bluuebunny/crossref_metadata_2025 huggingface dataset:
Animal models for central poststroke pain: a critical comprehensive review
Authors: De Vloo Philippe , Morlion Bart , van Loon Johannes , Nuttin Bart
Published: September 2016

Central poststroke pain (CPSP) is a severe type of neuropathic pain that can develop after stroke and is difficult to treat. Research into its underlying mechanisms and treatment options could benefit from a valid CPSP animal model. Nine different CPSP animal models have been published, but there are relatively few reports on successful reproductions of these models and so far only little advances in the understanding or the management of CPSP have been made relying on these models. In general, the construct validity (similarity in underlying mechanisms) of these CPSP animal models is relatively high, although this cannot be evaluated into depth because of lack of understanding the mechanisms through which thalamic stroke can lead to CPSP. The face validity (symptom similarity) is relatively low, mainly because pain in these models is tested almost exclusively through evoked mechanical/thermal hypersensitivity assessed by reflexive measures and given the conflicting results with similar tests in patients with CPSP. The predictive validity (similarity in treatment efficacy) has not been evaluated in most models and incorporates difficulties that are specific to CPSP. We compare the different models regarding these types of validity and discuss the robustness, reproducibility, and problems regarding the design and reporting of the articles establishing these models. We conclude with various proposals on how to improve the validity and reproducibility of CPSP animal models. Until further improvements are achieved, prudence is called for in interpreting results obtained through these models.
Reduced excitability and impaired nociception in peripheral unmyelinated fibers from Nav1.9-null mice
Authors: Hoffmann Tal , Kistner Katrin , Carr Richard W. , Nassar Mohammed A. , Reeh Peter W. , Weidner Christian
Published: September 2016

The upregulation of the tetrodotoxin-resistant voltage-gated sodium channel NaV1.9 has previously been associated with inflammatory hyperalgesia. Na1.9 knockout (KO) mice, however, did not seem insensitive in conventional tests of acute nociception. Using electrophysiological, neurochemical, and behavioral techniques, we now show NaV1.9-null mice exhibit impaired mechanical and thermal sensory capacities and reduced electrical excitability of nociceptors. In single-fiber recordings from isolated skin, the electrical threshold of NaV1.9 KO C fibers was elevated by 55% and the median von Frey threshold was 32 mN in contrast to 8 mN in wild types (WTs). The prevalence of C mechano-heat-sensitive (CMH) fibers was only 25.6% in NaV1.9 KO animals compared to 75.8% in the WT group, and the heat threshold of these CMH fibers was 40.4°C in the control vs 44°C in the KO group. Compound action potential recordings from isolated sciatic nerve segments of NaV1.9 KO mice revealed lower activity-induced slowing of conduction velocity upon noxious heat stimulation: 8% vs 30% in WTs. Heat-induced calcitonin gene-related peptide release from the skin was less in the KO than in the WT group. The reduced noxious heat sensitivity was finally confirmed with the Hargreaves test using 2 rates of radiant heating of the plantar hind paws. In conclusion, NaV1.9 presumably contributes to acute thermal and mechanical nociception in mice, most likely through increasing the excitability but probably also by amplifying receptor potentials irrespective of the stimulus modality.
Treatment of Severe Alcoholic Hepatitis With Corticosteroid, Pentoxifylline, or Dual Therapy
Authors: Lee Young-Sun , Kim Hyun Jung , Kim Ji Hoon , Yoo Yang Jae , Kim Tae Suk , Kang Seong Hee , Suh Sang Jun , Joo Moon Kyung , Jung Young Kul , Lee Beom Jae , Seo Yeon Seok , Yim Hyung Joon , Yeon Jong Eun , Kim Jae Seon , Park Jong-Jae , Um Soon Ho , Bak Young-Tae , Byun Kwan Soo
Published: September 2016

Background and Aims:

Although both corticosteroids and pentoxifylline are currently recommended drugs for the treatment of patients with severe alcoholic hepatitis, their effectiveness in reducing mortality remains unclear. In this systematic review, we aimed to evaluate the therapeutic and adverse effects of corticosteroids, pentoxifylline, and combination by using Cochrane methodology and therefore determine optimal treatment for severe alcoholic hepatitis.

Methods:

We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from their inauguration until October 2015. Combinations of the following keywords and controlled vocabularies were searched: alcoholic hepatitis, corticosteroid, and pentoxifylline.

Results:

A total of 2639 patients from 25 studies were included. The treatment groups did not differ significantly in terms of overall mortality. Analysis of 1-month mortality revealed corticosteroid monotherapy reduced mortality compared with placebo (OR=0.58; 95% CI, 0.34-0.98; P=0.04), but pentoxifylline monotherapy did not. The mortality with dual therapy was similar to corticosteroid monotherapy (OR=0.91; 95% CI, 0.62-1.34; P=0.63). However, dual therapy decreased the incidences of hepatorenal syndrome or acute kidney injury (OR=0.47; 95% CI, 0.26-0.86; P=0.01) and the infection risk (OR=0.63; 95% CI, 0.41-0.97; P=0.04) significantly more than corticosteroid monotherapy did. None of the treatments conferred any medium-term or long-term survival benefits in the present study.

Conclusions:

Dual therapy was not inferior to corticosteroid monotherapy and could reduce the incidence of hepatorenal syndrome or acute kidney injury and risk of infection. Therefore, dual therapy might be considered in treatment of patients with severe alcoholic hepatitis.
Bifidobacterium infantis NLS Super Strain Reduces the Expression of α-Defensin-5, a Marker of Innate Immunity, in the Mucosa of Active Celiac Disease Patients
Authors: Pinto-Sánchez Maria I. , Smecuol Edgardo C. , Temprano Maria P. , Sugai Emilia , González Andrea , Moreno María L. , Huang Xianxi , Bercik Premysl , Cabanne Ana , Vázquez Horacio , Niveloni Sonia , Mazure Roberto , Mauriño Eduardo , Verdú Elena F. , Bai Julio C.
Published: September 2016

Background:

We have previously shown a reduction of gastrointestinal symptoms after the oral administration of Bifidobacterium infantis Natren Life Start super strain (NLS-SS) in untreated celiac disease (CD) patients. The symptomatic improvement was not associated with changes in intestinal permeability or serum levels of cytokines, chemokines, or growth factors. Therefore, we hypothesized that the beneficial symptomatic effect observed previously in patients with CD treated with B. infantis may be related to the modulation of innate immunity.

Goals:

To investigate the potential mechanisms of a probiotic B. infantis Natren Life Start super strain on the mucosal expression of innate immune markers in adult patients with active untreated CD compared with those treated with B. infantis×6 weeks and after 1 year of gluten-free diet (GFD).

Methods:

Numbers of macrophages and Paneth cells and α-defensin-5 expression were assessed by immunohistochemistry in duodenal biopsies.

Results:

We showed that GFD decreases duodenal macrophage counts in CD patients more effectively than B. infantis. In contrast, B. infantis decreases Paneth cell counts and expression of α-defensin-5 in CD (P<0.001).

Conclusions:

The results identify differential innate immune effects of treatment with B. infantis compared with 1 year of GFD. Further studies are needed to investigate synergistic effects of GFD and B. infantis supplementation in CD.
Increased Prevalence of Metabolic Risk Factors in Asian Americans With Hepatocellular Carcinoma
Authors: Kutsenko Alina , Ladenheim Maya R. , Kim Nathan , Nguyen Pauline , Chen Vincent , Jayasekera Channa , Yang Ju Dong , Kumari Radhika , Roberts Lewis , Nguyen Mindie H.
Published: September 2016

Background:

We used metabolic risk factors to estimate the prevalence and clinical significance of nonalcoholic fatty liver disease in Asian Americans with hepatocellular carcinoma (HCC).

Methods:

This is a retrospective cohort study of 824 consecutive Asian HCC patients at Stanford University Medical Center from 1998 to 2015. Patients were subdivided as: Chinese, other East Asian (Japanese and Korean), South East Asian (Vietnamese, Thai, and Laotian), Maritime South East Asian (MSEA: Malaysian, Indonesian, Filipino, and Singaporean), and South West Asian (Indian, Pakistani, and Middle Eastern). Metabolic risk factors studied were body mass index, hypertension, type II diabetes, and hyperlipidemia.

Results:

Most patients were male (76%) with mean age 63 years. Metabolic risk factors were highly prevalent on presentation and increased over time (P<0.001), as did the prevalence of cryptogenic HCC (P<0.004). Compared with other Asian subgroups, MSEAs had the highest body mass index (26.3) and higher rates of type II diabetes (44% vs. 23% to 35%, P=0.004), hypertension (59% vs. 38% to 55%, P=0.04), and cryptogenic HCC (15% vs. 4% to 10%, P=0.01). They were more likely to be symptomatic on presentation (44% vs. 32% to 58%, P=0.07), less likely to present within Milan criteria (34% vs. 35% to 63%, P<0.0001), and trended toward decreased 10-year survival rates compared with other ethnic subgroups (9% vs. 25% to 32%, P=0.07).

Conclusions:

Metabolic risk factors were increasingly prevalent among Asian Americans with HCC. MSEAs, who had the highest incidence of these risk factors, had more advanced tumor stage and trended toward worse survival.
Longitudinal Patterns of Spending Enhance the Ability to Predict Costly Patients
Authors: Lauffenburger Julie C. , Franklin Jessica M. , Krumme Alexis A. , Shrank William H. , Brennan Troyen A. , Matlin Olga S. , Spettell Claire M. , Brill Gregory , Choudhry Niteesh K.
Published: September 2016

Background:

With rising health spending, predicting costs is essential to identify patients for interventions. Many of the existing approaches have moderate predictive ability, which may result, in part, from not considering potentially meaningful changes in spending over time. Group-based trajectory modeling could be used to classify patients into dynamic long-term spending patterns.

Objectives:

To classify patients by their spending patterns over a 1-year period and to assess the ability of models to predict patients in the highest spending trajectory and the top 5% of annual spending using prior-year predictors.

Subjects:

We identified all fully insured adult members enrolled in a large US nationwide insurer and used medical and prescription data from 2009 to 2011.

Research Design:

Group-based trajectory modeling was used to classify patients by their spending patterns over a 1-year period. We assessed the predictive ability of models that categorized patients in the top fifth percentile of annual spending and in the highest spending trajectory, using logistic regression and split-sample validation. Models were estimated using investigator-specified variables and a proprietary risk-adjustment method.

Results:

Among 998,651 patients, in the best-performing model, prediction was strong for patients in the highest trajectory group (C-statistic: 0.86; R
2: 0.47). The C-statistic of being in the top fifth percentile of spending in the best-performing model was 0.82 (R
2: 0.26). Approaches using nonproprietary investigator-specified methods performed almost as well as other risk-adjustment methods (C-statistic: 0.81 vs. 0.82).

Conclusions:

Trajectory modeling may be a useful way to predict costly patients that could be implementable by payers to improve cost-containment efforts.
Beyond dilation: current concepts in endoscopic airway stenting and reconstruction
Authors: Gnagi Sharon H. , White David R.
Published: September 2016

Purpose of review

To discuss current modalities of endoscopic airway management beyond balloon dilation therapy.

Recent findings

Advances continue to be made through technology and bioengineering with exciting potential in the pediatric airway. Smaller robots and instrumentation allow increased endoscopic surgical success. Biodegradable stents and bioengineered grafts are on the horizon for use in airway surgery. Dysphonia following airway reconstruction is of increasing recognition with new endoscopic treatments being performed. Supraglottoplasty is further recognized as a treatment for obstructive sleep apnea for laryngomalacia diagnosed on sleep endoscopy. Interarytenoid injection may be beneficial in the normal larynx for aspiration and dysphagia as well as diagnosing and treating type I laryngeal clefts.

Endoscopic airway surgery continues to be a popular and effective method of treating the pediatric airway. Technological advances such as in robotics may have an increasing role in the future of endoscopic airway surgery in children. Bioengineered airway adjuncts including biodegradable airway stents look to be promising in the future treatment of airway stenosis.
Stable Isotope Techniques for the Assessment of Host and Microbiota Response During Gastrointestinal Dysfunction
Authors: Butler Ross N. , Kosek Margaret , Krebs Nancy F. , Loechl Cornelia U. , Loy Alexander , Owino Victor O. , Zimmermann Michael B. , Morrison Douglas J.
Published: September 2016

The International Atomic Energy Agency convened a technical meeting on environmental enteric dysfunction (EED) in Vienna (October 28–30, 2015; https://nucleus.iaea.org/HHW/Nutrition/EED_Technical_Meeting/index.html) to bring together international experts in the fields of EED, nutrition, and stable isotope technologies. Advances in stable isotope–labeling techniques open up new possibilities to improve our understanding of gastrointestinal dysfunction and the role of the microbiota in host health. In the context of EED, little is known about the role gut dysfunction may play in macro‐ and micronutrient bioavailability and requirements and what the consequences may be for nutritional status and linear growth. Stable isotope labeling techniques have been used to assess intestinal mucosal injury and barrier function, carbohydrate digestion and fermentation, protein‐derived amino acid bioavailability and requirements, micronutrient bioavailability and to track microbe‐microbe and microbe‐host interactions at the single cell level. The noninvasive nature of stable isotope technologies potentially allow for low‐hazard, field‐deployable tests of gut dysfunction that are applicable across all age groups. The purpose of this review is to assess the state‐of‐the‐art use of stable isotope technologies and to provide a perspective on where these technologies can be exploited to further our understanding of gut dysfunction in EED.
Treatment of Functional Abdominal Pain With Antidepressants
Authors: Zar‐Kessler Claire A.M. , Belkind‐Gerson Jaime , Bender Suzanne , Kuo Braden M.
Published: September 2016

Objectives:

Pediatric functional abdominal pain is often treated with tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). The aim is investigating antidepressant use for treatment efficacy, correlation of response to psychiatric factors, and impact of adverse effects in regard to physicians’ prescribing patterns.

Methods:

Retrospective review (2005–2013) children (5–21 years old) with functional abdominal pain treated with SSRI or TCA. Of the 531 cases with functional abdominal pain, 192 initiated SSRIs or TCAs while followed by gastroenterology. Charts reviewed for symptoms, adverse effects, and response: decreased pain or increased daily functioning.

Results:

Sixty‐three of 84 (75%) SSRI patients improved, 56 of 92 (61%) TCA patients improved (P = 0.03). Logistic regression controlling for psychiatric factors: SSRI remained significant over TCA (P = 0.04). Thirty‐two of 67 (48%) patients with constipation received TCAs and 26 of 45 (58%) patients with diarrhea received SSRIs (P = 0.64). Three SSRI patients reported gastrointestinal effects, all diarrheal‐type symptoms, and 2 TCA patients reported gastrointestinal effects, both constipation, in all it led to discontinuation. Thirteen (29%) of diarrheal‐type patients reported adverse effects causing discontinuation as compared to 7 (8%) in the constipation group (P = .01). Twenty‐one (25%) SSRI patients reported adverse effects with 5 (6%) mood disturbances. Twenty (22%) TCA patients reported adverse effects, 13 (14%) with mood disturbances (P = .07). Overall, 12 (14%) SSRI patients discontinued medication due to adverse effects, whereas 16 (17%) TCA patients (P = 0.24) did.

Conclusions:

Patients had significantly greater response to SSRIs than TCAs, remaining significant after controlling for psychiatric factors. Little significance is given to patient's associated gastrointestinal symptoms, frequently resulting in adverse effects and termination of medication.
Understanding the Essential Meaning of Measured Changes in Weight and Body Composition Among Women During and After Adjuvant Treatment for Breast Cancer
Authors: Pedersen Birgith , Groenkjaer Mette , Falkmer Ursula , Delmar Charlotte
Published: September 2016

Background:

Changes in weight and body composition among women during and after adjuvant antineoplastic treatment for breast cancer may influence long-term survival and quality of life. Research on factual weight changes is diverse and contrasting, and their influence on women’s perception of body and self seems to be insufficiently explored.

Objective:

The aim of this study was to expand the understanding of the association between changes in weight and body composition and the women’s perception of body and selves.

Methods:

A mixed-methods research design was used. Data consisted of weight and body composition measures from 95 women with breast cancer during 18 months past surgery. Twelve women from this cohort were interviewed individually at 12 months. Linear mixed model and logistic regression were used to estimate changes of repeated measures and odds ratio. Interviews were analyzed guided by existential phenomenology.

Results:

Joint displays and integrative mixed-methods interpretation demonstrated that even small weight gains, extended waist, and weight loss were associated with fearing recurrence of breast cancer. Perceiving an ambiguous transforming body, the women moved between a unified body subject and the body as an object dissociated in “I” and “it” while fighting against or accepting the body changes.

Conclusions:

Integrating findings demonstrated that factual weight changes do not correspond with the perceived changes and may trigger existential threats.

Implications for Practice:

Transition to a new habitual body demand health practitioners to enter a joint narrative work to reveal how the changes impact on the women’s body and self-perception independent of how they are displayed quantitatively.
Feasibility of Endoscopic Submucosal Dissection for Submucosal-invasive Gastric Cancer and the Predictors of Residual or Recurrent Cancer
Authors: Ojima Toshiyasu , Takifuji Katsunari , Nakamura Masaki , Nakamori Mikihito , Yamaue Hiroki
Published: September 2016

Purpose of the Study:

The purpose of this study was to determine the feasibility of the endoscopic submucosal dissection (ESD) for submucosal-invasive gastric cancer (SMGC) by assessing the therapeutic outcomes in patients treated with ESD.

Materials and Methods:

From 2002 to 2013, ESD was performed for 597 lesions with early gastric cancer at our institute. ESD of the SMGC was performed for 85 patients.

Results:

Among these 85 patients, 35 patients underwent additional gastrectomy. Residual or recurrent cancer occurred in 12 patients treated through ESD method. The 5-year disease-specific survival rates were 94.9% for all 85 patients and 97.2% for 49 patients with follow-up examinations after ESD. The multivariate logistic regression analysis indicated that residual or recurrent cancer in the patients with SMGC was significantly associated with a tumor width in submucosa (P=0.0152).

Conclusions:

ESD for SMGC can be considered feasible in clinical practice in terms of the favorable long-term oncologic outcomes.
Large Balloon Dilation Treatment for Retrieval of Embedded Sharp-pointed Objects in the Esophagus: A New Technique
Authors: Disibeyaz Selcuk , Oztas Erkin , Kuzu Ufuk B. , Ozdemir Mustafa
Published: September 2016

Most ingested foreign bodies are best treated with endoscopically. If the sharp-pointed objects embedded in the esophageal wall, it may not be able to be removed by conventional endoscopic devices and surgery is required. Herein, we described a new technique for the extraction of both ends embedded sharp-pointed objects in the esophageal wall.
Patient Satisfaction With Nurse-Led Telephone Follow-up in an Ambulatory Setting
Authors: Schimpf Megan O. , Fenner Dee E. , Smith Tovia M. , Tucker Julie , Berger Mitchell B.
Published: September 2016

Objectives

We studied our practice of using nurse telephone follow-up under physician direction to assess symptom improvement and patient satisfaction.

Methods

Women were recruited when their clinical care merited nurse telephone follow-up in the opinion of the attending physician. Women specified a preferred telephone number and completed a symptom questionnaire at the time of enrollment. Nursing telephone follow-up was completed at an interval prescribed by the attending physician to answer specified clinical questions. Approximately 3 months after the initial in-office visit, a satisfaction questionnaire and repeat symptom measure were mailed to the subjects.

Results

A convenience sample of 83 women was analyzed. Of those, 91.6% were reached by telephone, and 47.0% returned the follow-up questionnaire. Mean (SD) age was 56.8 (16.6) years (range, 20–89 years). Younger women were less likely to be able to be contacted by telephone (P = 0.02) and less likely to return the questionnaire (P = 0.02). Most common diagnoses were overactive bladder and mixed urinary incontinence. Satisfaction rates were high, and level of convenience for patients was high. Women indicated an ease of speaking over the telephone about their condition and confidence in the treatment plan. Satisfaction with telephone follow-up did not significantly differ based on age or diagnosis.

Conclusions

Patient satisfaction was high for nurse telephone follow-up to replace in-office visits for selected diagnoses. This care strategy deserves further consideration for reimbursement purposes as health care evolves.
Health Care Disparities Among English-Speaking and Spanish-Speaking Women With Pelvic Organ Prolapse at Public and Private Hospitals: What Are the Barriers?
Authors: Alas Alexandriah N. , Dunivan Gena C. , Wieslander Cecelia K. , Sevilla Claudia , Barrera Biatris , Rashid Rezoana , Maliski Sally , Eilber Karen , Rogers Rebecca G. , Anger Jennifer Tash
Published: September 2016

Objectives

The objective of this study was to compare perceptions and barriers between Spanish-speaking and English-speaking women in public and private hospitals being treated for pelvic organ prolapse (POP).

Methods

Eight focus groups, 4 in English and 4 in Spanish, were conducted at 3 institutions with care in female pelvic medicine and reconstructive surgery. Standardized questions were asked regarding patients' emotions to when they initially noticed the POP, if they sought family support, and their response to the diagnosis and treatment. Transcripts were analyzed using grounded theory qualitative methods.

Results

Thirty-three women were Spanish-speaking and 25 were English-speaking. Spanish speakers were younger (P = 0.0469) and less likely to have a high school diploma (P < 0.0001) than English speakers. Spanish-speaking women had more concerns that the bulge or treatments could lead to cancer, were more resistant to treatment options, and were less likely to be offered surgery. Women in the private hospital desired more information, were less embarrassed, and were more likely to be offered surgery as first-line treatment. The concept emerged that patient care for POP varied based on socioeconomic status and language and suggested the presence of disparities in care for underserved women with POP.

Conclusions

The discrepancies in care for Spanish-speaking women and women being treated at public hospitals suggest that there are disparities in care for POP treatment for underserved women. These differences may be secondary to profit-driven pressures from private hospitals or language barriers, low socioeconomic status, low health literacy, and barriers to health care.
Outcomes of Robotic Sacrocolpopexy Using Only Absorbable Suture for Mesh Fixation
Authors: Linder Brian J. , Anand Mallika , Klingele Christopher J. , Trabuco Emanuel C. , Gebhart John B. , Occhino John A.
Published: September 2016

Objective

The optimal suture selection for mesh attachment during robotic sacrocolpopexy (RSC) is currently unknown. Here, we sought to evaluate the outcomes of RSC using absorbable sutures for vaginal and sacral mesh attachment.

Methods

We retrospectively reviewed 132 RSC surgeries that were performed for vaginal vault prolapse in the Division of Gynecologic Surgery at our institution from February 2007 to December 2013. All cases were performed with absorbable suture (polyglactin) for vaginal and sacral mesh fixation. Sacrocolpopexy failure was defined as patients undergoing either repeat prolapse surgery or pessary use for recurrent prolapse. The durability of RSC was assessed via Kaplan-Meier method.

Results

The median age at surgery was 61.1 years (interquartile range [IQR], 55.6–68.2) and the median length of postoperative follow-up was 33 months (IQR, 15.7–57). The median body mass index was 26.5 kg/m2 (IQR, 24.3–29.7). During follow-up, 10 patients underwent prolapse retreatment. There were 2 apical recurrences, 4 distal anterior recurrences, 2 posterior recurrences, and, in 2 cases, the location was unknown. One apical recurrence was confirmed to be secondary to detachment of the mesh from the sacral promontory. Among those with recurrence, the median time to recurrence was 15.5 months (IQR, 4.22–35.9). Overall, the 1-year and 3-year freedom from repeat surgery rates were 96% and 93%, respectively.

Conclusions

With a median follow-up of 33 months, the use of absorbable suture for both vaginal and sacral attachments during RSC is effective. Further studies evaluating suture selection and mesh attachment techniques for RSC are needed.
Transcriptional Regulation of Connective Tissue Metabolism Genes in Women With Pelvic Organ Prolapse
Authors: Borazjani Ali , Kow Nathan , Harris Samantha , Ridgeway Beri , Damaser Margot S.
Published: September 2016

Objective

The aim of this study was to compare differences in expressions and relationships between key genes involved in extracellular matrix metabolism and tissue cellularity in women with and without pelvic organ prolapse (POP).

Methods

A total of 80 biopsies (anterior cuff, posterior cuff, and/or leading edge) were obtained from 30 women: n = 10 premenopausal without POP (controls), n = 10 premenopausal with POP, and n = 10 postmenopausal with POP. Quantitative reverse-transcriptase polymerase chain reaction was used to assess gene expression of bone morphogenetic protein 1 (BMP1), collagen types I (COL1) and III (COL3), relaxin family peptide receptor 1 (RXFP1), matrix metallopeptidase 2, and TIMP metallopeptidase inhibitors 2 and 3. Hematoxylin and eosin staining was used to assess cellularity of the connective tissue layer. Kruskal-Wallis test, Mann-Whitney U test, Pearson correlation, or linear regression analyses were used, as appropriate.

Results

Bone morphogenetic protein 1 expression was significantly up-regulated in patients with POP compared with controls. Bone morphogenetic protein 1 expression was correlated with COL1 expression in all groups but only correlated with TIMP metallopeptidase inhibitor 3 expression in controls. Similarly, COL3 expression was correlated with RXFP1 expression in women with POP but not in controls. The degree of dependence (slope of the regression line) between COL1 and COL3 expressions was significantly elevated in premenopausal women with POP compared with the other 2 groups. The slopes between COL1-COL3, COL3–matrix metallopeptidase 2, COL1-RXFP1, and COL3-RXFP1 expressions were significantly lower in postmenopausal women compared with premenopausal women with POP. No differences were found in overall tissue cellularity.

Conclusions

Bone morphogenetic protein 1 expression may play a significant role in the pathophysiology of POP. The finding that BMP1 expression was correlated with COL1 expression in all groups suggests a conserved association between BMP1 and collagen synthesis in the vaginal wall. The elevated slope between COL1 and COL3 expressions may be associated with early (premenopausal) development of POP. The expression of RXFP1 in postmenopausal women and its altered intergene regulation suggests a role for RXFP1 in connective tissue metabolism outside pregnancy.
Avoiding Clinical Misinterpretation and Artifacts of Optical Coherence Tomography Analysis of the Optic Nerve, Retinal Nerve Fiber Layer, and Ganglion Cell Layer
Authors: Chen John J. , Kardon Randy H.
Published: September 2016

Background:

Optical coherence tomography (OCT) has become an important tool for diagnosing optic nerve disease. The structural details and reproducibility of OCT continues to improve with further advances in technology. However, artifacts and misinterpretation of OCT can lead to clinical misdiagnosis of diseases if they go unrecognized.

Evidence Acquisition:

A literature review using PubMed combined with clinical and research experience.

Results:

We describe the most common artifacts and errors in interpretation seen on OCT in both optic nerve and ganglion cell analyses. We provide examples of the artifacts, discuss the causes, and provide methods of detecting them. In addition, we discuss a systematic approach to OCT analysis to facilitate the recognition of artifacts and to avoid clinical misinterpretation.

Conclusions:

While OCT is invaluable in diagnosing optic nerve disease, we need to be cognizant of the artifacts that can occur with OCT. Failure to recognize some of these artifacts can lead to misdiagnoses and inappropriate investigations.
Retrolaminar Migration of Intraocular Silicone Oil
Authors: Boren Rance A. , Cloy Carson D. , Gupta Ankur S. , Dewan Vinay N. , Hogan R. Nick
Published: September 2016

Background:

Migration of intravitreal silicone to the retrolaminar optic nerve was detected pathologically in 1983, symptomatic migration to the subarachnoid space of the optic nerve was reported in 1994, and asymptomatic intraventricular silicone was first seen radiographically in 1999. Since then, little advance has been made in understanding this phenomenon despite numerous case reports. Although some authors have restricted their attention to cases of intraventricular silicone, we believe that these represent part of a clinical spectrum and that all cases with retrolaminar silicone should be considered. The pathophysiology of silicone migration may have significant implications for the management of patients after vitrectomy.

Evidence Acquisition:

Two patients were evaluated by the authors. An internet-based literature review was conducted, beginning with the key search terms “intraventricular, intracranial, subarachnoid, or optic nerve silicone,” and “complications of vitrectomy or intravitreal silicone.” Further searches cascaded from the initial search results. An additional 24 cases of retrolaminar migration of silicone oil were found and summarized. The relevant anatomy and pathophysiology were reviewed, with attention to additional information from enucleation studies, as well as to gaps in the current understanding of this process.

Results:

Retrolaminar migration of silicone oil may be more common than previously thought, especially in at-risk patient groups, and may be associated with visual and neurologic symptoms. Some impressions regarding the cause and significance of this syndrome seem incorrect. Although this process is likely linked to postoperative elevations of intraocular pressure, the exact mechanisms of silicone entry into the subarachnoid space remain undefined. A number of anatomic factors may influence the movement of silicone from the orbit and in the various compartments of the subarachnoid space and ventricular system, resulting in variability of clinical presentations and radiologic findings. Implications for clinical decision making and directions for further research are discussed.

Conclusion:

Greater awareness on the part of treating physicians, systematic study of at-risk populations, and advances in imaging technology will allow further insight into this phenomenon.
Metatranscriptomics supports mechanism for biocathode electroautotrophy by “Candidatus Tenderia electrophaga”
Authors: Eddie Brian J. , Wang Zheng , Hervey W. Judson , Leary Dagmar H. , Malanoski Anthony P. , Tender Leonard M. , Lin Baochuan , Strycharz-Glaven Sarah M.
Published: September 2016

Biocathodes provide a stable electron source to drive reduction reactions in electrotrophic microbial electrochemical systems. Electroautotrophic biocathode communities may be more robust than monocultures in environmentally relevant settings, but some members are not easily cultivated outside of the electrode environment. We previously used metagenomics and metaproteomics to propose a pathway for coupling extracellular electron transfer (EET) to carbon fixation in “Candidatus Tenderia electrophaga”, an uncultivated but dominant member of the Biocathode-MCL electroautotrophic community. Here we validate and refine this proposed pathway using differential metatranscriptomics of replicate MCL reactors poised at the growth potential 310 mV and the suboptimal 470 mV (vs. standard hydrogen electrode). At both potentials, transcripts from “Ca. Tenderia electrophaga” were more abundant than from any other organism and its relative activity was positively correlated with current. Several genes encoding key components of the proposed “Ca. Tenderia electrophaga” EET pathway were more highly expressed at 470 mV, consistent with a need for cells to acquire more electrons to obtain the same amount of energy as at 310 mV. These included cyc2, encoding a homolog of a protein known to be involved in iron oxidation, confirmed to be differentially expressed by droplet digital PCR of independent biological replicates. Average expression of all CO2 fixation related genes is 1.23-fold higher at 310 mV, indicating that reduced energy availability at 470 mV decreased CO2 fixation. Our results substantiate the claim that “Ca. Tenderia electrophaga” is the key MCL electroautotroph, which will help guide further development of this community for microbial electrosynthesis.

IMPORTANCE

Bacteria that directly use electrodes as metabolic electron donors (biocathodes) have been proposed for applications ranging from microbial electrosynthesis to advanced bioelectronics for cellular communication with machines. However, just as we understand very little about oxidation of analogous natural insoluble electron donors, such as iron oxide, the organisms and extracellular electron transfer (EET) pathways underlying the electrode-cell direct electron transfer processes are almost completely unknown. Biocathodes are a stable biofilm cultivation platform to interrogate both the rate and mechanism of EET using electrochemistry and study the electroautotrophic organisms that catalyze these reactions. Here we provide new evidence supporting the hypothesis that the uncultured bacterium “Candidatus Tenderia electrophaga” directly couples extracellular electron transfer to CO2 fixation. Our results provide insight into developing biocathode technology, such as microbial electrosynthesis, as well as advancing our understanding of chemolithoautotrophy.
Selective activation of ganglion cells without axon bundles using epiretinal electrical stimulation
Authors: Grosberg Lauren E. , Ganesan Karthik , Goetz Georges A. , Madugula Sasidhar , Bhaskar Nandita , Fan Victoria , Li Peter , Hottowy Paweł , Dabrowski Władysław , Sher Alexander , Litke Alan M. , Mitra Subhasish , Chichilnisky E.J.
Published: September 2016

Epiretinal prostheses for treating blindness activate axon bundles, causing large, arc-shaped visual percepts that limit the quality of artificial vision. Improving the function of epiretinal prostheses therefore requires understanding and avoiding axon bundle activation. This paper introduces a method to detect axon bundle activation based on its electrical signature, and uses the method to test whether epiretinal stimulation can directly elicit spikes in individual retinal ganglion cells without activating nearby axon bundles. Combined electrical stimulation and recording from isolated primate retina were performed using a custom multi-electrode system (512 electrodes, 10 µm diameter, 60 µm pitch). Axon bundle signals were identified by their bi-directional propagation, speed, and increasing amplitude as a function of stimulation current. The threshold for bundle activation varied across electrodes and retinas, and was in the same range as the threshold for activating retinal ganglion cells near their somas. In the peripheral retina, 45% of electrodes that activated individual ganglion cells (17% of all electrodes) did so without activating bundles. This permitted selective activation of 21% of recorded ganglion cells (7% of all ganglion cells) over the array. In the central retina, 75% of electrodes that activated individual ganglion cells (16% of all electrodes) did so without activating bundles. The ability to selectively activate a subset of retinal ganglion cells without axon bundles suggests a possible novel architecture for future epiretinal prostheses.

New & Noteworthy

Large-scale multi-electrode recording and stimulation were used to test how selectively retinal ganglion cells can be electrically activated without activating axon bundles. A novel method was developed to identify axon activation based on its unique electrical signature, and used to find that a subset of ganglion cells can be activated at single-cell, single-spike resolution without producing bundle activity, in peripheral and central retina. These findings have implications for the development of advanced retinal prostheses.
Minimal Tool Set for a Prokaryotic Circadian Clock
Authors: Schmelling Nicolas M , Lehmann Robert , Chaudhury Paushali , Beck Christian , Albers Sonja V , Axmann Ilka M , Wiegard Anika
Published: September 2016

Background

Circadian clocks are found in organisms of almost all domains including photosynthetic Cyanobacteria, whereby large diversity exists within the protein components involved. In the model cyanobacteriumSynechococcus elongatusPCC 7942 circadian rhythms are driven by a unique KaiABC protein clock, which is embedded in a network of input and output factors. Homologous proteins to the KaiABC clock have been observed in Bacteria and Archaea, where evidence for circadian behavior in these domains is accumulating. However, interaction and function of non-cyanobacterial Kai-proteins as well as homologous input and output components remain mainly unclear.

Results

Using a universal BLAST analyses, we identified putative KaiC-based timing systems in organisms outside as well as variations within Cyanobacteria. A systematic analyses of publicly available microarray data elucidated interesting variations in circadian gene expression between different cyanobacterial strains, which might be correlated to the diversity of genome encoded clock components. Based on statistical analyses of co-occurrences of the clock components homologous toSynechococcus elongatusPCC 7942, we propose putative networks of reduced and fully functional clock systems. Further, we studied KaiC sequence conservation to determine functionally important regions of diverged KaiC homologs. Biochemical characterization of exemplary cyanobacterial KaiC proteins as well as homologs from two thermophilic Archaea demonstrated that kinase activity is always present. However, a KaiA-mediated phosphorylation is only detectable in KaiC1 orthologs.

Conclusion

Our analysis of 11,264 genomes clearly demonstrates that components of theSynechococcus elongatusPCC 7942 circadian clock are present in Bacteria and Archaea. However, all components are less abundant in other organisms than Cyanobacteria and KaiA, Pex, LdpA, and CdpA are only present in the latter. Thus, only reduced KaiBC-based or even simpler, solely KaiC-based timing systems might exist outside of the cyanobacterial phylum, which might be capable of driving diurnal oscillations.
Noise-processing by signaling networks
Authors: Kontogeorgaki Styliani , Sánchez-García Rubén J. , Ewing Rob M. , Zygalakis Konstantinos C. , MacArthur Ben D.
Published: September 2016

Signaling networks mediate environmental information to the cell nucleus. To perform this task effectively they must be able to integrate multiple stimuli and distinguish persistent signals from transient environmental fluctuations. However, the ways in which signaling networks process environmental noise are not well understood. Here we outline a mathematical framework that relates a network’s structure to its capacity to process noise, and use this framework to dissect the noise-processing ability of signaling networks. We find that complex networks that are dense in directed paths are poor noise processors, while those that are sparse and strongly directional process noise well. These results suggest that while cross-talk between signaling pathways may increase the ability of signaling networks to integrate multiple stimuli, too much cross-talk may compromise the ability of the network to distinguish signal from noise. To illustrate these general results we consider the structure of the signaling network that maintains pluripotency in mouse embryonic stem cells, and find an incoherent feedforward loop structure involving Stat3, Tfcp2l1, Esrrb, Klf2 and Klf4 is particularly important for noise-processing. Taken together these results suggest that noise-processing is an important function of signaling networks and they may be structured in part to optimize this task.
Identification of Successful Mentoring Communities using Network-based Analysis of Mentor-Mentee Relationships across Nobel Laureates
Authors: Chariker Julia H. , Zhang Yihang , Pani John R. , Rouchka Eric C.
Published: September 2016

Skills underlying scientific innovation and discovery generally develop within an academic community, often beginning with a graduate mentor’s laboratory. In this paper, a network analysis of doctoral student-dissertation advisor relationships in The Academic Tree is used to identify successful mentoring communities in high-level science, as measured by number of Nobel laureates within the community. Nobel laureates form a distinct group in the network with greater numbers of Nobel laureate ancestors, descendants, mentees/grandmentees, and local academic family. Subnetworks composed entirely of Nobel laureates extend across as many as four generations. Successful historical mentoring communities were identified centering around Cambridge University in the latter 19thcentury and Columbia University in the early 20thcentury. The current practice of building web-based academic networks, extended to include a wider variety of measures of academic success, would allow for the identification of modern successful scientific communities and should be promoted.
Polarized regulatory landscape and Wnt responsiveness underlie Hox activation in embryos
Authors: Neijts Roel , Amin Shilu , van Rooijen Carina , Tan Sander , Creyghton Menno P. , de Laat Wouter , Deschamps Jacqueline
Published: September 2016

Sequential 3′-to-5′ activation of the Hox gene clusters in early embryos is a most fascinating issue in developmental biology. Neither the trigger nor the regulatory elements involved in the transcriptional initiation of the 3′-most Hox genes have been unraveled in any organism. We demonstrate that a series of enhancers, some of which are Wnt-dependent, is located within a HoxA 3′ subtopologically associated domain (subTAD). This subTAD forms the structural basis for multiple layers of 3′-polarized features, including DNA accessibility and enhancer activation. Deletion of the cassette of Wnt-dependent enhancers proves its crucial role in initial transcription of HoxA at the 3′ side of the cluster.
Post-retrieval extinction in adolescence prevents return of juvenile fear
Authors: Jones Carolyn E. , Monfils Marie-H.
Published: September 2016

Traumatic experiences early in life can contribute to the development of mood and anxiety disorders that manifest during adolescence and young adulthood. In young rats exposed to acute fear or stress, alterations in neural development can lead to enduring behavioral abnormalities. Here, we used a modified extinction intervention (retrieval+extinction) during late adolescence (post-natal day 45 [p45]), in rats, to target auditory Pavlovian fear associations acquired as juveniles (p17 and p25). The effects of adolescent intervention were examined by assessing freezing as adults during both fear reacquisition and social transmission of fear from a cagemate. Rats underwent testing or training at three time points across development: juvenile (p17 or p25), adolescent (p45), and adult (p100). Retrieval+extinction during late adolescence prevented social reinstatement and recovery over time of fears initially acquired as juveniles (p17 and p25, respectively). Adolescence was the only time point tested here where retrieval+extinction prevented fear recall of associations acquired 20+ days earlier.
PyNX.Ptycho: a computing library for X-ray coherent diffraction imaging of nanostructures
Authors: Mandula Ondřej , Elzo Aizarna Marta , Eymery Joël , Burghammer Manfred , Favre-Nicolin Vincent
Published: September 2016

X-ray imaging techniques have undergone a remarkable development during the past decade, taking advantage of coherent X-ray sources. Among these techniques, ptychography allows reconstruction of the specimen and the illumination probe from a series of diffraction patterns without any prior knowledge about the sample. However, the reconstruction of the ptychographic data remains challenging and the reconstruction software is often not publicly available. Presented here is an open-source library for the reconstruction of two-dimensional ptychographic data, written in Python. This library implements existing algorithms, with examples of data reconstruction on both simulated and experimental (Bragg ptychography on heterogeneous strained InAs/GaAs nanowires) data sets. It can be used for educational (simulation) purposes or experimental data analysis, and also features an OpenCL version of the ptychography algorithm for high-performance computing.
A radially accessible tubular in situ X-ray cell for spatially resolved operando scattering and spectroscopic studies of electrochemical energy storage devices
Authors: Liu Hao , Allan Phoebe K. , Borkiewicz Olaf J. , Kurtz Charles , Grey Clare P. , Chapman Karena W. , Chupas Peter J.
Published: September 2016

A tubular operando electrochemical cell has been developed to allow spatially resolved X-ray scattering and spectroscopic measurements of individual cell components, or regions thereof, during device operation. These measurements are enabled by the tubular cell geometry, wherein the X-ray-transparent tube walls allow radial access for the incident and scattered/transmitted X-ray beam; by probing different depths within the electrode stack, the transformation of different components or regions can be resolved. The cell is compatible with a variety of synchrotron-based scattering, absorption and imaging methodologies. The reliability of the electrochemical cell and the quality of the resulting X-ray scattering and spectroscopic data are demonstrated for two types of energy storage: the evolution of the distribution of the state of charge of an Li-ion battery electrode during cycling is documented using X-ray powder diffraction, and the redistribution of ions between two porous carbon electrodes in an electrochemical double-layer capacitor is documented using X-ray absorption near-edge spectroscopy.