Time-restricted eating and supervised exercise for improving hepatic steatosis and cardiometabolic health in adults with obesity: protocol for the TEMPUS randomised controlled trial.

INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease is a major public health problem considering its high prevalence and its strong association with extrahepatic diseases. Implementing strategies based on an intermittent fasting approach and supervised exercise may mitigate the risks. This study aims to investigate the effects of a 12-week time-restricted eating (TRE) intervention combined with a supervised exercise intervention, compared with TRE or supervised exercise alone and with a usual-care control group, on hepatic fat (primary outcome) and cardiometabolic health (secondary outcomes) in adults with obesity. METHODS AND ANALYSIS: An anticipated 184 adults with obesity (50% women) will be recruited from Granada (south of Spain) for this parallel-group, randomised controlled trial (TEMPUS). Participants will be randomly designated to usual care, TRE alone, supervised exercise alone or TRE combined with supervised exercise, using a parallel design with a 1:1:1:1 allocation ratio. The TRE and TRE combined with supervised exercise groups will select an 8-hour eating window before the intervention and will maintain it over the intervention. The exercise alone and TRE combined with exercise groups will perform 24 sessions (2 sessions per week+walking intervention) of supervised exercise combining resistance and aerobic high-intensity interval training. All participants will receive nutritional counselling throughout the intervention. The primary outcome is change from baseline to 12 weeks in hepatic fat; secondary outcomes include measures of cardiometabolic health. ETHICS AND DISSEMINATION: This study was approved by Granada Provincial Research Ethics Committee (CEI Granada-0365-N-23). All participants will be asked to provide written informed consent. The findings will be disseminated in scientific journals and at international scientific conferences. TRIAL REGISTRATION NUMBER: NCT05897073.

A common regulatory switch controls a suite of C4 traits in multiple cell types.

The C4 photosynthetic pathway provided a major advantage to plants growing in hot, dry environments, including the ancestors of our most productive crops. Two traits were essential for the evolution of this pathway: increased vein density and the functionalization of bundle sheath cells for photosynthesis. Although GRAS transcriptional regulators, including SHORT ROOT (SHR), have been implicated in mediating leaf patterning in both C3 and C4 species, little is known about what controls the specialized features of the cells that mediate C4 metabolism and physiology. We show in the model monocot, Setaria viridis, that SHR regulates components of multiple cell identities, including chloroplast biogenesis and photosynthetic gene expression in bundle sheath cells, a central feature of C4 plants. Furthermore, we found that it also contributes to the two-cell compartmentalization of the characteristic four-carbon shuttle pathway. Disruption of SHR function clearly reduced photosynthetic capacity and seed yield in mutant plants under heat stress. Together, these results show how cell identities are remodeled by SHR to host the suite of traits characteristic of C4 regulation, which are a main engineering target in non-C4 crops to improve climate resilience.

Efficacy of different 8 h time-restricted eating schedules on visceral adipose tissue and cardiometabolic health: A study protocol.

BACKGROUND AND AIMS: To investigate the efficacy and feasibility of three different 8 h time-restricted eating (TRE) schedules (i.e., early, late, and self-selected) compared to each other and to a usual-care (UC) intervention on visceral adipose tissue (VAT) and cardiometabolic health in men and women. METHODS AND RESULTS: Anticipated 208 adults (50% women) aged 30-60 years, with overweight/obesity (25 ≤ BMI<40 kg/m2) and with mild metabolic impairments will be recruited for this parallel-group, multicenter randomized controlled trial. Participants will be randomly allocated (1:1:1:1) to one of four groups for 12 weeks: UC, early TRE, late TRE or self-selected TRE. The UC group will maintain their habitual eating window and receive, as well as the TRE groups, healthy lifestyle education for weight management. The early TRE group will start eating not later than 10:00, and the late TRE group not before 13:00. The self-selected TRE group will select an 8 h eating window before the intervention and maintain it over the intervention. The primary outcome is changes in VAT, whereas secondary outcomes include body composition and cardiometabolic risk factors. CONCLUSION: This study will determine whether the timing of the eating window during TRE impacts its efficacy on VAT, body composition and cardiometabolic risk factors and provide insights about its feasibility.

Prevalence and Clinical Factors Associated With Pes Planus Among Children and Adults: A Population-Based Synthesis and Systematic Review.

Estimates of pes planus ("flatfoot") prevalence vary considerably across studies. Moreover, there is uncertainty over which factors are associated with the pes planus prevalence. We aimed to systematically review the prevalence and clinical factors associated with flatfoot among children and adults. We searched Web of Science, PubMed/MEDLINE, and Google Scholar databases reporting population-based flatfoot prevalence. Two reviewers independently extracted the data and assessed the qualities of the studies. Subgroup analysis was conducted to analyze the associated factors on flatfoot prevalence. Frequencies, odds ratios (OR), and 95% confidence intervals (CI) were performed using descriptive analysis and chi-square test accounting for heterogeneity. Any conflict in the data analysis was discussed by all the reviewers. Twelve studies including 2509 flatfoot cases were analyzed (overall prevalence 15.6%, n = 16,000). The subgroup analysis indicated that male gender (OR = 1.26, 95% CI: 1.15-1.37), age groups 3 to 5 years (OR = 2.02, 95% CI: 1.78-2.30) and 11 to 17 years (OR = 1.91, 95% CI: 1.64-2.22), Asian race (OR = 2.34, 95% CI: 2.10-2.60), and obesity (OR = 2.62, 95% CI: 2.06-3.32) were more associated with flatfoot (p < .001). Conversely, female gender (OR = 0.44, 95% CI: 0.40-0.48) and White race (OR = 0.52, 95% CI: 0.47-0.57) were less associated with flatfoot (p < .001). Our findings may be valuable for clinical/surgical settings, particularly, for those modifiable findings and targeted populations. However, we suggest that future studies estimating flatfoot should consider prospective/multicenter designs using a common screening methods in random samples populations.

Inverted Meckel's diverticulum diagnosed using capsule endoscopy: A case report.

BACKGROUND: Meckel's diverticulum is a common asymptomatic congenital gastrointestinal anomaly. However, its presentation as an inverted Meckel's diverticulum is a rare complication, of which few cases have been reported in the literature. CASE SUMMARY: Here, we report the case of a 33-year-old man with iron deficiency anemia without manifestation of gastrointestinal bleeding. An upper gastrointestinal endoscopy and total colonoscopy were performed, but no abnormalities were found within the observed area. Finally, a capsule endoscopy was performed and offered us a clue to subsequently confirm the diagnosis of inverted Meckel's diverticulum via computed tomography scan. Laparoscopic intestinal resection surgery was performed. The final pathology report described a Meckel's diverticulum. CONCLUSION: Since inverted Meckel's diverticulum is an uncommon disease and its clinical presentation is not specific, it may go undetected by capsule endoscopy. Successful diagnosis and treatment of this disease requires a high index of clinical suspicion.

An Indoor Navigation Methodology for Mobile Devices by Integrating Augmented Reality and Semantic Web.

Indoor navigation systems incorporating augmented reality allow users to locate places within buildings and acquire more knowledge about their environment. However, although diverse works have been introduced with varied technologies, infrastructure, and functionalities, a standardization of the procedures for elaborating these systems has not been reached. Moreover, while systems usually handle contextual information of places in proprietary formats, a platform-independent model is desirable, which would encourage its access, updating, and management. This paper proposes a methodology for developing indoor navigation systems based on the integration of Augmented Reality and Semantic Web technologies to present navigation instructions and contextual information about the environment. It comprises four modules to define a spatial model, data management (supported by an ontology), positioning and navigation, and content visualization. A mobile application system was developed for testing the proposal in academic environments, modeling the structure, routes, and places of two buildings from independent institutions. The experiments cover distinct navigation tasks by participants in both scenarios, recording data such as navigation time, position tracking, system functionality, feedback (answering a survey), and a navigation comparison when the system is not used. The results demonstrate the system's feasibility, where the participants show a positive interest in its functionalities.

A WoT-Based Method for Creating Digital Sentinel Twins of IoT Devices.

The data produced by sensors of IoT devices are becoming keystones for organizations to conduct critical decision-making processes. However, delivering information to these processes in real-time represents two challenges for the organizations: the first one is achieving a constant dataflow from IoT to the cloud and the second one is enabling decision-making processes to retrieve data from dataflows in real-time. This paper presents a cloud-based Web of Things method for creating digital twins of IoT devices (named sentinels).The novelty of the proposed approach is that sentinels create an abstract window for decision-making processes to: (a) find data (e.g., properties, events, and data from sensors of IoT devices) or (b) invoke functions (e.g., actions and tasks) from physical devices (PD), as well as from virtual devices (VD). In this approach, the applications and services of decision-making processes deal with sentinels instead of managing complex details associated with the PDs, VDs, and cloud computing infrastructures. A prototype based on the proposed method was implemented to conduct a case study based on a blockchain system for verifying contract violation in sensors used in product transportation logistics. The evaluation showed the effectiveness of sentinels enabling organizations to attain data from IoT sensors and the dataflows used by decision-making processes to convert these data into useful information.

Single-cell dissection of cellular components and interactions shaping the tumor immune phenotypes in ovarian cancer.

Distinct T cell infiltration patterns, i.e., immune infiltrated, excluded, and desert, result in different responses to cancer immunotherapies. However, the key determinants and biology underpinning these tumor immune phenotypes remain elusive. Here, we provide a high-resolution dissection of the entire tumor ecosystem through single-cell RNA-sequencing analysis of 15 ovarian tumors. Immune-desert tumors are characterized by unique tumor cell-intrinsic features, including metabolic pathways and low antigen presentation, and an enrichment of monocytes and immature macrophages. Immune-infiltrated and -excluded tumors differ markedly in their T cell composition and fibroblast subsets. Furthermore, our study reveals chemokine receptor-ligand interactions within and across compartments as potential mechanisms mediating immune cell infiltration, exemplified by the tumor cell-T cell cross talk via CXCL16-CXCR6 and stromal-immune cell cross talk via CXCL12/14-CXCR4. Our data highlight potential molecular mechanisms that shape the tumor immune phenotypes and may inform therapeutic strategies to improve clinical benefit from cancer immunotherapies.

Language ability and adult homelessness.

BACKGROUND: People experiencing homelessness are at increased risk of neurological disorder due to multiple factors such as substance abuse, infection, and higher rates of serious mental illness and traumatic brain injury. This could affect cognitive and language skills. Indeed, past research has suggested that certain language-related skills tend to be lower in people experiencing homelessness. However, that research has compared homeless samples with age-matched normative samples and not with samples of people from similar socio-economic backgrounds. Therefore, it is unclear whether homelessness is even a relevant factor, or if adults who are homeless tend to have appropriate linguistic skills relative to their social and educational background. AIMS: To compare the language skills of a group of adults with histories of homelessness with an education-matched control group. It was hypothesized that participants with histories of homelessness would have worse language performance than their matched controls. METHODS & PROCEDURES: A quasi-experimental design was employed involving 17 adults with histories of homelessness, mainly rough sleeping, in the city of Quito in Ecuador, and a sample of 16 adults who had never been homeless. All were assessed with measures of head injury, substance dependence, affective disorder and language skills. A paired-sample analysis was performed on homeless and control participants matched for educational background, used as an index of socio-economic background. OUTCOMES & RESULTS: The mean years of formal education was low in both the homeless sample (mean = 5.82 years) and the control sample (mean = 6.75 years). There were no differences between the groups for any demographic or clinical factors, nor for a measure of expected or 'premorbid' ability based on single-word reading, nor for current non-verbal cognitive functioning. In contrast, the homeless group scored significantly worse than the control group on measures of auditory comprehension and oral expression. CONCLUSIONS & IMPLICATIONS: Adults with histories of homelessness may have worse language skills than would be expected based on their educational backgrounds and non-verbal cognitive abilities. It is possible that some of this lower language ability is pathological, in the form of either a developmental language disorder or an acquired impairment. As such, some adults who are homeless may benefit from therapy directed at clinical language disorders.

Physical Activity, Sports Practice, and Cognitive Functioning: The Current Research Status.

The evidence for the benefits of physical activity on cognitive functioning has increased in recent years. Although the relationship between these variables has been analyzed for decades, the development of evaluation techniques has resolved several issues and advanced this area of knowledge. Moreover, several authors have pointed out the association between the cognitive functioning of athletes and their performance in competition. These recent studies suggest that some specific cognitive abilities of athletes could help them become more effective and improve their chances of success. The objective of this paper was to identify the most relevant advances in these areas of study and to highlight more promising lines of research for the next few years. We have discussed findings from the application of different physical activity programs as well as the most significant cognitive performance variables for sports practice. The limitations of the findings were also discussed.

Pars plana vitrectomy combined with scleral buckle versus pars plana vitrectomy for giant retinal tear.

BACKGROUND: A giant retinal tear (GRT) is a full-thickness neurosensory retinal break extending for 90° or more in the presence of a posterior vitreous detachment. OBJECTIVES: To evaluate the effectiveness and safety of pars plana vitrectomy combined with scleral buckle versus pars plana vitrectomy alone for eyes with giant retinal tear. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 8), which contains the Cochrane Eyes and Vision Trials Register; Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Literature on Health Sciences (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in our electronic search. We last searched the electronic databases on 16 August 2018. SELECTION CRITERIA: We included only randomized controlled trials (RCTs) comparing pars plana vitrectomy combined with scleral buckle versus pars plana vitrectomy alone for giant retinal tear regardless of age, gender, lens status (e.g. phakic or pseudophakic eyes) of the affected eye(s), or etiology of GRT among participants enrolled in these trials. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed titles and abstracts, then full-text articles, using Covidence. Any differences in classification between the two review authors were resolved through discussion. Two review authors independently abstracted data and assessed risk of bias of included trials. MAIN RESULTS: We found two RCTs in abstract format (105 participants randomized). Neither RCT was published in full. Based on the data presented in the abstracts, scleral buckling might be beneficial (relative risk of re-attachement ranged from 3.0 to 4.4), but the findings are inconclusive due to a lack of peer reviewed publication and insufficient information for assessing risk of bias. AUTHORS' CONCLUSIONS: We found no conclusive evidence from RCTs on which to base clinical recommendations for scleral buckle combined with pars plana vitrectomy for giant retinal tear. RCTs are clearly needed to address this evidence gap. Such trials should be randomized, and patients should be classified by giant retinal tear characteristics (extension (90º, 90º to 180º, > 180º), location (oral, anterior, posterior to equator)), proliferative vitreoretinopathy stage, and endotamponade. Analysis should include both short-term (three months and six months) and long-term (one year to two years) outcomes for primary retinal reattachment, mean change in best corrected visual acuity, study eyes that required second surgery for retinal reattachment, and adverse events such as elevation of intraocular pressure above 21 mmHg, choroidal detachment, cystoid macular edema, macular pucker, proliferative vitreoretinopathy, and progression of cataract in initially phakic eyes.

Clinical outcomes of temporary mechanical circulatory support as a direct bridge to heart transplantation: a nationwide Spanish registry.

BACKGROUND: In Spain, listing for high-urgent heart transplantation is allowed for critically ill candidates not weanable from temporary mechanical circulatory support (T-MCS). We sought to analyse the clinical outcomes of this strategy. METHODS AND RESULTS: We conducted a case-by-case, retrospective review of clinical records of 291 adult patients listed for high-urgent heart transplantation under temporary devices from 2010 to 2015 in 16 Spanish institutions. Survival after listing and adverse clinical events were studied. At the time of listing, 169 (58%) patients were supported on veno-arterial extracorporeal membrane oxygenation (VA-ECMO), 70 (24%) on temporary left ventricular assist devices (T-LVAD) and 52 (18%) on temporary biventricular assist devices (T-BiVAD). Seven patients transitioned from VA-ECMO to temporary ventricular assist devices while on the waiting list. Mean time on T-MCS was 13.1 ± 12.6 days. Mean time from listing to transplantation was 7.6 ± 8.5 days. Overall, 230 (79%) patients were transplanted and 54 (18.6%) died during MCS. In-hospital postoperative mortality after transplantation was 33.3%, 11.9% and 26.2% for patients bridged on VA-ECMO, T-LVAD and T-BiVAD, respectively (P = 0.008). Overall survival from listing to hospital discharge was 54.4%, 78.6% and 55.8%, respectively (P = 0.002). T-LVAD support was independently associated with a lower risk of death over the first year after listing (hazard ratio 0.52, 95% confidence interval 0.30-0.92). Patients treated with VA-ECMO showed the highest incidence rate of adverse clinical events associated with T-MCS. CONCLUSION: Temporary devices may be used to bridge critically ill candidates directly to heart transplantation in a setting of short waiting list times, as is the case of Spain. In our series, bridging with T-LVAD was associated with more favourable outcomes than bridging with T-BiVAD or VA-ECMO.

Preoperative platelet-lymphocyte ratio is an independent factor of poor prognosis after curative surgery for colon cancer.

Interaction between tumour and host triggers a systemic inflammatory response. This situation has been associated to cancer progression. Several peripheral blood inflammatory scores have been recently developed, as PLR. Data about the relationship between these scores and cancer prognosis are contradictory. Therefore, the aim of our work is to evaluate the capability of PLR to predict long-term outcomes (OS and RFS) in patients who underwent curative surgery for colon cancer. A retrospective study was designed with patients who underwent curative surgery for colon cancer between September 2008 and January 2012 at Rio Hortega University Hospital, Valladolid (Spain). We analysed the influence of PLR and other clinical variables on OS and RFS. Finally, 201 patients were analysed. Optimal cut-off value for PLR, established with ROC curves, was 153. 1-, 3- and 5-year OS were: 99.0, 90.4 and 82.3% for low PLR, and 93.8, 74.9 and 61.9% for high PLR, p < 0.001. 1-, 3- and 5-year RFS were: 92.4, 84.7 and 77.6% for low PLR, and 83.3, 64.5 and 52.6% for high PLR, p < 0.001. In MVA, high PLR was an independent negative prognostic factor for OS (HR = 2.11; 95% CI 1.22-3.66; p = 0.008) and RFS (HR = 1.99; 95% CI 1.19-3.34; p = 0.009). PLR represents an independent negative prognostic factor for OS and RFS in our sample of patients who underwent curative surgery for colon cancer. However, further studies with a larger sample size from different populations are necessary to confirm this conclusion.

Characteristics of Emergency Medicine Residency Programs in Colombia.

INTRODUCTION: Emergency medicine (EM) is in different stages of development around the world. Colombia has made significant strides in EM development in the last two decades and recognized it as a medical specialty in 2005. The country now has seven EM residency programs: three in the capital city of Bogotá, two in Medellin, one in Manizales, and one in Cali. The seven residency programs are in different stages of maturity, with the oldest founded 20 years ago and two founded in the last two years. The objective of this study was to characterize these seven residency programs. METHODS: We conducted semi-structured interviews with faculty and residents from all the existing programs in 2013-2016. Topics included program characteristics and curricula. RESULTS: Colombian EM residencies are three-year programs, with the exception of one four-year program. Programs accept 3-10 applicants yearly. Only one program has free tuition and the rest charge tuition. The number of EM faculty ranges from 2-15. EM rotation requirements range from 11-33% of total clinical time. One program does not have a pediatric rotation. The other programs require 1-2 months of pediatrics or pediatric EM. Critical care requirements range from 4-7 months. Other common rotations include anesthesia, general surgery, internal medicine, obstetrics, gynecology, orthopedics, ophthalmology, radiology, toxicology, psychiatry, neurology, cardiology, pulmonology, and trauma. All programs offer 4-6 hours of protected didactic time each week. Some programs require Advanced Cardiac Life Support, Pediatric Advanced Life Support and Advanced Trauma Life Support, with some programs providing these trainings in-house or subsidizing the cost. Most programs require one research project for graduation. Resident evaluations consist of written tests and oral exams several times per year. Point-of-care ultrasound training is provided in four of the seven programs. CONCLUSION: As emergency medicine continues to develop in Colombia, more residency programs are expected to emerge. Faculty development and sustainability of academic pursuits will be critically important. In the long term, the specialty will need to move toward certifying board exams and professional development through a national EM organization to promote standardization across programs.

Revisional Surgery Following Laparoscopic Gastric Plication.

BACKGROUND: The laparoscopic gastric plication (LGP) is a relative new bariatric procedure that has gained popularity over the last few years, but no real consensus exists and the evidence is unclear, especially in its real efficacy, safety, and durability. METHODS: Retrospective study analyzing the records patients submitted to LGP between 2009 and 2010. The primary objective was to describe the characteristics and outcomes of patients submitted to revisional surgery. Baseline data and evolution were obtained and analyzed. Surgical analysis included revision cause, perioperative outcome, type of surgery, complications, and weight loss after 18 months. A comparison between gastric bypass and sleeve gastrectomy was performed. RESULTS: One hundred LGP were performed. After a mean time of 13.5 months, 42 patients presented an overall excess weight loss (EWL) <50 % and 38 had severe symptoms. Thirty patients accepted revisional surgery with BMI before conversion of 38.6 ± 4.2 kg/m2. There were 17 laparoscopic sleeve gastrectomy (LSG) and 13 laparoscopic gastric bypass (LGBP) with comparable preoperative characteristics. The LSG group had lower pneumoperitoneum time and less hospital stay. At 18 months, the LGBP group had lower BMI (24.1 ± 1.1 vs. 25.8 ± 1.3 kg/m2 for the LSG; p = 0.006) and higher %EWL (75.7 ± 16.1 vs. 61.4 ± 14.5 % for the LSG; p = 0.008). CONCLUSION: In our series, LGP presented a high failure rate and an increased number of symptomatic patients. Revisional surgery proved to be safe and effective. Revision to LSG was faster and had less hospital stay. Revision to LGBP showed better %EWL at 18 months.

Identification of proliferative progenitors associated with prominent postnatal growth of the pons.

The pons controls crucial sensorimotor and autonomic functions. In humans, it grows sixfold postnatally and is a site of paediatric gliomas; however, the mechanisms of pontine growth remain poorly understood. We show that the murine pons quadruples in volume postnatally; growth is fastest during postnatal days 0-4 (P0-P4), preceding most myelination. We identify three postnatal proliferative compartments: ventricular, midline and parenchymal. We find no evidence of postnatal neurogenesis in the pons, but each progenitor compartment produces new astroglia and oligodendroglia; the latter expand 10- to 18-fold postnatally, and are derived mostly from the parenchyma. Nearly all parenchymal progenitors at P4 are Sox2(+)Olig2(+), but by P8 a Sox2(-) subpopulation emerges, suggesting a lineage progression from Sox2(+) 'early' to Sox2(-) 'late' oligodendrocyte progenitor. Fate mapping reveals that >90% of adult oligodendrocytes derive from P2-P3 Sox2(+) progenitors. These results demonstrate the importance of postnatal Sox2(+)Olig2(+) progenitors in pontine growth and oligodendrogenesis.

Duodenal involvement by seminomatous tumors.

Testicular germ cell tumors, though rare (1%), represent the most common neoplasm among young men. Gastrointestinal involvement from these malignancies usually presents as bowel obstruction and digestive bleeding, but their frequency is low (5%). The patterns of this involvement are: infiltration from affected retroperitoneal lymph nodes or, less frequently, by peritoneal seeding and direct hematogenous spread. Particularly, infiltration of duodenum is also rare, though its real frequency is not well defined. Moreover, the affinity for GI tract differs among the histological types of GCT, being seminomatous tumors an exceedingly unfrequent cause of duodenal infiltration. We herein present a recent case in our institution of severe anemia due to gastrointestinal bleeding in the context of giant retroperitoneal bulky metastatic mass infiltrating duodenum as first manifestation of a testicular pure seminoma.

A Dorsal SHH-Dependent Domain in the V-SVZ Produces Large Numbers of Oligodendroglial Lineage Cells in the Postnatal Brain.

Neural stem cells in different locations of the postnatal mouse ventricular-subventricular zone (V-SVZ) generate different subtypes of olfactory bulb (OB) interneurons. High Sonic hedgehog (SHH) signaling in the ventral V-SVZ regulates the production of specific subtypes of neurons destined for the OB. Here we found a transient territory of high SHH signaling in the dorsal V-SVZ beneath the corpus callosum (CC). Using intersectional lineage tracing in neonates to label dorsal radial glial cells (RGCs) expressing the SHH target gene Gli1, we demonstrate that this region produces many CC cells in the oligodendroglial lineage and specific subtypes of neurons in the OB. The number of oligodendroglial cells generated correlated with the levels of SHH signaling. This work identifies a dorsal domain of SHH signaling, which is an important source of oligodendroglial cells for the postnatal mammalian forebrain.

Differentially expressed microRNAs in postpartum breast cancer in Hispanic women.

The risk of breast cancer transiently increases immediately following pregnancy; peaking between 3-7 years. The biology that underlies this risk window and the effect on the natural history of the disease is unknown. MicroRNAs (miRNAs) are small non-coding RNAs that have been shown to be dysregulated in breast cancer. We conducted miRNA profiling of 56 tumors from a case series of multiparous Hispanic women and assessed the pattern of expression by time since last full-term pregnancy. A data-driven splitting analysis on the pattern of 355 miRNAs separated the case series into two groups: a) an early group representing women diagnosed with breast cancer ≤ 5.2 years postpartum (n = 12), and b) a late group representing women diagnosed with breast cancer ≥ 5.3 years postpartum (n = 44). We identified 15 miRNAs with significant differential expression between the early and late postpartum groups; 60% of these miRNAs are encoded on the X chromosome. Ten miRNAs had a two-fold or higher difference in expression with miR-138, miR-660, miR-31, miR-135b, miR-17, miR-454, and miR-934 overexpressed in the early versus the late group; while miR-892a, miR-199a-5p, and miR-542-5p were underexpressed in the early versus the late postpartum group. The DNA methylation of three out of five tested miRNAs (miR-31, miR-135b, and miR-138) was lower in the early versus late postpartum group, and negatively correlated with miRNA expression. Here we show that miRNAs are differentially expressed and differentially methylated between tumors of the early versus late postpartum, suggesting that potential differences in epigenetic dysfunction may be operative in postpartum breast cancers.