bluuebunny/crossref_metadata_2025 huggingface dataset:
Simbu Ptosis: An Outreach Approach to Myogenic Ptosis in Eastern Highlands of Papua New Guinea—Experience and Results From a High-Volume Oculoplastic Surgical Camp
Authors: Gushchin Anna G. , Crum Alison V. , Limbu Ben B. , Quigley Edward P. , Seward Michael S. , Tabin Geoffrey C.
Published: December 2016

Purpose:

To present the results of a high-volume oculoplastic surgical outreach in a remote region of Simbu Province in the Eastern Highlands of Papua New Guinea. The authors describe the clinical features and evaluation and treatment of a novel ptosis syndrome found in this area.

Design:

A team of 4 international ophthalmologists and 3 local doctors and 3 local nurses involved in a high-volume field intervention for all patients presenting with a bilateral ptosis to Mingende Rural Hospital.

Methods:

Patients were systematically evaluated and treated during a 6-day surgical outreach and followed daily for 1 week and as needed via telemedicine. Visiting surgeons provided skills-transfer instruction for 3 local doctors and 3 nurses. Data collected included demographic information, history of present illness, past medical history, family history, social history, and a complete ophthalmologic and targeted neurologic evaluation. Patients were offered surgical intervention if they met criteria for safe eyelid elevation and could present for follow ups. Detailed notes of patient geographic location, history, and risk factors were collected in addition to pre- and postoperative photos.

Main outcome measures:

Efficient triage and treatment of all patients referred to the remote oculoplastic clinic.

Results:

A total of 97 patients presented to the camp; of these, 87 underwent complete evaluation. There were 72 patients with ptosis, of which 60 were found to be of Simbu-type. These patients were grouped clinically by degree of ptosis: mild, moderate, and severe. Thirty-eight patients had moderate ptosis of which 34 underwent surgical intervention. Eleven patients with mild ptosis were counseled and observed. The 10 patients with severe ptosis and 2 with moderate ptosis were treated medically with ptosis crutches manufactured on site. A new technique for creating ptosis crutch glasses was developed.

Conclusions:

A new variant of progressive myogenic ptosis was identified. A high-volume oculoplastic surgical camp is an efficient way to systematically evaluate and treat this new entity. Skills-transfer training for local doctors and staff ensured continuity of care for the surgical patients.
The Brow Fat Pad Suspension Suture: Safety Profile and Clinical Observations
Authors: Eftekhari Kian , Peng Grace L. , Landsberger Hannah , Douglas Raymond , Massry Guy G.
Published: December 2016

Purpose:

To evaluate the safety, subjectively assess outcome, and emphasize surgical pearls and critical clinical observations of upper blepharoplasty performed in conjunction with the brow fat pad suspension suture procedure, previously referred to as a “browpexy variant” or “brassiere suture procedure.”

Methods:

A retrospective 4-year analysis of patients who underwent the brow fat pad suspension suture with upper blepharoplasty was performed. Adjunctive procedures (brow lift and ptosis repair) were categorized. The surgical technique is detailed with emphasis placed on nuances to aid in optimal outcome.

Results:

Two hundred and sixteen patients (149 women and 47 men) underwent upper blepharoplasty with the brow fat pad suspension suture. The average patient age is 54 years and follow up is 11 months. One hundred patients had adjudicative brow lift or ptosis repair, and in 20 patients the blepharoplasty was a revision procedure. Subjective assessment of outcome showed excellent aesthetic results with improved brow projection, and enhanced lateral tarsal platform show and eyebrow/eyelid contour. Surgical complications were infrequent and patient satisfaction was high.

Conclusions:

This initial large series description of the brow fat pad suspension suture demonstrates that it is a safe adjunct to upper blepharoplasty, which the authors believe subjectively improves overall outcome. Evidence-based quantitative assessments of objective measures of surgical results are currently underway.
Mycoplasma pneumoniae and Stevens-Johnson Syndrome
Authors: Álvarez Álvarez Nelly , Fernández-Luis Sheila , Sánchez-Villares Lorenzo Claudia , Roncero Toscano Mónica Lilian , Mendoza Sánchez María del Carmen
Published: December 2016

Stevens-Johnson syndrome is an uncommon mucocutaneous disease usually considered as severe drug reactions, and other different agents can take part in its etiopathogenesis, including infections such as the one caused by Mycoplasma pneumoniae. We describe the clinical evolution, diagnosis, and treatment of an 8-year-old boy with mucous injury associated to an infection by M. pneumoniae and present a review of all cases published in the last 8 years.
Abdominal compartment syndrome and the open abdomen: any unresolved issues?
Authors: Sugrue Michael
Published: December 2016

Purpose of review

This article reviews the key principles of abdominal compartment syndrome and the open abdomen, exploring some of the unresolved issues. It reviews new concepts in care.

Recent findings

Recent use of peritoneal resuscitation, and benefits of mesh-mediated traction are discussed. Abdominal compartment syndrome remains a result of complex interaction between general haemorrhage, sepsis and fluid resuscitation. Improved resuscitation and sepsis control has decreased but not abolished the need for the open abdomen and progression for abdominal compartment syndrome. Fourth-generation abdominal wall dressings need to be combined with a dynamic closure system; currently, negative pressure wound therapy at the index open abdomen coupled with mesh-mediated tractions offers the best outcome.

The key to optimizing outcome is early abdominal closure within 7 days because failure to do so will increase morbidity, mortality and fistulae formation. Novel techniques complementing existing de-resuscitation techniques are discussed.
Endoscopic Ultrasound–guided Drainage of Walled‐off Necrosis in Children With Fully Covered Self‐expanding Metal Stents
Authors: Nabi Zaheer , Lakhtakia Sundeep , Basha Jahangeer , Chavan Radhika , Ramchandani Mohan , Gupta Rajesh , Kalapala Rakesh , Darisetty Santosh , Talukdar Rupjyoti , Reddy Duvuur Nageshwar
Published: December 2016

Objectives:

Endoscopic ultrasound (EUS)‐guided drainage with fully covered self‐expanding metallic stents (FCSEMS) has been successfully used in adult patients. The utility of FCSEMS in children with walled‐off necrosis (WON) is, however, unknown. The aim of present study was to evaluate the feasibility, safety, and efficacy of EUS drainage of WON using FCSEMS in children.

Methods:

We retrospectively evaluated the data of children (18 years or younger) who underwent EUS drainage of WON using FCSEMS at our institution. All FCSEMS were removed between 1 and 3 months. Feasibility, safety, and efficacy were analysed.

Results:

Twenty‐one children (20 boys, mean age 14.9 ± 2.34 years, range 9–18 years) underwent EUS‐guided drainage of WON with FCSEMS. The median size of WON was 88 mm (55–148 mm). The median interval between onset of acute pancreatitis and EUS guided drainage was 58 days (range 30–288 days). The technical and clinical success rates were 100% and 95%, respectively. Nasocystic tube was placed in 3 children for lavage. Endoscopic necrosectomy was not required in any of the children. There were no major complications. Minor complications included bleeding (2), stent migration (1), and difficulty in removal of stent (1). After a median follow‐up of 360 days (range: 30–1020 days), there was 1 recurrence of WON.

Conclusions:

EUS drainage of WON using specially designed FCSEMS is safe and efficacious in children. The utility of FCSEMS in children should be further explored and compared with plastic stents.
A Comparison Study
Authors: Yoo Yang Gyeong , Yu Boas J. , Choi Eun-Hi
Published: December 2016

Background:

In South Korea, there has been a rapid increase in thyroid cancer diagnoses, and the thyroid cancer incidence rate is the highest in the world. This study explored possible risk factors that may influence the development of thyroid cancer by comparing life habits of thyroid cancer patients and healthy adults.

Objective:

The aims of this study were to identify lifestyle and habit differences in thyroid cancer patients and healthy adults and to investigate risk factors that influence the development of thyroid cancer.

Methods:

The study was designed as a retrospective comparison survey study of thyroid cancer patient group and healthy adult group. One hundred two thyroid cancer patients in a university hospital and 115 healthy adults were recruited for this study. Data were analyzed using descriptive statistics, χ
2 test/t test, and logistic regression with SPSS program.

Results:

Previous smoking history, lower physical activity level, higher stress, and unhealthy eating habits (consumption of instant food products) were shown to be risk factors in the development of thyroid cancer.

Conclusion:

Based on the results of this study comparing thyroid cancer patients and healthy adults, it is recommended to encourage an increase in physical activity, minimize both direct and indirect exposure to smoking, develop healthy eating habits of consuming more vegetables, and effectively manage stress levels.

Implications for Practice:

Lifestyle preferences and habits may influence the development of thyroid cancer. It is imperative to identify and modify the risk factors in order to prevent thyroid cancer development.
Cancer Survivors’ Experiences and Explanations of Postcancer Fatigue
Authors: Watson Amy , van Kessel Kirsten
Published: December 2016

Background:

Postcancer fatigue (PCF) is a form of chronic fatigue that is very common and can persist for years among disease-free cancer survivors. Despite this, PCF remains underreported and often goes untreated.

Objective:

The aim of this study is to explore PCF from the perspective of cancer survivors via online blogs, with a focus on their experiences and personal explanations of PCF.

Methods:

An online search identified 15 recent blogs written by cancer survivors who specifically discussed their PCF. Thematic analysis was used to analyze blog content.

Results:

Bloggers explained PCF as a severe and unpredictable symptom in their lives. They identified anxiety, emotional trauma, and cancer side effects to be the key causal factors of their PCF. Coping strategies adopted by bloggers included diet, exercise, acceptance and reducing workload to manage their fatigue.

Conclusions:

Online blogs are a rich source of qualitative data that can give unique insight into issues faced by cancer survivors. Bloggers’ accounts confirmed that PCF is a complex issue that can be a significant source of frustration in their everyday lives. This study highlighted that bloggers with PCF appear to have some coping strategies and understanding of PCF, yet these are not always consistent with current medical and psychological knowledge.

Implications for Practice:

This study has demonstrated that blogs can offer valuable information to existing knowledge of cancer survivors’ experiences and explanations of PCF. The findings may assist healthcare professionals with educating patients about PCF and with increasing the legitimacy, awareness, and understanding of PCF.
Performance of 4 Immunohistochemical Phosphohistone H3 Antibodies for Marking Mitotic Figures in Breast Cancer
Authors: Focke Cornelia M. , Finsterbusch Kai , Decker Thomas , van Diest Paul J.
Published: December 2016

Background:

Phosphohistone H3 (PHH3) has been suggested to facilitate and improve mitotic activity assessment in breast cancer and other tumor entities, but the reliability of respective immunohistochemical antibodies has not yet been compared for routine purposes. Our aim was to test the performance of 4 different PHH3 antibodies on a series of highly proliferating breast cancers with good preservation of morphology.

Methods:

Four commercially available PHH3 antibodies were tested on 9 grade 3 invasive breast cancers processed in the same batch. We analyzed the number of antibody stained and nonstained mitotic figures as well as the total of cells observed in 10 high power fields per tumor to calculate sensitivity, specificity, and accuracy of the respective antibodies for staining mitotic figures, taking morphologically defined mitotic figures as gold standard.

Results:

Sensitivity, specificity, and accuracy of the respective PHH3 antibodies for staining mitotic figures were 54.51%, 99.98%, and 98.79% for Cell Marque, 87.48%, 67.62%, and 67.47% for Epitomics, 98.62%, 99.73%, and 99.49% for Merck 06-570, and 99.74%, 99.52%, and 99.51% for Merck 09-797, respectively. Sensitivity was lowest for telophase. In statistical analysis, the Cell Marque antibody demonstrated significantly lower sensitivity and Epitomics substantially lower sensitivity and specificity than Merck 06-570 and Merck 09-797 antibodies (P<0.0001, respectively).

Conclusions:

Performance and reliability varied significantly between the 4 tested antibodies. For faster identification of mitotic hot spots and as potential marker in digital image analysis, the Merck antibodies seem to be most suitable.
Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine: Part 4: Tissue Tools for Quality Assurance in Immunohistochemistry
Authors: Cheung Carol C. , D’Arrigo Corrado , Dietel Manfred , Francis Glenn D. , Fulton Regan , Gilks C. Blake , Hall Jacqueline A. , Hornick Jason L. , Ibrahim Merdol , Marchetti Antonio , Miller Keith , van Krieken J. Han , Nielsen Soren , Swanson Paul E. , Taylor Clive R. , Vyberg Mogens , Zhou Xiaoge , Torlakovic Emina E.
Published: December 2016

The numbers of diagnostic, prognostic, and predictive immunohistochemistry (IHC) tests are increasing; the implementation and validation of new IHC tests, revalidation of existing tests, as well as the on-going need for daily quality assurance monitoring present significant challenges to clinical laboratories. There is a need for proper quality tools, specifically tissue tools that will enable laboratories to successfully carry out these processes. This paper clarifies, through the lens of laboratory tissue tools, how validation, verification, and revalidation of IHC tests can be performed in order to develop and maintain high quality “fit-for-purpose” IHC testing in the era of precision medicine. This is the final part of the 4-part series “Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine.”
The Role of Collagen IV and Cytokeratin 5/6 Immunohistochemistry in Identifying Subtypes of Hereditary Epidermolysis Bullosa
Authors: Alhumidi Ahmed
Published: December 2016

Hereditary epidermolysis bullosa (EB) constitute a genodermatosis group with variable clinical severity. Biopsies diagnosed as EB in the last 4 years were retrieved from the database of the king Khalid University Hospital and military hospital lab at Saudi Arabia. The current study was performed to examine the diagnostic usefulness of immunohistochemistry, as compared with electron microscopic examination, for subclassification of HEB. Fourteen cases were studied. Collagen IV immunostain was located above the blister in all dystrophic EB cases, and below the blister in all cases of epidermolytic and junctional EB. Cytokeratin 5/6 was visible above the blister in all cases of dystrophic and junctional types EB. In 2 out of 4 cases of epidermolytic EB, cytokeratin 5/6 was seen only above the cleft, whereas 1 case revealed positivity above and below the blister. One epidermolytic EB case showed scattered fragments of keratinocytes inside the blister.
Paired Box 5 (PAX5) Expression in Poorly Differentiated Neuroendocrine Carcinoma of the Gastrointestinal and Pancreatobiliary Tract: Diagnostic and Potentially Therapeutic Implications
Authors: Ainechi Sanaz , Mann Steven A. , Lin Jingmei , Patil Deepa , Sheehan Christine E. , Yang Zhaohai , Zuo Chunlai , Lee Hwajeong
Published: December 2016

Paired Box 5 (PAX5), a well-established B-cell marker, is preferentially expressed in small cell lung carcinoma and regulates the transcription of c-Met, offering a potential for therapeutic target. Its expression in poorly differentiated neuroendocrine carcinoma (PDNEC) of the digestive system has not been systemically evaluated. Archived pathology materials from 38 PDNEC in the gastrointestinal (GI) and pancreatobiliary (PB) tract were reviewed. Representative tumor sections were subject to immunohistochemical stain for PAX5, c-Met, and CD20. The extent of the staining [focal (<10%), patchy (10% to 50%), and diffuse (>50%)] and intensity (1+ to 3+) was evaluated. In total, 38 cases of well-differentiated neuroendocrine tumors from GI/PB tract served as controls. Nuclear PAX5 staining was observed in 16 (42%) cases in total, in 46% (11/24) of large cell neuroendocrine carcinoma, 67% (4/6) of small cell neuroendocrine carcinoma, and 13% (1/8) of mixed adenoneuroendocrine carcinoma, with diffuse (8), patchy (4), or focal (4) staining. The intensity was 3+ (2), 2+ (6), and 1+ (8). PAX5 expression was common in ampullary (4/5) and gastroesophageal junctional/esophageal (5/9) PDNEC. Two (5%) of 38 well-differentiated neuroendocrine tumors were positive for PAX5. Three PAX5 positive PDNEC showed weak cytoplasmic c-Met immunolabeling. CD20 was negative in all tumors. Our data show that PAX5 is commonly expressed in PDNEC of the GI/PB tract including small cell neuroendocrine carcinoma. This observation warrants a cautious approach when interpreting small biopsy of poorly differentiated neoplasms, especially when lymphoma is considered in the differentials. Further study of PAX5/c-Met signaling pathway and its potential therapeutic value in GI/PB PDNEC is warranted.
Folate Receptor Alpha Expression in Platinum Resistant/Refractory Ovarian Carcinomas and Primary Endocervical Adenocarcinomas
Authors: Rubinsak Lisa A. , Cohen Cynthia , Khanna Namita , Horowitz Ira R. , Hanley Krisztina Z.
Published: December 2016

Introduction:

Treatment of advanced stage ovarian carcinoma is challenging, and despite surgical treatment and chemotherapy, the 5-year survival rate is estimated around 30%. Early recurrence and resistance to platinum-based chemotherapy are associated with poor prognosis and limited response to available second-line chemotherapy. The relative incidence of endocervical adenocarcinoma (EAC) compared with squamous cell carcinoma is increasing. Although the first-line treatment modality for early stage EAC is surgical resection, for locally advanced disease chemoradiation or neoadjuvant chemotherapy is used. Recently, folate along with its receptor alpha (FRA) has been studied as a potential target in gynecologic malignancy. The objective of this study was to elucidate FRA expression in chemotherapy resistant ovarian cancer and primary EAC.

Methods:

FRA expression was evaluated in tissue samples in an epithelial ovarian tumor microarray and 2 study groups: platinum resistant ovarian cancer and primary EAC. Staining intensity was analyzed with a semiquantitative staining algorithm.

Results:

FRA expression was positive in 32 of 40 (80%) ovarian tumors in the control group. In the platinum resistant ovarian cancer group, FRA was expressed in all 30 samples with moderate to strong staining. None of the EAC samples stained positive for FRA expression.

Conclusions:

FRA expression occurs frequently in epithelial ovarian cancer. Our data supports that FRA expressions are maintained after chemotherapy treatment. Folate targeted therapies may be most useful in patients with chemotherapy resistant disease based on high levels of FRA expression in these tumors. There is likely no benefit to folate therapy as an adjuvant treatment in EAC.
A Systemic Inflammation Mortality Risk Assessment Contingency Table for Severe Sepsis*
Authors: Carcillo Joseph A. , Sward Katherine , Halstead E. Scott , Telford Russell , Jimenez-Bacardi Adria , Shakoory Bita , Simon Dennis , Hall Mark
Published: December 2016

Objectives:

We tested the hypothesis that a C-reactive protein and ferritin-based systemic inflammation contingency table can track mortality risk in pediatric severe sepsis.

Design:

Prospective cohort study.

Setting:

Tertiary PICU.

Patients:

Children with 100 separate admission episodes of severe sepsis were enrolled.

Interventions:

Blood samples were attained on day 2 of sepsis and bi-weekly for biomarker batch analysis. A 2 × 2 contingency table using C-reactive protein and ferritin thresholds was developed.

Measurements and Main Results:

A C-reactive protein of 4.08 mg/dL and a ferritin of 1,980 ng/mL were found to be optimal cutoffs for outcome prediction at first sampling (n = 100) using the Youden index. PICU mortality was increased in the “high-risk” C-reactive protein greater than or equal to 4.08 mg/dL and ferritin greater than or equal to 1,980 ng/mL category (6/13 [46.15%]) compared with the “intermediate-risk” C-reactive protein greater than or equal to 4.08 mg/dL and ferritin less than 1,980 ng/mL or C-reactive protein less than 4.08 mg/dL and ferritin greater than or equal to 1,980 ng/mL categories (2/43 [4.65%]), and the “low-risk” C-reactive protein less than 4.08 mg/dL and ferritin less than 1,980 ng/mL category (0/44 [0%]) (odds ratio, 36.43 [95% CI, 6.16–215.21]). The high-risk category was also associated with the development of immunoparalysis (odds ratio, 4.47 [95% CI, 1.34–14.96]) and macrophage activation syndrome (odds ratio, 24.20 [95% CI, 5.50–106.54]). Sixty-three children underwent sequential blood sampling; those who were initially in the low-risk category (n = 24) and those who subsequently migrated (n = 19) to the low-risk category all survived, whereas those who remained in the “at-risk” categories had increased mortality (7/20 [35%]; p < 0.05).

Conclusions:

A C-reactive protein- and ferritin-based contingency table effectively assessed mortality risk. Reduction in systemic inflammation below a combined threshold C-reactive protein of 4.08 mg/dL and ferritin of 1,980 ng/mL appeared to be a desired response in children with severe sepsis.
Stress, Illness Perceptions, Behaviors, and Healing in Venous Leg Ulcers: Findings From a Prospective Observational Study
Authors: Walburn Jessica , Weinman John , Norton Sam , Hankins Matthew , Dawe Karen , Banjoko Bolatito , Vedhara Kavita
Published: December 2016

Objective

The aim of the study was to investigate the impact of stress, illness perceptions, and behaviors on healing of venous leg ulcers.

Methods

A prospective observational study of 63 individuals for 24 weeks investigated possible psychosocial predictors of healing. There were two indices of healing: rate of change in ulcer area and number of weeks to heal. Psychological variables were assessed at baseline using self-report measures (Perceived Stress Scale, Hospital Anxiety and Depression Scale, Revised Illness Perception Questionnaire, adapted Summary of Diabetes Self-Care Activities, Adherence Questionnaire, and Short-Form Health Survey).

Results

Controlling for sociodemographic and clinical variables, for the 24 weeks, a slower rate of change in ulcer area was predicted by greater stress (standardized β = −0.61, p = .008), depression (standardized β = −0.51, p = .039), and holding negative perceptions or beliefs about the ulcer (standardized β = −1.4, p = .045). By 24 weeks, 69% of ulcers had closed. A more negative emotional response to the ulcer at baseline (i.e., emotional representation of the ulcer) was associated with a greater number of weeks to heal (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.41-0.95, p = .028). Higher educational attainment (HR = 3.22, 95% CI = 1.37–7.55, p = .007) and better adherence to compression bandaging (HR = 1.41, 95% CI = 1.06–1.88, p = .019) were associated with fewer weeks to heal. No other psychosocial variable (stress, perceptions about the ulcer, health behaviors) predicted weeks to heal.

Conclusions

Alongside ulcer-related predictors, psychological and sociodemographic factors were associated with healing. Future research should explore mediating mechanisms underlying these associations and develop interventions to target these variables.
An Attachment-Based Model of the Relationship Between Childhood Adversity and Somatization in Children and Adults
Authors: Maunder Robert G. , Hunter Jonathan J. , Atkinson Leslie , Steiner Meir , Wazana Ashley , Fleming Alison S. , Moss Ellen , Gaudreau Helene , Meaney Michael J. , Levitan Robert D.
Published: December 2016

Objective

An attachment model was used to understand how maternal sensitivity and adverse childhood experiences are related to somatization.

Methods

We examined maternal sensitivity at 6 and 18 months and somatization at 5 years in 292 children in a longitudinal cohort study. We next examined attachment insecurity and somatization (health anxiety, physical symptoms) in four adult cohorts: healthy primary care patients (AC1, n = 67), ulcerative colitis in remission (AC2, n = 100), hospital workers (AC3, n = 157), and paramedics (AC4, n = 188). Recall of childhood adversity was measured in AC3 and AC4. Attachment insecurity was tested as a possible mediator between childhood adversity and somatization in AC3 and AC4.

Results

In children, there was a significant negative relationship between maternal sensitivity at 18 months and somatization at age 5 years (B = −3.52, standard error = 1.16, t = −3.02, p = .003), whereas maternal sensitivity at 6 months had no significant relationship. In adults, there were consistent, significant relationships between attachment insecurity and somatization, with the strongest findings for attachment anxiety and health anxiety (AC1, β = 0.51; AC2, β = 0.43). There was a significant indirect effect of childhood adversity on physical symptoms mediated by attachment anxiety in AC3 and AC4.

Conclusions

Deficits in maternal sensitivity at 18 months of age are related to the emergence of somatization by age 5 years. Adult attachment insecurity is related to somatization. Insecure attachment may partially mediate the relationship between early adversity and somatization.
Trauma and Autonomic Dysregulation: Episodic—Versus Systemic—Negative Affect Underlying Cardiovascular Risk in Posttraumatic Stress Disorder
Authors: Dennis Paul A. , Kimbrel Nathan A. , Sherwood Andrew , Calhoun Patrick S. , Watkins Lana L. , Dennis Michelle F. , Beckham Jean C.
Published: December 2016

Objective

Posttraumatic stress disorder (PTSD) has been linked to elevated heart rate (HR) and reduced heart rate variability (HRV) in cross-sectional research. Recent evidence suggests that this link may be driven by individual differences in autonomic arousal associated with momentary negative affect (NA). Using ecological momentary assessment (EMA) of NA and minute-to-minute HR/HRV monitoring, we examined whether NA-related HR/HRV mediated the association of PTSD symptom severity with 24-hour HRV and endothelial functioning.

Methods

One hundred ninety-seven young adults (18–39 years), 93 with PTSD, underwent 1 day of Holter monitoring while concurrently reporting NA levels via EMA. Two noninvasive measures of endothelial functioning—flow-mediated dilation and hyperemic flow—were also collected. Multilevel modeling was used to assess the associations of momentary NA with HR and low- and high-frequency HRV during the 5-minute intervals after each EMA reading. Latent variable modeling was then used to determine whether individual differences in these associations mediated the association of PTSD symptom severity with 24-hour HRV, flow-mediated dilation, and hyperemic flow.

Results

PTSD symptom severity was positively associated with NA-related autonomic arousal (β = .21, p < .001), which significantly mediated the association of PTSD symptom severity with 24-hour HRV and hyperemic flow, accounting for 62% and 34% of their associations, respectively, while overshadowing the influence of smoking, lifetime alcohol dependence, sleep duration, mean NA, and episodes of acute NA.

Conclusions

Results suggest that NA-related autonomic arousal is both a primary factor driving cardiovascular risk in PTSD and a potential point of intervention.
Early Life Stress, FKBP5 Polymorphisms, and Quantitative Glycemic Traits
Authors: Suarez Anna , Lahti Jari , Kajantie Eero , Eriksson Johan G. , Räikkönen Katri
Published: December 2016

Objective

Early life stress (ELS) has been shown to influence health later in life. Functioning of the hypothalamic-pituitary-adrenal axis, regulated partly by FKBP5 gene, may moderate these effects. We examined whether FKBP5 single-nucleotide polymorphisms (SNPs) interact with ELS on Type 2 diabetes, cardiovascular disease, and quantitative glycemic traits.

Methods

A total of 1728 Helsinki Birth Cohort Study participants born from 1934 to 1944 were genotyped for FKBP5 SNPs (rs1360780, rs9394309, rs9470080) and were administered a 2-hour (75 g) oral glucose tolerance test and a questionnaire on physician-diagnosed and medication use for chronic diseases at a mean age of 61.5 years. Of the participants, 273 had been exposed to ELS, operationalized as separation from their parents, at a mean age of 4.7 years due to evacuations during World War II.

Results

ELS interacted with FKBP5 SNPs in the analyses of fasting (rs1360780, p = .015), 30-minute (rs1360780, p = .031; rs9394309, p = .041) and incremental insulin (rs1360780, p = .032; rs9394309, p = .028; rs9470080, p = .043), insulin area under the curve (rs1360780, p = .044), and impaired fasting glucose (rs9470080, p = .049); among carriers of at least one copy of minor allele, but not among major allele homozygotes, insulin values were higher, as were the odds for impaired fasting glucose if they had been separated compared with if they had not. Corresponding associations were found with a haplotype formed by minor alleles in all three SNPs for fasting, 30-minute, and incremental insulin (p < .05).

Conclusions

FKBP5 polymorphisms in combination with ELS exposure predict higher insulin and glucose values in midlife. Our findings support the role for hypothalamic-pituitary-adrenal axis dysregulation in health-related metabolic outcomes.
3-D spatial memory and navigation: functions and disorders
Authors: Brandt Thomas , Zwergal Andreas , Glasauer Stefan
Published: December 2016

Purpose of review

The aim of this review is to report on the specialized neuronal systems mediating spatial orientation and navigation discovered in animal experiments. These findings have important implications for the clinical management of patients with vestibular disorders or dementia and for translational research in these fields.

Recent findings

The following anatomically and functionally separate, but nevertheless cooperative cell types have been characterized: angular head velocity cells and head direction cells, which depend on vestibular input and interact with place cells and grid cells, which represent position and distance. The entire system is thought to encode internal cognitive maps whose spatial data can be utilized for navigation and orientation. Flying and swimming species use spatial orientation and navigation isotropically, i.e., in the earth-horizontal and vertical directions, whereas ground-based species, including humans, perform better in the earth-horizontal plane (anisotropically). Examples of clinical disorders with deficits of spatial orientation and navigation are bilateral peripheral vestibulopathy, mild cognitive impairment, and dementia.

Testing spatial orientation and navigation should become an integral part of routine neurological examinations, especially in the elderly. Also desirable are the further development and standardization of simple and reliable smart phone-based bedside tests to measure these functions in patients.
Nystagmus and central vestibular disorders
Authors: Choi Jeong-Yoon , Kim Ji-Soo
Published: December 2016

Purpose of review

This review will cover the recent advances in clinical and laboratory features, pathophysiology, and treatment of central vestibular disorders.

Recent findings

Several features and mechanisms of central nystagmus have been identified over the years. Application of head impulse tests and vestibular evoked myogenic potentials has expanded our understanding of altered processing of canal-driven and otolith-driven vestibular signals in lesions involving the central vestibular structures. Integrated approach based on the symptoms and neurotologic signs enhances the diagnostic accuracy of acute vascular vertigo. Identification of isolated central vestibular syndromes has improved the diagnosis of central vertigo and our understanding of anatomic and functional organization of the central vestibular structures.

With the developments of clinical and laboratory neurotology, the spectrum of central vestibular disorders has expanded markedly over the years.
Neuroprotection and visual function after optic neuritis
Authors: Petzold Axel
Published: December 2016

Purpose of review

This article discusses the advantages and pitfalls of testing neuroprotective treatment strategies in patients suffering from optic neuritis.

Recent findings

Spectral domain optical coherence tomography now permits for automated segmentation of individual retinal layers. The peripapillary retinal nerve fibre layer (pRNFL) has been used in 13 of the 15 trials reviewed. Twelve trials also made use of electrophysiology. Overestimation of good visual recovery in the past has recently been recognized. Assessment of low contrast visual acuity and colour vision are now mainstream.

The availability of highly accurate and robust trial outcome measures has facilitated research on this topic. A single long-term structural outcome measurement of the pRNFL is sufficient. For shorter term, assessments of the ganglion cell/inner plexiform layer and axonal birefringence are promising. Longitudinal blood levels of neurofilament proteins permit to recognize axonal loss at presentation and monitor changes longitudinally. Inner nuclear layer volume changes relate to inflammatory disease activity.

Pitfalls are related to the timing of events. Hyperacute recruitment is needed for future trials. The onset of demyelination is not known, which complicates timing of electrophysiological recordings. Optic disc oedema precludes the use of the pRNFL from the affected eye as a baseline variable. The concomitant use of corticosteroids complicates interpretation of trial data.
Epigallocatechin Gallate Extends Therapeutic Window of Recombinant Tissue Plasminogen Activator Treatment for Brain Ischemic Stroke: A Randomized Double-Blind and Placebo-Controlled Trial
Authors: Wang Xue-Hui , You Yi-Ping
Published: December 2016

Objectives

Recombinant tissue plasminogen activator (rt-PA) is a safe and effective treatment for acute brain ischemia stroke, albeit with a narrow therapeutic window. We aimed to assess the effect of epigallocatechin gallate (EGCG) in extending the rt-PA treatment window in this clinical trial among stroke patients.

Methods

Patients were randomly assigned according to their onset-to-treatment time (OTT) and were then treated with rt-PA simultaneously with EGCG or placebo. Treatment outcome was assessed by the National Institutes of Health stroke scale (NIHSS) and plasma levels of matrix metalloproteinases (MMP)-2 and 9.

Results

Administration of EGCG significantly improved treatment outcomes of patients in the delayed OTT strata, as evidenced by improved NIHSS scores. This improved treatment outcome was likely attributed to reduction in plasma levels of both MMP-2 and 9, as indicated by strong linear correlations between both MMPs and NIHSS scores in all patients.

Conclusions

Epigallocatechin gallate could potentially be used as a supplement of traditional rt-PA treatment among stroke patients, particularly those with delayed OTT, to extend the otherwise narrow therapeutic window and improve the outcome in late stroke treatment.
Alcohol-Sensitive Generalized Dystonia
Authors: Micheli Federico , Uribe-Roca Claudia , Saenz-Farret Michel
Published: December 2016

We report the case of a 29-year-old male patient with a generalized and progressive dystonia that led him unable to stand. Multiple antidystonic treatments were tried without benefit. Alcohol test was positive with a dramatic improvement. To the best of our knowledge, this is the first reported case of generalized dystonia without other clinical manifestations sensitive to alcohol.
A tale of two antennules: the performance of crab odour-capture organs in air and water
Authors: Waldrop Lindsay D. , Miller Laura A. , Khatri Shilpa
Published: December 2016

Odour capture is an important part of olfaction, where dissolved chemical cues (odours) are brought into contact with chemosensory structures. Antennule flicking by marine crabs is an example of discrete odour capture (sniffing) where an array of chemosensory hairs is waved through the water to create a flow–no flow pattern based on a narrow range of speeds, diameters of and spacings between hairs. Changing the speed of movement and spacing of hairs at this scale to manipulate flow represents a complicated fluid dynamics problem. In this study, we use numerical simulation of the advection and diffusion of a chemical gradient to reveal how morphological differences of the hair arrays affect odour capture. Specifically, we simulate odour capture by a marine crab (
Callinectes sapidus
) and a terrestrial crab (
Coenobita rugosus
) in both air and water to compare performance. We find that the antennule morphologies of each species are adaptions to capturing odours in their native habitats. Sniffing is an important part of odour capture for marine crabs in water where the diffusivity of odorant molecules is low and flow through the array is necessary. On the other hand, flow within the hair array diminishes odour-capture performance in air where diffusivities are high. This study highlights some of the adaptations necessary to transition from water to air.
Dietary adaptions in the ultrastructure of dinosaur dentine
Authors: Brink Kirstin S. , Chen Yu-Cheng , Wu Ya-Na , Liu Wei-Min , Shieh Dar-Bin , Huang Timothy D. , Sun Chi-Kuang , Reisz Robert R.
Published: December 2016

Teeth are key to understanding the feeding ecology of both extant and extinct vertebrates. Recent studies have highlighted the previously unrecognized complexity of dinosaur dentitions and how specific tooth tissues and tooth shapes differ between taxa with different diets. However, it is unknown how the ultrastructure of these tooth tissues contributes to the differences in feeding style between taxa. In this study, we use third harmonic generation microscopy and scanning electron microscopy to examine the ultrastructure of the dentine in herbivorous and carnivorous dinosaurs to understand how the structure of this tissue contributes to the overall utility of the tooth. Morphometric analyses of dentinal tubule diameter, density and branching rates reveal a strong signal for dietary preferences, with herbivorous saurischian and ornithischian dinosaurs consistently having higher dentinal tubule density than their carnivorous relatives. We hypothesize that this relates to the hardness of the dentine, where herbivorous taxa have dentine that is more resistant to breakage and wear at the dentine–enamel junction than carnivorous taxa. This study advocates the detailed study of dentine and the use of advanced microscopy techniques to understand the evolution of dentition and feeding ecology in extinct vertebrates.
Variability in individual activity bursts improves ant foraging success
Authors: Campos Daniel , Bartumeus Frederic , Méndez Vicenç , Andrade José S. , Espadaler Xavier
Published: December 2016

Using experimental and computational methods, we study the role of behavioural variability in activity bursts (or temporal activity patterns) for individual and collective regulation of foraging in
A. senilis
ants. First, foraging experiments were carried out under special conditions (low densities of ants and food and absence of external cues or stimuli) where individual-based strategies are most prevalent. By using marked individuals and recording all foraging trajectories, we were then able to precisely quantify behavioural variability among individuals. Our main conclusions are that (i) variability of ant trajectories (turning angles, speed, etc.) is low compared with variability of temporal activity profiles, and (ii) this variability seems to be driven by plasticity of individual behaviour through time, rather than the presence of fixed behavioural stereotypes or specialists within the group. The statistical measures obtained from these experimental foraging patterns are then used to build a general agent-based model (ABM) which includes the most relevant properties of ant foraging under natural conditions, including recruitment through pheromone communication. Using the ABM, we are able to provide computational evidence that the characteristics of individual variability observed in our experiments can provide a functional advantage (in terms of foraging success) to the group; thus, we propose the biological basis underpinning our observations. Altogether, our study reveals the potential utility of experiments under simplified (laboratory) conditions for understanding information-gathering in biological systems.
Genetic regulation and function of epidermal growth factor receptor signalling in patterning of the embryonicDrosophilabrain
Authors: Jussen David , von Hilchen Janina , Urbach Rolf
Published: December 2016

The specification of distinct neural cell types in central nervous system development crucially depends on positional cues conferred to neural stem cells in the neuroectoderm. Here, we investigate the regulation and function of the epidermal growth factor receptor (EGFR) signalling pathway in early development of theDrosophilabrain. We find that localized EGFR signalling in the brain neuroectoderm relies on a neuromere-specific deployment of activating (Spitz, Vein) and inhibiting (Argos) ligands. Activated EGFR controls the spatially restricted expression of all dorsoventral (DV) patterning genes in a gene- and neuromere-specific manner. Further, we reveal a novel role of DV genes—ventral nervous system defective(vnd),intermediate neuroblast defective (ind), Nkx6—in regulating the expression ofveinandargos, which feed back on EGFR, indicating that EGFR signalling stands not strictly atop the DV patterning genes. Within this network of genetic interactions, Vnd acts as a positive EGFR feedback regulator. Further, we show that EGFR signalling becomes dependent onsingle-minded-expressing midline cells in the posterior brain (tritocerebrum), but remains midline-independent in the anterior brain (deuto- and protocerebrum). Finally, we demonstrate that activated EGFR controls the proper formation of brain neuroblasts by regulating the number, survival and proneural gene expression of neuroectodermal progenitor cells. These data demonstrate that EGFR signalling is crucially important for patterning and early neurogenesis of the brain.
Modulations of viscous fluid conduit periodic waves
Authors: Maiden M. D. , Hoefer M. A.
Published: December 2016

Modulated periodic interfacial waves along a conduit of viscous liquid are explored using nonlinear wave modulation theory and numerical methods. Large-amplitude periodic-wave modulation (Whitham) theory does not require integrability of the underlying model equation, yet often either integrable equations are studied or the full extent of Whitham theory is not developed. Periodic wave solutions of the nonlinear, dispersive, non-integrable conduit equation are characterized by their wavenumber and amplitude. In the weakly nonlinear regime, both the defocusing and focusing variants of the nonlinear Schrödinger (NLS) equation are derived, depending on the carrier wavenumber. Dark and bright envelope solitons are found to persist in long-time numerical solutions of the conduit equation, providing numerical evidence for the existence of strongly nonlinear, large-amplitude envelope solitons. Due to non-convex dispersion, modulational instability for periodic waves above a critical wavenumber is predicted and observed. In the large-amplitude regime, structural properties of the Whitham modulation equations are computed, including strict hyperbolicity, genuine nonlinearity and linear degeneracy. Bifurcating from the NLS critical wavenumber at zero amplitude is an amplitude-dependent elliptic region for the Whitham equations within which a maximally unstable periodic wave is identified. The viscous fluid conduit system is a mathematically tractable, experimentally viable model system for wide-ranging nonlinear, dispersive wave dynamics.
Neural correlates of side-specific odour memory in mushroom body output neurons
Authors: Strube-Bloss Martin F. , Nawrot Martin P. , Menzel Randolf
Published: December 2016

Humans and other mammals as well as honeybees learn a unilateral association between an olfactory stimulus presented to one side and a reward. In all of them, the learned association can be behaviourally retrieved via contralateral stimulation, suggesting inter-hemispheric communication. However, the underlying neuronal circuits are largely unknown and neural correlates of across-brain-side plasticity have yet not been demonstrated. We report neural plasticity that reflects lateral integration after side-specific odour reward conditioning. Mushroom body output neurons that did not respond initially to contralateral olfactory stimulation developed a unique and stable representation of the rewarded compound stimulus (side and odour) predicting its value during memory retention. The encoding of the reward-associated compound stimulus is delayed by about 40 ms compared with unrewarded neural activity, indicating an increased computation time for the read-out after lateral integration.
Epidemiological models to control the spread of information in marine mammals
Authors: Schakner Zachary A. , Buhnerkempe Michael G. , Tennis Mathew J. , Stansell Robert J. , van der Leeuw Bjorn K. , Lloyd-Smith James O. , Blumstein Daniel T.
Published: December 2016

Socially transmitted wildlife behaviours that create human–wildlife conflict are an emerging problem for conservation efforts, but also provide a unique opportunity to apply principles of infectious disease control to wildlife management. As an example, California sea lions (
Zalophus californianus
) have learned to exploit concentrations of migratory adult salmonids below the fish ladders at Bonneville Dam, impeding endangered salmonid recovery. Proliferation of this foraging behaviour in the sea lion population has resulted in a controversial culling programme of individual sea lions at the dam, but the impact of such culling remains unclear. To evaluate the effectiveness of current and alternative culling strategies, we used network-based diffusion analysis on a long-term dataset to demonstrate that social transmission is implicated in the increase in dam-foraging behaviour and then studied different culling strategies within an epidemiological model of the behavioural transmission data. We show that current levels of lethal control have substantially reduced the rate of social transmission, but failed to effectively reduce overall sea lion recruitment. Earlier implementation of culling could have substantially reduced the extent of behavioural transmission and, ultimately, resulted in fewer animals being culled. Epidemiological analyses offer a promising tool to understand and control socially transmissible behaviours.