bluuebunny/crossref_metadata_2025 huggingface dataset:
Current indications for balloon sinuplasty
Authors: Cingi Cemal , Bayar Muluk Nuray , Lee Jivianne T.
Published: November 2018

Purpose of review

The purpose of the review is to evaluate the current indications and contraindications for balloon sinuplasty and review the clinical trials performed in this area.

Recent findings

The indications for balloon sinus dilatation are somewhat similar to those for endoscopic sinus surgery. Balloon sinus ostial dilation (BSD) has been found to be most effective in the treatment of recurrent acute sinusitis (RARS) and chronic rhinosinusitis without nasal polyposis (CRSsNP) that has been refractory to medical therapy. Multiple randomized clinical trials have demonstrated the efficacy of BSD in improving quality-of-life outcomes in patients with limited CRSsNP in both the clinic and operating room settings. However, because BSD merely dilates blocked sinusal ostia without removing tissue, it is typically restricted to addressing disorder involving the frontal, sphenoid, and maxillary sinuses. Individuals who have significant disease of the ethmoid sinus may have BSD adjunctively with endoscopic sinus surgery. BSD is unsuitable as a primary treatment modality in pansinus polyposis, widespread fungal sinusitis, connective tissue disorders at an advanced stage, or potential malignancy. A recent expert clinical consensus statement also concluded that BSD is not appropriate for treatment of patients with headache that do not meet the diagnostic criteria for CRS or RARS or patients who do not have both positive findings of sinus disease on computed tomography and sinonasal symptoms.

Balloon sinuplasty is an option in the treatment of sinusitis that has failed appropriate medical therapy. Evidence is best for limited disease in patients with CRSsNP affecting the frontal, sphenoid, and maxillary sinuses. Because BSD can be performed in the office setting, it can be a viable therapeutic alternative in patients with comorbidities who are unable to tolerate general anesthesia.
Differences of Immune Reconstitution of Dendritic Cells in Pediatric GvHD Patients After Allogenic Stem Cell Transplantation
Authors: Wiegering Verena , Peter Lisa , Frietsch Marieke , Schlegel Paul G. , Eyrich Matthias
Published: November 2018

Background:

Hematopoietic stem cell transplantation (HSCT) is a life-saving procedure for children with a variety of (non) malignant conditions. GvHD is a severe complication with high morbidity and mortality. The pathogenesis remains unclear. We studied dendritic cell (DC) reconstitution to detect potential differences, which may improve our knowledge in the development of chronic GvHD (cGvHD).

Procedure:

We examined immune reconstitution (T, B, and NK cells and dendritic cells) at defined time points in a pediatric cohort who underwent 61 allogeneic HSCTs.

Results:

Regarding DC reconstitution we found a fast reconstitution of the DC compartment negatively correlated with age. After HSCT, both myeloid DC (mDC) and plasmacytoid DC (pDC) counts recover to pre-HSCT levels within 2 months. Higher CCR7 positive cell counts were found in patients receiving TBI during engraftment and during the whole posttransplant period we found a correlation with an improved outcome. In cGVHD patients decreased total DC counts and increased pDCs were found after day+100. No relevant correlation was achieved regarding to HLA-matching, stem cell manipulation of the graft as well as HSCT-indication compared with different DC counts.

Discussion:

Pathogenesis of cGvHD remains complex. Our data suggest an influence of dendritic cells, which may contribute to the clinical picture and should be further investigated in future studies.
Cyclic Neutropenia From a Novel Mutation Ala57Asp of ELANE: Phenotypic Variability in Neutropenia From Mutated Ala57 Residue
Authors: Park Chang-Hun , Park Silvia , Kim Yae-Jean , Kim Sun-Hee , Kim Hee-Jin
Published: November 2018

ELANE-related neutropenia includes severe congenital neutropenia and cyclic neutropenia. Both are clinically characterized by recurrent fever, skin and oropharyngeal inflammation. We report a novel mutation inELANEin a 20-year-old man with a history of self-limiting febrile episodes and neutropenia with a cyclic pattern since 7 years of age. Direct sequencing analysis ofELANErevealed he was heterozygous for a novel missense mutation (p.Ala57Asp). The Ala57 residue is a mutation hotspot, and all previously reported missense mutations (Ala57Ser/Thr/Val) were observed in severe congenital neutropenia cases. Thus, the present case demonstrates a phenotypic variability inELANE-related neutropenia from mutated Ala57.
Treatment of Molecular Relapse by Cessation of Immunosuppression After Hematopoietic Stem Cell Transplantation in Pediatric FLT3-ITD AML Monitored by WT1 Expression in Peripheral Blood
Authors: Løvvik Juul-Dam Kristian , Ifversen Marianne , Guldborg Nyvold Charlotte , Hansen Maria , Hasle Henrik
Published: November 2018

Relapse after hematopoietic stem cell transplantation in pediatric acute myeloid leukemia is a fatal event in the majority of cases. Immunotherapy may prevent an impending relapse if instituted at first molecular evidence of disease recurrence. Wilms tumor gene 1 (WT1) is overexpressed in the majority of children and may constitute a useful molecular marker of measurable residual disease applicable for disease monitoring in peripheral blood where the background amplification from healthy hematopoiesis is less prevalent compared with bone marrow. We report the measurable residual disease kinetics from a child with FLT3-internal tandem duplication acute myeloid leukemia where sequential WT1 monitoring in peripheral blood-guided withdrawal of immunosuppression.
Health-related Quality of Life in Children With Sickle Cell Disease Undergoing Chronic Red Cell Transfusion Therapy
Authors: Maxwell Sarah L. , Schlenz Alyssa M. , Kanter Julie
Published: November 2018

Chronic red cell transfusion (CRCT) therapy is one of few disease-modifying treatments for sickle cell disease (SCD). This study evaluated health-related quality of life (HRQL) in children receiving CRCT relative to 2 comparison groups: children with similar, severe SCD and children with milder disease risk defined by SCD genotype. For this study, 67 children with SCD between the ages of 8 and 18 completed the self-report Pediatric Quality of Life Sickle Cell Disease module (PedsQL SCD) as part of a pilot clinical program during routine hematologic visits. A medical chart review was also performed. Linear regression suggested that children in the CRCT group had significantly higher self-reported HRQL ratings for domains related to pain, F
2,64=4.07 (P=0.022) and pain-related functioning, F
2,64=4.32 (P=0.017), compared with children with similar and milder disease risk. Exploratory analyses implied that children in the CRCT group also had fewer worries about SCD-related complications, F
3,63=9.68 (P<0.001). These patient-perceived benefits of CRCT may have important implications for treatment decisions and for providing ancillary support for children with SCD and their families.
Change in Emotional and Theory of Mind Processing in Borderline Personality Disorder
Authors: Kramer Ueli , Kolly Stéphane , Maillard Pauline , Pascual-Leone Antonio , Samson Andrea C. , Schmitt Ruth , Bernini Adriano , Allenbach Gilles , Charbon Patrick , de Roten Yves , Conus Philippe , Despland Jean-Nicolas , Draganski Bogdan
Published: November 2018

Changes in emotional processing (EP) and in theory of mind (TOM) are central across treatment approaches for patients with borderline personality disorder (BPD). Although the assessment of EP relies on the observation of a patient's self-criticism in a two-chair dialogue, an individual's TOM assessments is made based on responses to humorous stimuli based on false beliefs. For this pilot study, we assessed eight patients with BPD before and after a 3-month-long psychiatric treatment, using functional magnetic resonance imaging and behavioral tasks. We observed arousal increase within the session of the two-chair dialogue (d = 0.36), paralleled by arousal decrease between sessions (d = 0.80). We found treatment-associated trends for neural activity reduction in brain areas central for EP and TOM. Our exploratory findings using an integrative assessment procedure of changes in EP and TOM point toward evidence for treatment effects at the brain systems level related to behavioral modulation.
Effects of Mind-Body Exercise on Cognitive Function in Older Adults With Cognitive Impairment
Authors: Wang Shuo , Yin Huiru , Jia Yong , Zhao Lijing , Wang Lisheng , Chen Li
Published: November 2018

To quantify the effects of mind-body exercise on cognitive function in older adults with cognitive impairment, we systematically searched five databases. Findings were analyzed according to the mean change of global cognition, memory, and executive function. Subgroup analyses were conducted based on the level of cognitive impairment and types of exercise. Thirteen studies were included. Analyses revealed that mind-body exercise was effective in promoting global cognition in individuals with cognitive impairment (standardized mean difference [SMD] = 0.61; 95% confidence interval, 0.21–1.00; p = 0.003), as well as in individuals with mild cognitive impairment (SMD = 0.46; 95% confidence interval, 0.06–0.85; p = 0.02) or dementia; dance was effective in promoting global cognition (SMD = 0.84; 95% confidence interval, 0.23–1.46; p = 0.007) and memory (SMD = 0.27; 95% confidence interval, 0.02–0.52; p = 0.04) in individuals with cognitive impairment, but tai chi was not. Nevertheless, additional well-designed randomized clinical trials are further needed.
Depressions of Dermestes maculatus (Coleoptera: Dermestidae) on Bones Could be Pupation Chambers
Authors: Zanetti Noelia Inés , Ferrero Adriana Alicia , Centeno Néstor Daniel
Published: November 2018

Dermestes maculatus DeGeer beetles feed and can leave marks on bones. This species is of medical, veterinary, and forensic importance. The aim of this work was to determine if the depressions produced on bones by these beetles could be product of pupation. We studied under controlled conditions the behavior of D. maculatus larvae maintained at 24°C ± 3°C, 52.7% average relative humidity, and a 12:12-hour light/dark cycle and fed on pig carcasses. Observations were made, and photographs were taken. The results indicated that depressions produced by D. maculatus were consequence of feeding or pupation. This is the first time that pupation chambers on bones are confirmed.
Comparison of Dako HercepTest and Ventana PATHWAY Anti-HER2 (4B5) Tests and Their Correlation With Fluorescent In Situ Hybridization in Breast Carcinoma
Authors: Lucas Elena , Jabbar Seema B. , Molberg Kyle , Fang Yisheng , Xie Xian-Jin , Blacketer Sara , Sahoo Sunati
Published: November 2018

Objectives:

We compared the performance of two Food and Drug Administration–approved HER2 immunohistochemistry (IHC) tests: HercepTest (Dako) and PATHWAY anti-HER2 (4B5) (Ventana).

Materials and Methods:

In total, 180 invasive breast carcinomas previously tested by both HercepTest and fluorescent in situ hybridization (FISH) were retested with 4B5. Three pathologists scored the HER2 IHC using the 2013 American Society of Clinical Oncology/College of American Pathologists guidelines. The HER2 IHC results were correlated with FISH.

Results:

Among 135 equivocal cases by HercepTest, 100 (74.1%) were negative by 4B5. Among 45 positive HercepTest cases 9 (20%) were equivocal by 4B5. Among 135 equivocal HercepTest results, 100 (74.1%) were nonamplified, 18 (13.3%) equivocal, and 17 (12.6%) amplified by FISH. Among the 45 positive results with HercepTest, 2 (4.5%) were nonamplified and 1 (2.2%) was equivocal by FISH. All 37 positive and 3 negative by 4B5 cases were amplified by FISH. The absolute interobserver agreement was high for both tests (Fleiss kappa=0.838 for HercepTest and 0.771 for 4B5).

Conclusions:

PATHWAY anti-HER2 (4B5) significantly reduced the number of equivocal results that require additional testing. Although HercepTest was positive in a small number of HER2 nonamplified cases, 4B5 failed to detect 3 cases that were interpreted as positive by FISH, all with nonclassic or low levels of amplification.
Intracholecystic Papillary-Tubular Neoplasms (ICPN) of the Gallbladder: A Short Review of Literature
Authors: Saei Hamedani Farid , Garcia-Buitrago Monica
Published: November 2018

Increasing use of radiographic studies of the hepatobiliary system has led to a growing diagnostic rate of many asymptomatic polyps of the gallbladder which would have gone undiagnosed otherwise. Neoplastic polyps of the gallbladder are 5% of the total number of polyps of this organ. However, due to their malignant potential, the correct diagnosis and classification become of crucial importance. Lack of unified terminology and reporting criteria have led to a limited body of scientific evidence regarding their classification and management. Therefore in 2012 the novel and unified terminology, Intracholecystic papillary-tubular neoplasm was proposed for these lesions when they measure >1 cm. Smaller lesions are usually of no adverse outcome. Intracholecystic papillary-tubular neoplasms show 5 histologic subcategories: (1) pyloric gland subtype which is the most commonly encountered neoplastic polyp in the gallbladder and has the lowest rate of harboring high-grade dysplasia and invasive carcinoma and it shows diffuse cytoplasmic positivity with MUC6, a specific pyloric marker; (2) biliary subtype which is diffusely positive for MUC1 and has the highest risk of concurrent adenocarcinoma; (3) gastric foveolar subtype which is MUC5AC positive in all the cases. Most of the cases in this category are associated with some extent of high-grade dysplasia; (4) intestinal subtype which is the easiest one to recognize as it mimics tubular adenomas of the gastrointestinal tract and show MUC2 and CDX2 positivity; and (5) oncocytic subtype which is the least common.
Significance of Expression of Cancer Stem Cell Markers CD133 and Nestin in Pancreatic Intraepithelial Carcinoma-invasive Adenocarcinoma Sequence
Authors: Alshenawy Hanan A.
Published: November 2018

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies and one of the most leading causes of cancer related deaths. It has a very poor prognosis with high recurrence rate. We investigated the expression of CSC markers (CD133 and nestin) in 100 patients [30 pancreatic intraepithelial tumor cases (PanIN) and 70 PDAC cases] and correlate the expression levels of these markers with clinicopathological data with the aid of Ki67 expression. Our findings showed that both cancer stem markers are related to the grade, stage, metastasis of PDAC and to the grade of PanIN cases and revealed that both markers are associated with PanIN-PDAC sequence with inverse relation between them. Both markers may contribute to proliferation, differentiation, invasiveness, and histologic types of PDAC. Sothey may also be useful for developing new therapeutic modalities for PDAC.
Why Are Newborns Brought to the Emergency Department?
Authors: Ferreira Helena , Ferreira Carla , Tavares Cláudia , Aguiar Isolina
Published: November 2018

Objectives

Neonatal period is a peculiar life stage. This study aimed to characterize newborns' visits to the emergency department (ED) of a secondary care hospital.

Methods

Retrospective analysis of infants up to 28 days, who resorted to the ED between January and December of 2014, was performed. The data included newborn and maternal demographic characteristics and characterization of visits in the ED.

Results

From 378 newborns' visits in the ED, 77 were excluded because the visits did not meet the inclusion criteria. From the remaining 301 visits, corresponding to 266 newborns, 56 newborns were referred to hospital care by another doctor, and 34 returned to ED in the neonatal period. The majority of newborns were full term (94%), born by vaginal delivery (55.1%), and had an appropriate birth weight for gestational age (94%). The main reasons for ED visits were gastrointestinal symptoms (33.8%), mucocutaneous lesions (21.4%), and jaundice (16.2%). Half (53%) of the newborns' visits were considered nonurgent. Emergency department visits for reasons justifying medical evaluation were higher in those referred by another doctor (P < 0.001). The rate of hospitalization or guidance for consultation was higher in newborns referred by another doctor (P = 0.017), in those whose color attributed by Manchester Triage System was yellow or orange (P = 0.029) and in newborns older than 7 days (P = 0.035).

Conclusions

The majority of ED visits is owing to insufficient caretaker knowledge or benign symptoms without necessity of immediate medical evaluation. These results emphasize the need for parents' education by health professionals.
Findings of a Statewide Environmental Lead Inspection Program Targeting Homes of Children With Blood Lead Levels as Low as 5 μg/dL
Authors: Cluett Rachel , Fleisch Abby , Decker Kathy , Frohmberg Eric , Smith Andrew E.
Published: November 2018

Context:

There are limited data on the nature of environmental lead hazards identified during residential inspections for child blood lead levels (BLLs) of less than 10 μg/dL. We compare inspection findings for child BLLs of 5 to 9 μg/dL versus 10 μg/dL or more.

Design:

We reviewed inspection reports in Maine from September 2016 to March 2018. We used continuity-adjusted or Fisher's exact test for categorical variables and Wilcoxon rank-sum tests for continuous variables to compare differences in child, family, household, and lead hazard characteristics between BLL categories (5-9 μg/dL vs ≥10 μg/dL). We used Spearman correlation coefficients to assess relationships between home surface lead dust measurements and BLLs.

Results:

Of 351 residential inspections, 272 (77%) were for children with BLLs of 5 to 9 μg/dL. Children with BLLs of 5 to 9 μg/dL as compared with children with BLLs of 10 μg/dL or more were less likely to chew window sills and door frames (8% vs 21%; P = .01), but otherwise were similar with respect to other established risk factors for lead poisoning. Children with BLLs of 5 to 9 μg/dL tended to have fewer paint hazards inside their homes (64% vs 78%; P = .03), and they were more likely to have dust-only hazards (8% vs 3%) or no identified lead paint hazards (23% vs 15%), though these differences were not statistically significant. For children with BLLs of 5 to 9 μg/dL, BLL was weakly correlated with average window sill dust level (Spearman r = 0.16; P = .01) and average floor dust level (r = 0.13; P = .03), but these correlations were not observed for children with BLLs of 10 μg/dL and higher.

Conclusions:

We have found that inspections of homes of children with BLLs of 5 to 9 μg/dL are nearly as likely to identify lead hazards that require abatement as inspections of homes of children with BLLs of 10 μg/dL.
Evaluation of the Implementation of CDC's Health Alert Related to the FDA LeadCare Recall From the State Health Department Perspective
Authors: Trinh Eva , Mason Jacquelyn
Published: November 2018

On May 17, 2017, the Food and Drug Administration (FDA) issued a safety recall for the Magellan Diagnostics' LeadCare Testing Systems due to the potential for inaccurately low blood lead test results when used with venous blood samples. The Centers for Disease Control and Prevention (CDC) announced a health alert with retesting recommendations because those with a blood lead level of concern may have been missed and not connected to the appropriate follow-up services. A qualitative evaluation of 9 state childhood lead poisoning prevention programs' experiences is presented in this report. Interviewees reported using a variety of media and notification methods to inform key stakeholders about the recall and recommendations. Challenges experienced by programs in responding to retesting recommendations include incomplete and out-of-date lists of LeadCare users; missing or inaccurate information in their surveillance database; not having large laboratories and hospitals consider contacting persons for retesting to be within their purview; and having limited staff members to conduct emergency response activities. Two of the 9 states report subsequent challenges with their retesting rates. The retesting recommendations were generally viewed positively. The interviewees' comments provide insight into steps CDC might take to better serve state and local lead programs. Programs' experiences have led to a better understanding of the roles of their program when emergency events occur, their relationship with stakeholders as related to the blood lead testing and reporting process, and areas of improvement in surveillance databases. Public health agencies at all levels have important roles to play in preventing lead exposures and providing needed services when exposures occur. Programs may achieve long-term benefits by improving surveillance systems and having a better understanding of laboratory practices. CDC will continue to provide timely information and recommendations to state and local public health agencies to inform both routine and emergency response activities.
Improving Childhood Lead Poisoning Surveillance and Data Management in Arizona Through an Evaluation of the Transition to a New Surveillance System
Authors: Asburry Amber , Blatt Miyuki
Published: November 2018

The Arizona Childhood Lead Poisoning Prevention Program (CLPPP) worked with internal teams to identify opportunities for improvement in data quality and data management processes during the transition of lead poisoning surveillance into Arizona's communicable disease surveillance system. A pretransition review led to the determination of key strategies based on feasibility to implement and potential for impact on program operations. The strategies included standardizing reporting methods, automating data processing, and centralizing data management. The Childhood Lead Poisoning Prevention Program evaluated pre- and posttransition data management processes to determine whether improved efficiency was achieved. To evaluate the key strategies, indicators regarding data flow, data capture, and surveillance capacity were used. The key strategies were successful in improving data quality and efficiency. In addition, the implementation of these strategies has increased engagement among reporters, expanded surveillance capacity, and established a foundation to better understand lead poisoning challenges affecting Arizonan children.
Identifying and Chronicling Childhood Lead Poisoning Prevention Program Achievements With “Success Stories”
Authors: Lockamy-Kassim Elise , Friedberg Jared , Newby Christina , Lecours Carolina , Credle Kimball , Leonard Monica
Published: November 2018

Success stories showcase a public health program's progress toward achieving population health objectives. The Centers for Disease Control and Prevention's (CDC's) Childhood Lead Poisoning Prevention Program (CLPPP) develops “success stories” in partnership with state and local cooperative agreement recipients as one way to highlight lead poisoning prevention achievements. Success stories can be used to inform policy makers, stakeholders, and the general public. Over time, the process for collecting and developing CLPPP “successes” has evolved. Early efforts to collect success stories from funded recipients resulted in broad or unfocused reports that diminished the program's perceived impact. CDC's CLPPP revised the approach to success story development in order to better articulate the context, intervention or activity, and results related to programs' successes. The new approach results in stronger products ensuring that both CDC and program recipients can use the success stories to demonstrate achievement of key program objectives. We describe how success stories can be used to identify, chronicle, and mobilize public health program achievements using the example of lead poisoning prevention. Success stories allow programs to increase mission awareness, build stakeholder support, generate community interest, and collectively demonstrate progress toward meeting national program objectives.
Screening for Elevated Blood Lead Levels: False-Positive Rates of Tests on Capillary Samples, Minnesota, 2011-2017
Authors: Wang Amy , Rezania Zaynab , Haugen Kathryn M. B. , Baertlein Luke , Yendell Stephanie J.
Published: November 2018

Context:

A typical strategy for identifying children with elevated blood lead levels (BLL) is to use a test on a capillary sample as a screening tool and then perform a confirmatory test on a venous sample following an elevated capillary screen. However, tests on capillary samples are prone to false-positive results, which affect surveillance estimates of the prevalence of elevated BLL.

Objective:

We sought to measure the prevalence and risk of false-positive results in elevated tests on capillary samples based on various potential predictors.

Design, Setting, Participants, and Main Outcome Measures:

We analyzed blood lead results for children aged 0 to 6 years tested during 2011 to 2017 in Minnesota. A false positive was defined as a test on a capillary sample of at least 5 μg/dL, followed by a test result on a venous sample less than 5 μg/dL within 90 days. Binomial regression was used to estimate the probability of false-positive results dependent on the initial test result and the time between initial and confirmatory tests.

Results:

Results from 3898 children were included in analyses. Of these, 2330 (60%) had confirmatory results below 5 μg/dL and were classified as false positives. The proportion of false positives varied with time between tests, dependent on the initial result. Extrapolating the model to zero days between tests, without time for any change in the child's true BLL, we predicted 55% false positives in this study group (95% confidence interval: 53%-57%).

Conclusion:

Caution is warranted when interpreting elevated tests on capillary samples without confirmatory tests on venous samples. Providers should be encouraged to follow up all elevated capillary screens with confirmatory tests on venous samples.
Evaluation of the Blood Lead Screening Component of the Southern Nevada Childhood Lead Poisoning Prevention Program
Authors: Haboush-Deloye Amanda , Marquez Erika , Marshall Melissa , Gerstenberger Shawn L.
Published: November 2018

Context:

While public health programs and policies have worked to reduce lead exposure, lead poisoning remains a major preventable public health concern in the United States.

Objective:

In Clark County, Nevada, blood lead level (BLL) screening has historically been sparse. Thus, the purpose of this study was to evaluate the impact of the Southern Nevada Childhood Lead Poisoning & Prevention Program (CLPPP) in increasing screening efforts and identifying children with elevated blood lead levels (EBLLs).

Main Outcomes:

The proportion of children screened after the implementation of the CLPPP and the number of children identified with detectable BLLs.

Results:

A total of 43 028 BLL results for children younger than 6 years were assessed from 2006 to 2011. More than 19% of children tested during the project period had a detectable BLL. The number of BLL tests for children younger than 6 years increased from 4180 in 2005-2006 to 9304 in just the second year of CLPPP implementation. Once the initial implementation grant was over and additional funding was unavailable, the BLL screening once again declined to 5541 in 2016-2017.

Conclusion:

Evaluation of CLPPP activities suggests that outreach and education efforts, funded by the Centers for Disease Control and Prevention, played a significant role in increasing blood lead screening in Southern Nevada. However, despite these efforts, less than 5% of all children younger than 6 years were screened, which has declined further after the end of federal support.
Iatrogenic Colonic Perforations: Changing the Paradigm
Authors: Ulla-Rocha Jose Luis , Salgado Angel , Sardina Raquel , Souto Raquel , Sanchez-Santos Raquel , Turnes Juan
Published: November 2018

Purpose:

The purpose of our study was to investigate the clinical outcomes of colonoscopic perforations in patients.

Materials and Methods:

We retrospectively studied patients with perforations secondary to diagnostic/therapeutic colonoscopy between 2009 and 2015 at the Pontevedra Hospital Complex. We analyzed age, closure method, length of hospitalization, and long-term progress.

Results:

Of the 34 perforations detected, 67.6% occurred in patients aged below 75 years. Most perforations occurred in the descending colon (55%). Perforations occurred in 55.9% of outpatients and 45% of inpatients. Diagnostic and therapeutic colonoscopies caused perforations in 20.6% and 79.4% of patients, respectively. Conservative treatment alone was performed in 5.9%, complete or partial endoscopic closure in 14.7%, and surgery in 79.4% of patients. Patients treated only conservatively or with concomitant endoscopic closure showed no mortality. The mortality rate was 14.8% in those treated surgically, and 55% of these patients required a subsequent ostomy.

Conclusions:

Conservative management with antibiotics and parenteral nutrition concomitant with complete/partial endoscopic closure effectively treats perforations, provided intraprocedural diagnosis is possible with immediate administration of antibiotics after the procedure. Nevertheless, studies with larger number of patients and statistical analysis are necessary in the near future.
Generative modeling and latent space arithmetics predict single-cell perturbation response across cell types, studies and species
Authors: Lotfollahi M. , Wolf F. Alexander , Theis Fabian J.
Published: November 2018

Accurately modeling cellular response to perturbations is a central goal of computational biology. While such modeling has been proposed based on statistical, mechanistic and machine learning models in specific settings, no generalization of predictions to phenomena absent from training data (‘out-of-sample’) has yet been demonstrated. Here, we present scGen, a model combining variational autoencoders and latent space vector arithmetics for high-dimensional single-cell gene expression data. In benchmarks across a broad range of examples, we show that scGen accurately models dose and infection response of cells across cell types, studies and species. In particular, we demonstrate that scGen learns cell type and species specific response implying that it captures features that distinguish responding from non-responding genes and cells. With the upcoming availability of large-scale atlases of organs in healthy state, we envision scGen to become a tool for experimental design throughin silicoscreening of perturbation response in the context of disease and drug treatment.
Carbapenem-resistant Pseudomonas aeruginosa bloodstream infection: in vitro synergy, virulence and clinical outcome
Authors: Ramos Jessica Fernandes , Leite Gleice Cristina , Rizek Camila , Rossi Flavia , Guimarães Thais , Sanabani Sabri Saeed , Levin Anna Sara , Rocha Vanderson , Costa Silvia Figueiredo
Published: November 2018

In the current study carbapanem-resistant P. aeruginosa bloodstream infection (CRPA-BSI) was associated with high 14-day mortality. Although, highly resistant to meropenem, half of the isolates achieved in vitro synergy with the combination of meropenem with colistin, and the patients that received this combination therapy showed a tendency towards lower mortality. Our strains did not carry exoU gene, on the other hand, patients with CRPA-BSI caused by strains harboring gene lasB evolved more frequent to death.
Real-time monitoring of bacterial growth and fast antimicrobial susceptibility tests exploiting multiple light scattering
Authors: Han SeungYun , Kim HyunJung , Park Jongchan , Lee SangYun , Lee KyeoReh , Kim Ju-Kang , Chung Hyun Jung , Park YongKeun
Published: November 2018

Antimicrobial susceptibility test (AST) is widely used to provide the minimum inhibitory concentration of bacteria, and crucial to provide appropriate uses of antibiotics and to address the issue of drug-resistance bacteria. However, ASTs require the time-consuming incubation about 16-20 h for the visual determination of the growth of bacterial colonies, which has been a major obstacle to on-site applications of ASTs. In this study, we propose a rapid and non-invasive method based on laser speckles to evaluate the bacterial growth movements in real time, thus reducing the time for the agar dilution method. With a simple configuration compatible with conventional agar plates, the analysis of laser speckle from samples enables the early detection of the presence of growth as well as its detailed history of the colony-forming movement on agar plates. Using the samples prepared through the same procedure as the agar dilution method, we obtained the AST results at least 4-8 hours earlier than the conventional method without compromising the accuracy. This technique does not require for the use of exogenous agents, but works for most bacteria regardless of their species. Furthermore, the distinctive responses of several species to microbial agents were revealed through the present technique supporting a comprehensive analysis of the effect of the antibiotics. The findings suggest that this new method could be a useful tool for rapid, simple, and low-cost ASTs in addition to providing the historical information of the bacterial growth on agar plates.
A phylogeography of the second plague pandemic revealed through the analysis of historical Y. pestis genomes
Authors: Spyrou Maria A. , Keller Marcel , Tukhbatova Rezeda I. , Nelson Elizabeth A. , Andrades Valtueňa Aida , Walker Don , Alterauge Amelie , Carty Niamh , Fetz Hermann , Gourvennec Michaël , Hartle Robert , Henderson Michael , von Heyking Kristin , Kacki Sacha , Knox Elizabeth L. , Later Christian , Peters Joris , Schreiber Jürgen , Castex Dominique , Lösch Sandra , Harbeck Michaela , Herbig Alexander , Bos Kirsten I. , Krause Johannes
Published: November 2018

The second plague pandemic (14th - 18th century AD), caused by the bacterium Yersinia pestis, is infamous for its initial wave, the Black Death (1346-1353 AD), and its repeated scourges in Europe and the vicinity until the Early Modern Era. Here, we report 32 ancient Y. pestis genomes spanning the 14th to 17th century AD through the analysis of human remains from nine European archaeological sites. Our data support an initial entry of the bacterium from Eastern Europe and the absence of genetic diversity during the Black Death as well as low diversity during local outbreaks thereafter. Moreover, analysis of post-Black Death genomes shows the diversification of a Y. pestis lineage into multiple genetically distinct clades that may have given rise to more than one disease reservoir in, or close to, Europe. Finally, we show the loss of a genomic region that includes virulence-associated genes in strains associated with late stages of the second plague pandemic (17th - 18th century AD). This deletion could not be detected in extant strains within our modern dataset, though it was identified in a today-extinct lineage associated with the first plague pandemic (6th - 8th century AD), suggesting convergent evolution during both pandemic events.
Seasonal diets overwhelm host species in shaping the gut microbiota of Yak and Tibetan sheep
Authors: Wei Xiaojuan , Cheng Fusheng , Shi Hongmei , Zhou Xuzheng , Li Bing , Wang Ling , Wang Weiwei , Zhang Jiyu
Published: November 2018

Host genetics and environmental factors can both shaping composition of gut microbiota, yet which factors are more important is still under debating. Yak (Bos grunniens) and Tibetan sheep (Ovis aries) are very different from the size and genetics. Nomadic Tibetan people keep them as main livestock and feeding them with same grazing systems, which provide a good opportunity to study the effects of diet and host species on gut microbiome. We collected fecal samples from yaks and Tibetan sheeps at different seasons when they were feed with different diets. Illumina data showed that major bacterial phyla of both animals are Bacteroidetes and Firmicutes, which agree with the previous reports. And the season effect had a higher impact on the gut microbiota than that of host species, though the animals are taxonomically distinguished each other at subfamily level. Since that the animal grazing differently at different seasons, this study indicated that diet can trump the host genetics even at higher taxonomic level. This finding provides a cautionary note for the researchers to link host genetics to the composition and function of the gut microbiota.

Importance

Yak and Tibetan sheep are very different from the size and genetics (from different sub-family). Nomadic Tibetan people keep them as main livestock and feeding them with same grazing systems, which provide a good opportunity to study the effects of diet and host species on the gut microbiota. Results indicated that diet can trump the host genetics even at higher taxonomic level. This finding provides a cautionary note for the researchers to link host genetics to the composition and function of the gut microbiota.
Decoding the reproductive system of the olive fruit fly,Bactrocera oleae
Authors: Gregoriou M-E , Reczko M , Tsoumani K.T , Mathiopoulos K.D
Published: November 2018

A great deal of behavioral and molecular interactions between male and female insects takes place during insect reproduction. Here, we comprehensively analyze the reproductive system of the olive fruit fly. Specifically, transcriptomic and genomic analysis of the reproductive tissues from virgin and once mated insects were performed. Genes encoding proteins implicated in immune response, mucins, antigen 5 proteins, proteases inhibitors and proteins with putative secretory activity were identified. Comparison of the transcriptomes between virgin and mated insects resulted in the identification of genes that are up- or down-regulated after mating. In testes 106 genes were up-regulated and 344 genes were down-regulated, whereas in male accessory glands with ejaculatory bulb 1,607 genes were up-regulated and 384 genes were down-regulated in mated male insects. Respectively, in mated females 1,705 genes were up-regulated and 120 genes were down-regulated in mated insects. To get a deeper insight, the expression profiles of selected genes throughout sexual maturation for the male tissues and throughout different time points after mating for the female reproductive tissues were determined. Identification of genes that take part in the mating procedure not only gives an insight in the biology of the insects, but it could also help the identification of new target genes in order to disturb the reproductive success of the olive fly and thus develop alternative pest control method.
Functional Anatomy, Biomechanical Performance Capabilities and Potential Niche of StW 573: anAustralopithecusSkeleton (circa 3.67 Ma) From Sterkfontein Member 2, and its significance for The Last Common Ancestor of the African Apes and for Hominin Origins
Authors: Crompton Robin Huw , McClymont Juliet , Thorpe Susannah , Sellers William , Heaton Jason , Pickering Travis Rayne , Pataky Todd , Stratford Dominic , Carlson Kristian , Jashashvili Tea , Beaudet Amélie , Bruxelles Laurent , Goh Colleen , Kuman Kathleen , Clarke Ronald
Published: November 2018

Abstract (300 words)

StW 573, from Sterkfontein Member 2, dated ca 3.67 Ma, is by far the most complete skeleton of an australopith to date. Joint morphology is in many cases closely matched in available elements ofAustralopithecus anamensis(eg.proximal and distal tibial and humeral joint-surfaces) and there are also close similarities to features of the scapula, in particular, of KSD-VP-1/1A. afarensisfrom Woranso-Mille. The closest similarities are, however, to the partial skeleton of StW 431 from Sterkfontein Member 4. When considered together, both StW 573 and StW 431 express an hip joint morphology quite distinct from that ofA. africanusSts14, and a proximal femur of a presumedA. africanusfrom Jacovec Cavern at Sterkfontein, StW 598. This, and other evidence presented herein, suggests there are two pelvic girdle morphs at Sterkfontein, supporting Clarke (2013) in his recognition of a second species,A. prometheus,containing StW 573 and StW 431. StW 573 is the first hominid skeleton where limb proportions are known unequivocally. It demonstrates that some early hominins, at the time of formation of the Laetoli footprints (3.6 Ma), were large-bodied. with hindlimbs longer than forelimbs. Modelling studies on extant primates indicate that the intermembral index (IMI) of StW 573, low for a non-human great ape, would have substantially enhanced economy of bipedal walking over medium-to-long distances, but that it was still too high for effective walking while load-carrying. It would, however, have somewhat reduced the economy of horizontal climbing, but madeGorilla-like embracing of large tree-trunks less possible. Consideration of both ethnographic evidence from modern indigenous arboreal foragers and modern degeneracy theory cautions against prescriptive interpretations of hand- and foot-function, by confirming that both human-like upright bipedalism and functional capabilities of the hand and foot can be effective in short-distance arboreal locomotion.
Regulatory Changes in Pterin and Carotenoid Genes Underlie Balanced Color Polymorphisms in the Wall Lizard
Authors: Andrade Pedro , Pinho Catarina , de Lanuza Guillem Pérez i , Afonso Sandra , Brejcha Jindřich , Rubin Carl-Johan , Wallerman Ola , Pereira Paulo , Sabatino Stephen J. , Bellati Adriana , Pellitteri-Rosa Daniele , Bosakova Zuzana , Carretero Miguel A. , Feiner Nathalie , Marsik Petr , Paupério Francisco , Salvi Daniele , Soler Lucile , While Geoffrey M. , Uller Tobias , Font Enrique , Andersson Leif , Carneiro Miguel
Published: November 2018

Reptiles use pterin and carotenoid pigments to produce yellow, orange, and red colors. These conspicuous colors serve a diversity of signaling functions, but their molecular basis remains unresolved. Here, we show that the genomes of sympatric color morphs of the European common wall lizard, which differ in orange and yellow pigmentation and in their ecology and behavior, are virtually undifferentiated. Genetic differences are restricted to two small regulatory regions, near genes associated with pterin (SPR) and carotenoid metabolism (BCO2), demonstrating that a core gene in the housekeeping pathway of pterin biosynthesis has been co-opted for bright coloration in reptiles and indicating that these loci exert pleiotropic effects on other aspects of physiology. Pigmentation differences are explained by extremely divergent alleles and haplotype analysis revealed abundant trans-specific allele sharing with other lacertids exhibiting color polymorphisms. The evolution of these conspicuous color ornaments is the result of ancient genetic variation and cross-species hybridization.
High-throughput functional analysis of IncRNA core promoters elucidatesrules governing tissue-specificity
Authors: Mattioli Kaia , Volders Pieter-Jan , Gerhardinger Chiara , Lee James C. , Maass Philipp G. , Melé Marta , Rinn John L.
Published: November 2018

Transcription initiates at both coding and non-coding genomic elements, including mRNA and long non-coding RNA (lncRNA) core promoters and enhancer RNAs (eRNAs). However, each class has different expression profiles with lncRNAs and eRNAs being the most tissue-specific. How these complex differences in expression profiles and tissue-specificities are encoded in a single DNA sequence, however, remains unresolved. Here, we address this question using computational approaches and massively parallel reporter assays (MPRA) surveying hundreds of promoters and enhancers. We find that both divergent lncRNA and mRNA core promoters have higher capacities to drive transcription than non-divergent lncRNA and mRNA core promoters, respectively. Conversely, lincRNAs and eRNAs have lower capacities to drive transcription and are more tissue-specific than divergent genes. This higher tissue-specificity is strongly associated with having less complex TF motif profiles at the core promoter. We experimentally validated these findings by testing both engineered single-nucleotide deletions and human single-nucleotide polymorphisms (SNPs) in MPRA. In both cases, we observe that single nucleotides associated with many motifs are important drivers of promoter activity. Thus, we suggest that high TF motif density serves as a robust mechanism to increase promoter activity at the expense of tissue-specificity. Moreover, we find that 22% of common SNPs in core promoter regions have significant regulatory effects. Collectively, our findings show that high TF motif density provides redundancy and increases promoter activity at the expense of tissue specificity, suggesting that specificity of expression may be regulated by simplicity of motif usage.
Mountain lion genomes provide insights into genetic rescue of inbred populations
Authors: Saremi Nedda F. , Supple Megan A. , Byrne Ashley , Cahill James A. , Coutinho Luiz Lehmann , Dalén Love , Figueiró Henrique V. , Johnson Warren E. , Milne Heather J. , O’Brien Stephen J. , O’Connell Brendan , Onorato David P. , Riley Seth P.D. , Sikich Jeff A. , Stahler Daniel R. , Villela Priscilla Marqui Schmidt , Vollmers Christopher , Wayne Robert K. , Eizirik Eduardo , Corbett-Detig Russell B. , Green Richard E. , Wilmers Christopher C. , Shapiro Beth
Published: November 2018

Introduction paragraph/Abstract

Across the geographic range of mountain lions, which includes much of North and South America, populations have become increasingly isolated due to human persecution and habitat loss. To explore the genomic consequences of these processes, we assembled a high-quality mountain lion genome and analyzed a panel of resequenced individuals from across their geographic range. We found strong geographical structure and signatures of severe inbreeding in all North American populations. Tracts of homozygosity were rarely shared among populations, suggesting that assisted gene flow would restore local genetic diversity. However, the genome of an admixed Florida panther that descended from a translocated individual from Central America had surprisingly long tracts of homozygosity, indicating that genomic gains from translocation were quickly lost by local inbreeding. Thus, to sustain diversity, genetic rescue will need to occur at regular intervals, through repeated translocations or restoring landscape connectivity. Mountain lions provide a rare opportunity to examine the potential to restore diversity through genetic rescue, and to observe the long-term effects of translocation. Our methods and results provide a framework for genome-wide analyses that can be applied to the management of small and isolated populations.
Estimating fish population abundance by integrating quantitative data on environmental DNA and hydrodynamic modelling
Authors: Fukaya Keiichi , Murakami Hiroaki , Yoon Seokjin , Minami Kenji , Osada Yutaka , Yamamoto Satoshi , Masuda Reiji , Kasai Akihide , Miyashita Kazushi , Minamoto Toshifumi , Kondoh Michio
Published: November 2018

We propose a general framework of abundance estimation based on spatially replicated quantitative measurements of environmental DNA in which production, transport, and degradation of DNA are explicitly accounted for. Application to a Japanese jack mackerel (Trachurus japonicus) population in Maizuru Bay revealed that the method gives an estimate of population abundance comparable to that of a quantitative echo sounder method. These findings indicate the ability of environmental DNA to reliably reflect population abundance of aquatic macroorganisms and may oﬀer a new avenue for population monitoring based on the fast, cost-eﬀective, and non-invasive sampling of genetic information.