Incidence of Abnormal Findings During Pelvic Examinations in Women Aged 21-35 Years.

To describe the incidence of abnormal gynecologic examination findings in asymptomatic compared with symptomatic patients during preventive visits, we conducted a retrospective study of 1,121 visits for patients between the ages of 21 and 35 years from January 2017 to March 2017. Only 1.2% (95% CI, 0.5%,1.9%) of asymptomatic patients had abnormal findings on pelvic examination, compared with 32.4% (95% CI, 27.0%, 37.8%) of those with symptoms ( P ≤.001). In symptomatic patients, the most common symptoms were vaginal discharge (25.1%), pelvic pain (16.4%), and vaginal bleeding (15.7%). In asymptomatic patients, the most common findings were bacterial vaginosis and Candida infection. Asymptomatic patients presenting for a routine preventive visit have low rates of abnormalities detected on examination, and routine pelvic examinations should be re-considered.

Levels of Gynecologic Care: A Task Force Consensus Statement.

Systems of care have been established for obstetrics, trauma, and neonatology. An American College of Obstetricians and Gynecologists Presidential Task Force was established to develop a care system for gynecologic surgery. A group of experts who represent diverse perspectives in gynecologic practice proposed definitions of levels of gynecologic care using the Delphi method. The goal is to improve the quality of gynecologic surgical care performed in the United States by providing a framework of minimal institutional requirements for each level. Subgroups developed draft criteria for each level of care. The entire Task Force then met to reach consensus regarding the levels of care final definitions and parameters. The levels of gynecologic care framework focuses on systems of care by considering institutional resources and expertise, providing guidance on the provision of care in appropriate level facilities. These levels were defined by the ability to care for patients of increasing risk, complexity, and comorbidities, organizing gynecologic care around hospital capability. This framework can also be used to inform the escalation of care to appropriate facilities by identifying patients at risk and guiding them to facilities with the skills, expertise, and capabilities to safely and effectively meet their needs. The levels of gynecologic care framework is intended for use by patients, hospitals, and clinicians in the United States to guide where elective surgery can be done most safely and effectively by specialists and subspecialists in obstetrics and gynecology. The key features of the levels of gynecologic care include ensuring provision of risk-appropriate care and regionalization of care by facility capabilities.

A Retrospective Study of Implant Placement Lateral to the Inferior Alveolar Nerve (ILIAN) in Severely Atrophic Posterior Mandibular Ridges

Currently, there are several techniques being used in the posterior mandible to increase alveolar bone height and width. However, each of these has potential complications and limitations. The purpose of the current study was to present the surgical technique and restorative considerations for implant placement lateral to the inferior alveolar nerve (IAN) in cases of severely atrophic edentulous posterior mandibles. In the current study, 26 implants in 16 patients were successfully placed lateral to IAN and restored with splinted screw-retained prostheses with a follow-up time after loading ranging from 3 months to 6 years. Two patients reported complications. One patient had a temporary paresthesia that resolved 3 months after implant placement and the second patient had minor paresthesia which was reduced after implant removal but remained in a small area on the left corner of her lip.

Saúde mental, direitos humanos e justiça ambiental: a 'quimicalização da vida' como uma questão de violação de direitos humanos decorrente da intoxicação institucionalizada / Mental health, human rights and environmental justice: the chemicalization of life as a matter of violation of human rights due to institutionalized intoxication

RESUMO Este trabalho tematiza o problema das consequências sociossanitárias e ambientais do círculo vicioso que liga violação de direitos humanos, insegurança alimentar e intoxicação institucionalizada, principalmente em relação aos efeitos sobre a saúde mental decorrentes dos contaminantes ambientais e dos agrotóxicos. O modelo predatório do capitalismo pós-industrial nasceu vinculado a fatores centrais, como: a agricultura químico-dependente, a medicalização social e a transição nutricional, associadas à mercantilização perversa dos recursos naturais. A expansão de monoculturas de larga escala com uso de agrotóxicos e outros contaminantes ambientais, a expansão da indústria farmacêutica e da tecnificação médica, e a expansão do modelo de alimentação industrial aditivada são consequências associadas a esses fatores que estão interligados. Além disso, esse processo é estimulado e reproduzido de forma institucionalizada e legalizada e vem produzindo múltiplas violações de direitos humanos e o aprofundamento de diversas formas de intoxicação e adoecimento: esse modelo pode ser denominado de 'paradigma da quimicalização da vida'.

ABSTRACT This work thematizes the problem of socio-sanitary and environmental consequences of the vicious circle that links human rights violations, food insecurity, and institutionalized intoxication, mainly in relation to the effects on mental health resulting from environmental contaminants and pesticides. The predatory model of post-industrial capitalism was born linked to central factors, such as: chemical-dependent agriculture, social medicalization, and nutritional transition, associated with the perverse commodification of natural resources. The expansion of large-scale monocultures using pesticides and other environmental contaminants, the expansion of the pharmaceutical industry and medical technology, and the expansion of the industrial additivated food model are consequences associated with these interconnected factors. In addition, this process is stimulated and reproduced in an institutionalized and legalized way and has been producing multiple human rights violations and the deepening of various forms of intoxication and illness: this model can be called the 'paradigm of the chemicalization of life'.

Angiokeratoma-like purpuric palmar nodules following chemotherapy.

We describe a patient with leukemia undergoing chemotherapy who developed painful purpuric nodules of the digits. These findings were concerning for endocarditis (clinically) and angiokeratomas on gross histology. After extensive evaluation, we report the development of painful purpuric nodules as a likely side effect of the patient's therapeutic regimen (hydroxyurea, danorubicin, cytarabine, and methotrexate).

Improving Free Gingival Graft Success Around Implants Using a Completed Implant Restoration.

Keratinized mucosa around implants is considered essential for maintaining peri-implant health. Clinicians may find it necessary to augment keratinized tissue after implant loading when complications arise. Immobilizing the graft can be challenging when there is a complete absence of attached gingiva or when the vestibule is shallow creating an opportunity for muscle forces to move the graft. To overcome these limitations, various stents have been created aimed at improving the stability of soft-tissue grafts around implants; however, many of these stents have drawbacks. This case report presents a novel approach for improving free gingival graft immobility and success around implants that utilizes a completed implant restoration.

Variability within rare cell states enables multiple paths toward drug resistance.

Molecular differences between individual cells can lead to dramatic differences in cell fate, such as death versus survival of cancer cells upon drug treatment. These originating differences remain largely hidden due to difficulties in determining precisely what variable molecular features lead to which cellular fates. Thus, we developed Rewind, a methodology that combines genetic barcoding with RNA fluorescence in situ hybridization to directly capture rare cells that give rise to cellular behaviors of interest. Applying Rewind to BRAFV600E melanoma, we trace drug-resistant cell fates back to single-cell gene expression differences in their drug-naive precursors (initial frequency of ~1:1,000-1:10,000 cells) and relative persistence of MAP kinase signaling soon after drug treatment. Within this rare subpopulation, we uncover a rich substructure in which molecular differences among several distinct subpopulations predict future differences in phenotypic behavior, such as proliferative capacity of distinct resistant clones after drug treatment. Our results reveal hidden, rare-cell variability that underlies a range of latent phenotypic outcomes upon drug exposure.

Genetic screening for single-cell variability modulators driving therapy resistance.

Cellular plasticity describes the ability of cells to transition from one set of phenotypes to another. In melanoma, transient fluctuations in the molecular state of tumor cells mark the formation of rare cells primed to survive BRAF inhibition and reprogram into a stably drug-resistant fate. However, the biological processes governing cellular priming remain unknown. We used CRISPR-Cas9 genetic screens to identify genes that affect cell fate decisions by altering cellular plasticity. We found that many factors can independently affect cellular priming and fate decisions. We discovered a new plasticity-based mode of increasing resistance to BRAF inhibition that pushes cells towards a more differentiated state. Manipulating cellular plasticity through inhibition of DOT1L before the addition of the BRAF inhibitor resulted in more therapy resistance than concurrent administration. Our results indicate that modulating cellular plasticity can alter cell fate decisions and may prove useful for treating drug resistance in other cancers.

Memory Sequencing Reveals Heritable Single-Cell Gene Expression Programs Associated with Distinct Cellular Behaviors.

Non-genetic factors can cause individual cells to fluctuate substantially in gene expression levels over time. It remains unclear whether these fluctuations can persist for much longer than the time of one cell division. Current methods for measuring gene expression in single cells mostly rely on single time point measurements, making the duration of gene expression fluctuations or cellular memory difficult to measure. Here, we combined Luria and Delbrück's fluctuation analysis with population-based RNA sequencing (MemorySeq) for identifying genes transcriptome-wide whose fluctuations persist for several divisions. MemorySeq revealed multiple gene modules that expressed together in rare cells within otherwise homogeneous clonal populations. These rare cell subpopulations were associated with biologically distinct behaviors like proliferation in the face of anti-cancer therapeutics. The identification of non-genetic, multigenerational fluctuations can reveal new forms of biological memory in single cells and suggests that non-genetic heritability of cellular state may be a quantitative property.

Peri-implant Mucositis.

Peri-implant mucositis has been defined as a reversible inflammatory reaction in the soft tissues around a functioning implant with no bone loss. This paper reviews the prevalence, etiology, risk indicators, prevention, and treatment of mucositis. Relying on the literature concerning mucositis, the bacterial etiology is discussed as well as the varying ranges of prevalence, reported to be from 20% to 80% of subjects (13% to 62% of implants) after a minimum of 5 years of implant function. A discussion of the definition of mucositis questions the assumption of it being completely reversible following treatment and challenges the concept of mucositis "transfer" (conversion) to peri-implantitis.

"De volta à cidade, sr. cidadão!" - reforma psiquiátrica e participação social: do isolamento institucional ao movimento antimanicomial / "De vuelta a la ciudad, el sr. ciudadano" - reforma psiquiátrica y participación social: del aislamiento institucional al movimiento antimanicomial / "Back to the city, Mr. citizen!" — psychiatric reform and social participation: from institutional isolation to the anti-asylum movement

Resumo O modelo manicomial produziu a exclusão da loucura da vida social, fundado no princípio do isolamento terapêutico, que gerou a institucionalização do louco e sua retirada da cidade e do direito à participação social, com a perda do direito à cidade e da condição de cidadania. Atualmente, a reforma psiquiátrica no Brasil é um dos mais importantes processos de crítica à psiquiatrização da loucura, promovendo uma desconstrução das formas de exclusão social da loucura e o debate na sociedade acerca dos direitos e da cidadania dos sujeitos em sofrimento mental e vulnerabilidade social. Diversas frentes inovadoras, de inclusão pelo trabalho, pela arte-cultura, pela militância política e de ocupação da cidade, têm configurado novas possibilidades de vida e expressão para os sujeitos, numa nova concepção sobre a loucura e a diferença, na qual os sujeitos da diversidade têm direito à cidade e à participação social.

Resumen El modelo de asilo produjo la exclusión de la locura de la vida social, fundado en el principio de aislamiento terapéutico, lo que llevó a la institucionalización de los locos y su retirada de la ciudad y la participación social, la pérdida del derecho a la ciudad y la ciudadanía. Actualmente, la reforma psiquiátrica en Brasil es uno de los procesos críticos más importantes para psiquiatrización de la locura, la promoción de una deconstrucción de las formas de exclusión social de la locura y el debate en la sociedad sobre la ciudadanía de las personas en la angustia mental y la vulnerabilidad. Varios frentes innovadores, la integración a través del trabajo, el arte, la cultura, el activismo político y la ocupación de la ciudad, han creado nuevas posibilidades de vida y expresión al sujeto, una nueva concepción de la locura y la diferencia en el cual los sujetos de la diversidad tienen derecho a la ciudad y la participación social.

Abstract The asylum model produced the exclusion of madness from social life, adopting the principle of therapeutic isolation, which led to the institutionalization of the person with mental suffering and their removal from the city and the social participation, subtracting from them the right to the city and the condition of citizenship. Currently, psychiatric reform in Brazil is one of the most important processes of criticizing the psychiatrisation of madness, promoting a deconstruction of the forms of social exclusion and the debate in society about the citizenship of the subjects in mental suffering and social vulnerability. Several innovative fronts, including work, art, culture, political activism and occupation of the city, have set new possibilities for life and expression for the people, in a new conception of madness and difference, in which the diversity of individuals have the right to the city and social participation.

ClampFISH detects individual nucleic acid molecules using click chemistry-based amplification.

Methods for detecting single nucleic acids in cell and tissues, such as fluorescence in situ hybridization (FISH), are limited by relatively low signal intensity and nonspecific probe binding. Here we present click-amplifying FISH (clampFISH), a method for fluorescence detection of nucleic acids that achieves high specificity and high-gain (>400-fold) signal amplification. ClampFISH probes form a 'C' configuration upon hybridization to the sequence of interest in a double helical manner. The ends of the probes are ligated together using bio-orthogonal click chemistry, effectively locking the probes around the target. Iterative rounds of hybridization and click amplify the fluorescence intensity. We show that clampFISH enables the detection of RNA species with low-magnification microscopy and in RNA-based flow cytometry. Additionally, we show that the modular design of clampFISH probes allows multiplexing of RNA and DNA detection, that the locking mechanism prevents probe detachment in expansion microscopy, and that clampFISH can be applied in tissue samples.

SAVER: gene expression recovery for single-cell RNA sequencing.

In single-cell RNA sequencing (scRNA-seq) studies, only a small fraction of the transcripts present in each cell are sequenced. This leads to unreliable quantification of genes with low or moderate expression, which hinders downstream analysis. To address this challenge, we developed SAVER (single-cell analysis via expression recovery), an expression recovery method for unique molecule index (UMI)-based scRNA-seq data that borrows information across genes and cells to provide accurate expression estimates for all genes.

Gene expression distribution deconvolution in single-cell RNA sequencing.

Single-cell RNA sequencing (scRNA-seq) enables the quantification of each gene's expression distribution across cells, thus allowing the assessment of the dispersion, nonzero fraction, and other aspects of its distribution beyond the mean. These statistical characterizations of the gene expression distribution are critical for understanding expression variation and for selecting marker genes for population heterogeneity. However, scRNA-seq data are noisy, with each cell typically sequenced at low coverage, thus making it difficult to infer properties of the gene expression distribution from raw counts. Based on a reexamination of nine public datasets, we propose a simple technical noise model for scRNA-seq data with unique molecular identifiers (UMI). We develop deconvolution of single-cell expression distribution (DESCEND), a method that deconvolves the true cross-cell gene expression distribution from observed scRNA-seq counts, leading to improved estimates of properties of the distribution such as dispersion and nonzero fraction. DESCEND can adjust for cell-level covariates such as cell size, cell cycle, and batch effects. DESCEND's noise model and estimation accuracy are further evaluated through comparisons to RNA FISH data, through data splitting and simulations and through its effectiveness in removing known batch effects. We demonstrate how DESCEND can clarify and improve downstream analyses such as finding differentially expressed genes, identifying cell types, and selecting differentiation markers.

FPGA-Based High-Performance Embedded Systems for Adaptive Edge Computing in Cyber-Physical Systems: The ARTICo³ Framework.

Cyber-Physical Systems are experiencing a paradigm shift in which processing has been relocated to the distributed sensing layer and is no longer performed in a centralized manner. This approach, usually referred to as Edge Computing, demands the use of hardware platforms that are able to manage the steadily increasing requirements in computing performance, while keeping energy efficiency and the adaptability imposed by the interaction with the physical world. In this context, SRAM-based FPGAs and their inherent run-time reconfigurability, when coupled with smart power management strategies, are a suitable solution. However, they usually fail in user accessibility and ease of development. In this paper, an integrated framework to develop FPGA-based high-performance embedded systems for Edge Computing in Cyber-Physical Systems is presented. This framework provides a hardware-based processing architecture, an automated toolchain, and a runtime to transparently generate and manage reconfigurable systems from high-level system descriptions without additional user intervention. Moreover, it provides users with support for dynamically adapting the available computing resources to switch the working point of the architecture in a solution space defined by computing performance, energy consumption and fault tolerance. Results show that it is indeed possible to explore this solution space at run time and prove that the proposed framework is a competitive alternative to software-based edge computing platforms, being able to provide not only faster solutions, but also higher energy efficiency for computing-intensive algorithms with significant levels of data-level parallelism.

Rare Cell Detection by Single-Cell RNA Sequencing as Guided by Single-Molecule RNA FISH.

Although single-cell RNA sequencing can reliably detect large-scale transcriptional programs, it is unclear whether it accurately captures the behavior of individual genes, especially those that express only in rare cells. Here, we use single-molecule RNA fluorescence in situ hybridization as a gold standard to assess trade-offs in single-cell RNA-sequencing data for detecting rare cell expression variability. We quantified the gene expression distribution for 26 genes that range from ubiquitous to rarely expressed and found that the correspondence between estimates across platforms improved with both transcriptome coverage and increased number of cells analyzed. Further, by characterizing the trade-off between transcriptome coverage and number of cells analyzed, we show that when the number of genes required to answer a given biological question is small, then greater transcriptome coverage is more important than analyzing large numbers of cells. More generally, our report provides guidelines for selecting quality thresholds for single-cell RNA-sequencing experiments aimed at rare cell analyses.

Corrigendum: Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance.

This corrects the article DOI: 10.1038/nature22794.

Surgical considerations and challenges in the pediatric and adolescent gynecologic patient.

It is important for practitioners to recognize that there are special considerations when performing gynecologic surgery in a pediatric or adolescent patient. A provider must be familiar with differences in anatomy, physiology, surgical technique, and psychosocial concerns. This can be challenging for a provider who does not routinely operate on patients in this population. A minimally invasive surgical approach is preferred in the pediatric and adolescent patient whenever possible. While a good command of laparoscopy in the adult patient is certainly a useful skill when operating on pediatric and adolescent patients, there are technical adaptations and challenges to consider. This chapter reviews the pre-operative preparation, operative technique and challenges, and post-operative care of the surgical pediatric and adolescent gynecologic patient.