Breast reconstruction: a review

Surgeons in the late 19th - 20th century performed radical mastectomies as the only possible treatment for breast cancers. Since then, the medical-surgical/scientific community has been constantly encouraged to develop and study different less invasive alternatives in breast reconstruction. Over time, locoregional perforator flap options have served as practical alternatives to implant-based reconstruction and abdominal flaps, especially in the setting of patients who have received radiation therapy or have a history of failed reconstruction, as they effectively fill the missing volume and respect the musculature of the donor site. Breast reconstruction using strategies with one of the different locoregional flaps can preserve the musculature and innervation of the post-mastectomy site, which manages to reduce possible adverse events. In addition to evaluating the anatomical characteristics of the defect and affected quadrant, it is essential to assess the patient's body constitution and the skills of the surgical team as well as microsurgery training when designing a reconstructive plan. Different research protocols should be developed in the study and development of new medical-surgical therapeutic alternatives; we suggest joint development with tissue engineering

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Hazardous faults of South America; compilation and overview

The heterogeneous South American geology has coined a wide variety of neotectonic settings where crustal seismogenic sources do occur. This fact has led to different approaches for mapping and inventory neotectonic structures. The South American Risk Assessment project promoted the discussion and update under uniform standards of the available information on neotectonic deformation, for its application in regional Probabilistic Seismic Hazard Assessments. As a result, 1533 hazardous faults have been inventoried onshore South America, 497 of them qualifying to feed the engine model driving probabilistic maps. Main hazardous structures are concentrated throughout the eastern boundary of the Northern Andean Sliver and along the foreland-facing Andean Thrust Front. Space geodesy and seismicity illuminate the seismogenic significance of these deformation belts, although few neotectonic surveys have been conducted to date in the latter region. The characteristics of the main structures or deformation zones are here outlined according to their filiation to neotectonic domains, which are dependant on the geologic, seismotectonic, or morphotectonic settings in Andean and extra-Andean regions. The knowledge accrued on the hazardous faults in South America here compiled, reinforces the fact that some of these structures constitute significant hazard sources for many urban areas and critical facilities and should be incorporated in seismic hazard assessments. However, the available fault data are insufficient in many cases or carry significant epistemic uncertainties for fault source characterization. This contribution aims to summarize the present knowledge on the South American hazardous faults as well as the main challenges for successful fault data incorporation into seismic hazard models

Genomic context and TP53 allele frequency define clinical outcomes in TP53-mutated myelodysplastic syndromes

TP53 mutations are associated with adverse outcomes and shorter response to hypomethylating agents (HMAs) in myelodysplastic syndrome (MDS). Limited data have evaluated the impact of the type, number, and patterns of TP53 mutations in response outcomes and prognosis of MDS. We evaluated the clinicopathologic characteristics, outcomes, and response to therapy of 261 patients with MDS and TP53 mutations. Median age was 68 years (range, 18-80 years). A total of 217 patients (83%) had a complex karyotype. TP53 mutations were detected at a median variant allele frequency (VAF) of 0.39 (range, 0.01-0.94). TP53 deletion was associated with lower overall response rate (ORR) (odds ratio, 0.3; P = .021), and lower TP53 VAF correlated with higher ORR to HMAs. Increase in TP53 VAF at the time of transformation was observed in 13 patients (61%), and previously undetectable mutations were observed in 15 patients (65%). TP53 VAF was associated with worse prognosis (hazard ratio, 1.02 per 1% VAF increase; 95% confidence interval, 1.01-1.03; P \u3c .001). Integration of TP53 VAF and karyotypic complexity identified prognostic subgroups within TP53-mutant MDS. We developed a multivariable model for overall survival that included the revised International Prognostic Scoring System (IPSS-R) categories and TP53 VAF. Total score for each patient was calculated as follows: VAF TP53 + 13 × IPSS-R blast score + 16 × IPSS-R cytogenetic score + 28 × IPSS-R hemoglobin score + 46 × IPSS-R platelet score. Use of this model identified 4 prognostic subgroups with median survival times of not reached, 42.2, 21.9, and 9.2 months. These data suggest that outcomes of patients with TP53-mutated MDS are heterogeneous and that transformation may be driven not only by TP53 but also by other factors

Evaluation of bottom-up and top-down strategies for aggregated forecasts: state space models and arima applications

Abstract. In this research, we consider monthly series from the M4 competition to study the relative performance of top-down and bottom-up strategies by means of implementing forecast automation of state space and ARIMA models. For the bottomup strategy, the forecast for each series is developed individually and then these are combined to produce a cumulative forecast of the aggregated series. For the top-down strategy, the series or components values are first combined and then a single forecast is determined for the aggregated series. Based on our implementation, state space models showed a higher forecast performance when a top-down strategy is applied. ARIMA models had a higher forecast performance for the bottom-up strategy. For state space models the top-down strategy reduced the overall error significantly. ARIMA models showed to be more accurate when forecasts are first determined individually. As part of the development we also proposed an approach to improve the forecasting procedure of aggregation strategies

Human amylin aggregates release within exosomes as a protective mechanism in pancreatic β cells: Pancreatic β-hippocampal cell communication

Pancreatic β cells are essential in the maintenance of glucose homeostasis during the progression to type 2 Diabetes Mellitus (T2DM), generating compensatory hyperinsulinemia to counteract insulin resistance. It is well known, that throughout the process there is an increased mTORC1 signaling pathway, with an impairment in different quality control systems including ubiquitin-proteasome system and autophagy. In addition, under this situation, pancreatic β cells start to accumulate amylin protein (IAPP) in aggregates, and this accumulation contributes to the failure of autophagy, damaging different organelles such as plasma membrane, endoplasmic reticulum, mitochondria, and others. Here, we report that IAPP can be incorporated to multivesicular bodies (MVB) and secreted into exosomes, a mechanism responsible for the exportation of these toxic aggregates as vehicles of cell to cell communication. On this regard, we have demonstrated that the exosomes bearing toxic hIAPP released from pancreatic β cells are capable to induce hyperactivation of mTORC1 signaling, a failure in the autophagic cellular quality control, and favor pro-fission status of the mitochondrial dynamics in hippo-campal cells. In summary, our results show that harmful accumulation of hIAPP in pancreatic β cells may be detoxified by the release of exosomes, which may be captured by endocytosis mechanism damaging neuronal hippocampal cells, which suggest an underlying molecular mechanism to the link between type 2 diabetes and neurodegenerative diseases

Subducción de segmentos oceánicos e inversión de sus márgenes conjugados en la Cordillera Bética

Este estudio reexamina la estructura y evolución geodinámica de la Cordillera Bético-Rifeña con especial atención al control que ejercen las estructuras heredadas de los ciclos de rifting mesozoicos y los procesos de tectónica salina. Diez cortes geológicos a escala cortical ilustran las principales características del orógeno, las variaciones laterales de su estructura y la evolución 4D de la deformación. Además de la cartografía ya disponible, durante su elaboración se han utilizado mapas geológicos nuevos, perfiles de sísmica de reflexión y sondeos profundos, datos gravimétricos, magnéticos y paleomagnéticos. Las conclusiones más relevantes indican que: (i) El orógeno resulta de la subducción de un dominio estrecho de corteza oceánica, que da paso a un rift fallido hacia el este, y de la incorporación de los márgenes pasivos conjugados a la colisión. (ii) El paleo-margen sudibérico ocupa la placa inferior (Z. Externas y C. Nevado-Filábride) y el magrebí la superior (C. Alpujárride y Maláguide). (iii) La cobertera mesozoica invertida de ambos márgenes está preservada en el orógeno: el Subbético Externo y Medio, Dom. Intermedio y el Prebético sobre el paleo-margen sudibérico; y el Subbético Interno, las Unidades Frontales y la cobertera maláguide sobre el paleo-margen magrebí. (iv) Potentes secuencias evaporíticas triásicas favorecen los procesos de tectónica salina antes y durante la orogénesis en la parte occidental y oriental de la cordillera. (iv) Fallas de transferencia ENE-OSO heredadas del rifting segmentan el orógeno. (v) La subducción de corteza oceánica está restringida al dominio occidental y limitada por una tear lateral asociada a la zona de transferencia de Antequera (vi) En este sector, el frente de subducción está marcado por unidades pelágicas situadas al norte del Subbético Interno. (vii) El acortamiento de la cordillera aumenta de este a oeste y está variación explica las importantes rotaciones paleomagnéticas dextrales de eje vertical observadas en las Bética

Genomic variation in myeloma: design, content, and initial application of the Bank On A Cure SNP Panel to detect associations with progression-free survival

<p>Abstract</p> <p>Background</p> <p>We have engaged in an international program designated the <it>Bank On A Cure</it>, which has established DNA banks from multiple cooperative and institutional clinical trials, and a platform for examining the association of genetic variations with disease risk and outcomes in multiple myeloma.</p> <p>We describe the development and content of a novel custom SNP panel that contains 3404 SNPs in 983 genes, representing cellular functions and pathways that may influence disease severity at diagnosis, toxicity, progression or other treatment outcomes. A systematic search of national databases was used to identify non-synonymous coding SNPs and SNPs within transcriptional regulatory regions. To explore SNP associations with PFS we compared SNP profiles of short term (less than 1 year, <it>n </it>= 70) versus long term progression-free survivors (greater than 3 years, <it>n </it>= 73) in two phase III clinical trials.</p> <p>Results</p> <p>Quality controls were established, demonstrating an accurate and robust screening panel for genetic variations, and some initial racial comparisons of allelic variation were done. A variety of analytical approaches, including machine learning tools for data mining and recursive partitioning analyses, demonstrated predictive value of the SNP panel in survival. While the entire SNP panel showed genotype predictive association with PFS, some SNP subsets were identified within drug response, cellular signaling and cell cycle genes.</p> <p>Conclusion</p> <p>A targeted gene approach was undertaken to develop an SNP panel that can test for associations with clinical outcomes in myeloma. The initial analysis provided some predictive power, demonstrating that genetic variations in the myeloma patient population may influence PFS.</p

Psychometric properties of the Alcohol Use Disorders Identification Test (AUDIT) across cross-cultural subgroups, genders, and sexual orientations: Findings from the International Sex Survey (ISS)

© 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).INTRODUCTION: Despite being a widely used screening questionnaire, there is no consensus on the most appropriate measurement model for the Alcohol Use Disorders Identification Test (AUDIT). Furthermore, there have been limited studies on its measurement invariance across cross-cultural subgroups, genders, and sexual orientations. AIMS: The present study aimed to examine the fit of different measurement models for the AUDIT and its measurement invariance across a wide range of subgroups by country, language, gender, and sexual orientation. METHODS: Responses concerning past-year alcohol use from the participants of the cross-sectional International Sex Survey were considered (N = 62,943; M age: 32.73; SD = 12.59). Confirmatory factor analysis, as well as measurement invariance tests were performed for 21 countries, 14 languages, three genders, and four sexual-orientation subgroups that met the minimum sample size requirement for inclusion in these analyses. RESULTS: A two-factor model with factors describing 'alcohol use' (items 1-3) and 'alcohol problems' (items 4-10) showed the best model fit across countries, languages, genders, and sexual orientations. For the former two, scalar and latent mean levels of invariance were reached considering different criteria. For gender and sexual orientation, a latent mean level of invariance was reached. CONCLUSIONS: In line with the two-factor model, the calculation of separate alcohol-use and alcohol-problem scores is recommended when using the AUDIT. The high levels of measurement invariance achieved for the AUDIT support its use in cross-cultural research, capable also of meaningful comparisons among genders and sexual orientations.Peer reviewe

Problematic pornography use across countries, genders, and sexual orientations: Insights from the International Sex Survey and comparison of different assessment tools.

Problematic pornography use (PPU) is a common manifestation of the newly introduced Compulsive Sexual Behavior Disorder diagnosis in the 11th edition of the International Statistical Classification of Diseases and Related Health Problems. Although cultural, gender- and sexual orientation-related differences in sexual behaviors are well documented, there is a relative absence of data on PPU outside Western countries and among women as well as gender- and sexually-diverse individuals. We addressed these gaps by (a) validating the long and short versions of the Problematic Pornography Consumption Scale (PPCS and PPCS-6, respectively) and the Brief Pornography Screen (BPS) and (b) measuring PPU risk across diverse populations. Using data from the pre-registered International Sex Survey [n = 82 243; mean age (M &lt;sub&gt;age&lt;/sub&gt; ) = 32.4 years, standard deviation = 12.5], a study across 42 countries from five continents, we evaluated the psychometric properties (i.e. factor structure, measurement invariance, and reliability) of the PPCS, PPCS-6, and BPS and examined their associations with relevant correlates (e.g. treatment-seeking). We also compared PPU risk among diverse groups (e.g. three genders). The PPCS, PPCS-6, and BPS demonstrated excellent psychometric properties [for example, comparative fit index = 0.985, Tucker-Lewis Index = 0.981, root mean square error of approximation = 0.060 (90% confidence interval = 0.059-0.060)] in the confirmatory factor analysis, with all PPCS' inter-factor correlations positive and strong (rs = 0.72-0.96). A total of 3.2% of participants were at risk of experiencing PPU (PPU+) based on the PPCS, with significant country- and gender-based differences (e.g. men reported the highest levels of PPU). No sexual orientation-based differences were observed. Only 4-10% of individuals in the PPU+ group had ever sought treatment for PPU, while an additional 21-37% wanted to, but did not do so for specific reasons (e.g. unaffordability). This study validated three measures to assess the severity of problematic pornography use across languages, countries, genders, and sexual orientations in 26 languages: the Problematic Pornography Consumption Scale (PPCS, and PPCS-6, respectively), and the Brief Pornography Screen (BPS). The problematic pornography use risk is estimated to be 3.2-16.6% of the population of 42 countries, and varies among different groups (e.g. genders) and based on the measure used