Transient PU.1 low fetal progenitors generate lymphoid progeny that contribute to adult immunity.

Hematopoietic stem cells and multipotential progenitors emerge in multiple, overlapping waves of fetal development. Some of these populations seed the bone marrow and sustain adult B- and T-cell development long-term after birth. However, others are present transiently, but whether they are vestigial or generate B and T cells that contribute to the adult immune system is not well understood. We now report that transient fetal progenitors distinguished by expression of low levels of the PU.1 transcription factor generated activated and memory T and B cells that colonized and were maintained in secondary lymphoid tissues. These included the small and large intestines, where they may contribute to the maintenance of gut homeostasis through at least middle age. At least some of the activated/memory cells may have been the progeny of B-1 and marginal zone B cells, as transient PU.1low fetal progenitors efficiently generated those populations. Taken together, our data demonstrate the potential of B- and T-cell progeny of transient PU.1low fetal progenitors to make an early and long-term contribution to the adult immune system.

Effect of frailty on postoperative complications, mortality, and survival in older patients with non-metastatic colon cancer: A systematic review and meta-analysis.

INTRODUCTION: New evidence has emerged on the impact of frailty on prognosis in colon cancer, but the findings are not always consistent and conclusive. The aim of this systematic review was to assess the effect of frailty on postoperative complications and mortality in patients with non-metastatic colon cancer (CC) aged 65 years and older. MATERIALS AND METHODS: We systematically searched for original studies published in the PubMed and Web of Science databases up to June 2021. Two independent reviewers selected the studies and extracted predefined data. A meta-analysis was performed using the random effects model to assess the effect of frailty on 30-day, 3- to 6-month and 1-year mortality, survival, and postoperative complications. RESULTS: The search yielded 313 articles, of which 14 were included in this systematic review. The meta-analysis showed an effect for frailty on 30-day, 3- to 6-month, and 1-year mortality with respective pooled odds ratios (ORs) of 3.67 (95% confidence interval [CI] 1.53-8.79, p = 0.004), 8.73 (95% CI 4.03-18.94, p < 0.0001), and 3.99 (95% CI 2.12-7.52, p < 0.0001). Frailty also had an effect on survival, with a pooled hazard ratio of 2.99 (95% CI 1.70-5.25. p < 0.0001), and on overall and severe postoperative complications with pooled ORs of 2.34 (95% CI 1.75-3.15; p < 0.0001) and 2.43 (95% CI 1.72-3.43; p < 0.0001), respectively. DISCUSSION: Frailty in older patients with CC is a risk factor for postoperative complications and mortality in the short term (30 days), medium term (3-6 months), and long term (1 year).

DNA methylation-based profiling of horse archaeological remains for age-at-death and castration.

Age profiling of archaeological bone assemblages can inform on past animal management practices, but is limited by the fragmentary nature of the fossil record and the lack of universal skeletal markers for age. DNA methylation clocks offer new, albeit challenging, alternatives for estimating the age-at-death of ancient individuals. Here, we take advantage of the availability of a DNA methylation clock based on 31,836 CpG sites and dental age markers in horses to assess age predictions in 84 ancient remains. We evaluate our approach using whole-genome sequencing data and develop a capture assay providing reliable estimates for only a fraction of the cost. We also leverage DNA methylation patterns to assess castration practice in the past. Our work opens for a deeper characterization of past husbandry and ritual practices and holds the potential to reveal age mortality profiles in ancient societies, once extended to human remains.

Recovery of chloroplast genomes from medieval millet grains excavated from the Areni-1 cave in southern Armenia.

Panicum miliaceum L. was domesticated in northern China at least 7000 years ago and was subsequentially adopted in many areas throughout Eurasia. One such locale is Areni-1 an archaeological cave site in Southern Armenia, where vast quantities archaeobotanical material were well preserved via desiccation. The rich botanical material found at Areni-1 includes P. miliaceum grains that were identified morphologically and14C dated to the medieval period (873 ± 36 CE and 1118 ± 35 CE). To investigate the demographic and evolutionary history of the Areni-1 millet, we used ancient DNA extraction, hybridization capture enrichment, and high throughput sequencing to assemble three chloroplast genomes from the medieval grains and then compared these sequences to 50 modern P. miliaceum chloroplast genomes. Overall, the chloroplast genomes contained a low amount of diversity with domesticated accessions separated by a maximum of 5 SNPs and little inference on demography could be made. However, in phylogenies the chloroplast genomes separated into two clades, similar to what has been reported for nuclear DNA from P. miliaceum. The chloroplast genomes of two wild (undomesticated) accessions of P. miliaceum contained a relatively large number of variants, 11 SNPs, not found in the domesticated accessions. These results demonstrate that P. miliaceum grains from archaeological sites can preserve DNA for at least 1000 years and serve as a genetic resource to study the domestication of this cereal crop.

Discovering the Secrets of Ancient Plants: Recovery of DNA from Museum and Archaeological Plant Specimens.

Plant DNA preserved in ancient specimens has recently gained importance as a tool in comparative genomics, allowing the investigation of evolutionary processes in plant genomes through time. However, recovering the genomic information contained in such specimens is challenging owing to the presence of secondary substances that limit DNA retrieval. In this chapter, we provide a DNA extraction protocol optimized for the recovery of DNA from degraded plant materials. The protocol is based on a commercially available DNA extraction kit that does not require handling of hazardous reagents.

Analysis of pulmonary features and treatment approaches in the COPA syndrome.

The COPA syndrome is a monogenic, autoimmune lung and joint disorder first identified in 2015. This study sought to define the main pulmonary features of the COPA syndrome in an international cohort of patients, analyse patient responses to treatment and highlight when genetic testing should be considered. We established a cohort of subjects (N=14) with COPA syndrome seen at multiple centres including the University of California, San Francisco, CA, USA. All subjects had one of the previously established mutations in the COPA gene, and had clinically apparent lung disease and arthritis. We analysed cohort characteristics using descriptive statistics. All subjects manifested symptoms before the age of 12 years, had a family history of disease, and developed diffuse parenchymal lung disease and arthritis. 50% had diffuse alveolar haemorrhage. The most common pulmonary findings included cysts on chest computed tomography and evidence of follicular bronchiolitis on lung biopsy. All subjects were positive for anti-neutrophil cytoplasmic antibody, anti-nuclear antibody or both and 71% of subjects had rheumatoid factor positivity. All subjects received immunosuppressive therapy. COPA syndrome is an autoimmune disorder defined by diffuse parenchymal lung disease and arthritis. We analysed an international cohort of subjects with genetically confirmed COPA syndrome and found that common pulmonary features included cysts, follicular bronchiolitis and diffuse alveolar haemorrhage. Common extrapulmonary features included early age of onset, family history of disease, autoantibody positivity and arthritis. Longitudinal data demonstrated improvement on chest radiology but an overall decline in pulmonary function despite chronic treatment.

Viral hepatitis status does not affect survival in patients with hepatocellular carcinoma.

BACKGROUND: There have been few studies on the impact of viral etiology on the prognosis in patients with hepatocellular carcinoma (HCC). The aim of this study was to evaluate the clinical characteristics and survival of patients with viral hepatitis-associated HCC (V-HCC), compared to patients with HCC of non-hepatitis B, non-hepatitis C (NBNC-HCC) etiology. METHODS: We performed a retrospective analysis of all patients with HCC treated at our comprehensive cancer center from 2000 through 2014. Patients were divided into two groups according to their viral hepatitis status. Presentation patterns, treatments, and survival data were analyzed. RESULTS: We evaluated 366 patients: 233 patients (63.7%) had V-HCC while 133 (36.3%) patients had NBNC-HCC. V-HCC patients were younger (P<0.0001) and more likely to be male (P=0.001). Decompensated cirrhosis was more prevalent in V-HCC patients (P=0.01). There was no difference in the resectability rate or disease stage. In patients with resectable disease, those with V-HCC were less likely to undergo hepatectomy (23.7% vs. 38%; P=0.04) for more advanced liver disease. The estimated median survival for V-HCC was 13 months compared to 16 months in NBNC-HCC patients (P=0.57). On multivariate analysis, disease stage (P<0.0001) and Child-Pugh class (P<0.0001) were independent factors affecting survival, but viral status was not (P=0.75). CONCLUSION: Despite presenting with more advanced cirrhosis and being less likely to undergo surgery, V-HCC patients had similar survival to patients with NBNC-HCC.

Gas pockets in a wastewater rising main: a case study.

This paper presents a case study of an existing wastewater rising main (WWRM) in which an extreme transient event produced by simultaneous power failure of the pumps caused the rupture of a 1.2 m (48 in) prestressed concrete cylinder pipe (PCCP), causing an important leakage of sewage. The event and the methodology followed in order to validate the diagnostics of the failure are described. The detail study included in situ observation of the system, experimental investigation in a setup, hydraulic analysis, as well as details of the structural strength of the WWRM. After the extensive investigation and several simulations of fluid transients for different scenarios and flow conditions, it was found that stationary small gas pockets accumulated at high points of the WWRM were identified as the principal contributory factor of the failure. This case study serves as clear warning of the consequences of operating a WWRM with gas pockets at its high points.

[Planning, management and results of the implantation of laparoscopic surgery of the colon and rectum in a general hospital]. / Planificación, gestión y resultados de la implantación de la cirugía laparoscópica de colon y recto en un hospital general.

INTRODUCTION: The introduction of laparoscopic surgery in a hospital is a slow process requiring the involvement of a multidisciplinary team. PATIENTS AND METHOD: We performed a prospective, descriptive study of all patients who underwent laparoscopic surgery of the colon and rectum in the Mataró Hospital between 2003 and 2006. We also describe the model used to introduce laparoscopic surgery of the colon and rectum in our center. RESULTS: Between 2003 and 2006, 166 patients with colorectal disease underwent laparoscopic surgery. Patients included for rectal disease represented 36% of the total. The conversion rate was 7% of the mean in all the periods studied, with a complications rate of 13.25%. CONCLUSIONS: The controlled development of laparoscopic surgery allows satisfactory results to be obtained in colorectal disease.

Effects of corticosteroid-induced apoptosis on airway epithelial wound closure in vitro.

Damage to the airway epithelium is common in asthma. Corticosteroids induce apoptosis in and suppress proliferation of airway epithelial cells in culture. Whether apoptosis contributes to impaired epithelial cell repair after injury is not known. We examined whether corticosteroids would impair epithelial cell migration in an in vitro model of wound closure. Wounds (approximately 0.5-1.3 mm2) were created in cultured 1HAEo- human airway epithelial cell monolayers, after which cells were treated with up to 10 microM dexamethasone or budesonide for 24 h. Cultured cells were pretreated for 24 or 48 h with dexamethasone to observe the effect of long-term exposure on wound closure. After 12 h, the remaining wound area in monolayers pretreated for 48 h with 10 microM dexamethasone was 43+/-18% vs. 10+/-8% for untreated control monolayers. The addition of either corticosteroid immediately after injury did not slow closure significantly. After 12 h the remaining wound area in monolayers treated with 10 microM budesonide was 39+/-4% vs. 43+/-3% for untreated control monolayers. The proportion of apoptotic epithelial cells as measured by terminal deoxynucleotidyltransferase-mediated dUTP biotin nick end labeling both at and away from the wound edge was higher in monolayers treated with budesonide compared with controls. However, wound closure in the apoptosis-resistant 1HAEo-.Bcl-2+ cell line was not different after dexamethasone treatment. We demonstrate that corticosteroid treatment before mechanical wounding impairs airway epithelial cell migration. The addition of corticosteroids after injury does not slow migration, despite their ability to induce apoptosis in these cells.

Recognition of host immune activation by Pseudomonas aeruginosa.

It is generally reasoned that lethal infections caused by opportunistic pathogens develop permissively by invading a host that is both physiologically stressed and immunologically compromised. However, an alternative hypothesis might be that opportunistic pathogens actively sense alterations in host immune function and respond by enhancing their virulence phenotype. We demonstrate that interferon-gamma binds to an outer membrane protein in Pseudomonas aeruginosa, OprF, resulting in the expression of a quorum-sensing dependent virulence determinant, the PA-I lectin. These observations provide details of the mechanisms by which prokaryotic organisms are directly signaled by immune activation in their eukaryotic host.

Posttraumatic intrapancreatic aortosplenic fistula causing portal hypertension.

Arterioportal fistulas are uncommon. The case of a patient with massive uncontrollable esophageal variceal bleeding is presented. Reversible portal hypertension was caused by a posttraumatic giant intrapancreatic aortosplenic fistula. Percutaneous closure was unsuccessful, and pancreatectomy was performed to control the bleeding. The case is discussed and the literature on this exceptional cause of portal hypertension is reviewed.