Expert Recommendations from the AEDV on Legal Aspects Surrounding the Management of Sexually Transmitted Diseases. / Recomendaciones de expertos de la AEDV sobre los aspectos legales en el manejo de las infecciones de transmisión sexual.

The incidence of sexually transmitted diseases has been on the rise in our setting for decades. These infections represent not only an individual problem, but also a problem of public health. Therefore, the management of STDs involves reducing community incidence, which means that common issues in the clinical practice such as failure to attend may become a more complex problem, which adds to the difficult and delicate task of locating sexual contacts that would benefit from screening and the appropriate treatment. On the other hand, STDs have direct legal implications in cases of underage patients, or suspected sexual assault. Therefore, the correct handling of these scenarios requires knowledge of the legal framework that regulates them. Dermatologists are clinically trained and prepared to deal with these conditions. Nonetheless, the legal issues involved are often difficult to solve. This document stands as a simple reference guide to help solve the main legal issues we may encounter in a consultation when dealing with STDs.

Engineering repressors with coevolutionary cues facilitates toggle switches with a master reset.

Engineering allosteric transcriptional repressors containing an environmental sensing module (ESM) and a DNA recognition module (DRM) has the potential to unlock a combinatorial set of rationally designed biological responses. We demonstrated that constructing hybrid repressors by fusing distinct ESMs and DRMs provides a means to flexibly rewire genetic networks for complex signal processing. We have used coevolutionary traits among LacI homologs to develop a model for predicting compatibility between ESMs and DRMs. Our predictions accurately agree with the performance of 40 engineered repressors. We have harnessed this framework to develop a system of multiple toggle switches with a master OFF signal that produces a unique behavior: each engineered biological activity is switched to a stable ON state by different chemicals and returned to OFF in response to a common signal. One promising application of this design is to develop living diagnostics for monitoring multiple parameters in complex physiological environments and it represents one of many circuit topologies that can be explored with modular repressors designed with coevolutionary information.

Engineering DNA recognition and allosteric response properties of TetR family proteins by using a module-swapping strategy.

The development of synthetic biological systems requires modular biomolecular components to flexibly alter response pathways. In previous studies, we have established a module-swapping design principle to engineer allosteric response and DNA recognition properties among regulators in the LacI family, in which the engineered regulators served as effective components for implementing new cellular behavior. Here we introduced this protein engineering strategy to two regulators in the TetR family: TetR (UniProt Accession ID: P04483) and MphR (Q9EVJ6). The TetR DNA-binding module and the MphR ligand-binding module were used to create the TetR-MphR. This resulting hybrid regulator possesses DNA-binding properties of TetR and ligand response properties of MphR, which is able to control gene expression in response to a molecular signal in cells. Furthermore, we studied molecular interactions between the TetR DNA-binding module and MphR ligand-binding module by using mutant analysis. Together, we demonstrated that TetR family regulators contain discrete and functional modules that can be used to build biological components with novel properties. This work highlights the utility of rational design as a means of creating modular parts for cell engineering and introduces new possibilities in rewiring cellular response pathways.

Epidemiology of comorbidities in patients with hypertension.

PURPOSE OF REVIEW: Hypertension affects an enormous number of people and uncommonly presents in isolation. This review aims to summarize contemporary data that is relevant to the epidemiology of specific comorbidities occurring frequently in individuals with hypertension. RECENT FINDINGS: Hypertension is invariably diagnosed along with multiple comorbidities, particularly diabetes mellitus, obesity, chronic kidney disease, coronary artery disease, and heart failure. Evidence pertinent to prevalence, incidence, and temporal trends is reported, with an emphasis on differences according to age, gender, and race/ethnicity. SUMMARY: The clustering of these conditions requires a thorough-and often multidisciplinary-approach in the evaluation and management of individuals with hypertension. Populations with higher risk include the elderly, women, and racial/ethnic groups.

Anatomical and computed tomography study of the eighth costochondral junction: topography for costochondral graft harvesting.

INTRODUCTION: Costochondral grafts have long been used in maxillofacial reconstruction, but have been little used in trauma and orthopedic cases. This surgical technique requires that a graft be harvested from the thorax in the area of the eighth rib. Pleuropulmonary complications are very rare. Although the harvesting technique is simple, it needs to be demystified. GOAL OF STUDY: This study was performed to define anatomical relationships in the eighth costochondral junction and identify topographical and anatomical landmarks that will make it easier to harvest this structure. METHOD: This was a two-part study. First, an anatomical study was carried out on human cadaver thoraxes to define topographical landmarks and study the anatomical surroundings of the eighth costochondral junction. Second, an imaging study was performed using a database of existing patient computed tomography (CT) scans of the chest and abdomen to confirm the topographical landmarks defined in the first part of the study. The spine was used as a reference for both studies. The location of the eighth costochondral junction was defined relative to the spinal processes along with its location on the lower rib cage hemiperimeter in the transverse plane starting at the corresponding spinous process. RESULTS: The eighth costochondral junction was in line with the spinal process of the twelfth thoracic vertebra in the vast majority of cases and located at two-thirds of the lower rib cage hemiperimeter from the posterior median sulcus, regardless of the patient's chest shape, age and gender. This junction was always located under a single muscle (external oblique) and protected by a thick perichondrium layer, which separates it from the intercostal pedicles, endothoracic fascia and parietal pleura. DISCUSSION: This two-part study has identified reliable landmarks for harvesting of an osteochondral graft at the eighth costochondral junction and, by describing its anatomical surroundings, helps take the mystery out of its harvesting. These landmarks were identified in supine cadavers and in free-breathing patients lying in supine for the CT portion. This position must be used when identifying these landmarks in a patient undergoing costochondral autograft harvesting for cartilage reconstruction.

Dimensions of the trapezium bone: a cadaver and CT study.

PURPOSE: The primary purpose of this study was to define the size of the trapezium bone through measurements on cadaver specimens and CT scans of living subjects. The secondary purpose of this study was to determine if any correlation existed between the size of the trapezium and local anatomical parameters. METHODS: The radio-ulnar length (L), dorsopalmar width (ℓ) and height (h) of the distal surface of the trapezium were measured by two independent observers on 20 cadaver specimens. The same measurements were carried out by two other observers on anonymized CT scans from 18 patients. The inter- and intra-observer agreement was determined using the intraclass correlation coefficient. RESULTS: In the cadavers, the mean length, width and height of the trapezium were 22.8, 15.5 and 15.2 mm, respectively. On the CT scans, these same dimensions were 19.2, 11.4 and 11.6 mm. Inter-observer agreement was statistically significant in both parts of the study. DISCUSSION: The dimensions of the trapezium bone were about 3.33 mm larger in cadavers than on CT scans. These differences can be explained partially by a systematic under-sizing error on the CT scans and the fact that the cartilage layer cannot be directly visualized. CONCLUSION: This study was able to define the dimensions of the trapezium bone. It may be possible to predict the trapezium height from the length of the forearm or the width of the radial epiphysis. Our data can be used to adjust the size of trapezium implants to the dimensions of the patient's bone.

A Comparative Study on the Functional Outcomes of Patients who Underwent Internal versus External Fixation for Tibial Plateau Fractures Two Years Post-surgery.

Introduction: Tibial plateau fractures are due to high energy trauma brought about by axial compression forces and associated varus or valgus component. Objective: Patients diagnosed with tibial plateau fractures from January to December 2018 treated with internal vs external fixation will be described according to their Schatzker classification. The study further aims to compare the functional outcomes between the two groups in terms of surgery done. Methods: A chart review determined the distribution of demographics. The Modified Rasmussen Score (MRS) was used to determine the clinical and radiographic parameters after taking a new knee radiograph and assessment from the rehabilitation department. The MRS determined the functional outcomes of the said patients. Ethical considerations and proper informed consent were upheld after being reviewed by the hospital's research committee. Results: Out of 48 patients, 35 underwent internal fixation via open reduction using plates and/or screws, while 13 underwent external fixation using hybrid external fixator. The demographic profile showed mostly males between ages 20 to 49 years old. Most cases were due to vehicular accidents affecting the left lower extremity. In terms of Schatzker classification, the most common was type VI. The computed mean MRS of the internal fixation group was 30.43 while the external fixation group was 30.00, generally showing no significant difference. Conclusion: Surgical intervention of tibial plateau fractures aims for anatomic reduction using internal or external fixation. There was no significant difference on the functional outcome of the two groups despite classifying the respondents according to Schatzker type, hence we can conclude that external fixation be chosen as the treatment of choice for tibial plateau fractures when properly indicated.

Evaluation of fat grafting safety in patients with intraepithelial neoplasia: a matched-cohort study.

BACKGROUND: Fat grafting is widely carried out in breast cancer patients to improve quality in breast reconstruction. Recently, in vitro and animal studies have questioned the role of adipose tissues in cancer development. DESIGNS: Matched-cohort study. We analysed: (i) 59 intraepithelial neoplasia patients who had undergone lipofilling, with no recurrence between primary surgery and lipofilling. (ii) A control group of 118 matched patients (two controls per lipofilling patient) with the corresponding recurrence-free intervals. Both groups were also matched for main cancer criteria. A local event (LE) was the primary end point, with follow-up starting from the baseline. RESULTS: Median follow-up was 63 and 66 months from surgery, and 38 and 42 from baseline, for the lipofilling and control groups, respectively; the 5-year cumulative incidence of LE was 18% and 3% (P = 0.02). Ki-67 was the significant factor in univariate survival analysis. A subgroup analysis showed that lipofilling increased the risk of LE in women <50 years, with high grade neoplasia, Ki-67 ≥ 14 or who had undergone quadrantectomy. CONCLUSION: Higher risk of LE was observed in intraepithelial neoplasia patients following lipofilling. Although further studies are required to validate our conclusions, patients belonging to this subgroup should be informed of these results and the potential risks.

Risk factors associated with recurrence after nipple-sparing mastectomy for invasive and intraepithelial neoplasia.

BACKGROUND: To identify risk factors of recurrence in a large series of patients with breast cancer who underwent a nipple-sparing mastectomy (NSM). PATIENTS AND METHODS: Breast-related recurrences and local recurrences (LR) in the breast and the nipple areola complex (NAC) were studied. Cumulative incidences of events were estimated through competing risk analysis. Multivariate Cox regression models were also applied. RESULTS: We identified 934 consecutive NSM patients during 2002-2007. Median follow-up was 50 months. In 772 invasive carcinoma patients, the rate of LR in the breast and in the NAC was 3.6% and 0.8%, respectively. In the 162 patients with intraepithelial neoplasia, the rate of LR in the breast and in the NAC was 4.9% and 2.9%, respectively. The significant risk factors of LR in the breast for the group A were grade, overexpression/amplification of HER2/neu and breast cancer molecular subtype Luminal B. In group B, the risk factors of LR in the breast and in the NAC were age (<45 years), absence of estrogen receptors, grade, HER2/neu overexpression and high Ki-67. CONCLUSIONS: The LR rate after NSM in our series was low. Biological features of disease and young age should be taken into account when considering NSM in breast cancer patients.

Evolution of extrafloral nectaries: adaptive process and selective regime changes from forest to savanna.

Much effort has been devoted to understanding the function of extrafloral nectaries (EFNs) for ant-plant-herbivore interactions. However, the pattern of evolution of such structures throughout the history of plant lineages remains unexplored. In this study, we used empirical knowledge on plant defences mediated by ants as a theoretical framework to test specific hypotheses about the adaptive role of EFNs during plant evolution. Emphasis was given to different processes (neutral or adaptive) and factors (habitat change and trade-offs with new trichomes) that may have affected the evolution of ant-plant associations. We measured seven EFN quantitative traits in all 105 species included in a well-supported phylogeny of the tribe Bignonieae (Bignoniaceae) and collected field data on ant-EFN interactions in 32 species. We identified a positive association between ant visitation (a surrogate of ant guarding) and the abundance of EFNs in vegetative plant parts and rejected the hypothesis of phylogenetic conservatism of EFNs, with most traits presenting K-values < 1. Modelling the evolution of EFN traits using maximum likelihood approaches further suggested adaptive evolution, with static-optimum models showing a better fit than purely drift models. In addition, the abundance of EFNs was associated with habitat shifts (with a decrease in the abundance of EFNs from forest to savannas), and a potential trade-off was detected between the abundance of EFNs and estipitate glandular trichomes (i.e. trichomes with sticky secretion). These evolutionary associations suggest divergent selection between species as well as explains K-values < 1. Experimental studies with multiple lineages of forest and savanna taxa may improve our understanding of the role of nectaries in plants. Overall, our results suggest that the evolution of EFNs was likely associated with the adaptive process which probably played an important role in the diversification of this plant group.

Influence of Pythium oligandrum on the bacterial communities that colonize the nutrient solutions and the rhizosphere of tomato plants.

The influence exerted by the biocontrol oomycete Pythium oligandrum on the bacterial populations proliferating in the rhizosphere of tomato plants grown in a hydroponic system and in the circulating solutions is studied in the present experiment. Quantitative PCR and single-strand conformation polymorphism were used to investigate the genetic structure and dynamics of the bacterial communities colonizing the root systems and the various circulating solutions. Quantitative PCR assays showed that bacteria heavily colonized the rhizosphere of tomato plants with, however, no significant density changes throughout the cultural season (April-September). Single strand conformation polymorphism fingerprints revealed the occurrence of transient perturbations in the rhizospheric indigenous bacterial communities following P. oligandrum introduction in the root system of plants. This effect was, however, transient and did not persist until the end of the cropping season. Interestingly, the genetic structure of the bacterial microflora colonizing either the roots or the nutrient solutions evolved throughout the cropping season. This temporal evolution occurred whatever the presence and persistence of P. oligandrum in the rhizosphere. Evidence is also provided that bacterial microflora that colonize the root system are different from the ones colonizing the circulating solutions. The relationships between these 2 microflora (at the root and solution levels) are discussed.

COVID in Pediatric Age: an opinion paper.

The incidence of COVID in pediatrics was underestimated during the first months of the pandemic due to the oligosymptomatic nature of the infection in many children and the scarcity of diagnostic tests applied to this population. It is now accepted that children are infected and transmit the disease in the same way as adults. On the contrary, children have less severe and less lethal COVID, probably due to a lower maturity of the child's immune system, a lower number of ACE2 receptors and the lower presence of comorbidities in this population group. The development of a multisystemic inflammatory syndrome after SARS-CoV-2 infection in children, despite its rarity, is a very serious condition that frequently requires intensive care. Other less severe post-COVID manifestations have been described in children but are not yet well defined. COVID has had and continues to have a significant psychological impact on the children themselves, on their caregivers and on the exacerbation of pre-existing psychiatric conditions. We apply adult therapeutic principles to children but with very low levels of evidence. Information on the tolerability of the available medications in this population group is still scarce. The mortality of COVID in children is very low and generally affects children with significant comorbidities. There are, at present, three vaccines licensed for pediatric use which are compatible with all other vaccines applicable to children. In these circumstances, there has been much speculation about the indication for vaccination in the pediatric age group, but given its good tolerance, there are clinical and ethical reasons that, in our opinion, justify it.

Regional differences in clinical profile, quality of care, and outcomes among Hispanic patients hospitalized with acute myocardial infarction in the Get with Guidelines-Coronary Artery Disease (GWTG-CAD) registry.

BACKGROUND: Although Hispanics constitute the largest minority in the United States, it is unknown whether regional differences in quality of care and outcomes exist among Hispanic patients hospitalized with acute myocardial infarction (MI). METHODS: Using the GWTG-CAD Registry, clinical characteristics, conformity with quality measures, and in-hospital outcomes were assessed among Hispanic patients from different geographic regions admitted for acute MI in participating hospitals. RESULTS: A total of 11,299 Hispanic patients treated for acute MI at 277 hospitals from 4 regions were included in the study. Midwestern Hispanics were more likely to be younger, with male predominance in all regions. Northeastern Hispanics were more often insured with Medicaid. All subgroups showed high rates of hypertension, dyslipidemia, diabetes, and smoking, with the highest rates observed in the northeast region. Northeastern Hispanics were more likely to be discharged on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, ß-blockers, and statin or other lipid-lowering therapy. No significant regional differences were observed in aspirin, clopidogrel, and guideline-recommended door-to-balloon and door-to-thrombolysis times. Although Hispanics in the south and northeast were more likely to have a longer hospital stay compared with the west, there were no regional differences in in-hospital mortality. CONCLUSIONS: Among Hispanics with acute MI enrolled in the GWTG-CAD program, there were modest regional differences in clinical profile; high rates of use and, with few exceptions, no regional differences in guideline-recommended therapies; and no regional variation in in-hospital mortality.

Validity of procalcitonin and C-reactive protein measurement when differentiating between benign and malignant pleural effusion.

BACKGROUND: Procalcitonin (PCT) and C-reactive protein (CRP) measurements in pleural fluid and plasma have been proposed to facilitate differential diagnosis of pleural effusion (PE). The primary aim of this study was to evaluate the usefulness of these measurements when differentiating between benign (BPE) and malignant pleural effusion (MPE). METHODS: We prospectively studied 100 patients with the specific diagnosis of exudative PE. We analyzed the demographic data and the usual biochemical studies in PE. CRP and PCT were measured in pleural fluid and plasma before starting treatment. RESULTS: The CRP levels in pleural fluid were higher in patients with BPE than in patients with MPE [33.1 mg/L (16.8 to 52.1) vs. 11.8 (5.1 to 22); p = 0.001], as were the plasma CRP levels [68.4 mg/L (26.1 to 119.1) vs. 30.2 (11.7 to 64.8); p = 0.007]. No differences in PCT levels were detected between the two patient populations. The AUC derived from the ROC curve analysis for plasma CRP and pleural fluid CRP were 0.667 (CI 95%: 0.551 - 0.782) and 0.752 (CI 95%: 0.653 - 0.852), respectively. Plasma CRP levels > or = 35.5 mg/L exhibited 71% sensitivity and 56% specificity in discriminating between BPE and MPE. Pleural fluid CRP levels > or = 16.7 mg/L had 75% sensitivity and 68% specificity in the diagnosis of BPE. CONCLUSIONS: CRP levels in the pleural fluid and plasma were higher in patients with BPE, particulary infectious PE. However, the measurement of CRP and PCT is not a useful parameter for discriminating between BPE and MPE and does not provide useful information in clinical practice.

Rumination syndrome. A review article. / Síndrome de rumiación. Artículo de revisión.

Rumination syndrome is a functional gastrointestinal disorder characterized by effortless postprandial regurgitation of ingested food into the mouth. An unperceived postprandial contraction of the abdominal wall could be a key mechanism. In those patients, retrograde flow of the ingested gastric content into the mouth is produced due to a simultaneous combination of elevated intra-abdominal pressure and negative intrathoracic pressure. The estimated prevalence is around 2% in the general adult population. The main clinical characteristics include: a) early postprandial regurgitation, b) the effortlessly regurgitated material is similar to the ingested food, c) the regurgitated material is spit out or swallowed again. The clinical diagnosis of rumination syndrome relies on the clinical criteria. High resolution esophageal manometry, ideally including impedance monitoring, can be an important adjunct for making the clinical diagnosis. Its management is based on instruction as to the nature of the pathology, education in postprandial diaphragmatic breathing, and the assessment of possible psychiatric comorbidity. Baclofen use is reserved for second-line treatment in patients with refractory symptoms.

Coevolutionary methods enable robust design of modular repressors by reestablishing intra-protein interactions.

Genetic sensors with unique combinations of DNA recognition and allosteric response can be created by hybridizing DNA-binding modules (DBMs) and ligand-binding modules (LBMs) from distinct transcriptional repressors. This module swapping approach is limited by incompatibility between DBMs and LBMs from different proteins, due to the loss of critical module-module interactions after hybridization. We determine a design strategy for restoring key interactions between DBMs and LBMs by using a computational model informed by coevolutionary traits in the LacI family. This model predicts the influence of proposed mutations on protein structure and function, quantifying the feasibility of each mutation for rescuing hybrid repressors. We accurately predict which hybrid repressors can be rescued by mutating residues to reinstall relevant module-module interactions. Experimental results confirm that dynamic ranges of gene expression induction were improved significantly in these mutants. This approach enhances the molecular and mechanistic understanding of LacI family proteins, and advances the ability to design modular genetic parts.

Immune checkpoint inhibitor treatment of a first cancer is associated with a decreased incidence of second primary cancer.

BACKGROUND: Second primary cancers (SPCs) are diagnosed in over 5% of patients after a first primary cancer (FPC). We explore here the impact of immune checkpoint inhibitors (ICIs) given for an FPC on the risk of SPC in different age groups, cancer types and treatments. PATIENTS AND METHODS: The files of the 46 829 patients diagnosed with an FPC in the Centre Léon Bérard from 2013 to 2018 were analyzed. Structured data were extracted and electronic patient records were screened using a natural language processing tool, with validation using manual screening of 2818 files of patients. Univariate and multivariate analyses of the incidence of SPC according to patient characteristics and treatment were conducted. RESULTS: Among the 46 829 patients, 1830 (3.9%) had a diagnosis of SPC with a median interval of 11.1 months (range 0-78 months); 18 128 (38.7%) received cytotoxic chemotherapy (CC) and 1163 (2.5%) received ICIs for the treatment of the FPC in this period. SPCs were observed in 7/1163 (0.6%) patients who had received ICIs for their FPC versus 437/16 997 (2.6%) patients receiving CC and no ICIs for the FPC versus 1386/28 669 (4.8%) for patients receiving neither CC nor ICIs for the FPC. This reduction was observed at all ages and for all histotypes analyzed. Treatment with ICIs and/or CC for the FPC are associated with a reduced risk of SPC in multivariate analysis. CONCLUSION: Immunotherapy with ICIs alone and in combination with CC was found to be associated with a reduced incidence of SPC for all ages and cancer types.

Medical students' perceptions of their teachers' and their own cultural competency: implications for education.

BACKGROUND: Enhancing the cultural competency of students is emerging as a key issue in medical education; however, students may perceive that they are more able to function within cross-cultural situations than their teachers, reducing the effectiveness of cultural competency educational efforts. OBJECTIVE: The purpose of our study was to compare medical students' perceptions of their residents, attendings, and their own cultural competency. DESIGN: Cross-sectional study. MAIN MEASURES: A questionnaire containing previously validated instruments was administered to end-of-third-year medical students at four institutions throughout the US. Repeated measures multivariate analysis was used to determine differences in student ratings. PARTICIPANTS: Three hundred fifty-eight medical students from four schools participated, for an overall response rate of 65%. RESULTS: Analysis indicated overall statistically significant differences in students' ratings (p < 0.001, eta(2) = 0.33). Students rated their own cultural competency as statistically significantly higher than their residents, but similar to their attendings. For reference, students rated the patient care competency of themselves, their residents, and their attendings; they rated their attendings' skills as statistically significantly higher than residents, and residents as statistically significantly higher than themselves. There were differences between cultural competency and patient care ratings. CONCLUSIONS: Our results indicate that students perceive the cultural competency of their attendings and residents to be the same or lower than themselves. These findings indicate that this is an important area for future research and curricular reform, considering the vital role that attendings and residents play in the education of medical students.

Linking divergent selection on vegetative traits to environmental variation and phenotypic diversification in the Iberian columbines (Aquilegia).

Divergent selection is a key in the ecological theory of adaptive radiation. Most evidence on its causes and consequences relies on studies of pairs of populations or closely related taxa. However, adaptive radiation involves multiple taxa adapted to different environmental factors. We propose an operational definition of divergent selection to explore the continuum between divergent and convergent selection in multiple populations and taxa, and its links with environmental variation and phenotypic and taxonomic differentiation. We apply this approach to explore phenotypic differentiation of vegetative traits between 15 populations of four taxa of Iberian columbines (Gen. Aquilegia). Differences in soil rockiness impose divergent selection on inflorescence height and the number of flowers per inflorescence, likely affecting the processes of phenotypic and, in the case of inflorescence height, taxonomic diversification between taxa. Elevational variation imposes divergent selection on the number of leaves; however, the current pattern of divergent selection on this trait seems related to ecotypic differentiation within taxa but not to their taxonomic diversification.