bluuebunny/crossref_metadata_2025 huggingface dataset:
Ferritin 2 domain-containing protein found in lacquer tree (Toxicodendron vernicifluum) sap has negative effects on laccase and peroxidase reactions
Authors: Kitajima Sakihito , Imamura Taiki , Iibushi Junpei , Ikenaga Makoto , Tachibana Yoichi , Andoh Nobuyuki , Oyabu Hiroshi , Hirooka Kiyoo , Shiina Takashi , Ishizaki Yoko
Published: February 2017

Lacquer tree sap, a raw material of traditional paints in East Asia, is hardened through laccase-catalyzed oxidation and the following polymerization of phenolic compound urushiol. In the sap’s water-insoluble fraction, we found two plantacyanins and a ferritin 2 domain-containing protein (TvFe2D, a homolog of Arabidopsis AT1G47980 and AT3G62730). The recombinant TvFe2D protein suppressed the accumulation of laccase-catalyzed oxidation products of a model substrate syringaldazine without decreasing oxygen consumption, the second substrate of laccase. The suppression was also observed when another substrate guaiacol or another oxidizing enzyme peroxidase was used. The functional domain of the suppression was the C-terminal half, downstream of the ferritin 2 domain. The results suggest that this protein may be involved in regulating the sap polymerization/hardening. We also discuss the possibility that homologous proteins of TvFe2D in other plants might be involved in the laccase- or peroxidase-mediated polymerization of phenolic compounds, such as lignin and flavonoids.
DiagnoProt: a tool for discovery of new molecules by mass spectrometry
Authors: Silva André R.F , Lima Diogo B , Leyva Alejandro , Duran Rosario , Batthyany Carlos , Aquino Priscila F , Leal Juliana C , Rodriguez Jimmy E , Domont Gilberto B , Santos Marlon D.M , Chamot-Rooke Julia , Barbosa Valmir C , Carvalho Paulo C
Published: February 2017

Motivation

Around 75% of all mass spectra remain unidentified by widely adopted proteomic strategies. We present DiagnoProt, an integrated computational environment that can efficiently cluster millions of spectra and use machine learning to shortlist high-quality unidentified mass spectra that are discriminative of different biological conditions.

Results

We exemplify the use of DiagnoProt by shortlisting 4366 high-quality unidentified tandem mass spectra that are discriminative of different types of the Aspergillus fungus.

Availability and Implementation

DiagnoProt, a demonstration video and a user tutorial are available at http://patternlabforproteomics.org/diagnoprot.

Supplementary information

Supplementary data are available at Bioinformatics online.
Standard Setting for Clinical Performance of Basic Perioperative Transesophageal Echocardiography
Authors: Bick Julian S. , Wanderer Jonathan P. , Myler Conrad S. , Shaw Andrew D. , McEvoy Matthew D.
Published: February 2017

Background

Credible methods for assessing competency in basic perioperative transesophageal echocardiography examinations have not been reported. The authors’ objective was to demonstrate the collection of real-world basic perioperative transesophageal examination performance data and establish passing scores for each component of the basic perioperative transesophageal examination, as well as a global passing score for clinical performance of the basic perioperative transesophageal examination using the Angoff method.

Methods

National Board of Echocardiography (Raleigh, North Carolina) advanced perioperative transesophageal echocardiography–certified anesthesiologists (n = 7) served as subject matter experts for two Angoff standard-setting sessions. The first session was held before data analysis, and the second session for calibration of passing scores was held 9 months later. The performance of 12 anesthesiology residents was assessed via the new passing score grading system.

Results

The first standard-setting procedure resulted in a global passing score of 63 ± 13% on a basic perioperative transesophageal examination. The global passing score from the second standard-setting session was 73 ± 9%. Three hundred seventy-one basic perioperative transesophageal examinations from 12 anesthesiology residents were included in the analysis and used to guide the second standard-setting session. All residents scored higher than the global passing score from both standard-setting sessions.

Conclusions

To the authors’ knowledge, this is the first demonstration that the collection of real-world anesthesia resident basic perioperative transesophageal examination clinical performance data is possible and that automated grading for competency assessment is feasible. The authors’ findings demonstrate at least minimal basic perioperative transesophageal examination clinical competency of the 12 residents.
Older Adults’ Perceptions of and Preferences for a Fall Risk Assessment System
Authors: Galambos Colleen , Rantz Marilyn , Back Jessie , Jun Jung Sim , Skubic Marjorie , Miller Steven J.
Published: February 2017

Aging in place is a preferred and cost-effective living option for older adults. Research indicates that technology can assist with this goal. Information on consumer preferences will help in technology development to assist older adults to age in place. The study aim was to explore the perceptions and preferences of older adults and their family members about a fall risk assessment system. Using a qualitative approach, this study examined the perceptions, attitudes, and preferences of 13 older adults and five family members about their experience living with the fall risk assessment system during five points in time. Themes emerged in relation to preferences and expectations about the technology and how it fits into daily routines. We were able to capture changes that occurred over time for older adult participants. Results indicated that there was acceptance of the technology as participants adapted to it. Two themes were present across the five points in time—safety and usefulness. Five stages of acceptance emerged from the data from preinstallation to 2 years postinstallation. Identified themes, stages of acceptance, and design and development considerations are discussed.
Cutaneous Reactions to Targeted Therapy
Authors: Lee Jonathan J. , Kroshinsky Daniela , Hoang Mai P.
Published: February 2017

Over the past decade, numerous targeted therapeutic agents have become available for clinical use in the oncologic setting with the hopes of realizing personalized cancer treatment. These agents have achieved great improvements in clinical outcomes for patients suffering from solid and hematologic malignancies. However, adverse cutaneous reactions are among the most common toxicities observed in patients undergoing treatment with a targeted agent and can alter the overall clinical management strategy. For these reasons, the practicing dermatopathologist should be mindful of the breadth and depth of adverse cutaneous reaction patterns associated with this mechanistically diverse array of targeted agents.
Sclerosing Dermatofibrosarcoma Protuberans Shows Significant Overlap With Sclerotic Fibroma in Both Routine and Immunohistochemical Analysis: A Potential Diagnostic Pitfall
Authors: Abdaljaleel Maram Yousef Odeh , North Jeffrey P.
Published: February 2017

Dermatofibrosarcoma protuberans (DFSP) is an uncommon, low-to-intermediate grade sarcoma with several histologic variants, including pigmented (Bednar tumor), sclerosing, myxoid, atrophic, and DFSP with fibrosarcomatous changes. Two patterns of sclerosis in DFSP can be observed, a sclerotic fibroma-like pattern and a morphea/lichen sclerosus-like pattern. Partial biopsies of sclerosing DFSPs with the sclerotic fibroma pattern can be misdiagnosed as sclerotic fibroma or other benign sclerosing tumors (eg, perineurioma, dermatofibroma). DFSPs from our tissue archives were screened for tumors with a sclerosing pattern, and then studied with epithelial membrane antigen (EMA), CD34, and elastic tissue staining to investigate whether such stains can differentiate sclerosing DFSP from sclerotic fibroma. Ten cases of sclerotic fibroma were similarly studied. Two of the 27 DFSPs were predominantly sclerosing and 5 additional DFSPs had a mixed histopathologic pattern including a sclerosing component. Immunohistochemically, all DFSPs with sclerosing (predominant or mixed) pattern were positive for CD34, and 5/7 were at least focally positive for EMA. Elastic tissue staining was reduced or absent in the sclerotic areas. All cases of sclerotic fibroma were either positive or focally positive for CD34, whereas EMA was focally positive in 5/10. Elastic tissue staining ranged from reduced to totally absent in the sclerotic fibromas. In conclusion, the similar histopathologic and immunophenotypic characteristics in sclerotic fibroma and sclerosing DFSP found in this analysis highlight the importance of obtaining clinical information and potentially additional excision for partial biopsies showing a sclerotic fibroma-like pattern.
Marker Protein Expression Combined With Expression Heterogeneity is a Powerful Indicator of Malignancy in Acral Lentiginous Melanomas
Authors: Cintra Lopes Carapeto Fernando , Neves Comodo Andréia , Germano Andressa , Pereira Guimarães Daiane , Barcelos Denise , Fernandes Mariana , Landman Gilles
Published: February 2017

Patients and Methods:

Samples of acral lentiginous melanomas (ALMs) were obtained from the Department of Pathology at Escola Paulista de Medicina—Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. Demographic, clinical, and follow-up data were obtained from the charts of Hospital São Paulo. From 2 tissue microarrays containing 60 nevi and quadruplicate samples of ≥1.0-mm of 49 ALM, sections were stained to evaluate SCF, KIT, BRAF, CYCLIND1, MYC, and PTEN immunohistochemical protein expression.

Results:

Nevi and ALM from 2006 to 2010 were reviewed and collected. All specimens were in the vertical growth phase, and histopathological parameters indicated that tumors were at an advanced stage at diagnosis. Average tumor thickness was 6.95 mm, 63% were ulcerated, average mitotic index was 5 mitotic cells per mm2, and 43% were at Clark's level V. Compared with nevi, the χ2 test showed that ALM significantly correlated with SCF protein expression (P = 0.001) and expression heterogeneity (P < 0.000). Similar findings were observed for KIT (P = 0.005, P = 0.003, respectively), MYC (P < 0.000, P < 0.000), and PTEN (P = 0.005, P < 0.000). Malignancy did not correlate with BRAF and CYCLIN D1 expression (P = 0.053 and P = 0.259, respectively), but it did significantly correlate with their heterogeneous expression (P < 0.000, P = 0.024, respectively). Combined protein expression had an odds ratio of greater malignancy when BRAF and MYC were positive and/or heterogeneously expressed (OR of 78 and 95, respectively).

Discussion and Conclusion:

We show that marker protein expression, when combined with heterogeneous expression as shown by immunohistochemistry, is a powerful indicator of malignancy in ALMs, especially, when protein pairs are combined.
Papillary Dermal Elastosis
Authors: Val-Bernal José Fernando , González-Vela María Carmen , León-Castillo Alicia , Armesto Susana
Published: February 2017

Papillary dermal elastosis is a rare clinicopathological entity with only 1 case reported. The authors herein report a new case. A 38-year-old woman presented with a 10-month history of slowly progressive appearance of multiple, 1–2 mm, pruritic nonfollicular papules, located on the back. The study of the biopsy with the ordinary staining revealed numerous dermal papillae showing increased elastosis. The Verhoeff elastic stain demonstrated numerous foci of clumped and curled elastic fibers in the papillary dermis. The elastic component of the reticular dermis was normal. This case report confirms this entity and can contribute to a better understanding of the spectrum of the fibroelastolytic entities.
Unusual Interface Dermatoses Distributed Along Blaschko's Lines in Adult Patients
Authors: Suárez-Peñaranda J. M. , Figueroa O. , Rodríguez-Blanco I. , Aliste C. , Casas L.
Published: February 2017

Linear dermatoses are unusual entities whose distribution reflects cutaneous mosaicism, even when they occur in adult life. Adult blaschkitis (AB) and lichen striatus (LS) always follow this peculiar distribution. Although usually referred to as distinct entities, the clinical and histopathological presentation of lichen striatus in adults may be similar to those of adult blaschkitis. Moreover, some cases with overlapping features between lichen striatus and linear lichen planus have been published, making precise diagnosis very difficult. Recently, the concept of a wide spectrum of blaschkolinear dermatoses with AB and LS located somewhere within it has been proposed but it has not gained general recognition. We report three cases of dermatoses following the lines of Blaschko in adults (two women and one male, ages 35, 50 and 56, respectively). They involved the upper extremity in two cases and the lower in the third. Clinically, they were interpreted as linear lichen planus or blaschkitis but, histopathologically, they showed features consistent with lichen striatus. Lesions subsided with topic steroids and/or tacrolimus ointment, they are an example of the significant overlapping between these three entities, demonstrating that they may exist on a spectrum both clinically and histopathologically and clinico-pathologic correlation is essential to achieve an accurate final diagnosis. A detailed review of previously published cases has also been made.
Primary Cutaneous Follicular Helper T-cell Lymphoma in a Patient With Neurofibromatosis Type 1: Case Report and Review of the Literature
Authors: Shamsuyarova Anastasia , Kamil Zaid , Delabie Jan , Al-Faraidy Nadya , Ghazarian Danny
Published: February 2017

Patients with neurofibromatosis type 1 (NF-1) have a well-known predisposition for certain types of malignancies, including lymphoproliferative disorders. Cutaneous T-cell lymphoma (CTCL) has been reported in patients with NF-1, although it is considered a rare entity in this subset of patients. Cutaneous follicular helper T-cell lymphoma (CTFHCL) is a recently emerged rare subtype of CTCL with peculiar clinical and histopathological features and represents a diagnostic and therapeutic challenge. Only a few cases of CTFHCL have been reported in the literature. We report a case of CTFHCL in a patient with NF-1 and compare our findings with previously reported cases. We aim to raise awareness among pathologists regarding this rare subtype of CTCL and emphasize characteristic histological features of CTFHCL, which can be confused with B-cell lymphomas and lead to mismanagement.
Squamous Cell Carcinoma of the Lip—A Review of Squamous Cell Carcinogenesis of the Mucosal and Cutaneous Junction
Authors: Bota James P. , Lyons Alexis B. , Carroll Bryan T.
Published: February 2017

BACKGROUND

The lip is an anatomic junction for 2 disparate groups of cancer. Cutaneous squamous cell carcinoma (cSCC) is a common malignancy with a favorable prognosis, whereas oral-mucosal squamous cell carcinoma (omSCC) is associated with significantly higher rates of nodal disease and worse outcomes. The squamous cell carcinoma of the lip (lip SCC) is more aggressive than cSCC but less aggressive than omSCC. However, work-up and treatment vary between specialties.

OBJECTIVES

The authors sought to review and compare the risk factors and clinical behavior of cSCC, omSCC, and lip SCC, review tumor biology of squamous cell carcinoma, and compare work-up and treatment algorithms for lip SCC.

METHODS

A comprehensive PubMed and MEDLINE database search was performed with comparison of primary literature on cSCC, omSCC, and lip SCC.

RESULTS

Lip SCC exhibits rates of nodal metastasis and death that are intermediate between cSCC and omSCC, and shares many similar biologic mechanisms. There are variations in the treatment guidelines between dermatology and otolaryngology for lip SCC.

CONCLUSION

Lip SCC is an overlapping entity that poses many challenges to clinicians. Specialists should be aware of current staging modalities as well as imaging and treatment recommendations to optimize patient outcomes.
An Analysis of Laser Therapy for the Treatment of Nonmelanoma Skin Cancer
Authors: Soleymani Teo , Abrouk Michael , Kelly Kristen M.
Published: February 2017

BACKGROUND

Skin cancer remains the most prevalent type of cancer in the United States, and its burden on the health care system remains substantial. Standard treatments such as cryosurgery, electrodessication and curettage, topical and photodynamic therapies, and surgical excision including Mohs micrographic surgery are not without inherent morbidity, including risk of bleeding, infection, and scar.

OBJECTIVE

Lasers may be an alternative for treatment of nonmelanoma skin cancer, and this paper reviews this therapeutic option.

METHODS

A comprehensive search in the Cochrane Library, MEDLINE, and PUBMED databases was performed to identify relevant literature investigating the role of laser therapy in the treatment of nonmelanoma skin cancer.

RESULTS

New literature regarding laser treatment of nonmelanoma skin cancer is emerging, demonstrating promising clinical outcomes. The greatest efficacy has been seen with vascular-selective and ablative lasers in the treatment of basal cell carcinomas. Some success has been reported for laser treatment of squamous cell carcinoma, but data are less convincing. In summary, laser therapy offers an alternative treatment option for nonmelanoma skin cancer; however, its clinical efficacy is variable and, at this time, remains less than currently accepted standards of care.

CONCLUSION

Further studies are needed to optimize parameters, determine maximum efficacy, and provide long-term follow-up.
Noninvasive Measurement of Ear Cartilage Elasticity on the Cellular Level: A New Method to Provide Biomechanical Information for Tissue Engineering
Authors: Bos Ernst Jan , van der Laan Koen , Helder Marco N. , Mullender Margriet G. , Iannuzzi Davide , van Zuijlen Paul P.
Published: February 2017

Background:

An important feature of auricular cartilage is its stiffness. To tissue engineer new cartilage, we need objective tools to provide us with the essential biomechanical information to mimic optimal conditions for chondrogenesis and extracellular matrix (ECM) development. In this study, we used an optomechanical sensor to investigate the elasticity of auricular cartilage ECM and tested whether sensitivity and measurement reproducibility of the sensor would be sufficient to accurately detect (subtle) differences in matrix compositions in healthy, diseased, or regenerated cartilage.

Methods:

As a surrogate model to different cartilage ECM compositions, goat ears (n = 9) were subjected to different degradation processes to remove the matrix components elastin and glycosaminoglycans. Individual ear samples were cut and divided into 3 groups. Group 1 served as control and was measured within 2 hours after animal death and at 24 and 48 hours, and groups 2 and 3 were measured after 24- and 48-h hyaluronidase or elastase digestion. Per sample, 9 consecutive measurements were taken ±300 μm apart.

Results:

Good reproducibility was seen between consecutive measurements with an overall interclass correlation coefficient average of 0.9 (0.81–0.98). Although degradation led to variable results, overall, a significant difference was seen between treatment groups after 48 hours (control, 4.2 MPa [±0.5] vs hyaluronidase, 2.0 MPa [±0.3], and elastase, 3.0 MPa [±0.4]; both P < 0.001).

Conclusions:

The optomechanical sensor system we used provided a fast and reliable method to perform measurements of cartilage ECM in a reverse tissue-engineering model. In future applications, this method seems feasible for the monitoring of changes in stiffness during the development of tissue-engineered auricular cartilage.
Unilateral Pterional Polycraniosynostosis Treated with Craniectomy and Helmet Therapy
Authors: Law Jenaleen , Marucci Damian D. , Gates Robert J. , Fowler Adam
Published: February 2017

Craniosynostosis is a condition in which one or more of the cranial sutures have fused prematurely, affecting the growth pattern and contours of the infant skull. The pterion is the junction of temporal, frontal, parietal, and sphenoid bones of the skull. We present a case of unilateral pterional craniosynostosis, which was treated with strip craniectomy and helmet therapy.
Nosocomial Transmission from an Adolescent with Sputum Smear-Negative Pulmonary Tuberculosis
Authors: Khatami Ameneh , Outhred Alexander C. , Maldigri Patricia I. , Isaacs David , Marais Ben , Kesson Alison M.
Published: February 2017

We describe a case of sputum smear-negative pulmonary tuberculosis in an adolescent boy, where a delay in diagnosis and institution of appropriate infection control measures resulted in transmission of infection to at least 3 and possibly as many as 6 healthcare workers. Lapses in the use of standard precautions for infection control were also identified.
Cytokine Signatures Discriminate Highly Frequent Acute Hepatitis a Virus and Hepatitis E Virus Coinfections from Monoinfections in Mexican Pediatric Patients
Authors: Realpe-Quintero Mauricio , Copado-Villagrana Edgar Daniel , Trujillo-Ochoa Jorge Luis , Alvarez Angel Hilario , Panduro Arturo , Fierro Nora Alma
Published: February 2017

The frequency of hepatitis A virus and hepatitis E virus infections and their cytokine profiles were analyzed in Mexican pediatric patients with acute hepatitis. A high frequency of coinfections was found. Significant overexpression of interleukin (IL)-4, IL-12, IL-13 and interferon-gamma during hepatitis A virus monoinfections and limited secretion of cytokines in hepatitis E virus infections were observed.
How nurse gender influences patient priority assignments in US emergency departments
Authors: Vigil Jacob Miguel , Coulombe Patrick , Alcock Joe , Stith Sarah See , Kruger Eric , Cichowski Sara
Published: February 2017

The goals of this study were to compare whether emergency department (ED) patients' pain intensity (PI) is measured differently by male and female nurses and to determine whether PI, heart rate (HR), and respiratory rate (RR) were used to prioritize patient urgency differently by male and female nurses. The associations between patients' PI|HR|RR and the Emergency Severity Index (ESI) scores they were assigned by attending nurses were analyzed using a national database of electronic medical records of US Veterans Affairs ED patients from 2008 to 2012. A total of 129,991 patients presenting for emergency care (Mage = 59.5, 92% males) and their triage nurses (n = 774, Mage = 47.5, 18% males) were analyzed, resulting in a total of 359,642 patient–provider interactions. Patients' PI did not differ by the nurse's gender; however a cross-classified mixed-effects model showed that nurse gender influenced how PI and RR measurements informed the ESI levels that male patients received. Higher PI levels were associated with more urgent (higher priority) ESI levels by female nurses, yet less urgent ESI levels by male nurses. In contrast, male patients with high RR received more urgent ESI levels by male nurses, whereas the nurse gender did not influence ESI assignments for female patients. These findings show that ED patients receive disparate treatment based on inherent characteristics of their triage nurses, and more standardized (eg, automated) protocols that can account for implicit social factors on health care practice for reliably assessing and prioritizing ED patients may be currently warranted.
Physical activity behavior predicts endogenous pain modulation in older adults
Authors: Naugle Kelly M. , Ohlman Thomas , Naugle Keith E. , Riley Zachary A. , Keith NiCole R.
Published: February 2017

Older adults compared with younger adults are characterized by greater endogenous pain facilitation and a reduced capacity to endogenously inhibit pain, potentially placing them at a greater risk for chronic pain. Previous research suggests that higher levels of self-reported physical activity are associated with more effective pain inhibition and less pain facilitation on quantitative sensory tests in healthy adults. However, no studies have directly tested the relationship between physical activity behavior and pain modulatory function in older adults. This study examined whether objective measures of physical activity behavior cross-sectionally predicted pain inhibitory function on the conditioned pain modulation (CPM) test and pain facilitation on the temporal summation (TS) test in healthy older adults. Fifty-one older adults wore an accelerometer on the hip for 7 days and completed the CPM and TS tests. Measures of sedentary time, light physical activity (LPA), and moderate to vigorous physical activity (MVPA) were obtained from the accelerometer. Hierarchical linear regressions were conducted to determine the relationship of TS and CPM with levels of physical activity, while controlling for demographic, psychological, and test variables. The results indicated that sedentary time and LPA significantly predicted pain inhibitory function on the CPM test, with less sedentary time and greater LPA per day associated with greater pain inhibitory capacity. Additionally, MVPA predicted pain facilitation on the TS test, with greater MVPA associated with less TS of pain. These results suggest that different types of physical activity behavior may differentially impact pain inhibitory and facilitatory processes in older adults.
Observer influences on pain: an experimental series examining same-sex and opposite-sex friends, strangers, and romantic partners
Authors: Edwards Rhiannon , Eccleston Christopher , Keogh Edmund
Published: February 2017

Despite the well-documented sex and gender differences, little is known about the relative impact of male–female social interactions on pain. Three experiments were conducted to investigate whether the type of interpersonal relationship men and women have with an observer affects how they respond to experimental pain. Study 1 recruited friends and strangers, study 2 examined the effects of same- and opposite-sex friends, whereas study 3 investigated the differences between opposite-sex friends and opposite-sex romantic partners. One hundred forty-four dyads were recruited (48 in each study). One person from each dyad completed 2 pain tasks, whereas the other person observed in silence. Overall, the presence of another person resulted in an increase in pain threshold and tolerance on the cold-pressor task and algometer. The sex status of the dyads also had a role, but only within the friendship groups. In particular, male friends had the most pronounced effect on men's pain, increasing pain tolerance. We suggest that the presence of an observer, their sex, and the nature of the participant–observer relationship all influence how pain is reported. Further research should focus on dyadic relationships, and their influence on how men and women report and communicate pain in specific contexts.
A central role for R7bp in the regulation of itch sensation
Authors: Pandey Mritunjay , Zhang Jian-Hua , Mishra Santosh K. , Adikaram Poorni R. , Harris Benjamin , Kahler John F. , Loshakov Anna , Sholevar Roxanne , Genis Allison , Kittock Claire , Kabat Juraj , Ganesan Sundar , Neubig Richard R. , Hoon Mark A. , Simonds William F.
Published: February 2017

Itch is a protective sensation producing a desire to scratch. Pathologic itch can be a chronic symptom of illnesses such as uremia, cholestatic liver disease, neuropathies and dermatitis, however current therapeutic options are limited. Many types of cell surface receptors, including those present on cells in the skin, on sensory neurons and on neurons in the spinal cord, have been implicated in itch signaling. The role of G protein signaling in the regulation of pruriception is poorly understood. We identify here 2 G protein signaling components whose mutation impairs itch sensation. R7bp (a.k.a. Rgs7bp) is a palmitoylated membrane anchoring protein expressed in neurons that facilitates Gαi/o -directed GTPase activating protein activity mediated by the Gβ5/R7-RGS complex. Knockout of R7bp diminishes scratching responses to multiple cutaneously applied and intrathecally-administered pruritogens in mice. Knock-in to mice of a GTPase activating protein-insensitive mutant of Gαo (Gnao1 G184S/+) produces a similar pruriceptive phenotype. The pruriceptive defect in R7bp knockout mice was rescued in double knockout mice also lacking Oprk1, encoding the G protein-coupled kappa-opioid receptor whose activation is known to inhibit itch sensation. In a model of atopic dermatitis (eczema), R7bp knockout mice showed diminished scratching behavior and enhanced sensitivity to kappa opioid agonists. Taken together, our results indicate that R7bp is a key regulator of itch sensation and suggest the potential targeting of R7bp-dependent GTPase activating protein activity as a novel therapeutic strategy for pathological itch.
Pain and respiration: a systematic review
Authors: Jafari Hassan , Courtois Imke , Van den Bergh Omer , Vlaeyen Johan W.S. , Van Diest Ilse
Published: February 2017

Breathing techniques are commonly used to alleviate pain. Despite their frequent use, surprisingly little is known about their efficacy as well as their underlying physiological mechanisms. The purpose of this systematic review is to summarize and critically appraise the results of existing studies on the association between respiration and pain, and to highlight a potential physiological mechanism underlying the respiration–pain connection. A total of 31 publications from between 1984 and 2015 were retrieved and analyzed. These articles were classified into 4 groups: experimental and clinical studies of the effect of pain on respiration, clinical studies of the effects of breathing techniques on pain, and experimental studies of the influence of various forms of respiration on laboratory-induced pain. The findings suggest that pain influences respiration by increasing its flow, frequency, and volume. Furthermore, paced slow breathing is associated with pain reduction in some of the studies, but evidence elucidating the underlying physiological mechanisms of this effect is lacking. Here, we focus on the potential role of the cardiovascular system on the respiratory modulation of pain. Further research is definitely warranted.
A common pronociceptive pain modulation profile typifying subgroups of chronic pelvic pain syndromes is interrelated with enhanced clinical pain
Authors: Grinberg Keren , Granot Michal , Lowenstein Lior , Abramov Liora , Weissman-Fogel Irit
Published: February 2017

Provoked vestibulodynia (PVD) and painful bladder syndrome (PBS), subgroups of chronic pelvic pain syndromes (CPPS), are considered to share common biophysiological peripheral mechanisms. In addition, indications of a pronociceptive pain profile coexisting with psychological vulnerability suggest common dysfunctional pain processing and pain modulation in these 2 subgroups of CPPS. We therefore aimed at comparing the pain profile and psychological traits of patients with PVD and PBS to see whether the pain profile contributes to intersubject variability of clinical pain symptoms. Patients with PVD (n = 18) and PBS (n = 21) were compared with healthy controls (n = 20) in their responses to (1) pain psychophysical tests applied to both referred (suprapubis) and remote (hand) body areas and (2) pain-related psychological factors (pain catastrophizing, depression, anxiety, and somatization). We found a similar pronociceptive pain profile in the 2 subgroups of CPPS—enhanced facilitation (ie, hyperalgesia in the referred body area [P < 0.001]) and inefficient inhibition (ie, reduced conditioned pain modulation [P < 0.001] that were associated with both enhanced pain ratings evoked during trigger point examination [P < 0.037]) and higher Brief Pain Inventory ratings (P = 0.002). The latter was also correlated with pain catastrophizing (r = 0.504, P = 0.001) and depression symptoms (r = 0.361, P = 0.024). The findings suggest common mechanisms underlying a dysfunctional nociceptive system in both PVD and PBS. The intersubject variability in the level of dysfunction and its association with disease severity recommends a personalized pain treatment that may alleviate daily pain and dysfunction in patients with CPPS.
Side effects can enhance treatment response through expectancy effects: an experimental analgesic randomized controlled trial
Authors: Berna Chantal , Kirsch Irving , Zion Sean R. , Lee Yvonne C. , Jensen Karin B. , Sadler Pamela , Kaptchuk Ted J. , Edwards Robert R.
Published: February 2017

In randomized controlled trials, medication side effects may lead to beliefs that one is receiving the active intervention and enhance active treatment responses, thereby increasing drug–placebo differences. We tested these hypotheses with an experimental double-blind randomized controlled trial of a nonsteroidal anti-inflammatory drug with and without the addition of atropine to induce side effects. One hundred healthy volunteers were told they would be randomized to either combined analgesics that might produce dry mouth or inert placebos. In reality, they were randomized double blind, double-dummy to 1 of the 4 conditions: (1) 100 mg diclofenac + 1.2 mg atropine, (2) placebo + 1.2 mg atropine, (3) 100 mg diclofenac + placebo, or (4) placebo + placebo, and tested with heat-induced pain. Groups did not differ significantly in demographics, temperature producing moderate pain, state anxiety, or depression. Analgesia was observed in all groups; there was a significant interaction between diclofenac and atropine, without main effects. Diclofenac alone was not better than double-placebo. The addition of atropine increased pain relief more than 3-fold among participants given diclofenac (d = 0.77), but did not enhance the response to placebo (d = 0.09). A chain of mediation analysis demonstrated that the addition of atropine increased dry mouth symptoms, which increased beliefs that one had received the active medication, which, in turn, increased analgesia. In addition to this indirect effect of atropine on analgesia (via dry mouth and beliefs), analyses suggest that among those who received diclofenac, atropine directly increased analgesia. This possible synergistic effect between diclofenac and atropine might warrant future research.
Return to work helps maintain treatment gains in the rehabilitation of whiplash injury
Authors: Sullivan Michael , Adams Heather , Thibault Pascal , Moore Emily , Carriere Junie S. , Larivière Christian
Published: February 2017

This study examined the relation between return to work and the maintenance of treatment gains made over the course of a rehabilitation intervention. The study sample consisted of 110 individuals who had sustained whiplash injuries in rear collision motor vehicle accidents and were work-disabled at the time of enrolment in the study. Participants completed pre- and post-treatment measures of pain severity, disability, cervical range of motion, depression, posttraumatic stress symptoms, and catastrophizing. Pain severity was assessed again at 1-year follow-up. At 1-year follow-up, 73 participants had returned to work and 37 remained work-disabled. Analyses revealed that participants who returned to work were more likely to maintain treatment gains (77.5%) than participants who remained work-disabled (48%), χ2 = 6.3, P < 0.01. The results of a regression analysis revealed that the relation between return to work and the maintenance of treatment gains remained significant (β = 0.30, P < 0.01), even when controlling for potential confounders such as pain severity, restricted range of motion, depression, and pain catastrophizing. The Discussion addresses the processes by which prolonged work-disability might contribute to the failure to maintain treatment gains. Important knowledge gaps still remain concerning the individual, workplace, and system variables that might play a role in whether or not the gains made in the rehabilitation of whiplash injury are maintained. Clinical implications of the findings are also addressed.
The Effect of Glycopyrrolate on Nocturnal Sialorrhea in Patients Using Clozapine
Authors: Man Wai Hong , Colen–de Koning Jantine C.A. , Schulte Peter F.J. , Cahn Wiepke , van Haelst Ingrid M.M. , Doodeman Hieronymus J. , Egberts Toine C.G. , Heerdink Eibert R. , Wilting Ingeborg
Published: February 2017

Background

Nocturnal sialorrhea is one of the most frequent adverse events in clozapine treatment. Symptomatic management of sialorrhea usually consists of off-label treatment with anticholinergic agents. The aim of the current study is to evaluate the efficacy and safety of glycopyrrolate in patients using clozapine that experience sialorrhea.

Methods

In a double-blind randomized crossover trial, patients with nocturnal sialorrhea (n = 32) were randomized to treatment with glycopyrrolate 1 mg or placebo. This double-blinded phase was followed by an optional open label extension phase with glycopyrrolate 2 mg. Exposure periods consisted of 6 consecutive days and were separated with 1 washout week. The primary outcome was clinical improvement of nocturnal sialorrhea assessed by the Patient Global Impression of Improvement (PGI-I).

Results

The proportion of patients with a clinical improvement according to PGI-I did not significantly differ between 1 mg and placebo (18.8% vs 6.3%, P = 0.289); however, in patients using glycopyrrolate 2 mg once daily versus placebo, it did (43.5% vs 6.3%, P = 0.039). Glycopyrrolate was not associated with severe adverse events or worsening of cognitive adverse events.

Conclusions

Glycopyrrolate 1 mg was not superior to placebo, whereas 2 mg showed a significant clinical improvement of nocturnal sialorrhea compared with placebo. Glycopyrrolate seemed to be a tolerable anticholinergic agent in the treatment of clozapine-associated sialorrhea.
Activating and Sedating Adverse Effects of Second-Generation Antipsychotics in the Treatment of Schizophrenia and Major Depressive Disorder
Authors: Citrome Leslie
Published: February 2017

Purpose/Background

Activating and sedating adverse effects of antipsychotics can be obstacles to their use.

Methods/Procedures

This study quantified the activating and sedating properties of first-line oral second-generation antipsychotics by examining the rates of adverse reactions as reported in product labeling for the indications of schizophrenia and adjunctive treatment of major depressive disorder. Additional data sources included regulatory documents, study synopses, and published study reports. Attributable risk increase and number needed to harm (NNH) were calculated for each agent versus placebo.

Findings/Results

Heterogeneity among the different antipsychotics regarding activating or sedating adverse events was observed, with some agents displaying the potential for both activating and sedating properties. For agents indicated for the treatment of schizophrenia, predominantly activating medications include lurasidone (NNH, 11 for akathisia vs 20 for somnolence) and cariprazine (NNH, 15 for akathisia vs 65 for somnolence-combined terms). Similarly activating and sedating are risperidone (NNH, 15 for akathisia vs 13 for sedation) and aripiprazole (NNH, 31 for akathisia vs 34 for somnolence). Predominantly sedating are olanzapine, quetiapine immediate and extended release, ziprasidone, asenapine, and iloperidone. Agents that are neither activating nor sedating are paliperidone and brexpiprazole. For major depressive disorder, the overall findings regarding activation and sedation appear similar to those seen with schizophrenia. Data extracted were limited to those available from registrational studies that contributed to the adverse event tables contained in the product labels. Postregistrational comparative studies may yield different outcomes.

Implications/Conclusions

Differences in tolerability profiles regarding activation and sedation have implications in terms of selecting the optimal antipsychotic for a given individual.
5-HT6 Receptor Antagonist as an Adjunct Treatment Targeting Residual Symptoms in Patients With Schizophrenia
Authors: Morozova Margarita , Burminskiy Denis , Rupchev George , Lepilkina Taissia , Potanin Sergey , Beniashvili Allan , Lavrovsky Yan , Vostokova Natalia , Ivaschenko Alexander
Published: February 2017

Background

Treating patients who experience residual psychotic symptoms during remission of schizophrenia remains one of the most challenging problems. The mechanisms underlying these symptoms differ from those of acute hallucinations and delusions. 5-HT6 receptor antagonists have been considered promising agents in treatment of residual psychotic symptoms and cognitive dysfunction. The aim of the study was to assess the efficacy of a selective 5-HT6 inhibitor Avisetron in the reduction of residual psychotic symptoms in patients with schizophrenia on stable antipsychotic therapy.

Methods

Eighty clinically stable outpatient subjects with schizophrenia with residual psychotic symptoms were randomized in a double-blind manner to 6 weeks of Avisetron or placebo at 1:1 ratio. Subjects received 8 mg of Avisetron or placebo on top their stable antipsychotic treatment. Standard clinical scales and cognitive tests were used for endpoint assessment. The primary efficacy endpoint was the mean reduction of total Positive and Negative Syndrome Scale score after 6 weeks of treatment.

Results

No significant differences in the primary and secondary endpoints were found between the groups. However, based on the subgroup analysis, the significant improvement of total Positive and Negative Syndrome Scale score and residual psychotic symptoms was observed in female patients.

Conclusions

It was a negative study with unexpected benefits of the drug only in females. We hypothesized that the role of patients' sex can impact the treatment response to serotonergic drugs in general. We suggest a possible synergistic interaction between estrogen and Avisetron by means of modulating the effect of estrogens on the serotonergic system. Future studies targeting the sex-related effects of serotonergic drugs are warranted.
The Art of Pharmacotherapy
Authors: de Leon Jose , De las Cuevas Carlos
Published: February 2017

Purpose/Background

This commentary deals with the neglected issue of the art of psychopharmacology by recounting the authors’ journeys.

Methods/Procedures

First, a model of medical science situated within the history of medicine is described including (1) a limitation of the mathematical model of science, (2) the distinction between mechanistic science and mathematical science, (3) how this distinction is applied to medicine, and (4) how this distinction is applied to explain pharmacology to psychiatrists. Second, the neglected art of psychopharmacology is addressed by explaining (1) where the art of psychopharmacotherapy was hiding in the first author’s psychopharmacology research, (2) how the Health Belief Model was applied to the art of medicine, (3) how the second author became interested in the Health Belief Model, and (4) his studies introducing the Health Belief Model in psychopharmacology. The authors’ collaboration led to: (1) study of the effect of pharmacophobia on poor adherence and (2) reflection on the limits of the art of psychopharmacology.

Findings/Results

Low adherence was found in 45% (116/258) of psychiatric patients with pharmacophobia versus 22% (149/682) in those with no pharmacophobia, providing an odds ratio of 2.9 (95% confidence interval, 2.2–4.0) and an adjusted odds ratio of 2.5 (95% confidence interval, 1.8–3.5) after adjusting for other variables contributing to poor adherence.

Implications/Conclusions

Different cognitive patterns in different patients may contribute to poor adherence. Specific interventions targeting these varying cognitive styles may be needed in different patients to improve drug adherence.
Performance Plateau in Prelingually and Postlingually Deafened Adult Cochlear Implant Recipients
Authors: Cusumano Cristen , Friedmann David R. , Fang Yixin , Wang Binhuan , Roland J. Thomas , Waltzman Susan B.
Published: February 2017

Objective:

To characterize the performance plateau after unilateral cochlear implantation (CI) in prelingually and postlingually deafened adults and to compare their relative progress.

Study Design:

Retrospective chart review.

Setting:

Tertiary referral center.

Patients:

Prelingually and postlingually deaf adults who received a unilateral CI and completed a minimum of 2 years of follow-up at our center.

Intervention:

Unilateral CI.

Main Outcome Measures:

: Standard speech perception testing (consonant-nucleus-consonant [CNC] monosyllabic word test and hearing in noise test [HINT] or AzBio sentence test) were performed preoperatively and 3 and 12 months postoperatively, and annually thereafter.

Results:

In postlingually deaf patients (n = 102), there was a significant improvement in word scores for 3 years postimplantation (p < 0.01). Beyond the 3 years postoperative time point, word scores continued to improve, albeit at a flatter rate. In prelingually deaf patients (n = 16) word scores improved significantly for 5 years postimplantation (p = 0.03).

Conclusions:

Adults with postlingual deafness undergoing unilateral CI show significant improvement in speech perception for 3 years postimplantation, at which point their performance continues to improve, albeit at a flatter rate. The performance of adults with prelingual deafness improves significantly as late as 5 years postimplantation. These time intervals reflect a change to the currently reported 6 to 12 months period and should impact on counseling, especially in the prelingual CI candidate.
Cochlear Implantation in Children With Congenital Single-Sided Deafness
Authors: Thomas Jan Peter , Neumann Katrin , Dazert Stefan , Voelter Christiane
Published: February 2017

Objective:

To determine audiological and clinical results of cochlear implantation in children with congenital single sided deafness (SSD), with an emphasis on children implanted before and after 6 years of age.

Study Design:

Retrospective study.

Setting:

Tertiary referral center.

Subjects:

Twenty one children with congenital SSD who were implanted aged 10 months to 11;3 years.

Intervention:

Unilateral cochlear implantation.

Main Outcome Measures:

Speech recognition in noise via the German Oldenburg Sentence Test for Children (OlKiSa), lateralization ability, and subjective evaluation of hearing results using self- and third-party assessment questionnaires.

Results:

Significant improvements of all three aspects of true binaural hearing were found. The most striking improvement was the combined head shadow effect by 2.11 dB (squelch effect: 0.95 dB, summation effect 0.98 dB). An improvement of lateralization ability was also demonstrated. Parents had a high overall level of satisfaction with their children's cochlear implantation. Subjective benefit was verified in all three subscales of the Speech, Spatial, and Qualities of Hearing Questionnaire. No significant difference was found between subjects implanted before the age of 6 with those implanted later. Three of the five subjects with a follow-up of greater than 3 years were limited users or nonusers.

Conclusions:

Cochlear implant (CI) provision provides children with congenital SSD with significant audiological and subjective benefits which can be seen even in children implanted after the age of 3;6. The problem of limited use and nonuser, however, should not be ignored and has to be considered for further studies.