ASU/-7), on the day of (ASU/0) or 7 d after (ASU/+7) periodontitis induction. Periodontitis was induced by placing silk ligatures into the gingival sulcus of the second maxillary molars for 7 d; after 7 d, the ligatures were removed. Seven rats from each group were sacrificed, 7, 15 or 30 d after ligature removal. Bone resorption was evaluated by histomorphometry and micro-computed tomography (micro-CT). Immunohistochemistry was used to evaluate the expression of TRAP, RANKL and alkaline phosphatase (ALP), and quantitative PCR (qPCR) was used to evaluate the levels of interleukin-1beta (Il1ß), tumor necrosis factor alpha (Tnfα), interleukin-6 (Il-6), Rankl and Alp. Statistical analysis was performed using the Shapiro-Wilk test, ANOVA and Tukey's test for normal data, and using the Kruskall-Wallis and Dunnet's tests for non-normal data (p < 0.05). RESULTS: Histomorphometry and micro-CT analysis showed greater bone resorption in the CTR group than in the ASU/0 (15 d) and ASU/+7 (7 and 15 d) groups. The CTR group also presented with a higher expression of TRAP (15 and 30 d) and RANKL (7 and 15 d) compared with ASU/0 and ASU/+7 groups. Similarly, qPCR analysis showed higher levels of Rankl and Il1ß mRNAs, and lower levels of Alp mRNA, in the CTR group compared with all other groups (for all periods). CONCLUSION: ASU exhibited a positive effect on bone repair following ligature-induced periodontitis in rats.

Hierarchically structured nanowires on and nanosticks in ZnO microtubes.

We report both coaxial core-shell structured microwires and ZnO microtubes with growth of nanosticks in the inner and nanowires on the outer surface as a novel hierarchical micro/nanoarchitecture. First, a core-shell structure is obtained-the core is formed by metallic Zn and the semiconducting shell is comprised by a thin oxide layer covered with a high density of nanowires. Such Zn/ZnO core-shell array showed magnetoresistance effect. It is suggested that magnetic moments in the nanostructured shell superimposes to the external magnetic field enhancing the MR effect. Second, microtubes decorated with nanowires on the external surface are obtained. In an intermediate stage, a hierarchical morphology comprised of discrete nanosticks in the inner surface of the microtube has been found. Hyperfine interaction measurements disclosed the presence of confined metallic Zn regions at the interface between linked ZnO grains forming a chain and a ZnO thicker layer. Surprisingly, the metallic clusters form highly textured thin flat regions oriented parallel to the surface of the microtube as revealed by the electrical field gradient direction. The driving force to grow the internal nanosticks has been ascribed to stress-induced migration of Zn ions due to compressive stress caused by the presence of these confined regions.

Impact of puberty status and melengestrol acetate supplementation before the breeding period on reproductive efficiency of Bos indicus beef heifers.

Two experiments were designed to evaluate the impact of puberty status and the administration of melengestrol acetate (MGA) before onset of the breeding period on ovulatory responses (Exp. 1) and conception rate after AI performed on estrus detection during 10 d and the pregnancy rate through 80 d of breeding period (Exp. 2) of pasture-grazed beef heifers. In Exp. 1, heifers (15 pubertal and 15 prepubertal) received 0.5 mg per heifer/d -1 of MGA over 14 d. No differences in the ovulatory responses were found 10 d after the MGA administration (pubertal = 46.7% vs. prepubertal P = 53.3%; P = 0.72). In Exp. 2, 368 heifers were randomly assigned to groups according to pubertal status and the MGA treatment. All heifers were inseminated on estrus detection for up 10 d after MGA administration and following exposure to bulls between 20 and 80 d. The MGA-treated heifers exhibited a greater AI service rate than control heifers (72.1 vs. 41.6%;P < 0.01); however, heifers receiving MGA had lower conception results following AI (51.6 vs. 71.4%; P = 0.01). In addition, MGA-treated heifers were more likely to have a corpus luteum in the middle of the breeding period (95.3 vs. 87.5%;P < 0.01), although the Cox proportional hazard of pregnancy rate was similar (P = 0.29) at the end of the breeding period. At onset of the breeding period, pubertal heifers presented a greater pregnancy rate following AI (pubertal P = 42.2% vs. prepubertal P = 24.9%; P = 0.01). Therefore, pubertal heifers seem to have greater overall reproductive efficiency than prepubertal heifers, particularly at the beginning of the breeding period. Interestingly, administration of MGA before the onset of the breeding period increased AI service rate but did not alter the rate of pregnancy throughout the breeding period of pasture-grazed beef heifers.