bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital Colposcopy With Dynamic Spectral Imaging for Detection of Cervical Intraepithelial Neoplasia 2+ in Low-Grade Referrals: The IMPROVE-COLPO Study
Authors: Cholkeri-Singh Aarathi , Lavin Philip T. , Olson Christopher G. , Papagiannakis Emmanouil , Weinberg Lori
Published: September 2017

Objective

The aim of the study was to determine, in a wide “real-world” setting, whether digital colposcopy with adjunctive dynamic spectral imaging (DSI) mapping increases the detection of women with high-grade cervical intraepithelial neoplasia (CIN).

Materials and Methods

A multicenter, two-arm, observational, cross-sectional study that recruited women 21 years and older, having colposcopy after a low-grade abnormality screening result. The prospective arm collected outcomes of digital colposcopy with DSI used for identifying biopsy sites at the colposcopists' discretion. The retrospective control arm (number of subjects matched 1:1 per colposcopist) collected outcomes of standard colposcopy. The primary outcome was histopathological detection of women with CIN 2+ by colposcopic biopsy.

Results

The study included 1,788 women in the retrospective and 1,857 in the prospective arm from 39 US community-based clinics. Subject characteristics were comparable. A total of 71.6% of the women in the retrospective and 71.5% in the prospective arm underwent biopsy. The average number of biopsies increased from 1.032 (retrospective) to 1.256 (prospective). The yield of CIN 2+ patients was 7.21% in the retrospective and 9.48% in the prospective arm, a 2.27% difference (95% confidence interval = 0.47%–4.07%, p = .014) and 31.4% relative increase. The yield of CIN 3+ patients was 2.07% in the retrospective and 3.23% in the prospective arm, a 1.16% (95% confidence interval = 0.12%–2.24%, p = .031) absolute difference and 56.1% relative increase. The false-positive rates for biopsied patients were comparable (64.43% vs 62.04%, p = .139).

Conclusions

Digital colposcopy with the adjunctive DSI increased CIN 2+ and CIN 3+ detection in low-grade referrals compared with standard colposcopy, with a similar number of women undergoing biopsy.
Acute Opiate Overdose: An Update on Management Strategies in Emergency Department and Critical Care Unit
Authors: Parthvi Rukma , Agrawal Abhinav , Khanijo Sameer , Tsegaye Adey , Talwar Arunabh
Published: September 2017

Background:

Opioids are natural, semisynthetic, or synthetic substances that act on opioid receptors in the central nervous system. Clinically, they are prescribed for pain management. Opioid overdose (OOD) occurs when the central nervous system and respiratory drive are suppressed because of excessive consumption of the drug. Symptoms of OOD include drowsiness, slow breathing, pinpoint pupils, cyanosis, loss of consciousness, and death. Due to their addictive potential and easy accessibility opioid addiction is a growing problem worldwide. Emergency medical services and the emergency department often perform initial management of OOD. Thereafter, some patients require intensive care management because of respiratory failure, metabolic encephalopathy, acute kidney injury, and other organ failure.

Areas of Uncertainty:

We sought to review the literature and present the most up-to-date treatment strategies of patients with acute OOD requiring critical care management.

Data Sources:

A PubMed search was conducted to review all articles between 1950 and 2017 and the relevant articles were cited.

Results & Conclusions:

Worldwide, approximately 69,000 people die of OOD each year, and approximately 15 million people have opioid addiction. In the United States, death from OOD has increased almost 5-fold from 2001 to 2013. OOD leading to intensive care unit admission has increased by 50% from 2009 to 2015. At the same time, the mortality associated with these admissions has doubled. The management strategies include airway management, use of reversal agents, assessing and treating coingestions and associated complications, treatment of opioid withdrawal with alpha-agonists, and psychosocial support to help with opiate addiction and withdrawal. This warrants awareness among clinicians regarding the adverse effects associated with opioid use, management strategies, and calls for a multidisciplinary approach to treating these patients.
Parental Distress and Quality of Life in Pediatric Inflammatory Bowel Disease
Authors: Diederen Kay , Haverman Lotte , Grootenhuis Martha A. , Benninga Marc A. , Kindermann Angelika
Published: September 2017

Objectives:

The interrelation between the course of inflammatory bowel disease (IBD) in children and parent's distress, and the subsequent impact this may have on health‐related quality of life (HRQOL) of the child is unclear. Therefore, we investigated patient's HRQOL and parental distress and the association between the course of IBD, parental distress, and HRQOL of pediatric patients with IBD.

Methods:

Pediatric patients with IBD (8–18 years) and parents were invited. Patients completed the Pediatric Quality of Life Inventory, and parents the Distress Thermometer for Parents, simultaneously. Disease course was expressed as current clinical disease activity or months since last IBD flare. Patient's HRQOL and parental distress were compared to healthy controls.

Results:

In total, 87 patients (71% response rate, 59% boys, median age 15.2 years) and parents were included. Patients had an impaired total HRQOL (β = 0.125, P = 0.010), driven by lower physical (0.196, P = 0.001) and school (β = 0.232, P < 0.001) functioning. Parents of children with IBD exhibited comparable levels of distress to parents of healthy children on the total problem and most subdomain problem scores (practical, social, emotional, physical, and cognitive), yet experienced more frequent parenting problems (P = 0.025). More severe disease course (months since last IBD flare) was indirectly associated, through parental distress, with decreased HRQOL of patients.

Conclusions:

Worse disease course is directly associated with increased distress of parents and indirectly with lower HRQOL of children and adolescents with IBD. Distress of parents may be considered in management of pediatric IBD to improve HRQOL of children.
Iron Status in Pediatric Celiac Disease
Authors: Popov Jelena , Baldawi Mina , Mbuagbaw Lawrence , Gould Michelle , Mileski Heather , Brill Herbert , Pai Nikhil
Published: September 2017

The present study assessed the role of serum ferritin as a noninvasive biomarker in the diagnosis and monitoring of pediatric celiac disease. A retrospective chart review was performed on patients younger than 18 years old at time of diagnosis (n = 193) between 1998 and 2015. A total of 653 paired values demonstrated a weak negative correlation between serum ferritin and tissue transglutaminase‐immunoglobulin A (r = −0.114; P = 0.004), necessitating further evaluation. A significant relationship was found between reduction of tissue transglutaminase‐immunoglobulin A and increase in serum ferritin after institution of a gluten‐free diet (P < 0.0001), suggesting that resolution of villous damage is necessary for promoting adequate iron absorption.
Growth Trajectory in Children With Short Bowel Syndrome During the First 2 Years of Life
Authors: McLaughlin Cory M. , Channabasappa Nandini , Pace Jesse , Nguyen Hoa , Piper Hannah G.
Published: September 2017

Objectives:

Infants with short bowel syndrome (SBS) require diligent nutritional support for adequate growth. Enteral independence is a primary goal, but must be balanced with ensuring sufficient nutrition. We aimed to describe growth trajectory in infants with SBS as function of nutritional intake during first 2 years of life.

Methods:

Infants with SBS were reviewed (2008–2016). z Scores for weight, height, and head circumference (HC) were recorded at birth, 3, 6, 12, 18, and 24 months. Nutritional intake, serum liver enzyme, and bilirubin levels were assessed at all time points. Pearson correlation coefficients were used to measure association with P < 0.05 considered significant.

Results:

Forty‐one infants were included, with median gestational age of 34 weeks (interquartile range [IQR] 29–36 weeks). Median small bowel length was 36 cm (IQR 26–52 cm) and median % expected small bowel length was 28% (IQR 20%–42%). Mean z scores for weight and length were >0 at birth, but <0 from 3 months to 2 years. HC remained <0 throughout the study. Mean z scores at 2 years for weight, length, HC, and weight‐for‐length were −0.90 (SD 1.1), −1.33 (SD 1.4), −0.67 (SD 1.2), and −0.12 (SD 1.2), respectively. Percentage calories from PN was positively correlated with weight in the first 3 months of life (P = 0.01).

Conclusions:

Babies with SBS are high risk for poor growth during the first 2 years of life. Although weaning PN is important for these patients, doing so too quickly in infancy may contribute to compromised growth. The long‐term impact on overall development is not known.
Sonographically Occult Abscesses of the Buttock and Perineum in Children
Authors: Nelson Courtney E. , Kaplan Summer , Bellah Richard D. , Chen Aaron E.
Published: September 2017

Background

Ultrasound (US) is used to differentiate abscess from cellulitis. At our institution, we observed children who had purulent fluid obtained after a negative abscess US. We sought to determine the incidence of sonographically occult abscess (SOA) of the buttock and perineum, and identify associated clinical and demographic characteristics.

Methods

Retrospective chart review including children younger than 18 years old presenting to pediatric emergency department with soft tissue infection of the buttock or perineum and diagnostic radiology US read as negative for abscess. We defined SOA as wound culture growing pathogenic organism obtained within 48 hours of the US. Clinical and demographic characteristics included age, sex, race, ethnicity, fever, history of spontaneous drainage, duration of symptoms, previous methicillin resistant Staphylococcus aureus (MRSA) infection, or previous abscess. We used univariate and multivariate logistic regression to assess correlation between these characteristics and SOA.

Results

A total of 217 children were included. Sixty-one (28%) children had SOA; 33 of 61 (54%) had incision and drainage within 4 hours of the US. Of children with SOA, 49 (80%) grew MRSA and 12 (20%) grew methicillin-sensitive S. aureus. In univariate analysis, a history of MRSA, symptom duration 4 days or less, age of younger than 4 years, and Hispanic ethnicity increased the odds of having SOA. In multivariate analysis, history of MRSA and duration of 4 days or less were associated with SOA.

Conclusions

Twenty-eight percent of children in our institution with US of the buttock and perineum negative for abscess had clinical abscess within 48 hours, most within 4 hours. History of MRSA and shorter symptom duration increased the odds of SOA.
Comparing Unimanual and Bimanual Training in Upper Extremity Function in Children With Unilateral Cerebral Palsy
Authors: Klepper Susan E. , Clayton Krasinski Debra , Gilb Meaghan C. , Khalil Nashwa
Published: September 2017

Purpose:

This systematic review compared intensive bimanual therapy (IBT) and modified constraint-induced movement therapy (mCIMT) in upper limb function in children with unilateral cerebral palsy (CP).

Methods:

Four electronic databases were searched from 2009 through October 2015 for randomized control trials comparing IBT with mCIMT.

Results:

Eight articles met the inclusion criteria; 5 randomized clinical trials with 221 participants with unilateral CP, ages 1.5 to 16 years, who received the intervention in a day camp, clinical, or preschool setting were included. The IBT group performed bimanual motor activities; the mCIMT group performed unilateral motor activities.

Conclusion:

There was a strong, nonspecific recommendation for either approach to improve quality of unimanual movement, bimanual capacity, and movement efficiency. There was a weak, specific recommendation for IBT in improving movement quality and a specific but weak recommendation favoring IBT to improve the child's performance on parent-reported outcomes.
Gross Motor Outcomes After Dynamic Weight-Bearing in 2 Children With Trunk Hypotonia: A Case Series
Authors: Ardolino Elizabeth , Flores Megan , Manella Kathleen
Published: September 2017

Introduction:

Children with trunk hypotonia may have limited ability to maintain an upright weight-bearing position, resulting in decreased postural control and a delay in achieving gross motor milestones.

Purpose:

The purpose of this case series is to report the effect of a home-based dynamic standing program on postural control and gross motor activity in 2 children with trunk hypotonia.

Descriptions:

Child 1 (aged 24 months, Gross Motor Function Classification Scale Level IV) and Child 2 (aged 21 months, Gross Motor Function Classification Scale Level V) participated in a standing program using the Upsee harness at home 3 days per week for 12 weeks.

Outcomes:

Both children improved their gross motor function, and Child 1 demonstrated improved trunk control in sitting.

What this case adds:

The use of the Upsee harness was an effective intervention for these children with trunk hypotonia to achieve weight-bearing and improve gross motor abilities.
Implementation of a Multifaceted Interactive Electrodiagnostic Medicine Workshop in a Physical Medicine and Rehabilitation Residency Program
Authors: Donovan Jayne , van de Rijn Marc , McCabe Elizabeth L. , Shih Shirley , Paganoni Sabrina
Published: September 2017

Electrodiagnostic medicine is a required component of Physical Medicine and Rehabilitation residency education, but limited resources exist to guide curriculum development. Our objective was to create a focused workshop to enhance our residency program's electrodiagnostic curriculum. We created two separate 1.5-day workshops, one basic and one advanced, for all residents. Each workshop included didactic sessions, case discussion, question and answer sessions, demonstrations, and hands-on participation with direct supervision and feedback. Presurveys and postsurveys were administered to evaluate the value of the workshops. We also assessed trends in electrodiagnostic self-assessment examination scores. Residents reported clinical electrodiagnostic rotations to be more valuable to their education than previous didactic sessions and independent learning. Self-reported knowledge of electrodiagnostic concepts, resident comfort level in planning, performing, and interpreting studies, and perceived value in independent learning of electrodiagnostic medicine improved after implementation of the workshops. There was a 7% improvement in the American Association of Neuromuscular and Electrodiagnostic Medicine electrodiagnostic self-assessment examination score compared with the previous year and a 15% improvement in the Physical Medicine and Rehabilitation self-assessment examination electrodiagnostic subscore compared with the previous 5 yrs. All participants recommended similar educational experience for other residents. This successful workshop may serve as a resource for other training programs.
Demonstrating Improved Surgical Communication and HAndoveR Generates Earlier Discharges (DISCHARGED)
Authors: Dean Jonathon , Phillips Georgina , Turner Warren , Refson Jonathan
Published: September 2017

Background

Weekend surgical handover at the Princess Alexandra Hospital NHS Trust in Harlow, Essex, did not fully comply with Royal College of Surgeons England guidelines. Out-of-hours care is under increased scrutiny, and we implemented a quality improvement intervention of a mandatory, standardized weekend handover form to streamline weekend care. This was shown to increase discharges and decrease lengths of stay for patients whose hospital stay included a weekend.

Methods

Data were collected for 15-week preimplementation and postimplementation. The number of patients handed over for senior weekend review was recorded, and for each, the presence or absence of a working diagnosis, relevant investigations, a management plan, and any outstanding tasks was recorded. A standardized weekend handover form was implemented, and these criteria as well numbers of discharges and lengths of stay were compared.

Results

An average of 32 patients was handed over each weekend before and after implementation. The average number of handovers with a listed working diagnosis (19.20 to 30.80, Δ11.60, P < 0.0001), management plan (16.40 to 31.73, Δ15.33, P < 0.0001), and tasks (16.60 to 29.13, Δ12.53, P < 0.0001) significantly increased. Average weekend discharges increased (39.07 to 48.93, Δ9.86, P = 0.0034). Average lengths of stay for emergency patients whose stays included a weekend shortened by 1.96 days (11.11 to 9.15 days, Δ−1.96, P = 0.0192) in keeping with the length of a weekend, with estimated annual cost-savings of between £740 000 and £3.82 million.

Conclusions

Implementation of a standardized weekend handover form resulted in an increase in compliance to national guidelines as well as an increase in weekend discharges and decreased length of stay for emergency patients with significant cost-savings.
Local Flap Technique After Removing Premaxilla for Closure of Oronasal Fistula
Authors: Fernandes Ighor Andrade , Douglas-de-Oliveira Dhelfeson Willya , Falci Saulo Gabriel Moreira , Santos Cássio Roberto Rocha dos
Published: September 2017

This letter aimed to describe a surgical technique for oronasal fistula closure that promotes efficient healing and minimizes recurrence. The oronasal fistula was repaired by buccal flap. The technique proved to be simple and efficient.
Rapid Prototyping as an Auxiliary in Mandibular Reconstructions
Authors: Sales Pedro Henrique da Hora , Cetira Filho Edson Luiz , Oliveira Neto Jair Queiroz de , Silva Julianne Coelho da , Aguiar Andrea Silvia Walter de , Mello Manoel de Jesus Rodrigues
Published: September 2017

The reconstruction of mandible is a challenge with regard to aesthetic and reconstructive demands. The etiology of mandibular fractures is variable, trauma, pathology, bone infections. There are many materials that provide an excellent form of rehabilitation for these defects, where the autogenous graft presents important characteristics that favor a greater success rate. Furthermore, the rapid prototyping method is quite interesting, because it brings a series of advantages to the surgeon, like reducing the operative time, among others. The purpose of the present article is to describe a clinical case of a patient with mandible bone defect caused by gunshot perforation, treated through iliac crest bone graft with planning through rapid prototyping. The mandibular reconstruction can present a real challenge for the surgeon. Biomodels should be required in complex cases because they help to decrease surgical time and to increase the predictability of the procedure.
A Rare Cause of Headache: Pneumatized Nasal Septum Osteoma
Authors: Erdoğan Osman , Ismi Onur , Tezer Mesut Sabri
Published: September 2017

Paranasal sinus osteomas are among the rare causes of headache and they are most commonly seen in the frontal and ethmoid sinuses. In this report, we presented the first case of pneumatized nasal septum osteoma causing headache, successfully treated with endoscopic transnasal approach.
Mucosal Melanoma Originating From the Eustachian Tube
Authors: Kim Jeong Hong , Lim Gil-Chai , Kang Ju Wan
Published: September 2017

A 77-year-old man was referred with a 4-month history of hearing impairment and ear fullness of the left ear. Otoscopic examination revealed an effusion in the left middle ear, and nasal endoscopic examination revealed a dark polypoid lesion at the opening of the left Eustachian tube. In addition to the lesion of the Eustachian tube, a dark mucosal lesion was seen at the posterior choana and the posterior end of the nasal septum. Endoscopic biopsy was done and pathologic result was consistent with malignant melanoma. Wide surgical excision with postoperative radiotherapy was performed; multiple metastases were detected 4 months after the treatment. Mucosal melanoma originating from nasopharynx was extremely rare, but careful examination of nasopharyngeal area should be considered when the patient presents with unilateral middle ear effusion, especially in older age.
Bony Changes in a Unilateral Maxillary Sinus Fungal Ball
Authors: Jun Young Joon , Shin Jae Min , Lee Jae Yong , Baek Byoung Joon
Published: September 2017

Objectives:

In the paranasal sinus fungal ball (SFB), changes that occur in the underlying bone have not been well described. Recently, bacterial coinfection has been reported in patients with paranasal SFB. We evaluated whether bone changes occur in patients with unilateral maxillary SFB, and also how bacteria in an SFB affect the bony wall of the sinus.

Methods:

A retrospective study of patients with a unilateral maxillary SFB undergoing endoscopic sinus surgery was conducted from July 2009 to December 2015. Preoperative computed tomography images of the patients were reviewed. Wall thickness (WT) and wall density (WD) of the diseased sinus were measured and compared to the normal sinus. Specimens of the sinus aspirates were obtained during surgery for aerobic and anaerobic cultures.

Results:

Forty-three patients were included (mean, 55.7 ± 12.8 years). Thirty-one cultures (72.1%) were positive for bacteria. Thickening was evident in the anterior, lateral, and posterior walls of the diseased sinus. The average WT was 1.69 ± 0.45 mm on the diseased sinus and 1.14 ± 0.31 mm on the normal sinus (P < 0.001). In the diseased sinus, the difference in the average WT between the culture-positive and culture-negative groups was not significant (P = 0.44). The average WD on the diseased sinus was higher than that on the normal sinus (P < 0.001).

Conclusions:

Osteitic change occurred in most patients with a unilateral maxillary SFB. The presence of bacteria in sinus secretions does not greatly affect the development of osteitic changes in unilateral maxillary SFB.
Dorsal Augmentation of Saddle Nose Deformity With Toothpick-Shaped Costal Cartilage Grafts in the Secondary Septorhinoplasty
Authors: Cevizci Raşit , Üstün Bezgin Selin , Çakir Burak Ömür , Kersin Burak , Bayazit Yildirim Ahmet
Published: September 2017

Saddle nose deformity is a challenging complication of septoplasty or septorhinoplasty, characterized by underprojected cartilaginous dorsum. Nasal dorsal augmentation is a significant part of reconstructive surgery of saddle nose deformities. In this study, the authors aimed to discuss the results of using toothpick-shaped costal cartilage grafts in nasal dorsal augmentation of saddle nose deformity. Twelve patients who underwent nasal dorsal augmentation due to moderate to severe saddle nose deformity secondary to the previous septoplasty or septorhinoplasty were retrospectively reviewed. Costal cartilage grafts prepared in the shape of toothpicks were used in all patients. Costal cartilage was used as toothpick-shaped free grafts in 12 patients (female: 7, male: 5) with a mean age of 42 (range: 24–56) for dorsal augmentation in the secondary septorhinoplasty. All patients had a history of previous surgery (septoplasty, n = 9; and septorhinoplasty, n = 3). All patients were operated under general anesthesia with open technique septorhinoplasty. The mean follow-up was 18 (range: 9–48) months. In only 1 of the 12 patients, a postoperative complication was observed including an infection of the tip area in the second postoperative week. None of the patients experienced donor site complications or major graft resorption. All patients were satisfied with functional and esthetic outcomes. No revision surgery was needed in any patient. Toothpick-shaped costal cartilage grafts are useful in nasal dorsal augmentation of moderate to severe saddle nose deformity. This technique offers smooth camouflage, satisfactory accordance with the recipient region, and shorter operation time. In addition, it avoids the side effects from wrapping techniques such as foreign body reaction or additional donor site morbidities.
Epidemiology of Open Globe Injury in Children
Authors: Batur Muhammed , Seven Erbil , Akaltun Mahmut Nedim , Tekin Serek , Yasar Tekin
Published: September 2017

Purpose:

The purpose of this study was to evaluate the epidemiology and outcomes of pediatric open globe injury (OGI).

Method:

The medical records of all patients diagnosed with OGI in the authors’ clinic between 1996 and 2015 were screened retrospectively. A total of 893 eyes of 892 patients aged 16 years or younger were included in the study. Open globe injury was classified according to the ocular trauma classification (OTS). Age, sex, history, cause and month of trauma, treatment received, visual acuity at presentation, final visual acuity, and cause of vision loss were recorded.

Results:

Children aged 16 years or younger comprised 67.7% of all OGI patients within the studied time period. The annual incidence of OGI in children was 5.16 per 100,000 overall, with 6.12 per 100,000 boys and 4.14 per 100,000 girls. Open globe injuries occurred most frequently in the 3 to 7 year age group and in the summer months. The most common scene of injury was playgrounds (50.2%). A strong, linear, negative correlation was found between OTS values and final visual acuity in logMAR (rp = −0.550, P = 0.0001).

Conclusion:

The authors’ study revealed that a high proportion of all OGIs in the authors’ region occurred in children under 17 years old. As with adults, OGI in children often results in significant vision loss. However, considering the varying degrees of visual recovery demonstrated by some of the authors’ patients, particularly those with no light perception at admission, the authors believe an eye-sparing approach is warranted in pediatric OGI.
Rare Enterorectal Pelvic Floor Hernia—A Cadaveric Study
Authors: Hocking Jennifer C. , Hyakutake Momoe , Webber Christine A.
Published: September 2017

We present a cadaveric case study of an 88-year-old woman with an unusual posterior perineal hernia containing small bowel, rectum, and mesentery. Dissection revealed several loops of the small bowel occupying the presacral space and displacement of the rectum into a large perineal evagination. The intestinal mucosa appeared to have been healthy at the time of death, and we did not find any indication of rectal prolapse. There was also no evidence of past surgery, suggestive of a primary hernia. We conclude this patient had a posterior enterorectal perineal hernia. Suggestions for surgical repair are described.
Performance of an Ambulatory DRY-EEG Device for Auditory Closed-Loop Stimulations in the Home Environment
Authors: Debellemaniere E. , Chambon S. , Pinaud C. , Thorey V. , Léger D. , Chennaoui M. , Arnal P.J. , Galtier M.N.
Published: September 2017

Objective

Recent research has shown that auditory closed-loop stimulations can enhance sleep slow oscillations (SO) to improve N3 sleep quality and cognition. Previous studies have been conducted in a lab environment and on a small sample size. The present study aimed at validating and assessing the performance of a novel ambulatory wireless dry-EEG device (WDD), for auditory closed-loop stimulations of SO during N3 sleep at home.

Material and Methods

The performance of the WDD to detect N3 sleep automatically and to send auditory closed-loop stimulations on SO were tested on 20 young healthy subjects who slept with both the WDD and a miniaturized polysomnography (part 1) in both stimulated and sham nights within a double blind, randomized and crossover design.

The electrophysiological effects of auditory closed-loop stimulation on delta power increase were assessed after 1 and 10 nights of stimulations on an observational pilot study in the home environment including 90 middle-aged subjects (part 2).

Results

The sensitivity and specificity of the WDD to automatically detect N3 sleep in real-time were 0.70 and 0.90, respectively. The stimulation accuracy of the SO ascending-phase targeting was 45±52°. The stimulation protocol induced an increase of 39.5 % of delta power after the stimulations. The increase of SO response to auditory stimulations remained at the same level after 10 consecutive nights.

Conclusion

The WDD shows good performances to automatically detect in real-time N3 sleep and to send auditory closed-loop stimulations on SO accurately. These stimulations increased the SO amplitude during N3 sleep without any adaptation effect after 10 consecutive nights. This tool provides new perspectives to figure out novel sleep EEG biomarkers in longitudinal studies and can be interesting to conduct broad studies on the effects of auditory stimulations during sleep.
Human olfactory cortex contributes to emotional and perceptual aspects of aversive associative learning and memory
Authors: You Yuqi , Novak Lucas R. , Clancy Kevin , Li Wen
Published: September 2017

The role of the sensory cortex, beyond the amygdala, has been increasingly recognized in animal associative learning and memory. Here, we examined olfactory cortical plasticity in human olfactory associative learning and memory, while elucidating related changes in emotional and perceptual responses. Psychophysical and neurometric analyses were conducted across an odor-morphing continuum, with the two extreme levels differentially conditioned with aversive and neutral stimuli. Conditioned odors acquired distinct emotional values, tracked by ensemble response patterns in the orbitofrontal (high-level) olfactory cortex. Also observed were enhanced perceptual discrimination and divergent ensemble neuronal response patterns in the anterior and posterior piriform (low-to-intermediate-level) olfactory cortices. Whereas emotional-learning-related changes, both behavioral and neural, maintained 8 days later, perceptual-learning-related changes, also both behavioral and neural, recovered by then, highlighting the human aptitude of forming persistent emotional memory and related sensory cortical plasticity in contrast to transient perceptual alterations of sensory stimuli associated with mild aversive experiences.
Developing anin silicominimum inhibitory concentration panel test forKlebsiella pneumoniae
Authors: Nguyen Marcus , Brettin Thomas , Long S. Wesley , Olsen Randall J. , Musser James M. , Olson Robert , Shukla Maulik , Stevens Rick L. , Xia Fangfang , Yoo Hyunseung , Davis James J.
Published: September 2017

Antimicrobial resistant infections are a serious public health threat worldwide. Whole genome sequencing approaches to apidly identify pathogens and predict antibiotic resistance phenotypes are becoming more feasible and may offer a way to reduce clinical test turnaround times compared to conventional culture-based methods, and in turn, improve patient outcomes. In this study, we use whole genome sequence data from 1668 clinical isolates ofKlebsiella pneumoniaeto develop a XGBoost-based machine learning model that accurately predicts minimum inhibitory concentrations (MICs) for 20 antibiotics. The overall accuracy of the model, within ±1 two-fold dilution factor, is 92%. Individual accuracies are≥90% for 15/20 antibiotics. We show that the MICs predicted by the model correlate with known antimicrobial resistance genes. Importantly, the genome-wide approach described in this study offers a way to predict MICs for isolates without knowledge of the underlying gene content. This study shows that machine learning can be used to build a completein silicoMIC prediction panel forK. pneumoniaeand provides a framework for building MIC prediction models for other pathogenic bacteria.
In vivoanalysis of theEscherichia coliultrastructure by small-angle scattering
Authors: Semeraro Enrico F. , Devos Juliette M. , Porcar Lionel , Forsyth V. Trevor , Narayanan Theyencheri
Published: September 2017

The flagellated Gram-negative bacteriumEscherichia coliis one of the most studied microorganisms. Despite extensive studies as a model prokaryotic cell, the ultrastructure of the cell envelope at the nanometre scale has not been fully elucidated. Here, a detailed structural analysis of the bacterium using a combination of small-angle X-ray and neutron scattering (SAXS and SANS, respectively) and ultra-SAXS (USAXS) methods is presented. A multiscale structural model has been derived by incorporating well established concepts in soft-matter science such as a core-shell colloid for the cell body, a multilayer membrane for the cell wall and self-avoiding polymer chains for the flagella. The structure of the cell envelope was resolved by constraining the model by five different contrasts from SAXS, and SANS at three contrast match points and full contrast. This allowed the determination of the membrane electron-density profile and the inter-membrane distances on a quantitative scale. The combination of USAXS and SAXS covers size scales from micrometres down to nanometres, enabling the structural elucidation of cells from the overall geometry down to organelles, thereby providing a powerful method for a non-invasive investigation of the ultrastructure. This approach may be applied for probingin vivothe effect of detergents, antibiotics and antimicrobial peptides on the bacterial cell wall.
Phototrophic microbes form endolithic biofilms in ikaite tufa columns (SW Greenland)
Authors: Trampe Erik , Castenholz Richard W. , Larsen Jens E. N. , Kühl Michael
Published: September 2017

Marine tufa‐columns, formed by the hydrated carbonate mineral ikaite, present a unique alkaline microbial habitat only found in Ikka Fjord (SW‐Greenland). The outermost parts of the ikaite columns exhibit a multitude of physico‐chemical gradients, and the porous ikaite is colonized by endolithic phototrophic biofilms serving as a substrate for grazing epifauna, where scraping by sea urchins affects overall column‐topography. We present a detailed study of the optical microenvironment, spatial organization, and photosynthetic activity of endolithic phototrophs within the porous ikaite crystal matrix. Cyanobacteria and diatoms formed distinctly coloured zones and were closely associated with ikaite‐crystals via excretion of exopolymers. Scalar‐irradiance measurements showed strong attenuation of visible light (400–700 nm), where only ∼1% of incident irradiance remained at 20 mm depth. Transmission spectra showed in vivo absorption signatures of diatom and cyanobacterial photopigments, which were confirmed by HPLC‐analysis. Variable‐chlorophyll‐fluorescence‐imaging showed active photosynthesis with high‐light acclimation in the outer diatom layer, and low‐light acclimation in the underlying cyanobacterial part. Phototrophs in ikaite thus thrive in polymer‐bound endolithic biofilms in a complex gradient microhabitat experiencing constant slow percolation of highly alkaline phosphate‐enriched spring water mixing with cold seawater at the tufa‐column‐apex. We discuss the potential role of these biofilms in ikaite column formation.
Sexually divergent DNA methylation patterns with hippocampal aging
Authors: Masser Dustin R. , Hadad Niran , Porter Hunter L. , Mangold Colleen A. , Unnikrishnan Archana , Ford Matthew M. , Giles Cory B. , Georgescu Constantin , Dozmorov Mikhail G. , Wren Jonathan D. , Richardson Arlan , Stanford David R. , Freeman Willard M.
Published: September 2017

DNA methylation is a central regulator of genome function, and altered methylation patterns are indicative of biological aging and mortality. Age‐related cellular, biochemical, and molecular changes in the hippocampus lead to cognitive impairments and greater vulnerability to neurodegenerative disease that varies between the sexes. The role of hippocampal epigenomic changes with aging in these processes is unknown as no genome‐wide analyses of age‐related methylation changes have considered the factor of sex in a controlled animal model. High‐depth, genome‐wide bisulfite sequencing of young (3 month) and old (24 month) male and female mouse hippocampus revealed that while total genomic methylation amounts did not change with aging, specific sites in CG and non‐CG (CH) contexts demonstrated age‐related increases or decreases in methylation that were predominantly sexually divergent. Differential methylation with age for both CG and CH sites was enriched in intergenic and intronic regions and under‐represented in promoters, CG islands, and specific enhancer regions in both sexes, suggesting that certain genomic elements are especially labile with aging, even if the exact genomic loci altered are predominantly sex‐specific. Lifelong sex differences in autosomal methylation at CG and CH sites were also observed. The lack of genome‐wide hypomethylation, sexually divergent aging response, and autosomal sex differences at CG sites was confirmed in human data. These data reveal sex as a previously unappreciated central factor of hippocampal epigenomic changes with aging. In total, these data demonstrate an intricate regulation of DNA methylation with aging by sex, cytosine context, genomic location, and methylation level.
Effects of wetland hydroperiod length on the functional structure of assemblages of Odonata
Authors: Pires Mateus M , Stenert Cristina , Maltchik Leonardo
Published: September 2017

The role of hydroperiod as an environmental filter in structuring wetland assemblages is usually associated with trait selection in invertebrates. However, the effects of changes in the hydroperiod of non‐permanent wetlands on invertebrate assemblages are still unclear, and few studies have assessed the functional structure of insect assemblages along the hydroperiod gradient. In this study, we investigated the effects of different hydroperiod lengths on the functional structure of Odonata assemblages in non‐permanent wetlands (posteriorly classified as ‘short‐’, ‘medium‐’ and ‘long‐hydroperiod’) in southern Brazil in 2013 and 2014. Biological traits related to life‐history strategies in temporary waters were assessed according to seasonal patterns of occurrence of nymphal and adult stages of odonates. Following the rationale of an environmental filter produced by hydroperiod, we expected to find (1) higher functional diversity in longer hydroperiods and (2) trait‐convergence patterns in odonate assemblages in shorter hydroperiods. Patterns of functional diversity were detected along the hydroperiod gradient. More specifically, higher functional dispersion was found in long‐hydroperiod wetlands and trait‐convergence patterns occurred in wetlands with shorter hydroperiods, supporting our general hypothesis. Odonate taxa with life‐history traits associated with shorter life cycles predominated in medium‐ and short‐hydroperiod wetlands. Our results thus suggest that more pronounced reductions in wetland hydroperiod length should produce odonate assemblages functionally more similar, and these results gain special importance as climate change scenarios indicate that the hydrology of wetlands will be affected by variation in rainfall regimes.
Effect of individual dietetic intervention on gestational weight gain and associated complications in obese pregnant women
Authors: Robertson Nicole , Ladlow Bridget
Published: September 2017

Background

Maternal obesity and excessive gestational weight gain (GWG) are prevalent in Australia and associated with an increased risk of birth complications, gestational diabetes and caesarean delivery.

Aim

To assess the effect of a pilot dietetic intervention in supporting the achievement of appropriate GWG.

Materials and methods

Pregnant women with a pre‐pregnancy body mass index (BMI) ≥ 35 kg/m2 (n = 174, mean BMI 40.6 ± 4.3 kg/m2) were referred for individual assessment and dietary counselling conducted by a dietitian with subsequent reviews. Education was based on the Australian Guide to Healthy Eating (AGTHE), encouraged nutritional adequacy and promoted GWG in line with current Institute of Medicine (IOM) guidelines.

Results

The intervention was associated with a significant reduction (P = 0.00) in gestational weight gain (3.57 ± 5.37 kg) when compared to previous pregnancies (14.31 ± 11.23 kg). Women who attended three or more appointments gained significantly less weight compared with those who attended the initial assessment only (P < 0.05). Rates of caesarean delivery and macrosomia were lower among participants compared to obese populations in comparable studies.

Conclusions

Dietetic intervention in obese pregnant women can assist in achieving and limiting gestational weight gain to within current IOM guidelines and reduced rates of gestational diabetes and caesarean section.
Nausea and vomiting of pregnancy: Effects on quality of life and day‐to‐day function
Authors: Tan Amelia , Lowe Sandra , Henry Amanda
Published: September 2017

Aims

To investigate the effect of nausea and vomiting of pregnancy (NVP) on quality of life (QoL) and activities of daily living/socioeconomic function in a contemporary Australian setting.

Materials and Methods

Observational, single centre prospective cohort study using validated survey instruments in pregnant women at 9–16 weeks gestation at a tertiary metropolitan women's hospital in Sydney, Australia. QoL measured by the Short‐Form Health Survey (SF‐12) was compared between those with and without NVP. NVP severity scores were correlated with QoL scores, work patterns and medication use.

Results

Of 116 participants, 72% had NVP, with no baseline (including mental health) differences between women with or without NVP. As classified by modified Pregnancy‐Unique‐Quantified‐Emesis (PUQE) survey, 42% had mild symptoms, 55% moderate and 1% severe. SF‐12 Physical Component Summary (PCS) scores were significantly lower for those with NVP (P < 0.001), but not Mental Component Summary (MCS) scores (P = 0.11). Decreasing QoL was associated with increasing NVP severity (P < 0.001), most markedly in the physical domain (P < 0.001). Only 39% of women used any NVP treatment and 15% pharmacotherapy. Most used treatments were vitamin B6, ginger, metoclopramide and natural remedies. Significantly more women with NVP required time off work (45% vs 16%, P = 0.003).

Conclusions

NVP is a physically morbid disease, affecting most pregnancies. NVP has a significant detrimental impact on QoL, especially physical QoL and work function. Despite this, we found low treatment utilisation, even in those with moderate/severe symptoms. Women should be encouraged to seek assistance for NVP and further education is required to improve practitioner awareness and management.
Paternal age and risk of testicular germ cell tumors: a cohort study of 1,000,000 men
Authors: Levine H. , Keinan‐Boker L. , Leiba A. , Derazne E. , Rais A. , Kark J. D.
Published: September 2017

Testicular germ cell tumors (TGCT) are the most frequent cancer among young men, with increasing incidence worldwide. Advanced paternal age has been linked to adverse health outcomes in offspring, but reports on the association of paternal age with TGCT are few and inconsistent. We aimed to examine the relationship of paternal age (PAB) at birth with the risk of TGCT and by histologic type: seminoma and non‐seminoma. A population‐based cohort of 1,056,058 males, examined at ages 16–19 between the years 1980–2011, was linked to the Israel National Cancer Registry to obtain incident TGCT through 2012. We applied multivariable Cox regression. During 16.5 million person‐years of follow‐up, 1247 incident cases (604 seminomas and 643 non‐seminomas) were detected. Increasing PAB was linearly associated with lower risk of TGCT (HRper year = 0.983, 95% CI: 0.974–0.993, p = 0.001), after adjustment for year of birth, years of education, height, cryptorchidism history and origin, and also with additional adjustment for maternal age at birth (MAB) (HRper year = 0.980: 0.965–0.995, p = 0.008). The association was stronger for seminoma (HRper year = 0.968: 0.946–0.989, p = 0.004) and persisted in a subset adjusted for sibship size (HRper year = 0.950: 0.917–0.983, p = 0.003). In the fully adjusted model, young PAB (15–24 vs. ≥30) was a risk factor for seminoma (HR = 1.41: 1.07–1.85, p = 0.014). In models adjusted for PAB, MAB was not associated with risk of TGCT. In conclusion, our findings suggest that young paternal age is a risk factor of TGCT, especially seminoma. The findings warrant further investigation into the possible impact of young paternal age on their offsprings’ testes.
Effects of testosterone supplementation therapy on lipid metabolism in hypogonadal men with T2DM: a meta‐analysis of randomized controlled trials
Authors: Zhang K.‐S. , Zhao M.‐J. , An Q. , Jia Y.‐F. , Fu L.‐L. , Xu J.‐F. , Gu Y.‐Q.
Published: September 2017

Testosterone supplementation may be effective for the treatment of hypogonadism in men with type 2 diabetes mellitus (T2DM), but the evidence from randomized controlled trials (RCTs) is inconclusive. We aimed to systematically summarize results from intervention studies and assess the effects of testosterone supplementation therapy (TST) on lipid metabolism in RCTs of hypogonadal men with T2DM by meta‐analysis. PubMed, Embase, and Cochrane Library databases were searched for studies reporting the effect of TST on lipid metabolism in hypogonadal men with T2DM until December 31, 2016. Seven RCTs from 252 trials, enrolling a total of 612 patients in the experimental and control groups with a mean age of 58.5 years, were included in this study. The pooled results of the meta‐analysis demonstrated that TST significantly decreased TC and TG levels in hypogonadal men with T2DM compared with the control group, with mean differences (MDs) of −6.44 (95% CI: −11.82 to −1.06; I2 = 28%; p = 0.02) and −27.94 (95% CI: −52.33 to −3.54; I2 = 76%; p = 0.02). Subgroup analyses revealed that the heterogeneity (I2 = 76%) of TG originated from different economic regions, in which economic development, genetic and environmental factors, and dietary habits affect lipid metabolism of human, with a decrease (I2 = 45%) in developed countries. Additionally, subgroup analyses showed that TST increased HDL‐C level in developing countries compared with the control group (MD = 2.79; 95% CI: 0.73 to 4.86; I2 = 0%; p = 0.008), but there was no improvement in developed countries (MD = 1.02; 95% CI: −4.55 to 6.60; I2 = 91%; p = 0.72). However, LDL‐C levels were not improved consistently. Because the relationship between lipid metabolism and atherosclerosis is unequivocal, TST, which ameliorates lipid metabolism, may decrease the morbidity and mortality of cardiovascular disease in hypogonadal men with T2DM by preventing atherogenesis.
Parathyroid hormone is related to QT interval independent of serum calcium in patients with coronary artery disease
Authors: Palmeri Nicholas O. , Davidson Karina W. , Whang William , Kronish Ian M. , Edmondson Donald , Walker Marcella D.
Published: September 2017

Background

Elevated serum parathyroid hormone (PTH) is associated with increased risk of cardiovascular death, including sudden cardiac death, in patients with and without parathyroid disease. In small studies, PTH levels have been associated with changes in cardiac conduction and repolarization. Changes in the corrected QT interval (QTc) in particular are thought to be mediated by the effect of PTH on serum calcium. There is limited evidence to suggest PTH may affect cardiac physiology independent of its effects on serum calcium, but there is even less data linking PTH to changes in electrical conduction and repolarization independent of serum calcium.

Methods

ECG data were examined from the PULSE database—an observational cohort study designed to examine depression after acute coronary syndromes (ACS) at a single, urban American medical center. In all, 407 patients had PTH and ECG data for analysis.

Results

The QTc was longer in patients with elevated PTH levels compared with those without elevated PTH levels (451 ± 38.6 ms vs. 435 ± 29.8 ms; p < .001). The difference remained statistically significant after controlling for calcium, vitamin D, and estimated glomerular filtration rate (p = .007). Inclusion of left ventricular ejection fraction in the model attenuated the association (p = .054), suggesting that this finding may be partly driven by changes in cardiac structure.

Conclusions

In one of the largest series to examine PTH, calcium, and QT changes, we found that elevated PTH is associated with longer corrected QT interval independent of serum calcium concentration in ACS survivors.