bluuebunny/crossref_metadata_2025 huggingface dataset:
Perspectives of 30 English Patients on Call Light Technology, Eloquence Revisited
Authors: Montie Mary , Shuman Clayton , Galinato Jose , Patak Lance , Titler Marita
Published: March 2017

Call light technology is important because it serves as a direct link for patients to get their healthcare needs fulfilled by their healthcare providers. As primary users of call light technology, patient perspectives are important and warranted. Despite this fact, there is a lack of published literature regarding patient perspectives and call light technology. The present study examined a technologically advanced call light system (Eloquence) by incorporating 30 patient participants' perspectives regarding its usefulness, effectiveness, and appropriateness gathered from individual interviews. Using qualitative descriptive research methods, five major themes and multiple minor themes emerged from the data.
Growth hormone in IVF cycles: any hope?
Authors: Hart Roger J. , Rombauts Luk , Norman Robert J.
Published: March 2017

Purpose of review

Growth hormone (GH) has been used as an adjunct in ovulation induction and IVF for 25 years, particularly as an adjunct to ovarian stimulation for women who had a previous poor response to stimulation in an IVF cycle. It does not have US Food and Drug Administration approval for this use. Unfortunately, due to the problems inherent with recruiting women who have undergone unsuccessful IVF treatment cycles and their inevitable low live birth rate per initiated cycle, many studies performed to date have been underpowered.

Recent findings

Previous meta-analyses of studies performed in populations of women with a poor response to ovarian stimulation, demonstrated an increase in the live birth rate for the use of GH. With the recent publication of three studies and the presentation of the Australian LIGHT study, we undertook an updated meta-analysis.

Meta-analysis demonstrated a benefit for the use of the adjunct GH, with a reduction in the duration of ovarian stimulation required for oocyte retrieval, the collection of a greater number of oocytes than placebo, and an improvement in many of the early clinical parameters; however, there was no evidence of an increased chance of a live birth for the use of GH.
Free-style Deepithelialized Propeller Flaps: An Ideal Local Flap to Obliterate Wounds with Dead Space
Authors: Datli Asli , Suh HyunSuk , Kim Young Chul , Choi Doon Hoon , Hong Joon Pio (Jp)
Published: March 2017

Background:

The reconstruction of the posterior trunk, especially with large dead spaces, remains challenging. Regional muscle flaps may lack adequate volume and reach. The purpose of this report was to evaluate the efficacy of deepithelialized free-style perforator-based propeller flaps to obliterate defects with large dead space.

Methods:

A total of 7 patients with defects on the posterior trunk with large dead spaces were evaluated. After complete debridement or resection, all flaps were designed on a single perforator adjacent to the defect, deepithelialized, and then rotated in a propeller fashion. Flaps were further modified in some cases such as folding the flap after deepithelialization to increase bulk and to obliterate the dead space.

Results:

The flap dimension ranged from 10 × 5 × 1 to 15 × 8 × 2.5 cm based on a single perforator. The rotation arch of the flap ranged from 90 to 180 degrees. Uneventful healing was noted in all cases. One case showed latent redness and swelling at 7 months after falling down, which resolved with medication. During the average follow-up of 28 months, there were no other flap and donor site complications.

Conclusion:

The deepithelialized propeller flap can be used efficiently to obliterate dead spaces in the posterior trunk and retains advantages such as having a good vascular supply, adequate bulk, sufficient reach without tension, and minimal donor site morbidity.
Various Types of Minor Trauma to Hair Follicles During Follicular Unit Extraction for Hair Transplantation
Authors: Park Jae Hyun , You Seung Hyun
Published: March 2017

Background:

When performing follicular unit extraction (FUE), various types of minor hair follicle trauma unapparent during follicular unit strip surgery are likely to occur. However, no studies have examined such damage.

Methods:

In total, 100 grafts were randomly selected from each of 42 patients who underwent FUE with a 1-mm-diameter sharp punch. A ×5.5 magnifying loupe and a ×60 magnifying binocular microscope were used. The transection rate (TR), paring, fractures of and damage to the dermal papilla (DP) areas, and hair bulb partial injury were assessed.

Results:

Observation with the magnifying loupe revealed an average TR of 7.40%, and 4.31, 1.90, 1.52, and 0.43 hair follicles per 100 grafts exhibited paring, fracture, DP partial injury, and hair bulb partial injury, respectively. An average of 9.21 telogen hairs were observed. Microscopic examination revealed a TR of 6.34%, and 9.07, 1.95, 0.79, and 1.24 hair follicles per 100 grafts exhibited paring, fracture, DP injury, and hair bulb partial injury, respectively. An average of 16.62 telogen hairs were observed.

Conclusions:

Various types of minor hair follicle damage occur during FUE as shown by loupe and microscopic examination of the grafts. Especially paring and hair bulb injury were more apparent under microscopic examination. These minor hair follicle injuries should be considered when choosing operative method or surgical techniques.
Pretrimmed versus Direct Nonshaven Follicular Unit Extraction
Authors: Park Jae Hyun , You Seung Hyun
Published: March 2017

Background:

Shaving the donor area is one of the major deterrents preventing hair transplant patients from selecting follicular unit extraction (FUE). A minimal shaved donor area is possible in strip surgery, but the strip method is not applicable if the patient wishes to avoid a linear donor scar, wishes to minimize postoperative pain, or has insufficient scalp laxity. In these cases, nonshaven FUE (NS-FUE) is potentially a very good choice.

Methods:

A total of 42 patients were enrolled. Both pretrimmed and direct NS-FUE were performed during a single session in each patient. The 2 methods were compared regarding the time taken to punch 50 grafts, transection rate, and calculated density (number of hairs per graft).

Results:

The mean time taken to punch 50 grafts was significantly longer in the pretrimmed method than the direct method (3.4 minutes versus 2.6 minutes; P < 0.001). The mean transection rate was similar in both methods (8.8% for the pretrimmed method and 7.5% for the direct method; P > 0.05). The mean calculated density was significantly higher in the pretrimmed method than the direct method (2.23 hairs per graft versus 2.15 hairs per graft; P < 0.05). The length of the harvested hair was 1–4 mm in the pretrimmed method, compared with 0.4–0.8 mm in the direct method.

Conclusion:

Depending on the proficiency and preference of doctors and the case indications, pretrimmed and direct NS-FUE are both useful techniques for hair transplantation.
Knowledge and Attitude Toward Corneal Donation Among High School Children in Northern India
Authors: Gupta Parul Chawla , Duggal Mona , Jamir Limalemla , Sharma Drishti , Kankaria Ankita , Sathyanath Shreyaswi , Kaur Rupinder , Rana Kirtan , Ram Jagat
Published: March 2017

Purpose:

To assess the knowledge and attitude of school-going adolescents regarding corneal donation in government and private schools in an urban area of Northern India.

Methods:

A school-based cross-sectional study was conducted in an urban field practice area of Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. A total of 365 participants of the seventh to 10th grade were enrolled from a government school and a private school. A pretested, semistructured, self-administered, bilingual (English and Hindi) questionnaire was used to assess the sociodemographic profile and knowledge and attitude related to corneal donation.

Results:

Most (87%) (confidence interval, 83.1%–90.0%) participants had heard about corneal donation. Only 2% of students answered all the knowledge-related questions correctly. None knew about the national toll-free number for corneal donation. Three-fourth (72%) supported the idea of corneal donation. Of them, only 44% (confidence interval, 41.0–47.1) were willing to pledge to donate their own eyes. Fears and myths were the persistent barriers. The government and private schools differed in both knowledge and attitude, with the latter performing better.

Conclusions:

Knowledge among the selected high school children was poor. Although many supported the idea, only a few were willing to donate. We suggest that program components be evaluated from time to time. Future studies should explore the role of strengthening Information Education and Communication (IEC) activities among high school students for motivating community members to pledge to donate for corneal donation.
Comparing the Effects of Particulate Matter on the Ocular Surfaces of Normal Eyes and a Dry Eye Rat Model
Authors: Han Ji Yun , Kang Boram , Eom Youngsub , Kim Hyo Myung , Song Jong Suk
Published: March 2017

Purpose:

To compare the effect of exposure to particulate matter on the ocular surface of normal and experimental dry eye (EDE) rat models.

Methods:

Titanium dioxide (TiO2) nanoparticles were used as the particulate matter. Rats were divided into 4 groups: normal control group, TiO2 challenge group of the normal model, EDE control group, and TiO2 challenge group of the EDE model. After 24 hours, corneal clarity was compared and tear samples were collected for quantification of lactate dehydrogenase, MUC5AC, and tumor necrosis factor-α concentrations. The periorbital tissues were used to evaluate the inflammatory cell infiltration and detect apoptotic cells.

Results:

The corneal clarity score was greater in the EDE model than in the normal model. The score increased after TiO2 challenge in each group compared with each control group (normal control vs. TiO2 challenge group, 0.0 ± 0.0 vs. 0.8 ± 0.6, P = 0.024; EDE control vs. TiO2 challenge group, 2.2 ± 0.6 vs. 3.8 ± 0.4, P = 0.026). The tear lactate dehydrogenase level and inflammatory cell infiltration on the ocular surface were higher in the EDE model than in the normal model. These measurements increased significantly in both normal and EDE models after TiO2 challenge. The tumor necrosis factor-α levels and terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling–positive cells were also higher in the EDE model than in the normal model.

Conclusions:

TiO2 nanoparticle exposure on the ocular surface had a more prominent effect in the EDE model than it did in the normal model. The ocular surface of dry eyes seems to be more vulnerable to fine dust of air pollution than that of normal eyes.
Optimal Dosing of Risperidone and Olanzapine in the Maintenance Treatment for Patients With Schizophrenia and Related Psychotic Disorders
Authors: Yoshimura Yusaku , Takeda Toshihiko , Kishi Yoshiki , Harada Toshiki , Nomura Akira , Washida Kenji , Yoshimura Bunta , Sato Kojiro , Yada Yuji , Aoki Shozo
Published: March 2017

Objectives

This study aims to determine the optimal tolerability dose ranges of risperidone (RIS) and olanzapine (OLZ) administered during schizophrenia maintenance phase.

Methods

Two-year continuation rates of prescription at discharge were examined using a retrospective cohort study method. Adult patients with schizophrenia and related psychotic disorders, receiving antipsychotic monotherapy with RIS or OLZ at discharge, were included. The primary outcome measures were the time to treatment discontinuation and 2-year continuation rates at 4 modal dose ranges of each drug. We estimated the optimal tolerability dose ranges by comparing the continuation rates at various modal doses.

Results

Of 648 patients, 344 received RIS and 304 received OLZ. The RIS 2-year continuation rates at 4 daily modal dose ranges were significantly different (0.5–2.5 mg: 46.0%, 3.0–5.0 mg: 40.0%, 5.5–7.5 mg: 30.0%, and 8.0–10.0 mg: 28.0%), with the difference favoring RIS at lower doses (0.5–5.0 mg) more than higher doses (5.5–10.0 mg). In contrast, there were no significant differences among OLZ 4 modal dose ranges (2.5–7.5 mg: 49.1%, 10.0–15.0 mg: 42.6%, 17.5–22.5 mg: 40.9%, and 25.0–30.0 mg: 39.0%). The time to treatment discontinuation significantly favored OLZ over RIS. However, it did not significantly differ between RIS and OLZ at lower doses.

Conclusions

It is suggested that the optimal tolerability dose range during maintenance treatment is 0.5 to 5.0 mg/d for RIS and 2.5 to 30 mg/d for OLZ, and that RIS at lower doses is comparable with OLZ at lower doses.
New Scoring System for Evaluating Patulous Eustachian Tube Patients
Authors: Ikeda Ryoukichi , Kikuchi Toshiaki , Oshima Hidetoshi , Miyazaki Hiromitsu , Hidaka Hiroshi , Kawase Tetsuaki , Katori Yukio , Kobayashi Toshimitsu
Published: March 2017

Objective:

To assess the efficacy of patulous Eustachian tube handicap inventory (PHI) for patulous Eustachian tube (PET) patients.

Study Design:

Prospective.

Setting:

Tertiary referral center.

Subjects:

A prospective survey of medical records in Sen-En Hospital identified 31 ears of 31 patients with definite PET who received insertion of the silicone plug as surgical treatment group, 29 ears of 29 patients treated with self-instillation of physiological saline solution as conservative treatment group, and 29 ears of 29 patients of sensorineural hearing loss without findings of PET treated between June 2015 and December 2015.

Method:

Diagnosis of definite PET was based on the proposal on PET diagnosis criteria announced by the Otological Society of Japan. The evaluation scale of PHI was modified from the Japanese version of the tinnitus handicap inventory-12 (THI-12). The classification for grading of severity is defined as follows: 1) no handicap (0–8), 2) mild handicap (10–16), 3) moderate handicap (18–24), and 4) severe handicap (26–40), matching the severity grades of tinnitus handicap inventory-25 (THI-25). The outcome measurement was modified from the previous scoring system and is defined as 1) complete relief, 2) significant improvement, 3) slight improvement, 4) unchanged, and 5) worse, and is applied according to the classification for grading of severity. The PHI was conducted at the first visit to our center for all patients in the three groups. For cases requiring surgery for plug insertion, patulous Eustachian tube handicap inventory 10 (PHI 10) was also conducted postsurgery after the treatment (postsurgery).

Results:

The findings from questions 1 to 7 and 9 to 11 were significantly different between the surgical (presurgery) and conservative treatment groups (p < 0.05). Taking these results, we analyzed 10 questions excluding questions 8 and 12 (PHI 10). The total score of PHI 10 averaged 19.5 ± 9.3 (n = 31) and 30.6 ± 8.6 (n = 29) in the surgical treatment (presurgery) and conservative treatment groups, respectively, with a significant difference (p < 0.05). Internal consistency reliability testing of the PHI 10 yielded a Cronbachαof 0.887 for all questions. In the surgical treatment (presurgery) and conservative treatment groups, there were 0 (0%) and 3 cases (12%) of no handicap, 3 (10%) and 13 cases (50%) of mild handicap, 6 (19%) and 4 cases (15%) of moderate handicap, and 22 (71%) and 6 cases (23%) of severe handicap, respectively. There was a significant correlation between the PHI 10 and Likert scale (r = 0.796,p < 0.01). In the surgical group, the presurgery and postsurgery PHI 10 scores (n = 25) were 29.6 ± 8.5 and 7.8 ± 11.3, respectively.

Conclusion:

The PHI 10 is suitable for evaluating severity of PET if the patients have been diagnosed as definite PET. Furthermore, this scoring system could be suitable for surgical treatment assessment.
Tests of Eustachian Tube Function: the Effect of Testing Technique on Tube Opening in Healthy Ears
Authors: Smith Matthew E. , Blythe Andrew J. C. , Baker Charlotte , Zou Charlie C. , Hutchinson Peter J. A. , Tysome James R.
Published: March 2017

Objective:

There is no agreement on the best clinical test for Eustachian tube (ET) dysfunction. Numerous tests have been developed to detect ET opening, and all require a patient to perform a Valsalva, Toynbee or sniff maneuver, or to swallow on demand. We aimed to characterize existing tests of ET function in healthy ears, and identify the optimal method and patient maneuver for each test. Our own normative data is presented alongside published comparisons.

Study Design:

Diagnostic test cohort study.

Setting:

Tertiary referral center.

Patients:

Seventy-five healthy ears from 42 volunteers.

Interventions:

Six tests of ET function, each performed using multiple different patient maneuvers.

Main Outcome Measure:

Detected ET opening rate for each test-maneuver combination.

Results:

The highest detected opening rates were: Sonotubometry 94%; nine-step test inflation/deflation 93/94%; continuous impedance 88%, patient-reported opening 79%; observed tympanic membrane movement 78%; and Tubo-tympano-aerodynamic-graphy 76%. Valsalva maneuvers were most effective at opening the ET. Toynbee and swallow maneuvers were more effective when performed without water, when compared to with water. For Valsalva and sniff maneuvers, there was significant correlation between the peak nasopharyngeal pressure generated and the ET opening rate.

Conclusion:

Based on ET opening detection rates, we recommend the use of dry swallows with sonotubometry and the nine-step test. When testing patient-reported opening and observed membrane movement, and when performing Tubo-tympano-aerodynamic-graphy and impedance tests, we recommend the use of Valsalva maneuvers. Further studies are required to explore the association between the test technique and results in ears with ET dysfunction.
Secondary Endolymphatic Hydrops
Authors: Ferster Ashley P. O’Connell , Cureoglu Sebahattin , Keskin Nevra , Paparella Michael M. , Isildak Huseyin
Published: March 2017

Hypothesis:

A review of the most recent literature will provide clinicians with an update of secondary endolymphatic hydrops, aiding in diagnosis and treatment of affected patients.

Background:

Secondary endolymphatic hydrops is a pathologic finding of the inner ear resulting in episodic vertigo and intermittent hearing loss. It is a finding for which extensive research is being performed.

Methods:

A review of the most recent literature on secondary endolymphatic hydrops was performed using PubMed literature search.

Results:

Recent investigation of secondary endolymphatic hydrops has brought attention to traumatic and inflammatory insults as causes for secondary endolymphatic hydrops. Such etiologies, including postsurgical effects of cochlear implantation and endolymphatic sac ablation; otosclerosis and its operative intervention(s); acoustic and mechanical trauma; medications; and systemic inflammatory processes, have been determined as causes of secondary lymphatic hydrops. Histopathological slides for many of the etiologies of secondary endolymphatic hydrops are presented.

Conclusion:

Through an understanding of the pathophysiology and etiologies of secondary endolymphatic hydrops, clinicians will gain a better understanding of this complex disease process, which will aid in treatment of patients with this disease process.
New biomarkers and imaging approaches for the diagnosis of deep venous thrombosis
Authors: Schaefer Jordan K. , Jacobs Benjamin , Wakefield Thomas W. , Sood Suman L.
Published: March 2017

Purpose of review

Symptoms suggestive of deep vein thrombosis (DVT) are extremely common in clinical practice, but unfortunately nonspecific. In both ambulatory and inpatient settings, clinicians are often tasked with evaluating these concerns. Here, we review the most recent advances in biomarkers and imaging to diagnose lower extremity DVT.

Recent findings

The modified Wells score remains the most supported clinical decision rule for risk stratifying patients. In uncomplicated patients, the D-dimer can be utilized with risk stratification to reasonably exclude lower extremity DVT in some patients. Although numerous biomarkers have been explored, soluble P-selectin has the most promise as a novel marker for DVT. Imaging will be required for many patients and ultrasound is the primary modality. Nuclear medicine techniques are under development, and computed tomography (CT) and magnetic resonance venography are reasonable alternatives in select patients.

D-dimer is the only clinically applied biomarker for DVT diagnosis, with soluble P-selectin a promising novel biomarker. Recent studies have identified several other potential biomarkers. Ultrasound remains the imaging modality of choice, but CT, MRI, or nuclear medicine tests can be considered in select scenarios.
Management of acute asthma exacerbations
Authors: Stenson Erin K. , Tchou Michael J. , Wheeler Derek S.
Published: March 2017

Purpose of review

Herein, we review the current guidelines for the management of children with an acute asthma exacerbation. We focus on management in the emergency department, inpatient, and ICU settings.

Recent findings

The most recent statistics show that the prevalence of asthma during childhood has decreased in certain demographic subgroups and plateaued in other subgroups. However, acute asthma accounts for significant healthcare expenditures. Although there are few, if any, newer therapeutic agents available for management of acute asthma exacerbations, several reports leveraging quality improvement science have shown significant reductions in costs of care as well as improvements in outcome.

Asthma is one of the most common chronic conditions in children and the most common reason that children are admitted to the hospital. Nevertheless, the evidence to support specific agents in the management of acute asthma exacerbations is surprisingly limited. The management of acute exacerbations focuses on reversal of bronchospasm, correction of hypoxia, and prevention of relapse and recurrence. Second-tier and third-tier agents are infrequently used outside of the ICU setting. Reducing the variation in treatment is likely to lead to lower costs and better outcomes.
Thermoregulate, autoregulate and ventilate: brain-directed critical care for pediatric cardiac arrest
Authors: Kurz Jonathan E. , Smith Craig M. , Wainwright Mark S.
Published: March 2017

Purpose of review

Cardiac arrest in childhood is associated with a high risk for mortality and poor long-term functional outcome. This review discusses the current evidence for neuroprotective therapies and goals for postarrest care in the context of the pathophysiology of hypoxic–ischemic injury, modalities for neurologic prognostication in these children and potential future monitoring paradigms for maximizing cerebral perfusion in the postarrest period.

Recent findings

The recent publication of the in-hospital and out-of-hospital Therapeutic Hypothermia After Cardiac Arrest trials demonstrated a lack of statistically significant benefit for the use of postarrest therapeutic hypothermia. As a result, targeted normothermic temperature management has become standard of care. Continuous electroencephalographic monitoring during the acute postarrest period provides useful additional data for neurologic prognostication, in addition to its value for detection of seizures. Ongoing research into noninvasive monitoring of cerebrovascular autoregulation has the potential to individualize blood pressure goals in the postarrest period, maximizing cerebral perfusion in these patients.

Therapeutic strategies after cardiac arrest seek to maximize cerebral perfusion while mitigating the effects of secondary brain injury and loss of autoregulation. Future research into new monitoring strategies and better long-term outcome measures may allow more precise targeting of therapies to these goals.
Nonoperative management of appendicitis in children
Authors: López Joseph J. , Deans Katherine J. , Minneci Peter C.
Published: March 2017

Purpose of review

The aim of this review is to summarize the recent literature investigating nonoperative management of uncomplicated and complicated appendicitis and highlight recent data establishing its safety and efficacy.

Recent findings

Recent studies and clinical trials have demonstrated the efficacy of nonoperative treatment of both uncomplicated and complicated appendicitis, defined as perforated appendicitis with or without formed abscess or phlegmon. Nonoperative management of uncomplicated appendicitis has been reported to be effective in approximately 71–94% of cases. In complicated appendicitis, treatment with antibiotics alone or antibiotics with interval appendectomy has been shown to be a well tolerated and reasonable treatment alternative.

Appendicitis is one of the most common surgical diagnoses in children. The standard of care for many years has been surgical appendectomy; however, it carries with it risks including bleeding, wound complications, injury to surrounding structures, and the potential need for reoperation. Nonoperative management of both uncomplicated and complicated appendicitis in children is well tolerated and efficacious in select populations.
Early and Late Factors Impacting Patient and Graft Outcome in Pediatric Liver Transplantation
Authors: McLin Valérie A. , Allen Upton , Boyer Olivia , Bucuvalas John , Colledan Michele , Cuturi Maria‐Cristina , d'Antiga Lorenzo , Debray Dominique , Dezsofi Antal , de Goyet Jean de Ville , Dhawan Anil , Durmaz Ozlem , Falk Christine , Feng Sandy , Fischler Björn , Franchi‐Abella Stéphanie , Frauca Esteban , Ganschow Rainer , Gottschalk Stephen , Hadzic Nedim , Hierro Loreto , Horslen Simon , Hubscher Stefan , Karam Vincent , Kelly Deirdre , Maecker‐Kolhoff Britta , Mazariegos George , McKiernan Patrick , Melk Anette , Nobili Valerio , Ozgenç Funda , Reding Raymond , Sciveres Marco , Sharif Khalid , Socha Piotr , Toso Christian , Vajro Pietro , Verma Anita , Wildhaber Barbara E. , Baumann Ulrich
Published: March 2017

As pediatric liver transplantation comes of age, experts gathered to discuss current paradigms and define gaps in knowledge warranting research to further improve patient and graft outcomes. Identified areas ripe for collaborative research include understanding the molecular and cellular mechanisms of tolerance and the role of donor‐specific antibodies, considering ways to expand donor pool, minimizing long‐term side effects of immunosuppression, and fine‐tuning surgical techniques to minimize biliary and vascular complications.
Reduced Bone Mineral Density in Children With Screening‐detected Celiac Disease
Authors: Björck Sara , Brundin Charlotte , Karlsson Magnus , Agardh Daniel
Published: March 2017

Objectives:

The aim of the study was to assess whether bone mass and metabolism are impaired in genetically at‐risk children with screening‐detected celiac disease.

Methods:

Included were 71 children with screening‐detected celiac disease diagnosed at 10.0 ± 0.7 (mean ± standard deviation) years and 142 matched controls and 30 children with screening‐detected celiac disease diagnosed at 3.3 ± 0.4 years of age presently on a gluten‐free diet for 6.9 ± 1.1 years and 60 matched controls. All participants were assessed for bone mineral density (BMD) of total body and spine by dual x‐ray absorptiometry, serum 25(OH) vitamin D3, parathyroid hormone (PTH), interleukin (IL)‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, IL‐12p70, IL‐13, IL‐15, interferon gamma, and tumor necrosis factor alpha.

Results:

At diagnosis, screening‐detected celiac disease children as compared to controls had a mean −0.03 g/cm2 reduced BMD of both total body and spine (P = 0.009 and P = 0.005, respectively), a mean −11.4 nmol/L lower level of 25(OH) vitamin D3 (P < 0.001), and a mean +1.0 pmol/L higher PTH level (P < 0.001). Systemic levels of the cytokines IL‐1β, IL‐6, IL‐8, IL‐10, IL‐12p70, IL‐13, and tumor necrosis factor alpha were all increased in screening‐detected celiac disease as compared to controls (P < 0.001). No difference in BMD, 25(OH) vitamin D3, PTH, and cytokine levels were detected in children on a gluten‐free diet compared with controls.

Conclusions:

Children with screening‐detected celiac disease have reduced BMD, lower levels of vitamin D3, higher levels of PTH, and signs of systemic inflammation compared with controls. These differences were not found in celiac disease children on a gluten‐free diet, indicating that children with screening‐detected celiac disease benefit from an early diagnosis and treatment.
Effectiveness of Double‐balloon Enteroscopy‐facilitated Polypectomy in Pediatric Patients With Peutz‐Jeghers Syndrome
Authors: Belsha Dalia , Urs Arun , Attard Thomas , Thomson Mike
Published: March 2017

Sizable small‐bowel (SB) polyps in Peutz‐Jeghers syndrome (PJS) pose a high risk for intussusception, often necessitating laparotomy and intraoperative enteroscopy. This series examines the effectiveness of double‐balloon enteroscopy (DBE) facilitated polypectomy for pediatric patients with PJS. Prospective analysis of collected data (6 years) on all patients with PJS referred for DBE‐facilitated SB polypectomy at a pediatric tertiary‐referral center. A total of 16 pediatric patients with PJS were referred for DBE‐facilitated SB polypectomy. Twenty‐two DBEs were performed. Large polyps (≥1 cm) were confirmed in 14 patients. Successful clearance of large SB polyps by DBE or laparoscopically assisted DBE (Lap‐DBE) was achieved in all patients. One patient experienced post‐Lap‐DBE pelvic abscess. All other patients remained asymptomatic and intervention free throughout follow‐up (median 26 months). This series demonstrates that DBE‐facilitated polypectomy is an effective therapeutic option in pediatric patients with PJS. It should be considered at an early age where possible.
Pulmonary Relapse of Osteosarcoma Following Presentation With a Pneumomediastinum and Localized Disease at Diagnosis
Authors: Kumar Sarayu , Alazraki Adina , George Bradley , Martin Melissa , Katzenstein Howard M. , Cash Thomas
Published: March 2017

Pneumothorax is a well-described complication of osteosarcoma. Conversely, the presence of a pneumomediastinum to our knowledge has been reported just once in a patient with osteosarcoma, and never without detectable lung metastasis. We report the case of an 18-year-old male with a localized, distal femur osteosarcoma who was found to have an asymptomatic pneumomediastinum and pneumatocele at diagnosis, and then 16 months later experienced a pulmonary relapse. Our case suggests that these findings may represent the presence of occult metastatic disease and cautions providers to treat appropriately and provide surveillance with a high index of suspicion for pulmonary recurrence.
Risk of Epilepsy in Individuals With Posttraumatic Stress Disorder: A Nationwide Longitudinal Study
Authors: Chen Yu-Hsiung , Wei Han-Ting , Bai Ya-Mei , Hsu Ju-Wei , Huang Kai-Lin , Su Tung-Ping , Li Cheng-Ta , Lin Wei-Chen , Wu Yi-Hui , Pan Tai-Long , Chen Tzeng-Ji , Tsai Shih-Jen , Chen Mu-Hong
Published: March 2017

Objective

Several cross-sectional studies have reported a relationship between posttraumatic stress disorder (PTSD) and epilepsy. However, the temporal association between PTSD and epilepsy has rarely been investigated. We hypothesized that the risk of developing epilepsy later in life would be higher in patients with PTSD than in those without PTSD.

Methods

Using the Taiwan National Health Insurance Research Database, 6425 individuals with PTSD and 24,980 age-/sex-matched controls were enrolled between 2002 and 2009 in our study and followed up to the end of 2011. Those who developed epilepsy during the follow-up period were identified.

Results

Individuals with PTSD had a higher incidence of developing epilepsy (2.65 versus 0.33 per 1000 person-years, p < .001), with an earlier onset of epilepsy (37.53 years [15.80 years] versus 48.11 years [23.97 years], p = .002) than did the controls. Individuals with PTSD had an elevated risk of developing epilepsy (hazard ratio [HR] = 3.72, 95% confidence interval [CI] = 2.27–6.11) during the follow-up after adjustment for demographic data and medical and psychiatric comorbidities. Sensitivity analyses after excluding the observation in the first year (HR = 2.53, 95% CI = 1.44–4.47) and the first 3 years (HR = 2.14, 95% CI = 1.15–4.01) revealed consistent results.

Conclusions

These results supported a temporal association between PTSD and the development of epilepsy. Further studies are warranted to investigate the underlying pathophysiological pathways that explain the longitudinal association of PTSD with subsequent epilepsy.
Pain prevalence in cancer patients: status quo or opportunities for improvement?
Authors: Haumann Johan , Joosten E. (Bert) A. , Everdingen Marieke H.J. van den Beuken-van
Published: March 2017

Purpose of review

Cancer incidence increases worldwide and thus more patients will suffer from cancer pain. As cancer pain severely affects quality of life, the decrease of pain should be of high priority for every clinician. In the last decade, attention for cancer pain and for its treatment has increased, and new pharmacological based treatment options became available. This gave reason to hypothesize a decrease in pain prevalence in cancer patients over the last decade.

Recent findings

Despite increased attention to cancer pain, pain prevalence in cancer patients has not significantly changed over the last decade as compared to the four decades before. This absence of change might be because of comorbidities cancer patients have, but also to undertreatment of pain, because of a lack of knowledge and pain measurement. Other factors underlying this absence of change are the use of incorrect coanalgesics in the case of treatment of neuropathic pain, as well as the present absence of potent analgesics with little side effects.

Consistent screening of pain in cancer patients and consequent correct treatment of pain might result in an impressive decrease in cancer pain. For further reduction of pain, new pharmacological analgesics need to be developed.
Ketamine for cancer pain: what is the evidence?
Authors: Jonkman Kelly , van de Donk Tine , Dahan Albert
Published: March 2017

Purpose of review

In this review, we assess the benefit of ketamine in the treatment of terminal cancer pain that is refractory to opioid treatment and/or complicated by neuropathy.

Recent findings

While randomized controlled trials consistently show lack of clinical efficacy of ketamine in treating cancer pain, a large number of open-label studies and case series show benefit.

Ketamine is an N-methyl-d-aspartate receptor antagonist that at low-dose has effective analgesic properties. In cancer pain, ketamine is usually prescribed as adjuvant to opioid therapy when pain becomes opioid resistant or when neuropathic pain symptoms dominate the clinical picture. A literature search revealed four randomized controlled trials that examined the benefit of oral, subcutaneous or intravenous ketamine in opioid refractory cancer pain. None showed clinically relevant benefit in relieving pain or reducing opioid consumption. This suggests absence of evidence of benefit for ketamine as adjuvant analgesic in cancer pain. These findings contrast the benefit from ketamine observed in a large number of open-label studies and (retrospective) case series. We relate the opposite outcomes to methodological issues. The complete picture is such that there is still insufficient evidence to state with certainty that ketamine is not effective in cancer pain.
CNS syndromes associated with antibodies against metabotropic receptors
Authors: Lancaster Eric
Published: March 2017

Purpose of review

Autoantibodies to Central nervous system (CNS) metabotropic receptors are associated with a growing family of autoimmune brain diseases, including encephalitis, basal ganglia encephalitis, Ophelia syndrome, and cerebellitis. The purpose of this review is to summarize the state of knowledge regarding the target receptors, the neurological autoimmune disorders, and the pathogenic mechanisms.

Recent findings

Antibodies to the γ-aminobutyric acid B receptor are associate with limbic encephalitis and severe seizures, often with small cell lung cancers. Metabotropic glutamate receptor 5 (mGluR5) antibodies associate with Ophelia syndrome, a relatively mild form of encephalitis linked to Hodgkin lymphoma. mGluR1 antibodies associate with a form of cerebellar degeneration, and also Hodgkin lymphoma. Antibodies to Homer 3, a protein associated with mGluR1, have also been reported in two patients with cerebellar syndromes. Dopamine-2 receptor antibodies have been reported by one group in children with basal ganglia encephalitis and other disorders.

CNS metabotropic receptor antibodies may exert direct inhibitory effects on their target receptors, but the evidence is more limited than with autoantibodies to ionotropic glutamate receptors. In the future, improved recognition of these patients may lead to better outcomes. Understanding the molecular mechanisms of the diseases may uncover novel treatment strategies.
Deconvolution of DNA methylation signatures identifies common differentially methylated gene regions on 1p36 across breast cancer subtypes
Authors: Titus Alexander J. , Way Gregory P. , Johnson Kevin C. , Christensen Brock C.
Published: March 2017

Breast cancer is a complex disease and studying DNA methylation (DNAm) in tumors is complicated by disease heterogeneity. We compared DNAm in breast tumors with normal-adjacent breast samples from The Cancer Genome Atlas (TCGA). We constructed models stratified by tumor stage and PAM50 molecular subtype and performed cell-type reference-free deconvolution on each model. We identified nineteen differentially methylated gene regions (DMGRs) in early stage tumors across eleven genes (AGRN, C1orf170, FAM41C, FLJ39609, HES4, ISG15, KLHL17, NOC2L, PLEKHN1, SAMD11, WASH5P). These regions were consistently differentially methylated in every subtype and all implicated genes are localized on chromosome 1p36.3. We also validated seventeen DMGRs in an independent data set. Identification and validation of shared DNAm alterations across tumor subtypes in early stage tumors advances our understanding of common biology underlying breast carcinogenesis and may contribute to biomarker development. We also provide evidence on the importance and potential function of 1p36 in cancer.
Transcription through the eye of a needle: daily and annual cycles of gene expression variation in Douglas-fir needles
Authors: Cronn Richard , Dolan Peter C. , Jogdeo Sanjuro , Wegrzyn Jill L. , Neale David B. , St. Clair J. Bradley , Denver Dee R.
Published: March 2017

Background

Perennial growth in plants is the product of interdependent cycles of daily and annual stimuli that induce cycles of growth and dormancy. In conifers, needles are the key perennial organ that integrates daily and seasonal signals from light, temperature, and water availability. To understand the relationship between seasonal rhythms and seasonal gene expression responses in conifers, we examined diurnal and circannual needle mRNA accumulation in Douglas-fir (Pseudotsuga menziesii) needles at diurnal and circannual scales. Using mRNA sequencing, we sampled 6.1×109microreads from 19 trees and constructed ade novopan-transcriptome reference that includes 173,882 tree-derived transcripts. Using this reference, we mapped RNA-Seq reads from 179 samples that capture daily, seasonal, and annual variation.

Results

We identified 12,042 diurnally-cyclic transcripts, 9,299 of which showed homology to annotated genes from other plant genomes, including angiosperm core clock genes. Annual analysis revealed 21,225 an-nually-cyclic transcripts, 17,335 of which showed homology to annotated genes from other plant genomes. The timing of maximum gene expression is associated with light quality at diurnal and photoperiod at annual scales, with two-thirds of transcripts reaching maximum expression +/− 2 hours from sunrise and sunset, and half reaching maximum expression +/− 20 days from winter and summer solstices. Comparison to published microarray-based gene expression studies in spruce (Picea) show that the rank order of expression for 760 putatively orthologous genes was significantly preserved, highlighting the generality of our findings.

Conclusions

This finding highlights the extensive annual and seasonal transcriptome variability demonstrated in conifer needles. At these temporal scales, 29% of expressed transcripts showed a significant diurnal rhythm, and 58.7% showed a significant circannual rhythm. Remarkably, thousands of genes reach their annual peak activity during winter dormancy, a time of metabolic stasis. Photoperiod appears to be a dominant driver of annual transcription patterns in Douglas-fir, and these results may be general for predicting rhythmic transcription patterns in emerging gymnosperm models.
Periaqueductal efferents to dopamine and GABA neurons of the VTA
Authors: Ntamati Niels R. , Creed Meaghan , Lüscher Christian
Published: March 2017

Neurons in the periaqueductal gray (PAG) modulate threat responses and nociception. Activity in the ventral tegmental area (VTA) on the other hand can cause reinforcement and aversion. While in many situations these behaviors are related, the anatomical substrate of a crosstalk between the PAG and VTA remains poorly understood. Here we describe the anatomical and electrophysiological organization of the VTA-projecting PAG neurons. Using rabies-based, cell type-specific retrograde tracing, we observed that PAG to VTA projection neurons are evenly distributed along the rostro-caudal axis of the PAG, but concentrated in its posterior and ventrolateral segments. Optogenetic projection targeting demonstrated that the PAG-to-VTA pathway is predominantly excitatory and targets similar proportions ofIh-expressing VTA DA and GABA neurons. Taken together, these results set the framework for functional analysis of the interplay between PAG and VTA in the regulation of reward and aversion.
Cadherin Fat2 directs cellular mechanics to promote epithelial rotation
Authors: Viktorinová Ivana , Henry Ian , Tomancak Pavel
Published: March 2017

Left and right symmetry breaking is involved in many developmental processes that are important to form bodies and organs. One of them is the epithelial rotation of developing organs. However, how epithelial cells move, how they break symmetry to define common direction of their collective movement and what function rotational epithelial motions have in morphogenesis remain elusive. Here, we identified a dynamic actomyosin network with preferred retrograde contractility at the basal side of the rotating follicle epithelium inDrosophilaoogenesis. We provide evidence that unidirectional epithelial rotation is a result of actomyosin asymmetry cue transmission onto a tissue plane synchronized by the atypical cadherin Fat2, a key planar cell polarity regulator inDrosophilaoogenesis. We found that Fat2 directs actomyosin contractility to move the epithelial tissue in order to provide directed elongation of follicle cells. In contrast, loss of Fat2 results in anisotropic non-muscle Myosin II pulses that are disorganized in plane and deform cell shape, tissue andDrosophilaeggs. Our data indicate that directed elongation of follicle cells is critical for properDrosophilaegg morphogenesis. Together, we demonstrate the importance of atypical cadherins in the control of cell mechanics, left/right symmetry breaking and its propagation onto the tissue scale to facilitate proper organ morphogenesis. This process may be evolutionarily conserved in rotating animal organs.
Adult sex ratio bias in snowy plovers is driven by sex-specific early survival: implications for mating systems and population growth
Authors: Eberhart-Phillips Luke J. , Küpper Clemens , Miller Tom E. X. , Cruz-López Medardo , Maher Kathryn H. , dos Remedios Natalie , Stoffel Martin A. , Hoffman Joseph I. , Krüger Oliver , Székely Tamás
Published: March 2017

Adult sex ratio (ASR) is a central concept in population biology and a key factor in sexual selection, yet why do most demographic models ignore sex-biases? Vital rates often vary between the sexes and across life history, but their relative contributions to ASR variation remain poorly understood—an essential step to evaluate sex ratio theories in the wild and inform conservation. Here we combine structured two-sex population models with individual-based mark-recapture data from an intensively monitored polygamous population of snowy plovers. We show that a strongly male-biased ASR is primarily driven by sex-specific survival of juveniles, rather than adults or dependent offspring. This provides empirical support for theories of unbiased sex allocation when sex-differences in survival arise after the period of parental investment. Importantly, a conventional model ignoring sex-biases significantly overestimated population viability. We suggest that sex-specific population models are essential to understand the population dynamics of sexual organisms: reproduction and population growth is most sensitive to perturbations in survival of the limiting sex. Overall, our study suggests that sex-biased early survival may contribute towards mating system evolution and population persistence, with implications for both sexual selection theory and biodiversity conservation.

SIGNIFICANCE STATEMENT

Sex biases are widespread in nature and represent a fundamental component of sexual selection and population biology—but at which point in life history do these biases emerge? Here we report a detailed individual-based demographic analysis of an intensively studied wild bird population to evaluate the origins of sex biases and their consequences on mating strategies and population dynamics. We document a strongly male-biased adult sex ratio, which is consistent with behavioral observations of female-biased polygamy. Notably, sex-biased juvenile, rather than adult survival, contributed most to the adult sex ratio. Sex-biases also strongly influenced population viability, which was significantly overestimated when sex ratio and mating system were ignored. Our study therefore has implications for both sexual selection theory and biodiversity conservation.
Vast population genetic diversity underlies the treatment dynamics ofETV6-RUNX1acute lymphoblastic leukemia
Authors: Gonzalez-Pena Veronica , MacKay Matthew , De Vlaminck Iwijn , Easton John , Gawad Charles
Published: March 2017

Ensemble-averaged genome profiling of diagnostic samples suggests that acute leukemias harbor few somatic genetic alterations. We used single-cell exome and error-corrected sequencing to survey the genetic diversity underlyingETV6-RUNX1acute lymphoblastic leukemia (ALL) at high resolution. The survey uncovered a vast range of low-frequency genetic variants that were undetected in conventional bulk assays, including additional clone-specific “driver” RAS mutations. Single-cell exome sequencing revealed APOBEC mutagenesis to be important in disease initiation but not in progression and identified many more mutations per cell than previously found. Using this data, we created a branching model ofETV6-RUNX1ALL development that recapitulates the genetic features of patients. Exposure of leukemic populations to chemotherapy selected for specific clones in a dose-dependent manner. Together, these data have important implications for understanding the development and treatment response of childhood leukemia, and they provide a framework for using population genetics to deeply interrogate cancer clonal evolution.

One-Sentence Summary

APOBEC and replication-associated mutagenesis contribute to the development of ETV6-RUNX1 ALL, creating massive leukemic population genetic diversity that results in clonal differences in susceptibilities to chemotherapy.