bluuebunny/crossref_metadata_2025 huggingface dataset:
A Statewide Study of the Epidemiology of Emergency Medical Services' Management of Pediatric Asthma
Authors: Fishe Jennifer N. , Palmer Eugene , Finlay Erik , Smotherman Carmen , Gautam Shiva , Hendry Phyllis , Hendeles Leslie
Published: March 2019

Objectives

Little is known about emergency medical services' (EMS') management of pediatric asthma. This study's objective was to describe the demographic, clinical, and geographic characteristics of current EMS' management of pediatric asthma in the state with the fourth-largest pediatric population.

Methods

This was a retrospective observational study of EMS patients ages 2 to 18 years with an asthma exacerbation from 2011 to 2016. Patients from Florida's EMS Tracking and Reporting System were included if their EMS chief complaint indicated respiratory distress, if they received at least 1 albuterol treatment, and if they were transported to a hospital.

Results

A total of 11,226 patients met the inclusion criteria. The median age was 9 years, and 49% were African-American. Geospatial analysis revealed 4 rural counties with disproportionate numbers of African-American patients. In addition to albuterol, 37% of patients received ipratropium bromide and 9% received systemic corticosteroids. Adjusted logistic regression revealed that the strongest predictors of receiving systemic corticosteroids from EMS were intravenous access (odds ratio, 33.4; 95% confidence interval, 24.4–45.6) and intravenous magnesium sulfate administration (odds ratio, 5.0; 95% confidence interval, 3.4–7.3), indicating a more severe presentation.

Conclusions

This statewide study demonstrated low rates of EMS administration of ipratropium bromide and systemic corticosteroids, both evidence-based treatments for asthma exacerbations. Targeted EMS education should attempt to increase utilization of both those medications. In addition, the feasibility and efficacy of EMS administration of oral systemic corticosteroids for children should be explored.
Use of Point-of-Care Ultrasound to Assess and Guide Renal Stent Repositioning in the Pediatric Emergency Department
Authors: Garcia Angélica Marie , Riera Antonio
Published: March 2019

Point-of-care ultrasound can be used as an assessment tool during the evaluation of children with renal colic. We discuss the case of a 7-year-old girl presenting to the pediatric emergency department with left flank pain, vomiting, and urinary incontinence status post–left renal stent placement. Renal ultrasound revealed ureteral obstruction caused by renal stent displacement. Point-of-care ultrasound performed by pediatric emergency department physicians was used to assess renal stent location, repositioning, and confirmation of the new location by the urology team. We discuss the role of transabdominal point-of-care ultrasound for the evaluation and treatment of the symptomatic child with recent ureter stent placement.
Antibiotic Prescription Practice for Pediatric Urinary Tract Infection in a Tertiary Center
Authors: Alghounaim Mohammad , Ostrow Olivia , Timberlake Kathryn , Richardson Susan E. , Koyle Martin , Science Michelle
Published: March 2019

Objectives

Prescribing antibiotics for suspected urinary tract infection (UTI) is common practice and may lead to unnecessary antibiotic exposure. We aimed to review UTI diagnosis and management in the emergency department and to identify targets for antimicrobial stewardship.

Methods

Single-center, retrospective cohort study of children aged 12 weeks to younger than 18 years discharged from the emergency department with a diagnosis of UTI between October and December 2016. Children with genitourinary malformations were excluded. Clinical information, urine collection method, laboratory findings, and urine culture results were gathered. The sensitivity and specificity of nitrite and leukocyte esterase for UTI diagnosis were calculated. The relationship between urinalysis characteristics and confirmed UTI was examined using logistic regression.

Results

A total of 183 children with a median (interquartile range) age of 4.2 (1.1–7.5) years were included; 82.5% were female. Almost all children were discharged home on antibiotics (n = 180, 98%) for a median (interquartile range) duration of 7 (7–10) days. A total of 85 patients (46.4%) received antibiotics despite negative urine cultures leading to 525 unnecessary antibiotic days. The presence of nitrites was the strongest predictor of UTI (odds ratio = 20.22, P < 0.001) and was highly specific.

Conclusions

Current practice in managing suspected pediatric UTIs in our ED resulted in significant and unnecessary antibiotic exposure. We identified targets to reduce unnecessary antibiotic exposure including improving the diagnostic accuracy of UTIs, a process to discontinue antibiotics for negative cultures and standardizing antimicrobial duration.
Characteristics That Distinguish Abusive From Nonabusive Causes of Sudden Unexpected Infant Deaths
Authors: Bechtel Kirsten , Derbyshire Meagan , Gaither Julie R. , Leventhal John M.
Published: March 2019

Background

Fatal child abuse can be mistaken for sudden unexpected infant death (SUID) in the emergency department setting. It is unknown if there are characteristics that distinguish abusive from nonabusive causes of SUIDs in the emergency department.

Methods

Using a matched case-control design, we reviewed the medical examiner records of deaths of infants younger than 12 months who were found unresponsive at a residence, required cardiopulmonary resuscitation, and had a complete forensic autopsy between 2009 and 2015. Infants with a manner of death as homicide were cases; controls were those with the manner of death as accident, natural, or undetermined. Each case was matched with 5 controls based on age (months). Differences between cases and controls were evaluated with respect to demographic, parental, and household characteristics and clinical outcomes.

Results

We identified 12 cases (homicides) and 169 controls (nonhomicides), of which 60 were selected for the matched analysis. We found no significant differences between cases and controls with respect to age, race, sex, maternal substance use, Child Protective Services involvement prior to death, presence of male head of household, surviving siblings, or emergency medical services transport. Cases were more likely to have Child Protective Services involvement at the time of death (83% vs 38%; P = 0.01), sentinel injuries (odds ratio, 9.67; 95% confidence interval, 1.30–122.43), and return of spontaneous circulation (odds ratio, 29.99; 95% confidence interval, 3.70–241.30).

Conclusions

Child Protective Services agency involvement at time of death, sentinel injury, and return of spontaneous circulation were more often associated with abusive causes of SUID. Further study is needed to confirm these findings.
CDX2, SATB2, GATA3, TTF1, and PAX8 Immunohistochemistry in Krukenberg Tumors
Authors: Chiesa-Vottero Andres
Published: March 2019

Twenty-six Krukenberg tumors (16 lower gastrointestinal, 4 upper gastrointestinal, and 6 of unknown origin) and their primaries when known were stained with CDX2, SATB2, GATA3, TTF1, and PAX8 using a tissue microarray containing predominantly or exclusively signet ring cells. The most common primary was appendiceal mixed adenoneuroendocrine carcinoma. CDX2 and SATB2 were positive in all known lower gastrointestinal primary tumors and negative in nearly all known upper gastrointestinal primary tumors. Primaries showed identical immunophenotypes to their metastases. Among cases of unknown primary origin, 3 were positive and 3 were negative for CDX2 and SATB2. Chest images, upper endoscopies, colonoscopies, appendectomies, and mammogram were performed with negative results in all, 4, 2, 2, and 1 cases, respectively. No cystoscopies were attempted. PAX8, GATA3, and TTF1 were negative in all cases. The literature was reviewed with emphasis on immunohistochemistry of signet ring cell–containing carcinomas from the appendix, colon, stomach, breast, lung, and bladder. Three quarters of gastric primaries stain for CDX2 and only rare examples stain for SATB2. Colorectal primaries (most of them) and appendiceal primaries (all of them) are positive for CDX2 and SATB2. GATA3 stains almost all breast primaries and approximately half of bladder primaries. All pulmonary primaries are positive for TTF1. PAX8 is negative in the gastric, colorectal, and appendiceal primaries reported. This study shows that the panel of immunostains is useful in confirming the site of origin of a metastatic Krukenberg tumor when one is known and has limited diagnostic value for diagnosing metastases of unknown origin.
Evidence for a Novel Endometrioid Carcinogenic Sequence in the Fallopian Tube With Unique Beta-Catenin Expression
Authors: Brouwer Jan , Strickland Kyle C. , Ning Gang , Schmelkin Cindy B. , Kolin David L. , Hecht Jonathan , Nucci Marisa R. , Mourits Marian J. , Xian Wa , Crum Christopher P.
Published: March 2019

Epithelial proliferations in the fallopian tube have been characterized by some as stem cell outgrowths (SCOUTs) and divided into type I and type II. Type II SCOUTs exhibit diffuse cellular beta-catenin nuclear staining (β-catenin+), implying a CTNNB1 mutation. SCOUTs are more common in perimenopausal and postmenopausal women and are associated with ovarian cancer but have not been linked directly to malignancy. We analyzed type II SCOUTs in various gynecologic conditions, and searched for endometrioid atypical hyperplasias (tubal endometrioid intraepithelial neoplasia) or adenocarcinomas in the tube. β-catenin+ SCOUT frequency in cases of neoplasia was 66.7% per case and 30.7% per nonfimbrial cross-section for uterine endometrioid carcinomas versus 25% and 13.3% for controls, respectively (P=0.02 and 0.09). Multiple (3 or more) β-catenin+ SCOUTs in a single section were uncommon; 6 of 9 were associated with a carcinoma or proliferative lesion in the endometrium. Tubal endometrioid intraepithelial neoplasia/atypical hyperplasia displayed complex growth, including focal cribriform growth patterns and squamous morules. Two cases of type II SCOUTs associated with tubal endometrioid intraepithelial neoplasia/atypical hyperplasia and/or adenocarcinomas in the fallopian tube were identified, both of which coexisted with a separate endometrioid adenocarcinoma, one with bilateral ovarian endometrioid adenocarcinomas. Both benign and neoplastic tubal lesions were β-catenin+. This report is the first to link components of a unique β-catenin+ endometrioid carcinogenic sequence in the fallopian tube. It further emphasizes the multifocal nature of endometrioid neoplasia in the female genital tract and poses questions regarding the frequency and biologic underpinnings of β-catenin+ proliferations in the oviduct.
Tumor-to-Tumor Metastasis of Colorectal Adenocarcinoma to Ovarian Cystadenofibroma: A Case Report and Review of the Literature
Authors: Fahoum Ibrahim , Brazowski Eli , Hershkovitz Dov , Aizic Asaf
Published: March 2019

Tumor-to-tumor metastasis is being described in different types of tumors and in increasing amount of cases. Being aware of this phenomenon is important, as it affects disease stage and treatment approach. In this report, we descried an incidental histopathologic finding of metastatic adenocarcinoma to an ovarian cystadenofibroma and review cases published previously in the literature.
A Rare Case of Atypical Placental Site Nodule With an Emerging Intermediate Trophoblastic Tumor
Authors: Dholakia Jhalak , Chen Wei , O’Malley David M. , Ronnett Brigitte M.
Published: March 2019

Placental site nodule (PSN) is a benign lesion composed of chorionic-type intermediate trophoblastic cells and is typically an incidental finding in uterine or endocervical curettage specimens. Epithelioid trophoblastic tumor (ETT) and placental site trophoblastic tumor (PSTT) are intermediate trophoblastic neoplasms of chorionic and implantation site types, respectively. ETT is speculated to be the neoplastic counterpart of PSN. The term atypical placental site nodule (APSN) has been proposed for PSN-type lesions displaying one or more concerning features, including larger size/more abundant lesional tissue, more extensive plaque-like growth, increased cellularity with more cohesive nests and cords of cells, a greater extent/distribution of necrosis, increased atypia, mitotic activity, and/or a Ki-67 proliferation index greater than usually encountered in the typical PSN. It has been proposed that APSN is an intermediary lesion between PSN and intermediate trophoblastic tumors, more commonly ETT but also PSTT. We report a case of a 39-yr-old woman who developed abnormal uterine bleeding 44 mo after her last recognized pregnancy. An endometrial curettage specimen demonstrated an APSN with some features concerning for an intermediate trophoblastic tumor. A hysterectomy specimen demonstrated residual APSN with foci consistent with emerging PSTT and ETT. This case illustrates the earliest form of PSTT and ETT arising in association with an APSN and supports interpretation of APSN as an intermediary lesion between typical PSN and intermediate trophoblastic tumors.
A Short History of Medical Expert Guidelines and How They Pertain to Tracheostomy Tubes and Physical Medicine and Rehabilitation
Authors: Bach John R.
Published: March 2019

Continuous noninvasive ventilatory support (CNVS) and mechanical insufflation-exsufflation have been used since 1953 to spare patients with ventilatory pump failure from ever-requiring tracheostomy tubes for ventilatory support or secretion management. Today there are patients with spinal muscular atrophy type 1 who are 25 yrs old and CNVS dependent since 4 months or age, postpolio survivors CNVS dependent for 64 yrs, Duchenne muscular dystrophy patients over age 45 CNVS dependent for over 25 yrs, high-level spinal cord injured patients CNVS dependent for over 20 yrs, and even lung disease patients dependent on CNVS. All these patients, although unweanable from ventilatory support and with little or no measurable vital capacity, can also be extubated to CNVS and mechanical insufflation-exsufflation when necessary to continue CNVS. No patients want tracheostomy tubes. However, for various reasons, this is not cited in academic society expert guidelines. This article considers the extent of the damage being caused by this.
Reconstruction of Large Facial Malignant Tumor Defects Using Local Angular Perforator Flap
Authors: Weng Xiao-Juan , Li Xiao-Jing
Published: March 2019

Objective:

To investigate the 1-stage repair for postoperative wound of large facial malignant tumors.

Materials and Methods:

The angular perforator flap of the face and neck was used for 1-stage rotary advancement repair of the large skin wound following tumor resection.

Results:

After using the angular perforator flap for 1-stage wound repair, the flap was completely preserved, and the donor incision site healed well. The suture was removed after some 7 to 9 days, and the flap color was similar to that of the surrounding skin. After 12 months follow-up, there was no obvious scar growth observed.

Conclusion:

The design of the neck and face angular perforator flap was flexible with a good blood supply, and thus can be used for 1-stage repair of the large defect wound after facial malignant tumor resection. Also, the observed prognosis was good.
Utilization of Intermaxilar Fixation Screws as Anchors in the Treatment of the Mandible Recurrent Dislocation
Authors: Pessoa Petros Fernandes , de Brito Silva Lucas Nunes , de Souza André Lustosa , de Carvalho Nogueira Emerson Filipe , Brainer Diogo Luiz Bastos
Published: March 2019

Propose:

This paper aims to describe a modification of the Wolford technique by replacing the Mitek anchors with bone screws.

Technical description:

Two intermaxillary fixation screws locking screws, with 2.0 mm in diameter and 8 mm in length, are used in each temporomandibular joint, one of which is fixed to the root of the zygomatic arch and another to the lateral pole of the mandibular condyle. Ethibond 2-0 thread is passed through the holes in the 2 ipsilateral screws, thus acting as an artificial ligament limiting the range of the mouth opening.

Conclusion:

The technique described was effective in preventing mandibular dislocation while allowing satisfactory mouth opening range. This technique has easy handling and low cost.
Histological Evaluation of the Effects of Growth Factors in a Fibrin Network on Bone Regeneration
Authors: Cakir Sevki , Gultekin B. Alper , Karabagli Murat , Yilmaz Tugba Ekiz , Cakir Esra , Guzel E. Elif , Yalcin Serdar , Mortellaro Carmen , Mijiritsky Eitan
Published: March 2019

Objective:

The aim of this study was to evaluate the effect of mineralized plasmatic matrix (MPM), comprising a combination of synthetic graft and platelet concentrates, on bone regeneration.

Methods:

Critical size defects of 6-mm diameter were created on the tibias of 6 male sheep, with the animals subsequently assigned into 2 groups. Of the 5 bone defects generated per animal, 4 were randomly filled with MPM, beta-tricalcium phosphate graft (β-TCP), platelet-rich fibrin (PRF) + β-TCP, and autogenous graft. One defect was left empty as a control group. Animals were killed at 3 weeks (early healing group) and 6 weeks (late healing group). The specimens underwent histologic and histomorphometric analysis to evaluate new bone formation.

Results:

In both healing periods, new bone formation from autogenous bone was observed significantly more often than from biomaterials or the empty defect. The degree of new bone formation for MPM was significantly higher than that of the control group at all healing periods. In addition, it was significantly higher in both healing periods than that of β-TCP albeit only in the late healing period than that of the PRF + β-TCP combination. In all biomaterial groups, residual graft ratios decreased from early to late healing periods.

Conclusion:

The results indicated that MPM, representing growth factors in a fibrin network, increases new bone formation in surgically created defects in sheep tibia as confirmed by histologic assessment.
Population-Specific Metabolic Alterations in Professional Antigen-Presenting Cells Contribute to Sepsis-Associated Immunosuppression
Authors: Schenz Judith , Tamulyte Sandra , Nusshag Christian , Brenner Thorsten , Poschet Gernot , Weigand Markus A. , Uhle Florian
Published: March 2019

Sepsis is a complex host response triggered by an infection, with the patient's immune system between hyper- and hypo-responsiveness being the main reason for the syndromes’ development and propagation. Studies conducted in peripheral blood mononuclear cells uncovered an association between an impaired immunometabolism and the severity and outcome of the disease. With this prospective observational study, we aimed to evaluate the immunometabolic phenotype of monocytes and B cells and its association with the cell function.

Monocytes and B cells were isolated from patients with sepsis (n = 10; onset, days 4 and 8) and healthy volunteers (n = 10) and subsequently analyzed for metabolic changes and human leukocyte antigen-DR (HLA-DR) expression. Contemporaneously, immune checkpoints on monocytes and the ex vivo cytokine responses (interleukins 6 and 8) upon lipopolysaccharide or zymosan stimulation were analyzed. The distribution of B cell subsets was assessed, and plasma levels of immunoglobulins and tricarboxylic acid cycle intermediates were quantified.

Both monocytes and B cells exhibited decreased HLA-DR expression in patients with sepsis. Monocytes displayed a stable upregulated glycolysis while B cells augmented glycolysis and respiration over time. The monocytes’ ability to respond to stimulation was stimuli-dependently reduced but recovered over time. The B cell compartment shifted toward antibody-producing subsets and elevated immunoglobulins within the first days.

Our results provide evidence for the induction of a state of trained immunity in monocytes and an early but transient immunosuppressive phenotype accounting for peripheral sepsis-induced vulnerability to infections. B cells exhibit an unsustainable activation contributing to adaptive immunosuppression.
Fatty Acid-Saturated Albumin Reduces High Mortality and Fluid Requirements in a Rat Model of Hemorrhagic Shock Plus Tourniquet and Hypotensive Resuscitation
Authors: Penn Alexander H. , Williams Charnae E. , Walters Thomas J. , Dubick Michael A. , Torres Filho Ivo P.
Published: March 2019

Military prehospital care for hemorrhage is often characterized by use of tourniquets (TQ) and permissive hypotensive resuscitation (PHR) with crystalloids or colloids, but these treatments have not been previously combined in an animal model. Although albumin resuscitation solutions have been tested, the potential effects of nonesterified fatty acids (NEFAs) bound to albumin have not been evaluated in vivo, and few studies have investigated concentrated albumin solutions to reduce fluid requirements. We created a militarily relevant rat model of trauma and hemorrhagic shock (T/HS) (27 mL/kg hemorrhage) with TQ and PHR. We investigated the ability of resuscitation with concentrated (250 mg/mL) albumin, followed by Plasmalyte as needed to maintain PHR, to reduce fluid volumes (vs. Plasmalyte alone, N = 17). Albumin was free of nonesterified fatty acids (N = 15) or saturated with oleic acid (OA; N = 13). The model resulted in high (53%) mortality within 3 h of injury. Only OA-saturated albumin was able to significantly reduce mortality (from 47% to 8%) and fluid requirements (from 56 to 6 mL/kg) compared to Plasmalyte alone. Plasma NEFA-binding capacity was saturated earliest in the OA-saturated albumin group. Likewise, OA-saturated albumin tended to increase cell-free hemoglobin in the broncheoalveolar lavage fluid, which was significantly associated with survival. Our findings suggest incorporating TQ and PHR in T/HS models may result in high mortality and fluid requirements and that OA-saturated albumin, but not NEFA-free albumin or Plasmalyte alone, may provide a benefit to early survival and resuscitation volume, though a hemolytic mechanism may have later consequences, so caution is advised.
Trends in Surgical Exposure and Experience in Female Pelvic Medicine and Reconstructive Surgery Fellowship Programs
Authors: Andiman Sarah E. , Fantl John A.
Published: March 2019

Objectives

This study aimed to characterize variations in female pelvic medicine and reconstructive surgery (FPMRS) fellows’ surgical experiences, concurrence with Accreditation Council for Graduate Medical Education (ACGME) proposed procedural volume guidelines, and to explore how these factors affect self-assessed preparedness to practice independently upon graduation.

Methods

An electronic survey was sent to 166 fellows enrolled in ACGME-approved FPMRS fellowship programs during the 2017–2018 academic year. The survey included questions on demographics, program specifics, desires for future practice, case volume, and self-assessed ability to independently perform selected procedures.

Results

A total of 99 fellows responded, yielding a 59.6% (99/166) response rate. Procedures assessed as “core” urogynecologic surgeries were midurethral sling, sacral nerve stimulator placement, abdominal sacrocolpopexy, laparoscopic sacrocolpopexy, extraperitoneal colpopexy, intraperitoneal colpopexy, anterior colporrhaphy, posterior colporrhaphy, colpocleisis, rectovaginal fistula repair, vesicovaginal fistula repair, and urethral diverticulectomy. The percentage of third-year respondents meeting proposed ACGME guidelines varied from 56.3% (18/32; sling procedures) to 96.9% (31/32; intraperitoneal colpopexy and rectovaginal fistula repair). Although 67.7% (67/99) of all respondents reported that they did not expect to feel qualified to perform at least one of these procedures independently upon graduation from fellowship, 99.0% (98/99) predicted that they would be adequately trained overall to practice independently upon graduation.

Conclusions

Surgical experience varied among FMPRS surgical fellows. Case volume was somewhat but not completely associated with self-perceived ability to practice a procedure independently.
Superior Outcomes and Reduced Wait Times in Pediatric Recipients of Living Donor Liver Transplantation
Authors: Kehar Mohit , Parekh Rulan S. , Stunguris Jennifer , De Angelis Maria , Van Roestel Krista , Ghanekar Anand , Cattral Mark , Fecteau Annie , Ling Simon , Kamath Binita M. , Jones Nicola , Avitzur Yaron , Grant David , Ng Vicky Lee
Published: March 2019

Background

Living donor liver transplantation (LDLT) is increasingly used to bridge the gap between the current supply and demand imbalance for deceased donor organs to provide lifesaving liver transplantation.

Methods

Outcomes of 135 children who underwent LDLT were compared with 158 recipients of deceased donor liver transplantation (DDLT) at the largest pediatric liver transplant program in Canada.

Results

Recipients of LDLT were significantly younger than deceased donor recipients (P ≤ 0.001), less likely to require dialysis pretransplant (P < 0.002) and had shorter wait time duration when the primary indication was cholestatic liver disease (P = 0.003). The LDLT donors were either related genetically or emotionally (79%), or unrelated (21%) to the pediatric recipients. One-, 5-, and 10-year patient survival rates were significantly higher in LDLT (97%, 94%, and 94%) compared with DDLT (92%, 87%, and 80%; log-rank P = 0.02) recipients, as were graft survival rates (96%, 93%, and 93% for LDLT versus 89%, 81.4%, and 70%, respectively, for DDLT; log-rank P = 0.001). Medical and surgical complications were not statistically different between groups. Graft failure was higher in recipients of DDLT (odds ratio, 2.60; 95% confidence interval, 1.02, 6.58) than in the LDLT group after adjustment for clinical characteristics and propensity score.

Conclusions

Living donor liver transplantation provides superior outcomes for children and is an excellent and effective strategy to increase the chances of receiving a liver transplant.
Utility of Magnetic Resonance Imaging Features for Improving the Diagnosis of Idiopathic Intracranial Hypertension Without Papilledema
Authors: Mallery Robert M. , Rehmani Obeidurahman F. , Woo John H. , Chen Yin Jie , Reddi Sudama , Salzman Karen L. , Pinho Marco C. , Ledbetter Luke , Tamhankar Madhura A. , Shindler Kenneth S. , Digre Kathleen B. , Friedman Deborah I. , Liu Grant T.
Published: March 2019

Objective:

Revised diagnostic criteria for idiopathic intracranial hypertension (IIH) were proposed in part to reduce misdiagnosis of intracranial hypertension without papilledema (WOP) by using 3 or 4 MRI features of intracranial hypertension when a sixth nerve palsy is absent. This study was undertaken to evaluate the sensitivity and specificity of the MRI criteria and to validate their utility for diagnosing IIH in patients with chronic headaches and elevated opening pressure (CH + EOP), but WOP.

Methods:

Brain MRIs from 80 patients with IIH with papilledema (WP), 33 patients with CH + EOP, and 70 control patients with infrequent episodic migraine were assessed in a masked fashion for MRI features of intracranial hypertension.

Results:

Reduced pituitary gland height was moderately sensitive for IIH WP (80%) but had low specificity (64%). Increased optic nerve sheath diameter was less sensitive (51%) and only moderately specific (83%). Flattening of the posterior globe was highly specific (97%) but had low sensitivity (57%). Transverse venous sinus stenosis was moderately sensitive for IIH WP (78%) but of undetermined specificity. A combination of any 3 of 4 MRI features was nearly 100% specific, while maintaining a sensitivity of 64%. Of patients with CH + EOP, 30% had 3 or more MRI features, suggesting IIH WOP in those patients.

Conclusion:

A combination of any 3 of 4 MRI features is highly specific for intracranial hypertension and suggests IIH WOP when present in patients with chronic headache and no papilledema.
Epithelial retinoic acid receptor β regulates serum amyloid A expression and vitamin A-dependent intestinal immunity
Authors: Gattu Sureka , Bang Ye-Ji , Pendse Mihir , Dende Chaitanya , Chara Andrew L. , Harris Tamia A. , Wang Yuhao , Ruhn Kelly A. , Kuang Zheng , Sockanathan Shanthini , Hooper Lora V.
Published: March 2019

Vitamin A is a dietary component that is essential for the development of intestinal immunity. Vitamin A is absorbed and converted to its bioactive derivatives retinol and retinoic acid by the intestinal epithelium, yet little is known about how epithelial cells regulate vitamin A-dependent intestinal immunity. Here we show that epithelial cell expression of the transcription factor retinoic acid receptor β (RARβ) is essential for vitamin A-dependent intestinal immunity. Epithelial RARβ activated vitamin A-dependent expression of serum amyloid A (SAA) proteins by binding directly to Saa promoters. In accordance with the known role of SAAs in regulating Th17 cell effector function, epithelial RARβ promoted IL-17 production by intestinal Th17 cells. More broadly, epithelial RARβ was required for the development of key vitamin A-dependent adaptive immune responses, including CD4+ T cell homing to the intestine and the development of immunoglobulin A-producing intestinal B cells. Our findings provide insight into how the intestinal epithelium senses dietary vitamin A status to regulate adaptive immunity and highlight the role of epithelial cells in regulating intestinal immunity in response to diet.

Significance Statement

Vitamin A is a nutrient that is essential for the development of intestinal immunity. It is absorbed by gut epithelial cells which convert it to retinol and retinoic acid. Here we show that the transcription factor retinoic acid receptor β (RARβ) allows epithelial cells to sense vitamin A in the diet and regulate vitamin A-dependent immunity in the intestine. We find that epithelial RARβ regulates several intestinal immune responses, including production of the immunomodulatory protein serum amyloid A, T cell homing to the intestine, and B cell production of immunoglobulin A. Our findings provide new insight into how epithelial cells sense vitamin A to regulate intestinal immunity and highlight why vitamin A is so important for immunity to infection.
Global transcriptome analysis of theMyxococcus xanthusmulticellular developmental program
Authors: Muñoz-Dorado J. , Moraleda-Muñoz A. , Marcos-Torres F.J. , Contreras-Moreno F.J. , Martin-Cuadrado A.B. , Schrader J.M. , Higgs P.I. , Pérez J.
Published: March 2019

The bacteriaMyxococcus xanthusexhibit a complex multicellular life cycle. In the presence of nutrients, cells prey cooperatively. Upon starvation, they enter a developmental cycle wherein cells aggregate to produce macroscopic fruiting bodies filled with resistant myxospores. We used RNA-Seq technology to examine the global transcriptome of the 96 h developmental program. This data revealed that many genes were sequentially expressed in discrete modules, with expression peaking during aggregation, in the transition from aggregation to sporulation, or during sporulation. Analysis of genes expressed at each specific time point provided a global framework integrating regulatory factors coordinating motility and differentiation in the developmental program. These data provided insights as to how starving cells obtain energy and precursors necessary for assembly of fruiting bodies and into developmental production of secondary metabolites. This study offers the first global view of developmental transcriptional profiles and provides an important scaffold for future studies.

IMPACT STATEMENT

Investigation of global gene expression profiles during formation of theMyxococcus xanthusspecialized biofilm reveals a genetic regulatory network that coordinates cell motility, differentiation, and secondary metabolite production.
Signatures of divergent antimalarial treatment responses in peripheral blood from infants and adults in Malawi
Authors: Maurizio Paul L. , Fuseini Hubaida , Tegha Gerald , Hosseinipour Mina , Paris Kristina De
Published: March 2019

Background

Heterogeneity in the immune response to parasite infection is mediated in part by differences in host genetics, sex, and age group. In neonates and infants, ongoing immunological maturation often results in increased susceptibility to infection and variable responses to drug treatment, increasing the risk of complications. Even though significant age-specific effects on host cytokine responses to Plasmodium falciparum infection have been identified, age effects on uncomplicated malaria infection and antimalarial treatment remain poorly understood.

Methods

In samples of whole blood from a cohort of naturally infected malaria-positive individuals in Malawi (n=63 total; 34 infants <2 years old, 29 adults >18 years old), we assessed blood cytokine levels and characterized monocyte and dendritic cell frequencies at two timepoints: acute infection, and four weeks post antimalarial treatment. We modeled the effects of age group, sex, and timepoint, and evaluated the role of these factors on infection and treatment outcomes.

Results

Regardless of treatment timepoint, in our population age was significantly associated with overall blood hemoglobin, which was higher in adults, and plasma nitric oxide, IL-10, and TNF-α levels, which were higher in infants. We found a significant effect of age on the hemoglobin treatment response, whereby after treatment, levels increased in infants and decreased in adults. Furthermore, we observed significant age-specific effects on treatment response for overall parasite load, IFN-γ and IL-12(p40), and these effects were sex-dependent. We uncovered significant age effects on the overall levels and treatment response of myeloid dendritic cell frequencies. In addition, within each age group, we found continuous age effects on gametocyte levels (Pfs16), TNF-α, and nitric oxide.

Conclusions

In a clinical study of infants and adults experiencing natural malaria infection and receiving antimalarial treatment, we identified age-specific signatures of infection and treatment responses in peripheral blood. We describe host markers that may indicate, and potentially mediate, differential post-treatment outcomes for malaria in infants versus adults.
Evolutionary analyses unveil the molecular mechanism of fast inactivation in calcium-permeable TRP channels
Authors: Flores-Aldama Lisandra , Vandewege Michael W. , Zavala Kattina , Colenso Charlotte K. , Bustos Daniel , Gonzalez Wendy , Brauchi Sebastian E. , Opazo Juan C.
Published: March 2019

Fundamental for calcium homeostasis in vertebrates, TRPV5 and TRPV6 are calcium-selective ion channels belonging to the Transient Receptor Potential (TRP) gene family. Detailed phylogenetic analysis suggests that duplications from which TRPV5 and TRPV6 originated occurred independently in the ancestors of mammals, sauropsids, amphibians, and chondrichthyans. Coincident with the conquest of land and the physiological changes needed to maintain calcium homeostasis, our expression analyses suggest a change in the expression pattern from gills to kidney. Within amniotes, we identified a traceable sequence signature of three amino acids at the amino-terminal intracellular region that correlates well with both of the duplication events and the phenotype of fast inactivation observed in TRPV6 channels. Electrophysiological recordings and mutagenesis suggest that calcium-induced fast inactivation is an evolutionary innovation that emerged independently from each duplication event. Simulations of molecular dynamics suggest that calcium-induced channel rearrangements are important modulatory regions of TRP channels.
Shotgun proteomics analysis of nanoparticle-synthesisingDesulfovibrio alaskensisin response to platinum and palladium
Authors: Capeness Michael J. , Imrie Lisa , Mühlbauer Lukas F. , Bihan Thierry Le , Horsfall Louise E.
Published: March 2019

Platinum and palladium are much sought-after metals of global critical importance in terms of abundance and availability. At the nano-scale these metals are of even higher value due to their catalytic abilities for industrial applications.Desulfovibrio alaskensisis able to capture ionic forms of both of these metals, reduce them, and synthesize elemental nanoparticles. Despite this ability very little is known about the biological pathways involved in the formation of these nanoparticles. Proteomic analysis ofD. alaskensisin response to platinum and palladium has highlighted those proteins involved in both the reductive pathways and the wider stress-response system. A core set of 13 proteins was found in both treatments and consisted of proteins involved in metal transport and reduction. There were also 7 proteins specific to either platinum or palladium. Over-expression of one of these platinum-specific genes, a NiFe hydrogenase small subunit (Dde_2137), resulted in the formation of larger nanoparticles. This study improves our understanding of the pathways involved in the metal resistance mechanism ofDesulfovibrioand informs how we can tailor the bacterium for nanoparticle production, enhancing its application as a bioremediation tool and as way to capture contaminant metals from the environment.

Importance

Bacteria, in particularlyD. alaskensis, represent a biological and greener way to capture high value metals such as platinum group metals from environmental and industrial waste streams. The recovery of these metals in nanoparticle forms adds extra value to this process as they can be used in a variety of different industrial applications as they have exceptional catalytic capabilities.D. alaskensisability to do this, has been widely reported, though very little is understood about the underlying protein and genetic components. It is by understanding the biological basis of this capability that we can further improve and adapt this bacterium to be better at bioremediation and to control its ability to do so.
Learning what is irrelevant or relevant: Expectations facilitate distractor inhibition and target facilitation through distinct neural mechanisms
Authors: van Moorselaar Dirk , Slagter Heleen A.
Published: March 2019

It is well known that attention can facilitate performance by top-down biasing processing of task-relevant information in advance. Recent findings from behavioral studies suggest that distractor inhibition is not under similar direct control, but strongly dependent on expectations derived from previous experience. Yet, how expectations about distracting information influence distractor inhibition at the neural level remains unclear. The current study addressed this outstanding question in three experiments in which search displays with repeating distractor or target locations across trials allowed observers to learn which location to selectively suppress or boost. Behavioral findings demonstrated that both distractor and target location learning resulted in more efficient search, as indexed by faster response times. Crucially, benefits of distractor learning were observed without target location foreknowledge, unaffected by the number of possible target locations, and could not be explained by priming alone. To determine how distractor location expectations facilitated performance, we applied a spatial encoding model to EEG data to reconstruct activity in neural populations tuned to the distractor or target location. Target location learning increased neural tuning to the target location in advance, indicative of preparatory biasing. This sensitivity increased after target presentation. By contrast, distractor expectations did not change preparatory spatial tuning. Instead, distractor expectations reduced distractor-specific processing, as reflected in the disappearance of the Pd ERP component, a neural marker of distractor inhibition, and decreased decoding accuracy. These findings suggest that the brain may no longer process expected distractors as distractors, once it has learned they can safely be ignored.

Significance statement

We constantly try hard to ignore conspicuous events that distract us from our current goals. Surprisingly, and in contrast to dominant attention theories, ignoring distracting, but irrelevant events does not seem to be as flexible as is focusing our attention on those same aspects. Instead, distractor suppression appears to strongly rely on learned, context-dependent expectations. Here, we investigated how learning about upcoming distractors changes distractor processing and directly contrasted the underlying neural dynamics to target learning. We show that while target learning enhanced anticipatory sensory tuning, distractor learning only modulated reactive suppressive processing. These results suggest that expected distractors may no longer be considered distractors by the brain once it has learned that they can safely be ignored.
A smooth muscle-like niche facilitates lung epithelial regeneration
Authors: Moiseenko Alena , Vazquez-Armendariz Ana Ivonne , Chu Xuran , Günther Stefan , Lebrigand Kevin , Kheirollahi Vahid , Herold Susanne , Braun Thomas , Mari Bernard , De Langhe Stijn , Chen Chengshui , Li Xiaokun , Seeger Werner , Zhang Jin-San , Bellusci Saverio , Agha Elie El
Published: March 2019

The mammalian lung is a highly complex organ due to its branched, tree-like structure and diverse cellular composition. Recent efforts using state-of-the-art genetic lineage tracing and single-cell transcriptomics have helped reduce this complexity and delineate the ancestry and fate of various cell subpopulations during organogenesis, homeostasis and repair after injury. However, mesenchymal cell heterogeneity and function in development and disease remain a longstanding issue in the lung field. In this study, we break down smooth muscle heterogeneity into the constituent subpopulations by combiningin vivolineage tracing, single-cell RNA sequencing andin vitroorganoid cultures. We identify a repair-supportive mesenchymal cell (RSMC) population that is distinct from pre-existing airway smooth muscle cells (ASMC) and is critical for regenerating the conducting airway epithelium. Progenitors of RSMCs are intertwined with airway smooth muscle, undergo active WNT signaling, transiently acquire the expression of the smooth muscle marker ACTA2 in response to epithelial injury and are marked by PDGFRα expression. Our data simplify the cellular complexity of the peribronchiolar domain of the adult lung and represent a forward step towards unraveling the role of mesenchymal cell subpopulations in instructing epithelial behavior during repair processes.
A state-dependent mean-field formalism to model different activity states in conductance based networks of spiking neurons
Authors: Capone Cristiano , Volo Matteo di , Romagnoni Alberto , Mattia Maurizio , Destexhe Alain
Published: March 2019

Higher and higher interest has been shown in the recent years to large scale spiking simulations of cerebral neuronal networks, coming both from the presence of high performance computers and increasing details in the experimental observations. In this context it is important to understand how population dynamics are generated by the designed parameters of the networks, that is the question addressed by mean field theories. Despite analytic solutions for the mean field dynamics has already been proposed generally for current based neurons (CUBA), the same for more realistic neural properties, such as conductance based (COBA) network of adaptive exponential neurons (AdEx), a complete analytic model has not been achieved yet. Here, we propose a novel principled approach to map a COBA on a CUBA. Such approach provides a state-dependent approximation capable to reliably predict the firing rate properties of an AdEx neuron with non-instantaneous COBA integration. We also applied our theory to population dynamics, predicting the dynamical properties of the network in very different regimes, such as asynchronous irregular (AI) and synchronous irregular (SI) (slow oscillations, SO).

This results show that a state-dependent approximation can be successfully introduced in order to take into account the subtle effects of COBA integration and to deal with a theory capable to correctly predicts the activity in regimes of alternating states like slow oscillations.
Top-down and bottom-up controls on soil carbon and nitrogen cycling with repeated burning across four ecosystems
Authors: Pellegrini Adam F. A. , Hobbie Sarah E. , Reich Peter B. , Jumpponen Ari , Brookshire E. N. Jack , Caprio Anthony C. , Coetsee Corli , Jackson Robert B.
Published: March 2019

Fires shape the biogeochemistry and functioning of many ecosystems, but fire frequencies are changing across large areas of the globe. Frequent fires can change soil carbon (C) and nitrogen (N) storage through both “top-down” pathways, by altering inputs through shifting plant composition and biomass, and “bottom-up” ones, by altering losses through decomposition and turnover of soil organic matter. However, the relative importance of these different pathways and the degree to which they regulate ecosystem responses to decades of changing fire frequencies is uncertain. Here, we sampled soils and plant communities in four North American and African sites spanning tropical savanna, temperate coniferous savanna, temperate broadleaf savanna, and temperate coniferous forest that each contained multiple plots repeatedly burned for 33-61 years and nearby plots that were protected from fire over the same period. The sites varied markedly in temperature, precipitation, species composition, fire history and soil chemistry; thus they represent a broad test for the generality of fire impacts on biogeochemical cycling. For all four sites, bulk soil C and N by were 25-180% higher in unburned vs. frequently burned plots, with greater soil losses occurring in areas with greater declines in tree cover and biomass inputs into soils. Fire reduced the activity of soil extracellular enzymes that hydrolyze labile C and N from soil organic matter by two- to ten-fold, whereas tree cover was the predominant control on the oxidation of recalcitrant C compounds. C-acquisition enzyme activity tended to decline with decreasing soil N, suggesting that N losses may contribute to limited decomposition, buffering systems against increased losses of soil C with fire. In conclusion, variability in how fire alters soil C and N across ecosystems can be explained partly by fire-driven changes in tree cover and biomass, but the slower turnover of organic matter we observed may offset some of the reduction of C inputs from plants after fire.
Exon-mediated activation of transcription starts
Authors: Fiszbein Ana , Krick Keegan S. , Burge Christopher B.
Published: March 2019

The processing of transcripts from mammalian genes often occurs near in time and space to their transcription. Here we describe a phenomenon we call exon-mediated activation of transcription starts (EMATS) that affects thousands of mammalian genes in which the splicing of internal exons impacts the spectrum of promoters used and expression level of the host gene. We observed that evolutionary gain of new internal exons is associated with gain of new TSSs nearby and increased gene expression. Inhibiting exon splicing reduced transcription from nearby promoters. Conversely, creation of new splice sites and enable splicing of new exons activated transcription from cryptic promoters. The strongest effects were associated with weak promoters located proximal and upstream of efficiently spliced exons. Together, our findings support a model in which splicing factors recruit transcription machinery locally to influence TSS choice, and identify exon gain, loss and regulatory change as major contributors to the evolution of alternative promoters and altered gene expression in mammals.