bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and Safety of Once-Daily Controlled-Release Pregabalin for the Treatment of Patients With Postherpetic Neuralgia
Authors: Huffman Cynthia L. , Goldenberg James N. , Weintraub James , Sanin Luis , Driscoll Joseph , Yang Ruoyong , Chew Marci L. , Scavone Joseph M. 
Published: October 2016

Objectives:
To assess efficacy and safety of once-daily controlled-release (CR) formulation of pregabalin in patients with postherpetic neuralgia.

Methods:
An enriched enrollment, randomized withdrawal trial, with 6-week single-blind pregabalin treatment phase and 13-week double-blind phase, where patients with ≥50% decrease in mean pain score at single-blind end point from baseline were randomized (1:1) to pregabalin CR (82.5 to 660 mg/d) or placebo. Primary efficacy outcome was time to loss of therapeutic response (LTR) (<30% decrease in weekly mean pain score from single-blind baseline or discontinuation due to adverse event or lack of efficacy). Secondary efficacy outcomes included change in weekly mean pain score (1-wk recall period) at double-blind end point.

Results:
In total, 801 patients were randomized and treated in the single-blind phase, and 413 in the double-blind phase (208, pregabalin CR; 205, placebo). Pregabalin CR significantly increased time to LTR versus placebo (Kaplan-Meier analysis) with significantly fewer LTR events with pregabalin CR than with placebo (29 [13.9%] vs. 63 [30.7%]; P<0.0001). Median time to LTR was not estimable. Pregabalin CR significantly improved weekly mean pain score versus placebo: LS mean difference (95% CI) of −1.11 (−1.47, −0.75) and −1.00 (−1.34, −0.65) (P<0.0001) from single-blind baseline and double-blind baseline, respectively. Most commonly reported adverse events in the single-blind phase were dizziness, somnolence, and peripheral edema. Pregabalin CR was well tolerated.

Discussion:
Time to LTR was significantly longer with pregabalin CR than with placebo. Safety profile of pregabalin CR was comparable to that reported for the immediate-release formulation in patients with postherpetic neuralgia.
Dose–response and Cardiopulmonary Side Effects of the Novel Neuromuscular-blocking Drug CW002 in Man
Authors: Heerdt Paul M. , Sunaga Hiroshi , Owen Joel S. , Murrell Matthew T. , Malhotra Jaideep K. , Godfrey Deena , Steinkamp Michelle , Savard Peter , Savarese John J. , Lien Cynthia A. 
Published: October 2016

AbstractBackgroundCW002 is a benzylisoquinolinium nondepolarizing neuromuscular-blocking drug found to be inactivated by cysteine in preclinical studies. The current study represents a dose escalation clinical trial designed to describe CW002 potency, duration, cardiopulmonary side effects, and histamine release.MethodsHealthy subjects anesthetized with sevoflurane/nitrous oxide were divided into five groups (n = 6), each receiving a fixed CW002 dose (0.02, 0.04, 0.06, 0.08, or 0.10 mg/kg), and one group (n = 4) receiving 0.14 mg/kg. Blood pressure and heart rate were continuously recorded along with airway dynamic compliance. Neuromuscular blockade was assessed with mechanomyography at the adductor pollicis. Arterial blood was obtained before and after CW002 injection for analysis of plasma histamine concentration. Potency was estimated from a baseline sigmoid Emax model.ResultsED50 was found to be 0.036 mg/kg (95% CI, 0.020 to 0.053 mg/kg) and ED95 0.077 mg/kg (95% CI, 0.044 to 0.114 mg/kg). At 0.14 mg/kg (1.8 × ED95), 80% twitch depression occurred in 94 ± 18 s with complete block in 200 ± 87 s. Clinical recovery (25% of maximum twitch) occurred in 34 ± 3.4 min, with a 5 to 95% recovery interval of 35.0 ± 2.7 min. The time to a train-of-four ratio greater than 0.9 ranged from 59 to 86 min. CW002 did not elicit histamine release or significant (greater than 10%) changes in blood pressure, heart rate, or dynamic airway compliance.ConclusionsIn healthy subjects receiving sevoflurane/nitrous oxide, CW002 at 1.8 × estimated ED95 produces a clinical duration less than 40 min, elicits no histamine release, and has minimal cardiopulmonary side effects.
Evaluation of the Effects of Physical Activity, Cardiorespiratory Condition, and Neuromuscular Fitness on Direct Healthcare Costs and Sickness-Related Absence Among Nursing Personnel With Recurrent Nonspecific Low Back Pain
Authors: Kolu Päivi , Tokola Kari , Kankaanpää Markku , Suni Jaana 
Published: October 2016

Study Design.
A cross-sectional study, part of a randomized controlled trial.

Objective.
To evaluate the association of physical activity, cardiorespiratory fitness, and neuromuscular fitness with direct healthcare costs and sickness-related absence among nursing personnel with nonspecific low back pain.

Summary of Background Data.
Low back pain creates a huge economic burden due to increased sick leave and use of healthcare services.

Methods.
Female nursing personnel with nonspecific low back pain were included (n = 219). Physical activity was assessed with accelerometry and a questionnaire. In addition, measurements of cardiorespiratory and muscular fitness were conducted. Direct costs and sickness-related absence for a 6-month period were collected retrospectively by questionnaire. Health care utilization and absence from work were analyzed with a general linear model.

Results.
The mean total costs were 80.5% lower among women who met physical activity recommendations than inactive women. Those with a higher mean daily intensity level of 10-minute activity sessions showed lower total costs than women in the lowest tertile (middle: 64.0% of the lowest; highest: 54.3% of the lowest). Women with good cardiorespiratory fitness (the highest tertile) as measured with the 6-minute-walk test (based on walking distance) had 77.0% lower total costs when compared with the lowest tertile. Women in the highest third for the modified push-up test had 84.0% lower total costs than those with the poorest results (the bottom tertile).

Conclusion.
High cardiorespiratory and muscular fitness and meeting physical activity recommendations for aerobic and muscular fitness were strongly associated with lower total costs among nursing personnel with pain-related disorders of recurrent nonspecific low back pain. Actions to increase physical activity and muscle conditioning may significantly save on healthcare costs and decrease sick-leave costs due to low back pain.

Level of Evidence: 3
BILATERAL INTRAOCULAR HEMORRHAGE SECONDARY TO CEREBRAL VENOUS SINUS THROMBOSIS
Authors: Kunle-Hassan Feyi , Dattani Minaxi , Snead Martin , Subash Mala 
Published: October 2016

Purpose:
To report a case of bilateral intraocular hemorrhage secondary to cerebral venous sinus thrombosis with no associated intracranial hemorrhage.

Methods:
Case report.

Results:
A 32-year-old Asian gentleman presented with left reduced vision as a result of a left subhyaloid macular hemorrhage associated with severe headache. Right retinal hemorrhages were also present. Magnetic resonance imaging and computed tomography brain imaging demonstrated cerebral transverse venous sinus thrombosis.

Conclusion:
Intraocular hemorrhage has previously been described in association with intracranial hemorrhage and in particular subarachnoid hemorrhage (Terson syndrome). We describe a similar clinical picture in the context of cerebral venous sinus thrombosis with no associated intracranial hemorrhage.
Nodulo-Ulcerative Ocular Surface Squamous Neoplasia in 6 Patients: A Rare Presentation
Authors: Kaliki Swathi , Freitag Suzanne K. , Chodosh James 
Published: October 2016

Purpose:
To describe clinical presentation and histopathological features of a nodulo-ulcerative variant of ocular surface squamous neoplasia (OSSN).

Methods:
Retrospective study.

Results:
Six patients were identified with a nodulo-ulcerative variant of OSSN. Mean age at presentation was 56 years. One patient was immunosuppressed because of human immunodeficiency virus infection. The initial misdiagnosis was necrotizing scleritis/sclerokeratitis (n = 4), intraepithelial neoplasia (n = 1), and chalazion (n = 1). The mean delay in diagnosis as OSSN was 6 months. The lesion involved bulbar conjunctiva in 5 patients and tarsal conjunctiva in 1 patient. The mean maximum tumor dimension was 16 mm, and the mean area of conjunctivoscleral/conjunctivotarsal necrosis was 8 mm. The primary treatment for nodulo-ulcerative OSSN included excisional biopsy (n = 2), plaque radiotherapy (n = 1), and orbital exenteration (n = 3). Tumor recurrence was noted in two patients necessitating orbital exenteration. At last follow-up, globe salvage could be achieved in only 1 case. Histopathology showed invasive conjunctival squamous cell carcinoma in all cases with lesions being well-differentiated (n = 4), moderately differentiated (n = 1), and with mucoepidermoid differentiation (n = 1). Underlying scleral/tarsal tumor infiltration was evident in all 6 (100%) cases. Intraocular tumor extension was evident in 3 cases infiltrating the iris (n = 2), ciliary body (n = 3), and choroid (n = 3). Orbital tumor extension was evident in 2 cases because of tumor recurrence. No metastasis or death was recorded at a mean follow-up of 26 months.

Conclusions:
The nodulo-ulcerative variant of OSSN is rare and is most often misdiagnosed as necrotizing scleritis/sclerokeratitis causing a delay in the diagnosis. It is an aggressive lesion with increased occurrence of intraocular or orbital tumor extension.
Kojic Acid
Authors: Gust Peter J. , Luke Janiene D. 
Published: October 2016

ABSTRACT
A drug is defined in physiology as being a substance that exerts an effect on the body once it has been ingested. Drugs take many forms in their attempt to enter the body including capsules, injections, creams, ointments, inhalants, liquids, and dermal patches. The purpose of this column is to take a closer look at drugs that are used in the field of dermatology. More specifically, this column hopes to bring an understanding to the reader regarding mechanism of action, administration, dosage, adverse effects, and viable alternatives to each particular drug being discussed. In this article, the role of the drug kojic acid, as a dermatologic treatment for hyperpigmentation disorders, as well as other novel uses will be discussed.
Itchy Blisters and Pink Bumps on the Hands and Elbows
Authors: So Jessica Kim , Jacob Sharon E. 
Published: October 2016

ABSTRACT
Teledermatology is a term to describe the provision of dermatologic medical services through telecommunication technology. In this modality, there is transfer of patient medical information electronically (including history and visual data) obtained in one location to a provider who is in another location (Roman & Jacob, 2015). The construct of the TeleDermViewPoint column is such that cases are presented in a standardized teledermatology reader format reflective of an actual teledermatology report. This is a case of itchy blisters and pink bumps on the hands and elbows.
Racial Discrimination and Psychological Wellbeing of Pregnant Women
Authors: Giurgescu Carmen , Zenk Shannon N. , Engeland Christopher G. , Garfield Lindsey , Templin Thomas N. 
Published: October 2016

Abstract

Purpose:
African American women are more likely to be exposed to racial discrimination and to experience psychological distress compared with white women. Although studies have shown that social support is positively related to psychological wellbeing, little is known about the potential buffering effect of social support on the relationship between racial discrimination and psychological wellbeing of pregnant women. The purpose of this study was to determine if social support moderates effects of racial discrimination on psychological wellbeing among pregnant African American women.

Study Design and Methods:
Using a cross-sectional design, 107 African American women between 15 and 26 weeks gestation from an urban university-based midwifery practice completed questionnaires.

Results:
Women who reported more experiences of racial discrimination also reported lower levels of social support and psychological wellbeing (p <.05).

Clinical Implications:
Maternal child nurses should be aware that experiences of racial discrimination have negative effects on psychological wellbeing of pregnant African American women regardless of their levels of social support. However, social support can reduce psychological distress and improve wellbeing of pregnant women. Therefore, nurses need to provide pregnant women with positive and supportive experiences that may improve their psychological wellbeing.
Percutaneous Lung Biopsy in the Molecular Profiling Era
Authors: Lee Christopher , Guichet Phillip L. , Abtin Fereidoun 
Published: October 2016

Purpose:
This study aimed to assess the current practice patterns of radiologists performing percutaneous lung biopsies.

Materials and Methods:
This cross-sectional study used a web-based survey sent to the Society of Thoracic Radiology membership from August to October 2015. Responses were collected anonymously, and results were tallied.

Results:
A total of 244 Society of Thoracic Radiology members responded to the survey. One hundred thirty-seven radiologists regularly perform percutaneous lung biopsies, of whom 102 (74%) practice at an academic teaching hospital. Computed tomography (CT) and CT fluoroscopy were the modalities of choice for image guidance, preferred by 82 (60%) and 48 (35%) respondents, respectively. Twenty (15%) respondents preferred fine-needle aspiration (FNA) alone, 57 (42%) preferred core needle biopsy (CNB) alone, and 59 (43%) preferred both FNA and CNB in the same setting. On-site cytology was routinely requested by 70 (71%) respondents with access to such services. In cases of suspected lung cancer, 79 (60%) respondents estimated sending tissue for molecular analysis >25% of the time. Forty-three (32%) respondents reported using intraprocedural preventive measures to minimize risk of pneumothorax.

Conclusions:
Among surveyed radiologists who perform percutaneous lung biopsies, most utilize CT guidance with either CNB alone or in conjunction with FNA. A small minority routinely performs FNA alone, which may negatively impact diagnostic accuracy and provide insufficient tissue for molecular profiling. Education of all radiologists regarding the importance of routinely acquiring and sending greater amounts of tissue for molecular/genomic assessment of suspected lung cancer is needed.
Extensive Horizontal Gene Transfer in Cheese-Associated Bacteria
Authors: Bonham Kevin S. , Wolfe Benjamin E. , Dutton Rachel J. 
Published: October 2016

AbstractAcquisition of genes through horizontal gene transfer (HGT) allows microbes to rapidly gain new capabilities and adapt to new or changing environments. Identifying widespread HGT regions within multispecies microbiomes can pinpoint the molecular mechanisms that play key roles in microbiome assembly. We sought to identify horizontally transferred genes within a model microbiome, the cheese rind. Comparing 31 newly-sequenced and 134 previously sequenced bacterial isolates from cheese rinds, we identified over 200 putative horizontally transferred genomic regions containing 4,733 protein coding genes. The largest of these regions are enriched for genes involved in siderophore acquisition, and are widely distributed in cheese rinds in both Europe and the US. These results suggest that horizontal gene transfer (HGT) is prevalent in cheese rind microbiomes, and the identification of genes that are frequently transferred in a particular environment may provide insight into the selective forces shaping microbial communities.
A dual-strategy expression screen for candidate connectivity labels in the developing thalamus
Authors: Bibollet-Bahena Olivia , Okafuji Tatsuya , Hokamp Karsten , Mitchell Kevin J. 
Published: October 2016

AbstractThe thalamus or “inner chamber” of the brain is divided into ~30 discrete nuclei, with highly specific patterns of afferent and efferent connectivity. To identify genes that may direct these patterns of connectivity, we used two strategies. First, we used a bioinformatics pipeline to survey the predicted proteomes of nematode, fruitfly, mouse and human for extracellular proteins containing any of a list of motifs found in known guidance or connectivity molecules. Second, we performed clustering analyses on the Allen Developing Mouse Brain Atlas data to identify genes encoding surface proteins expressed with temporal profiles similar to known guidance or connectivity molecules. In both cases, we then screened the resultant genes for selective expression patterns in the developing thalamus. These approaches identified 82 candidate connectivity labels in the developing thalamus. These molecules include many members of the Ephrin, Eph-receptor, cadherin, protocadherin, semaphorin, plexin, Odz/teneurin, Neto, cerebellin, calsyntenin and Netrin-G families, as well as diverse members of the immunoglobulin (Ig) and leucine-rich receptor (LRR) superfamilies, receptor tyrosine kinases and phosphatases, a variety of growth factors and receptors, and a large number of miscellaneous membrane-associated or secreted proteins not previously implicated in axonal guidance or neuronal connectivity. The diversity of their expression patterns indicates that thalamic nuclei are highly differentiated from each other, with each one displaying a unique repertoire of these molecules, consistent with a combinatorial logic to the specification of thalamic connectivity.
Measuring the criticality of the `magic condition' for a beam-expanding monochromator
Authors: Martinson Mercedes , Chapman Dean 
Published: October 2016

It has been established that for cylindrically bent crystals the optimal beam characteristics occur when the geometric and single-ray foci are matched. In the beam-expanding monochromator developed for the BioMedical Imaging and Therapy beamlines at the Canadian Light Source, it was unclear how critical this `magic condition' was for preserving the transverse coherence of the beam. A study was conducted to determine whether misalignments away from the ideal conditions would severely affect the transverse coherence of the beam, thereby limiting phase-based imaging techniques. The results were that the magic condition has enough flexibility to accommodate deviations of about ±1° or ±5 keV.
Cyclosporin a induces renal episodic hypoxia
Authors: Fähling M. , Mathia S. , Scheidl J. , Abramovitch R. , Milman Z. , Paliege A. , Peters H. , Persson P. B. , Heyman S. N. , Rosenberger C. 
Published: October 2016

AbstractAimCyclosporin A (CsA) causes renal toxicity. The underlying mechanisms are incompletely understood, but may involve renal hypoxia and hypoxia‐inducible factors (Hifs). We sought for hypoxia and Hif in mouse kidneys with CsA‐induced toxicity, assessed their time course, Hif‐mediated responses and the impact of interventional Hif upregulation.MethodsMice received CsA or its solvent cremophore for up to 6 weeks. Low salt diet (Na+↓) was given in combination with CsA to enhance toxicity. We assessed fine morphology, renal function, blood oxygen level‐dependent magnetic resonance imaging under room air and following changes in breathing gas composition which correlate with vascular reactivity, pimonidazole adducts (which indicate O2 tensions below 10 mmHg), Hif‐α proteins, as well as expression of Hif target genes. Stable Hif upregulation was achieved by inducible, Pax8‐rtTA‐based knockout of von Hippel–Lindau protein (Vhl‐KO), which is crucial for Hif‐α degradation.ResultsCyclosporin A transiently increased renal deoxyhaemoglobin (R2*). Augmented vascular reactivity was observed at 2 h, but decreased at 24 h after CsA treatment. Na+↓/CsA provoked chronic renal failure with tubular degeneration and interstitial fibrosis. Nephron segments at risk for injury accumulated pimonidazole adducts, as well as Hif‐α proteins. Remarkably, Hif target gene expression remained unchanged, while factor‐inhibiting Hif (Fih) was enhanced. Na+↓/CsA/Vhl‐KO aggravated morpho‐functional outcome of chronic renal CsA toxicity.ConclusionsCyclosporin A provokes episodic hypoxia in nephron segments most susceptible to chronic CsA toxicity. Fih is upregulated and likely blocks further Hif activity. Continuous tubular Hif upregulation via Vhl‐KO worsens the outcome of chronic CsA‐induced renal toxicity.
Trading direct for indirect defense? Phytochrome B inactivation in tomato attenuates direct anti‐herbivore defenses whilst enhancing volatile‐mediated attraction of predators
Authors: Cortés Leandro E. , Weldegergis Berhane T. , Boccalandro Hernán E. , Dicke Marcel , Ballaré Carlos L. 
Published: October 2016

Summary

Under conditions of competition for light, which lead to the inactivation of the photoreceptor phytochrome B (phyB), the growth of shade‐intolerant plants is promoted and the accumulation of direct anti‐herbivore defenses is down‐regulated. Little is known about the effects of phyB on emissions of volatile organic compounds (VOCs), which play a major role as informational cues in indirect defense.

We investigated the effects of phyB on direct and indirect defenses in tomato (Solanum lycopersicum) using two complementary approaches to inactivate phyB: illumination with a low red to far‐red ratio, simulating competition, and mutation of the two PHYB genes present in the tomato genome.

Inactivation of phyB resulted in low levels of constitutive defenses and down‐regulation of direct defenses induced by methyl jasmonate (MeJA). Interestingly, phyB inactivation also had large effects on the blends of VOCs induced by MeJA. Moreover, in two‐choice bioassays using MeJA‐induced plants, the predatory mirid bug Macrolophus pygmaeus preferred VOCs from plants in which phyB was inactivated over VOCs from control plants.

These results suggest that, in addition to repressing direct defense, phyB inactivation has consequences for VOC‐mediated tritrophic interactions in canopies, presumably attracting predators to less defended plants, where they are likely to find more abundant prey.
Shigella Vaccine Development: Finding the Path of Least Resistance
Authors: Chen Wilbur H. , Kotloff Karen L. 
Published: October 2016

ABSTRACT

Shigella
spp. represent the second most common etiologic pathogen causing childhood diarrhea in developing countries. There are no licensed
Shigella
vaccines, and progress for such vaccines has been limited. In this issue of
Clinical and Vaccine Immunology
, Riddle and colleagues (M. S. Riddle, R. W. Kaminski, C. Di Paolo, C. K. Porter, R. L. Gutierrez, et al., Clin Vaccine Immunol 23:908–917, 2016,
http://dx.doi.org/10.1128/CVI.00224-16
) report results from a phase I study of a parenterally administered monovalent O-polysaccharide “bioconjugate” directed against
Shigella flexneri
2a. Ultimately, the goal is to develop a broad-spectrum
Shigella
vaccine to address this public health concern. A parenteral
Shigella
vaccine capable of eliciting protection in children of developing countries would be an important tool to reach this goal.