Development of a Model to Predict Invasiveness in Ductal Carcinoma In Situ Diagnosed by Percutaneous Biopsy—Original Study and Critical Evaluation of the Literature

Background

Approximately 30% of ductal carcinoma in situ (DCIS) cases have an invasive component discovered on the final analysis that could affect surgical management. The aims of the present study were to determine the risk factors associated with the underestimation of DCIS and to develop a model to predict the probability of invasiveness.

A Hypoxia-Targeted Boron Neutron Capture Therapy Agent for the Treatment of Glioma

Purpose

Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation has been limited by the poor tumor selectivity of agents. To address this unmet need, a boronated 2-nitroimidazole derivative (B-381) was synthesized and evaluated for its capability of targeting hypoxic glioma cells.

Methods

B-381 has been synthesized from a 1-step reaction. Using D54 and U87 glioma cell lines, the in vitro cytotoxicity and cellular accumulation of B-381 has been evaluated under normoxic and hypoxic conditions compared to L-boronophenylalanine (BPA). Furthermore, tumor retention of B-381 was evaluated in vivo.

Results

B-381 had low cytotoxicity in normal and cancer cells. Unlike BPA, B-381 illustrated preferential retention in hypoxic glioma cells compared to normoxic glioma cells and normal tissues in vitro. In vivo, B-381 illustrated significantly higher long-term tumor retention compared to BPA, with 9.5-fold and 6.5-fold higher boron levels at 24 and 48 h, respectively.

Conclusions

B-381 represents a new class of BNCT agents in which their selectivity to tumors is based on hypoxic tumor metabolism. Further studies are warranted to evaluate B-381 and similar compounds as preclinical candidates for future BNCT clinical trials for the treatment of glioma.

     

Disrupting Short-Term Memory Maintenance in Premotor Cortex Affects Serial Dependence in Visuomotor Integration

Human behavior is biased by past experience. For example, when intercepting a moving target, the speed of previous targets will bias responses in future trials. Neural mechanisms underlying this so-called serial dependence are still under debate. Here, we tested the hypothesis that the previous trial leaves a neural trace in brain regions associated with encoding task-relevant information in visual and/or motor regions. We reasoned that injecting noise by means of transcranial magnetic stimulation (TMS) over premotor and visual areas would degrade such memory traces and hence reduce serial dependence. To test this hypothesis, we applied bursts of TMS pulses to right visual motion processing region hV5/MT+ and to left dorsal premotor cortex (PMd) during intertrial intervals of a coincident timing task performed by twenty healthy human participants (15 female). Without TMS, participants presented a bias toward the speed of the previous trial when intercepting moving targets. TMS over PMd decreased serial dependence in comparison to the control Vertex stimulation, whereas TMS applied over hV5/MT+ did not. In addition, TMS seems to have specifically affected the memory trace that leads to serial dependence, as we found no evidence that participants'' behavior worsened after applying TMS. These results provide causal evidence that an implicit short-term memory mechanism in premotor cortex keeps information from one trial to the next, and that this information is blended with current trial information so that it biases behavior in a visuomotor integration task with moving objects.SIGNIFICANCE STATEMENT Human perception and action are biased by the recent past. The origin of such serial bias is still not fully understood, but a few components seem to be fundamental for its emergence: the brain needs to keep previous trial information in short-term memory and blend it with incoming information. Here, we present evidence that a premotor area has a potential role in storing previous trial information in short-term memory in a visuomotor task and that this information is responsible for biasing ongoing behavior. These results corroborate the perspective that areas associated with processing information of a stimulus or task also participate in maintaining that information in short-term memory even when this information is no longer relevant for current behavior.     

Autoimmune/inflammatory syndrome induced by mineral oil: a health problem

Autoimmune/inflammatory syndrome induced by adjuvant (ASIA) includes the following conditions: siliconosis, Gulf War syndrome, macrophagic myofasciitis syndrome, and post-vaccination phenomena. Afterward, other syndromes have been recognized, such as in ASIA by mineral oil (ASIA-MO). These conditions are triggered by adjuvants and they are the result of the interplay of genetic and environmental factors. ASIA-MO is defined as the infiltration of oily type modeling substances for cosmetic purposes. It has been reported in many countries and used surreptitiously. Pathogenesis of ASIA-MO is not clear, but is characterized by chronic granulomatous inflammation, like the pristane model in mice, with increase of proinflammatory cytokines: type I interferons (IFNα and IFNß), systemic lupus erythematosus (SLE), and erosive arthritis. In humans, an increase of interleukin 1 (IL-1) has been found. Clinical spectrum of ASIA-MO is heterogeneous, varying from mild to severe and being local and systemic. The systemic manifestations can be non-specific and specific, meeting criteria for any autoimmune disease (AID), i.e., SLE, rheumatoid arthritis, and systemic sclerosis, among others. The areas of the body where the mineral oil is mostly applied include the following: buttocks (38–72%), breasts (12–16%), lower extremities (18–22%), and face (6–10%). The penis augmentation is also common. Treatment is focused on local and systemic manifestations and requires medical and surgical management representing a challenge for the physician.     

Levocarnitine Decreases Intradialytic Hypotension Episodes: A Randomized Controlled Trial

Intradialytic hypotension is common complication in stage 5 chronic kidney disease patients on hemodialysis. Incidence ranges from 15 to 30%. These patients have levocarnitine deficiency. A randomized, placebo‐controlled quadruple‐blinded trial was designed to demonstrate the levocarnitine efficiency on intradialytic hypotension prevention. Patients were randomized into four groups, to receive levocarnitine or placebo. During the intervention period, levocarnitine and placebo was administered 0 and 30 min before each hemodialysis session, respectively. During the trial, 33 patients received 1188 hemodialysis sessions. We identified 239 (21.3%) intradialytic hypotension episodes. The intradialytic hypotension episodes were less frequent in the levocarnitine group (9.3%, 60 IH events) (P < 0.001). Hemodialysis is frequently perplexed by intradialytic hypotension episodes. Levocarnitine supplementation before each hemodialysis session efficiently diminishes the intradialytic hypotension episodes. This is a new application method that must be considered and explored.     

Frequency and expression of ALS and HWP1 genotypes in Candida albicans strains isolated from Mexican patients suffering from vaginal candidosis

To detect the frequency and expression of eight ALS (agglutinin‐like sequence) genes and the HWP1 genotype in a group of Candida albicans strains isolated from Mexican women suffering from vaginal candidosis. A group of 264 women (age 15–57 years) with vaginal infections were evaluated. C. albicans was identified by PCR amplification of the rRNA internal transcribed spacer regions ITS1 and ITS2. The ALS and HWP1 genes were identified by conventional PCR, and their expression levels were determined by real‐time PCR after growing C. albicans strains in reconstituted human vaginal epithelium (RHVE). C. albicans was identified in 50 women (18.9%). The genotypic frequencies were ALS1 100%, ALS2 60%, ALS3 36%, ALS4 54%, ALS5 70%, ALS6 56%, ALS7 64%, ALS9 66% and HWP1 92%. The most frequently expressed genes in the strains harbouring all of the genes were ALS4 (100%), ALS1 (87.5%), ALS2 (87.5%), ALS3 (87.5%), ALS5 (87.5%), ALS7 (87.5%) and HWP1 (75.0%). Nineteen per cent of the vaginal infections were caused by C. albicans, and a high proportion of the strains carried genes encoding proteins involved in adhesion to epithelia. The ALS and HWP1 genes were expressed in RHVE, suggesting that the Als and Hwp1 proteins play an important role in the pathogenesis of the infection.     

On the functional integration between postural and supra-postural tasks on the basis of contextual cues and task constraint

In order to evaluate the effects of uncertainty about direction of mechanical perturbation and supra-postural task constraint on postural control, young adults had their upright stance perturbed while holding a tray in a horizontal position. Stance was perturbed by moving forward or backward a supporting platform, contrasting situations of certainty versus uncertainty of direction of displacement. Increased constraint on postural stability was imposed by a supra-postural task of equilibrating a cylinder on the tray. Performance was assessed through EMG of anterior leg muscles, angular displacement of the main joints involved in the postural reactions and displacement of the tray. Results showed that both certainty on the direction of perturbation and increased supra-postural task constraint led to decreased angular displacement of the knee and the hip. Furthermore, combination of certainty and high supra-postural task constraint produced shorter latency of muscular activation. Such postural responses were paralleled by decreased displacement of the tray. These results suggest a functional integration between the tasks, with central set priming reactive postural responses from contextual cues and increased stability demand.     

Metabolic disorder and obesity in 5027 Brazilian postmenopausal women

Objectives: To evaluate the frequency of obesity in postmenopausal women and assess the potential effects of increased body mass index (BMI) on lipoprotein profile and on risk factors for arterial hypertension and diabetes.

Design: A cross-sectional study was conducted with 5027 postmenopausal Brazilian women. Analyses were performed of BMI and cardiovascular factors (systemic blood pressure [BP], total cholesterol, low-density lipoprotein, high-density lipoprotein [HDL-C], triglyceride, and fast glucose). The statistical analysis included the chi-square and Mann-Whitney tests. The significance level was set at 5%.

Results: Obesity (BMI >30) in our study characterized approximately 30% of the 5027 postmenopausal women. The comparison of patients with normal BMI and those with high BMI showed that high BMI had a significant negative effect on BP, as evidenced by the increased frequency of hypertension in overweight and obese patients (>25) (p?p?p?Conclusion: Our data showed the high frequency of obesity in our population and of the cardiovascular risks (glucose, systemic arterial hypertension, and low HDL-C) associated with high BMI.