Three-dimensional Simulation on Patient-reported Outcomes Following Oncoplastic and Reconstructive Surgery of the Breast: A Randomized Trial.

Background: Three-dimensional (3D) imaging using computer simulations is an evolving technology. There is a lack of strong data on the use of this technology for oncoplastic (OP) and reconstructive surgery. Methods: A prospective, randomized, single-center trial including breast cancer patients undergoing OP or mastectomy with immediate breast reconstruction with implant (IBR) enrolled from November 2019 to October 2021 at the Hospital Nossa Senhora das Graças, Breast Unit in Curitiba, Brazil. Both patients undergoing OP and those in the IBR group were randomized to undergo 3D imaging and simulation of postoperative results (intervention group) or 3D imaging without simulation (control group). All patients were invited to complete a patient-reported outcome (BREAST-Q) expectations module and breast reconstruction or reduction/mastopexy module before and 6 months after surgery. Results: A total of 96 patients were enrolled. Sixty-nine patients (45 OP and 24 IBR) completed the pre- and postoperative questionnaires and were randomized for the simulation. Women in the OP group had higher expectations for breast appearance when clothed than those in the IBR implant group (93.4 ± 16.3 versus 82.9 ± 26.5; P = 0.03). The intervention group was more satisfied with information than the control group (P = 0.021). Both patients who underwent OP and IBR believed that the 3D simulation helped them understand the surgical process (86.6% and 75%, respectively). Conclusions: Preoperative 3D simulation significantly improved patient's satisfaction with information and did not decrease postoperative satisfaction with the outcomes. The incorporation of preoperative 3D simulation may be a valuable tool in breast reconstruction.

Leiomyosarcoma of the lower rectum managed by radiotherapy and surgery: A case report and review of literature.

Rectal leiomyosarcoma is a very rare entity. Surgery is the main treatment, but the place of radiation therapy remains unclear. A 67-year-old woman was referred for a few-weeks' history of bleeding and anal pain intensified during defecation. Pelvic magnetic resonance imaging (MRI) showed a rectal lesion and biopsies revealed a leiomyosarcoma of the lower rectum. She was free of metastasis on computed tomography imaging. The patient refused radical surgery. After discussion by a multidisciplinary team, the patient received pre-operative long-course radiotherapy followed by surgery. The tumor was treated with 50Gy delivered in 25 fractions, within 5 weeks. The aim of radiotherapy was local control, allowing organ-preservation. Four weeks after radiation therapy, organ-preservation surgery could be performed. She had no adjuvant treatment. At 38-months follow-up, she had no local recurrence. However, distant recurrence (lung, liver, and bone) was detected 38 months after the resection and was managed by intra-venous doxorubicin 60mg/m2 and dacarbazine 800mg/m2 every 3 weeks. The patient was in a stable condition for nearly 8 months. The patient died 4 years and 3 months after the diagnosis.

Impact of simultaneous management of hypertension and hypercholesterolemia with ACE inhibitors and statins on cardiovascular outcomes in the Brisighella Heart Study: A 8-year follow-up.

BACKGROUND AND AIMS: To evaluate the long-term effect of simultaneous treatment of hypertension and hypercholesterolemia with angiotensin-converting enzyme (ACE) inhibitors and statins on the incidence of major cardiovascular events (MACE) and other clinical outcomes. METHODS AND RESULTS: We considered data from a subset of Brisighella Heart Study (BHS) participants who were consecutively evaluated in three epidemiological surveys between 2012 and 2020. We excluded normotensive subjects and individuals with a low calculated 10-year CVD risk, hypertensive patients treated with antihypertensive drugs different from ACE inhibitors and patients who changed antihypertensive medications during follow-up. The remaining participants were divided into four groups depending on whether they were treated with (I) perindopril ± amlodipine without statin treatment (N. 132), (II) perindopril ± amlodipine and atorvastatin (N. 132), (III) an ACE inhibitor other than perindopril ± a calcium-channel blocker without statin therapy (N. 133), (IV) an ACE inhibitor other than perindopril ± a calcium-channel blocker and statin therapy (N. 145). The long-term (8 years) effects of the different combined treatment were compared among the pre-defined groups. Over the follow-up period of 8 years, the proportion of subjects who developed MACE, type 2 diabetes mellitus and hyperuricemia, and the proportion of subjects needing for the intensification of antihypertensive treatment to improve blood pressure control were statistically different among the predefined groups (P < 0.05). CONCLUSION: Combined treatment with ACE inhibitors and statins (especially atorvastatin) in hypertensive patients seems to significantly reduce the risk of developing CVD in comparison with treatment with ACE inhibitors alone.

Combined action of SAMe, Folate, and Vitamin B12 in the treatment of mood disorders: a review.

Mood disorders affect more than 500 million people around the world. In the last decade, their prevalence has increased, and many people suffer from nervousness, anxiety, and stress at least once in their lives. The incidence of mood disorders and anxiety increases during perimenopause or under stressful conditions. The social restrictions introduced during the COVID-19 pandemic have significantly increased the normal burden of psychological and psychic disorders. In moderate to severe cases, pharmacological treatment is currently recommended, while in mild disorders, especially in the initial phase, psychological therapy is preferable. It is known that several nutrients are crucial for brain function. Among them, folate (vitamin B9), cyanocobalamin (vitamin B12), and S-adenosyl-L-methionine (SAMe) have been shown to influence various neurobiological processes. Overall, the available evidence suggests that dietary supplementation with folic acid, vitamin B12, and SAMe can be beneficial for people with mild mood disorders.

COX-2 pathway is upregulated in ultra-high risk individuals for psychosis.

BACKGROUND: The identification of Ultra-High Risk (UHR) individuals is thought to be useful for early intervention to improve psychosis outcomes. However, transition rates vary widely, and there is an effort to make these criteria more specific and accurate. Neuroinflammation has been discussed in the pathophysiology of psychosis. The metabolism of eicosanoids is a key process in inflammatory states. Therefore, we investigated whether the study of the inflammatory COX-2 pathway through the quantification of the eicosanoid levels can be a useful approach for the characterisation of UHR individuals. METHODS: One hundred and twenty-two individuals were included in this study (67 UHR and 55 controls) based on performance on the Prodromal Questionnaire. UHR status was assessed by Structured Interview for Prodromal Syndromes (SIPS). We determined the levels of Prostaglandin F2α (PGF2α), Prostaglandin E2 (PGE2), and Thromboxane B2 (TxB2) in plasma using ELISA assays. RESULTS: Concentrations of PGE2 and TxB2 were increased in UHR compared to controls (p = 0.01 and p < 0.05, respectively). PGE2 and PGF2α levels were correlated to negative symptoms (p < 0.01 and p < 0.05), whereas TxB2 correlated with positive symptoms (p = 0.05) as assessed by the SIPS. CONCLUSIONS: Our findings suggest that overactivation of the COX-2 pathway may be related to an increased risk for psychosis. However, our data do not allow us to draw conclusions related to the cause-effect mechanisms. Future studies should determine whether the levels of the eicosanoids have a predictive value for the transition of UHR to frank psychosis.

Plasmatic endocannabinoids are decreased in subjects with ultra-high risk of psychosis.

The onset of frank psychosis is usually preceded by a prodromal phase characterized by attenuated psychotic symptoms. Currently, research on schizophrenia prodromal phase (ultra-high risk for psychosis [UHR]) has focused on the risk of developing psychosis, on the transition to full blown psychosis and on its prediction. Neurobiological differences between UHR individuals who fully recover (remitters) versus those who show persistent/progressive prodromal symptoms (nonremitters) have been little explored. The endocannabinoid system constitutes a neuromodulatory system that plays a major role in brain development, synaptic plasticity, emotional behaviours and cognition. It comprises two cannabinoid receptors (CB1/CB2), two endocannabinoid ligands, arachidonylethanolamide (AEA) and 2-arachidonoylglycerol (2AG) along with their inactivation enzymes. Despite much evidence that the endocannabinoid system is imbalanced during psychosis, very little is known about it in UHR. Therefore, we aimed to quantify the plasma endocannabinoid levels in UHR and healthy controls (HC) and verify if these metabolites could differentiate between remitters and nonremitters. Circulating concentrations of AEA (p = .003) and 2AG (p < .001) were lower in UHR when compared with HC, with no difference between remitters and nonremitters. Regarding clinical evolution, it was observed that out of 91 UHRs initially considered, 16 had psychiatric complaints (3 years of follow-up). Considering those subjects, there were weak correlations between clinical parameters and plasma concentrations of endocannabinoids. Our results suggest that the endocannabinoids are imbalanced before frank psychosis and that changes can be seen in plasma of UHR individuals. These molecules proved to be potential biomarkers to identify individuals in the prodromal phase of psychosis.

Investigation of the relaxing effect of a camphor nanoemulsion on rat isolated trachea.

Asthma is a chronic inflammatory disease that targeting lower airways, being characterized by bronchial smooth muscle hyper responsiveness and mucus hypersecretion. Asthma is considered the most common respiratory disease in the world, affecting approximately 235 million individuals. The main therapy sometimes fails to establish clinical improvement in patients, which leads to a constant search for new alternatives. Camphor is a transparent solid monoterpene with a strong aroma, which due to its high lipophilicity is insoluble in water. Nanostructured carrier systems have shown promise as a delivery system for lipophilic compounds such as monoterpenes. Therefore, the objective of this work was to evaluate the relaxant effect of nanoemulsified camphor (NEC), as well as the mechanism of action of that monoterpene, in isolated rat trachea. The results obtained demonstrated that NEC promote relaxation of the isolated rat trachea when smooth muscle contraction was induced by both carbachol (CCh) and KCl, presenting a pCE50 of 2.25 ± 0.27 and 3.30 ± 0.07, respectively. In the presence of dexamethasone (DEXA), tetraethylammonium (TEA), glibenclamide (GLIB), 1H-[1,2,4]-oxadiazole-[4,3,-a]-quinoxaline-1-one (ODQ) and ruthenium red (RR) there was a significant difference in at least one of the evaluated pharmacological parameters, such as concentration-response curves shape, Emax or pCE50. As conclusion, NEC may be involved with ß-adrenergic receptors, channels for K+ sensitive to ATP (KATP) or Channels for K+ opened by Ca2+ (KCa), increase in prostanoids and with receptor channel with transient potential (TRPv). In conclusion, ß-adrenergic receptors, prostanoids, nitric oxide (NO), ATP-sensitive K+ channels (KATP), Ca2+-opened K+ channels (KCa), and transient receptor potential cation channel subfamily V (TRPV) are involved in the relaxing effect of NEC. In addition, the mechanism of action of NEC may be involved with the signal transduction pathway Nitric Oxide/soluble guanylyl cyclase/cGMP/cGMP-activated protein kinase. NEC, therefore, demonstrates spasmolytic activity when presenting tracheal relaxation compared to CCh and KCl contracturants.

Vasectomy re-reversal: effectiveness and parameters associated with its success

ABSTRACT Introduction: When the vasectomy reversal (VR) fails, and the patient desires natural conception with his sperm, vasectomy re-reversal (VRR) is the only alternative. Purpose: To determine the VRR effectiveness and whether specific parameters can be associated with its success. Materials and Methods: We retrospectively evaluated 18 consecutive vasectomized patients, who had failed their VR through bilateral vasovasostomy, and posteriorly were submitted to VRR. The parameters of the study were: age of the patients, elapsed time between vasectomy and VRR (V-VRRt), elapsed time between VR and VRR (VR-VRRt), presence of spermatozoa in the proximal vas deferens fluid (SptzVDF) in the VRR and results of semen analysis after VRR (SA-VRR). Results: The mean of the age of the patients was 44.11±6.55 years (32.0-57.0), the mean of V-VRRt was 11.76±6.46 years (1.5-25.0) and the mean of VR-VRRt was 2.13±2.27 years (0.5-10.0). SptzVDF in the VRR were found bilaterally in 8 patients, unilaterally in 4 and absent in 6. SA-VRR demonstrated normozoospermia in 9 patients, oligozoospermia in 3 and azoospermia in 6, with patency rate of 66.67%. SA-VRR showed statistically significant dependence only with SptzVDF in the VRR (p <0.01). Conclusions: VRR was effective in restoring the obstruction in more than half of the patients. Furthermore, the presence of spermatozoa in the vas deferens fluid was the parameter associated with the VRR success.

Novel lncRNAs Co-Expression Networks Identifies LINC00504 with Oncogenic Role in Luminal A Breast Cancer Cells.

Long non-coding RNAs (lncRNAs) are functional transcripts with more than 200 nucleotides. These molecules exhibit great regulatory capacity and may act at different levels of gene expression regulation. Despite this regulatory versatility, the biology of these molecules is still poorly understood. Computational approaches are being increasingly used to elucidate biological mechanisms in which these lncRNAs may be involved. Co-expression networks can serve as great allies in elucidating the possible regulatory contexts in which these molecules are involved. Herein, we propose the use of the pipeline deposited in the RTN package to build lncRNAs co-expression networks using TCGA breast cancer (BC) cohort data. Worldwide, BC is the most common cancer in women and has great molecular heterogeneity. We identified an enriched co-expression network for the validation of relevant cell processes in the context of BC, including LINC00504. This lncRNA has increased expression in luminal subtype A samples, and is associated with prognosis in basal-like subtype. Silencing this lncRNA in luminal A cell lines resulted in decreased cell viability and colony formation. These results highlight the relevance of the proposed method for the identification of lncRNAs in specific biological contexts.

Increased PLA2 activity in individuals at ultra-high risk for psychosis.

Phospholipase A2 is the main enzyme in the metabolism of membrane phospholipids. It comprises a family of enzymes divided into iPLA2, cPLA2 and sPLA2. Studies have reported increased PLA2 activity in psychotic patients, which suggests an accelerated breakdown of membrane phospholipids. In the present study we investigated whether increased PLA2 activity is also present in individuals at ultra-high risk (UHR) for psychosis. One-hundred fifty adults were included in this study (85 UHR and 65 controls). UHR was assessed using the "structured interview for prodromal syndromes". PLA2 activity was determined in platelets by a radio-enzymatic assay. We found in UHR individuals increased activities of iPLA2 (p < 0.001) and cPLA2 (p = 0.012) as compared to controls. No correlations were found between socio-demographic and clinical parameters and PLA2 activity. Our findings suggest that increased PLA2 activities may be useful as a biological risk-marker for psychotic disorders.

Vasectomy re-reversal: effectiveness and parameters associated with its success.

INTRODUCTION: When the vasectomy reversal (VR) fails, and the patient desires natural conception with his sperm, vasectomy re-reversal (VRR) is the only alternative. PURPOSE: To determine the VRR effectiveness and whether specific parameters can be associated with its success. MATERIALS AND METHODS: We retrospectively evaluated 18 consecutive vasectomized patients, who had failed their VR through bilateral vasovasostomy, and posteriorly were submitted to VRR. The parameters of the study were: age of the patients, elapsed time between vasectomy and VRR (V-VRRt), elapsed time between VR and VRR (VR-VRRt), presence of spermatozoa in the proximal vas deferens fluid (SptzVDF) in the VRR and results of semen analysis after VRR (SA-VRR). RESULTS: The mean of the age of the patients was 44.11±6.55 years (32.0-57.0), the mean of V-VRRt was 11.76±6.46 years (1.5-25.0) and the mean of VR-VRRt was 2.13±2.27 years (0.5-10.0). SptzVDF in the VRR were found bilaterally in 8 patients, unilaterally in 4 and absent in 6. SA-VRR demonstrated normozoospermia in 9 patients, oligozoospermia in 3 and azoospermia in 6, with patency rate of 66.67%. SA-VRR showed statistically significant dependence only with SptzVDF in the VRR (p <0.01). CONCLUSIONS: VRR was effective in restoring the obstruction in more than half of the patients. Furthermore, the presence of spermatozoa in the vas deferens fluid was the parameter associated with the VRR success.

3D Virtual Planning for Rhinoplasty Using a Free Add-On for Open-Source Software.

BACKGROUND: Rhinoplasty is one of the most frequent aesthetic surgeries; the procedure can be challenging for inexperienced surgeons, and positive outcomes depend on good communication with the patient, proper planning, and precise execution. Three-dimensional (3D) technology has emerged to address these issues, but specific software for 3D planning tends to be expensive. OBJECTIVES: This study presents a simple, low-cost method for 3D simulation to plan rhinoplasty. METHODS: This preliminary report describes 3D rhinoplasty planning in a series of 3 cases employing free software and an add-on especially developed for rhinoplasty (Blender and RhinOnBlender, respectively). The photogrammetry protocol, which can be performed easily with a smartphone, is described in detail along with all the steps in 3D planning. RESULTS: The software and add-on automated the process, making the tool environment accessible to surgeons who are not familiar with graphic design software. The surgeries were uneventful in all cases, and the patients were satisfied with the outcomes. CONCLUSIONS: 3D graphic technology has provided significant advances in health research, improvement, and teaching for surgeons and communication between surgeons and patients. Free open-source software and add-ons are excellent options that offer proven utility, affordability, and ease of utilization to healthcare providers.

Frequency of the TP53 R337H variant in sporadic breast cancer and its impact on genomic instability.

The R337H is a TP53 germline pathogenic variant that has been associated with several types of cancers, including breast cancer. Our main objective was to determine the frequency of the R337H variant in sporadic breast cancer patients from Paraná state, South Brazil, its association with prognosis and its impact in genomic instability. The genotyping of 805 breast cancer tissues revealed a genotypic and allelic frequency of the R337H variant of 2.36% and 1.18%, respectively. In these R337H+ cases a lower mean age at diagnosis was observed when compared to the R337H-cases. Array-CGH analysis showed that R337H+ patients presented a higher number of copy number alterations (CNAs), compared to the R337H-. These CNAs affected genes and miRNAs that regulate critical cancer signaling pathways; a number of these genes were associated with survival after querying the KMplot database. Furthermore, homozygous (R337H+/R337H+) fibroblasts presented increased levels of copy number variants when compared to heterozygous or R337H- cells. In conclusion, the R337H variant may contribute to 2.36% of the breast cancer cases without family cancer history in Paraná. Among other mechanisms, R337H increases the level of genomic instability, as evidenced by a higher number of CNAs in the R337H+ cases compared to the R337H-.

Communities of arthropods associated with the composting process of the organic solid waste produced in a landfill in Brazil.

Composting is a process recommended as a way to recycle the organic part of the solid waste in which several micro and macroorganisms act as decomposers of the organic matter, in a process that takes around 120 days and faces roughly three different phases. Because we do not know the community of arthropods associated with the compost produced in one of the biggest landfills placed in Brazil, here we collected and identified the community of arthropods present in each phase of the organic compost. Our hypothesis is that the abundance and diversity of arthropods are different within each phase of the compost and we hope to find particular groups of arthropods that can be used as indicator of specific phases. In total, we identified the taxa of 1204 arthropods (insects, arachnidan and diplopods). We found that diversity and abundancy of arthropods were indeed different for each maturation phase of the compost, but we did not find families that are good indicators of each phase. In addition, to be certain about the safety of the compost produced, we investigated the presence of microorganisms in the final product and we found considerable levels of Escherichia coli and Enterococcus faecalis in some samples. Finally, we argue that the presence of these macro and microorganisms during the process may be beneficial or harmful. Since their presence decreased greatly by the end of the process, we acknowledge that composting works efficiently as a way to recycle the organic part of the waste generated in Brazil.

Hyperuricemia and Risk of Cardiovascular Outcomes: The Experience of the URRAH (Uric Acid Right for Heart Health) Project.

The latest European Guidelines of Arterial Hypertension have officially introduced uric acid evaluation among the cardiovascular risk factors that should be evaluated in order to stratify patient's risk. In fact, it has been extensively evaluated and demonstrated to be an independent predictor not only of all-cause and cardiovascular mortality, but also of myocardial infraction, stroke and heart failure. Despite the large number of studies on this topic, an important open question that still need to be answered is the identification of a cardiovascular uric acid cut-off value. The actual hyperuricemia cut-off (> 6 mg/dL in women and 7 mg/dL in men) is principally based on the saturation point of uric acid but previous evidence suggests that the negative impact of cardiovascular system could occur also at lower levels. In this context, the Working Group on uric acid and CV risk of the Italian Society of Hypertension has designed the Uric acid Right for heArt Health project. The primary objective of this project is to define the level of uricemia above which the independent risk of CV disease may increase in a significantly manner. In this review we will summarize the first results obtained and describe the further planned analysis.

Real-Time Exploration of Large Spatiotemporal Datasets Based on Order Statistics.

In recent years sophisticated data structures based on datacubes have been proposed to perform interactive visual exploration of large datasets. While powerful, these approaches overlook the important fact that aggregations used to produce datacubes do not represent the actual distribution of the data being analyzed. As a result, these methods might produce biased results as well as hide important features in the data. In this paper, we introduce the Quantile Datacube Structure (QDS) that bridges this gap by supporting interactive visual exploration based on order statistics. To achieve this, QDS makes use of an efficient non-parametric distribution approximation scheme called p-digest and employs a novel datacube indexing scheme that reduces the memory usage of previous datacube methods. This enables interactive slicing and dicing while accurately approximating the distribution of quantitative variables of interest. We present two case studies that illustrate the ability of QDS to not only build order statistics based visualizations interactively but also to perform event detection on very large datasets. Finally, we present extensive experimental results that validate the effectiveness of QDS regarding memory usage and accuracy in the approximation of order statistics for real-world datasets.

Integrated copy number and miRNA expression analysis in triple negative breast cancer of Latin American patients.

Triple negative breast cancer (TNBC), a clinically aggressive breast cancer subtype, affects 15-35% of women from Latin America. Using an approach of direct integration of copy number and global miRNA profiling data, performed simultaneously in the same tumor specimens, we identified a panel of 17 miRNAs specifically associated with TNBC of ancestrally characterized patients from Latin America, Brazil. This panel was differentially expressed between the TNBC and non-TNBC subtypes studied (p ≤ 0.05, FDR ≤ 0.25), with their expression levels concordant with the patterns of copy number alterations (CNAs), present mostly frequent at 8q21.3-q24.3, 3q24-29, 6p25.3-p12.2, 1q21.1-q44, 5q11.1-q22.1, 11p13-p11.2, 13q12.11-q14.3, 17q24.2-q25.3 and Xp22.33-p11.21. The combined 17 miRNAs presented a high power (AUC = 0.953 (0.78-0.99);95% CI) in discriminating between the TNBC and non-TNBC subtypes of the patients studied. In addition, the expression of 14 and 15 of the 17miRNAs was significantly associated with tumor subtype when adjusted for tumor stage and grade, respectively. In conclusion, the panel of miRNAs identified demonstrated the impact of CNAs in miRNA expression levels and identified miRNA target genes potentially affected by both CNAs and miRNA deregulation. These targets, involved in critical signaling pathways and biological functions associated specifically with the TNBC transcriptome of Latina patients, can provide biological insights into the observed differences in the TNBC clinical outcome among racial/ethnic groups, taking into consideration their genetic ancestry.