Use of a skin flap has been a common technique in reconstructive surgery for more than five decades. However, partial necrosis of its distal end is still a serious postoperative complication. Many theories about this problem have been proposed, including deficient blood supply, which is the most accepted theory. In this study we demonstrated that hypoxic preconditioning enhanced the viability of adipose-derived stem cells (ADSCs) in vivo and improved their ability to increase the survival rate of ischemic skin flaps in rats. Seven days after flap elevation, the flap survival rate in the hypoxic preconditioned ADSC group was higher than that in the control group. Moreover, histological examination showed that more ADSCs survived in flaps treated by hypoxic preconditioning. Vascular density in the hypoxic preconditioned ADSC group was 30-90 % greater than that in the control group. In addition, the expressions of vascular endothelial growth factor and hypoxia inducible factor-1α (HIF-1α) were higher in the hypoxic preconditioned ADSC group than in the control group (p < 0.05). This enhancive phenomenon reached its highest level at the precondition times of 3 and 7 days in the hypoxic preconditioned ADSC group. We conclude that hypoxia preconditioning effectively enhances the viability of ADSCs to increase the survival rate of ischemic skin flaps. Furthermore, 3 days is the optimal preconditioning time point.

METHODS

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

BACKGROUND

Studies of colorectal cancer (CRC) have shown that hundreds to thousands of genes are differentially expressed in tumors when compared to normal tissue samples. In this study, we evaluate how genes that are differentially expressed in colon versus normal tissue influence survival.

METHODS

We performed RNA-seq on tumor/normal paired samples from 175 colon cancer patients. We implemented a cross validation strategy to determine genes that were significantly differentially expressed between tumor and normal samples. Differentially expressed genes were evaluated with Ingenuity Pathway Analysis to identify key pathways that were de-regulated. A summary differential pathway expression score (DPES) was developed to summarize hazard of dying while adjusting for age, American Joint Committee on Cancer (AJCC) stage, sex, and tumor molecular phenotype, i.e., MSI, TP53, KRAS, and CIMP.

RESULTS

A total of 1,138 genes were up-regulated and 695 were down-regulated. These de-regulated genes were enriched for 19 Ingenuity Canonical Pathways, with the most significant pathways involving cell signaling and growth. Of the enriched pathways, 16 were significantly associated with CRC-specific mortality, including 1 metabolic pathway and 15 signaling pathways. In all instances, having a higher DPES (i.e., more de-regulated genes) was associated with better survival. Further assessment showed that individuals diagnosed at AJCC Stage 1 had more de-regulated genes than individuals diagnosed at AJCC Stage 4.

CONCLUSIONS

Our data suggest that having more de-regulated pathways is associated with a good prognosis and may be a reaction to key events that are disabling to tumor progression. Please see related article: http://dx.doi.org/10.1186/s12916-015-0307-6 .

Molecular and biochemical expressions of matrix metalloproteinases in breast cancer tissue and cells offers promise in helping us understand the breast cancer microenvironment, and also in the future it is hoped this will improve its detection, treatment and prognosis. In a retrospective study recently published in BMC Cancer, microenvironment predisposing to breast cancer progression, metastatic behavior and the expression of matrix metalloproteinase-1 (MMP-1) and its correlation with well-known biochemical, molecular and clinicopathologic factors in breast cancer cells and cancer-associated stromal cells was examined; this study also analyzed patient survival in different breast cancer subtypes. The positive correlation in breast tumor and stromal cells between MMP-1 expression and several markers of tumor grade and stage provide us with some useful new insights into important questions about the molecular profiling of the stromal microenvironment in metastatic breast cancer. The study showed that MMP-1 expression is strongly associated with poor clinical outcome, so now we look forward to future larger studies in breast cancer patients in which we can relate wider MMP molecular profiling to identify lethal tumor and stromal microenvironments predisposing to breast cancer progression, metastatic behavior and poor prognosis. Please see related article http://www.biomedcentral.com/1471-2407/11/348.

Despite the common use of immunohistochemistry in autopsy tissues, the stability of most proteins over extended time periods is unknown. The robustness of signal for 16 proteins (MMP1, MMP2, MMP3, MMP9, TIMP1, TIMP2, TIMP3, AGER, MSR, SCARB1, OLR1, CD36, LTF, LGALS3, LYZ, and DDOST) and two measures of advanced glycation end products (AGE, CML) was evaluated. Two formalin-fixed, paraffin-embedded human tissue arrays containing 16 tissues each were created to evaluate 48 hr of autolysis in a warm or cold environment. For these classes of proteins, matrix metalloproteinases and their inhibitors, scavenger receptors, and advanced glycation end product receptors, we saw no systematic diminution of signal intensity during a period of 24 hr. Analysis was performed by two independent observers and confirmed for a subset of proteins by digital analysis and Western blotting. We conclude that these classes of proteins degrade slowly and faithfully maintain their immunohistochemistry characteristics over at least a 24-hr time interval in devitalized tissues. This study supports the use of autopsy tissues with short postmortem intervals for immunohistochemical studies for diseases such as diabetic vascular disease, cancer, Alzheimer's disease, atherosclerosis, and other pathological states. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.

We examined the associations between chronic diseases requiring hospitalization and the risk of non-melanoma skin cancers (NMSCs) in a population-based case-control study of 4,187 patients diagnosed with a first primary NMSC in 1995 in Denmark. From the National Patient Registry covering all Danish hospitals, we obtained data on hospitalizations with chronic diseases, recorded before the date of NMSC diagnosis. Using incidence density sampling, we selected 10 age-, gender-, and residence-matched controls from the Danish Civil Registration System. We used conditional logistic regression to compute incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Although no overall association was found between basal cell carcinoma (BCC) and hospitalization for chronic diseases, an elevated IRR for BCC was found among patients with connective tissue disease (IRR 1.34 (95% CI: 0.99-1.82)), transplants (IRR 8.00 (95% CI: 2.15-30)), and lymphoma (IRR 2.50 (95% CI: 1.29-4.84)). An overall association between squamous cell carcinoma (SCC) and hospitalization for chronic diseases was found and specific among patients with leukemia (IRR 7.75 (95% CI: 2.35-26)), lymphoma (IRR 3.86 (95% CI: 0.99-15)), and skin diseases (IRR 5.28 (95% CI: 1.95-14)). Our study supports the presence of an association between certain chronic diseases and NMSC, and further suggests that these results unlikely are due to bias. JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article please go to http://network.nature.com/group/jidclub.

Throughout the long history of the hemostasis laboratory, and as an evaluation of the coagulation cascade, the results of the activated partial thromboplastin time (APTT) have primarily been considered as an index of loss-of-function and rarely as an index of gain-of-function. Nevertheless, there are now several clinical and technical reasons that no longer allow us to simply ignore or overlook shortened APTTs in laboratory practice. It has long been suspected that the leading cause of shortened APTTs are related to preanalytical problems, in which case it would be inappropriate for a laboratory to issue such a test result, which would expectedly not adequately mirror the patient's true condition. Should such artifactual results be reliably ruled out, that is by confirming short APTT values on subsequent samples, it would then be worth considering to troubleshoot potential causes, inasmuch as this phenomenon may reflect a variety of clinically meaningful conditions, including an increased risk of thromboembolic events, cancer, myocardial infarction, thyroid disorders, diabetes, and pregnancy. Although there are no univocal data supporting the origin of this singular phenomenon as yet, we strongly encourage the utility of postanalytical laboratory guidance, including a relevant short accompanying comment in the laboratory report linked to the APTT test result, for example, noting 'Short APTT-potentially reflective of in-vitro activation of blood coagulation due to difficult collection. If the value is systematically confirmed in subsequent samples, please contact the laboratory to help assess the cause'.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Authors. Since learning of potential discrepancies between the raw data from the animal pulmonary physiology laboratory at Duke that were used to calculate the in vivo pulmonary mechanics and the re-exported machine-generated raw data, some studies published elsewhere have been replicated successfully. However it is not possible to replicate this study as the NQO1-deficient mice on the C57BL/6 background are no longer available from the NCI. The authors recognize that previous work to identify differences in alveolar size can vary dependent on background strain when comparing inbred mouse strains (Soutiere SE et al Resp Physiol Neurobiol 2004;140(3)183–91 doi: 10.1016/j.resp.2004.02.003). Because of the prolonged period of time required to successfully backcross NQO1-deficient animals onto C57BL/6J background and the time required to repeat studies presented in this manuscript the authors think it does not seem feasible to conduct replicate studies in a reasonable timeline. Therefore, the most appropriate course of action is to retract the report as it is the authors' goal to maintain accuracy of the scientific record to the best of their ability. The authors offer sincere apologies to the scientific community.

BACKGROUND

The Chin State of Burma (also known as Myanmar) is an isolated ethnic minority area with poor health outcomes and reports of food insecurity and human rights violations. We report on a population-based assessment of health and human rights in Chin State. We sought to quantify reported human rights violations in Chin State and associations between these reported violations and health status at the household level.

RESULTS

Multistaged household cluster sampling was done. Heads of household were interviewed on demographics, access to health care, health status, food insecurity, forced displacement, forced labor, and other human rights violations during the preceding 12 months. Ratios of the prevalence of household hunger comparing exposed and unexposed to each reported violation were estimated using binomial regression, and 95% confidence intervals (CIs) were constructed. Multivariate models were done to adjust for possible confounders. Overall, 91.9% of households (95% CI 89.7%-94.1%) reported forced labor in the past 12 months. Forty-three percent of households met FANTA-2 (Food and Nutrition Technical Assistance II project) definitions for moderate to severe household hunger. Common violations reported were food theft, livestock theft or killing, forced displacement, beatings and torture, detentions, disappearances, and religious and ethnic persecution. Self reporting of multiple rights abuses was independently associated with household hunger.

CONCLUSIONS

Our findings indicate widespread self-reports of human rights violations. The nature and extent of these violations may warrant investigation by the United Nations or International Criminal Court. Please see later in the article for the Editors' Summary.

Paul Glasziou and colleagues discuss methods to guide selection of an intervention from individual trials within a systematic review. Please see later in the article for the Editors' Summary.

Pass the salt, please! State-of-the-art computations indicate that the stacking complex of a guanine quartet and an adenine quartet (G(4)A(4)) can function as a potent ditopic receptor for NaCl in aqueous solution (see picture; Na(+), Cl(-) yellow, O red, N blue, C black, H white).

Liquid silicone is a permanent filler. Its use to augment soft tissues for aesthetic purposes was widespread worldwide in the 1960s. Although initially considered to be biologically inert, this substance may cause, after its injection, an inflammatory granulomatous effect of variable severity and, in very rare cases, a severe hypercalcemia, which can be life threatening. The reported case highlights the well-known physiopathology of hypercalcemia, and the various therapeutic options are discussed.

METHODS

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Attentional modulation along the object-recognition pathway of the cortical visual system of primates has been shown to consist of enhanced representation of the retinal input at a specific location in space, or of objects located anywhere in the visual field which possess a critical object feature. Moreover, selective attention mechanisms allow the visual system to resolve competition among multiple objects in a crowded scene in favor of the object that is relevant for the current behavior. Finally, selective attention affects the spontaneous activity of neurons as well as their visually driven responses, and it does so not only by modulating the spiking activity of individual neurons, but also by modulating the degree of coherent firing within the critical neuronal populations. WIREs Cogni Sci 2011 2 392-407 DOI: 10.1002/wcs.117 For further resources related to this article, please visit the WIREs website.

In June 2008, the Medical Advisory Secretariat began work on the Diabetes Strategy Evidence Project, an evidence-based review of the literature surrounding strategies for successful management and treatment of diabetes. This project came about when the Health System Strategy Division at the Ministry of Health and Long-Term Care subsequently asked the secretariat to provide an evidentiary platform for the Ministry's newly released Diabetes Strategy.After an initial review of the strategy and consultation with experts, the secretariat identified five key areas in which evidence was needed. Evidence-based analyses have been prepared for each of these five areas: insulin pumps, behavioural interventions, bariatric surgery, home telemonitoring, and community based care. For each area, an economic analysis was completed where appropriate and is described in a separate report.To review these titles within the Diabetes Strategy Evidence series, please visit the Medical Advisory Secretariat Web site, http://www.health.gov.on.ca/english/providers/program/mas/mas_about.html,DIABETES STRATEGY EVIDENCE PLATFORM: Summary of Evidence-Based AnalysesContinuous Subcutaneous Insulin Infusion Pumps for Type 1 and Type 2 Adult Diabetics: An Evidence-Based AnalysisBehavioural Interventions for Type 2 Diabetes: An Evidence-Based AnalysisBARIATRIC SURGERY FOR PEOPLE WITH DIABETES AND MORBID OBESITY: An Evidence-Based SummaryCommunity-Based Care for the Management of Type 2 Diabetes: An Evidence-Based AnalysisHome Telemonitoring for Type 2 Diabetes: An Evidence-Based AnalysisApplication of the Ontario Diabetes Economic Model (ODEM) to Determine the Cost-effectiveness and Budget Impact of Selected Type 2 Diabetes Interventions in Ontario

OBJECTIVE

The objective of this analysis is to review the efficacy of continuous subcutaneous insulin infusion (CSII) pumps as compared to multiple daily injections (MDI) for the type 1 and type 2 adult diabetics.

UNASSIGNED

Insulin therapy is an integral component of the treatment of many individuals with diabetes. Type 1, or juvenile-onset diabetes, is a life-long disorder that commonly manifests in children and adolescents, but onset can occur at any age. It represents about 10% of the total diabetes population and involves immune-mediated destruction of insulin producing cells in the pancreas. The loss of these cells results in a decrease in insulin production, which in turn necessitates exogenous insulin therapy. Type 2, or 'maturity-onset' diabetes represents about 90% of the total diabetes population and is marked by a resistance to insulin or insufficient insulin secretion. The risk of developing type 2 diabetes increases with age, obesity, and lack of physical activity. The condition tends to develop gradually and may remain undiagnosed for many years. Approximately 30% of patients with type 2 diabetes eventually require insulin therapy. CSII PUMPS: In conventional therapy programs for diabetes, insulin is injected once or twice a day in some combination of short- and long-acting insulin preparations. Some patients require intensive therapy regimes known as multiple daily injection (MDI) programs, in which insulin is injected three or more times a day. It's a time consuming process and usually requires an injection of slow acting basal insulin in the morning or evening and frequent doses of short-acting insulin prior to eating. The most common form of slower acting insulin used is neutral protamine gagedorn (NPH), which reaches peak activity 3 to 5 hours after injection. There are some concerns surrounding the use of NPH at night-time as, if injected immediately before bed, nocturnal hypoglycemia may occur. To combat nocturnal hypoglycemia and other issues related to absorption, alternative insulins have been developed, such as the slow-acting insulin glargine. Glargine has no peak action time and instead acts consistently over a twenty-four hour period, helping reduce the frequency of hypoglycemic episodes. Alternatively, intensive therapy regimes can be administered by continuous insulin infusion (CSII) pumps. These devices attempt to closely mimic the behaviour of the pancreas, continuously providing a basal level insulin to the body with additional boluses at meal times. Modern CSII pumps are comprised of a small battery-driven pump that is designed to administer insulin subcutaneously through the abdominal wall via butterfly needle. The insulin dose is adjusted in response to measured capillary glucose values in a fashion similar to MDI and is thus often seen as a preferred method to multiple injection therapy. There are, however, still risks associated with the use of CSII pumps. Despite the increased use of CSII pumps, there is uncertainty around their effectiveness as compared to MDI for improving glycemic control. PART A: TYPE 1 DIABETIC ADULTS (#ENTITYSTARTX02265;19 YEARS) An evidence-based analysis on the efficacy of CSII pumps compared to MDI was carried out on both type 1 and type 2 adult diabetic populations.

OBJECTIVE

Are CSII pumps more effective than MDI for improving glycemic control in adults (≥19 years) with type 1 diabetes?Are CSII pumps more effective than MDI for improving additional outcomes related to diabetes such as quality of life (QoL)?

METHODS

METHODS

Randomized controlled trials, systematic reviews, meta-analysis and/or health technology assessments from MEDLINE, EMBASE, CINAHLAdults (≥ 19 years)Type 1 diabetesStudy evaluates CSII vs. MDIPublished between January 1, 2002 - March 24, 2009Patient currently on intensive insulin therapy

METHODS

Studies with <20 patientsStudies <5 weeks in durationCSII applied only at night time and not 24 hours/dayMixed group of diabetes patients (children, adults, type 1, type 2)Pregnancy studies

METHODS

The primary outcomes of interest were glycosylated hemoglobin (HbA1c) levels, mean daily blood glucose, glucose variability, and frequency of hypoglycaemic events. Other outcomes of interest were insulin requirements, adverse events, and quality of life.

METHODS

The literature search strategy employed keywords and subject headings to capture the concepts of: 1) insulin pumps, and 2) type 1 diabetes. The search was run on July 6, 2008 in the following databases: Ovid MEDLINE (1996 to June Week 4 2008), OVID MEDLINE In-Process and Other Non-Indexed Citations, EMBASE (1980 to 2008 Week 26), OVID CINAHL (1982 to June Week 4 2008) the Cochrane Library, and the Centre for Reviews and Dissemination/International Agency for Health Technology Assessment. A search update was run on March 24, 2009 and studies published prior to 2002 were also examined for inclusion into the review. Parallel search strategies were developed for the remaining databases. Search results were limited to human and English-language published between January 2002 and March 24, 2009. Abstracts were reviewed, and studies meeting the inclusion criteria outlined above were obtained. Reference lists were also checked for relevant studies.

RESULTS

The database search identified 519 relevant citations published between 1996 and March 24, 2009. Of the 519 abstracts reviewed, four RCTs and one abstract met the inclusion criteria outlined above. While efficacy outcomes were reported in each of the trials, a meta-analysis was not possible due to missing data around standard deviations of change values as well as missing data for the first period of the crossover arm of the trial. Meta-analysis was not possible on other outcomes (quality of life, insulin requirements, frequency of hypoglycemia) due to differences in reporting. HBA1C: In studies where no baseline data was reported, the final values were used. Two studies (Hanaire-Broutin et al. 2000, Hoogma et al. 2005) reported a slight reduction in HbA1c of 0.35% and 0.22% respectively for CSII pumps in comparison to MDI. A slightly larger reduction in HbA1c of 0.84% was reported by DeVries et al.; however, this study was the only study to include patients with poor glycemic control marked by higher baseline HbA1c levels. One study (Bruttomesso et al. 2008) showed no difference between CSII pumps and MDI on Hba1c levels and was the only study using insulin glargine (consistent with results of parallel RCT in abstract by Bolli 2004). While there is statistically significant reduction in HbA1c in three of four trials, there is no evidence to suggest these results are clinically significant. MEAN BLOOD GLUCOSE: Three of four studies reported a statistically significant reduction in the mean daily blood glucose for patients using CSII pump, though these results were not clinically significant. One study (DeVries et al. 2002) did not report study data on mean blood glucose but noted that the differences were not statistically significant. There is difficulty with interpreting study findings as blood glucose was measured differently across studies. Three of four studies used a glucose diary, while one study used a memory meter. In addition, frequency of self monitoring of blood glucose (SMBG) varied from four to nine times per day. Measurements used to determine differences in mean daily blood glucose between the CSII pump group and MDI group at clinic visits were collected at varying time points. Two studies use measurements from the last day prior to the final visit (Hoogma et al. 2005, DeVries et al. 2002), while one study used measurements taken during the last 30 days and another study used measurements taken during the 14 days prior to the final visit of each treatment period. GLUCOSE VARIABILITY: All four studies showed a statistically significant reduction in glucose variability for patients using CSII pumps compared to those using MDI, though one, Bruttomesso et al. 2008, only showed a significant reduction at the morning time point. Brutomesso et al. (ABSTRACT TRUNCATED)

Predicting regulatory potential from primary DNA sequences or transcription factor binding patterns is not possible. However, the annotation of the genome by chromatin proteins, histone modifications, and differential compaction is largely sufficient to reveal the locations of genes and their differential activity states. The Polycomb Group (PcG) and Trithorax Group (TrxG) proteins are the central players in this cell type-specific chromatin organization. PcG function was originally viewed as being solely repressive and irreversible, as observed at the homeotic loci in flies and mammals. However, it is now clear that modular and reversible PcG function is essential at most developmental genes. Focusing mainly on recent advances, we review evidence for how PcG and TrxG patterns change dynamically during cell type transitions. The ability to implement cell type-specific transcriptional programming with exquisite fidelity is essential for normal development. Expected final online publication date for the Annual Review of Biochemistry, Volume 89 is June 22, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Four boys with autism were taught via echoic prompting and constant prompt delay to mand for answers to questions by saying "I don't know please tell me" (IDKPTM). This intervention resulted in acquisition of the IDKPTM response for all 4 participants and in acquisition of correct answers to most of the previously unknown questions for 2 participants. For 1 participant, tangible reinforcement resulted in increased frequency of correct answers, and direct prompting of correct answers was eventually conducted for the final participant. The IDKPTM response generalized to untargeted unknown questions with 3 participants. Results of person and setting generalization probes varied, but some generalization eventually occurred for all participants following additional training or interspersal of probe trials with training trials.

BACKGROUND

Aripiprazole, a second-generation antipsychotic medication, has been increasingly used in the maintenance treatment of bipolar disorder and received approval from the U.S. Food and Drug Administration for this indication in 2005. Given its widespread use, we sought to critically review the evidence supporting the use of aripiprazole in the maintenance treatment of bipolar disorder and examine how that evidence has been disseminated in the scientific literature.

RESULTS

We systematically searched multiple databases to identify double-blind, randomized controlled trials of aripiprazole for the maintenance treatment of bipolar disorder while excluding other types of studies, such as open-label, acute, and adjunctive studies. We then used a citation search to identify articles that cited these trials and rated the quality of their citations. Our evidence search protocol identified only two publications, both describing the results of a single trial conducted by Keck et al., which met criteria for inclusion in this review. We describe four issues that limit the interpretation of that trial as supporting the use of aripiprazole for bipolar maintenance: (1) insufficient duration to demonstrate maintenance efficacy; (2) limited generalizability due to its enriched sample; (3) possible conflation of iatrogenic adverse effects of abrupt medication discontinuation with beneficial effects of treatment; and (4) a low overall completion rate. Our citation search protocol yielded 80 publications that cited the Keck et al. trial in discussing the use of aripiprazole for bipolar maintenance. Of these, only 24 (30%) mentioned adverse events reported and four (5%) mentioned study limitations.

CONCLUSIONS

A single trial by Keck et al. represents the entirety of the literature on the use of aripiprazole for the maintenance treatment of bipolar disorder. Although careful review identifies four critical limitations to the trial's interpretation and overall utility, the trial has been uncritically cited in the subsequent scientific literature. Please see later in the article for the Editors' Summary.

Nanoscale engineering is revolutionizing the development of vaccines and immunotherapies. Viruses have played a key role in this field because they can function as prefabricated nanoscaffolds with unique properties that are easy to modify. Viruses are immunogenic via multiple pathways, and antigens displayed naturally or by engineering on the surface can be used to create vaccines against the cognate virus, other pathogens, specific molecules or cellular targets such as tumors. This review focuses on the development of virus-based nanoparticle systems as vaccines indicated for the prevention or treatment of infectious diseases, chronic diseases, cancer, and addiction. WIREs Nanomed Nanobiotechnol 2016, 8:554-578. doi: 10.1002/wnan.1383 For further resources related to this article, please visit the WIREs website.

Svea Closser and Rashid Jooma argue that achieving polio eradication and strengthening Pakistan's health system must focus not just on international engagement but also on local partnerships with Lady Health Workers and other ground-level staff. Please see later in the article for the Editors' Summary.

BACKGROUND

The aims of our study were to identify studies that evaluated patient satisfaction after transsexual surgery, analyze existing questionnaires, and summarize their development, psychometric properties, and content.

METHODS

A systematic review of the English-language literature was performed. Patient-reported outcome measures designed to assess patient satisfaction and quality of life following transsexual surgery were identified. Qualifying instruments were assessed for content and adherence to international guidelines for development and validation.

RESULTS

From 796 articles, 19 studies had sufficient data and met the inclusion criteria. Included were a total of 2299 patients and 17 patient-reported outcome measures: 10 generic instruments that assessed quality of life, 4 specific for female genital or sexual satisfaction, 2 specific for transsexual body image or gender dysphoria, and 1 specific for plastic surgery. The questionnaires were analyzed by reviewers to assess the adherence to the rules of the US FDA and the Scientific Advisory Committee of the Medical Outcomes Trust. We identified 17 individual questionnaires that were included. All measures were limited by either their development, their validation, or their content.

CONCLUSIONS

There is a need for a new self-assessment tool, which should include functional, psychorelational, and cosmetic components, to measure satisfaction and quality of life of patients who have undergone transsexual surgery.

UNASSIGNED

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

BACKGROUND

Autologous fat grafting has rapidly become an important treatment for soft tissue defects in cosmetic and reconstructive surgery. However, consensus is lacking on the ideal donor site for harvesting and isolating stromal vascular fraction (SVF) cells to improve survival of fat grafts. We aimed to determine the best donor site for tissue harvesting and isolation of SVF cells for fat graft survival.

METHODS

Adipose tissue samples were harvested from six women who underwent an aesthetic procedure. The samples were harvested by needle aspiration of five commonly used donor sites: flank, upper and lower abdomen, and lateral and inner thigh. The adipose tissue was injected subcutaneously into nude mice and grafts were harvested at 12 weeks. We evaluated graft volume, weight, and histologic parameters of the grafts: integrity, cysts/vacuoles, inflammation, fibrosis, and neovascularization. SVF cells isolated from donor sites were counted and assayed by flow cytometry.

RESULTS

At 12 weeks post-transplantation, weight, volume, and histologic parameters did not differ among the grafts from the five tissue donor sites. Also, SVF and levels of cell surface markers did not differ by donor site.

CONCLUSIONS

This study revealed no ideal tissue donor site for fat grafting and SVF isolation. Choosing a site should be based on ease and safety of access and the preference and request of the patient.

METHODS

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A new study finds that splicing disruption is a frequent consequence of mutations generated by CRISPR/Cas9 gene-editing technology, and alleles designed to be null can express aberrant proteins. This new information allows enhanced quality control procedures to select the best mutant alleles generated by CRISPR/Cas9.Please see related Method article: https://www.doi.org/10.1186/s13059-017-1237-8.

Derived from the term exposure, the exposome is an omic-scale characterization of the nongenetic drivers of health and disease. With the genome, it defines the phenome of an individual. The measurement of complex environmental factors that exert pressure on our health has not kept pace with genomics and historically has not provided a similar level of resolution. Emerging technologies make it possible to obtain detailed information on drugs, toxicants, pollutants, nutrients, and physical and psychological stressors on an omic scale. These forces can also be assessed at systems and network levels, providing a framework for advances in pharmacology and toxicology. The exposome paradigm can improve the analysis of drug interactions and detection of adverse effects of drugs and toxicants and provide data on biological responses to exposures. The comprehensive model can provide data at the individual level for precision medicine, group level for clinical trials, and population level for public health. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 59 is January 6, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

BACKGROUND

Previous studies have indicated that the wide variation in intron density (the number of introns per gene) among different eukaryotes largely reflects varying degrees of intron loss during evolution. The most popular model, which suggests that organisms lose introns through a mechanism in which reverse-transcribed cDNA recombines with the genomic DNA, concerns only one mutational force.

OBJECTIVE

Using exons as the units of splicing-site recognition, exon definition constrains the length of exons. An intron-loss event results in fusion of flanking exons and thus a larger exon. The large size of the newborn exon may cause splicing errors, i.e., exon skipping, if the splicing of pre-mRNAs is initiated by exon definition. By contrast, if the splicing of pre-mRNAs is initiated by intron definition, intron loss does not matter. Exon definition may thus be a selective force against intron loss. An organism with a high frequency of exon definition is expected to experience a low rate of intron loss throughout evolution and have a high density of spliceosomal introns.

CONCLUSIONS

The majority of spliceosomal introns in vertebrates may be maintained during evolution not because of potential functions, but because of their splicing mechanism (i.e., exon definition). Further research is required to determine whether exon definition is a negative force in maintaining the high intron density of vertebrates.

METHODS

This article was reviewed by Dr. Scott W. Roy (nominated by Dr. John Logsdon), Dr.Eugene V. Koonin, and Dr. Igor B. Rogozin (nominated by Dr. Mikhail Gelfand). For the full reviews,please go to the Reviewers' comments section.

BACKGROUND

Inadequate illness recognition and access to antibiotics contribute to high case fatality from infections in young infants (<2 months) in low- and middle-income countries (LMICs). We aimed to address three questions regarding access to treatment for young infant infections in LMICs: (1) Can frontline health workers accurately diagnose possible bacterial infection (pBI)?; (2) How available and affordable are antibiotics?; (3) How often are antibiotics procured without a prescription?

RESULTS

We searched PubMed, Embase, WHO/Health Action International (HAI), databases, service provision assessments (SPAs), Demographic and Health Surveys, Multiple Indicator Cluster Surveys, and grey literature with no date restriction until May 2014. Data were identified from 37 published studies, 46 HAI national surveys, and eight SPAs. For study question 1, meta-analysis showed that clinical sign-based algorithms predicted bacterial infection in young infants with high sensitivity (87%, 95% CI 82%-91%) and lower specificity (62%, 95% CI 48%-75%) (six studies, n = 14,254). Frontline health workers diagnosed pBI in young infants with an average sensitivity of 82% (95% CI 76%-88%) and specificity of 69% (95% CI 54%-83%) (eight studies, n = 11,857) compared to physicians. For question 2, first-line injectable agents (ampicillin, gentamicin, and penicillin) had low variable availability in first-level health facilities in Africa and South Asia. Oral amoxicillin and cotrimoxazole were widely available at low cost in most regions. For question 3, no studies on young infants were identified, however 25% of pediatric antibiotic purchases in LMICs were obtained without a prescription (11 studies, 95% CI 18%-34%), with lower rates among infants <1 year. Study limitations included potential selection bias and lack of neonatal-specific data.

CONCLUSIONS

Trained frontline health workers may screen for pBI in young infants with relatively high sensitivity and lower specificity. Availability of first-line injectable antibiotics appears low in many health facilities in Africa and Asia. Improved data and advocacy are needed to increase the availability and appropriate utilization of antibiotics for young infant infections in LMICs.

BACKGROUND

PROSPERO International prospective register of systematic reviews (CRD42013004586). Please see later in the article for the Editors' Summary.