bluuebunny/crossref_metadata_2025 huggingface dataset:
Lateral Inframammary Approach for Asian Augmentation Mammaplasty
Authors: Zelken Jonathan , Tobbia Dalia , Lin Yi-Ling , Cheng Ming-Huei
Published: July 2018

Background:

The inframammary fold (IMF) approach for augmentation mammaplasty is less popular in Asia. The incision was modified to lateral IMF(L-IMF) for easy access and better outcome. The aim of this study was to evaluate if L-IMF approach is feasible in Asian women.

Methods:

Between 2002 and 2016, 53 patients with 96 augmentation mammaplasties were performed using lateral (L-IMF, 31 cases, 56 breasts) and traditional IMF approaches (T-IMF, 22 cases, 40 breasts). Surgical outcome was compared between L-IMF and T-IMF groups. Scar was assessed using photographic images by 4 assessors with a modified Manchester Scar Score, and telephone surveys available in L-IMF group.

Results:

The average age was 41 ± 10.7 years (range, 20–73 years). There were no statistical differences in demographics in both groups besides of implant type (P < 0.01). At a follow-up of 80.1 months (range, 20–173 months), the capsular contracture rate and overall complication rate were statistically lower in L-IMF group, 3.6%, and 3.6%, than in T-IMF group, 15%, and 20% (P = 0.05, and P < 0.01, respectively). The modified Manchester Scar for L-IMF scars was 8.47 ± 2.4. The average score of 24 of 31 patients with L-IMF incision was 3.8 ± 0.96/5 points with patient-reported questionnaire. Nineteen patients (79.2%) would recommend or strongly recommend the procedure to friends.

Conclusions:

The scar of L-IMF group healed satisfactorily with lower capsular contracture and overall complication rates than T-IMF group. Patients were satisfied with the outcome of breast augmentation and scar appearance using L-IMF approach.
PEDIATRIC RETINAL DETACHMENT IN AN ASIAN POPULATION WITH HIGH PREVALENCE OF MYOPIA
Authors: Tsai Andrew S. H. , Wong Chee Wai , Lim Laurence , Yeo Ian , Wong Doric , Wong Edmund , Ang Chong Lye , Ong Sze Guan , Lee Shu Yen , Tan Gavin
Published: July 2018

Purpose:

To evaluate the clinical characteristics and surgical outcomes of pediatric retinal detachments (RDs) in an Asian population.

Methods:

Retrospective review of 171 eyes of 152 pediatric patients with rhegmatogenous RD over a 20-year period.

Results:

Myopia was the most common risk factor in our population. At 6 months, primary anatomical success was 60.7%, and overall anatomical success was 86.7%. A total of 46.8% had best-corrected visual acuity of 20/40 or better, and 81.6% had best-corrected visual acuity of 20/200 or better. In primary RDs, high myopia (≤−6D) patients had a lower primary anatomical success compared to patients with moderate myopia (≤−2D) (59.3 vs. 100% P = 0.03). Increasing age and absence of proliferative vitreoretinopathy were associated with anatomical and visual success. Pars plana vitrectomy as the primary procedure was associated with decreased odds of anatomical success. A longer duration of symptoms, cataract, and a larger RD extent were associated with poorer functional outcome.

Conclusion:

Myopia was the commonest risk factor for pediatric RD in our population. Good anatomical and functional outcome can be achieved with surgery. Increasing age at presentation and absence of proliferative vitreoretinopathy was associated with anatomical and functional success. High myopia was associated with poorer anatomical and functional outcome.
INTRAOPERATIVE OCULAR MANOMETRY IN SILICONE OIL–FILLED EYES WITH A BOSTON TYPE 1 KERATOPROSTHESIS
Authors: Toygar Okan , Mestanoglu Mert , Riemann Christopher D.
Published: July 2018

Purpose:

To demonstrate a novel technique to measure the intraocular pressure in silicone oil (SO)-filled eyes with Boston Type 1 keratoprosthesis (KPro) during intraocular surgery.

Methods:

In this retrospective case series, an ocular manometer that is predicated on a continuous fluid column between a pressure sensor and interior of the eye was designed and used to directly measure intraocular pressure during intraocular surgery in SO-filled eyes with KPro.

Results:

Six eyes of six patients were included in the study. The indications for SO injection with ocular manometry were hypotony in five patients, and endophthalmitis and complex retinal detachment with proliferative vitreoretinopathy in one patient. All patients had a successful reinflation of their globes without any evidence of SO underfill, without evidence of SO overfill, and without progression of glaucomatous optic neuropathy. Visual acuity increased in five eyes and was maintained in one eye.

Conclusion:

Intraoperative ocular manometry is a safe and effective technique in determining intraocular pressure in SO-filled eyes with KPro.
Risk Factors and Main Indications for Palivizumab Prophylaxis in a Second Season Population
Authors: Simon Arne , Gehrmann Susanne , Wagenpfeil Gudrun , Wagenpfeil Stefan
Published: July 2018

Background:

After national recommendations, palivizumab is administered in Germany to high-risk infants to prevent hospitalizations related to respiratory syncytial virus (RSV) infection. Limited data are available to characterize those children who receive palivizumab in 2 consecutive RSV seasons.

Methods:

This was a comparative analysis of data from a postmarketing observational study (German SYNAGIS Registry, AbbVie Germany GmbH & Co.KG, Wiesbaden) detailing RSV-related risk factors and main indications for palivizumab in 920 children who received at ≥1 palivizumab injection in a second season between 2010 and 2016 [second season population (SSP)].

Results:

Median birth weight and gestational age at birth as well as the proportion of children with hemodynamically significant congenital heart disease, with any form of chronic lung disease of prematurity or with any form of neuromuscular impairment, were significantly higher in the SSP. Accordingly, hemodynamically significant congenital heart disease, chronic lung disease and other reasons (including neuromuscular impairment) and not prematurity were the main indications for palivizumab in the SSP. The RSV-related hospitalization rate confirmed by viral testing in the SSP (receiving palivizumab prophylaxis) was 0.9%. No deaths due to RSV were reported.

Conclusions:

Second season recipients of palivizumab differ from one season recipients of palivizumab in terms of risk factors and main indications for prophylaxis. Keeping in mind the limitations of an uncontrolled prospective observational study, these results support the effectiveness of palivizumab (concerning the RSV rehospitalization rate) and do not reveal new safety alerts in a large SSP.
Effects of Exercise on Sport Concussion Assessment Tool-Third Edition Performance in Women
Authors: Chung Pin Yong Jean-Paul , Lee Jin H. , Howell David R. , Meehan William P. , Iverson Grant L. , Gardner Andrew J.
Published: July 2018

Objective:

The purpose of this study was to examine the influence of a brief exercise protocol on Sport Concussion Assessment Tool-Third Edition (SCAT3) performance in amateur women athletes.

Design:

Cross-over repeated-measures design. Setting: Off-season, uninjured community amateur athletes. Participants: We examined 87 amateur women athlete volunteers (age = 29.9, SD = 6.9 years).

Independent Variables:

Participants were assessed using the SCAT3 under 2 conditions: at rest and after a 5-minute physical exertion protocol, completed in a counterbalanced order.

Main Outcome Measures:

Participants' performance on the various components of the SCAT3 under the 2 conditions: at rest and after a 5-minute physical exertion protocol.

Results:

No significant differences were detected between at-rest and postexercise conditions for the balance, orientation, or cognitive components of the SCAT3. There were no significant differences in the proportion of participants who endorsed specific symptoms at rest compared with the postexercise condition (P > 0.05). However, women athletes who rated their exertion after exercise as “hard” or greater (Borg scale rating 13-20) reported significantly greater blurred vision (M = 0.25, SD = 0.62 vs M = 0.00, SD = 0.00; P = 0.006) and fatigue/low energy (M = 1.38, SD = 1.17 vs M = 0.66, SD = 0.91; P = 0.002) symptoms after exercise than those who rated their exertion as “light” or lower (Borg scale rating 6-12).

Conclusions:

In this study of women athletes, a brief bout of exercise did not seem to adversely affect SCAT3 performance and had only small effects on self-reported symptoms. There were differences in symptom reporting, however, in the subgroup of women who rated their exertion levels as “hard” or greater; they reported more blurred vision and fatigue/low energy.
Analysis of Different Approaches for Clinical Cochlear Coverage Evaluation After Cochlear Implantation
Authors: Schurzig Daniel , Timm Max Eike , Batsoulis Cornelia , John Samuel , Lenarz Thomas
Published: July 2018

Hypothesis:

Methods for cochlear coverage determination vary in their accuracy and are hence not equally reliable.

Background:

The audiological outcome after cochlear implantation is known to depend on several factors. One factor shown to positively correlate with speech perception is the insertion angle. This parameter is one of the ways to describe the fraction of the cochlea spiral exposed to electric stimulation after implantation, also known as cochlear coverage, which itself is dependent on the length and type of electrode array as well as the size and shape of the implanted cochlea. While the assessment of cochlear coverage as the insertion angle is quick and uncomplicated, the accuracy of representing the relative fraction of the cochlea exposed to electric stimulation by this single measurement value remains unknown.

Methods:

Both the cochlea spiral and implanted electrode array of N = 10 cochlear implant patients were traced within clinical imaging data and processed to derive the respective cochlear coverage values. These values were compared to ones derived with alternative measures like the insertion angle as well as other methods to yield the accuracy and reliability of these approaches.

Results:

The insertion angle as well as two novel approaches were found to be superior to all other analyzed assessment options and well suited for clinical cochlear coverage evaluations.

Conclusion:

Insertion angle measurements are well suited for cochlear coverage determination, especially regarding retrospective analyses. Prospective studies independent of anatomical irregularities should be performed with the newly proposed approaches.
The Novel Peptide Vaccine GV1001 Protects Hearing in a Kanamycin-induced Ototoxicity Mouse Model
Authors: Kim So Young , Jung Gaon , Shim Ye Ji , Koo Ja-Won
Published: July 2018

Hypothesis:

We tested whether GV1001 has any ototoxic side effects at different doses and whether it protects hearing in an aminoglycoside-induced ototoxicity mouse model.

Background:

GV1001, a novel peptide vaccine currently being examined in a Phase 3 clinical trial to treat pancreatic cancer, also has anti-inflammatory and antioxidant effects.

Methods:

In the first experiment, C57/BL6 mice were injected with GV1001 preparations at concentrations of 0.1 to 100 mg/kg for 7 days to evaluate the toxicity of GV1001 on the inner ear and kidneys. In the second experiment, the protective effect of GV1001 was tested in an ototoxicity mouse model that was generated by injecting 800 mg/kg kanamycin (KM) for 2 weeks. The hearing threshold and hair cell loss were compared between the KM + GV1001 group (treated with 10 mg/kg GV1001 for 2 wk) and the KM + saline group. The hearing threshold was measured before, and 7, 14, and 21 days after the initial treatment. The blood urea nitrogen level was measured.

Results:

No ototoxicity or renal toxicity was found following treatment with different doses of GV1001 (0.1–100 mg/kg). The KM + saline group showed impaired auditory function and markedly disoriented and missing cochlear hair cells, while the KM + GV1001 group showed significant hearing and hair cell preservation in comparison (p < 0.05).

Conclusion:

GV1001 itself did not have any detrimental effects on the inner ear or kidney. In the KM induced ototoxicity model, concomitant administration of GV1001 protected against cochlear hair cell damage and preserve hearing.
Flipping the Classroom in Health Care Higher Education
Authors: Evans Leda , Vanden Bosch Melodee L. , Harrington Susan , Schoofs Nancy , Coviak Cynthia
Published: July 2018

Background

The flipped classroom is an approach to teaching with independent and asynchronous study of content by students and active learning during scheduled class times.

Purpose

The purpose of this review was to systematically examine research on the use of the flipped classroom approach in health professions education.

Methods

Eleven electronic databases were searched for peer-reviewed literature from 2005 through September 2017. Inclusion criteria for studies addressed health professions students and quantitative outcomes (quizzes, examinations, course grades).

Results

Of the 49 articles identified, 24 met the inclusion criteria. The majority of studies (n = 17) noted a significant improvement in at least 1 student academic outcome using the flipped classroom compared with the traditional lecture.

Conclusions

This systematic review of the effects of the flipped classroom approach for the education of health professions students did not reveal compelling evidence for the effectiveness of the method in improving academic outcomes above that of traditional classroom approaches.
Prognostic Factors of Children Admitted to a Pediatric Intensive Care Unit After an Episode of Drowning
Authors: Salas Ballestín Alberto , de Carlos Vicente Juan Carlos , Frontera Juan Guillem , Sharluyan Petrosyan Artur , Reina Ferragut Cristina M. , González Calvar Amelia , Clavero Rubio Maria del Carmen , Fernández de la Ballina Andrea
Published: July 2018

Objective

The aim of this study was to evaluate the prognostic factors of patients admitted to a pediatric intensive care unit (PICU) after drowning.

Methods

Retrospective observational study from January 1992 to December 2004 and prospective study from January 2005 to December 2015 were conducted in a tertiary children's hospital PICU. The data analyzed refer to the patient, event, type of resuscitation performed, and clinical situation after resuscitation and at arrival to the PICU; results of additional tests; and clinical evolution and neurological status at discharge from the PICU (categorized as death, severe encephalopathy, or normal). The considered potential prognostic factors were whether drowning was witnessed, the type of initial resuscitation, Glasgow Coma Scale score at admission, pupil status and reactivity, and pH.

Results

One hundred thirty-one patients were registered. Mortality was 16.7%, and 8.3% had significant neurological sequelae. The clearest factor associated with poor outcome was the type of initial resuscitation performed. All patients who did not require cardiopulmonary resuscitation (CPR), or only basic CPR, had good outcomes; 96.3% of those who required advanced CPR with epinephrine administration had poor outcomes. Patients who needed advanced resuscitation with administration of epinephrine had lower temperature, Glasgow Coma Scale score, pH, and bicarbonate at admission and higher level of glucose. In this group, there was also a higher incidence of seizures, acute respiratory distress syndrome, hemodynamic compromise, and acute renal failure.

Conclusions

The need for advanced CPR with epinephrine administration on the scene predicts poor neurological outcome (severe encephalopathy or death) in drowned children.
Measuring Anxiety in the Pediatric Emergency Department
Authors: Rochat Cosette Pharisa , Gaucher Nathalie , Bailey Benoit
Published: July 2018

Objectives

The objective of this study was to evaluate the agreement between the State Trait Anxiety Inventory (STAI) and other anxiety scales to determine whether these shorter to administer scales could replace the STAI.

Methods

This was a prospective cohort study on a convenience sample of children, aged 9 to 17 years, presenting to a pediatric emergency department. Patients were divided into 2 groups: preteens (PT) (aged 9–12 years) completed the pediatric STAI and teens (T) (aged 13–17 years) completed the adult STAI. Participants also completed a visual analog scale (0–100 mm), a Likert scale (1–5), and a short version of the STAI. Intraclass correlation (2-way mixed model, average measures) was used to evaluate agreement between the STAI and the other scales. A sample size of 100 patients per group was estimated as sufficient.

Results

The median (interquartile range) STAI state anxiety scores were 33 (28.25–36.75) and 37.5 (32–44), in the PT (n = 100) and T (n = 100) groups, respectively. The median (interquartile range) STAI trait anxiety scores were 33.5 (28–38.75) and 36 (31–44), in the PT and T groups, respectively. Agreements between the STAI and the other scales were poor for all scales. At best, the intraclass correlation was 0.71 for the agreement between the STAI and the short version of the STAI.

Conclusions

There appears to be poor agreement between the STAI and the other scales designed to measure anxiety in children 9 to 17 years presenting to the pediatric emergency department.
Differentiation of Glioblastoma and Solitary Brain Metastasis by Gradient of Relative Cerebral Blood Volume in the Peritumoral Brain Zone Derived from Dynamic Susceptibility Contrast Perfusion Magnetic Resonance Imaging
Authors: She Dejun , Xing Zhen , Cao Dairong
Published: July 2018

Objective

The purpose of our study was to evaluate the efficacy of the relative cerebral blood volume (rCBV) gradient in the peritumoral brain zone (PBZ)—the difference in the rCBV values from the area closest to the enhancing lesion to the area closest to the healthy white matter—in differentiating glioblastoma (GB) from solitary brain metastasis (MET).

Methods

A 3.0-T magnetic resonance imaging (MRI) machine was used to perform dynamic susceptibility contrast perfusion MRI (DSC-MRI) on 43 patients with a solitary brain tumor (24 GB, 19 MET). The rCBV ratios were acquired by DSC-MRI data in 3 regions of the PBZ (near the enhancing tumor, G1; intermediate distance from the enhancing tumor, G2; far from the enhancing tumor, G3). The maximum rCBV ratios in the PBZ (rCBVp) and the enhancing tumor were also calculated, respectively. The perfusion parameters were evaluated using the nonparametric Mann-Whitney test. The sensitivity, specificity, accuracy, and the area under the receiver operating characteristic curve were identified.

Results

The rCBVp ratios and rCBV gradient in the PBZ were significantly higher in GB compared with MET (P < 0.05 for both rCBVp ratios and rCBV gradient). The threshold values of 0.50 or greater for rCBVp ratios provide sensitivity and specificity of 57.69% and 79.17%, respectively, for differentiation of GB from MET. Compared with rCBVp ratios, rCBV gradient had higher sensitivity (94.44%) and specificity (91.67%) using the threshold value of greater than 0.06.

Conclusions

The parameter of rCBV gradient derived from DSC-MRI in the PBZ seems to be the most efficient parameter to differentiate GB from METs.
Biochemical Recurrence of Prostate Cancer Presenting as Solitary Testicular Metastasis on 68Ga-Labeled Prostate-Specific Membrane Antigen Ligand Positron Emission Tomography/Computed Tomography
Authors: Ege Aktas Gul , Yürüt Çaloğlu Vuslat , Akdere Hakan , Tutuğ Busem Binboğa , Altun Gülay Durmuş
Published: July 2018

Prostate adenocarcinoma (PCa) is the most frequently diagnosed malignancy in the male population, with the most common sites for secondary lesions being the lymph nodes, bones, and lungs. Testicular metastases from PCa are very rare and mostly identified incidentally after therapeutic orchiectomy for advanced PCa or during autopsy. Here we present a case involving a 64-year-old man with biochemical recurrence of castrated oligometastatic PCa that presented as solitary testicular metastasis on 68Ga-PSMA ligand positron emission tomography/computed tomography.
Recurrence of Biphenotypic Sinonasal Sarcoma With Cerebral Hemorrhaging
Authors: Fudaba Hirotaka , Momii Yasutomo , Hirano Takashi , Yamamoto Hidetaka , Fujiki Minoru
Published: July 2018

Biphenotypic sinonasal sarcoma (BSNS) is a newly classified tumor that is characterized by neural and myogenic differentiation. The authors herein report a rare patient of the recurrence of BSNS with intracranial hemorrhaging and a review of the literature. A 70-year-old man presented with disturbance of consciousness and vomiting blood. He had undergone resection of a sinonasal tumor 11 years earlier and shown no recurrence at his last follow-up 4 years ago. Computed tomography showed cerebral hemorrhaging around a low-density mass that occupied the left frontal base and left ethmoid sinus. Total resection was performed. A histological examination of tumor specimens obtained from the first and the second resections revealed almost the same characteristic morphological features and the patient was diagnosed with BSNS. The lesion was negative for any fusion genes, as previously reported. The long-term progression of BSNS is not clear. This case appears to be the first reported recurrence of BSNS with cerebral hemorrhaging. Biphenotypic sinonasal sarcoma should be considered to need long-term follow-up.
Three-Dimensional Analysis of Perioperative Condylar Displacement After Mandibular Setback Surgery With Intended Manual Condylar Positioning
Authors: Park Jong-Cheol , Kim Uk-Kyu , Hwang Dae-Seok
Published: July 2018

Purpose:

The purpose of this study is to investigate the effect of orthognathic surgery with intended manual condylar positioning on condyle by examining a change in its position.

Method:

About 18 patients with mandibular prognathism who underwent orthognathic surgery with intentional manual condyle positioning were included. Condyle displacement was analyzed through 3D cone-beam computed tomography before and after operation. The patients were categorized into 2 experimental groups: group A (1-jaw) and group B (2-jaw). The experimental groups were examined before surgery (T0), 3 days (T1), and 6 months (T2) after surgery. Condylar displacement direction was investigated in terms of bodily shift and rotational movement.

Results:

Downward bodily shift of condyle after surgery was significantly apparent from all of the patients. Condylar bodily shift in other directions was statistically insignificant. Gross bodily shift of condyle right after surgery was anterolateral-inferior direction. In perspective of rotational movement, condyle rotated in infero-medial direction right after operation, but no significant change was presented afterwards. In addition, no significant difference in the amounts of condylar shift and pattern existed between groups A and B.

Conclusion:

Intended manual condylar positioning may minimize postoperative displacement of condyle while accomplishing skeletal stability.
Bilateral Cleft Lip and Palate, With Facial Dysplasia: Interdisciplinary Treatment and Long-Term Follow-Up
Authors: Bennun Ricardo D. , Harfin Julia H.
Published: July 2018

Bilateral complete clefts represent the result of an incomplete fusion with all the morphologic components present. It is well known that patients with bilateral cleft lip and palate have typical characteristics such as insufficient medial face development with an orthodontic class III tendency, flat nose and short columella with abnormal nasolabial angle, bilateral oronasal fistulas, alterations in the number and position of the lateral incisors, and agenesis or supernumerary teeth. Successfully solving these cases, results in a difficult challenge and studies showing extended follow-up are not frequent. Bilateral complete clefts, including medial facial dysplasia, are a rare condition, not only difficult to be included in any classification but also of complex solution. These patients require multiple surgical procedures throughout life, and long-term results are often still far from ideal. Due to surgical intervention and diminished intrinsic growth potential, surgical results may change from initially good into a progressively disappointing outcome. However, if the ideal timing and type of surgery are known, in combination with the intrinsic growth potential, these results could be ameliorated. A patient with complete bilateral cleft, presenting hypoplasia of philtrum and premaxilla, flat nose with rudimentary columella and septum, is reported. A description of her interdisciplinary treatment and long-term outcome with an adequate and stable result was observed. Being the intrinsic growth restriction mainly localized in the central mid-face, a protocol oriented to stimulate facial development during growth period could be essential to reduce the number of surgical procedures and prevent sequels. Early referral to a specialized center is mandatory to achieve a correct treatment and result.
Anatomical Reconstruction in Bilateral Cleft Lip With Mendoza Technique
Authors: Pérez González Araceli , Arámburo-García Rigoberto
Published: July 2018

The bilateral cleft lip (BCL) is the most severe manifestation of orofacial clefts. Multiple techniques have been described to reconstruct BCL to obtain good aesthetic and functional results with minimal complications.

Objective:

Description of surgical technique for BCL reconstruction and present the postoperative results obtained.

Methods:

Patients with BCL of the cleft lip and palate at ABC Medical Center from June 2013 to June 2017 operated with Mendoza bilateral cheiloplasty were included. The procedure includes an anatomical reconstruction of the lip with minimal resection of tissue, alignment of the orbicularis muscle, vestibule creation, and complete use of the prolabium. The evaluation was carried out by photographs analyzing parameters of quality, symmetry, and alignment of lip and nose structures.

Results:

The authors included 36 patients, 15 women and 16 men. The average procedure time was 57 minutes. Photographs were evaluated 1 year postoperatively, symmetry in lip was observed in 91.6% of the patients, muscle continuity in 100%, deep gingivolabial sulcus in 94.5% of cases, closed nasal floor in 100% with no presence of nasovestibular fistulas.

Conclusions:

This technique allows an anatomical BCL reconstruction with good aesthetic and functional results.
Hypertelorism Secondary to Mucocele in the Paranasal Sinuses
Authors: Solano Nicolas , Castro Bairon , Sarmiento Luis , Lopez Jondalys , Añez Luis
Published: July 2018

Ocular hypertelorism was introduced by Greig as an increased interpupillary distance. The paranasal sinus mucoceles are acquired lesions for various reasons; however, their behavior is progressive, capable of eroding the bone and extending to the orbital and intracranial regions. The objective is to present a clinical case of orbital hypertelorism secondary to mucocele in the paranasal sinuses. This is a 72-year-old male patient who came presenting an increase in volume in the right nasoorbitoethmoidal region. The isodense lesion occupying the maxillary and right ethmoidal sinuses was confirmed by an intimate relationship with the ipsilateral frontal and sphenoidal sinus, with osteolytic involvement of the orbit and nasal region. After incisional biopsy with mucocele results, a wide resection plus facial reconstruction was performed with autologous grafts and osteosynthesis material. Currently, the patient has 1 year of evolution, without significant functional commitment. It is important to consider giant mucoceles as part of the differential diagnoses in patients with deformities in the middle and upper third of the face.
Prospective Validation of Prediction Model for Kidney Discard
Authors: Zhou Sheng , Massie Allan B. , Holscher Courtenay M. , Waldram Madeleine M. , Ishaque Tanveen , Thomas Alvin G. , Segev Dorry L.
Published: July 2018

Background.

Many kidneys are discarded every year, with 3631 kidneys discarded in 2016 alone. Identifying kidneys at high risk of discard could facilitate “rescue” allocation to centers more likely to transplant them. The Probability of Delay or Discard (PODD) model was developed to identify marginal kidneys at risk of discard or delayed allocation beyond 36 hours of cold ischemia time. However, PODD has not been prospectively validated, and patterns of discard may have changed after policy changes such as the introduction of Kidney Donor Profile Index and implementation of the Kidney Allocation System (KAS).

Methods.

We prospectively validated the PODD model using Scientific Registry of Transplant Recipients data in the KAS era (January 1, 2015, to March 1, 2018). C statistic was calculated to assess accuracy in predicting kidney discard. We assessed clustering in centers’ utilization of kidneys with PODD >0.6 (“high-PODD”) using Gini coefficients. Using match run data from January 1, 2015, to December 31, 2016, we examined distribution of these high-PODD kidneys offered to centers that never accepted a high-PODD kidney.

Results.

The PODD model predicted discard accurately under KAS (C-statistic, 0.87). Compared with utilization of low-PODD kidneys (Gini coefficient = 0.41), utilization of high-PODD kidneys was clustered more tightly among a few centers (Gini coefficient, 0.84 with >60% of centers never transplanted a high-PODD kidneys). In total, 11684 offers (35.0% of all high-PODD offers) were made to centers that never accepted a high-PODD kidney.

Conclusions.

Prioritizing allocation of high-PODD kidneys to centers that are more likely to transplant them might help reduce kidney discard.
Chimpanzees and death
Authors: Anderson James R.
Published: July 2018

Information about responses to death in nonhuman primates is important for evolutionary thanatology. This paper reviews the major causes of death in chimpanzees, and how these apes respond to cues related to dying and death. Topics covered include disease, human activities, predation, accidents and intra-species aggression and cannibalism. Chimpanzees also kill and sometimes eat other species. It is argued that, given their cognitive abilities, their experiences of death in conspecifics and other species are likely to equip chimpanzees with an understanding of death as cessation of function and irreversible. Whether they might understand that death is inevitable—including their own death, and biological causes of death is also discussed. As well as gathering more fundamental information about responses to dying and death, researchers should pay attention to possible cultural variations in how great apes deal with death.

This article is part of the theme issue ‘Evolutionary thanatology: impacts of the dead on the living in humans and other animals’.
Managing the risks and rewards of death in eusocial insects
Authors: Sun Qian , Haynes Kenneth F. , Zhou Xuguo
Published: July 2018

Eusocial insects frequently face death of colony members as a consequence of living in large groups where the success of the colony is not dependent on the fate of the individual. Whereas death of conspecifics commonly triggers aversion in many group-living species due to risk of pathogens, eusocial insects perform cooperative corpse management. The causes and social context of the death, as well as feeding and nesting ecology of the species, influence the way that corpses are treated. The corpse itself releases cues that dictate the colony's response. As a result, social insects exhibit behavioural responses that promote disease resistance, colony defence and nutrient recycling. Corpse management represents a unique adaption that enhances colony success, and is another factor that has enabled eusocial insects to be so successful. In this review, we summarize the causes of death, the sensory detection of death and corpse management strategies of social insects. In addition, we provide insights into the evolution of behavioural response to the dead and the ecological relevance of corpse management.

This article is part of the theme issue ‘Evolutionary thanatology: impacts of the dead on the living in humans and other animals’.
Sources of children's knowledge about death and dying
Authors: Longbottom Sarah , Slaughter Virginia
Published: July 2018

In the last century, decreases in infant and child mortality, urbanization and increases in healthcare efficacy have reduced children's personal exposure to death and dying. So how do children acquire accurate conceptions of death in this context? In this paper, we discuss three sources of children's learning about death and dying, namely, direct experience of death, parental communication about death and portrayals of death in the media and the arts. We conclude with recommendations about how best to teach modern children about this aspect of life.

This article is part of the theme issue ‘Evolutionary thanatology: impacts of the dead on the living in humans and other animals’.
The regulatory control ofCebpaenhancers and silencers in the myeloid and red-blood cell lineages
Authors: Repele Andrea , Krueger Shawn , Tuineau Michelle Y. , Manu
Published: July 2018

During development, cell identity is determined by lineage-specific transcriptional programs en-coded in thecis-regulatory DNA sequence of developmental genes. The sequence-level regulatory logic—identities of bound transcription factors (TFs), TF binding sites, and TF regulatory roles—of most developmentalcis-regulatory modules (CRMs) is yet to be determined. We had previously developed an approach for inferring regulatory logicde novoby training sequence-based thermo-dynamic models on comprehensive reporter activity and gene expression datasets and applied it toCebpa, an important hematopoietic gene. Here, we experimentally test thermodynamic models to decode thecis-regulatory logic of 4 enhancers and 3 silencers neighboringCebpaat the resolution of individual binding sites.Cebpais expressed at high and intermediate levels in neutrophils and macrophages respectively and downregulated in non-myeloid lineages. We tested the binding sites and functional roles of inferred TFs by designing and constructing mutated CRMs and comparing theoretical predictions of their activity against empirical measurements. Reporter activity was measured in PUER cells, which can be induced to differentiate into macrophages or neutrophils. All four enhancers were found to be simultaneously active in undifferentiated PUER cells and early-stage macrophages and neutrophils, and activated by combinations of PU.1, C/EBP family TFs, Egr1, and Gfi1. We show that silencers repress the activity of the proximal promoter in a dominant manner in G1ME cells, which are derived from the red-blood cell lineage. Dominant repression in G1ME cells can be traced to binding sites for GATA and Myb, a motif shared by all of the silencers. Finally, we demonstrate that GATA and Myb act redundantly to silence the proximal promoter. The result that silencers quench the promoter selectively in non-myeloid cells indicates that dominant repression is a novel mechanism for resolving hematopoietic lineages. Furthermore,Cebpahas a fail-safecis-regulatory architecture, featuring several functionally similar CRMs, each of which contains redundant binding sites for multiple TFs. Lastly, by experimentally demonstrating the predictive ability of our sequence-based thermodynamic models, this work highlights the utility of this computational approach for decoding the logic of mammalian gene regulation.
Local Attachment Explains Small-World-Like Properties of Fibroblastic Reticular Cell Networks in Lymph Nodes
Authors: Soekarjo Kasper M.W. , Textor Johannes , de Boer Rob J.
Published: July 2018

Fibroblastic reticular cells (FRCs) form a cellular network that serves as the structural backbone of lymph nodes and facilitates lymphocyte migration. This FRC network has been found to have small-world properties. Using a model based on geographical preferential attachment, we simulated the formation of a variety of cellular networks and show that similar small-world properties robustly emerge under such natural conditions. By estimating the parameters of this model, we generated FRC network representations with realistic topological properties. We found that these properties change markedly when the network is expanded from a thin slice to a 3D cube. Typical small-world properties were found to persist as network size was increased. The simulated networks were very similar to 2D and 3D lattice networks. According to the used metrics, these lattice networks also have small-world properties, indicating that lattice-likeness is sufficient to become classified as a small-world network. Our results explain why FRC networks have small-world properties and provide a framework for simulating realistic FRC networks.
Long-term impact of intensive postgraduate laboratory training at the Cold Spring Harbor Neurobiology of Drosophila summer course
Authors: Ly Sarah , Kaun Karla , Lee Chi-Hon , Stewart David , Pulver Stefan R. , Keene Alex C.
Published: July 2018

Intensive postgraduate courses provide an opportunity for junior and senior level scientists to learn concepts and techniques that will advance their training and research programs. It is commonly assumed that short intensive courses have positive impacts within fields of research; however, these assumptions are rarely tested. Here we describe the framework of a long running postgraduate summer course at Cold Spring Harbor and attempt to quantify the impact made over its history. For over three decades, the Drosophila Neurobiology: Genes, Circuits & Behavior Summer Course at Cold Spring Harbor Laboratories (CSHL) has provided participants with intense instruction on a wide variety of topics and techniques in integrative neuroscience using Drosophila as a model organism. Students are introduced to the latest approaches for studying nervous system development, activity and connectivity, as well as complex behaviors and diseases. The course has a long history of successful alumni, many of whom describe participation in the course as foundational to their training. Student surveys of recent participants indicate a high level of satisfaction, improved career outcomes, and direct impact on publications. Analysis of student success reveals that over 64% of participants obtain independent faculty positions. Further, we describe ongoing efforts to enhance diversity and encourage access to scientific research at undergraduate-focused institutions. Together, our findings suggest that laboratory-intensive postgraduate courses provide a highly effective mechanism for scientific training that has lasting positive impacts on trainees.
A broad-host-range event detector: expanding and quantifying performance across bacterial species
Authors: Khan Nymul , Yeung Enoch , Farris Yuliya , Fansler Sarah J. , Bernstein Hans C.
Published: July 2018

Modern microbial biodesign relies on the principle that well-characterized genetic parts can be reused and reconfigured for different functions. However, this paradigm has only been successful in a limited set of hosts, mostly comprised from common lab strains ofEscherichia coli. It is clear that new applications – such as chemical sensing and event logging in complex environments – will benefit from new host chassis. This study quantitatively compared how a chemical event logger performed across multiple microbial species. An integrase-based sensor and memory device was operated by two representative soil Pseudomonads –Pseudomonas fluorescensSBW25 andPseudomonas putidaDSM 291. Quantitative comparisons were made between these two non-traditional hosts and two bench-markEscherichia colichassis including the probiotic Nissle 1917 and common cloning strain DH5α. The performance of sensor and memory components changed according to each host, such that a clear chassis effect was observed and quantified. These results were obtained via fluorescence from reporter proteins that were transcriptionally fused to the integrase and down-stream recombinant region and via data-driven kinetic models. ThePseudomonadsproved to be acceptable chassis for the operation of this event logger, which outperformed the commonE. coliDH5α in many ways. This study advances an emerging frontier in synthetic biology that aims to build broad-host-range devices and understand the context by which different species can execute programmable genetic operations.
The landscape of S100B+ and HLA-DR+ dendritic cell subsets in tonsils at the single cell level via high-parameter mapping
Authors: Bolognesi Maddalena Maria , Bosisio Francesca Maria , Manzoni Marco , Schapiro Denis , Tagliabue Riccardo , Faretta Mario , Parravicini Carlo , Haberman Ann M , Cattoretti Giorgio
Published: July 2018

Dendritic cells (DC) (classic, plasmacytoid, inflammatory) are an intense focus of interest because of their role in inflammation, autoimmunity, vaccination and cancer. We present a tissue-based classification of human DC subsets in tonsils with a high-parameter (>40 markers) immunofluorescent approach, cell type-specific image segmentation and the use of bioinformatics platforms. Through this deep phenotypic and spatial examination, classic cDC1, cDC2, pDC subsets have been further refined and a novel subset of DC co-expressing IRF4 and IRF8 identified. Based on unique tissue locations within the tonsil, and close interactions with T cells (cDC1) or B cells (cDC2), DC subsets can be further subdivided by correlative phenotypic changes associated with these interactions. In addition, monocytes and macrophages expressing HLA-DR or S100AB are identified and localized in the tissue. This study thus provides a whole tissue in situ catalog of human DC subsets and their cellular interactions within spatially defined niches.
Comparing fMRI inter-subject correlations between groups using permutation tests
Authors: Tohka Jussi , Pollick Frank E. , Pajula Juha , Kauppi Jukka-Pekka
Published: July 2018

Inter-subject correlation (ISC) based analysis is a conceptually simple approach to analyze functional magnetic resonance imaging (fMRI) data acquired under naturalistic stimuli such as a movie. We describe and validate the statistical approaches for comparing ISCs between two groups of subjects implemented in the ISC toolbox, which is an open source software package for ISC-based analysis of fMRI data. The approaches are based on permutation tests. We validated the approaches using five different data sets from the ICBM functional reference battery tasks. First, we created five null datasets (one for each task) by dividing the subjects into two matched groups and assumed that no group difference exists. Second, based on one null dataset, we created datasets with simulated ISC differences of varying size between the two groups. Based on the experiments with these two types of data, we recommend the use of subject-wise permutations, instead of element-wise permutations. The tests based on subject-wise permutations led to correct false positive rates. We observed that the null-distributions should be voxel-specific and not based on pooling all voxels across the brain as is typical in fMRI. This was the case even if studentized permutation tests were used. Additionally, we experimented with an fMRI dataset acquired using a dance movie stimulus for comparison of a group of adult males on the autism spectrum to a matched typically developed group. The experiment confirmed the differences between voxel-based permutation tests and global model based permutation tests.
Moderate developmental alcohol exposure reduces repetitive alternation in a zebrafish model of fetal alcohol spectrum disorders
Authors: Cleal Madeleine , Parker Matthew O.
Published: July 2018

The damaging effects of alcohol on a developing fetus are well known and cause a range of conditions known as fetal alcohol spectrum disorder (FASD). High levels of alcohol exposure lead to physical deformity and severe cognitive deficits, but more moderate exposure leads to a range of subtle cognitive effects such as reduced social behavior, higher propensity to develop addictions, and reduced spatial working memory. Previous studies have demonstrated that following exposure to relatively low levels of ethanol during early brain development (equivalent in humans to moderate exposure) zebrafish display a range of social and behavioral differences. Here, our aim was to test the hypothesis that moderate developmental ethanol exposure would affect aspects of learning and memory in zebrafish. In order to do this, we exposed zebrafish embryos to 20mM [0.12% v/v] ethanol from 2 to 9 dpf to model the effects of moderate prenatal ethanol (MPE) exposure. At 3 months old, adult fish were tested for appetitive and aversive learning, and for spatial alternation in a novel unconditioned y-maze protocol. We found that MPE did not affect appetitive or aversive learning, but exposed-fish showed a robust reduction in repetitive alternations in the y-maze when compared to age matched controls. This study confirms that moderate levels of ethanol exposure to developing embryos have subtle effects on spatial working memory in adulthood. Our data thus suggest that zebrafish may be a promising model system for studying the effects of alcohol on learning and decision-making, but also for developing treatments and interventions to reduce the negative effects of prenatal alcohol.
Morphofunctional analysis of antigen uptake mechanisms following sublingual immunotherapy with beads in mice
Authors: Ali Elewa Yaser Hosny , Mizoguchi Tatsuya , Ichii Osamu , Nakamura Teppei , Kon Yasuhiro
Published: July 2018

Background

Recently, sublingual immunotherapy (SLIT) has been used as a safe and efficient method for the treatment of and immunization against asthma and various allergies. However, the routes of antigen uptake through the mucosa of the oral cavity remain incompletely understood, as do the roles of sex and age in the process. For this purpose, to elucidate the mechanism and efficacy of SLIT among different sexes and ages microbeads were dripped into the sublingual region to mimic antigen uptake by the sublingual mucosa.

Methods

Twenty microliters of either phosphate buffered saline (PBS) or fluorescently labelled microbeads (latex and silica beads) were placed under the tongue of both male and female C57BL/6 mice at young (3 months) and old (6 months) ages. The lower jaw was examined 30 min after administration, and beads were detected with a fluorescence stereomicroscope. Morphological observations of the mucosa of the fluorescent areas were made with scanning electron microscopy (SEM) and an all-in-one light fluorescence microscope (LM). Fluorescence intensity was compared between both sexes and ages.

Results

Stereomicroscopic observation revealed fluorescent illuminations in three compartments of the sublingual mucosa: the sublingual caruncles (SC), the oral rostral mucosa (OR) and the buccal mucosa (BM). Interestingly, the fluorescence intensity tended to be higher among females than among males in the SC region in particular. However, there were no significant age-related differences. SEM and LM revealed beads in the lumina of both mandibular ducts and sublingual ducts (Sd). Additionally, the apical cytoplasm of some Sd cells contained silica beads. However, there were no specification in the OR mucosa or BM.

Conclusions

This study reveals the major role Sd play in local immunity via the antigen uptake mechanisms. Furthermore, our data suggest that the efficacy of SLIT in humans could be affected by sex.