bluuebunny/crossref_metadata_2025 huggingface dataset:
Alterations in Spanish Language Interpretation During Pediatric Critical Care Family Meetings*
Authors: Sinow Carolyn S. , Corso Irene , Lorenzo Javier , Lawrence Kiley A. , Magnus David C. , Van Cleave Alisa C.
Published: August 2017

Objectives:

To characterize alterations in Spanish language medical interpretation during pediatric critical care family meetings.

Design:

Descriptive, observational study using verbatim transcripts of nine PICU family meetings conducted with in-person, hospital-employed interpreters.

Setting:

A single, university-based, tertiary children’s hospital.

Subjects:

Medical staff, family members, ancillary staff, and interpreters.

Interventions:

None.

Measurements and Main Results:

Interpreted speech was compared with original clinician or family speech using the qualitative research methods of directed content analysis and thematic analysis. Alterations occurred in 56% of interpreted utterances and included additions, omissions, substitutions, editorializations, answering for the patient/clinician, confessions, and patient advocacy. Longer utterances were associated with more alterations.

Conclusions:

To minimize interpreter alterations during family meetings, physicians should speak in short utterances (fewer than 20 words) and ask interpreters to interrupt in order to facilitate accurate interpretation. Because alterations occur, physicians may also regularly attempt to assess the family’s understanding.
Adaptation of the Acute Organ Failure Score for Use in a Medicare Population
Authors: Courtright Katherine R. , Halpern Scott D. , Bayes Brian , Harhay Michael O. , Raneses Eli , Kipnis Patricia , Escobar Gabriel J. , Kerlin Meeta Prasad
Published: August 2017

Objectives:

Without widely available physiologic data, a need exists for ICU risk adjustment methods that can be applied to administrative data. We sought to expand the generalizability of the Acute Organ Failure Score by adapting it to a commonly used administrative database.

Design:

Retrospective cohort study.

Setting:

One hundred fifty-one hospitals in Pennsylvania.

Patients:

A total of 90,733 ICU admissions among 77,040 unique patients between January 1, 2009, and December 1, 2009, in the Medicare Provider Analysis and Review database.

Measurements and Main Results:

We used multivariable logistic regression on a random split cohort to predict 30-day mortality, and to examine the impact of using different comorbidity measures in the model and adding historical claims data. Overall 30-day mortality was 17.6%. In the validation cohort, using the original Acute Organ Failure Score model’s β coefficients resulted in poor discrimination (C-statistic, 0.644; 95% CI, 0.639–0.649). The model’s C-statistic improved to 0.721 (95% CI, 0.711–0.730) when the Medicare cohort was used to recalibrate the β coefficients. Model discrimination improved further when comorbidity was expressed as the COmorbidity Point Score 2 (C-statistic, 0.737; 95% CI, 0.728–0.747; p < 0.001) or the Elixhauser index (C-statistic, 0.748; 95% CI, 0.739–0.757) instead of the Charlson index. Adding historical claims data increased the number of comorbidities identified, but did not enhance model performance.

Conclusions:

Modification of the Acute Organ Failure Score resulted in good model discrimination among a diverse population regardless of comorbidity measure used. This study expands the use of the Acute Organ Failure Score for risk adjustment in ICU research and outcomes reporting using standard administrative data.
P-407-induced Mouse Model of Dose-controlled Hyperlipidemia and Atherosclerosis: 25 Years Later
Authors: Johnston Thomas P. , Korolenko Tatyana A. , Sahebkar Amirhossein
Published: August 2017

The poloxamer 407 (P-407) nongenetic, nondiet–induced mouse model of dose-controlled hyperlipidemia and atherosclerosis was first introduced in 1992. Dyslipidemia is produced in C57BL/6 mice of either sex after intraperitoneal administration of P-407 that is a polyether-based nonionic surface active agent. Aortic atherosclerotic lesions begin to form after 1 month of repeated P-407 administration and obtain maximum size, numerical density, and human-like pathological features by 4 months. Our laboratory published a review of this model in 2004, although an update would seem both appropriate and timely based on new findings since 2004. Using P-407–treated mice, we have investigated the effect that hyperlipidemia has on the activity of several classes of proteases in the heart, liver, and serum; extensively characterized lipoprotein fractions and subfractions associated with atherogenic plasma lipids; investigated whether several key vascular cell adhesion molecules were perturbed; and determined whether the biological activity of 2 peroxisome proliferator–activated receptors was modulated both in vitro and in vivo. Based on our findings since 2004, as well as those before 2004 (1992–2004), we would strongly suggest that the P-407–induced hyperlipidemic mouse model represents a convenient, inexpensive, and well-documented alternative mouse model with which to study cardiovascular heart disease arising from dyslipidemia and atherosclerosis.
Sexual function after prolapse repair
Authors: Shatkin-Margolis Abigail , Pauls Rachel N.
Published: August 2017

Purpose of review

The purpose of this review is to summarize available literature (from the last 18 months) assessing sexual function following pelvic reconstructive surgery for pelvic organ prolapse (POP). We include vaginal native tissue repair, abdominal/laparoscopic sacrocolpopexy, transvaginal mesh repair, and obliterative procedures. The goal is to assist providers in counseling patients and to identify areas needed for further research.

Recent findings

When compared with pessary management, women who undergo POP surgical repair achieve their sexual function goals more often. In particular, vaginal native tissue repair has consistently been shown to improve sexual function. Furthermore, there does not appear to be a difference between uterosacral ligament suspension and sacrospinous ligament suspension (with or without uterine conservation) with regard to postoperative sexual function. Although less robust, literature evaluating the impact of abdominal/robotic sacrocolpopexy also supports benefit from surgical correction. However, data are conflicted with regard to transvaginal mesh repair and suggest the potential for a negative impact.

POP often affects a woman's sexual function. Following surgical repair, most patients experience improvements in their sexual response. However, surgical approaches involving abdominal or transvaginal mesh may result in a decline in sexual function and worsening dyspareunia.
OCRIPLASMIN FOR VITREOMACULAR TRACTION: LOOKING OUTSIDE THE MACULA
Authors: Cereda Matteo G. , Preziosa Chiara , D'Agostino Isabella , Cozzi Mariano , Bottoni Ferdinando , Pellegrini Marco , Giani Andrea , Staurenghi Giovanni
Published: August 2017

Purpose:

To evaluate baseline features and morphologic changes of vitreoretinal adhesion and outer retinal layers outside the macula after intravitreal ocriplasmin injection. To study the relation between vitreous detachment and attenuation of retinal outer segments signal.

Methods:

Retrospective cases series of 15 eyes. Each eye was scanned with the 55° wide-field optical coherence tomography lens in 6 different locations, three horizontal B-scan (central, temporal, and nasal) and three vertical B-scan (central, superior, and inferior) at baseline, 1 week, 1 month, 3 months, and 6 months after injection.

Results:

After ocriplasmin injection, vitreomacular traction (VMT) resolved in 12 patients (80%), 3 of them presenting a complete posterior vitreous detachment. Eight patients (53%) showed a panretinal attenuation of photoreceptors outer segment signal, 7 with VMT resolution and 1 with non-posterior vitreous detachment and no VMT resolution. In three patients after VMT resolution the attenuation involved also areas with no posterior vitreous detachment. The attenuation resolved during follow-up in 7/8 eyes (87.5%).

Conclusion:

Intravitreal ocriplasmin injection induced resolution of VMT in most cases and more rarely a release of vitreopapillary adhesion and a complete posterior vitreous detachment. An acute panretinopathy was visible in more than half of the patients and was not related to vitreous detachment.
New Graft Insertion Device for Descemet Stripping Automated Endothelial Keratoplasty
Authors: Soma Takeshi , Koh Shizuka , Maeda Naoyuki , Mitomo Kikuo , Quantock Andrew J. , Nishida Kohji
Published: August 2017

Purpose:

Corneal endothelial dysfunction is a major indication for corneal graft surgery worldwide, and although surgical intervention through a range of posterior lamellar surgeries has proven to be hugely beneficial, challenges remain. This is especially so where the anterior chamber is relatively shallow, as is often the case in the Asian population, though not exclusively so. In this study, we introduce a new insertion device to deliver endothelial graft tissue for Descemet stripping automated endothelial keratoplasty (DSAEK).

Methods:

A new surgical tool was designed and manufactured so as to enable a 1-step insertion of corneal graft tissue into the anterior chamber based on a pressure–flow concept, rather than the a pull-through one. This was tested ex vivo to assess endothelial cell damage, and then performed in 12 first-in-human surgeries.

Results:

Precut DSAEK lenticules implanted in donor corneas ex vivo through the new technique showed that less endothelial cell damage occurs compared with a pull-through technique. Grafts were successful in all patients receiving the new surgery, with no cases of primary graft failure.

Conclusions:

The newly developed DSAEK inserter is a simple and useful tool for endothelial graft delivery, lessening intraoperative mechanical stress on the graft tissue.
Short-term Results of Trabeculectomy Using Adjunctive Intracameral Bevacizumab Versus Mitomycin C: A Randomized Controlled Trial
Authors: Vahedian Zakieh , Mafi Mostafa , Fakhraie Ghasem , Zarei Reza , Eslami Yadollah , Ghadimi Hadi , Mohebbi Masomeh
Published: August 2017

Purpose:

To compare the outcome of trabeculectomy using adjunctive intracameral bevacizumab versus intraoperative mitomycin C (MMC).

Materials and Methods:

In this double-blind, randomized clinical trial 87 eyes of 87 patients with primary open-angle or pseudoexfoliation glaucoma were assigned to each treatment group (44 cases received 1.25 mg intracameral bevacizumab at the end of operation and in 43 cases MMC was applied during surgery). Success was defined as intraocular pressure (IOP) between 6 and 21 mm Hg and at least 30% IOP drop with (qualified) or without (complete) glaucoma medications without additional glaucoma surgery.

Results:

The follow-up time was 17.12±2.58 months in the bevacizumab group and 17.23±2.42 months in the MMC group (P=0.845). The preoperative IOP was 29.17±3.94 and 28.8±4.08 mm Hg in the bevacizumab and MMC groups, respectively (P=0.689). Last visit IOP was 17.41±3.11 mm Hg in the bevacizumab group and 15.34±3.62 mm Hg in the MMC group (P<0.009). Compared with baseline, IOP drop at last visit was 11.76±5.51 and 13.43±5.92 in the bevacizumab and MMC groups, respectively (P=0.207). At last visit, complete success was achieved in 25 cases (61%) of bevacizumab group and 23 cases (66%) of MMC group (P=0.669). Early filtering bleb leak was more prevalent in bevacizumab group (29% vs. 11%).

Conclusions:

A single 1.25 mg dose of intracameral bevacizumab improves the success of trabeculectomy comparable with MMC; however, it increases the risk of early filtering bleb leakage.
Impact of Birth HIV-PCR Testing on the Uptake of Follow-up Early Infant Diagnosis Services in Cape Town, South Africa
Authors: Dunning Lorna , Kroon Max , Fourie Lezanne , Ciaranello Andrea , Myer Landon
Published: August 2017

Introduction:

Polymerase chain reaction testing at birth (“birth-testing”) is suggested by new World Health Organization guidelines for rapid diagnosis of infants infected with HIV in utero. However, there are few data on the implementation of this approach in sub-Saharan Africa, and whether birth testing affects uptake of subsequent routine early infant diagnosis (EID) testing at 6–10 weeks of age is unknown.

Methods:

We reviewed 575 consecutive infants undergoing targeted high-risk birth testing in Cape Town, South Africa, and matched those testing HIV negative at birth (n = 551) to HIV-exposed infants who did not receive birth testing (n = 551). Maternal and infant clinical and demographic data, including EID testing uptake, were abstracted from routine records.

Results:

Overall, 3.8% of all birth tests conducted were positive while later EID testing positivity rates were 0.5% for those infants testing HIV negative at birth and 0.4% for those without birth testing. Infants who underwent birth testing were less likely to present for later EID compared with those without a birth test (73% vs. 85%; P < 0.001). This difference persisted after adjusting for maternal and infant characteristics (adjusted odds ratio, 0.60; 95% confidence interval: 0.41–0.86) and across demographic and clinical subgroups. Infants undergoing birth testing also presented for later EID at a significantly older age (mean age, 60 vs. 50 days; P < 0.001).

Conclusions:

While the yield of targeted high-risk birth testing in this setting appears high, neonates testing HIV negative at birth may be less likely to present for subsequent EID testing. For birth testing implementation to contribute to overall EID program goals, structured interventions are required to support follow-up EID services after negative birth test results.
Probiotics for Modification of the Incidence or Severity of Respiratory Tract Infections
Authors: Robinson Joan L.
Published: August 2017

There is increasing interest in probiotics for therapy and prevention of infectious diseases. There are no published trials of probiotics as therapy for respiratory tract infections (RTIs) in children or adults. There is low quality, inconsistent evidence for the efficacy of probiotics for prevention of RTIs or ventilator-associated pneumonia or for modification of the severity of RTIs.
Better Completion of Pediatric Latent Tuberculosis Treatment Using 4 Months of Rifampin in a US-based Tuberculosis Clinic
Authors: Gaensbauer James , Aiona Kaylynn , Haas Michelle , Reves Randall , Young Janine , Belknap Robert
Published: August 2017

Background:

Children less than 5 years of age have the highest age-specific rate of progression from latent tuberculosis infection (LTBI) to active disease. Therefore, regimens for treatment of pediatric LTBI must be not only efficacious but practical enough to overcome the unique childhood barriers to regimen adherence. Since 2012, a 4-month regimen of daily rifampin (4R) has been the standard recommendation for pediatric LTBI at the Denver Metro Tuberculosis Clinic.

Methods:

Using univariate and multivariate analyses, we compared treatment completion rates between 4R and 9-month isoniazid (9H) regimens for all pediatric patients treated for LTBI at the Denver Metro Tuberculosis Clinic between January 1, 2006, and December 31, 2015, and assessed the influence of clinical and demographic characteristics on successful completion of the 2 regimens.

Results:

There were 395 children in the 4R cohort and 779 in the 9H cohort. Completion rates overall were significantly higher for 4R than 9H (83.5% vs. 68.8%, P < 0.001). Drug toxicity leading to treatment noncompletion was low in both groups (1.5% in 4R and 0.7% in 9H, P = 0.23), and no patient progressed to active tuberculosis in either cohort. The 9H cohort was more likely to fail treatment completion because of barriers potentially related to the longer duration of treatment such as relocation or loss to follow-up.

Conclusions:

Pediatric patients were significantly more likely to complete LTBI treatment using a 4R than with a 9-month isoniazid regimen. Better completion rates of 4R may increase efficacy of tuberculosis prevention and decrease demand on public health resources.
Five-year Study of Viral Etiology and Features of Febrile Respiratory Tract Infections With Prolonged Fever in Japanese Pediatric Outpatients
Authors: Hara Michimaru , Takao Shinichi
Published: August 2017

Over 5 years, we prospectively collected nasopharyngeal aspirate samples from pediatric outpatients with prolonged fever (≥5 days, ≥38.0°C). Real-time polymerase chain reaction assays identifying 13 different respiratory viruses and Mycoplasma pneumoniae were performed on the test samples. Real-time polymerase chain reaction assays identified at least 1 pathogen in 273 (75.4%) of the 362 samples assessed (239 single and 34 multiple infections).
Lyme Borreliosis in Children: A Tertiary Referral Hospital–Based Retrospective Analysis
Authors: Nassar-Sheikh Rashid Amara , Boele van Hensbroek Michael , Kolader Marion , Hovius Joppe W. , Pajkrt Dasja
Published: August 2017

Lyme borreliosis (LB) is an endemic disease in adults in Western countries. Although children may also be infected, pediatric studies on LB are scarce. This study aims to estimate the incidence of LB among children with a clinical suspicion for Lyme in a tertiary referral center in the Netherlands. Patient chart data on medical history, clinical signs and symptoms, diagnostic test results and diagnoses were collected using standardized case record forms. Patients were categorized based on clinical and laboratory findings using a modified, previously published classification system. We included 325 children, with a median age of 11.9 years, of whom 61.8% were female. LB was diagnosed in 38 of the referred children (11.7%). However, of the 85 patients who were specifically referred to the Lyme clinic, 28 (32.9%) were diagnosed with LB. Of the specifically referred Lyme-positive patients, 11 (39.3%) had a definitive LB diagnosis. Twelve children had a posttreatment LB syndrome. In line with previous reports in adults, only a small proportion of children referred with a suspicion of LB were diagnosed with definite or probable LB, which illustrates the difficulty in diagnosing LB by the general practitioner or pediatrician in a district hospital.
Ultrasonographic Assessment of Bladder Volumes in Children Undergoing Penile Surgery: Does the Type of Anesthesia Matter?
Authors: Ekstein Margaret , Bar-Yosef Yuval , Ben-Chaim Jacob , Flaishon Ron , Weinbroum Avi A.
Published: August 2017

Background:

There are scant data reporting postoperative ultrasonographically measured bladder volumes in children undergoing penile surgery.

Study Question:

We studied the effect of various anesthesia techniques on return of micturition after penile surgery in children, using ultrasonographically measured bladder volumes.

Data Sources:

Ultrasonographically measured postvoiding residual bladder volumes indexed to age-appropriate capacity, and time elapsed between the end of surgery and spontaneous voiding after pediatric circumcision, distal hypospadias repair, or repair of urethrocutaneous fistula, were studied.

Study Design:

Children between 4 months and 12 years were randomized to caudal block, intravenous (IV) fentanyl or penile block, in association with inhaled general anesthesia. Bladder volumes were measured before surgery and immediately after voiding for the first time. Time to first postsurgery void was also recorded.

Results:

Thirty-one children completed all assessments; 12 underwent caudal block, 9 IV fentanyl anesthesia, and 7 were given penile block. The mean first postvoid bladder residual volumes were highest in the caudal and lowest in the penile block children (27.5 vs. 17.3 mL, P = 0.003). The time elapsing between the end of surgery and first voiding was the longest in the fentanyl group compared with caudal and penile blocks (232, 178, 150 minutes, respectively, P = 0.02).

Conclusions:

None of the anesthetic techniques provoked postoperative urinary retention after minor penile surgery in children. The penile block appears superior to caudal block or to IV fentanyl–based anesthesia with regard to postoperative recovery of normal micturition.
Neighborhood Health Care Access and Sexually Transmitted Infections Among Women in the Southern United States: A Cross-Sectional Multilevel Analysis
Authors: Haley Danielle F. , Edmonds Andrew , Belenky Nadya , Hickson DeMarc A. , Ramirez Catalina , Wingood Gina M. , Bolivar Hector , Golub Elizabeth , Adimora Adaora A.
Published: August 2017

Introduction

The United States has experienced an increase in reportable sexually transmitted infections (STIs) while simultaneously experiencing a decline in safety net services for STI testing and treatment. This multilevel study assessed relationships between neighborhood-level access to health care and STIs among a predominantly Human Immunodeficiency Virus (HIV)-seropositive cohort of women living in the south.

Methods

This cross-sectional multilevel analysis included baseline data from HIV-seropositive and HIV-seronegative women enrolled in the Women’s Interagency HIV Study sites in Alabama, Florida, Georgia, Mississippi, and North Carolina between 2013 and 2015 (N = 666). Administrative data (eg, United States Census) described health care access (eg, percentage of residents with a primary care provider, percentage of residents with health insurance) in the census tracts where women lived. Sexually transmitted infections (chlamydia, gonorrhea, trichomoniasis, or early syphilis) were diagnosed using laboratory testing. Generalized estimating equations were used to determine relationships between tract-level characteristics and STIs. Analyses were conducted using SAS 9.4.

Results

Seventy percent of participants were HIV-seropositive. Eleven percent of participants had an STI. A 4-unit increase in the percentage of residents with a primary care provider was associated with 39% lower STI risk (risk ratio, 0.61, 95% confidence interval, 0.38–0.99). The percentage of tract residents with health insurance was not associated with STIs (risk ratio, 0.98, 95% confidence interval, 0.91–1.05). Relationships did not vary by HIV status.

Conclusions

Greater neighborhood health care access was associated with fewer STIs. Research should establish the causality of this relationship and pathways through which neighborhood health care access influences STIs. Structural interventions and programs increasing linkage to care may reduce STIs.
Qualitative Comparison Between Carrier-based and Classical Tissue Microarrays
Authors: Lisenko Katharina , Leichsenring Jonas , Zgorzelski Christiane , Longuespée Rémi , Casadonte Rita , Harms Alexander , Kazdal Daniel , Stenzinger Albrecht , Warth Arne , Kriegsmann Mark
Published: August 2017

Tissue microarrays (TMAs) are commonly used in biomarker research. To enhance the efficacy of TMAs and to avoid floating or folding of tissue cores, various improvements such as the application of carriers and melting techniques have been proposed. Compared with classical TMAs (cTMAs), carrier-based TMAs (cbTMAs) have been shown to have several advantages including sample handling and sectioning. Up to now, little is known about the efficacy and quality of cbTMAs compared with cTMAs. Thus, we set out to compare both types systematically. We constructed 5 spleen-based TMAs and 5 cTMAs with 10×10 different tissue types each. The total number of available cores, the number of folded cores, and the total core area was measured and evaluated by digital pathology. About 2% of cores got lost due to floating in both, cbTMAs and cTMAs, respectively. The remaining cores showed significant differences with regard to core integrity as about 1% of cbTMA cores and 9% of cTMA cores were folded (P<0.01). Folding or rolling was associated with specific tissue types. The size of the cores was smaller and less variable in cbTMAs (0.86±0.06 mm2) compared with cTMAs (0.97±0.14 mm2). The application of cbTMAs is an easy, inexpensive, and effective way to improve TMA-based research.
New Mechanisms of mTOR Pathway Activation in KIT-mutant Malignant GISTs
Authors: Lasota Jerzy , Kowalik Artur , Felisiak-Golabek Anna , Zięba Sebastian , Wang Zeng-Feng , Miettinen Markku
Published: August 2017

A great majority of gastrointestinal stromal tumors (GISTs) are primarily driven by gain-of-function KIT receptor tyrosine kinase mutations that subsequently lead to activation of phosphatidiylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway, a downstream effector of KIT signaling. KIT tyrosine kinase inhibitor, imatinib mesylate, has been successfully used for the treatment of primary, advanced, and disseminated GISTs. Recently, activation of mTOR pathway independent of KIT signaling was demonstrated in imatinib mesylate naïve malignant GISTs and treatment-resistant metastatic tumors. This activation was attributed to oncogenic mutations in PIK3CA encoding PI3K 110α subunit, or to the inactivation of PTEN tumor suppressor, a potent mTOR negative regulator. In this study, mTOR pathway genes were evaluated in 14 imatinib mesylate naïve, KIT-mutant, malignant small intestinal GISTs using next-generation sequencing. Mutations were detected in 3 (21%) of 14 analyzed tumors: (1) c.3200A>T substitution in PIK3CB encoding PI3K 110β subunit, (2) c.1040A>G substitution in tuberous sclerosis complex (TSC2) encoding tuberin, mTOR down-regulator (3) c.6625C>G substitution in mTOR. At the protein level, these changes were predicted to cause, respectively, PIK3CB p.D1067V, TSC2 p.K347R, and mTOR p.L2209V mutations. Previously reported “in vitro” experiments with mouse 3T3 fibroblasts demonstrated oncogenic potential of PIK3CB p.D1067V and mTOR p.L2209V mutants; whereas, PolyPhen-2 software analysis predicted TSC2 p.K347R mutation to likely have a damaging impact on tuberin function. The results of this and previous studies indicate diversity of genetic changes leading to activation of PI3K-AKT-TSC-mTOR pathway in malignant GISTs. Extensive genotyping of the genes involved in mTOR pathway demonstrates common alterations that need to be considered in targeted treatment.
Utility of Stathmin-1 as a Novel Marker in Evaluating Anal Intraepithelial Neoplasia (AIN)
Authors: Hissong Erika , Cimic Adela , Leeman Annemiek , Pirog Edyta C.
Published: August 2017

The aim of this study is to determine whether immunohistochemistry for Stathmin-1 enhances diagnostic accuracy of anal dysplasia. The study included 40 biopsies with diagnosis of benign anal transitional zone (n=10), low-grade anal intraepithelial neoplasia (AIN) (AIN1, n=10), and high-grade AIN (AIN2, n=10, AIN3, n=10). The cases were selected to represent classic features. Immunohistochemistry for Stathmin-1, p16, and Ki-67 was performed and assessed for distribution within epithelial thickness. Stathmin-1 was expressed only in the basal layer of benign anal epithelium. Similar pattern of distribution was seen in all low-grade AIN cases (100%). In total, 40% of AIN2 showed Stathmin-1 staining pattern similar to AIN1. The other 60% of cases showed staining extending into the middle third of the epithelial thickness. Of AIN3 cases, 20% showed staining confined to the lower third epithelium, 20% showed staining extending to the middle third, and 60% showed staining extending into the upper third epithelium. The pattern of stain distribution suggested that staining extending above the lower one-third of the epithelial thickness discriminates between low-grade and high-grade AIN. With this cutoff, the sensitivity for the diagnosis of high-grade AIN was 70%, specificity was 100%, positive predictive value equaled 100%, and negative predictive value equaled 77%. P16INK4a showed 100% sensitivity for AIN2 and AIN3, whereas Ki-67 had 100% sensitivity for any AIN grade. In conclusion, Stathmin-1 has excellent specificity for the diagnosis of high-grade AIN; however, Stathmin-1 alone may not be sufficiently sensitive. Use in conjunction with other sensitive markers, such as p16 or Ki-67 may be considered.
A Splenic IgG4+ Sclerosing Angiomatoid Nodular Transformation (SANT) Treated by Hemisplenectomy: A Radiologic, Histochemical, and Immunohistochemical Study
Authors: Gaeta Raffaele , Donati Francescamaria , Kauffmann Emanuele F. , Campani Daniela
Published: August 2017

Introduction:

Sclerosing angiomatoid nodular transformation (SANT) is a rare benign lesion of unknown origin for which total splenectomy is the standard treatment.

Case Presentation:

A 54-year-old man with a history of recurrent pancreatitis, bicuspid aortic valve, and aortic dissection underwent abdominal ultrasound, Computed tomography and magnetic resonance imaging, which revealed a 6-cm hypoechoic splenic mass diagnosed as cavernous hemangioma. Owing to his relevant past history, he was considered eligible for emisplenectomy and not for total excision, which is associated with long-term risks, especially infections.

Results:

Histologic examination revealed several nodules of varying size separated by sclerotic stroma with scattered inflammatory cells rich in IgG4+ in a background of splenic red pulp. Immunohistochemical stains showed a characteristic panel for CD34, CD31, and CD8.

Conclusions:

The diagnosis of SANT should be considered in any patient presenting with a splenic lesion containing an angiomatoid or inflammatory component. The only method able to establish a correct diagnosis is histologic and immunohistochemical evaluation. Complete splenectomy is generally considered the best approach. However, if the patient is at high risk of infection and localization of the lesion allows for selective devascularization of the affected part of the spleen, the lesion could be removed by hemisplenectomy. In some patients SANT is related to high blood levels of IgG4. Thus, corticosteroids might be useful for treating IgG4+ SANT and for preventing other IgG4-related diseases.
The Molecular Landscape of Noninvasive Follicular Thyroid Neoplasm With Papillary-like Nuclear Features (NIFTP): A Literature Review
Authors: Basolo Fulvio , Macerola Elisabetta , Ugolini Clara , Poller David N. , Baloch Zubair
Published: August 2017

The encapsulated and noninvasive follicular variant of papillary thyroid carcinoma has been recently reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). These tumors demonstrate indolent behavior. This change in nomenclature will have great clinical impact by avoiding overtreatment of patients with NIFTP lesions who in the past were diagnosed with thyroid carcinoma and typically received completion thyroidectomy followed by radioactive iodine ablation. The pathologic diagnosis of NIFTP requires surgical removal of the thyroid lesion or the lobe harboring it, and thorough sampling of the complete interface between the tumor capsule and the thyroid parenchyma, to exclude foci of invasion. From a cytologic point of view, the unequivocal differential diagnosis between NIFTP and infiltrative follicular variant of papillary thyroid carcinoma in fine-needle aspiration is close to impossible based on cellular and architectural features. Therefore, use of adjunct molecular testing on fine-needle aspiration specimens may be essential for the preoperative diagnosis of low-risk tumors such as NIFTP for appropriate patient management. This review discusses and summarizes the existing known literature on molecular characteristics of NIFTP tumors, so far reported, including cases retrospectively classified or prospectively diagnosed as NIFTP. Brief reference is also made to new and promising approaches applicable to the diagnosis of this tumor.
Fluid Bolus Over 15–20 Versus 5–10 Minutes Each in the First Hour of Resuscitation in Children With Septic Shock: A Randomized Controlled Trial*
Authors: Sankar Jhuma , Ismail Javed , Sankar M. Jeeva , C.P. Suresh , Meena Rameshwar S.
Published: August 2017

Objectives:

To compare the effect of administration of 40–60 mL/kg of fluids as fluid boluses in aliquots of 20 mL/kg each over 15–20 minutes with that over 5–10 minutes each on the composite outcome of need for mechanical ventilation and/or impaired oxygenation—increase in oxygenation index by 5 from baseline in the initial 6 and 24 hours in children with septic shock.

Design:

Randomized controlled trial.

Setting:

Pediatric emergency and ICU of a tertiary care institute.

Patients:

Children (< 18 yr old) with septic shock.

Interventions:

We randomly assigned participants to 15–20 minutes bolus (study group) or 5–10 minutes bolus groups (control group).

Measurements and Main Results:

We assessed the composite outcomes in the initial 6 and 24 hours after fluid resuscitation in both groups. We performed logistic regression to evaluate factors associated with need for ventilation in the first hour. Data were analyzed using Stata 11.5. Of the 96 children, 45 were randomly assigned to “15–20 minutes group” and 51 to “5–10 minutes group.” Key baseline characteristics were not different between the groups. When compared with 5–10 minutes group, fewer children in 15–20 minutes group needed mechanical ventilation or had an increase in oxygenation index in the first 6 hours (36% vs 57%; relative risk, 0.62; 95% CI, 0.39–0.99) and 24 hours (43% vs 68%; relative risk, 0.63; 95% CI, 0.42–0.93) after fluid resuscitation. We did not find any difference in secondary outcomes such as death (1.2; 0.70–2.03), length of stay (mean difference: 0.52; –1.72 to 2.7), or resolution of shock (0.98; 0.63–1.53).

Conclusion:

Children receiving fluid boluses over 5–10 minutes each had a higher risk of intubation than those receiving boluses over 15–20 minutes each. Notwithstanding the lack of difference in risk of mortality and the possibility that a lower threshold of intubation and mechanical ventilation was used in the presence of fluid overload, our results raise concerns on the current recommendation of administering boluses over 5–10 minutes each in children with septic shock.
Point-of-Care Ultrasound Identification of an Abdominal Hernia
Authors: Alfonzo Michael , von Reinhart Anna , Riera Antonio
Published: August 2017

Pediatric emergency medicine physicians may be able to use point-of-care ultrasound (POCUS) as a tool to evaluate abdominal wall masses. We present a case of a 2-month-old infant with a lower abdominal mass identified as a hernia sac by POCUS. It was initially thought to represent a Spigelian-type abdominal wall hernia but subsequently determined to be an unusual presentation of an inguinal hernia with testicular entrapment. We review each of these diagnoses in addition to relevant POCUS findings.
Orphanhood and Self-Esteem: An 18-Year Longitudinal Study From an HIV-Affected Area in Tanzania
Authors: De Weerdt Joachim , Beegle Kathleen , Dercon Stefan
Published: August 2017

Background:

The HIV epidemic exacerbated the prevalence of prime-aged adult death in many parts of sub-Saharan Africa, resulting in increased rates of orphanhood. Little is known about whether this will coincide with adverse psychosocial well-being in adulthood for those who were orphaned at childhood.

Methods:

We studied a cohort of 1108 children from Kagera, a region of Tanzania that was heavily affected by HIV early in the epidemic. During the baseline data collection in 1991–1994, these children were aged 0–16 years and had both parents alive. We followed them roughly 16–19 years later in 2010, by which time 531 children (36%) had lost either one or both parents before their 19th birthday. We compared the 2010 10-item Rosenberg Self-Esteem Scale (RSES) score between children who lost a parent before the age of 19 and those who did not. We used the baseline data to control for preorphanhood confounders. This is important because we find that children who will lose their fathers in the future before age 19 came from somewhat lower socioeconomic backgrounds.

Results:

We found no correlation between maternal death and self-esteem measured through RSES. Paternal death was strongly correlated with lower levels of self-esteem (0.2 SDs lower RSES 95% confidence interval: 0.059 to 0.348), and the correlation was stronger when the death occurred during the child's teenage years. These effects are a net of socioeconomic differences that existed before the orphanhood event.

Conclusions:

Our study supports the further development and piloting of programs that address psychosocial problems of orphans.
Feasibility, Acceptability, and Adherence with Short-Term HIV Preexposure Prophylaxis in Female Sexual Partners of Migrant Miners in Mozambique
Authors: Lahuerta Maria , Zerbe Allison , Baggaley Rachel , Falcao Joana , Ahoua Laurence , DiMattei Pietro , Morales Fernando , Ramiro Isaias , El-Sadr Wafaa M.
Published: August 2017

Background:

Preexposure prophylaxis (PrEP) offers protection from HIV acquisition if taken as prescribed. We evaluated the feasibility, acceptability, and adherence with short-term PrEP among female sexual partners of migrant miners in Mozambique.

Methods:

HIV-negative female sexual partners of migrant miners were offered daily tenofovir/emtricitabine (TDF/FTC) for 6 weeks concurrent with miners' return home. Study visits occurred at baseline, week 4, 6, and 8. Dried blood spots (DBSs) were collected at week 4 and 6.

Results:

Seventy-four women (median age: 42 years) were enrolled, 95% reported having 1 sexual partner and 80% reported never or rarely using condoms. At baseline, 41% had never tested for HIV; 65% were unaware of partners' HIV status. Of all women, 72 (97%) initiated PrEP, 7 (9%) discontinued PrEP before week 6; only 1 due to adverse events. Missed doses in the last week were self-reported by 8% and 3% of women at week 4 and 6, respectively. Of 66 (89%) women with DBS at week 4, 79% had detectable tenofovir diphosphate (TFV-DP) and 44% had levels consistent with ≥4 pills/wk (≥700 fmol/punch). Of 63 (88%) women with DBS at week 6, 76% had detectable TFV-DP and 42% had levels consistent with ≥4 pills/wk.

Conclusions:

In this first study assessing the use of short-term PrEP, a high percent of female partners of migrant workers initiated PrEP and had detectable DP levels during follow-up. Further efforts are needed to enhance adherence to ensure protection from HIV acquisition. Short-term PrEP offers promise for populations who are at high risk of HIV during specific periods of time.
Controllable biomimetic birdsong
Authors: Mukherjee Aryesh , Mandre Shreyas , Mahadevan L.
Published: August 2017

Birdsong is the product of the controlled generation of sound embodied in a neuromotor system. From a biophysical perspective, a natural question is that of the difficulty of producing birdsong. To address this, we built a biomimetic syrinx consisting of a stretched simple rubber tube through which air is blown, subject to localized mechanical squeezing with a linear actuator. A large static tension on the tube and small dynamic variations in the localized squeezing allow us to control transitions between three states: a quiescent state, a periodic state and a solitary wave state. The static load brings the system close to threshold for spontaneous oscillations, while small dynamic loads allow for rapid transitions between the states. We use this to mimic a variety of birdsongs via the slow–fast modulated nonlinear dynamics of the physical substrate, the syrinx, regulated by a simple controller. Finally, a minimal mathematical model of the system inspired by our observations allows us to address the problem of song mimicry in an excitable oscillator for tonal songs.
Structural coloured feathers of mallards act by simple multilayer photonics
Authors: Stavenga Doekele G. , van der Kooi Casper J. , Wilts Bodo D.
Published: August 2017

The blue colours of the speculum of the mallard (Anas platyrhynchos), both male and female, and the green head feathers of the male arise from light interacting with stacks of melanosomes residing in the feather barbules. Here, we show that the iridescent colours can be quantitatively explained with an optical multilayer model by using a position-dependent effective refractive index, which results from the varying ratio of melanin and keratin. Reflectance spectra obtained by multilayer modelling and three-dimensional finite-difference time-domain calculations were virtually identical. The spectral properties of the barbules' photonic structures are sensitive to variations in the multilayer period and the cortex thickness, but they are surprisingly robust to variations in the spatial parameters of the barbules' melanosome stacks. The blue and green reflectance spectra of the structural-coloured feathers correspond with the sensitivity spectra of the short- and middle-wavelength-sensitive photoreceptors, indicating their biological significance for intraspecific signalling.
Genome-wide characterization of Phytophthora infestans metabolism: a systems biology approach
Authors: Rodenburg Sander Y.A. , Seidl Michael F. , de Ridder Dick , Govers Francine
Published: August 2017

Genome-scale metabolic models (GEMs) provide a functional view of the complex network of biochemical reactions in the living cell. Initially mainly applied to reconstruct the metabolism of model organisms, the availability of increasingly sophisticated reconstruction methods and more extensive biochemical databases now make it possible to reconstruct GEMs for less characterized organisms as well, and have the potential to unravel the metabolism in pathogen-host systems. Here we present a GEM for the oomycete plant pathogen Phytophthora infestans as a first step towards an integrative model with its host. We predict the biochemical reactions in different cellular compartments and investigate the gene-protein-reaction associations in this model to get an impression of the biochemical capabilities of P. infestans. Furthermore, we generate life stage-specific models to place the transcriptomic changes of genes encoding metabolic enzymes into a functional context. In sporangia and zoospores there is an overall downregulation, most strikingly reflected in the fatty acid biosynthesis pathway. To investigate the robustness of the GEM, we simulate gene deletions to predict which enzymes are essential for in vitro growth. While there is room for improvement, this first model is an essential step towards an understanding of P. infestans and its interactions with plants as a system, which will help to formulate new hypotheses on infection mechanisms and disease prevention.
Navigating infection risk during oviposition and larval foraging in a holometabolous insect
Authors: Siva-Jothy Jonathon A. , Monteith Katy M. , Vale Pedro F.
Published: August 2017

Deciding where to eat and raise offspring carries important fitness consequences for all animals, especially if foraging, feeding and reproduction increase the risk of exposure to pathogens. In insects with complete metamorphosis, foraging occurs mainly during the larval stage, while oviposition decisions are taken by adult-stage females. Selection for infection avoidance behaviours may therefore be developmentally uncoupled. Using a combination of experimental infections and behavioural choice assays, here we tested ifDrosophila melanogasterfruit flies avoid potentially infectious environments at distinct developmental stages. When given conspecific fly carcasses as a food source, larval-stage flies did not discriminate between carcasses that were clean or infected with the pathogenic Drosophila C Virus (DCV), even though scavenging was a viable route of DCV transmission. Adult females however, discriminated between different oviposition sites, laying more eggs near a clean rather than an infectious carcass if they were healthy; DCV-infected females did not discriminate between the two environments. While potentially risky, laying eggs near potentially infectious carcasses was always preferred to sites containing only fly medium. Our findings suggest that infection avoidance can play an important role in how mothers provision their offspring, and underline the need to consider infection avoidance behaviours at multiple life-stages.
Genome-reconstruction for eukaryotes from complex natural microbial communities
Authors: West Patrick T. , Probst Alexander J. , Grigoriev Igor V. , Thomas Brian C. , Banfield Jillian F.
Published: August 2017

Microbial eukaryotes are integral components of natural microbial communities and their inclusion is critical for many ecosystem studies yet the majority of published metagenome analyses ignore eukaryotes. In order to include eukaryotes in environmental studies we propose a method to recover eukaryotic genomes from complex metagenomic samples. A key step for genome recovery is separation of eukaryotic and prokaryotic fragments. We developed a kmer-based strategy, EukRep, for eukaryotic sequence identification and applied it to environmental samples to show that it enables genome recovery, genome completeness evaluation and prediction of metabolic potential. We used this approach to test the effect of addition of organic carbon on a geyser-associated microbial community and detected a substantial change of the community metabolism, with selection against almost all candidate phyla bacteria and archaea and for eukaryotes. Near complete genomes were reconstructed for three fungi placed within the eurotiomycetes and an arthropod. While carbon fixation and sulfur oxidation were important functions in the geyser community prior to carbon addition, the organic carbon impacted community showed enrichment for secreted proteases, secreted lipases, cellulose targeting CAZymes, and methanol oxidation. We demonstrate the broader utility of EukRep by reconstructing and evaluating relatively high quality fungal, protist, and rotifer genomes from complex environmental samples. This approach opens the way for cultivation-independent analyses of whole microbial communities.
Bond softness sensitive bond-valence parameters for crystal structure plausibility tests
Authors: Chen Haomin , Adams Stefan
Published: August 2017

Based on a description of bond valence as a function of valence electron density, a systematic bond softness sensitive approach to determine bond-valence parameters and related quantities such as coordination numbers is elaborated and applied to determine bond-valence parameters for 706 cation–anion pairs. While the approach is closely related to the earliersoftBVparameter set, the newsoftNC1parameters proposed in this work may be simpler to apply in plausibility checks of crystal structures, as they follow the first coordination shell convention. The performance of thissoftNC1bond-valence parameter set is compared with that of the previously derivedsoftBVparameter set that also factors in contributions from higher coordination shells, and with a benchmarking parameter set that has been optimized following the conventional choice of a universal value of the bond-valence parameterb. The results show that a systematic adaptation of the bond-valence parameters to the bond softness leads to a significant improvement in the bond-valence parameters, particularly for bonds involving soft anions, and is safer than individual free refinements of bothR0andbfrom a limited number of reference cation environments.